Surgery of the Salivary Glands [1 ed.] 2019950665, 9780323672368

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Surgery of the Salivary Glands

Surgery of the Salivary Glands Edited by

Robert L. Witt, MD, FACS Helen F. Graham Cancer Center and Research Institute Christiana Care, Newark, DE, USA Professor of Otolaryngology – Head & Neck Surgery Thomas Jefferson University, Philadelphia, PA, USA Affiliate Professor, Biological Sciences University of Delaware, Newark, DE, USA

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Edinburgh London New York Oxford Philadelphia St Louis Sydney 2021

© 2021, Elsevier Inc. All rights reserved. Videos 37.1–37.4 Extracapsular dissection technique for superficial tumor, Extracapsular dissection technique for deep tumor to facial nerve, Extracapsular dissection technique for tumor wedged between mandible and mastoid, Extracapsular dissection technique for a deep tumor copyright Mark McGurk. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Control Number: 2019950665 ISBN: 978-0-323-67236-8

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Contents Foreword, viii Preface, ix List of Contributors, x Acknowledgments, xvii Dedication, xvii Video List, xviii

Section 1 Foundational Content 1. Salivary Gland Anatomy, 2 Yves Saban, Tevfik Sözen, Peter Palhazi, and Roberto Polselli

2. Salivary Gland Embryology, Physiology, and Stem Cell Complexity, 12 Harleen K. Athwal and Isabelle M. A. Lombaert

3. Salivary Gland Imaging, 19 Urban Geisthoff, Alberto Iaia, Brady Laughlin, Arpit Gandhi, and Hung Dam

4. Fine Needle Aspiration Cytology, Core Needle Biopsy, and Frozen Section, 33 Peter Zbären

5. Salivary Gland Histology, 37 John D. Harrison

6. Pathology and Molecular Pathology of Salivary Tumors: General Considerations, 43 Stephan Ihrler

Section 2 Inflammatory Conditions 7. Sialadenitis, 48 Crystal Shuk Jin Cheong, Woei-Shyang Loh, Thomas Kwok Seng Loh, Priscilla Ching-Han Wong, Pilar Brito-Zerón, Soledad Retamozo, Alejandra Flores-Chavez, Manuel Ramos-Casals, Hui-Ching Chuang, Chih-Yen Chien, Sheng-Po Hao and Chung-Yu Hao

8. Pediatric Salivary Gland Diseases, 64 Patrick J. Bradley, Raymond W. Clarke, Oded Nahlieli, and Victor J. Abdullah

9. Benign Cystic Lesions, 79 Sumit Samant, Zahoor Ahmad, Randall P. Morton, and Alfred E. Bacon III

10. Pathogenesis of Salivary Calculi, 85 John D. Harrison

11. Conventional Surgery for Salivary Inflammatory Diseases, 92 Eugene N. Myers

Section 3 Diagnostic Sialendoscopy 12. Salivary Duct Anatomy for Sialendoscopy, 98 Yves Saban, Tevfik Sözen, Peter Palhazi, and Roberto Polselli

13. Sialendoscopy: Getting Started, 101 David M. Cognetti

14. Types of Sialendoscopes and Accessories, 108 Francis Marchal, Frederic Faure, Michael Koch, Heinrich Iro, Mark McGurk, and Rohan R. Walvekar

15. Management of the Submandibular Duct Papilla and other Approaches to Salivary Ducts, 119 Pauline Pouzoulet, Nicolas Graillon, Jean Marc Foletti, Marc-Kevin Le Roux, and Cyrille Chossegros

16. Operative Techniques with Diagnostic Sialendoscopy, 122 Olivier Abboud

Section 4 Interventional Sialendoscopy for Stones 17. Sialendoscopy for Submandibular Duct Stone Extraction, 132 Monika E. Freiser and Barry M. Schaitkin

18. Submandibular Gland Sialendoscopy-Assisted Transoral Technique, 137 Johannes Zenk and Tobias Strenger v

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Contents

19. Endoscopic Transoral Removal of Distal and Proximal Stones from the Parotid Duct, 146 Oded Nahlieli

20. Parotid Gland Proximal Stones, Combined Transoral and External Approach, 153 Urban Geisthoff

21. Interventional Sialendoscopy for Stones: Robotic Approaches, 158 Christopher H. Rassekh

22. Laser Fragmentation of Salivary Stones, 161 Robert A. Irvine

23. Stone Fragmentation with Pneumatic Lithotripsy, 164 Michael Koch and Heinrich Iro

24. Extracorporeal Lithotripsy, 169 Michael Koch and Heinrich Iro

Section 6 Benign Neoplasms 34. Benign Tumors, 216 Babak Larian, Bonnie Lei Balzer, Yoav P. Talmi, Doron Sagiv, and Jorge Rosa Santos

35. Surgery for Benign Salivary Gland Tumors: Classic Approaches, 227 Daniella Karassawa Zanoni, Snehal G. Patel, Jacob Kahane, Robert C. Wang, Daniel Deschler, Joseph Zenga, Fernando L. Dias, Claudio R. Cernea, and Roberto A. Lima

36. Facial Nerve Monitoring, 244 Rebecca J. Hammon and David W. Eisele

37. Minimally Invasive Approaches – Extracapsular Dissection, 248 Mark McGurk, Konstantinos Mantsopoulos, and Heinrich Iro

38. Retroauricular Approach to the Submandibular Gland, 252 Eddy W. Y. Wong and Jason Y. K. Chan

25. Stenting/Marsupialization, 177 Jean-Michel Lopez

26. Interventional Sialendoscopy: Complications, 180 Kevin Oshiro Do and M. Boyd Gillespie

Section 5 Interventional Sialendoscopy for Stenosis 27. Parotid Gland Intraoral Dilation of Strictures, 186 Siu Kwan Ng

28. Parotid Gland Intraoral/External Combined Approaches for Strictures, 191 Michael Koch and Heinrich Iro

29. Submandibular Gland Duct Strictures, 200 Hila Klein

30. Salivary Stents for Stenosis, 204 Rohan R. Walvekar

31. Sialendoscopy for Stenosis: Complications, 206 Kevin Oshiro Do and M. Boyd Gillespie

32. Sialendoscopy for Sjögren Syndrome, 210 Rohan R. Walvekar

33. Sialendoscopy for Radiation Sialadenitis, 212 Hok Nam Li

39. Management of Parotidectomy Complications, 254 Pavel Dulguerov and Philippe Pasche

40. Parotidectomy: Deformity and Reconstruction, 258 Philippe Pasche and Pavel Dulguerov

41. Management of Recurrent Pleomorphic Adenoma, 264 Davide Lombardi, Davide Farina, Michele Tomasoni, Davide Lancini, and Piero Nicolai

42. Parapharyngeal Tumors, 268 Kyung Tae, Christopher H. Rassekh, Gregory S. Weinstein, and Bert W. O’Malley Jr

43. Buccal Space Tumors, 274 Zaid Al-Qurayshi, Joseph D. Peterson, and Henry T. Hoffman

44. Vascular Lesions of the Salivary Glands, 279 Doh Young Lee and Kwang Hyun Kim

Section 7 Malignant Neoplasms 45. Malignant Tumors, 286 Jennifer R. Wang, Diana Bell, Renata Ferrarotto, Randal S. Weber, and Shirley Y. Su

46. Prognostic Scoring for Salivary Gland Malignancy, 302 Vincent Vander Poorten

Contents

47. Malignant Tumors: Surgery, 307 Daniella Karassawa Zanoni, Snehal G. Patel, Daniel Deschler, Joseph Zenga, Fernando L. Dias, Claudio R. Cernea, and Roberto A. Lima

48. Surgery of the Neck for Malignant Salivary Gland Tumors, 324 Nathaniel Reeve and Robert C. Wang

49. Surgery for Metastasis to the Parotid Gland and Tumor Infiltration of the Parotid Gland, 327 Zahoor Ahmad and John M. Chaplin

50. Facial Paralysis Rehabilitation, 332 Nelson Kwong Lun Lai

51. Lymphoma, 340 Mimi Lee Kun Min and Thomas Lau Kwan Hang

52. Radiation Therapy for Malignant Salivary Gland Tumors, 342 David Gasalberti and Adam Raben

53. Salivary Gland Tissue Engineering to Relieve Xerostomia, 348 Padma Pradeepa Srinivasan, Swati Pradhan-Bhatt, Mary C. Farach-Carson, and Daniel A. Harrington

54. Chemotherapy and Molecular Targeted Therapy, 353 SuJung Park

Section 8 Social Impact 55. Salivary Gland Surgery in Developing Countries, 360 Johannes J. Fagan

56. Quality of Life, 364 Yoav P. Talmi

57. Malpractice in Salivary Gland Surgery, 368 Joshua H. Meyeroff

58. European Salivary Gland Society and the Evolution to a World Salivary Gland Society, 371 Pavel Dulguerov, Vincent Vander Poorten, and Francis Marchal

Index, 377

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Foreword

I met Bob Witt for the first time at the 2nd International Conference on Salivary Gland Disorders in Pittsburgh in 2007. We found that we shared an interest in this topic and many others. Over the years, Bob and I have met in many other meetings across the world. I’ve followed his career with great interest and have been impressed with the leadership he has provided in the previously neglected area of salivary gland disorders. He is a Professor of Otolaryngology – Head and Neck Surgery at Thomas Jefferson University School of Medicine and is an internationally recognized surgeon and researcher in salivary gland disorders and thyroid cancer. He has contributed many important observations on salivary gland disorders in both clinical and research domains. Dr. Witt’s book – Salivary Gland Disease – published in 2006, was the first textbook in the field in many years. The current book Surgery of the Salivary Glands builds on the foundation of the previous book. He has recruited an allstar team of authors from around the world. While the book provides sections on foundational content, inflammatory conditions, and the pathogenesis of salivary gland calculi, clearly surgery is the dominant theme. The sections on surgery describe the remarkable advances in technology, which are the product of the collaboration between the surgeons interested in salivary glands and industry that has

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driven the amazing advances in this field. Thousands of patients have been rescued from removal of an obstructed gland using the techniques of sialendoscopy. Other technological advances described include lithotripsy, lasers, and robotic surgery. Important non-surgical topics of importance are not neglected. For instance, Strategies for Xerostomia describes modern tissue engineering techniques that are being used to solve this vexing problem. A section on Social Impact brings the issues of quality of life, ethics, and legal matters into sharp focus. The important role of education is also highlighted, describing the positive impact of the European Salivary Gland Society (ESGS) under the leadership of Professor Francis Marchal, who was influential in founding the ESGS and traveling around the world teaching surgeons the technique of sialendoscopy. While I’ve written the Foreword to many textbooks, this is the first time an author has dedicated a book to me. I’m honored and flattered by this gesture, and I express my deep appreciation and gratitude to Dr. Robert L. Witt. Eugene N. Myers, MD – FACS – FRCS Edin (Hon.) Distinguished Professor and Emeritus Chair Department of Otolaryngology University of Pittsburgh School of Medicine

Preface

Surgery of the Salivary Glands is a comprehensive, state of the art study of all aspects of surgery and medicine of the salivary glands. It provides unique coverage of the foundational content (anatomy from cadaveric dissection, physiology, cytology, histology, pathology, and imaging), inflammatory conditions, diagnostic and interventional sialendoscopy for stones and stenosis, robotics, as well as pathology, surgery, and complete management for benign and malignant neoplasms. It encompasses their social impact. Each contributing author is drawn from among the very best worldwide in the fields of Head & Neck Surgery, Otolaryngology, Pediatric Otolaryngology, Oral and MaxilloFacial Surgery, Plastic Surgery, Rheumatology, Pathology, Radiation Oncology, Medical Oncology Radiology, and Salivary Gland Science.

Thus far, books on this topic are largely limited to authors from North America and Europe. Leading authors from Asia, South America, Oceana, the Middle East, and Africa provide a broad perspective. Equally important are the many chapters authored by my colleagues in oral and maxillo-facial surgery. This book represents a detailed surgical text and atlas. It includes a video library that is a first for textbooks on salivary gland surgery. It is intended for physicians in residency, fellowship training, clinical practice, and academic medicine. It has been a personally gratifying privilege to work with this prestigious and thoughtful group of authors. Robert L. Witt, MD

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List of Contributors

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List of Contributors

Olivier Abboud, MD, FRCSC, MSC

Assistant Clinical Professor Division of Otolaryngology – Head and Neck Surgery, University of Montreal, Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada

Victor James Abdullah, BSc (Hons), MBBS (Lond.), FRCS (Engl.), FRCS (Edin.), FHKCS FHKCORL FHKAM (Otorhinolaryngology)

Consultant, Chief of Service Otorhinolaryngology, United Christian Hospital/ Tseung Kwan O Hospital, Kowloon East Cluster, The Hospital Authority of Hong Kong, Hong Kong SAR, Nil, China Chief of Paediatric Otorhinolaryngology, Honorary Associate Professor Otorhinolaryngology, The Chinese University of Hong Kong, Hong Kong SAR, China

Zahoor Ahmad, MBBS, MS, FRACS

Senior Consultant Otolaryngology – Head & Neck Surgery, Counties Manukau Health, Auckland, New Zealand Associate Professor Otolaryngology – Head & Neck Surgery, Auckland University, Auckland, New Zealand

Zaid Al-Qurayshi, MBChB, MPH

Resident Physician Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States

Harleen K. Athwal

Bonnie Lei Balzer, MD, PhD

Vice Chair of Anatomic Pathology Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States Director of Head and Neck Pathology Services Pathology, Cedars-Sinai Medical Center, Los Angeles, California, United States Director of Musculoskeletal Pathology Services Pathology, Cedars-Sinai Medical Center, Los Angeles, California, United States

Diana Bell, MD

Associate Professor Pathology/Head and Neck, MD Anderson Cancer Center, Houston, Texas, United States

Patrick James Bradley, MBBCh, FRCS (Ir.Ed.Eng.), FRACS (Hon), FRCS (Eng. Hon), FRCSLT (Hon), MBA Professor Emeritus Otorhinolaryngology – Head & Neck Surgery, Nottingham University Hospitals, Queens Medical Campus, Nottingham, United Kingdom

Pilar Brito-Zerón, MD, PhD

Research Coordinator Autoimmune Disease Unit, Department of Medicine, Hospital CIMA-Sanitas, Barcelona, Spain

Claudio R. Cernea, MD, PhD

University of São Paulo School of Medicine Surgery, University of São Paulo Medical School, São Paulo, Brazil

Department of Biologic & Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan, United States Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, United States

Jason YK Chan, MBBS

Alfred E. Bacon III, MD

John M. Chaplin, MBChB, FRACS

Medical Director Clinical Trials Medicine, Christiana Care Health System, Wilmington, Delaware, United States

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Assistant Professor Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong Head and Neck, Endocrine and Reconstructive Surgeon Otolaryngology Head and Neck Surgery, Auckland City Hospital, Auckland, New Zealand

List of Contributors

Crystal Shuk Jin Cheong, MBBS, MRCS (Edin), MMed (ORL), FAMS

Associate Consultant Department of Otolaryngology – Head & Neck Surgery, National University Hospital, Singapore

Chih-Yen Chien, MD, FACS

Professor Department of Otolaryngology – Head and Neck Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Cyrille Chossegros, MD, PhD

Aix Marseille University Oral and Maxillofacial Surgery, Conception University Hospital, Marseilles, France

Hui-Ching Chuang, MD, PhD, FACS

Associate Professor Department of Otolaryngology – Head and Neck Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Raymond William Clarke, BA, BSc, DCH, FRCS, FRCS(ORL) Professor University of Liverpool, Paediatric Otolaryngologist, Royal Liverpool Children’s Hospital (Alder Hey), Liverpool, United Kingdom

David M. Cognetti, MD

Associate Professor Department of Otolaryngology – Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United States

Hung Dam, MD

Chief, Nuclear Medicine Radiology, Christiana Care Health System, Newark, Delaware, United States

Daniel Deschler, MD, FACS

Vice-Chair Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, Massachusetts, United States Professor Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States

Fernando L. Dias, MD, MSc, PhD

Chief Head and Neck Surgery Service, Brazilian National Cancer Institute – INCa, Rio de Janeiro, Rio de Janeiro, Brazil Chairman Head and Neck Surgery Department, Catholic University – PUC, Rio de Janeiro, Rio de Janeiro, Brazil

Kevin Oshiro Do, BSc

Medical Student Department of Otolaryngology, Head & Neck Surgery, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Pavel Dulguerov, MD, PD

Director Centre ORL et Chirurgie Maxillo-Cervico-Faciale, La Tour Medical Group, Meyrin, Switzerland Professor ORL-HNS, Geneva University, Geneva, Switzerland

David W. Eisele, MD FACS

Andelot Professor and Director Department of Otolaryngology – Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Johannes J. Fagan, MBChB, MMed, FCS (ORL) Professor and Chair Otorhinolaryngology, University of Cape Town, Cape Town, South Africa

Mary C. Farach-Carson, PhD

Professor Diagnostic and Biomedical Sciences, University of Texas Health Science Center at Houston School of Dentistry, Houston, Texas, United States

Davide Farina, MD

Professor Department of Radiology, Università degli Studi, Brescia, Italy

Frederic Faure, MD, PhD

Doctor ENT, Lyon University Hospital, Lyon, France

Renata Ferrarotto, MD

Associate Professor Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas, United States

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List of Contributors

Alejandra Flores-Chavez, MsCN, PhD

Research Fellow Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS Hospital Clinic, Barcelona, Spain

Jean Marc Foletti, MD, PhD

Doctor Associate Professor Aix Marseille Université, Oral and Maxillo-Facial Departement, Hôpital de la Conception, APHM, Marseille, France

Monika E. Freiser, MD, MPH

Resident Physician Otolaryngology – Head & Neck Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States

Arpit Gandhi, MD

Resident Physician Diagnostic Radiology, Christiana Hospital, Newark, Delaware, United States

David Gasalberti, MD

Physician Radiation Oncology, Christiana Care Health System, Newark, Delaware, United States

Urban Geisthoff, Prof. Dr.

Vice Chairman Department of Otorhinolaryngology, Head and Neck Surgery, Marburg University Hospital, Marburg, Germany

M. Boyd Gillespie, MD, MSc

Sheng-Po Hao, MD

Professor and Chairman Department of Otolaryngology Head and Neck Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Director Comprehensive Oral Cancer Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Professor of Otolaryngology School of Medicine, Fu-Jen University, Taipei, Taiwan

Daniel A. Harrington, PhD

Assistant Professor Diagnostic & Biomedical Sciences, University of Texas Health Science Center at Houston, Houston, Texas, United States

John D. Harrison, PhD, FDSRCSEng, FRCPath

Visiting Reader Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London, United Kingdom

Henry T. Hoffman, MD, MS, FACS

Professor Otolaryngology, University of Iowa, Iowa City, Iowa, United States

Alberto Iaia, MD

Chief of Neuroradiology Radiology, Christiana Care Health Services, Newark, Delaware, United States Assistant Professor of Radiology Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania, United States

Professor and Chair Otolaryngology – Head & Neck Surgery, University of Tennessee Health Science Center, Memphis, Tennessee, United States

Stephan Ihrler

Nicolas Graillon, MD

Heinrich Iro

Rebecca J. Hammon, MD

Robert A. Irvine, MD

Service de chirurgie maxillo-faciale et stomatologie Oral and Maxillofacial Department, Hôpital Conception, APHM, Marseille, France Instructor Otolaryngology – Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, United States

Chung-Yu Hao

Chief Resident Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Professor Laboratory of Dermatopathology and Oral Pathology, Muenchen, Germany Professor, Chair ENT, Head and Neck surgery, University of ErlangenNuremberg, D-91054 Erlangen, Germany Clinical Associate Professor Surgery, University of British Columbia, Vancouver, British Columbia, Canada Otolaryngologist Surgery, St. Paul’s Hospital, Vancouver, British Columbia, Canada

List of Contributors

Jacob Kahane, MD

Doctor Otolaryngology – Head and Neck Surgery, University of Nevada Las Vegas School of Medicine, Las Vegas, Nevada, United States

Daniella Karassawa Zanoni, MD

Senior Scientist Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Kwang Hyun Kim, MD, PhD

Professor Emeritus Otolaryngology – Head and Neck Surgery, Seoul National University, College of Medicine, Seoul, Republic of Korea Otolaryngology – Head and Neck Surgery, Bundang Jesaeng Hospital, Seongnam Si/Bundang Gu, Republic of Korea

Hila Klein, DMD, OMFS

Oral and Maxillofacial Department, Rambam Health Care Campus, Haifa, Israel

Michael Koch, MD, PhD

Professor ENT, Head & Neck Surgery, FAU Erlangen-Nuremberg, Erlangen, Germany

Nelson Kwong Lun Lai, MBChB (CUHK), FHKCORL, FHKAM (Otorhinolaryngology), FRCSEd (ORL)

Honorary Clinical Assistant Professor Otorhinolaryngology, Head & Neck Surgery, The Chinese University of Hong Kong, Hong Kong, China

Davide Lancini, MD

Resident Department of Otorhinolaryngology – Head and Neck Surgery, University of Brescia, Brescia, Italy

Babak Larian, MD

Clinical Chief Division of Otolaryngology, Head and Neck Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States Assistant Clinical Professor of Surgery Division of Otolaryngology, Head and Neck Surgery, UCLA David Geffen School of Medicine, Los Angeles, California, United States

Thomas Kwan Hang Lau, MBChB, MRCP(UK), FHKAM(Medicine)

Honorary Clinical Assistant Professor Clinical Oncology, Chinese University of Hong Kong, Hong Kong Associate Consultant Department of Clinical Oncology, Prince of Wales Hospital, Shatin, Hong Kong

Brady Laughlin, DO

Resident Physician Diagnostic Radiology, Christiana Care Health System, Newark, Delaware, United States

Marc-Kevin Le Roux, MD

Maxillo-Facial and Stomatology, Conception’s University Hospital, Marseille, France

Doh Young Lee, MD, PhD

Assistant Professor Department of Otorhinolaryngology Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul, Republic of Korea

Mimi Lee Kun Min, MBChB, FRCR, FHKAM, FHKCR

Honorary Clinical Assistant Professor Clinical Oncology, Chinese Univeristy of Hong Kong, Hong Kong

Hok Nam Li, MBChB, FRCS(ORL), FHKCORL, FHKAM(ORL)

Honorary Clinical Assistant Professor Otorhinolaryngology, Head & Neck Surgery, The Chinese University of Hong Kong, Hong Kong, Hong Kong Associate Consultant Otorhinolaryngology, Head & Neck Surgery, Prince of Wales Hospital, Hong Kong, China

Roberto A. Lima, MD, PhD

Director Attending Surgeon, Service of Head and Neck Surgery, Cancer Hospital 1, Brazilian National Cancer Institute, Rio de Janeiro, RJ, Brazil

Thomas K.S. Loh, MBBS(S’pore), FRCS(Glasg)

Associate Professor Department of Otolaryngology – Head & Neck Surgery, National University Hospital, Singapore Senior Consultant, Division of Surgical Oncology, National University Cancer Institute, Singapore Deputy Director (Clinical), National University Cancer Institute, Singapore

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List of Contributors

Woei-Shyang Loh, MBBS(S’pore), FRCS(Edin)

Associate Professor and Head Department of Otolaryngology – Head & Neck Surgery, National University Hospital, Singapore

Isabelle M.A. Lombaert, PhD, MSc, Ir

Assistant Professor Biologic & Materials Sciences, University of Michigan, Ann Arbor, Michigan, United States

Davide Lombardi, MD

Consultant Department of Otorhinolaryngology – Head and Neck Surgery, University of Brescia, Brescia, Italy

Jean-Michel Lopez, MD

ENT, Head and Neck Surgeon, Maxillo-Facial Surgeon Head of Department ENT and Head and Neck surgery, Centre Hospitalier Saint Jean, Perpignan, France

Konstantinos Mantsopoulos, Msc, MD, PhD

Assistant Professor, Consultant Otolaryngology, Head and Neck surgery, University of Erlangen-Nürnberg, Erlangen, Germany

Francis Marchal, MD, FACS

Professor of ORL, Head and Neck Surgery Otorhinolaryngology, Head and Neck Surgery, University Hospitals Geneva, Geneva, Switzerland

Mark McGurk, MD, FRCS, FDSRCS, DLO

Professor Head and Neck Service, University College Hospital London, Director Head & Neck Centre, UCL Division of Surgical Interventional Sciences, University College Hospital London, London, United Kingdom

Joshua H. Meyeroff, JD

Medical Malpractice – Defense, Morris James LLP, Wilmington, Delaware, United States

Randall P. Morton, PhD, MB, BS, MSc, FRACS, FRCSEd Professor Otolaryngology – Head & Neck Surgery, CountiesManukau Health, Auckland, New Zealand

Eugene Nicholas Myers, MD, FACS, FRCS, Edin (Hon.)

Distinguished Professor and Emeritus Chair, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States Professor Department of Oral and Maxillofacial Surgery, University of Pittsburgh School of Dental Medicine, Eye and Ear Institute, Pittsburgh, Pennsylvania, United States

Oded Nahlieli, DMD

Professor and Chairman Oral and Maxillofacial Surgery Department, Barzilai University Medical Center, Ashkelon, Israel Faculty of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel Adjunct Professor Eastman Institute for Oral Health, University of Rochester, Rochester NY, USA

Siu-Kwan Ng, MBChB, FRCS.Ed (ORL), FHKCORL, FHKAM(ORL) Clinical Associate Professor (honorary) Department of Otorhinolaryngology, Head & Neck Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong

Piero Nicolai, MD

Professor and Chairman Department of Otorhinolaryngology – Head and Neck Surgery, University of Padua, Padua, Italy

Bert W. O’Malley Jr., MD

Professor and Chair Otorhinolaryngology – Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, Pennsylvania, United States

Peter Palhazi, MD

Anatomist Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary Plastic Surgery Resident University of Pecs, Pecs, Hungary

SuJung Park, MD

Physician Department of Medicine, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware, United States

Philippe Pasche, MD

Professor ORL Head & Neck Surgery, Centre Hospitalier, Universitaire Vaudois, Lausanne, Vaud, Switzerland

Snehal G. Patel, MD

Attending Surgeon Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Joseph D. Peterson, MD

Resident Physician Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States

List of Contributors

Roberto Polselli, Medicine PhD ENT Specialist ENT, INAIL, La Spezia, Italy

Pauline Pouzoulet

Doctor APHM, Marseille, France

Swati Pradhan-Bhatt, PhD

Jorge Rosa Santos

Professor of Surgery Chairman, Head and Neck Surgery Service, Portuguese Oncological Institute, Lisbon, Portugal

Yves Saban, MD, PHM

Chairman EAFPS Surgical Anatomy Facial Plastic Surgery, Private Practice, Nice, France

Director of Tissue Engineering Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, Delaware, United States Affiliated Assistant Professor Biological Sciences, University of Delaware, Newark, Delaware, United States Affiliated Assistant Professor Biomedical Engineering, University of Delaware, Newark, Delaware, United States Associate Director, Scientific Affairs Medical Affairs, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey, United States

Doron Sagiv, MD

Adam Raben, MD

Tevfik Sözen, MD

Chairman Radiation Oncology, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware, United States

Manuel Ramos-Casals, MD, PhD

Research Coordinator Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS Hospital Clinic, Barcelona, Spain

Christopher H. Rassekh, MD

Professor Otorhinolaryngology – Head & Neck Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Nathaniel Reeve, MD

Resident Department of Otolaryngology – Head & Neck Surgery, University of Nevada, Las Vegas School of Medicine, Las Vegas, Nevada, United States

Soledad Retamozo, MD, PhD

Research Assistant Rheumatology, Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Córdoba, Consejo Nacional de Investigaciones Científicas y Técnicas (INICSA-UNC-CONICET), Córdoba, Argentina Professor Epidemiology, Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Córdoba, Argentina

Otolaryngology, Head and Neck Surgery The Chaim Sheba Medical Center, Ramat Gan, Israel

Sumit Samant, MBBS, MS, DORL, FRACS

Otolaryngologist and Sleep Surgeon Otolaryngology and Head Neck Surgery, Auckland City Hospital, Auckland, New Zealand

Barry M. Schaitkin, MD

Professor Otolaryngology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States Associate Professor Department of Otolaryngology – Head & Neck Surgery, Hacettepe University, Ankara, Turkey

Padma Pradeepa Srinivasan, MD, PhD

Post-doctoral Research Scientist Biological Sciences, University of Delaware, Newark, Delaware, United States

Tobias Strenger, MD

Executive Senior Physician and Deputy Medical Director Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Augsburg, Augsburg, Germany

Shirley Y. Su, MBBS, FRACS

Associate Professor Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Kyung Tae, MD, PhD

Professor Department of Otolaryngology – Head and Neck Surgery, Hanyang University, Seoul, Republic of Korea

Yoav P. Talmi, MD, FACS

Vice Chairman and Chief, Head and Neck Service OTO-HNS, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

xv

xvi

List of Contributors

Michele Tomasoni, MD

Resident Department of Otorhinolaryngology – Head and Neck Surgery, University of Brescia, Brescia, Italy

Vincent Vander Poorten, MD, PhD, MSc

Gregory S. Weinstein, MD

Professor and Vice Chair Otorhinolaryngology – Head and Neck Surgery, The University of Pennsylvania, Philadelphia, Pennsylvania, United States

Clinical Head Otorhinolaryngology, Head and Neck Surgery, University Hospitals Leuven, Leuven, Belgium Full Professor and Section Head Department of Oncology, section Head and Neck Oncology, KU Leuven, Leuven, Belgium

Eddy WY Wong, MBChB

Rohan R. Walvekar, MD

Associate Consultant Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China

Associate Professor Otolaryngology Head Neck Surgery, LSU Health Sciences Center, New Orleans, Louisiana, United States

Jennifer R. Wang, MD, ScM

Clinical Fellow Head and Neck Surgery, MD Anderson Cancer Center, Houston, Texas, United States

Robert C. Wang, MD, FACS

Consultant Department of Otorhinolaryngology, Head & Neck Surgery, Prince of Wales Hospital, Hong Kong, China

Priscilla Ching-han Wong, MB ChB, MRCP, FHKCP, FHKAM

Peter Zbären, MD

Professor ENT Head and Neck Surgery, University Hospital, Bern, Switzerland

Joseph Zenga, MD

Professor and Chair Department of Otolaryngology – Head & Neck Surgery, UNLV School of Medicine, Las Vegas, Nevada, United States

Assistant Professor Otolaryngology and Communication Sciences, Division of Head and Neck Surgical Oncology and Reconstruction, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Randal S. Weber, MD

Johannes Zenk, MD

Professor Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Professor and Medical Director Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Augsburg, Augsburg, Germany

Acknowledgments I would like to thank all the chapter authors who committed their time, effort, and experience to this book. I would like to extend my appreciation to Elsevier Publisher’s development editor, Kim Benson, for her expertise, always prompt responses, and cheerfulness; Julie Taylor, project manager, Lyn Taylor, copy-editor, and MPS North America, LLC, illustrators. My appreciation also goes to Belinda Kuhn, the senior content strategist, for her astute insights. For Chapter 2, we thank George Murphy III for proofreading, and both Murphy III and Ashley Cornett for the staining on fetal human glands (Dr. Lombaert’s group). The

human material was obtained from the University of Washington, Seattle, WA, under IRB-approved protocols of the University of Washington and University of Michigan (Dr. Lombaert). This work was supported by 5R24HD000836 (University of Washington) and R01-DE027034 (Dr. Lombaert). We also thank Dr. Katja Dalkowski, MD, from Erlangen/Buckenhof for finishing of the illustrations in Chapter 28 and Mrs. Margareth Baldissara for the illustrations in Chapters 35.3 and 47.3.

xvii

Dedication I dedicate this book, Surgery of the Salivary Glands, to Dr. Eugene N. Myers. This book includes authors throughout the world, many who have been introduced to me by Dr. Myers. The international scope of this book is reflected by the worldwide inclusion and outreach of Dr. Myers, a cornerstone of his career. Dr. Myers, a Master of Head & Neck Surgery, has cared for thousands of patients with complex diseases. His academic accomplishments include over 300 manuscripts, 39 books, 153 chapters, over 500 lectures, 169 panels, 52 visiting professorships, 48 eponymous lectureships, and 7 federal grants. He is past President of the American Academy of Otolaryngology – Head & Neck Surgery, American Board of Otolaryngology, American Head & Neck Society, American Laryngological Society, and the Pan American Association of Otolaryngology – Head and Neck Surgery. Dr.

Myers’ stewardship of the Otolaryngology – Head & Neck Surgery Department at the University of Pittsburgh transformed the program into a world-renowned institution. This touches only on a small part of his career highlights. Dr. Myers defines integrity in his work and as a dedicated husband. He is the father of children who have become highly successful in their professions. His son, Jeffrey N. Myers, MD, PhD, is the Alando J. Ballantyne Distinguished Chair of Head and Neck Surgery at the University of Texas MD Anderson Cancer Center in Houston, Texas. His interests are diverse and range from the arts to personal fitness. He has an intangible quality of generosity that has touched so many people both here in the US and in so many countries abroad. Thank you, Gene, for your kindness to me, and I am certain I speak for countless others!

xviii

Video List

Video List

View in the eBook at www.ExpertConsult.com

Chapter 3.

Salivary Gland Imaging

Urban Geisthoff, Alberto Iaia, Brady Laughlin, Arpit Gandhi, and Hung Dam

Video 3.2.1 Video 3.2.2

Video 3.2.3

Adenocarcinoma of parotid with metastasis. Fine needle aspiration cytology (FNAC) of the pleomorphic adenoma shown in Fig. 3.2.10 using the long axis technique. Core bore biopsy (CBB) of the adenocarcinoma from Fig. 3.2.11 and Video 3.2.1 using the “long axis” technique.

Chapter 13. Sialendoscopy: Getting Started David M. Cognetti

Video 13.1 Video 13.2 Video 13.3

Endoscopic view of a floating stone ideal for purely endoscopic retrieval. Massive submandibular duct stone being removed from under the lingual nerve. Endoscopic view of ductal perforation.

Chapter 14. Types of Sialendoscopes and Accessories Francis Marchal, Frederic Faure, Michael Koch, Heinrich Iro, Mark McGurk and Rohan R. Walvekar

Video 14.4.1

xviii

Dilation of the submandibular papilla with disposable Cook Dilator Set.

Chapter 17. Sialendoscopy for Submandibular Duct Stone Extraction Monika E. Freiser and Barry M. Schaitkin

Video 17.1 Video 17.2 Video 17.3 Video 17.4 Video 17.5 Video 17.6 Video 17.7 Video 17.8

Free-floating stone. Dilation using Schaitkin dilators. Using Cook dilators to dilate Wharton’s papilla for sialendoscopy. Classic stenosis where a stone will typically become lodged. Troubleshooting poor visualization during sialendoscopy. Small stone basket retrieval. Stone basket retrieval with papillotomy. Using the basket even if the stone is too big to pass.

Chapter 20. Parotid Gland Proximal Stones, Combined Transoral and External Approach Urban Geisthoff

Video 20.1

Proximal Stensen’s duct stone.

Chapter 21. Interventional Sialendoscopy for Stones: Robotic Approaches Christopher H. Rassekh

Video 21.1 Video 21.2

TORS-Sialo approach. Sialo-TORS-Sialo approach.

Video List

Chapter 22. Laser Fragmentation of Salivary Stones

Chapter 33. Sialendoscopy for Radiation Sialadenitis

Robert A. Irvine

Hok Nam Li

Video 22.1

Video 22.2 Video 22.3

Floating stone in proximal Wharton’s duct requires laser fragmentation to remove because of more distal duct stenosis. Non palpable stone in hilum of Wharton’s duct requiring laser fragmentation. Laser fragmentation of Stensen’s duct stone, perforation of duct identified.

Video 33.1 Video 33.2 Video 33.3

Parotid duct is congested with pale ductal mucosa that has a mucus plug along the wall after radioactive iodine. Radiation sialadentis submandibular duct stenosis is improved after dilation. Parotid main duct stenosis with pale ductal mucosa, congested capillaries after RAI.

Chapter 26. Interventional Sialendoscopy: Complications

Chapter 37. Minimally Invasive Approaches – Extracapsular Dissection

Kevin Oshiro Do and M. Boyd Gillespie

Mark McGurk, Konstantinos Mantsopoulos and Heinrich Iro

Video 26.1

Video 37.1

Video 26.2

Duct wall trauma with bleeding and thermal burn after laser treatment of stone. Left floor of mouth ranula from sublingual gland trauma from previous attempt at stone removal.

Chapter 27. Parotid Gland Intraoral Dilation of Strictures Siu-Kwan Ng

Video 27.1 Video 27.2

Dilation of parotid ductal stricture by sialendoscopes. Dilation by angiocatheter sheath preloaded on 1.1 mm sialendoscope.

Chapter 31. Sialendoscopy for Stenosis: Complications Kevin Oshiro Do and M. Boyd Gillespie

Video 31.1 Video 31.2

Sialendoscopy for stenosis. Ductal perforation.

Chapter 32. Sialoendoscopy for Sjogren Syndrome Rohan R. Walvekar

Video 32.1

Sialendoscopic view of patients with SS with particulate debris being washed out of the salivary duct followed by an infusion of dilute Kenalog under vision.

Video 37.2 Video 37.3 Video 37.4

Extracapsular dissection technique for superficial tumor. Extracapsular dissection technique for deep tumor to facial nerve. Extracapsular dissection technique for tumor wedged between mandible and mastoid. Extracapsular dissection technique for a deep tumor.

Chapter 38. Retroauricular approach to the submandibular gland Eddy WY Wong and Jason YK Chan

Video 38.1

Retroauricular approach to the submandibular gland.

Chapter 42. Parapharyngeal Tumors Kyung Tae, Christopher H. Rassekh, Gregory S. Weinstein and Bert W. O’Malley Jr.

Video 42.2.1

xix

Transoral robotic surgery with prestyloid parapharyngeal space salivary gland tumor removal.

1 

Salivary Gland Anatomy YVES SABAN, TEVFIK SÖZEN, PETER PALHAZI, AND ROBERTO POLSELLI

Introduction The major salivary glands: parotid, submandibular, and sublingual glands, are paired and symmetric. In the oral cavity 700–900 minor salivary glands are found, the majority of which are located at the junction of the hard and soft palates. In this chapter, anatomic relations of the main salivary glands are shown in a layered fashion.

Parotid Gland Location The face (Fig. 1.1) is divided into two main compartments: the superficial compartments dedicated to mimicry and innervated by the facial nerve; and the deep visceral compartment innervated by the other cranial nerves. The superficial compartments are constituted by five layers: (1) skin; (2) subcutaneous tissue including fat and telaretinaculum cutis (Fig. 1.2); (3) submuscular aponeurotic system (SMAS) (Fig. 1.3); (4) deep facial space; (5) deep facial fascia. The parotid gland is in the visceral compartment (Fig. 1.4), under the deep facial fascia, i.e., deep to the 5th superficial compartment layer. It lies within a deep hollow, known as the parotid region. The parotid region is bounded by the: superiorly–zygomatic arch; anteriorly–masseter muscle and mandible bone (Fig. 1.5); posteriorly–external ear tragal cartilage and sternocleidomastoid muscle; inferiorly, the inferior parotid pole is between the ramus of the mandible and sternocleidomastoid muscle overlying the digastric muscle (Fig. 1.5). The deep aspect rests in the prestyloid compartment of the parapharyngeal space (Fig. 1.6).

Description Shape The parotid gland is a bilateral prismatic structure that looks like an inverted three-sided pyramid, which displays a lobular and irregular morphology (Fig. 1.1). It presents at four surfaces: superior, superficial, anteromedial, and posteromedial; separated by three borders: anterior, posterior, and medial. 2

Constitution Anatomically, the parotid can be divided into deep and superficial lobes, which are separated by the facial nerve. Approximately 80% of the parenchyma is located as superficial lobe.

Vascularization and Innervation Vasculature

Blood is supplied by the posterior auricular and superficial temporal arteries. They are both branches of the external carotid artery, which arise within the parotid gland (Figs. 1.7, 1.8). Venous drainage is achieved via the retromandibular vein. It is formed by unification of the superficial temporal and maxillary veins (Figs. 1.7, 1.8). Innervation

The parotid gland receives sensory and autonomic innervation. The autonomic innervation controls the rate of saliva production. Sensory innervation is supplied by the auriculotemporal nerve (gland) and the great auricular nerve. The parasympathetic innervation to the parotid gland has a complex path. It begins with the glossopharyngeal nerve (cranial nerve IX). This nerve synapses with the otic ganglion (a collection of neuronal cell bodies). The auriculotemporal nerve then carries parasympathetic fibers from the otic ganglion to the parotid gland. Parasympathetic stimulation causes an increase in saliva production. Sympathetic innervation originates from the superior cervical ganglion, part of the paravertebral chain. Fibers from this ganglion travel along the external carotid artery to reach the parotid gland. Increased activity of the sympathetic nervous system inhibits saliva secretion, via vasoconstriction.

Anatomic Relationships The Parotid Bed The gland is embedded in its capsule and the parotidmasseteric fascia (layer 5), which attaches to the root of the zygoma and continues as a thin fascia that can be separated from tragal and conchal cartilage by blunt dissection. A

CHAPTER 1  Salivary Gland Anatomy

Keywords Anatomy Parotid Gland Submandibular Gland Sublingual Gland

2.e1

CHAPTER 1  Salivary Gland Anatomy

• Fig. 1.1

 

The parotid gland has a lobular morphology.

• Fig. 1.3

 

3

The submuscular aponeurotic system (SMAS) layer.

• Fig. 1.4

  The parotid gland with Stensen’s duct (green marker). Inferior to Stensen’s duct and anterior to the parotid gland is the masseter muscle.

• Fig. 1.2

 

The superficial surface, subcutaneous tissue, and fat.

thick fascia is attached to the periosteum of the mastoid process and tympano-mastoid suture, the so-called Loré’s fascia. A thick fascia at the antero–inferior tip of the parotid separates it from the submandibular gland. Anteriorly, this parotid-masseteric fascia extends to the buccinator aponeurosis, embedding Stensen’s duct until its penetration through the buccinator muscle (Fig. 1.4). The Facial Nerve (Cranial Nerve VII)

The extratemporal segment exits the skull base through the stylomastoid foramen posterolateral to the styloid process

and anteromedial to the mastoid process. The facial nerve as it enters the parotid forms the pes anserinus (Figs. 1.7–1.10). The upper divisions include the temporal–facial branches and the lower divisions include the cervicofacial branches. These branches innervate the muscles of facial expression. The anatomic landmarks identifying the facial nerve in antegrade fashion are: (1) the tympano-mastoid suture is the direction landmark, as it shows the direction of the stylomastoid foramen, located ~2 mm superior to the facial nerve; (2) the posterior belly of the digastric is the depth landmark, located 1 cm inferior to the facial nerve (Fig. 1.5); (3) the tragal cartilage “pointer” indicates the location

4 se c t i o n 1 4

Foundational Content

• Fig. 1.5

  The parotid gland is removed: anteriorly, the mandible and masseter muscle; posteriorly, the external auditory canal and the retracted sternocleidomastoid muscle; the inferior pole of the parotid overlies the digastric muscle.

• Fig. 1.7

  The parotid gland is retracted posteriorly, with blood supply to the parotid gland from the postauricular artery and superficial temporal artery; both branches of the external carotid artery. The retromandibular vein joins the external jugular vein via the posterior facial vein. The retromandibular facial vein can join the anterior facial vein that joins the internal jugular vein.

Retromandibular Vein

The retromandibular vein is formed within the parotid gland by the convergence of the superficial temporal and maxillary veins. It is one of the major structures responsible for venous drainage of the face. The retromandibular vein joins the external jugular vein via the posterior facial vein (Fig. 1.7). It can give off an anterior facial vein that joins the internal jugular vein, which is just deep to the marginal mandibular nerve. External Carotid Artery and Branches

• Fig. 1.6  The parapharyngeal space (the parotid gland is removed) includes the visualized external carotid artery that courses medial to the parotid gland. The external carotid artery divides into two terminal branches: the maxillary artery and the superficial temporal artery. The superficial temporal artery gives off the transverse facial artery. Anteriorly and inferiorly the facial artery is visualized.

of the facial nerve exit as it is located ~8 mm cranial to the foramen; (4) the styloid process is not considered as a surgical landmark as it is deeper and cephalic to the facial nerve; however, by digital palpation, it constitutes a helpful landmark.

The external carotid artery (ECA) courses medial to the parotid gland. Within the gland, the ECA gives rise to the posterior auricular artery. The ECA then divides into its two terminal branches: the maxillary artery and the superficial temporal artery. The superficial temporal artery also gives off the transverse facial artery (Figs. 1.6–1.8). Great Auricular Nerve

The great auricular nerve is a superficial branch of the cervical plexus and contributed to by fibers from C2 and C3 spinal nerves. It leaves the cervical plexus at the posterior border of sternocleidomastoid muscle (Erb’s point). It courses superiorly, dividing into anterior and posterior branches. The posterior branch supplies the skin over the mastoid process and lower external ear and anterior branch

CHAPTER 1  Salivary Gland Anatomy

5

• Fig. 1.10  The parotid gland. The facial nerve branches anterior to the parotid gland (black markers).

• Fig. 1.8  The external carotid artery gives rise to the maxillary artery, postauricular artery, and superficial temporal artery, that gives rise to the transverse facial artery. The facial nerve, pes anserinus, and peripheral branches are noted superficial to the external carotid artery. The tympano-mastoid suture can be visualized just superior to the pes anserinus of the facial nerve.

• Fig. 1.11

 

Great auricular nerve, anterior and posterior branches.

sends a small twig into the substance of the parotid gland and connects to the facial nerve. The posterior branch can often be saved during parotid surgery, potentially reducing auricular numbness, as shown in Fig. 1.11.

Submandibular Gland • Fig. 1.9  The facial nerve is superficial to the external carotid artery. The pes anserinus gives rise to temporal, orbital, buccal, marginal mandibularis, and cervical branches of the facial nerve.

The submandibular gland (SMG) is one of the major salivary glands. Submandibular glands are bilateral and are located in the anterior part of the submandibular triangle, which is bordered by: superiorly, the inferior body of the mandible;

6 se c t i o n 1 6

Foundational Content

anteriorly, the anterior belly of the digastric muscle; posteriorly, the posterior belly of the digastric muscle; and medially, by the base by the hyoglossus muscle. Approximately 70% of total saliva is produced by submandibular glands. A submandibular gland weighs 7–12 g. In this section, the location, vasculature, and innervation of the submandibular glands are discussed, and the relevant clinical correlations are demonstrated.

Location Deep to the 5th soft tissues layer, embedded in a division of the deep cervical fascia (layer 5), the SMG is located under the mandible bone, bordered by the digastric and mylohyoid muscles and corresponds to the lateral mouth floor. SMGs are located at each side of the neck in the submandibular triangle, placed deep to the platysma muscle and anterior to the sternocleidomastoid muscle. Morphologically, the submandibular glands are a pair of elongated, flattened hooks, which have two sets of lobes: superficial and deep. The positioning of these lobes is in relation to the mylohyoid muscle, which the gland hooks around. The superficial lobe comprises the greater portion of the gland and lies partially inferior to the posterior half of the mandible, within an impression on its medial aspect (the submandibular fossa). It is situated outside the boundaries of the oral cavity. The deep lobe hooks around the posterior margin of mylohyoid muscle through a triangular aperture to enter the oral cavity proper. It lies on the lateral surface of the hyoglossus, lateral to the root of the tongue.

• Fig. 1.12

 

Skin over the submandibular gland.

Description The SMG can be compared with a triangular almond, where the anterior border is divided by the mylohyoid muscle in two lobes: superficial and deep. Secretions from the submandibular glands travel into the oral cavity via the submandibular duct (Wharton’s duct). This is approximately 5 cm in length and emerges anteromedially from the deep lobe of the gland between the mylohyoid, hypoglossus, and genioglossus muscles. The duct ascends on its course to open as one or two orifices on a small sublingual papilla (caruncle) at the base of the lingual frenulum bilaterally.

Anatomic Relations Submandibular Bed and Deep Cervical Fascia The lateral surface corresponds to the cervical soft tissues and to the surgical access. Skin (layer 1) (Fig. 1.12) and subcutaneous tissue (layer 2) (Fig. 1.13) consist of subcutaneous fat and tela-retinaculum cutis; the platysma muscle forms the SMAS for the SMG (layer 3) (Figs. 1.14, 1.15). It is divided into two main portions: the anterior mentalis portion inserted onto the mandible caudal border, and the lateral labialis portion that passes over the mandible and connects to the depressor anguli oris muscle and the

• Fig. 1.13

 

Subcutaneous tissue below the skin.

modiolus. The subSMAS plane is an areolar plane, easy to undermine, in which the marginal mandibularis branch of the facial nerve is running (Fig. 1.16). The ramus marginalis mandibularis is running over the facial vascular pedicle – facial artery and facial vein that are still deep to the 5th layer (Fig. 1.17). In this layer are also running the branches of the cervical nerves, mostly the transverse branch that anastomoses with the cervical branch of the facial nerve (Fig. 1.18). In the submandibular gland bed, the facial artery courses deeply between the posterior belly of digastric muscle and stylohyoid muscle. It enters to the gland capsule by the

CHAPTER 1  Salivary Gland Anatomy

• Fig. 1.14

 

The platysma muscle.

7

• Fig. 1.16  The marginal mandibularis branch of the facial nerve runs in the subSMAS plane.

•

Fig. 1.15  The SMAS layer formed by the platysma muscle is elevated.

• Fig. 1.17

posterior aspect of the gland and traverses through the gland parenchyma (Fig. 1.19). It is a branch of the ECA and runs from deep to the SMG posterior border and to the mandibular bony notch, where it crosses and becomes superficial over the mandible bone lateral surface (Fig. 1.20). The facial artery is closely attached to the SMG to which it gives 3–5 branches. It gives off the submental artery. In the dissection presented in Fig. 1.21, the submental artery is also providing blood supply to the SMG.

Facial Vein

  The marginal mandibularis branch of the facial nerve (black marker) is superficial to the facial artery and vein. The facial vein is marked in blue. The facial artery courses anterior to the facial vein.

Venous drainage is through the submental veins, which drain into the facial vein and then the internal jugular vein. The facial vein lies superficial to the gland and to the artery; it does not enter the parenchyma. Lingual Nerve

The lingual nerve is one of the main anatomic danger points during surgery. It provides secretory innervation to the

8 se c t i o n 1 8

Foundational Content

• Fig. 1.18  Marginal mandibularis branch of facial nerve (black markers) and inferior to it, branches of the cervical branch of the facial nerve, the transverse branches of facial nerve (black markers). The facial vein is shown with blue markers.

• Fig. 1.20

• Fig. 1.19  Submandibular gland partially removed. The marginal mandibularis branch of facial nerve (black marker) and facial vein (blue markers). The hypoglossal nerve is deep to the anterior belly of the digastric muscle.

• Fig. 1.21

  The hypoglossal nerve runs deep to the anterior belly of the digastric muscle and superficial to the hyoglossus muscle. The carotid artery is posterior to the hypoglossal nerve.

  The course of the facial artery and the submental artery. The submandibular gland is retracted inferiorly.

CHAPTER 1  Salivary Gland Anatomy

9

Hypoglossal Nerve The hypoglossal nerve provides motor function to the tongue and it lies deep to the submandibular gland and runs superficial to hyoglossus muscle, protected by a tiny fascia deep to the digastric muscle. It lies medial to the common tendon of the digastric muscle. At this point, just posterior to the hypoglossal nerve, the facial artery traverses through the gland. During ligation of the facial artery, effort should be given not to injure the hypoglossal nerve.

Facial Nerve

• Fig. 1.22

  The lingual nerve just above the digastric tendon is visualized by retraction of the hyoglossus muscle. The submandibular gland is retracted inferiorly.

The marginal mandibular branch of the facial nerve exits the anterior–inferior portion of the parotid gland at the angle of the mandible and transverses the margin of the mandible in the plane between platysma and the investing layer of deep cervical fascia curving down toward and sometimes inferior to the submandibular gland (Figs. 1.17, 1.18). In most cases, the nerve continues forward above the inferior border of the mandible deep to the masseteric fascia. It crosses the anterior facial artery to enter the buccal space, where it provides branches to the depressor anguli oris, the depressor labii inferioris, and mentalis muscles. Surgical Implications

SMG and sensory innervation to the tongue. Its injury causes hemi-tongue anesthesia (Fig. 1.22).

Lymph Nodes Four groups of lymph nodes can be described – from anterior to posterior: preglandular, prevascular, retrovascular, and retroglandular.

Relationship With Nerves Both the submandibular gland and duct share an intimate anatomic relationship with three main nerves: the lingual nerve, hypoglossal nerve, and facial nerve (marginal mandibular branch). The courses of these nerves are briefly outlined next.

Lingual Nerve The lingual nerve is a sensory nerve that traverses the floor of the mouth. During submandibular gland surgery, it attaches to the deep superior surface of the submandibular gland via the submandibular ganglion (Fig. 1.22). Starting lateral to the submandibular duct, this nerve courses anteromedially by looping beneath the duct and then terminating as several medial branches. The terminal branches ascend on the external and superior surface of the hyoglossus muscle to provide general somatic afferent innervation to the mucus membrane of the anterior two-thirds of the tongue. During the ligation of Wharton’s duct in transcervical submandibular gland excision surgery, the duct crosses deep to the lingual nerve; it is important to avoid a nerve injury.

Dissection between platysma and deep cervical fascia may cause injury risk to the marginal mandibular nerve during surgical procedures such as submandibular gland excision or rhytidectomy. In transcervical submandibular gland excision the precautions start at the skin incision. An incision is made 4 cm inferior to the inferior border of the mandible and parallel to the neutral skin lines. The easiest way to protect the nerve is to open the SMG capsule and to proceed deep to this capsule through a subcapsular dissection. This subcapsular dissection also protects the hypoglossal nerve as it leaves the deep fascia overlying this nerve. Deep to platysma, the marginal mandibular nerve can be identified. Care must be taken by the assistant not to pull too vigorously upward, as that could result in a stretch injury. It is feasible to preserve marginal mandibular nerve by ligation of the posterior facial vein and reflect the investing fascia superiorly upward over the mandible.

Sublingual Gland and Wharton’s Submandibular Salivary Duct The sublingual glands are the smallest of the three paired major salivary glands and the most deeply situated. Both glands contribute to only 3–5% of overall salivary volume, producing mixed secretions which are predominately mucous in nature.

Location The sublingual glands are almond-shaped (ovoid) and lie on the floor of the oral cavity proper (Figs. 1.23, 1.24).

Foundational Content

10 se c t i o n 1 10

• Fig. 1.23

  The floor of the mouth with sublingual glands below the mucosal surface.

• Fig. 1.25

 

The submandibular duct passes superficial to the lingual

nerve.

• Fig. 1.24

 

The lingual gland exposed submucosally.

They are situated under the tongue, bordered laterally by the mandible and medially by genioglossus muscle. The glands form a shallow groove on the medial surface of the mandible known as the sublingual fossa. Medially, the submandibular duct and its lingual nerve relation pass immediately next to the sublingual glands between genioglossus (Figs. 1.25–1.28). Both sublingual glands unite anteriorly and form a single mass through a horseshoe configuration around the lingual frenulum. The superior aspect of this U-shape forms an elevated, elongated crest of mucous membrane called the sublingual fold (plica sublingularis). Each sublingual fold extends from a posterolateral position and traverses anteriorly to join the sublingual papillae at the midline bilateral to the lingual frenulum. Secretions drain into the oral cavity by minor sublingual ducts (of Rivinus), of which there are 8–20 excretory ducts per gland, each opening out onto the sublingual folds. Through anatomic variance, a major sublingual duct (of Bartholin) can be present in some people. This large accessory duct arises from the inferior aspect of the sublingual gland and then adheres to the passing submandibular duct on its medial side. Drainage then follows the submandibular duct out through the sublingual papillae.

• Fig. 1.26  Anterior mandibulotomy demonstrating the relationship of the sublingual gland to the lingual nerve. The mylohyoid is de-inserted.

Vasculature Blood supply is via the sublingual and submental arteries, which arise from the lingual and facial arteries respectively; both from the ECA.

• Fig. 1.27

  A closer view, demonstrating the relationship of the sublingual gland to the lingual nerve.

CHAPTER 1  Salivary Gland Anatomy

11

Venous drainage is through the sublingual and submental veins, which drain into the lingual and facial veins, respectively; both then draining into the internal jugular vein.

Innervation The sublingual glands receive autonomic innervation through parasympathetic and sympathetic fibers, which directly and indirectly regulate salivary secretions, respectively. Their innervation is the same as that of the submandibular glands.

• Fig. 1.28  The relationship of lingual nerve to hypoglossal nerve after the lateral wall has been removed.

2 

Salivary Gland Embryology, Physiology, and Stem Cell Complexity HARLEEN K. ATHWAL AND ISABELLE M. A. LOMBAERT

Introduction Salivary glands play an essential role in maintaining oral homeostasis by secreting saliva under unstimulated (resting) and stimulated (neuronal-regulated) conditions. For example, saliva functions as a barrier for bacterial infestations due to its antibacterial composition. It also plays the essential roles of oral lubricant, protecting tooth enamel, providing enzymes for digestion of food, and is an indicator of overall health.1 Unfortunately, cancer treatments (radiation and/or chemotherapy), certain drug medications, and/ or immune system disorders, such as Sjögren syndrome, can all lead to severe hyposalivation.2 Radiation in particular propagates a multitude of chronic oral health-related ailments such as xerostomia or dry mouth, which entails difficulty in swallowing, increased risk for dental caries, oral fungal infections, and overall poor quality of life.3 Combatting these conditions and/or syndromes requires a deep understanding of factors and mechanisms regulating glandular physiology, development, homeostatic maintenance and/or repair by stem/progenitor cells, which are described below.

Salivary Gland Biochemistry and Physiology Both humans and mice harbor three major salivary glands: submandibular (SMG), sublingual (SLG), and parotid (PAR) glands, and numerous minor salivary glands (see Chapter 1). Unlike the human situation (Fig. 2.1A), the SLG and SMG in the rodent model are found together in the anterior space of the neck, encapsulated with common fascia (Fig. 2.1B). Rodent SMGs are triangular in shape and the round-shaped SLGs are located on the latero-rostral one fourth of the SMG.4 Rodent PAR glands are found embedded in subcutaneous adipose tissue posterior inferiorly to the ear, bordering the submandibular gland (Fig. 2.1B).5 While minor salivary glands in mice have not been well described, there are seven subtypes of human minor salivary glands: the buccal, incisive, labial, anterior and posterior 12

lingual, molar, and palatine glands. These minor salivary glands are labeled based on their anatomic location in the oral cavity.6,7 In both the human and murine situation, the three major salivary glands are responsible for producing >90% of total saliva.8 Less than 10% of saliva is secreted from mucosal minor salivary glands. Saliva secreted from the minor salivary glands is mostly mucosal in content, which serves mainly as a protective lubricant.9 More specifically, saliva from minor salivary glands, except the von Ebner glands, plays a crucial role in dental biofilm formation, which coats the oral and tooth enamel surfaces. Cumulative saliva secretion from major salivary glands is unique in composition per gland.9,10 SMG, SLG, and PAR glands are composed of acinar cells that are secretory units responsible for serous or mucous saliva production. Every acinar cell produces saliva composed of proteins, enzymes, ions, and water, and secretes it into the central lumen.5,6 The serous and mucous acini (cluster of acinar cells) can be characterized based on their secretion of specific types of granules. Mucous-rich secretory acini contain granules with large amounts of mucintype glycoproteins, which compose the viscous saliva. Serous-rich acini contain granules high in ions, water, amylases, secretory immunoglobulins, and proline-rich proteins, but very low levels of mucin-type glycoproteins.5 As such, both types of acini contribute differently to the overall functions of saliva. Mucous rich saliva acts more as a lubricant and protective barrier for the oral cavity. In contrast, serous saliva mainly aids in food digestion.11 Histologically, the human PAR glands are exclusively composed of serous acini. In contrast, the SLGs are predominantly made of mucous acini. The SMGs contain a mix of serous and mucous acini where variable levels of serous acini may be dominating. Also part of the epithelial compartment are contractile myoepithelial cells, which surround the acini and the ducts that directly connect to the acini (Fig. 2.2).12 Both murine and human salivary glands comprise of three major ductal structures: intercalated (ID), striated (SD), and excretory ducts (ED). Ducts play a large role in modifying saliva before it is secreted to the oral cavity. IDs are connected

CHAPTER 2  Salivary Gland Embryology, Physiology, and Stem Cell Complexity

Abstract

Keywords

Salivary glands are exocrine organs that produce and secrete saliva into the oral cavity. Through the use of rodent models, the cellular and molecular processes leading to the development and functionality of secretory branching organs, such as the salivary glands, have been studied in great detail. Gland ontogenesis, development, and maturation are regulated by a series of signaling mechanisms and cellular interactions between the mesenchyme, nerves, blood vessels, and epithelium. Several recent studies have reported the presence of epithelial stem/progenitor cells, which respond to the surrounding environment to expand themselves and/or differentiate into specific cell types of functional salivaproducing gland. This type of research has significantly expanded our understanding of how organs develop and function. It also enhanced the translational concepts of manipulating signaling pathways and/or various cell types in the gland to aid patients who suffer from debilitating diseases, conditions, or syndromes that lead to loss in saliva production. While rodent models are used to analyze these processes, multiple labs have highlighted the comparison of gene expression, cell surface markers, stem cell markers, and protein expression to the human system. Here we summarize and compare our current knowledge on the embryology and physiology of the mouse and human salivary glands, and how stem/progenitor cell populations may contribute to these processes.

Salivary Gland Stem Cell Embryology Physiology Biochemistry

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CHAPTER 2  Salivary Gland Embryology, Physiology, and Stem Cell Complexity

Parotid Sublingual Submandibular

B

Stensen’s duct Wharton’s duct Parotid Sublingual

• Fig. 2.1

  (A) Representation of human major salivary gland anatomic localization. (B) Representation of mouse major salivary gland anatomic localization.

Submandibular

A

Myoepithelial cells ID

SD Mucous acini

A

Basal

Serous demilunes

K+

Na+ K+ Cl−

K+ channel Ca

Ca2+

Na+

+

+

2+

−

Na K Cl

K+

K+

Cl−

Acetylcholine M3 receptor Duct cell

Ca2+ Ca2+ Na+ K+

Apical tight junction

K+

Cl−

H2O

K+ Cl−

Na+ K+

Cl−

Lumen

Na+ NaCl

Cl− K+ and HCO3− secretion

H2O

Lumen

B • Fig. 2.2

C

(A) Structural schematic of adult salivary gland cells. (B) Schematic of physiologic regulation of the saliva flow and ion exchange in the acinar cells. (C) Schematic of ion exchange in the ductal cells.  

13

14 se c t i o n 1 14

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directly to acini from which they receive primary saliva. Saliva is then pushed to the lumen of SDs for ion reabsorption and then transported to the EDs for excretion to the oral cavity via an additional connecting duct (Fig. 2.2A).13 More in-depth histologic information can be found in Chapter 5. Initial saliva by acini is generated by the transmission of water via the basement membrane and aquaporin-5 water channels.14 This electrochemical gradient is maintained by the adenosine-triphosphatase (ATPase) and sodiumpotassium pumps in the basolateral membrane. In brief, the acinar cells are concentrated in K+ and Cl− above the electrochemical equilibrium. Autonomic neuronal stimulation opens Ca+2 sensitive ion channels, allowing permeability of potassium ions to the basolateral membrane and interstitium, as well as chloride ions into the lumen of acini. The negative charge created by the Cl− draws Na+ through the tight junctions between acinar cells to the lumen. As a result of NaCl accumulation in the lumen, water moves to the lumen via osmotic pressure (Fig. 2.2B). While this is a brief and more commonly accepted method of ion transfer in the acinar cells, a more detailed description on additional exchange mechanisms has been previously described.15 Apart from the electrochemical gradient that allows for transport of saliva, myoepithelial cells also contribute in an indirect manner. Myoepithelial cells surrounding the acini can contract to push the saliva out, and aid in the movement of saliva to the connected ducts where the saliva gets modified.12 IDs contain microvilli projections facing the lumen where it aids in initiating the absorption of a small portion of chloride ions out of the acinar product, thereby changing the electrochemical gradient of saliva. The second intraglandular duct, the striated duct, functions in regulating the secretion and absorption of electrolytes. In a bidirectional way, it absorbs sodium chloride (NaCl) and secretes potassium (K+) and bicarbonate (HCO3−). Saliva is then transported to the lumen of excretory ducts, where there is a small contribution to the ion exchange (Fig. 2.2C).4,13 This entire process makes the initial isotonic saliva, which contains similar ionic concentrations as plasma, into a hypotonic fluid before it enters the mouth. The latter is established through three major ducts: Bartholin’s, Stensen’s, and Wharton’s from the SLG, PAR, and SMG, respectively.13 It is worth noting that ducts are water-impermeable, thereby limiting fluid release in injured states, such as radiation-induced xerostomia, in which acini bundles are lost and several ducts remain. A current gene therapy clinical trial with water-channel aquaporin-1 gene (AQP-1) is making segue into delivering long-term water release from remaining ducts in irradiated glands. Rodent glands are similar to human glands in terms of their histologic appearance and physiologic functions. An exception to this is the SMG, which is predominantly comprised of serous acini. Also, an additional granular convoluted tubule (GCT) is found between the ID and SD in rodent glands, which secretes growth factors into the saliva. It is important to note, for research purposes, that sexual

differences occur in rodents where GCTs are more abundant in males compared with females. Such dimorphism has not been reported for the human system.13,16 While cellular entities play unique roles in manipulating and excreting saliva, regulation of saliva flow and composition is mediated by the autonomic nervous system. Both sympathetic and parasympathetic innervate the salivary glands with the parasympathetic system playing a dominant role. In both human and rodent glands, it was noted that the parasympathetic nerves are present at gland ontogenesis, while the sympathetic nervous system innervates the gland later when branching, cell differentiation, and lumen formation has been initiated. Hence, stimulus for glandular development, growth, vasodilation, and saliva formation and flow are mediated by parasympathetic innervation. In contrast, exocytosis, protein composition, and secretion are dependent on sympathetic innervation. While these systems have unique roles, both can have additive and synergistic effects on fluid secretion by contraction of myoepithelial cells. In brief, saliva flow is regulated by neurotransmitter receptors on the basolateral membranes of the acini and ducts. More specifically, neurotransmitter acetylcholine binds to the muscarinic cholinergic M3 receptors. This leads to the activation and binding of heterotrimeric guanine nucleotide-binding proteins. The ultimate product is formation of inositol triphosphate and the release of a second messenger, Ca+2. Ca+2 plays an intimate role in saliva and ion flow to the ductal lumen.13 Additional movement of Ca+2 is induced by norepinephrine binding to alpha-receptors. While Ca+2 release via acetylcholine parasympathetic stimulation induces saliva flow, beta-adrenergic sympathetic stimulation from binding of norepinephrine to beta-adrenergic receptors mediates saliva composition and exocytosis. In brief, it activates the second messenger, cAMP, leading to exocytosis of proteins such as amylases and mucins.13 The sympathetic nerves also align with the blood vessels to induce vasoconstriction, although this does not influence the saliva reflex.

Salivary Gland Embryogenesis Ontogenesis of all glands is initiated by interactions between epithelial cells from the oral lining and the surrounding environment (Table 2.1). In short, a thickening of the oral epithelium (termed “bud”) in the cheek towards the ear initiates the development of the PAR at 5–6 weeks of intrauterine gestation.17 In humans, this is the first gland to initiate and will form the largest one (25–30 g). Canalization of the PAR is completed by gestational age of 6 months. The ontogenesis of the second largest gland, the SMG (7–15 g), starts at gestational weeks 6–7.17 Hereto, epithelial outgrowth into the mesenchyme starts at the floor of the mouth where it rapidly proliferates to form numerous branching structures.18 Lastly, epithelial thickening for the SLG (3 g weight in adulthood) is initiated at gestational week 7–8 in the linguogingival groove, leading to individual canals from the small epithelial thickenings.17,19 Minor glands develop

CHAPTER 2  Salivary Gland Embryology, Physiology, and Stem Cell Complexity

later around the 3rd month of gestation. The time frame for gland ontogenesis in rodents is different.19 For example, mouse SMG initiates first around embryonic day (E)11.5, and the SLG and PAR follow later at E12.5 and E13.5.20,21 Interestingly, it is still debatable whether the epithelia of the salivary glands are ectodermal or endodermal in origin. At least in the mouse model, research revealed that the major glands are not derived from the ectoderm.22 In contrast, some minor mucous glands of the tongue and palate were fully or partially ectodermal-derived, respectively. After ontogenesis, both human and rodent glands follow a similar developmental pattern (Fig. 2.3). The epithelial bud cells rapidly proliferate. Several phases of branching evoked by repetitive bud clefting and ductal elongation subsequently lead to the characteristic tree-like structure of the gland. Lumen formation starts when cells in the center of the duct undergo cell death, and this has been observed in rodents as early as the 4–5 bud stage (E12.5). After the branching morphogenesis phase (E15–16 in mice), the first pro-acinar cells and pro-myoepithelial cells initiate. In this phase, the ductal lumen still expands and has become polarized.22 Subsequently, the glands keep increasing to their full adult size. At least in rodents, an early postnatal development still occurs where pro-acinar cells become fully functioning acini by secreting their full plethora of enzymes and proteins.21 The authors refer to several reviews that described paracrine factors, growth factors, and signaling mechanisms regulating this gland development in detail.20,21,23,24 The chapter will now briefly touch base on a few of them to explain the major interactions between the epithelial stem/progenitors and their environment. TABLE Initiation Day of the Major Salivary Glands 2.1  in Mouse and Human Species

Type of Gland

Mouse (Embryonic Day, E)

Human (Week)

Submandibular

E11.5

6–7

Sublingual

E12

7–8

Parotid

E13

5–6

Salivary Gland Stem/Progenitor Cells Epithelial stem/progenitor cells are essential for gland ontology, development, and homeostasis. Stem cells are defined by their ability to self-renew and differentiate into specialized cell types. In contrast, a progenitor cell is already more defined but still harbors some self-renewing and differentiation potential. In recent years, it has been found that multiple salivary gland epithelial stem/progenitor cells are present, and that cells can initiate a stem/progenitor celllike plasticity under several environmental changes and/or injury responses.25–27 As such, the authors will refer to all those cells as stem/progenitor cells. For fetal development, the majority of information on stem/progenitor cells has been revealed via mouse genetic lineage tracings. Herein, a genetically fluorescent-labeled cell of interest is followed and all its progeny can be determined at any given time. Stem cells and signaling mechanisms that regulate embryonic epithelial outgrowth and differentiation have been extensively described before.8,20,26,28–31 Briefly, epithelial SMG cells expressing cytokeratin 5 (K5), K14, ASCL3 and/or KIT (CD117) show indications of stem/progenitor cell properties.25,31 The KIT cells, located in the buds, require surrounding mesenchymal cells for their expansion and maintenance as they rely on their fibroblast growth factor and stem cell factor production. Inquisitively, a subpopulation of the initial KIT+ cells, which are located in the buds, express transcription factor SOX10 and are highly proliferative.31 In these early stages, lineage tracing of the SOX10 cells revealed that they are multipotent as they contributed to all epithelial cell lineages in adulthood (myoepithelial, ductal, and acinar cells). Also in the human fetal SMG, we found the presence of KIT+ bud cells expressing SOX10 (Fig. 2.4A). Fetal mouse glands have also been instrumental in defining the interactions between epithelial stem/progenitor cells and the environment. Recent studies have highlighted the significance of blood vessels and innervation to gland development and stem/progenitor cell maintenance. Parasympathetic innervation is essential for the maintenance of fetal K5+ cells and their differentiation into luminal duct cells.29 Additionally, vasoactive intestinal peptide (VIP) from parasympathetic neurons regulate tubule-genesis via

Blood vessels Mesenchyme Epithelium Neuronal cells

Endbud

E11

E12

• Fig. 2.3

 

15

E13–14

Salivary gland schematic of mouse fetal gland development.

Adult

16 se c t i o n 1 16

Foundational Content

E-CADHERIN KIT SOX10

A

E-CADHERIN TUBB3

B • Fig. 2.4  (A) SOX10 is expressed in a subpopulation of KIT+ cells in the human embryonic 110-day submandibular salivary glands. (B) Neuronal cells, as marked by TUBB3 (Tubulin3), envelope the 67-dayold embryonic submandibular salivary gland buds. E-cadherin outlines the epithelial tissue of the developing gland (scale bar: 20 µm).

ductal expansion and lumen formation.32 On the other hand, epithelial end-bud progenitor cells, expressing the receptor KIT (CD117), are enriched in secreting neurotropic factor neurturin (NRTN), which tightly regulates neuronal survival and axonal growth towards the buds.33 At least in humans, fetal SMGs are also innervated and surrounding the KIT+ buds, with comparative adult neuronal patterning with mouse, and thus a similar mechanism may be present (Figs. 2.4B, 2.5). Recent studies have also shown the necessity of endothelial cells in regulation of salivary gland epithelial patterning. Loss of CD31+ endothelial cells through inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) resulted in loss of KIT+ bud cells, thus playing an important role in KIT cell maintenance. Moreover, multiple studies have elucidated the crucial role of endothelial cells in cell fate, organ development and patterning.34,35 Thus, the cumulative effects of parasympathetic innervation, mesenchymal and endothelial cells play a crucial development in organ development and stem/ progenitor cell maintenance. To date, little information is known about the communication between the sympathetic nerves and surrounding cell types during development. Questions remain whether the findings in fetal mouse glands are completely identical in human fetal glands. While epithelial stem/progenitor cells in fetal glands provide tremendous information on how they interact with the environment and how they differentiate, the ultimate goal, therapeutic potential of stem/progenitor cells lies within adult glands. Adult stem/progenitor cells can be used as a therapeutic tool to replace the pool of acini after irradiation and/or to replenish the loss of reservoir stem/

progenitor cells. Thus far, epithelial cells from the mouse submandibular gland with surface receptors EPCAM/KIT, CD133, CD49f, CD24, and/or CD29 have been able to successfully restore irradiated salivary submandibular gland tissue in rodents.36–41 There is also evidence that human KIT cells can restore irradiated mouse submandibular glands.41 However, recent studies also indicated that adult mouse acinar cells, expressing MIST1, have self-renewing capacities that can contribute to new acinar formation.28 Moreover, lineage tracing and cell ablation via irradiation has highlighted the significance of SOX2+ cells in establishing acini and SLG repair.26,42 Ultimately, it remains to be seen whether similar results can be found in humans. Alternatively, adult stem/progenitor cells can be used in bioengineered glands that can aid in repair and/or replace surgically removed glands. These approaches are discussed into more detail in Chapter 53.

KEY POINTS • Multiple groups are currently working on validating and applying findings of rodent studies in human glands. These studies are largely promoting the translation of growth factors, stem/progenitor cells, bio-engineered glands, and gene therapy for clinical settings. • Efficient cell delivery, vector gene infusion, localized delivery, and safe diffusion is currently being explored. • Targets of interest are being classified and validated for functionality and safety for regenerative therapies. • The overall goal is to utilize current scientific knowledge of fetal and adult cell biology and physiology to enhance personalized or combinatorial regenerative therapies.

CHAPTER 2  Salivary Gland Embryology, Physiology, and Stem Cell Complexity

17

KRT18 TUBB3

• Fig. 2.5  TUBB3+ neuronal cells are found surrounding the acini and ducts, which are outlined by epithelial KRT18 marker, in both adult mouse and adult human submandibular salivary glands.

References 1. Carlén A, Olsson J, Ramberg P. Saliva mediated adherence, aggregation and prevalence in dental plaque of streptococcus mutans, streptococcus sanguis and actinomyces spp. in young and elderly humans. Arch Oral Biol 1996;41(12):1133–40. 2. Eisbruch A, Ten Jaken RK, Kim HM, et al. Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys 1999;45(3):577–87. 3. Delli K, Spijkervet FKL, Kroese FGM, Bootsma H. Xerostomia. Monogr Oral Sci 2014;24:109–25. 4. Amano O, Mizobe K, Bando Y, et al. Anatomy and histology of rodent and human major salivary glands. Acta Histochem Cytochem 2012;45(5):241–50. 5. Treuting PM, Dintis SM. Salivary glands. In: Treuting PM, Dintzis SM, editors. Comparative anatomy and histology: a mouse and human atlas. Cambridge, MA: Academic Press; 2012. p. 111–20. 6. Dobrosielski VK, editor. Biology of the salivary glands. Boca Raton: CRC Press; 1993. 7. Holsinger FC, Bui DT. Anatomy, function, and evaluation of the salivary glands. In: Myers EN, Ferris RL, editors. Salivary gland disorders. Berlin: Springer; 2007. p. 1–16. 8. Miletich I. Introduction to salivary glands: structure, function and embryonic development. Front Oral Biol 2010;14:1–20. 9. Smith DJ, Taubman MA, King WF. Immunological features of minor salivary gland saliva. J Clin Immunol 1987;7(6):449–55. 10. Braxton L, Quinn S, editors. Salivary glands: anatomy, functions in digestion and role in disease. New York: Nova Science; 2013. 11. Ligtenberg AJ, Brand HS, Van Den Keijbus PA, Veerman EC. The effect of physical exercise on salivary secretion of MUC5B, amylase and lysozyme. Arch Oral Biol 2015;60(11):1639–44. 12. Segawa A, Shoi N, Yamashina S. Function of myoepithelial cells in salivary secretion: reevaluation of the expulsion theory. Kaibogaku Zasshi 1995;70(4):330–7.

13. Nissim K, Witt R, Ship JA. Embryology, physiology, and biochemistry of the salivary glands. In: Witt RL, editor. Salivary gland diseases. New York: Thieme Medical; 2006. p. 27–43. 14. Izutsu KT. Salivary electrolytes and fluid production in health and disease. In: Sreebny LM, editor. The salivary system. Boca Raton: CRC Press; 1987. p. 95–122. 15. Findlay I. A patch-clamp study of potassium channels and wholecell currents in acinar cells of the mouse lacrimal gland. J Physiol 1984;350(1):179–95. 16. Maruyama CL, Monroe MM, Hunt JP, et al. Comparing human and mouse salivary glands: a practice guide for salivary researchers. Oral Dis 2018;25(2):403–15. 17. Ellis GL, Auclair PL. The normal salivary glands. In: Ellis GL, Auclair PL, editors. AFIP atlas of tumor pathology: tumors of the salivary glands. Washington: American Registry of Pathology; 2008. 18. Carlson ER. Diagnosis and management of salivary lesions of the neck. Atlas Oral Maxillofac Surg Clin North Am 2015; 23(1):49–61. 19. de Paula F, Teshima THN, Hsieh R, et al. Overview of human salivary glands: highlights of morphology and developing processes. Anat Rec (Hoboken) 2017;300(7):1180–8. 20. Emmerson E, Knox SM. Salivary gland stem cells: a review of development, regeneration and cancer. Genesis 2018;56(5):e23211. 21. Tucker AS. Salivary gland development. Semin Cell Dev Biol 2007;18(2):237–44. 22. Rothova M, Thompson H, Lickert H, Tucker AS. Lineage tracing of the endoderm during oral development. Dev Dyn 2012;241(7):1183–91. 23. Lombaert IMA. Implications of salivary gland developmental mechanisms for the regeneration of adult damaged tissues. In: Cha S, editor. Salivary gland development and regeneration. Cham: Springer; 2017. p. 3–22. 24. Nanduri LS, Lombaert IM, van der Zwaag M, et al. Salisphere derived C-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland. Radiother Oncol 2013;108(3): 458–63.

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25. Rugel-Stah A, Elliot ME, Ovitt CE. Ascl3 marks adult progenitor cells of the mouse salivary gland. Stem Cell Res 2012;8(3):379–87. 26. Emmerson E, May AJ, Nathan S, et al. SOX2 regulates acinar cell development in the salivary gland. Elife 2017;e26620. 27. Weng PL, Aure MH, Maruyama T, Ovitt CE. Limited regeneration of adult salivary glands after severe injury involves cellular plasticity. Cell Rep 2018;24(6):1464–70. 28. Aure MH, Konieczny SF, Ovitt CE. Salivary gland homeostasis is maintained through acinar cell self-duplication. Dev Cell 2015;33(2):231–7. 29. Knox SM, Lombaert IM, Reed X, et al. Parasympathetic innervation maintains epithelial progenitor cells during salivary organogenesis. Science 2010;329(5999):1645–7. 30. Kwak M, Alston N, Ghazizadeh S. Identification of stem cells in the secretory complex of salivary glands. J Dent Res 2016;95(7):776–83. 31. Lombaert IMA, Abrams SR, Li L, et al. Combined KIT and FGFR2b signaling regulates epithelial progenitor expansion during organogenesis. Stem Cell Reports 2013;1(6):604–19. 32. Nedvetsky PI, Emmerson E, Finley JK, et al. Parasympathetic innervation regulates tubulogenesis in the developing salivary gland. Dev Cell 2014;30(4):449–62. 33. Knox SM, Lombaert IM, Haddox CL, et al. Parasympathetic stimulation improves epithelial organ regeneration. Nat Commun 2013;4:1494. 34. Kwon HR, Nelson DA, DeSantis KA, et al. Endothelial cell regulation of salivary gland epithelial patterning. Development 2017;144(2):211–20.

35. Magenheim J, Ilovich O, Lazarus A, et al. Blood vessels restrain pancreas branching, differentiation and growth. Development 2011;138(21):4743–52. 36. Lombaert IMA, Brunsting JF, Wierenga PK, et al. Keratinocyte growth factor prevents radiation damage to salivary glands by expansion of the stem/progenitor pool. Stem Cells 2008;26(10):2595–601. 37. Feng J, van der Zwaag M, Stokman MA, et al. Isolation and characterization of human salivary gland cells for stem cell transplantation to reduce radiation-induced hyposalivation. Radiother Oncol 2009;92(3):466–71. 38. Maimets M, Bron R, de Haan G, et al. Similar ex vivo expansion and post-irradiation regenerative potential of juvenile and aged salivary gland stem cells. Radiother Oncol 2015;116(3):443–8. 39. Nanduri LS, Maimets M, Pringle SA, et al. Regeneration of irradiated salivary glands with stem cell marker expressing cells. Radiother Oncol 2011;99(3):367–72. 40. Nanduri LS, Baanstra M, Faber H, et al. Purification and ex vivo expansion of fully functional salivary gland stem cells. Stem Cell Reports 2014;3(6):957–64. 41. Pringle S, Maimets M, van der Zwaag M, et al. Human salivary gland stem cells functionally restore radiation damaged salivary glands. Stem Cells 2016;34(3):640–52. 42. Emmerson E, May AJ, Berthoin L, et al. Salivary glands regenerate after radiation injury through Sox2-mediated secretory cells. EMBO Mol Med 2018;10(3):e8051.

3 

Salivary Gland Imaging URBAN GEISTHOFF (3.1, 3.2), ALBERTO IAIA (3.3–3.6), BRADY LAUGHLIN (3.3, 3.5, 3.6), ARPIT GANDHI (3.4), AND HUNG DAM (3.4)

3.1  CONVENTIONAL PLAIN FILMS Conventional X-ray imaging of the salivary gland has diminished relevance. The soft tissue X-ray does not depict a salivary stone well, and the summation effects of conventional X-ray images can make it difficult to locate the few visible structures. The main importance lies in incidental findings of calcifications in the salivary glands. Key examples are X-rays of the cervical spine (Fig. 3.1.1) and dental films (Fig. 3.1.2). However, it is sometimes difficult to differentiate salivary stones from other calcifications, including phleboliths or calcified lymph nodes. Additionally, up to 20% of stones cannot be detected by standard X-ray, as they are not radiographically opaque.1 Other imaging modalities enhance evaluation for stones. Ultrasound is often the next step (Fig. 3.1.3).

KEY POINT • Conventional X-ray imaging of the salivary gland has diminished relevance.

3.2  ULTRASOUND, ULTRASOUND GUIDED FINE NEEDLE ASPIRATION CYTOLOGY, AND CORE BORE BIOPSY Ultrasonography is a noninvasive, relatively inexpensive, real-time examination method, without radiation exposure. It is suitable for the examination of the salivary glands as most relevant aspects are located quite superficially. The reader is also referred to head and neck ultrasound textbooks.2–4

Ultrasound Anatomy The parotid gland lies partially superior to the masseter muscle and in between the retromandibular space, anterior to the mastoid (Fig. 3.2.1). Stensen’s duct navigates around the masseter muscle, perforates the buccinator muscle, and

enters the oral cavity. It normally is not visible on ultrasound; however, this often can be achieved by administering the patient a sialagogue (Fig. 3.2.2). Obstructions, including stones or stenosis, can dilate the duct. Sometimes an accessory gland can be found next to the duct. It can be difficult or even impossible to visualize the complete deep lobe of the gland by ultrasound. Penetration of the ultrasound waves is limited due to tissue attenuation and the shadow of the mandible that prevent visualization of parts lying in the deep parotid lobe. The submandibular gland is situated in the submandibular triangle, formed by the body of the mandible, and the anterior and posterior bellies of the digastric muscle. The mylohyoid muscle often indents the gland near to the hilum of the gland. When examining the gland by ultrasound, it is often possible to visualize the tongue and the pharyngeal tonsil at the same time (Fig. 3.2.3). The mandible is in close proximity to the submandibular gland (Fig. 3.2.4). The facial artery and vein cross the gland. The visualization of Wharton’s duct is also possible by provocation with a sialagogue. The sublingual gland in the longitudinal view is positioned above the mylohyoid muscle behind the front part of the mandible, lateral to muscles of the tongue (Fig. 3.2.5). Both sublingual glands and associated muscles can be visualized on transverse view (Fig. 3.2.6). The duct system of the sublingual gland is normally not visible. However, it has a close relationship to Wharton’s duct, which runs superficially. When Wharton’s duct is dilated by an obstruction from a stone, this relationship can become visible (Fig. 3.2.7).

Inflammatory Diseases An acute viral or bacterial infection leads to a swollen gland with a hypoechoic texture (see Fig. 3.2.7). In a bacterial infection, the duct system may become visible due to thickened secretion. In contrast, the ultrasonographic appearance of a chronic inflammatory process (e.g., Sjögren syndrome or chronic recurrent juvenile parotitis) is characterized by multiple hypoechoic lesions within the gland (Fig. 3.2.8). 19

CHAPTER 3  Salivary Gland Imaging

Keywords Imaging Plain Films Ultrasound Ultrasound Guided Fine Needle Aspiration Core Needle Biopsy Salivary Gland

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20 se c t i o n 1 20

Foundational Content

• Fig. 3.1.3

  Ultrasonography of the left submandibular gland depicting the same stone from Fig. 3.1.2.

• Fig. 3.1.1

  X-ray of the cervical spine depicting a huge sialolith in the right submandibular gland.

• Fig. 3.2.1

  Ultrasound anatomy of the parotid gland: the retromandibular vein (rv) is often at the depth of the facial nerve and therefore divides the deep from the superficial lobe. The temporal artery (ta) lies even deeper than the vein. mm, masseter muscle; ln, lymph node.

• Fig. 3.1.2

  Dental X-ray with an incidental finding of a sialolith in the left submandibular gland.

•

Fig. 3.2.2  Stensen’s duct is normally not visible by ultrasound. However, provocation of salivary production by use of a sialagogue (e.g., ascorbic acid) can dilate the Stensen’s duct (sd, v arrowheads). Deep to the duct, the masseter muscle is visible.

CHAPTER 3  Salivary Gland Imaging

• Fig. 3.2.3

  The submandibular gland (gsm) can often be visualized together with the tongue (lingua) and pharyngeal tonsil (to).

21

• Fig. 3.2.6

  The transverse view of the floor of the mouth includes the sublingual gland (gsl); the mylohyoid muscle (mmh); the anterior belly of the digastric muscle (mdg); the genioglossal muscle (mgg); the geniohyoid muscle (mgh); and the tongue (lingua). Sometimes even in front, accessory parts of the submandibular gland (gsm) can be found.

• Fig. 3.2.4

  The transverse view of the submandibular gland (gsm) also shows the close relationship with the mandible. mmh, mylohyoid muscle, lingua (tongue).

• Fig. 3.2.7

  A stone obstructs Wharton’s duct (wd) of the right submandibular gland (gsm). The dilated duct is in direct contact with the sublingual gland (the gray area on the image above the duct, just left and above the stone). Note the different echogenity of the sublingual gland (normal echotexture for a salivary gland, similar to the thyroid gland) and of the swollen submandibular gland (less echogenity). An acute infection of the gland can lead to a similar loss of echogenity due to edematous swelling.

Neoplasms

• Fig. 3.2.5

  The longitudinal view of the sublingual gland (gsl) shows its close relationship to the mandible, the tongue (lingua), and the mylohyoid muscle (mmh). md v ant, anterior belly of the digastric muscle.

Many types of benign and malignant neoplasms can be found in the salivary glands. The most frequent benign neoplasms of the parotid salivary glands are pleomorphic adenoma and Warthin tumor. A Warthin tumor (papillary cystadenoma lymphomatosum) is a benign lesion which not infrequently can be found in both parotid glands or as multiple lesions in one gland. They appear as oval, hypoechoic, partially anechoic, wellcircumscribed lesions (Fig. 3.2.9A). Due to their low echogenicity they show distal acoustic enhancement and they can sometimes present with hypervascularity on ultrasound

22 se c t i o n 1 22

Foundational Content

pg pg

• Fig. 3.2.8

  The ultrasound of this parotid gland (pg) shows signs of a chronic inflammatory process with multiple hypoechoic lesions. This pattern can be seen in Sjögren syndrome or in chronic recurrent juvenile parotitis. In this case it was the latter one.

A

B • Fig. 3.2.9

  A Warthin tumor in the right parotid gland. (A) The tumor is hypoechoic and well-circumscribed. Note the distal acoustic enhancement. (B) With color Doppler (duplex mode), hypervascularization can infrequently be observed. In this case it made it difficult to distinguish the tumor from a lymph node as the vascularization in this case mimics a lymph node hilum. pg, parotid gland; retrom v, retromandibular vein; ta, temporal artery.

• Fig. 3.2.10

  Pleomorphic adenoma of the right parotid gland (pg): the lesion is hypoechoic with a distal echo enhancement. It frequently presents with lobulated but well-defined borders.

(Fig. 3.2.9B). It can be difficult to distinguish a Warthin tumor from a cyst, a lymph node, or other benign neoplasms such as a pleomorphic adenoma. Pleomorphic adenomas are also hypoechoic with welldefined borders, with distal enhancement. They often can be differentiated from a Warthin tumor by a lobulated or polycyclic appearance (Fig. 3.2.10). Their echotexture can be homogenous, inhomogeneous, or even with calcifications. Vascularity is usually poor on color Doppler; however, the pseudo-capsule can contain several vessels. A multitude of other benign tumors exist. Vascular lesions can show increased vascularity on color Doppler and calcified-like phleboliths. Lipomas are hypoechoic with multiple hyperechoic linear structures regularly distributed within the lesions. Other benign tumors (e.g., oncocytomas, schwannomas) mostly do not have any specific or distinctive features on ultrasound examination. The characteristics of malignant tumors can vary. They are often characterized by irregular shapes and borders, heterogeneity, often hypoechogenicity, and locoregional metastasis (Fig. 3.2.11 and Video 3.2.1). However, their appearance can mimic benign tumors. The histologic types of malignant tumors do not have any pathognomonic sign on ultrasound.

Minimally Invasive Tissue Acquisition in Salivary Gland Lesions With Ultrasound Guidance Both fine needle aspiration cytology (FNAC) and core bore biopsies (CBB) can be performed under sonographic control. The diameter of the needles for CBB is usually larger than for FNA. The risk for complications including bleeding and cell seeding is likely correlating with the diameter of the needle utilized. The amount of tissue harvested also correlates with the diameter. Multiple systems exist (Fig. 3.2.12). The right setting is important: the patient

CHAPTER 3  Salivary Gland Imaging

23

pg

A • Fig. 3.2.11

  Malignant tumor of the right parotid gland (pg): the larger lesion above the mandible is inhomogenous, mostly hypoechoic, has blurred margins, and cannot be differentiated from the masseter muscle (mm) above the mandible. On the left side a local metastasis can be seen (smaller lesion). The histology of the lesion was an adenocarcinoma.

and the area of interest should be situated between the examiner and the ultrasound screen, so that the examiner can view and work in the same direction without having to turn around (Fig. 3.2.13). There are principally two techniques used: the “long axis” and “short axis” techniques. In the long axis technique (also shown in Fig. 3.2.13) the needle is advanced along the plane of the ultrasound beam (parallel technique). The movement of the needle tip can be visualized for most of the technique. This gives good control and can reduce the risk of traumatizing adjacent structures. However, adjacent structures are often not visualized using the long axis technique. Adjacent structures are more readily visualized for the short axis technique. Here the needle is not advanced within the plane of the ultrasound beam but usually is first visualized when the needle tip strikes the plane of the target lesion. The needle is seldom exactly perpendicular to the plane; however, some authors refer to the technique as a “perpendicular technique.” Sometimes anatomy and space available do not allow the use of the parallel long axis technique. Videos 3.2.2 and 3.2.3 show the parallel technique. The target structure is visualized and the trajectory for the instrument planned. The ultrasound transducer and instrument are aligned so that the instrument will advance in the plane of the ultrasound beam. The instrument should be inserted with some distance to the transducer. Otherwise, the instrument might not go deep enough, or damage the transducer. While advancing the instrument, it might be necessary to correct the ultrasound head position to visualize the target and the instrument at the same time. Especially the tip of the instrument should be seen to avoid trauma to surrounding structures. In the event that it is not possible to reach the target using the initiated path, it is advisable to pull the instrument back and start with a new direction instead of trying to bend the instrument. Video 3.2.2 shows an FNAC of a pleomorphic adenoma depicted

B • Fig. 3.2.12

  Various biopsy devices exist. The devices on the images are (from left to right): (1) Chiba biopsy needle, 23 G × 5 cm, with “echotip” (a roughened surface near the tip for better echogenity), Cook Inc., Bloomington, IN, USA. (2) Quick core biopsy needle, 20 G × 15 cm, Cook Inc. (3) Temno biopsy system, 20 G × 6 cm, Merit Medical Systems, Inc., South Jordan, Utah, USA. (4) BioPince, full core biopsy instrument, 18 G × 10 cm, Argon Medical Devices Inc., Athens, TX, USA. (5) Tru-Cut biopsy device, 18 G × 24 cm, Merit Medical Systems, Inc. (6) Spirotome, soft tissue biopsy needle set, outer needle (right side around the trocar): 8 G × 15 cm; inner needle with spiral cutting tip (left side): 10 G × 22 cm, Cook Inc. (7) Biopsie handy, 18 G × 10 cm, SOMATEX Medical Technologies GmbH, Teltow, Germany. Optional port systems are offered by some manufacturers (e.g., coaxial introducer systems). They allow obtaining multiple tissue samples through a single insertion site. (A) Overview of the devices. (B) Tips of the devices.

in Fig. 3.2.10. Video 3.2.3 is a record of a CBB of the adenocarcinoma shown in Fig. 3.2.11 and in Video 3.2.1.

KEY POINTS • Conventional X-ray imaging of the salivary gland has diminished relevance. • An acute infection has an ultrasound appearance of a hypoechoic texture and the ultrasonographic appearance of a chronic inflammatory process is characterized by multiple hypoechoic lesions within the gland. • Pleomorphic adenoma is characterized by a lobular appearance. • There are principally two techniques used for FNAC, the “long axis” and “short axis” techniques.

24 se c t i o n 1 24

Foundational Content

perineural tumor spreading in the small foramina of the skull base.9 Signal intensity of a salivary tumor on T2 weighted imaging may correlate with its malignant potential. Typically, masses demonstrating bright signal on T2 are benign or of lower grade, whereas masses with dark T2 signal tend be malignant.10 Diffusion weighted imaging (DWI) is a technique that identifies tissues with restriction of movement of unbound intracellular water. Apparent diffusion coefficient (ADC) map is derived from DWI and some investigators have found that low ADC values correlate with salivary malignancy.11,12 Analysis of contrast enhancement and dynamic washout can add to the diagnostic accuracy of MRI.13 • Fig. 3.2.13

  Setting for interventional ultrasound: the area of interest of the patient is situated between the examiner and the ultrasound screen. The direction of view and manipulation are the same and the examiner does not have to turn around. The plane of the ultrasound and the direction of the needle are parallel (“long axis” technique). A handle for aspiration is used.

3.3  COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING Computed Tomography Computed tomography (CT) performed without intravenous contrast is the modality with the highest sensitivity for detection of radiopaque sialoliths.5 CT performed without contrast cannot reliably differentiate the various salivary gland tumors, as most malignant and benign tumors demonstrate similar CT attenuation values. CT performed with contrast will reveal enhancement in areas of increased tumor vascularity.6 Administration of intravenous contrast is a safe practice with added diagnostic benefits that largely outweigh some infrequent risks, including rare allergic reactions or transient decline in renal function.7

Magnetic Resonance Imaging Soft-tissue contrast on magnetic resonance imaging (MRI) is superior to other imaging modalities but its spatial resolution is inferior to CT.6 Some anatomic locations are best investigated with MR, including the deep lobe of the parotid gland, the submandibular glands, and the parapharyngeal space. Normal salivary glandular tissue is bright on T1 weighted images because of its fatty content and a salivary gland tumor will appear as a dark lesion in the background of bright T1 signal.8 Fat suppression is an MR technique that darkens the bright T1 signal arising from fat and, with contrast enhancement, this sequence can define perineural tumor spread, vascular infiltration, or bone marrow invasion.6 This technique increases visibility of subtle enhancing

Cystic Lesions On CT, simple cysts demonstrate low attenuation and appear demarcated by thin, nonenhancing walls. On MR, they are bright on T2 and dark on T1 weighted images. Highly proteinaceous or hemorrhagic cysts may have high attenuation on CT and bright signal on T1 weighted images. Uncomplicated cystic lesions will not enhance on either modality. Peripheral enhancement of the cysts’ walls may indicate a superimposed infection, whereas nodular enhancement may suggest a cystic neoplasm. Abscesses, lymphoepithelial lesions, ranulas, pleomorphic adenomas, Warthin tumors, sialectasia, and sialoceles may demonstrate cystic imaging features.14

Infection and Inflammation Inflammation of a salivary gland is characterized by increased blood flow and increased vascular permeability, features readily identifiable on CT or MRI. Tissue edema is seen as a bright T2 signal. On CT, hazy or reticular stranding in the fat surrounding the inflammatory process may be present. A painful, enhancing salivary gland with edema of the periglandular fascia is compatible with acute sialadenitis. An acutely swollen gland due to an obstructing sialolith is best imaged with noncontrast CT (Fig. 3.3.1).5 HIV-positive patients may present with parotid masses, which may represent lymphoepithelial cysts or intraparotid lymph nodes due to lymphoma, and these entities are best distinguished on MRI.15

Benign Neoplasms A pleomorphic adenoma is seen on CT as a high attenuation, well-circumscribed mass that classically reveals delayed enhancement, a feature that helps in differentiating it from other benign tumors.16 On MRI, pleomorphic adenomas are a similar signal to muscle on T1 (Fig. 3.3.2) and demonstrate a bright signal on T2. Warthin tumors are often found in the parotid tail and may present as a single mass or as multiple encapsulated masses, frequently containing mucinous or serous cysts.10 Other benign tumors share similar imaging characteristics.10

CHAPTER 3  Salivary Gland Imaging

• Fig. 3.3.1

  Sialolithiasis with obstructive sialadenitis. Noncontrast CT. Several sialoliths involving the dilated intraglandular ducts (straight arrow) and Stensen’s duct (curved arrow). Diffuse gland enlargement and stranding of overlying subcutaneous adipose tissue is consistent with acute inflammation.

25

•

Fig. 3.3.3  High-grade mucoepidermoid carcinoma. Axial T2, fatsuppressed MR demonstrating a parotid mass (arrows) with poorly defined margins and low T2 signals, suggesting a malignancy.

irregular margins, visible on either CT or MR but usually more conspicuous on the latter. Imaging evidence of perineural spread or cervical lymphadenopathy strongly suggests malignancy.17 Mucoepidermoid carcinoma is an infiltrative tumor with variable imaging appearances, with the lowergrade lesions typically demonstrating smooth margins and high-grade tumors demonstrating low T2 signal and poorly defined borders, suggesting peripheral invasion (Fig. 3.3.3).10 Adenoid cystic carcinoma (ACC) accounts for 25% of all salivary gland malignancies.18 While its imaging features are nonspecific, evidence of perineural spread (Fig. 3.3.4) is a strong indicator of ACC.19 Squamous cell carcinoma and acinic cell carcinoma can have similar imaging appearance to ACC on MR and CT. While poor margins might suggest malignancy, these tumors cannot be distinguished from other salivary malignancies on cross-sectional imaging.19 • Fig. 3.3.2

  Pleomorphic adenoma. Axial T1 weighted image without contrast demonstrates a well-marginated lesion (arrow) in the deep lobe of the right parotid gland, isointense to muscle tissue, impinging the parapharyngeal space.

Malignant Neoplasms Malignancy is inferred by aggressive imaging features, including large size, low T2 signal, heterogeneous enhancement, infiltration of adjacent tissues, and rapid growth. Infiltration of adjacent tissues is indicated by indistinct,

KEY POINTS • CT without contrast is the modality of choice to detect a sialolith. • Low T2 signal and restricted diffusion on MRI suggests malignancy. • Cystic lesions have a thin, imperceptible wall and are fluid-filled, demonstrating low attenuation on CT and a bright signal on T2 MR. • Homogeneous, well-marginated tumors are more likely benign, whereas tumors with indistinct borders and a low signal on T2 are more likely malignant.

26 se c t i o n 1 26

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of radiotracer uptake. For head and neck pathology, many authors advocate the use of high resolution PET/CT with a small field of view, longer acquisition time per bed position, and thinner slices. Intravenous contrast administration is also recommended, as it allows full diagnostic CT capability.20

Benign and Malignant Neoplasms 18

• Fig. 3.3.4

  Perineural tumor spread. Coronal T1, fat suppressed, post- gadolinium image demonstrates adenoid cystic carcinoma spreading along the trigeminal nerve, ascending across the right foramen ovale (curved arrow), and invading Meckel’s cave (straight arrow).

3.4  POSITRON EMISSION TOMOGRAPHY WITH COMPUTED TOMOGRAPHY Introduction Positron emission tomography (PET) is a nuclear medicine functional imaging technique. A PET radiotracer emits a positron that travels a short distance before interacting with an electron. This interaction is called annihilation and it results in the creation of two 511 keV photons that travel ~180° apart. The two photons traveling in opposite directions are detected simultaneously by a ring of crystals, allowing for the determination of the location of the original annihilation event. This process is known as coincidence detection and it permits mapping of the distribution of the injected radiotracer. The most common PET radiotracer is 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG), which is a glucose analog used to observe metabolic pro­ cesses in the body. The degree of radiotracer uptake is quantified as standardized uptake values (SUV). Combining PET with CT permits functional and anatomic imaging in a single study.

Imaging Protocol The standard body PET/CT scan is performed from the base of the skull to mid-thighs without intravenous contrast material using low dose CT technique. The unenhanced low dose CT scan is used for attenuation correction of PET data and fusion of PET and CT images, permitting localization

F-FDG is taken up by the salivary glands and excreted into the saliva. Low level, bilateral symmetric, and diffuse uptake is usually physiological. Asymmetric uptake, especially when focal, is suspicious for malignancy, either primary or metastatic (Fig. 3.4.1). Differentiating benign from malignant neoplasms is difficult because of high 18 F-FDG uptake in benign tumors such as Warthin tumors (Fig. 3.4.2) and low uptake in some malignant tumors, including low grade mucoepidermoid carcinoma, necrotic squamous cell, and ACC. 18F-FDG PET/CT is useful in staging and follow-up of salivary gland malignancies. It provides more accurate diagnostic information for evaluation of high grade salivary malignancies than CT and MRI21–23 and it impacts management in >40% of patients.24 Incidental focal uptake of 18F-FDG is found in parotid glands in 0.4% of PET/CT studies.25 Such focal uptake is likely to represent benign lesions, particularly Warthin tumor, even in patients with known malignancy elsewhere. Nevertheless, these lesions warrant further radiologic and pathologic correlation if parotid disease would alter the treatment plan.26

Infection and Inflammation 18

F-FDG accumulates in benign infectious or inflammatory processes, including viral infections, bacterial infections, tuberculosis, and sarcoidosis. This occurs because of increased glycolysis in activated inflammatory cells. It typically presents as increased diffuse uptake. SUVs >3.7 have been suggested to indicate tumor uptake, rather than uptake related to infection or inflammation.27 Postchemoradiation and postsurgical inflammatory tissue may be mistaken for residual or recurrent tumor on follow-up PET/CT. Therefore, it is recommended to defer the follow-up study for 2–3 months after chemoradiation and 4–6 weeks after surgery, to allow inflammation to subside.20

Potential Pitfalls Obstructed sialadenitis may demonstrate high 18F-FDG activity, as normally excreted radiotracer is trapped in the dilated ductal system. Asymmetric physiologic activity may be seen in patients who have undergone surgical removal of a salivary gland or unilateral radiation therapy, with hypertrophy and increased activity in the contralateral gland. Lesions 3 in the labial salivary gland biopsy.51–54

Treatment The goals of treatment for patients with SS include: (1) to relieve dryness symptoms; (2) to prevent complications of mucosal dryness, e.g., dental decay, corneal ulceration; (3) to detect and manage systemic manifestations and lymphoma early. Each patient should be offered holistic evaluation and management by a multidisciplinary team, which includes a rheumatologist, an ophthalmologist, and a dentist. The management approach is generally the same for primary or secondary SS. All patients should receive comprehensive education on the importance of meticulous self-care and preventive intervention.

Dry Mouth The mainstay of symptomatic treatment is water. The importance of adequate hydration of the oral cavity cannot be overemphasized. Water should be taken with small sips frequently. Water is not only able to relieve the immediate sense of dryness and to hydrate the oral mucosa, it also helps with chewing and swallowing. Medications that may worsen oral dryness, especially those with anticholinergic side effects, should be avoided. Patients should be counseled on general environmental measures designed to enhance moisture, such as the use of humidifier and the avoidance of hot-air heating systems and excessive air-conditioning. Due to the loss of antimicrobial, remineralizing, and cleansing properties of saliva, there is a marked increase in dental caries. Fungal infections of candida species are frequent and may be resistant to treatment. Meticulous oral hygiene should include toothbrushing after each meal and the use of dental floss and dental appliances such as interdental brushes for cleaning between teeth. Regular and frequent dental checks are needed. Sugar intake should be minimized. When sugary foods are consumed, the teeth should be brushed, or at least rinsed immediately. Regular

use of acidic beverages, like soft drinks, should be avoided. A fluoride-containing toothpaste should be used, since fluoride helps to repair early demineralization of the tooth and strengthens the tooth surface. Saliva can be stimulated by any oral activity. Patients may use sugar-free gums, lozenges, candies, or mints for symptomatic relief of xerostomia. The use of sugar-free and lowacid products must be stressed. Xylitol is an acceptable sweetener that has been shown to reduce dental caries. In patients who do not respond adequately to the basic measures mentioned above, and who continue to find the symptoms distressing, further measures of muscarinic agonists, including pilocarpine and cevimeline could be considered.55 The benefits of pilocarpine and cevimeline have been shown in several randomized trials of each drug.56–62 These include increased salivary flow and improvement in symptoms of dry mouth when compared with placebo.

Dry Eye The initial management should focus on symptomatic relief and the prevention of ocular damage. The treatment is determined by the severity of the dryness and the severity of symptoms. Patients should be educated on the strategies for tear conservation and the effective use of artificial tears.

Systemic Manifestations While some treatments may improve symptoms and prevent complications of SS, currently there is no cure. There are both gaps and challenges in treatments involving both local and systemic manifestations of SS and, to date, no immunomodulatory drug has proved to be efficacious in primary SS.63 The decision to adopt systemic treatment and the choice of the specific treatment in primary SS is often driven by the organ involved and the severity of the disease activity. The few randomized controlled trials evaluating the use of conventional disease-modifying antirheumatic drugs and biologics in patients with SS did not provide conclusive evidence supporting their efficacy.63,64 Treatment strategies are often based on personal experience acquired in other autoimmune rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, rather than on strong scientific evidence. Despite a better understanding of the pathogenesis of SS, together with the advances in molecular biology and engineering, the development of targeted therapies to interfere with or to block the various pathologic pathways in SS remains a great challenge for both the scientists and researchers. More studies are needed to combat this complex autoimmune disease, with an ultimate aim to improve the quality of life for all the SS patients.

KEY POINTS • Minor salivary gland biopsy with focal lymphocytic sialadenitis and a focus score of ≥1 foci/4 mm2 provides a histological ground for the diagnosis.

CHAPTER 7  Sialadenitis

(Fig. 7.2.2.1). A review65 of nearly 3500 reported patients found a mean age at diagnosis of 61 years with a clear male predominance (73% of patients). In 2012, an international multidisciplinary study group suggested the name “IgG4-RD”.67

K E Y P O I N T S —cont’d • The frequency of anti-Ro/SSA and/or anti-La/SSB antibodies has varied between studies, but generally 60–80% of patients with primary SS exhibit one or both of these autoantibodies. • The risk of lymphoma is about 15–20 times as high among patients with primary SS as in the general population.

Clinical Presentation

7.2.2  IgG4-Related Disease IgG4-related disease (IgG4-RD) is a systemic, chronic, immune-mediated systemic disease described in Japan in the first years of the 21st century.65 The key histopathologic feature of the disease is the infiltration of IgG4bearing plasma cells.66 Many diseases previously considered “idiopathic” are now included in the clinical IgG4-RD spectrum (Mikulicz disease, Küttner tumor, Riedel thyroiditis, Ormond disease).66 Although the disease has been described in nearly all racial and ethnic groups, more than two-thirds of cases have been reported from Asian countries

IgG4-RD has now been reported in nearly every organ of the human body (Fig. 7.2.2.2). The pancreas is the organ most frequently involved in >40% of reported cases presenting as a systemic disease,68 but IgG4-RD also affects a large number of other organs and systems, including the lungs, pleura, mediastinum, kidneys, retroperitoneum, mesentery, urinary tract, meninges, thyroid, hypophysis, joints and bones, peripheral nerves, prostate, breasts, testes, and the gut.65 Therefore, the presenting features of the disease vary substantially according to which specialty evaluates the patient first, but the physicians most frequently involved are gastroenterologists,69 ophthalmologists,70 otolaryngologists,71 nephrologists,72,73 urologists,74 dermatologists,75 neurologists,76 and rheumatologists/internists. The key for clinical suspicion of IgG4-RD is a patient presenting

77 234 141* 118 118 41 15 18 278* 117 1917 28 559* 0

100

200

300

North America 12.8% 0

500

600

700

800

900 1000 1100 1200 1300 1400 1500 1600 1700 1800 1900 2000

Europe 13.2%

10

• Fig. 7.2.2.1

400

20

Asia 74% 30

40

50

60

70

80

Worldwide distribution of reported IgG4-RD cases; asterisks refer to the number of patients in multicenter studies.1  

53

90

100

54 se c t i o n 2 54

Inflammatory Conditions

Submaxillary

• Fig. 7.2.2.2

 

Frequency of the main organs involved by IgG4-RD.1

with tumefactive lesions in one or more organs (40% of patients have single-organ involvement),65 lesions that may be diagnosed incidentally through radiologic findings or unexpectedly in pathologic specimens. The enlarged organs may be visible on the physical examination (salivary or lacrimal gland swelling, lymphadenopathy, thyroid enlargement) or in imaging diagnostic tests (enlargement of the pancreas, liver, spleen, or kidneys).77 Signs and symptoms at presentation are diverse and may be divided into general and organ-specific. Head and Neck Involvement

The major salivary glands are the second most frequently involved organ in IgG4-RD, including patients with Mikulicz disease (bilateral swelling of at least two major salivary or lacrimal glands) and those with Küttner disease (chronic sclerosing sialadenitis that affects the submandibular glands).65 IgG4-related glandular involvement has been specifically studied in 10 studies, including 158 patients with Mikulicz disease and 42 with Küttner disease.65 Glandular swelling, often subacute, was the key sign on examination: submandibular glands were affected in 94% of patients,

parotid glands 29%, and sublingual glands only in eight cases. Bilateral involvement was more frequent in systemic than in localized IgG4-RD. A recent study has reported that all affected glands showed well-defined borders, with two types of sonographic appearance (localized tumorforming and diffuse focal involvement).78 In patients with IgG4-related glandular disease, sicca symptoms have been reported in 62% of patients. Two studies have analyzed nasal involvement specifically.79,80 The main nasal symptoms reported were crusting, rhinorrhea, postnasal drip and polyposis. Rhinitis (often in an allergic/atopic context) and sinusitis are prevalent. Nasal biopsy has been suggested as a safe and useful diagnostic tool. Allergic processes or an atopic background have been reported in ~20% of systemic patients. The two main types of cutaneous lesions are erythematous plaques and subcutaneous nodules. The main locations of cutaneous lesions are often related to the main head and neck involvements (salivary and lacrimal glands), including the periauricular, eyelid, cheek, temporal, and mandible regions. Adenopathies are often associated with local or regional IgG4-related extranodal involvement: the most frequent location is cervical in patients with salivary

CHAPTER 7  Sialadenitis

gland involvement. Involvement of cranial nerves is often related to adjacent tumoral masses. The best examples are the involvement of the optic nerves and trigeminal branches (supra/infraorbital nerves) by ocular masses. Other infrequent upper airway involvements included hearing loss, mastoiditis, otitis media, larynx involvement, and destructive bone involvement affecting the bones of the orbit, or the temporal, maxillary, or mastoid bones.

Diagnostic Approach The diagnosis of IgG4-RD relies on the coexistence of various clinical, laboratory, and histopathologic findings, although none are pathognomonic alone. IgG4-RD should be suspected in patients presenting with unexplained enlargement or swelling of one or more organs. Four laboratory abnormalities may lead to suspicion of IgG4-RD: eosinophilia, hypergammaglobulinemia, elevated serum immunoglobulin(Ig)E levels, and hypocomplementemia.81 Raised IgG4 levels were the key feature in identifying the first cases of IgG4-RD (autoimmune pancreatitis, Mikulicz disease), and were subsequently considered a key diagnostic feature. However, IgG4 levels are raised in a wide range of diseases, and recent studies have reported some significant limitations of serum IgG4 measurement and their role in making the diagnosis should be de-emphasized.82 Histopathologic studies and IgG4 tissue immunostaining are the most reliable diagnostic tools at this time, although they are not pathognomonic and may show significant variations according to the organ biopsied, the time of disease evolution, or the therapies administered (Fig. 7.2.2.3). Flow cytometry measuring circulating plasmablasts is likely to play an increasingly important role in the diagnosis and longitudinal management of IgG4-RD in the future.82 The great majority of reported studies based the diagnosis of IgG4-RD on a compatible clinical picture, together with elevated serum IgG4 levels and a highly suggestive histopathologic scenario. International multidisciplinary collaboration

55

is near to publish the new set of ACR/EULAR classification criteria.

Treatment The optimum therapeutic management of IgG4-RD has not yet been established.83 Glucocorticoids (GC) remain the main therapeutic approach, although no controlled studies have specifically evaluated their use in unselected IgG4-RD series.84 Therapeutic guidelines recommend the use of GC as first-line therapeutic agents, with 94% of agreement between experts83 on the use of prednisolone (0.6 mg/kg per day) for 4 weeks as induction therapy. After the first 4 weeks of induction therapy, the GC dose can be tapered gradually during a 3–6-month period to a maintenance dose of 2.5–5.0 mg/day for up to 3 years. The selection of a “steroid-sparing” agent is challenged by the paucity of data on the efficacy of conventional agents for IgG4-RD, since the use of immunosuppressive agents in IgG4-RD is based on the same level of evidence as that for GC (uncontrolled studies).84 The emergence of biologic therapies has increased the therapeutic armamentarium available for treating the most refractory/severe cases of IgG4-RD, but their use is limited by the lack of licensing. Rituximab (RTX) was first reported to be useful in 2010 and is the biologic option typically used as the first option following GC85; it was used less frequently as induction therapy (only eight cases with an efficacy of 75%),86,87 and more frequently as rescue therapy in patients who failed to achieve or sustain disease remission with GC treatment.88–94 Finally, the lack of any therapeutic intervention has been reported in 13% of patients.84 In some specific organ involvements, this percentage was higher, reaching 71% in IgG4-related lymphadenopathy, 35% in IgG4-related salivary involvement, or 40% in IgG4-related skin involvement. Wait-and-see management may be appropriate in asymptomatic patients with lymphadenopathy, cutaneous features, or mild salivary gland enlargement.

KEY POINTS • IgG4-related disease is a systemic, chronic, immunemediated systemic disease. • The major salivary glands are among the most frequently involved organs. • The diagnosis relies on the coexistence of various clinical, laboratory, and histopathologic findings. • Glucocorticoids are the main therapeutic approach.

7.3  GRANULOMATOUS DISEASES

• Fig. 7.2.2.3  Histopathologic analysis characteristic of IgG4-RD: dense lymphoplasmacytic infiltrates.

Granulomatous disease is of two types: that of infectious origin and that of noninfectious origin. Common infectious diseases in the head and neck regions include Mycobacterium tuberculosis (TB), nontuberculous mycobacteria (NTM), and cat-scratch disease; a common noninfectious disease is sarcoidosis. The human immune system causes

56 se c t i o n 2 56

Inflammatory Conditions

• Fig. 7.3.1  Multinucleated giant cell formation (black arrow) is noted in the granuloma within the lymphoid stroma of the Warthin tumor. (Original magnification, ×100) (H&E)

• Fig. 7.3.2

  Granulomatous formation is noted within the parenchyma of the parotid gland. (Original magnification, ×20) (H&E)

granulomatous inflammation in response to specific offending antigens, encouraging the aggregation then fusion of macrophages to form multinuclear giant cells, called “Langhans giant cells”. These cells resemble epithelioid cells, whose cytoplasm eosin stains pink, as is evident in the microscopic findings (Fig. 7.3.1). Microscopically, multiple eosinophils’ infiltration into the granuloma is suggestive of fungal infection. If neutrophils are dominant in the granuloma, granulomatosis with polyangiitis or cat-scratch disease is likely in the head and neck regions. Granuloma with necrotic tissue is called caseous necrosis, usually related to the infectious process, especially that of TB.

Salivary Gland Tuberculosis Extrapulmonary TB in the head and neck regions accounts for ~15% of all mycobacterial infection, commonly cervical TB lymphadenitis, known historically as scrofula.95,96 Major salivary gland TB infection is rare. The most involved major salivary gland is the parotid gland, followed by the submandibular gland.97 Where salivary gland TB is concerned, surgical intervention plays a very limited role in case of medical treatment failure.

• Fig. 7.3.3

  A central necrotic mass is noted over the right parotid gland in the image of CT scan.

Diagnosis of Salivary Gland Tuberculosis Salivary gland TB usually presents as a progressive lump in the parotid or submandibular area. Fever or tenderness in the infected area is uncommon. The involved skin can be violaceous. The findings of histology show chronic granulomatous inflammation (Fig. 7.3.2). It frequently presents as a central necrotic mass (Fig. 7.3.3) on CT.98 Fine needle aspiration with acid-fast smear by Ziehl–Neelsen staining and/ or the TB polymerase chain reaction (PCR) test can confirm the diagnosis. The pathologic presentations of parotid TB among patients with HIV infection may be different from immunocompetent patients, presenting with noncaseating

granuloma and occasionally presenting without granuloma formation.99

Treatment of Salivary Gland Tuberculosis Antimycobacterial therapy for extrapulmonary cervical TB lymphadenitis is a multiple drug-based regimen for non-HIV adults.100,101 The clinical outcomes of a 6-month treatment regimen for cervical TB lymphadenitis is comparable with a 9-month treatment regimen.102 HIV patients’ therapeutic duration should be longer.

CHAPTER 7  Sialadenitis

Nontuberculous Mycobacterial Infection of the Salivary Gland Nontuberculous mycobacteria (NTM) are mycobacteria that are clinically less virulent than TB in nonimmunocompromised patients. NTM are divided into two types based on their growth in culture media: rapidly growing mycobacteria, such as Mycobacterium marinum (MAC), and slowly growing mycobacteria, such as M. fortuitum.103 Patients usually acquire them from environment, such as water, soil, dust, food products, and even animals. Extrapulmonary NTM infection accounts for ~10% of all NTM infection.104 NTM infection of the salivary gland may come from regional lymph nodes, intraparotid lymph nodes, or regional skin involvement. Subsites of NTM infection in the head and neck regions are submandibular (46%), cervical (38%), parotid (17%), and submental (4%).105 The most common type of NTM infection is MAC (61–91%).106 The involved skin may present as violaceous discoloration or even suppuration from progressively infected tissue.

Diagnosis of Nontuberculous Mycobacterial Infection of the Salivary Gland NTM infection of the salivary gland is rare and it commonly involves young children aged 1–5 years. HIV infection in adult patients with NTM infection of the salivary gland and any other immunosuppressive status is similar to salivary gland TB.107 Otherwise, cough, fever, loss in body weight, and other constitutional symptoms are rare among patients with NTM infection of the salivary gland. Positive chest films are uncommon. The images from CT scan study may show identical findings for salivary gland TB. Pus drainage from the infected region may develop. A positive acid-fast bacilli (AFB) stain and histopathologic features in the infective area are very similar to those associated with TB. A negative AFB stain does not exclude the possibility of NTM infection. Currently, interferon gamma release assays (IGRAs) can differentiate between NTM and TB. A positive IGRA favors the diagnosis of TB.108 A precise diagnosis using nucleic acid probes (Accuprobe, GenProbe, Inc.) is available commercially.

Treatment of Nontuberculous Mycobacterial Infection of the Salivary Gland The treatment of NTM infection in head and neck regions comprises antimycobacterial treatment, surgical intervention, or a combination of the two. Optimal treatment is complete surgical removal of NTM lymphadenitis,109,110 with better expected clinical outcomes than curettage or antibiotic treatment.111–113 Antibiotic therapy for salivary NTM infection before surgery to control active inflammatory soft tissue is an option for avoiding high-risk extensive surgery and potential facial nerve damage.114,115 Clinicians should be aware of the adverse effects of longer periods of anti-NTM medicine, including fever,

57

fatigue, abdominal pain, tooth discoloration, headache, and vomiting.112 The optimal antimycobacterial regimen for NTM infection is not well established. The empiric therapy for NTM infection, especially for commonly found species of NTM such as MAC, includes the combination of a macrolide, ethambutol, or rifampin for a period of 3–6 months; however, the suitable treatment duration is still unknown.109,110,116

Cat-Scratch Disease Cat-scratch disease (CSD) is an infectious disease resulting from a cat’s bite or fleas. It is characterized by self-limited regional lymphadenopathy and papules at the inoculated site. The bacterial pathogen most frequently found is Bartonella henselae. The Afipia felis and Bartonella clarridgeiae are also isolated. In general, CSD is common in children. Each year, between 2005 and 2013, it was estimated that CSD resulted in 12,000 outpatients and 500 inpatients in the USA.117

Diagnosis of Cat-Scratch Disease The parenchyma of parotid or submandibular gland can exhibit necrotizing granulomas. Serologic testing by enzyme immunoassay (EIA) of indirect fluorescence assay (IFA) could be used to confirm the presence of the disease, but a negative test result does not exclude CSD. The PCR-based test for Bartonella has a higher positive rate within the first 6 weeks of infection.118 A Warthin-Starry stain may typically show clumps of Bartonella henselae bacilli.

Treatment of Cat-Scratch Disease in a Salivary Gland Most patients will experience the regressive symptoms of typical CSD even without any antibiotic treatment. Susceptibility testing for bacteria is not advised for the choice of antibiotics.119 To date, only one prospective randomized trial shows the effectiveness of a 5-day course of azithromycin in the treatment of involved lymph nodes.120 Rifampin, ciprofloxacin, and gentamycin showed efficacy in the treatment of CSD.121

Sarcoidosis The etiology of sarcoidosis is not known. It is a noncaseating granulomatous disorder with multiorgan involvement. Major salivary gland involvement accounts for ~2–6% of cases.122–125 There is an ethnic difference in the prevalence of sarcoidosis, higher for African Americans than for Caucasians, Hispanics, or Asian patients.126–131

Diagnosis of Salivary Gland Sarcoidosis Bilateral parotid sarcoidosis accounts for up to 70% of the cases.125 Elevated angiotensin-converting enzyme levels and

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hypercalcemia are often noted in patients with pulmonary sarcoidosis. On rare occasions, if the lung is not involved, tissue proof of the parotid gland is necessary. Gallium-67 scintigraphy could reveal a “panda sign” if the sarcoidosis simultaneously involves the major bilateral salivary glands and lacrimal glands. FDG-PET/CT scan has been suggestive in the detection of extrapulmonary sarcoidosis; however, caution must be exercised in its use in the interpretation.132 Heerfordt syndrome or uveoparotid fever includes an enlargement of the parotid gland, uveitis, and low-grade fever, and accounts for only 0.3% of all cases of sarcoidosis.133

Treatment of Salivary Sarcoidosis The literature reports that the mainstay of treatment for salivary sarcoidosis, including Heerfordt disease, is oral prednisolone.123,134–136 If patients cannot tolerate corticosteroids, methotrexate, azathioprine, leflunomide, chloroquine, pentoxifylline, hydroxychloroquine, cyclophosphamide, and mycophenolate are alternatives.137,138 In the refractory cases, antitumor necrosis factor antibody, infliximab, can be considered.139

• Fig. 7.4.1

 

Sialadenosis involving bilateral parotid glands.

KEY POINTS • Granulomatous disease is of two types: infectious origin and noninfectious origin. • Parotid TB among patients with HIV infection may present without granuloma formation. • IGRAs can differentiate between NTM and TB. • Susceptibility testing for bacteria is not advised for antibiotics for cat-scratch disease. • The etiology of sarcoidosis is not known.

7.4  SIALADENOSIS Introduction Sialadenosis is a nonspecific term used to describe an uncommon, benign, noninflammatory, non-neoplastic enlargement of a salivary gland.140 This enlargement is usually, bilateral, symmetrical, and painless (Fig. 7.4.1).140,141 Sialadenosis usually involves the parotid gland, occasionally affects the submandibular glands, and rarely, the minor salivary glands.142

• Fig. 7.4.2

  The involved parotid gland is diffusely enlarged without palpable nodule.

History and Physical Examination Patients usually seek medical attention because of uncertainty about the diffusely enlarged glands without other symptoms. The involved salivary glands are mostly soft and nontender to palpation, without evidence of a nodule. Sialadenosis may occasionally involve both bilateral parotid and submandibular glands. If there is only unilateral asymetric enlargement (Fig. 7.4.2), imaging such as ultrasound, MR, or CT may be indicated. Patients are generally

aged 30–69 years at diagnosis and both sexes are equally involved.140

Etiology The cause is generally idiopathic. Sialadenosis has been reported to be associated with alcoholic liver disease,143 malnutrition,143 diabetes,144 and especially bulimia.145,146

CHAPTER 7  Sialadenitis

59

Autonomic Neuropathy There is a common feature of autonomic neuropathy in bulimia patients with sialadenosis.145,146 The sympathetic nerve supply to the secreting acinar cell in the salivary gland is associated with the production and secretion of zymogen, the precursor of amylase. Because of sympathetic nerve impairment in autonomic neuropathy, the individual acinar cell enlarges due to zymogen granule engorgement. Because of sympathetic nerve dysfunction, there is an increase in zymogen storage in the cell, owing to increased production, decreased secretion of the granules, or both. The ensuing cellular enlargement, which is evidenced by fine needle aspiration biopsy and electronmicroscopy, leads to the clinically visible gland enlargement.145,146

Nutritional Disorders (Malnutrition) Any disorder that affects the digestion of food, or its absorption over a prolonged period, can result in sialadenosis. Malnutrition may contribute to sialadenosis, especially in alcoholic hepatitis. Sialadenosis can impact up to 30–80% of patients with alcoholic cirrhosis.143

• Fig. 7.4.3

Metabolism (Endocrine)

In general, sialadenosis requires no treatment. However, regular clinical follow-up is suggested. The disease is usually self-limited. If the glands are disfiguring, superficial parotidectomy to improve the appearance may be considered but is generally not suggested.

The reported prevalence of sialadenosis in diabetes patients ranges from 10–80%.144

Drugs Antihypertensive agents, sympathomimetics such as isoprenaline, antithyroids, or phenylbutazone, are among the wide range of pharmaceuticals that can induce sialadenosis.

Investigations and Imaging The biochemical blood analysis is generally normal in patients with sialadenosis. There is no specific blood test for the diagnosis of sialadenosis. The amylase level is not elevated as this is not an inflammatory disorder of the salivary glands. However, blood tests can detect some of the associated disorders in sialadenosis, such as malnutrition, diabetes, or alcoholic liver disease, etc., which should be managed accordingly. Imaging studies, such as ultrasound, CT, or MRI are usually not indicated; however, they do help to detect space occupying lesions and differentiate from sialadenosis. The typical CT or MRI feature in sialadenosis is a diffuse and homogenous enlarged gland (Fig. 7.4.3). Biopsy is rarely indicated in cases of sialadenosis. If biopsy is performed, the pathology may show the acinar cells to be enlarged to almost twice the normal diameter and the cytoplasm packed with enzyme granules.147

  CT scan shows diffusely homogenous enlargement of the bilateral parotid glands.

Treatment

KEY POINTS • Sialadenosis is an uncommon, benign, noninflammatory, non-neoplastic enlargement of a salivary gland, and usually involves bilateral parotid glands. • The involved glands are diffusely enlarged with very vague symptoms. • Sialadenosis is self-limited and biopsy is not indicated unless suspicious for neoplasm, nor is treatment necessary.

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100. Nahid P, Dorman SE, Alipanah N, et al. Official American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis. Clin Infect Dis 2016;63:e147–95. 101. Jawahar MS, Rajaram K, Sivasubramanian S, et al. Treatment of lymph node tuberculosis–a randomized clinical trial of two 6-month regimens. Trop Med Int Health 2005;10:1090–8. 102. Yuen AP, Wong SH, Tam CM, et al. Prospective randomized study of thrice weekly six-month and nine-month chemotherapy for cervical tuberculous lymphadenopathy. Otolaryngol Head Neck Surg 1997;116:189–92. 103. Chesney PJ. Nontuberculous mycobacteria. Pediatr Rev 2002;23:300–9. 104. Kasperbauer S, Huitt G. Management of extrapulmonary nontuberculous mycobacterial infections. Semin Respir Crit Care Med 2013;34:143–50. 105. Mahadevan M, Neeff M, Van Der Meer G, et al. Nontuberculous mycobacterial head and neck infections in children: analysis of results and complications for various treatment modalities. Int J Pediatr Otorhinolaryngol 2016;82:102–6. 106. Spaulding AB, Lai YL, Zelazny AM, et al. Geographic distribution of nontuberculous mycobacterial species identified among clinical isolates in the United States, 2009–2013. Ann Am Thorac Soc 2017;14:1655–61. 107. Lawn SD, Checkley A, Wansbrough-Jones MH. Acute bilateral parotitis caused by Mycobacterium scrofulaceum: immune reconstitution disease in a patient with AIDS. Sex Transm Infect 2005;81:517–18. 108. Staufner C, Sommerburg O, Holland-Cunz S. Algorithm for early diagnosis in nontuberculous mycobacterial lymphadenitis. Acta Paediatr 2012;101:e382–5. 109. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416. 110. American Academy of Pediatrics. Diseases caused by nontuberculous mycobacteria. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, editors. Red book: 2015 – report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village: American Academy of Pediatrics; 2015. p. 831. 111. Shah MB, Haddad J. Nontuberculous mycobacteria-induced parotid lymphadenitis successfully limited with clarithromycin and rifabutin. Laryngoscope 2004;114:1435–7. 112. Lindeboom JA, Kuijper EJ, Bruijnesteijn van Coppenraet ES, et al. Surgical excision versus antibiotic treatment for nontuberculous mycobacterial cervicofacial lymphadenitis in children: a multicenter, randomized, controlled trial. Clin Infect Dis 2007;44:1057–64. 113. Iversen RH, Illum P. Cervicofacial nontuberculous mycobacterial lymphadenitis in children. Dan Med J 2012;59: A4349. 114. Parker NP, Scott AR, Finkelstein M, et al. Predicting surgical outcomes in pediatric cervicofacial nontuberculous mycobacterial lymphadenitis. Ann Otol Rhinol Laryngol 2012;121:478–84. 115. Berkovic J, Vanchiere JA, Gungor A. Non tuberculous mycobacterial lesion of the parotid gland and facial skin in a 4 year old girl: a proposed treatment strategy. Am J Otolaryngol 2016; 37:89–94. 116. Griffith DE. Therapy of nontuberculous mycobacterial disease. Curr Opin Infect Dis 2007;20:198–203.

CHAPTER 7  Sialadenitis

117. Nelson CA, Saha S, Mead PS. Cat-scratch disease in the United States, 2005–2013. Emerg Infect Dis 2016;22:1741–6. 118. Ridder GJ, Boedeker CC, Technau-Ihling K, et al. Role of catscratch disease in lymphadenopathy in the head and neck. Clin Infect Dis 2002;35:643–9. 119. Rolain JM, Brouqui P, Koehler JE, et al. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004;48:1921–33. 120. Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J 1998;17:447–52. 121. Margileth AM. Antibiotic therapy for cat-scratch disease: clinical study of therapeutic outcome in 268 patients and a review of the literature. Pediatr Infect Dis J 1992;11:474–8. 122. Rizzato G, Tinelli C. Unusual presentation of sarcoidosis. Respiration 2005;72:3–6. 123. Ungprasert P, Crowson CS, Matteson EL. Clinical characteristics of parotid gland sarcoidosis: a population-based study. JAMA Otolaryngol Head Neck Surg 2016;142:503–4. 124. Mana J, Rubio-Rivas M, Villalba N, et al. Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore) 2017;96:e7595. 125. James DG, Sharma OP. Parotid gland sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2000;17:27–32. 126. Rybicki BA, Major M, Popovich J Jr, et al. Racial differences in sarcoidosis incidence: a 5-year study in a health maintenance organization. Am J Epidemiol 1997;145:234–41. 127. Dumas O, Abramovitz L, Wiley AS, et al. Epidemiology of sarcoidosis in a prospective cohort study of U.S. women. Ann Am Thorac Soc 2016;13:67–71. 128. Baughman RP, Field S, Costabel U, et al. Sarcoidosis in America. Analysis based on health care use. Ann Am Thorac Soc 2016;13:1244–52. 129. Arkema EV, Grunewald J, Kullberg S, et al. Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. Eur Respir J 2016;48:1690–9. 130. Anantham D, Ong SJ, Chuah KL, et al. Sarcoidosis in Singapore: epidemiology, clinical presentation and ethnic differences. Respirology 2007;12:355–60. 131. Park JE, Kim YS, Kang MJ, et al. Prevalence, incidence, and mortality of sarcoidosis in Korea, 2003–2015: a nationwide population-based study. Respir Med 2018;144S:S28–34.

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132. Sobic-Saranovic D, Artiko V, Obradovic V. FDG PET imaging in sarcoidosis. Semin Nucl Med 2013;43:404–11. 133. Sugawara Y, Sakayama K, Sada E, et al. Heerfordt syndrome initially presenting with subcutaneous mass lesions: usefulness of gallium-67 scans before and after treatment. Clin Nucl Med 2005;30:732–3. 134. Cakmak SK, Gönül M, Gül U, et al. Sarcoidosis involving the lacrimal, submandibular, and parotid glands with panda sign. Dermatol Online J 2009;15:8. 135. Dua A, Manadan A. Images in clinical medicine. Heerfordt’s syndrome, or uveoparotid fever. N Engl J Med 2013;369:458. 136. Fujiwara K, Furuta Y, Fukuda S. Two cases of Heerfordt’s syndrome: a rare manifestation of sarcoidosis. Case Rep Otolaryngol 2016;2016:3642735. 137. Baughman RP, Lower EE. Treatment of sarcoidosis. Clin Rev Allergy Immunol 2015;49:79–92. 138. Judson MA. Sarcoidosis: clinical presentation, diagnosis and approach to treatment. Am J Med Sci 2008;335:26–33. 139. Russell E, Luk F, Manocha S, et al. Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy. Semin Arthritis Rheum 2013;43:119–24. 140. Peel RL. Diseases of the salivary glands. In: Barnes L, editor. Surgical pathology of the head and neck. 2nd ed. New York: Marcel Dekker; 2001. p. 644–6. 141. Mandel L. Surattanont F. Bilateral parotid swelling: a review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:221–37. 142. Pape SA, MacLeod RI, McLean RN, Soames JV. Sialadenosis of the salivary glands. Br J Plast Surg 1995;48:419–22. 143. Guggenheimer J, Close JM, Eghtesad B. Sialadenosis in patients with advanced liver disease. Head Neck Pathol 2009;3:100–5. 144. Russotto SB. Asymptomatic parotid gland enlargement in diabetes mellitus. Oral Surg Oral Med Oral Pathol 1981;52:594–8. 145. Garcia Garcia B, Dean Ferrer A, Diaz Jimenez N, Alamillos Granados FJ. Bilateral parotid sialadenosis associated with long-standing bulimia: a case report and literature review. J Maxillofac Oral Surg 2018;17:117–21. 146. Coleman H, Altini M, Nayler S, Richards A. Sialadenosis: a presenting sign in bulimia. Head Neck 1998;20:758–62. 147. Satoh M, Yoshihara T. Clinical and ultracytochemical investigation of sialadenosis. Acta Otolaryngol Suppl 2004;553:122–7.

8 

Pediatric Salivary Gland Diseases PATRICK J. BRADLEY (8.1–8.3), RAYMOND W. CLARKE (8.1–8.3), ODED NAHLIELI (8.4), AND VICTOR J. ABDULLAH (8.5)

8.1  PEDIATRIC SALIVARY GLAND NEOPLASMS Salivary neoplasms are uncommon in children. They may arise in the acini and ducts (epithelial tumors) or in mesenchymal tissue, e.g., the intraparotid lymphoid (lymphoma) or connective tissue (neurofibroma, schwannoma, rhabdomyosarcoma). They may be benign or malignant. Head and neck tumors of non-salivary origin may infiltrate the salivary glands, and the most common tumors encountered in children are lymphovascular lesions, which may be locally aggressive and rapidly proliferate, but are not true neoplasms.

Vascular Anomalies Infantile Hemangiomas Infantile hemangiomas are the most common tumors of the salivary glands in children.1 Some 90% occur in the parotid, usually presenting within a few weeks of birth. They follow a proliferative phase for 6–9 months, followed by involution, usually completed by 3–5 years. Most have extensive cutaneous involvement such that the diagnosis is clinically obvious, but some present as a palpable mass or an area of focal swelling with normal overlying skin. They cause a great deal of parental anxiety and are often thought to represent advanced malignancy, but imaging will show the characteristic appearance (Figs. 8.1.1, 8.1.2) and avoid the need for biopsy.2 Hemangiomas can usually be observed with no active medical or surgical intervention. Resolution can be hastened by the use of systemic propranolol. A small number of highly proliferative cases show rapid proliferation – e.g., Kaposiform hemangioendothelioma, an intermediate between a hemangioma and a malignant angiosarcoma3 – and in some cases there is extensive swelling encroaching on the orbit, or infiltrating the airway. Treatment with chemotherapy agents such as methotrexate, under the supervision of a pediatric oncologist, may be offered in these rare cases. 64

Lymphatic Malformations Lymphatic malformations may originate within the parotid (Type 1) but more often the gland is infiltrated by a lymphatic malformation of the surrounding tissue (Type II). The majority of patients with lymphatic malformations present at birth or within a few months, but cases have been diagnosed in late childhood and into adulthood.4 The typical presentation is of a painless, soft, fluctuant mass. Their growth is generally in proportion to the patient’s body growth, but infection and bleeding can lead to an acute increase in size. Clinical examination alone is insufficient to identify the extent, especially in the deep portion of the parotid gland. Sonography is useful but the deeper invasive disease is best shown by MRI. A T2-weighted image will enhance the malformation very effectively. Complete excision via a partial or total parotidectomy with facial nerve preservation is the method of choice for type I lymphatic malformation of the parotid gland. Preservation of the facial nerve should be achievable in all cases, but the nerve is often elongated and its course is aberrant as the malformation encompasses, deflects or buries it. Type II malformations may be more complex. Complete excision as a one-stage procedure is most likely to achieve complete eradication, but attempts to completely remove the deep infiltrative malformation may result in a serious functional deficit, and sclerosing agents, usually administered under the supervision of an interventional radiologist, are becoming more widely used either alone or as an adjunct to surgery.

Neoplasms Benign Epithelial Tumors Benign epithelial tumors typically present as a painless, palpable, asymptomatic, slow-growing mass. Minor salivary gland neoplasms, though rare, have been reported in children. As in adults, the commonest benign tumor is the pleomorphic salivary adenoma (PSA). Parotid gland PSAs occur most commonly in the lateral lobe, followed by the deep lobe and the parapharyngeal space. They occur in

CHAPTER 8  Pediatric Salivary Gland Diseases

Keywords Child Salivary Glands Hemangioma Lymphangioma Sialadenitis Parotitis Branchial Fistula Sialorrhoea

64.e1

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A

A

B • Fig. 8.1.1

  (A) Ultrasound scan of a parotid hemangioma in a 1-yearold child. (B) Note the extensive cavernous vessels.

children as young as 1 year old, but the mean age in children is 15 years.5 Investigation and management is similar to adult practice, but fine needle aspiration (FNA) is less reliable in children, who may not tolerate it well. Imaging is an essential part of the work-up, but MRI scanning in children will often require a general anesthetic.

Malignant Epithelial Tumors Malignant epithelial tumors are rare in children, with an incidence of 1 per million population. Parotid tumors in children cause a great deal of anxiety and it is often said that the proportion of malignant-to-benign tumors is higher in children than in adults, but a recent National Cancer Registration-based report from Denmark reports that this was not so. Most cases present in the second decade of life, but if such a tumor presents in a child under 10 years old, then it is more likely to be of a high grade with a poorer prognosis.6 Approximately 50% will report pain, and occasionally there is facial nerve palsy or tethering of the skin. Mucoepidermoid carcinoma is the most common (50%) followed by acinic cell (35%), with adenocarcinoma and adenoid cystic carcinoma accounting for most of the rest.7

B • Fig. 8.1.2

  MRI showing the characteristic “blush” of a parotid hemangioma. STIR sequence. (A) Coronal view. (B) Axial view.

Mesenchymal Tumors Mesenchymal tumors such as benign neuroblastoma, schwannoma, and primary neuroectodermal/Ewing sarcoma can also present. The salivary glands in children – particularly the parotid – have a high proportion of lymphoid tissue, and head and neck lymphomas not infrequently involve the parotid gland. Diagnosis can be delayed in children due to the rarity of these lesions and because they are assumed to be “reactive lymph nodes”. Rhabdomyosarcomas (RMS) are the most common malignancies of the head and neck in children,8 and not infrequently involve the salivary glands (Figs. 8.1.3, 8.1.4). They are designated by their location, and involvement of salivary glands is classified as

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A • Fig. 8.1.4  Rhabdomyosarcoma (RMS) parotid gland. MRI image, STIR sequence.

and staging involves imaging: ultrasound, CT, and MRI. Tissue diagnosis is essential and usually requires open biopsy. Genetic testing on the tissue helps to classify the pathologic group and aids the selection of treatment.

Treatment

B • Fig. 8.1.3  Rhabdomyosarcoma (RMS) involving the parotid gland. Post-gadolinium image. (A) Coronal view. (B) Axial view.

“non-orbital, non-parameningeal”. RMS usually affects young children and adolescents, with most cases occurring before the age of 10 years. All three histologic variants of RMS have been reported as affecting salivary glands: embryonal (most common), spindle cell, and alveolar (the poorest prognosis). The presenting signs and symptoms may include a slow-growing facial lump, and pain while eating or chewing. There may be a facial palsy.9 Initially, the overlying skin appears normal, but as the tumor progresses in size, changes including ulceration become obvious. Diagnosis

Benign tumors are managed much as in adults. Parotid surgery in children is especially challenging due to the small size and superficial position of the facial nerve.9 Bony landmarks, e.g., the mastoid process and the stylomastoid foramen, are less well-defined. Malignant tumors may involve a treatment combination of surgery, chemotherapy, and radiotherapy. Surgery has little role in the management of lymphoma or RMS, other than in diagnosis. Radiotherapy is increasingly important in pediatric oncology with proton therapy assuming a greater role in recent years.10 Malignant tumors are managed under the supervision of a pediatric oncologist with the support of a multidisciplinary team (MDT), and survival figures for pediatric malignancies are improving rapidly.

KEY POINTS • Hemangioma is the commonest congenital mass found in the parotid. • Imaging is essential. Multidisciplinary teams have improved prognosis. • Fine needle aspiration is of limited use in pediatric tumors. • The facial nerve may be very superficial and is easily vulnerable to iatrogenic trauma in children.

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8.2  PEDIATRIC SALIVARY GLAND INFLAMMATORY CONDITIONS Pediatric Salivary Inflammatory Diseases Inflammatory disorders/diseases may involve the parenchymal tissue (acini and ducts) causing a true sialadenitis of one or more of the major or the minor salivary glands, or as in the case of connective tissue disorders such as Sjögren syndrome, there may be a generalized pan-sialadenitis. Viral infections of the parotid tend to be bilateral, as in mumps; bacterial infection tends to affect a single gland, e.g., acute suppurative parotitis or parotid abscess. Salivary glands in children, especially the parotid, contain lymphoid tissue interspersed between the ductal and acinar tissue. Lymph nodes are intimately related to the capsule of the submandibular gland. Swellings in the parotid or submandibular area may be due, not to parenchymal salivary disease, but to lymphadenopathy. Parotidomegaly in a child should raise suspicion of lymphoid pathology.

• Fig. 8.2.1

 

Acute parotitis in a newborn.

Acute Viral Sialadenitis Viruses, e.g., mumps, coxsackie virus, echovirus, cytomegalovirus (CMV), and HIV, can present with acute enlargement of one or more salivary glands. Mumps – a once-common childhood infection caused by a paramyxovirus – is now rare in developed countries where the mumps, measles, and rubella (MMR) vaccination is widely available but outbreaks still occur, especially in adolescence.11 Presentation is with a mild febrile illness and bilateral enlargement of the parotid glands. The child is often fractious with fever and trismus. The parotid duct papillae may be swollen. Mumps is usually a benign childhood illness with uneventful recovery but aseptic meningitis, encephalitis, and acute pancreatitis are potentially fatal complications. Orchitis can lead to infertility in boys, and is still an important cause of sensorineural deafness, particularly in parts of the developing world where vaccination rates are low.

HIV Infection in Children HIV infection in children (see Chapter 9.3) may be complicated by enlargement of the parotid glands, typically bilateral. There is infiltration of lymphocytes, with follicular hyperplasia of intraparotid lymphoid tissue and the development of lymphoepithelial cysts. Ultrasound scanning may show multicystic intraparotid disease and should alert the clinician to the possibility of HIV infection acquired in the perinatal period.

Bacterial (Pyogenic) Sialadenitis Bacteria may infect the salivary glands, particularly if there are predisposing factors such as stasis of secretions, ectatic ducts and acini, and dental or gingival sepsis. Children with

reduced immunity, e.g., premature infants and children receiving chemotherapy for malignant disease, are especially at risk. Pyogenic organisms such as Streptococcus pyogenes, Haemophilus influenza and Staphylococcus aureus predominate, but anaerobic organisms and a host of unusual and antibiotic-resistant organisms may be implicated (see Chapter 7.1).12 Acute suppurative sialadenitis most frequently involves the parotid gland (Fig. 8.2.1). Treatment is initially medical and involves hydration, analgesics, and IV antibiotics. Infection may track beyond the gland and give rise to parapharyngeal abscess, or in the case of the submandibular gland a spreading cellulitis (Ludwig’s angina). Abscess formation and failure to respond to antibiotics will require surgical drainage. An acute abscess can be decompressed by needle aspiration. Should the abscess persist or be deeply seated, then formal open drainage may need to be performed. To decompress a parotid abscess, a preauricular incision is best. The parotid fascia is incised parallel to the facial nerve, bearing in mind the extremely superficial position of the facial nerve in children. For a submandibular gland abscess use a standard submandibular approach, taking care not to traumatize the marginal mandibular nerve. In both cases a drain may be needed.

Intrasalivary Lymphadenopathy Acute Lymphadenitis Enlargement of the neck lymph nodes in childhood is a normal feature of the developing immune system and will often involve the intraparotid nodes, causing transient parotidomegaly. Pathologic cervical lymphadenitis can result from pharyngeal or sinonasal sepsis and progress to a coalescent mass of necrotic tissue within the capsule of the

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gland. Pyogenic organisms such as Staphylococcus aureus and Streptococcus pyogenes are usually to blame. This can become intensely painful and may need drainage in the same way as an intraparotid parenchymal abscess.

Granulomatous Infection Mycobacterium tuberculosis infection of the neck is still common, particularly in the developing world. It may involve nodes adjacent to and within the parotid and submandibular glands. Non-tuberculous mycobacterial (NTM) infection of the neck is now far more common in Western communities.13,14 It mainly affects otherwise healthy children between 1 and 3 years of age. The responsible organisms (Mycobacterium avium-intracellulare, Mycobacterium kansasii, and Mycobacterium scrofulaceum) are widely distributed in soil and rarely cause pathology in older children or in adults. The condition is sometimes termed atypical mycobacteria (ATM) or environmental mycobacteria. The glands enlarge painlessly and the child is generally perfectly well other than that the parents notice a neck swelling (Fig. 8.2.2). As the disease progresses, lymph nodes coalesce, there may be central liquefaction with superimposed infection and abscess formation, and the overlying skin develops

• Fig. 8.2.2

 

Non-tuberculous mycobacteria.

a characteristic discoloration. It may break down to cause an unsightly wound. Ultrasound (Fig. 8.2.3) and MRI – if available – will help to delineate the extent of involvement. Histologic diagnosis will show non-caseating necrotic granulomatous tissue, but culturing the organism is notoriously difficult. Spontaneous resolution over a period of several months can be expected, even with no treatment. The infection is not transmitted by direct contact and the child can continue to go to school during the active phase of the disease. If there are loculi of infection or abscess formation, this can be dealt with by aspiration under a short general anesthetic. Surgery is often considered but the position of the involved glands and the state of the overlying skin are such as to present a significant risk to one or more of the branches of the facial nerve. Surgery – by incision and drainage with curettage or full excision if it can be done safely – is reserved for extensive disease or where there is impending or established skin necrosis. Chemotherapy using a combination of macrolide antibiotics and antituberculous medication can be offered to hasten resolution, but many prefer a “watch-and-wait” approach. The esthetic result is usually excellent but the scarring may take many months to resolve. Cat-scratch disease (Fig. 8.2.4) is a granulomatous lymphadenitis caused by Bartonella henselae. Infection occurs through a scratch or bite from a cat or kitten. Most cases involve the lymph nodes and skin surrounding the parotid and submandibular glands. Aspiration and microscopy can be helpful to identify the organism. Management is symptomatic. The adenopathy generally resolves in a few months. Actinomycosis involving the salivary glands is rare in children. It usually presents as a painless, slowly growing hard mass that develops multiple sinus tracts. On imaging, multiple areas of necrosis can be seen. The presence of sulfur-like granules in the purulent discharge, aspirate, or tissue biopsy, is pathognomonic for the disease. Treatment includes surgical drainage or excision and long-term (6–12 months) antibiotics (penicillin, clindamycin, or tetracycline).

• Fig. 8.2.3  Ultrasound scan showing “collar stud abscess” in NTM. The abscess has ruptured through the cervical fascia.

CHAPTER 8  Pediatric Salivary Gland Diseases

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• Fig. 8.2.5  MRI scan showing mass in the right submandibular region in a 14-year-old girl. A neoplasm was suspected but excision biopsy was performed and histology showed Langerhans cell histiocytosis. • Fig. 8.2.4

 

Cat-scratch disease.

Non-Infective Sialadenitis Sarcoidosis may affect the parotids. A number of disorders, which give rise to cervical adenopathy and are often initially thought to represent lymphoma, may present in the salivary glands. These are sometimes referred to as the “pseudolymphomas”.15 They include Kimura disease – a rare chronic inflammatory disorder involving subcutaneous tissue and frequently associated with head and neck lymphadenopathy and/or salivary gland enlargement. Kawasaki disease is an acute inflammatory vasculitis of early childhood, presenting with fever, rash, unilateral cervical lymphadenopathy, and

KEY POINTS • Parotid enlargement in a child is often due to lymphoid pathology. • Neonatal parotitis is commoner in babies with immune dysfunction. • NTM is self-limiting, and does not always need active treatment. • Surgery for inflammatory parotid disease in children should be undertaken with extreme care and by an experienced parotid surgeon.

coronary artery disease. Rosai–Dorfman syndrome is a selflimiting rare disorder characterized by proliferation of histiocytes within lymph nodes. Langerhans cell histiocytosis is another variant (Fig. 8.2.5). These conditions are usually diagnosed histologically when a salivary gland mass has been excised for suspected neoplasia.

8.3  BRANCHIAL ARCH ANOMALIES Branchial (Pharyngeal) Arch Clefts and Sinuses In a developing embryo, the structures that make up the head and neck region are formed from a series of pharyngeal or “branchial” arches. These are bars of mesenchymal tissue separated by deep external clefts and internal pouches. Branchial arch anomalies have been classified into cysts, sinuses, and fistulas, based on the number of surface openings.16 Anomalies are caused by incomplete or anomalous development of the ectoderm, and usually present in infancy and childhood but can be diagnosed for the first time at any age. The first branchial arch includes the maxillary and mandibular processes and many of the structures that form the ear. The first cleft gives rise to the external auditory meatus.

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The parotid gland is closely related to any first branchial cleft anomaly. Presentation may be chronic purulent drainage from the ear, periauricular swelling in the parotid area, and abscess or persistent fistula in the neck. Abnormalities of the first arch or cleft are often intimately related to the parotid gland, hence their importance to surgeons who operate in this area. Second arch anomalies are far more common than first arch anomalies but present lower in the neck, typically with an opening along the anterior border of the sternomastoid.

must follow the tract, which may be intimately related to the facial nerve. Pediatric parotidectomy should be undertaken by specialist surgeons using a facial nerve monitor and not by the occasional surgeon, and parents need to be carefully counselled preoperatively so that they are aware of the risk to the facial nerve trunk and its branches. The nerve is far more superficial than in adults, and bony landmarks such as the mastoid process are poorly developed.

First Arch Anomalies

The sinus runs along up the carotid sheath and up towards the tonsil and the neck orifice. It may discharge saliva due to the presence of salivary acinar tissue within the tract. If surgical intervention is indicated, then, as in the case of first arch anomalies, complete excision of the sinus or fistula is recommended. This is usually performed through a single skin incision around the external opening with upward dissection along the tract, following it in some cases into the tonsil bed. A second higher incision (step-ladder technique) may be required and while these tracts are not intimately related to the facial nerve, the branches of the nerve may be at risk during incision and dissection.

These may take the form of a cyst, a sinus, or a fistula in the periauricular area. A fistula will typically have one opening in the neck above the level of the hyoid bone and another in the ear canal. Cysts may be intraparotid, and are frequently misdiagnosed. They will often not present until there has been one or more acute infection. An acute infection is managed with antibiotics, but consider elective surgery when the inflammatory episode has resolved. The diagnosis is often made following several episodes of infection, so that surgery is delayed due to scarring, making identification of landmarks even more difficult. Ultrasound and contrast sinograms have a role in diagnosis and in delineating the extent of lesions but an MRI scan or CT scan may give some information about the deep extent of any sinus or swelling and its proximity to the facial nerve and middle ear.17,18 Because of the close anatomic relationship of any cyst or tract to the facial nerve, a parotidectomy incision is recommended with the use of a nerve monitor and with formal identification and dissection of the facial nerve (Fig. 8.3.1). Gentle insertion of a lacrimal probe can be useful, as can instillation of methylene blue. Complete excision of the lesion is essential to prevent recurrence and the surgeon

Second Arch Anomalies

KEY POINTS • Abnormalities of the branchial arches can cause cysts, sinuses, and fistulas in the neck. • First arch abnormalities are often intimately related to the parotid gland. • Branchial cysts may become infected, and elective surgery is best undertaken when the infection has subsided. • Imaging is an important element of the diagnosis and management of branchial arch anomalies. • Definitive surgery may involve formal superficial parotidectomy. • Recurrence is common following incomplete excision.

Incision

Facial nerve

Fistula tract Opening of fistula SCM

• Fig. 8.3.1

Parotid gland (retracted)

Digastric muscle SCM

 

Surgical excision of a first arch fistula. SCM, sternocleidomastoid muscle.

CHAPTER 8  Pediatric Salivary Gland Diseases

8.4  JUVENILE RECURRENT PAROTITIS

71

Inflammatory salivary gland disease represents more than one-third of salivary gland pathology in childhood.19 Specifically, juvenile recurrent parotitis (JRP, the alternative term: juvenile recurrent sialadenitis) is defined as recurrent nonsuppurative parotid inflammation, generally associated with non-obstructive sialectasis of the parotid gland, with a usual age of onset at 3–6 years. It may resolve after puberty,19,20 however, it also may remain after puberty, and such cases are appropriate to call an adult type JRP.21

Etiology and Pathogenesis A variety of etiologic factors have been proposed, including allergy, viral infection, hereditary and genetic factors (autosomal dominant inheritance), autoimmunity, and congenital structural defects, but most of these factors were excluded in recent works.19–22 Currently, ductal and gland malformation may be considered as the main causes of JRP.21,23 Congenital ectasia and retrograde infection from the mouth are reasonable explanations of the pathogenesis of JRP. Another explanation for the pathogenesis of JRP is the retrograde infection that may produce a decrease in salivary secretion and decreased salivary flow in the parotid gland.21–24

Clinical Picture and Examination Children usually complain of pain and swelling occurring minutes to several hours after a meal. JRP affects children from infancy to age 12 but the onset of symptoms in older children is possible. The condition is characterized by swelling of the parotid gland and systemic symptoms such as fever and malaise. It is most commonly unilateral, but bilateral exacerbation can occur.19,21,24 When the symptoms are bilateral, they are usually more prominent on one side. Swelling appears suddenly over a period of a few hours and may be accompanied by xerostomia. The swelling often will recede slowly with time, and often the parents and child relate that massage of the gland relieves the symptoms. Exacerbation lasts for several days, and the episodes may recur over many years with variable frequency. The morbidity during the years of active disease can be significant, with multiple recurrences, days lost from school, and the requirement for therapy. The child should have a history of multiple episodes, treated with and responding to antibiotic therapy. Observation of submandibular, preauricular, and postauricular regions followed by intraoral examination assesses swelling and erythema (Fig. 8.4.1A). Surgical magnification loops (2.5–3.5) are very useful to improve visualization of the orifice of Stensen’s duct (Fig. 8.4.1B). The orifice may be red and edematous and appear dilated in many cases. Plaques or whitish secretions from the duct may represent frank infection. Palpation while examining the parotid gland and duct helps to differentiate the gland from adjacent lymph nodes; manual palpation allows the

A

B • Fig. 8.4.1

  (A) A 7-year-old girl with juvenile recurrent parotitis (JRP) of the right parotid gland. (B) A wide opening of the Stensen’s duct of a child suffering from JRP. The Stensen’s duct may appear red and edematous.

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B A • Fig. 8.4.2

  (A) Ultrasonography image of a child suffering from JRP demonstrate sialectasis of the parotid gland. (B) A sialendoscopic image of a child with JRP. Note the white appearance of the Stensen’s duct.

surgeon to determine the consistency of the gland. One should also massage the gland, to milk and inspect the saliva with the help of magnification loops.

Laboratory, Histopathology, and Imaging Results of routine laboratory tests are usually normal except amylase that is elevated in the acute phase. Autoimmune antibody titers are usually negative. Histopathologic evaluation of the diseased gland reveals a lymphocytic infiltrate that tends to form lymphoid follicles and small ductal dilations.25 These intraductal cyst-like dilations are demonstrated clearly by sialography and are called sialectasis or sialectasia. Sialectasis is usually present in the asymptomatic contralateral gland, as well. Ultrasonographic examinations (Fig. 8.4.2A) demonstrate multiple small hypoechogenic areas and occasionally punctate calcifications, corresponding to the sialectasis demonstrated by sialography.26 CT and MRI demonstrate the sialectasis and nonspecific enlargement of the parotid glands, with heterogeneous density and signal intensity.27

Sialendoscopy Diagnostic and interventional sialendoscopy is described in detail Sections 3 and 5 of this book. The following endoscopic findings are indicative (Fig. 8.4.2B): (1) wide orifice of the Stensen’s duct; (2) sialectasis, strictures, and kinks in the main and secondary ducts; and (3) white appearance of the main duct, without the natural proliferation of blood vessels as seen in a healthy gland (hypovascularization).22,28–31 These findings support the theory that ductal malformation is responsible for the formation of JRP.

Differential Diagnosis The differential diagnosis must be performed with obstructive, sialolith, lymphoepithelial, granulomatous, immunoglobulin

G4-related, radiation-induced, and radioactive iodineinduced sialadenitis, sialadenosis, pneumoparotitis, and necrotizing sialometaplasia.21,27,32 Primary Sjögren syndrome is considered when JRP is assessed, despite the rarity of this condition.

Management Treatment of the acute phase of JRP is observation, supportive care, and antibiotic therapy. Antibiotic treatment prevents further damage to the glandular parenchyma. Standard treatment consists of antibiotics for at least 10 days at the acute phase of the disease.30,32,33 Between episodes, a regimen of massage, encouragement of fluid intake, application of heat, use of chewing gum or sour candy, and sialagogues have been advocated. Intermittent duct probing and dilation, as well as overfilling of the gland during sialography, have also been recommended. Other management methods include duct ligation to produce glandular atrophy, parotidectomy, and tympanic neurectomy. Operative sialendoscopy of the affected gland or glands with steroid irrigation can be considered currently as the best therapeutic treatment for JRP.22,30,31,34–37 Lavage may be performed with saline solution, hydrocortisone, antibiotics or a combination of these solutions (Fig. 8.4.3).

KEY POINTS • Currently, ductal and gland malformation are considered as the main causes of JRP. • Sialendoscopy findings include wide orifice and white appearance of the Stensen’s duct; sialectasis, strictures, and kinks in the main and secondary ducts. • Operative sialendoscopy of the affected gland with steroid irrigation is currently the best therapeutic treatment.

CHAPTER 8  Pediatric Salivary Gland Diseases

73

scales);44 frequency, drooling quotient,45 number of bibs used per day, and the Suskind Scale.46

Non-Surgical Treatment

• Fig. 8.4.3  Intraoperative view during sialendoscopic treatment of a 4-year-old boy suffering from JRP. Note the transillumination effect during the procedure helping the surgeon to locate the endoscope.

8.5  SALIVARY DROOLING IN CHILDREN Introduction Saliva is not healthy for the external skin in a drooling child. On the other hand, the lack of saliva in the oral cavity in the over-zealously treated child for excessive salivation can result in a significant impact on the protective mechanisms for the teeth and oral mucosa. Drooling is the unintentional spillage of saliva from the oral cavity either anteriorly soiling the perioral region, neck and clothes, or posteriorly causing aspiration and recurrent pneumonia. Most drooling patients are those with cerebral palsy, neuromuscular disorders, and mental retardation. Of patients with cerebral palsy, 25–35% suffer from drooling.38,39 Approximately 10% of children with mental retardation may drool.39 Their deficits lie in their poor mouth closure and poor coordination of the oral and pharyngeal phases of swallowing, which may be in part a sensory deficit or secondary to dystonia.40,41 Congenital or acquired pediatric neuromuscular diseases are broadly divided into the muscular dystrophies, myopathies, and neuropathies.42 Drugs may also cause drooling, particularly those with cholinergic effects such as anticonvulsants, nitrazepam, ketamine, morphine, and haloperidol. Mercury toxicity and insecticides, which contain irreversible anticholinesterases, may also cause drooling. Gastroesophageal reflux may induce a hypersalivation reflex resulting in episodic drooling.43 The successful management of drooling children requires, ideally, a MDT composed of a pediatric neurologist, an otolaryngologist, a pediatric speech therapist/occupational therapist, a physiotherapist, supported by a pediatric radiologist, and an anesthesiologist. At the authors’ institution, it is routine to perform the following assessment: a Visual Analogue Scale (from 1–10: 1 is dry and 10 is wet); Modified Thomas-Stonell Drooling Scale (severity and frequency

Pharmacologic agents commonly used in children include hyoscine hydrobromide (scopolamine hydrobromide) and glycopyrrolate. The more potent agent, oral glycopyrrolate 20–100 µg/kg three times a day, has been shown to be effective in decreasing sialorrhea in children with cerebral palsy and neurodevelopmental disabilities.47 Oral appliances are also available such as the Castillo Morales appliance, which is a dental plate with a bead attached to the plate inside the oral cavity to stimulate tongue and lip movements, thus enhancing dorsal cranial displacement of the tongue to facilitate salivary clearance.48 Parasympathetic stimulation is via the release of acetylcholine (Ach) and its effect on M3 muscarinic receptors, which increases the blood flow, acinar flow, ductal secretions and salivary expulsion. Use of anticholinergic agent neurotoxin botulinum blocks the release of synaptic Ach. There are seven distinct types of botulinum toxins (Types A–G). Types A and B are the ones mostly used in sialorrhea. These neurotoxins work on different presynaptic proteins, resulting in the inhibition of Ach release, effectively a chemical parasympathetic denervation, which occurs over 48–72 hours. Its effect usually lasts 3–6 months.49 A mixed treatment network meta-analysis by Sridharan and Sivaramakrishnan50 revealed the superiority of botulinum toxins A and B over oral agents except for benztropine, a drug used for Parkinsonian patients, which was as effective if not more effective in symptom reduction when compared with placebo. Botulinum toxin A has different subtypes. Onabotulinumtoxin A (Allergan) is the one commonly used for sialorrhea. It requires storage at –5°C until usage and reconstitution.49 The newer botulinum toxin A (Xeomin) has a less complex protein and can be stored at room temperature. Some centers use rimabotulinum toxin B (Myobloc) with good results. Botulinum toxin B may have systemic anticholinergic effects. As for dosage, our institution uses Allergan and follows the Auckland Starship Guidelines,51 20 units per submandibular gland and 10 units per parotid gland, totalling 60 units maximum for all four glands. The dose is reduced for children younger than 10 years. As for Xeomin, 25 units to each of the four glands, two submandibular and two parotid glands, and 50 units to each of the two parotid glands only, have worked well in symptomatic control.52,53 Xeomin has recently been approved by the Food and Drug Administration (FDA) for drooling patients. It is presently the only FDA-approved neurotoxin for the treatment of sialorrhea. In our institution, as a first-line treatment, 2–3 site injection of the submandibular glands under general anesthesia and ultrasound control is performed with at least 3 months’ intervals, four times. Three-point injection to the parotid glands may be further undertaken if required (Fig. 8.5.1).

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Surgical Treatment Sectioning of the chorda tympani and severing the tympanic plexus are generally not favored today because of their limited and unpredictable efficacy and associated morbidity such as taste disturbance in chorda sectioning. Salivary duct ligation is suitable for posterior drooling or coexisting posterior and anterior drooling (Fig. 8.5.2). It is simple to perform with no external scars and minimal risks to nearby nerves. A report of 4-duct ligation, which included 38 children with neurologic impairment, found the mean duration of effect was 52.6 months and 80% of caregivers reported an improvement at 1 month; and 69% and 71% reported improvement at 1 year and at the most recent followup. Thirteen complications were reported in 12 patients.

• Fig. 8.5.1  Ultrasound guided botulinum toxin injection of the right submandibular gland.

2

1

A

3

4

• Fig. 8.5.2

 

Parotid and submandibular duct ligation. (A) Parotid duct ligation.

CHAPTER 8  Pediatric Salivary Gland Diseases

75

Orifice

B

Double ligature placed

Closure

• Fig. 8.5.2, cont’d  (B) Submandibular gland ligation.

Complications included persistent facial/glandular swelling and aspiration pneumonia.54 Submandibular duct transposition first described in 1969 has been a favored procedure for patients with moderate to severe anterior drooling in most institutions (Fig. 8.5.3).55 Excellent outcome in the short, medium, and long term has been observed.56 It is not necessary to remove the tonsils, though it is this author’s practice to remove tonsils grade II or above alongside the transposition. The submandibular duct opening may be placed between the back of the tongue and the anterior tonsillar pillar or in the tonsillar fossa after a tonsillectomy. Excising an ample sized piece of mucosa lateral to the duct opening generally helps in suture placement. The floor of the mouth should be loosely sutured. This author does not routinely excise the sublingual glands, despite a small risk of ranula formation. Reserved as a last resort is the excision of the salivary glands. If 4-duct ligation fails in posterior drooling, bilateral

submandibular gland excision is an option reducing most of the resting saliva. A case series of primary bilateral submandibular gland excision with bilateral parotid duct ligation revealed 87% of caregivers reporting no drooling, or significant improvement. The parotid duct ligation reduced in addition, the masticatory saliva from the parotid.57

KEY POINTS • The multidisciplinary team is important in the selection of treatment. • Anticholinergics may result in unpleasant side effects. • Botulinum injection requires repeated short sessions of anesthesia or deep sedation. • Salivary duct ligation is suitable for posterior drooling or coexisting posterior and anterior drooling. • Submandibular duct transposition is favored for patients with moderate to severe anterior drooling.

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1

2

3

4

• Fig. 8.5.3

Right submandibular duct transposition with floor of mouth tunneling and placement at the tongue base and anterior tonsillar pillar junction.  

CHAPTER 8  Pediatric Salivary Gland Diseases

References 1. Fowell C, Monaghan A, Nishikawa H. Infantile haemangiomas of the head and neck: current concepts in management. Br J Oral Maxillofac Surg 2016;54:488–95. 2. Weber FC, Greene AK, Adams DM, et al. Role of imaging in the diagnosis of parotid infantile hemangiomas. Int J Pediatr Otorhinolaryngol 2017;102:61–6. 3. Rekhi B, Sethi S, Kulkarni SS, Jambhekar NA. Kaposiform hemangioendothelium in tonsil of a child associated with cervical lymphangioma: a rare case report. World J Surg Oncol 2011;9:57. 4. Wiegand S, Zimmermann AP, Eivazi B, et al. Lymphatic malformations involving the parotid gland. Eur J Pediatr Surg 2011;21:242–5. 5. Bradley PJ, Eisele DW. Salivary gland neoplasms in children and adolescents. Adv Otorhinolaryngol 2016;78:175–81. 6. Stevens E, Andreasen S, Bjorndal K, Homoe P. Tumors in the parotid are not relatively more often malignant in children than in adults. Int J Pediatr Otorhinolaryngol 2015;79:1192–5. 7. Yoshida EJ, Garcia J, Eisele DW, Chen AM. Salivary gland malignancy in children. Int J Pediatr Otorhinolaryngol 2014;78:174–8. 8. Reilly BK, Kim A, Pena MT, et al. Rhabdomyosarcoma of the head and neck in children: review and update. Int J Pediatr Otorhinolaryngol 2015;79:1477–83. 9. Lee GS, Perkins JA, Oliaei S, Manning SC. Facial nerve anatomy, dissection and preservation in lymphatic malformation management. Int J Pediatr Otorhinolaryngol 2008;72:759–66. 10. Vogel J, Both S, Kirk M, et al. Proton therapy for pediatric head and neck malignancies. Pediatr Blood Cancer 2018;65(2):26858. 11. Lopez-Perea N, Masa-Calles J, Torres de Mier MV, et al. Shift within age-groups of mumps incidence, hospitalizations and severe complications in a highly vaccinated population. Spain, 1998–2014. Vaccine 2017;35(34):4339–45. 12. Dias Costa F, Ramos Andrade D, Cunha FI, Fernandes A. Group B streptococcal neonatal parotitis. BMJ Case Rep 2015. 13. Spinelli G, Mannelli G, Arcuri F, et al. Surgical treatment for chronic cervical lymphadenitis in children. Experience from a tertiary care paediatric centre on non-tuberculous mycobacterial infections. Int J Pediatr Otorhinolaryngol 2018;108:137–42. 14. Mahadevan M, Neeff M, Van Der Meer G, et  al. Non-tuberculous mycobacterial head and neck infections in children: analysis of results and complications for various treatment modalities. Int J Pediatr Otorhinolaryngol 2016;82:102–6. 15. Piris MA, Aguirregoicoa E, Montes-Moreno S, Celeiro-Munoz C. Castleman disease and Rosai-Dorfman disease. Semin Diagn Pathol 2018;35(1):44–53. 16. Schroeder JW Jr, Mohyuddin N, Maddalozzo J. Branchial anomalies in the pediatric population. Otolaryngol Head Neck Surg 2007;137(2):289–95. 17. Li W, Xu H, Zhao L, Li X. Branchial anomalies in children: a report of 105 surgical cases. Int J Pediatr Otorhinolaryngol 2018;104:14–18. 18. Bajaj Y, Ifeacho S, Tweedie D, et al. Branchial anomalies in children. Int J Pediatr Otorhinolaryngol 2011;75(8):1020–3. 19. Chitre VV, Premchandra DJ. Recurrent parotitis. Arch Dis Child 1997;77:359–63. 20. Francis CL, Larsen CG. Pediatric sialadenitis. Otolaryngol Clin North Am 2014;47(5):763–78. 21. Shacham R, Droma EB, London D, et al. Long-term experience with endoscopic diagnosis and treatment of juvenile recurrent parotitis. J Oral Maxillofac Surg 2009;67(1):162–7.

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22. Reid E, Douglas F, Crow Y, et al. Autosomal dominant juvenile recurrent parotitis. J Med Genet 1998;35(5):417–19. 23. Bernkopf E, Colleselli P, Broia V, de Benedictis FM. Is recurrent parotitis in childhood still an enigma? A pilot experience. Acta Paediatr 2008;97(4):478–82. 24. Xie LS, Pu YP, Zheng LY, et al. Function of the parotid gland in juvenile recurrent parotitis: a case series. Br J Oral Maxillofac Surg 2016;54(3):270–4. 25. Hellquist H, Skalova A. Histopathology of the salivary glands. Berlin: Springer-Verlag; 2014. p. 37–48. 26. Friedman E, Patiño MO, Udayasankar UK. Imaging of pediatric salivary glands. Neuroimaging Clin N Am 2018;28(2):209–26. 27. Abdel Razek AAK, Mukherji S. Imaging of sialadenitis. Neuroradiol J 2017;30(3):205–15. 28. Nahlieli O, Shacham R, Shlesinger M, Eliav E. Juvenile recurrent parotitis: a new method of diagnosis and treatment. Pediatrics 2004;114(1):9–12. 29. Erkul E, Gillespie MB. Sialendoscopy for non-stone disorders: the current evidence. Laryngoscope Investig Otolaryngol 2016;1(5):140–5. 30. Berta E, Angel G, Lagarde F, et al. Role of sialendoscopy in juvenile recurrent parotitis (JRP). Eur Ann Otorhinolaryngol Head Neck Dis 2017;134(6):405–7. 31. Silva L, Babicsak G, Dolci RL. Salivary gland endoscopy in children: a systematic review. Rev Assoc Med Bras (1992) 2016;62(8):795–9. 32. Leerdam CM, Martin HC, Isaacs D. Recurrent parotitis of childhood. J Paediatr Child Health 2005;41:631–4. 33. Isaacs D. Recurrent parotitis. J Paediatr Child Health 2002;38(1):92–4. 34. Berlucchi M, Rampinelli V, Ferrari M, et al. Sialoendoscopy for treatment of juvenile recurrent parotitis: the Brescia experience. Int J Pediatr Otorhinolaryngol 2018;105:163–6. 35. Singh PP, Goyal M, Goyal A. Sialendoscopic approach in management of juvenile recurrent parotitis. Indian J Otolaryngol Head Neck Surg 2017;69(4):453–8. 36. Schwarz Y, Bezdjian A, Daniel SJ. Sialendoscopy in treating pediatric salivary gland disorders: a systematic review. Eur Arch Otorhinolaryngol 2018;275(2):347–56. 37. Ogden MA, Rosbe KW, Chang JL. Pediatric sialendoscopy indications and outcomes. Curr Opin Otolaryngol Head Neck Surg 2016;24(6):529–35. 38. Becmeur F, Horta-Geraud P, Brunot B, et al. Diversion of salivary flow to treat patients with cerebral palsy. J Pediatr Surg 1996;31:1629–33. 39. Sellars SL. Surgery of sialorrhoea. J Laryngol Otol 1985;99:1107–9. 40. Lespargot A, Langevin MF, Muller S, Guillemont S. Swallowing disturbances associated with drooling in cerebral-palsied children. Dev Med Child Neurol 1993;35:298–304. 41. Ekedahl C, Månsson I, Sandberg N. Swallowing dysfunction in the brain-damaged with drooling. Acta Otolaryngol 1974;78:141–9. 42. van den Engel-Hoek L, de Groot IJ, de Swart BJ, Erasmus CE. Feeding and swallowing disorders in pediatric neuromuscular diseases: an overview. J Neuromuscul Dis 2015;2:357–69. 43. Mandel L, Tamari K. Sialorrhea and gastroesophageal reflux. J Am Dent Assoc 1995;126:1537–41. 44. Thomas-Stonell N, Greenberg J. Three treatment approaches and clinical factors in the reduction of drooling. Dysphagia 1988;3:73–8. 45. van Hulst K, Lindeboom R, van der Burg J, Jongerius P. Accurate assessment of drooling severity with the 5-minute drooling

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quotient in children with developmental disabilities. Dev Med Child Neurol 2012;54:1121–6. 46. Suskind DL, Tilton A. Clinical study of botulinum-A toxin in the treatment of sialorrhea in children with cerebral palsy. Laryngoscope 2002;112:73–81. 47. Eiland LS. Glycopyrrolate for chronic drooling in children. Clin Ther 2012;34:735–42. 48. Marinone S, Gaynor W, Johnston J, Mahadevan M. Castillo Morales Appliance Therapy in the treatment of drooling children. Int J Pediatr Otorhinolaryngol 2017;103:129–32. 49. Daniel SJ. Botulinum toxin injection techniques for pediatric sialorrhoea. Operat Tech Otolaryngol Head Neck Surg 2015;26:42–9. 50. Sridharan K, Sivaramakrishnan G. Pharmacological interventions for treating sialorrhea associated with neurological disorders: a mixed treatment network meta-analysis of randomized controlled trials. J Clin Neurosci 2018;51:12–17. 51. Mahadevan M. Starship Clinical Guidelines: Botox A for use in sialorrhoea (drooling). New Zealand: Starship Child Health. Available from: https://www.starship.org.nz/for-healthprofessionals/starship-clinical-guidelines/b/botox-a-for-use-insialorrhoea-drooling/#table1/.

52. Restivo DA, Panebianco M, Casabona A, et al. Botulinum toxin A for sialorrhoea associated with neurological disorders: evaluation of the relationship between effect of treatment and the number of glands treated. Toxins (Basel) 2018;10:55. 53. Martínez-Poles J, Nedkova-Hristova V, Escribano-Paredes JB, et al. Incobotulinumtoxin A for sialorrhea in neurological disorders: a real-life experience. Toxins (Basel) 2018;10(6):E217. 54. Khan WU, Islam A, Fu A, et al. Four-duct ligation for the treatment of sialorrhea in children. JAMA Otolaryngol Head Neck Surg 2016;142:278–83. 55. Laage-Hellman JE. Retroposition augl submandibularis utforsgong som behandling vid drazling. Nordisk Med 1969;82:1522. 56. Kok SE, van der Burg JJ, van Hulst K, et al. The impact of submandibular duct relocation on drooling and the well-being of children with neurodevelopmental disabilities. Int J Pediatr Otolaryngol 2016;88:173–8. 57. Stern Y, Feinmesser R, Collins M, et al. Bilateral submandibular gland excision with parotid duct ligation for treatment of sialorrhea in children: long-term results. Arch Otolaryngol Head Neck Surg 2002;128:801–3.

9 

Benign Cystic Lesions SUMIT SAMANT (9.1, 9.2), ZAHOOR AHMAD (9.1, 9.2), RANDALL P. MORTON (9.1, 9.2), AND ALFRED E. BACON III (9.3)

9.1  RANULA

Pathogenesis

Introduction

Harrison has proposed two theories for pathologenesis: extravasation of mucus through damaged duct of Rivinus or from herniated SLG, secondary to trauma or obstruction.3 The SLG secretes mucinous saliva spontaneously without the need of neurological stimulus. Outside the confines of the sublingual gland and duct system, extravasated saliva is only limited by either the space between mylohyoid and mucosa in the oral cavity or by inflammatory fibrosis within tissues in the neck and removal of mucin by macrophages. The former process forms a simple ranula and the latter forms a plunging ranula, both bounded by inflammatory granulation tissue, not epithelium. Epidemiologic study has revealed a high risk of plunging ranula among Maori and Pacific Islanders.6

A cyst can be defined as a pathologic cavity having fluid, semifluid, or gaseous contents, and not created by accumulation of pus.1 It does not necessarily have an epithelial or endothelial lining; inclusion of lining in the definition results in a somewhat artificial distinction between pseudocysts and “true” cysts. Benign cystic lesions of salivary glands may be developmental, degenerative, or neoplastic.2 In Sections 9.1 and 9.2, we focus on degenerative lesions that include mucoceles, mucous retention cysts, salivary duct cysts, and the specific entity of ranula. Ranula presents as a translucent submucosal swelling in the floor of mouth, arising from collection of saliva extravasated from a sublingual salivary gland (SLG). Wiseman stated in 1676 that ranulas could cause a croaking speech, and this, together with the resemblance of the oral ranula to the belly or air sac of a frog, justified the term ranula, meaning little frog (Latin: rana = “frog”; ulus = “small”).3 If extravasated saliva tracks inferior to the floor of mouth formed by the pair of mylohyoid muscles, the term diving, plunging, or cervical ranula is applied.4

Relevant Anatomy The anatomy of the sublingual space dictates the pathogenesis of ranula and the rationale behind its definitive treatment. The SLG consists of unencapsulated mucinogenic glandular tissue lying within areolar tissue between the mylohyoid muscle and oral mucosa.3 Several lesser sublingual glands commonly drain through individual ducts of Rivinus into plica sublingualis. Greater SLG, if present, lies posteromedial to the lesser glands and drains via Bartholin’s duct into either Wharton’s duct or directly into the caruncula sublingualis.5 Over 40% of cadavers have a dehiscence in the mylohyoid muscle that can allow herniation of the SLG or saliva extravasation into the neck.

Clinical Presentation Most ranulas appear within the first three decades of life.7,8 Common presenting features are disruption to normal oral function from floor of mouth swelling (Fig. 9.1.1), and cosmetic concerns in cases of plunging ranula (Fig. 9.1.2). Specific history of trauma is usually absent. Episodes of increase in swelling associated with pain and tenderness secondary to inflammation may occur. Indeed, many misdiagnosed cases of plunging ranula may undergo incision and drainage for a presumed (dental) abscess that turns out to be an inflamed pseudocyst.9

Differential Diagnosis Differential diagnosis for this clinical presentation includes abscess, simple (e.g., dermoid) cyst, thyroglossal duct cyst, cystic hygroma, lymphangioma, and lipoma.10 Clinical diagnosis of ranula is usually straightforward. However, diagnostic errors may still arise. Atypical presentation may confound, as described by Abt et al., who reported a case of plunging ranula with direct extension to the prestyloid parapharyngeal space, masticator space, and parotid gland without involving the submandibular space.11 79

CHAPTER 9  Benign Cystic Lesions

Keywords Ranula Lingual Gland Salivary Gland HIV Benign Salivary Cyst

79.e1

Inflammatory Conditions

80 se c t i o n 2 80

• Fig. 9.1.1

 

Clinical photograph of simple ranula.

A

B • Fig. 9.1.2

 

Clinical photograph of plunging ranula.

Investigations It is recommended that aspiration of cervical ranula be performed.10,12 Testing of classical thick, mucinous aspirate for presence of salivary amylase, after dilution with normal saline, confirms the diagnosis. Radiological confirmation can be performed with ultrasonography (Fig. 9.1.3). MRI scan is recommended for recurrent or atypical cases.

• Fig. 9.1.3  (A) Coronal ultrasound (US) view of the midline neck. Herniation of the bilateral sublingual glands (SLG) through the bilateral mylohyoid muscle dehiscence (MH). (B) Panoramic sagittal oblique US of the right anterior neck. Cystic fluid component shown by white arrow and R.

The focus for treatment is generally removing the sublingual gland or sclerotherapy with OK-432. For simple ranula, there are various treatments. We favor micromarsupialization, a minimally invasive procedure, in which a suture is passed through the lesion at its greatest diameter.13 This forms an epithelialized tract through which the accumulated saliva drains. If this fails, definitive treatment by SLG excision is recommended.

on its lingual aspect.12 Mucosa overlying the SLG is then dissected off the gland using sharp dissection. Traction is then applied to the gland and blunt dissection will identify Wharton’s duct and lingual nerve. These structures are gently reflected off the gland and any sublingual (Bartholin’s) duct encountered is divided. The gland is then dissected from its bed. A fibrous tract is usually encountered passing through a dehiscence of the mylohyoid muscle (Fig. 9.1.4). Some patients have obvious herniation of the SLG through this dehiscence. Occasionally, the pseudocyst tracks around the posterior free margin of the mylohyoid, rather than passing directly through the dehiscence. The tract is followed into the neck and any residual collection may be expressed through the dehiscence into the mouth (Fig. 9.1.5).

Definitive Surgical Technique

Outcomes

SLG excision is performed transorally via an incision in the floor of mouth, in line with the submandibular duct

In our series of 81 plunging ranulas, we had a 99% success rate by excising the sublingual gland alone.14 That has since

Management of Ranula

CHAPTER 9  Benign Cystic Lesions

81

9.2  OTHER BENIGN CYSTIC SALIVARY LESIONS Mucocele

• Fig. 9.1.4

  Intraoperative photograph showing left sublingual glands excised en bloc with the herniated tract being dissected through the mylohyoid dehiscence.

• Fig. 9.1.5  Intraoperative photograph showing extravasated mucinous contents of cervical pseudocyst being aspirated via a transoral approach during excision of the sublingual glands.

been augmented by a further 53 published cases with no recurrence. If the SLG is not completely excised, a recurrence of ranula is possible. Most complications are minor and consist of postoperative infection or bruising in submandibular space that settles quickly. Two patients in our series suffered inadvertent trauma to Wharton’s duct leading to excision of the submandibular gland. Seven patients experienced lingual nerve neuropraxia.12

Mucoceles, also called extravasation mucoceles or mucous escape reaction, are the most common lesions that occur on the lower lip in males in the second to third decade of life.15 Submucosal spillage of mucin imparts a bluish translucent color to the swelling. These lesions present with a history of intermittent rupture. Habits such as lip biting may favor mucocele development in the lower lip. Also, compared with the upper lip, the lower lip has greater mass and moves more during speech.16,17 Finally, the greater number and density of salivary glands in the lower lip may play a role in the predilection for mucoceles in the lower lip. The term “extravasation mucocele” has an initial stage (interstitial mucus lakes), a resorption stage (mucus granulomas with macrophages, foam cells, and foreign bodies giant cells), and a terminal stage with the development of a pseudocyst (capsule of collagen tissue, no epithelial demarcation).18 A variant called superficial mucocele is seen in other parts of the oral cavity such as soft palate or retromolar trigone and may be associated with lichenoid inflammation such as lichen planus, lichenoid drug eruptions, and chronic graft-versus-host disease.15 Some mucoceles are short-lived lesions that rupture and heal by themselves. Many lesions, however, are chronic and surgical excision is necessary. To minimize the risk of recurrence, any adjacent minor salivary glands that may be feeding into the lesion should also be removed. Excised tissue should be submitted for microscopic examination to confirm the diagnosis. The prognosis is excellent, although mucoceles will occasionally recur, especially if feeding glands are not removed.15

Mucous Retention Cyst Mucous retention cysts or retention mucoceles are developmental lesions with a complete epithelial lining and are filled with mucus with no inflammatory reaction. They can occur anywhere in the oral cavity, typically in an older female patient.

Salivary Duct Cyst KEY POINTS • Two theories for pathologenesis: extravasation of mucus through damaged duct of Rivinus or from herniated SLG, secondary to trauma or obstruction. • If the SLG is not completely excised, a recurrence of ranula is possible.

These resemble mucous retention cysts, having an epithelial lining, but are not developmental in origin. Rather, partial obstruction of salivary flow is postulated to be the trigger. This either leads to increased luminal pressure and proximal dilatation or incites oncocytic metaplasia as a response to the obstruction.17

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Isolated salivary duct cysts are treated by conservative surgical excision. For cysts in the major glands, partial or removal of the gland may be necessary. For rare patients who develop multifocal salivary ductal ectasia, excision may be performed for the more problematic swellings. However, surgical management does not appear feasible for all lesions, which may number as many as 100. In some cases, systemic antibiotics and disinfectant mouth rinses can be helpful in relieving pain and reducing drainage of pus. Sialagogues may stimulate salivary flow, thereby preventing the accumulation of inspissated mucus within the dilated excretory ducts.

Kussmaul Disease or Sialodochitis Fibrinosa This rare disease is characterized by recurrent swelling of the salivary glands, which then discharge clots of fibrin into the oral cavity. First described by Kussmaul in 1879, it also typically includes history of allergy, elevated blood eosinophils or serum immunoglobulin E (IgE), mucofibrous ductal plugs, and stromal infiltration of lymphocytes or eosinophils.19 Autoimmune diseases and other causes of ductal obstruction do need to be ruled out. Management depends on severity of clinical picture. Rehydration and massage form the mainstay of treatment for milder cases. Dilatation of the duct and irrigation with saline or steroid-saline solution may be used as second-line treatment. Antihistamine and steroid therapy to address allergies is often useful.

KEY POINTS • Excision of a mucocele should include the adjacent minor salivary gland. • Isolated salivary duct cysts are treated by conservative surgical excision.

9.3  HUMAN IMMUNODEFICIENCY VIRUS AND CYSTIC SALIVARY GLAND DISEASE Introduction Salivary gland enlargement occurs in up to 10% of adults, with HIV disease often as the presenting symptom.20–22 More common in the pediatric HIV population, it also has variability in international geography.20,23 An RNA retrovirus, it infects and destroys CD4+ lymphocytes, diminishing humoral and cell mediated immunity manifested by opportunistic infections, malignancies, and dysfunction of organ. HIV trophism for lymphatic tissue invasion and inflammation is the sentinel aspect of HIV salivary gland disease (HIV-SGD) typically presenting as asymptomatic bilateral parotid gland enlargement associated with advancing

immunologic dysfunction first described in the era prior to effective highly active antiretroviral therapy (HAART).24,25 Initial descriptions noted diffuse lymphocytic infiltration (DLIS) with extensive glandular and lymphatic infiltration by CD8+ lymphocytes.20,22,24 DLIS in the HIV adult is associated with a progressive generalized lymphadenopathy stage of HIV host response.20,24,26,27 Histologic study reveals extensive CD8+ cell infiltration with periductal and perivascular inflammation with giant cells involving intraglandular lymphatic tissue.24,26,27 Primary HIV infection of the glands may be the key event with HIV p-24 antigen present in tissue.21 Although less common, glandular infection with EBV and BK virus has been described.26 The majority of enlarged glands now appear as benign lymphoepithelial cysts (BLEC).26,27 HIV-associated BLEC are benign single or multiple cysts, where pathology reveals multiple epithelial lined cystic spaces surrounded by germinal centers with dilated ducts.28 The unifying pathophysiology appears to be glandular lymphatic tissue infiltration by lymphocytes with obstruction of normal ductal architecture.28–30 Unilateral presentation is more common in the non-HIV described BLEC syndrome, and the predilection for the parotid glands reflects the higher presence of remnant lymphoid tissue.20,27

Diagnosis Inadequately controlled or newly diagnosed HIV disease with painless, bilateral parotid swelling in the absence of systemic symptoms with xerostomia is a classic presentation of BLEC.20,22 Atypical presentation with unilateral disease (20–50%), pain, rapid growth, and lack of response to HAART treatment, suggests additional differential diagnosis options, including a wide array of opportunistic infections or malignancies.27 Imaging with ultrasound (US) or CT would identify cystic lesions with ease.22,30 In the pediatric population, ultrasound would be preferred to avoid radiation.22 In unresponsive, unilateral disease or with systemic symptoms, fine needle aspiration (FNA) or biopsy would be appropriate and cost-effective. In the HIV population, 92.5–94.2% sensitivity in achieving a diagnosis has been described.31,32 HIV BLEC cytology is characterized by inflammatory cells, lymphocytes, vacuolated histiocytes in a proteinaceous or serous background.31,32

Treatment Initiation of HAART leads to improvement in gland enlargement in most cases.27,33 Time frame to improvement mirrors the reestablishment of immune activity with rising CD4 cells and diminishing HIV viral load occurring in the first 8–12 weeks of HAART therapy. The return of immune status can also lead to more robust inflammatory activity (IRIS) with a transient increase in symptoms occurring 6–10 weeks after HAART has been started.20 Continuation of HAART throughout the course of IRIS will lead to optimal outcome. Options for refractory cases are not

CHAPTER 9  Benign Cystic Lesions

well-defined. Aspiration or sclerotherapy with various agents has been described.34,35 Diagnostic or therapeutic parotidectomy is not commonly required. Radiation therapy (XRT) appears most efficacious for long-term resolution of HIV-associated BLEC.36–38 Short-term responses of 93% have been described but long-term follow-up suggests higher doses of XRT at 24 Gy total would be needed to achieve 68% remission of disease.38 BLEC as a manifestation of HIV disease reflects the HIV viral tropism for lymphatic tissue and the subsequent robust host response within salivary gland lymphatic tissue. The lymphatic inflammatory response leads to obstruction of flow limiting function and then development of squamous cell-lined cysts with inflammatory cells within the walls. Ultrasound CT imaging followed by FNA for atypical cases that do not respond to HAART may be needed to exclude additional pathology. Refractory cases may be successfully treated with high dose XRT.

KEY POINTS • HIV trophism for lymphatic tissue invasion and inflammation is the sentinel aspect of HIV salivary gland disease (HIV-SGD) typically presenting as asymptomatic bilateral parotid gland enlargement. • The pathophysiology is glandular lymphatic tissue infiltration by lymphocytes with obstruction of normal ductal architecture. • Atypical presentation with unilateral disease (20–50%), pain, rapid growth, and lack of response to HAART treatment suggests additional differential diagnosis options, including a wide array of opportunistic infections or malignancies. • Aspiration or sclerotherapy with various agents is a treatment option for refractory cases.

References 1. Kramer IR. Changing view on oral disease. Proc R Soc Med 1974;67(4):271–6. 2. Layfield LJ, Gopez EV. Cystic lesions of the salivary glands: cytologic features in fine-needle aspiration biopsies. Diagn Cytopathol 2002;27(4):197–204. 3. Harrison JD. Modern management and pathophysiology of ranula: literature review. Head Neck 2010;32(10):1310–20. 4. Jain P, Jain R, Morton RP, Ahmad Z. Plunging ranulas: highresolution ultrasound for diagnosis and surgical management. Eur Radiol 2010;20(6):1442–9. 5. Harrison JD. Ranula: a misunderstood disease. J Cranio Max Dis 2014;3(2):77–8. 6. Morton RP, Ahmad Z, Jain P. Plunging ranula: congenital or acquired? Otolaryngol Head Neck Surg 2010;142(1):104–7. 7. Zhao YF, Jia Y, Chen XM, Zhang WF. Clinical review of 580 ranulas. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;98(3):281–7. 8. Parekh D, Stewart M, Joseph C, Lawson HH. Plunging ranula: a report of three cases and review of the literature. Br J Surg 1987;74(4):307–9. 9. Jain R, Morton RP, Ahmad Z. Diagnostic difficulties of plunging ranula: case series. J Laryngol Otol 2012;126(5):506–10.

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10. Jain P. High-resolution sonography of sublingual space. J Med Imaging Radiat Oncol 2008;52(2):101–8. 11. Abt NB, Sethi RK, Lehmann AE, et al. Plunging ranula with prestyloid parapharyngeal space, masticator space, and parotid gland extension. B-ENT 2017;13(1 Suppl. 27):57–60. 12. Samant S, Morton RP, Ahmad Z. Surgery for plunging ranula: the lesson not yet learned? Eur Arch Otorhinolaryngol 2011; 268(10):1513–18. 13. Rachana PB, Singh RS, Patil VV. Modified micro-marsupialization in pediatric patients: a minimally invasive technique. SRM J Res Dent Sci 2018;9:83–6. 14. Morton RP. Surgical management of ranula revisited. World J Surg 2018;42(9):3062–3. 15. Neville BW, Damm DD, Allen CM, et al. Salivary gland pathology. In: Neville BW, Damm DD, Allen CM, et al, editors. Oral and maxillofacial pathology. 4th ed. St Louis: Elsevier; 2015. p. 422–72. 16. Chi AC, Lambert PR III, Richardson MS, Neville BW. Oral mucoceles: a clinicopathologic review of 1,824 cases, including unusual variants. J Oral Maxillofac Surg 2011;69(4):1086–93. 17. Harrison JD. Salivary mucocoeles. Oral Surg Oral Med Oral Pathol 1975;39(2):268–78. 18. Seifert G, Donath K, Gumberz C. Mucoceles of the minor salivary glands. Extravasation mucoceles (mucus granulomas) and retention mucoceles (mucus retention cysts. HNO 1981;29:179–91. (Author’s trans.). 19. Ray A, Burgin SJ, Spector ME. A Kussmaul disease (sialodochitis fibrinosa). J Case Rep Med 2015;4:1–3. 20. Ebrahim S, Singh B, Ramklass SS. HIV-associated salivary gland enlargement: a clinical review. SADJ 2014;69(9):400–3. 21. Sekikawa Y, Hongo I. HIV-associated benign lymphoepithelial cysts of the parotid glands confirmed by HIV-1 p24 antigen immunostaining. BMJ Case Rep 2017;pii: bcr-2017-221869. 22. Shanti RM, Aziz SR. HIV-associated salivary gland disease. Oral Maxillofac Surg Clin North Am 2009;21:339–43. 23. Dave SP, Pernas FG, Roy S. The benign lymphoepithelial cyst and a classification system for lymphocytic parotid gland enlargement in the pediatric HIV population. Laryngoscope 2007; 117:106–13. 24. Itescu S, Brancato LJ, Buxbaum J, et al. A CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a HLA-DR5. Ann Intern Med 1990;112(1):3–10. 25. Jeffers L, Webster-Cyriaque JY. Viruses and salivary gland disease (SGD): lessons from HIVSGD. Adv Dent Res 2011;23(1): 79–83. 26. Sharma G, Nagpal A. Salivary gland disease in human immunodeficiency virus/acquired immunodeficiency syndrome: a review. World J Dermatol 2015;4(1):57–62. 27. Craven DE, Duncan RA, Stram JR, et al. Response of lymphoepithelial parotid cysts to antiretroviral treatment in HIV-infected adults. Ann Intern Med 1998;128:455–9. 28. Kreisel FH, Frater JL, Hassan A, El-Mofty SK. Cystic lymphoid hyperplasia of the parotid gland in HIV-positive and HIVnegative patients: quantitative immunopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109(4):567–74. 29. Meer S, Dulabh S. Human immunodeficiency virus-associated cystic lymphoid hyperplasia: an immunohistochemical description. Indian J Pathol Microbiol 2017;60:336–40. 30. Shivhare P, Shankarnarayan L, Jambunath U, Basavaraju SM. Benign lymphoepithelial cysts of parotid and submandibular glands in an HIV-positive patient. J Oral Maxillofac Pathol 2015; 19(1):107.

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31. Chhieng DC, Argosino R, McKenna BJ, et al. Utility of fineneedle aspiration in the diagnosis of salivary gland lesions in patients infected with human immunodeficiency virus. Diagn Cytopathol 1999;21(4):260–4. 32. Michelow P, Dezube BJ, Pantanowitz L. Fine needle aspiration of salivary gland masses in HIV-infected patients. Diagn Cytopathol 2012;40(8):684–90. 33. Syebele K. Regression of both oral mucocele and parotid swellings, following antiretroviral therapy. Int J Pediatr Otorhinolaryngol 2010;74:89–92. 34. Berg EE, Moore CE. Office-based sclerotherapy for benign parotid lymphoepithelial cysts in the HIV-positive patient. Laryngoscope 2009;119:868–70. 35. Meyer E, Lubbe DE, Fagan JJ. Alcohol sclerotherapy of human immunodeficiency virus related parotid lymphoepithelial cysts. J Laryngol Otol 2009;123:422–5.

36. Kooper DP, Leemans CR, Hulshof MCCM, et al. Management of benign lymphoepithelial lesions of the parotid gland in human immunodeficiency virus-positive patients. Eur Arch Otorhinolaryngol 1998;255(8):427–9. 37. Mourad WF, Hu KS, Shourbaji RA, et al. Radiation therapy for benign lymphoepithelial cysts of parotid glands in HIV patients. Laryngoscope 2013;123:1184–9. 38. Mourad WF, Young R, Kabarriti R, et al. 25-Year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review. Anticancer Res 2013; 33:4927–32.

10 

Pathogenesis of Salivary Calculi JOHN D. HARRISON

Introduction There was a paradigm shift in the understanding of the pathogenesis of sialoliths, also known as salivary calculi, at the turn of the century.1,2 This was the result of experimental and clinicopathologic investigations that led to the discovery that sialolithiasis (the presence of a sialolith) was secondary to chronic sialadenitis. Rediscovery, however, would be more appropriate, because this conclusion had been reached in 1896 by Küttner,3 who described his clinical and microscopic investigations of two patients each with a swollen submandibular gland that had originally attracted a diagnosis of malignancy. He realized that the swellings were caused by chronic inflammation that, together with fibrosis, had led to the clinical appearance of malignancy (Fig. 10.1). He found a sialolith the size of a cherrystone in the gland of one of the patients, who had complained of a submandibular swelling for 10 years. He considered that the sialolith was secondary to the inflammation because the sialolith was far too small for a concretion of 10 years’ accumulation, and because of the absence of a sialolith in the other case, in which the duration was only 1.5 months. Küttner’s opinion that chronic sialadenitis is primary and leads to the formation of a sialolith was confirmed by extensive clinical experience (Fig. 10.2).4 However, there was negligible appreciation of Küttner’s work in the English-language medical literature, in which the notion that the sialolith is primary and the chronic sialadenitis is secondary held sway, although there was no evidence to account for the formation of the sialolith.

Clinicopathologic Investigations One of the clinicopathologic investigations that led to the paradigm shift and the rediscovery that sialolithiasis is secondary to chronic sialadenitis involved 154 cases of chronic submandibular sialadenitis, in which 18 different clinical and histologic features were statistically analyzed.5 It revealed that there is a chronological progression of increasingly severe chronic sialadenitis with, in many cases, the eventual development of a sialolith. The search for possible pathogenic factors that could transform a normal gland into a diseased gland led to a postmortem investigation in which microscopic concretions,

called sialomicroliths, were found in all normal submandibular glands and 20% of normal parotids.1,2 This distribution relates to a higher concentration of ionic calcium in the submandibular gland. Ionic calcium is present to shield the anionic charges of molecules of acidic secretory material and thus to allow them to be condensed into secretory granules. The concentration of calcium thus corresponds to the acidity of the secretory material in the secretory granules. (More details are given in Chapter 5.) The realization of the extent of the occurrence of sialomicroliths was only achieved through electronmicroscopy (Fig. 10.3), because many sialomicroliths are indistinguishable from secretory granules lightmicroscopically or are below the level of lightmicroscopic resolution. Sialomicroliths were occasionally seen obstructing small intraglandular ducts and causing focal obstructive atrophy (Fig. 10.4). This led to the hypothesis that sialomicroliths impact in ducts and accrete to form sialoliths, which led to a search for sialomicroliths in cases of chronic submandibular sialadenitis. They were found in all cases, which appeared to support the hypothesis. However, no relation between sialomicroliths and sialoliths or between sialomicroliths and duration of symptoms in chronic submandibular sialadenitis could be found.1,2,5 This indicated that sialomicroliths are not incipient sialoliths.

Experimental Investigations The search for pathogenic factors was finally resolved by experimental investigations using rat, cat, and ferret. Sialomicroliths and chronic obstructive sialadenitis were produced in the parotid and submandibular gland of rats made hypercalcemic and given repeated high doses of isoprenaline.1,2 Isoprenaline given in repeated high doses produces a great increase in the size and weight of the parotid and submandibular gland of rat as a result of hyperplasia and hypertrophy of the acinar cells. The acinar enlargement is sufficient to result in compression of the intraglandular ducts. Every dose of isoprenaline is followed by an explosive release of secretory material from the acinar cells that is unable to flow freely through the lumina of the compressed ducts, and the resultant increase of luminal pressure damages acinar cells. The partial obstruction thus results in a mixture of stagnant secretory material, which 85

CHAPTER 10  Pathogenesis of Salivary Calculi

Abstract

Keywords

There has been a paradigm shift in the understanding of the pathogenesis of sialoliths, also known as salivary calculi, as a result of clinicopathologic and experimental investigations that revealed that sialolithiasis is secondary to chronic sialadenitis. Clinical and histologic features were statistically analyzed in cases of chronic submandibular sialadenitis and revealed that there is a chronological progression of increasingly severe chronic sialadenitis with, in many cases, the eventual development of a sialolith. Postmortem and electronmicroscopic investigations revealed that microscopical concretions called sialomicroliths are present in all normal submandibular glands and a minority of normal parotids, and in all cases of chronic submandibular sialadenitis. However, sialomicroliths do not develop into sialoliths, and experimental investigations added the missing pathogenic link. Parasympathectomy of the submandibular gland of cat caused a greatly increased occurrence of sialomicroliths, which led to the realization that a lack of secretory activity causes sialomicroliths. The present understanding of the pathogenesis of sialoliths is as follows: secretory inactivity leads to an accumulation of sialomicroliths and allows ascent of the main duct by commensal microbes; impaction of sialomicroliths in small intraglandular ducts produces obstructive atrophic foci, in which the microbes can proliferate and cause inflammatory swelling, which is obstructive and may eventually involve the entire gland; partial obstruction of a large duct allows calcification of stagnant secretory material, which is rich in calcium, to accrete and become a sialolith. Any form of chronic sialadenitis or partial obstruction may eventually lead to the development of a sialolith.

Salivary Glands Salivary Gland Disease Sialadenitis Sialolithiasis Calculi Calcification Secretion

85.e1

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• Fig. 10.1

Chronic submandibular sialadenitis with moderate inflammation, atrophy, and fibrosis. (H&E, ×33)  

• Fig. 10.2

  Submandibular gland with a large sialolith. (Fig. 357 from Küttner, 19264.)

is particularly rich in calcium because of the hypercalcemia, and cellular debris. Cellular membranes present in the debris contain phospholipid that is exposed when they are damaged. This exposed phospholipid is a potent nucleator of calcification. The combination of stagnant calcium-rich secretory material together with phospholipid allows the calcium to precipitate on the phospholipid to form sialomicroliths. This occurs in the small intraglandular ducts and the sialomicroliths can obstruct them to give rise to chronic obstructive sialadenitis (Fig. 10.5). The salivary glands of cat were found to be a particularly valuable experimental model.1,2 Parasympathectomy caused a greatly increased occurrence of sialomicroliths in submandibular glands, in which they were extensively present in most of the parasympathectomized glands.6 This led to the realization that the lack of parasympathetic secretory stimulation caused a pathologic accumulation of sialomicroliths (Fig. 10.6). The acinar secretory granules of the submandibular gland of cat contain a high level of

• Fig. 10.3

  Electronmicrograph shows a sialomicrolith in an autophagosome (arrow) in a serous acinar cell of submandibular gland. The sialomicrolith would not be identifiable except by electronmicroscopy because it is of a similar size to the secretory granules. Electronmicroscopical microanalysis identified crystals containing calcium and phosphorus in the sialomicrolith. (×12,600)

• Fig. 10.4  Sialomicroliths are impacted in a striated duct (arrow) of submandibular gland causing focal obstructive atrophy of the associated parenchyma (A), which elsewhere is of a normal appearance. (H&E, ×130)

sequestered ionic calcium associated with acidic secretory material. The sequestered calcium is released in an ionized form during the normal discharge of secretory granules from the cell or during the degradation of secretory granules in autophagosomes when there is secretory inactivity, such as caused by parasympathectomy. The phospholipid of cellular membranes becomes exposed during degradation in autophagosomes and the ionic calcium precipitates on the phospholipid to form calcified sialomicroliths. This saves the cell from toxic death owing to an overwhelming sudden release of ionic calcium. Sialomicroliths may be expelled from cells and pass into lumina. They may also be formed in stagnant secretory material in lumina (Fig. 10.7). Luminal sialomicroliths may be flushed away in the saliva, although if they impact in a small intraglandular duct, a focus of obstructive atrophy may be produced. This is more likely

CHAPTER 10  Pathogenesis of Salivary Calculi

87

• Fig. 10.5  Sialomicroliths are impacted in a collecting duct (arrow) of submandibular gland of rat causing obstruction, atrophy, and inflammation of the associated lobule. Rat given isoprenaline and calcium gluconate. (H&E, ×43)

• Fig. 10.7

  Needle-shaped crystals of apatite are forming in association with secretory material and cellular debris in the lumen of an intralobular duct of parasympathectomized submandibular gland of cat. (×35,400)

Pathogenesis of Sialoliths

•

Fig. 10.6  Electronmicrograph shows a large sialomicrolith in an intraglandular duct of parasympathectomized submandibular gland of cat. It consists of numerous cores and lamellae that indicate growth by accretion. Stagnant secretory material and debris are also present in the lumen. (×4640)

to occur when a pathologic accumulation of sialomicroliths occurs, such as when there is secretory inactivity. The parotid of ferret frequently contains sialomicroliths.7 Secretory inactivity causes stagnation and autophagy of calcium-rich secretory material, which leads to the production of sialomicroliths that can obstruct small intraglandular ducts and produce atrophic foci. Investigations on ductal ligation of the salivary glands of cat yielded information on obstructive atrophy and recovery.1,2 The parotid is the most susceptible to obstruction, with progressive atrophy; the submandibular gland is more resistant, with variable atrophy; and the sublingual gland is the most resistant, with not only variable atrophy but extravasation of mucus that sometimes forms an extravasation mucocele. The parenchyma of obstructed glands can adapt and survive, and obstructed glands are capable of recovery, which depends on the duration and degree of obstruction. Complete obstruction does not lead to an accumulation of sialomicroliths or produce sialoliths.

The experimental and clinicopathologic investigations led to a detailed understanding of the pathogenesis of sialoliths.1,2 Secretory inactivity in a normal gland leads to an accumulation of sialomicroliths and allows ascent of the main duct by commensal microbes. Impaction of a sialomicrolith in a small intraglandular duct causes focal obstructive atrophy (Fig. 10.4). Microbes proliferate in atrophic parenchyma, where they are protected from the flushing and microbicidal activity of saliva and from systemic immunity by the surrounding fibrosis. The diffusion of their waste products and local invasion cause inflammation, the fluid and cellular exudate of which compresses surrounding parenchyma and causes further atrophy. This process eventually spreads to involve more of the lobules until the inflammatory swelling and fibrosis compress large intraglandular ducts. This causes partial obstruction that leads to ductal dilatation and stagnation of the calcium-rich secretory material in the lumina. This can precipitate on the phospholipid exposed in degenerating cellular membranes in the lumen of a large intraglandular duct, where there is sufficient space to form a sialolith (Figs. 10.8, 10.9). As the process progresses, the gland becomes increasingly obstructed, invaded by ascending microbes, inflamed, atrophic, and fibrosed. The stenosis of the main duct sometimes found in chronic sialadenitis is secondary to chronic inflammation and causes partial obstruction that is a factor in the persistence of the chronic sialadenitis and the eventual formation of sialoliths. The lining of Stensen’s duct in juvenile recurrent parotitis is seen endoscopically to be white and avascular and the

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• Fig. 10.8  A nascent sialolith is forming by calcification (stained black) in stagnant mucopus in a large, dilated, partially obstructed, interlobular duct of submandibular gland with chronic sialadenitis. (H&E, ×84)

• Fig. 10.9  A sialolith is seen in a large, dilated, partially obstructed interlobular duct of submandibular gland with chronic sialadenitis. Lamellae and globules are present in the sialolith. (Decalcified section, H&E, ×32)

duct to be stenotic,8 which represents the fibrosis of chronic inflammation and could cause partial obstruction. Plugs found in the ducts in chronic sialadenitis consist of desquamated parenchymal cells, inflammatory cells and the albuminous coagulum formed when plasma proteins leak into the lumina of inflamed glands.1,2 They are obstructive and the removal of them by irrigation is beneficial. A sphincter is present in Stensen’s duct and in Wharton’s duct, and a layer of smooth muscle has been found histologically in the wall of both ducts.1,2 Malfunction could cause partial obstruction or allow migration by microbes and foreign bodies. Foreign bodies that migrate from the orifice of the main duct or penetrate the main duct have only occasionally been found.9,10 They cause inflammation leading to partial obstruction and the consequent formation of a sialolith. Foreign bodies do not appear to be potent nucleators of

calcification, but the inflammation and partial obstruction that they cause lead to stagnation and calcification in the associated cellular debris until a sialolith may develop that partially or completely encloses the foreign body.1,2 Any chronic inflammatory condition of the salivary glands may cause partial obstruction and tissue damage and lead to sialolithiasis. This includes chronic recurrent parotitis, lymphoepithelial sialadenitis in Sjögren’s syndrome, and radioactive-iodine-induced sialadenitis.8,11,12 Another chronic inflammatory condition that can lead to sialolithiasis is IgG4-related sialadenitis, which is a rare autoimmune disease that is sometimes associated with autoimmune pancreatitis and inflammatory lesions in other organs and tissues including the lacrimal glands.13,14 Anatomic features such as kinks of Wharton’s duct, ductal polyps, ductal invaginations, and pelvis-like abnormalities of the duct at the submandibular hilum, can lead to partial obstruction, tissue damage and stagnation, which can lead to sialolithiasis.2 Occlusal disharmony has been reported to lead to increased tone of the masseter muscle, which then obstructs Stensen’s duct.2 Fibers of the buccinator muscle are inserted into the anterior part of Stensen’s duct and fibers also run parallel to the duct, which raises the possibility that partial obstruction could be caused by the buccinator muscle.2 Many cases of chronic sialadenitis are of a normal appearance on diagnostic imaging, endoscopy, or histologic examination, which confirms that chronic sialadenitis is a primary condition.5,15,16 Irrigation, even by saline alone, is effective in many cases of chronic obstructive sialadenitis.1,2 The irrigation dilutes and flushes microbes out of atrophic foci into regions where the microbicidal capacity of the saliva is effective. It flushes out obstructing plugs, dilates ducts and thus allows small sialoliths to be passed, and dislodges sialoliths adherent to the walls of ducts. Irrigation, usually with the addition of a steroid, is also effective in many cases of juvenile or adult chronic recurrent parotitis, lymphoepithelial sialadenitis in Sjögren’s syndrome, and radioactive-iodine-induced sialadenitis for similar reasons, as well as the effect of steroid on the inflammation, although the possible benefit of steroid has not been established.11,12,15–17 There is an increased incidence of sialomicroliths with age, which appears to relate to degenerative changes in the salivary glands related to ageing that lead to a decrease of secretory activity and to stagnation of secretory material. The level of sequestered ionic calcium in the secretory granules is lower in the parotid than in the submandibular gland because the secretory material is less acidic and requires less cationic shielding. This accounts for the lower incidence of sialomicroliths and sialoliths in the parotid, and also for the slightly older age at which parotid sialolithiasis occurs.18 There is a high level of sequestered ionic calcium in the secretory granules of the sublingual gland and the mucous minor salivary glands because the secretory material is generally more acidic than in the submandibular gland.

CHAPTER 10  Pathogenesis of Salivary Calculi

However, sialoliths are rare in these glands. This is because the spontaneous secretion of these glands, which occurs continuously without stimulation, reduces the likelihood of secretory inactivity until eventually age-related degenerative changes occur. This degeneration may lead to stagnation of the calcium-rich secretory material and to the formation of sialomicroliths and ultimately of sialoliths, which occur later than in the submandibular gland.1,2 Smoking favors sialolithiasis, which can be explained by the effect of smoking to reduce the salivary flow and the antimicrobial activity of saliva.19–23 Reduced salivary flow would lead to an increase of sialomicroliths and ascent of the main duct by microbes, which would be more likely to survive because of the decreased antimicrobial activity. This may lead to the development of inflamed atrophic foci and chronic sialadenitis, which may lead to sialolithiasis. A cohort of patients with sialolithiasis was found to be more likely to use diuretics than the general population,19 which could cause a decreased salivary flow leading to an increase of sialomicroliths, chronic sialadenitis, and finally sialolithiasis. Patients with a prior diagnosis of chronic periodontitis were found to be more likely to develop sialolithiasis,21 which raises the possibility that this relates to an increased oral microbial presence that could more effectively ascend the main duct and become established in atrophic foci, particularly as there was a greater proportion of smokers among patients than among controls. Sialolithiasis has been found to be associated with cholelithiasis and nephrolithiasis.22,23 Possibly all three of these conditions share common predisposing factors, such as smoking, as there was a greater proportion of smokers among patients than among controls. Positive correlations between the level of calcium in the drinking-water, the concentration of salivary calcium, and the incidence of sialolithiasis suggest that a higher level of calcium in drinking-water leads to a higher concentration of salivary calcium and favors sialolithiasis.24,25 A higher concentration of salivary calcium would favor crystallization of calcium salts. Phytate, which is an abundant component of plant seeds and is a potent inhibitor of calcification, is present at a lower concentration in the saliva of patients with calcified sialoliths, which indicates that a diet poor in phytate favors sialolithiasis.26

Structure of Sialoliths The mineral of sialoliths has been found to be mainly hydroxyapatite and carbapatite with occasionally whitlockite.26 An investigation using computed microtomography and electronmicroscopy has shed new light on the mechanisms involved in the formation of sialoliths,27 and is summarized as follows. Cores were found by computed microtomography in most of the sialoliths, were often not at the center, and could be missed by conventional microscopy. Highly calcified cores possibly represent a nucleation process based on calcification in stagnant debris, whereas weakly calcified cores possibly represent a nucleation process based on

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degenerate and condensed stagnant secretory material and cellular components poor in calcium. Long-range inward diffusion of calcifying agents into the growing sialolith does not appear to occur and the growth and calcification processes occur at the periphery of the sialolith subsequent to the nucleation stage in which the core or cores are produced. Sialoliths exhibit great structural diversity, which can be divided into concentric and irregular patterns with high or low levels of calcification. Sialoliths often exhibit more than one type of growth pattern. The concentric patterns correspond to quasi steady-state growth, whereas the irregular patterns are likely to be caused by recurrent episodes of inflammation and infection that induce growth perturbations. The predominant growth mechanism involves the deposition of organic matter that is subsequently mineralized. This is seen to involve lamellar and globular patterns (Fig. 10.9). In the lamellar regions, there is a quasiperiodic spatial distribution of crystallites that indicates a Liesegang-Ostwald precipitation mechanism, whereby an initial supersaturation of calcium and phosphorus is followed by precipitation to produce a highly mineralized band, which depletes the neighborhood of calcium and phosphorus so that a poorly mineralized band is produced next. This process is repeated to produce the rhythmic banding. Convoluted organic lamellae detected in peripheral regions probably arise from adherence of the sialolith to ductal epithelium that is subsequently integrated into the calcifying structure. Globular patterns (Fig. 10.9) are produced by forces of surface tension that act on organic material to produce globular accumulations. Chemical gradients drive a diffusion of electrolytes into the globules, and subsequent precipitation in the globules increases the pressure and forces organic material out through the calcifying walls of the globules to produce adjacent finger-like globules, and the process is repeated. The globular structures are self-similar at different scales, which is a feature of fractals, and would be expected to increase the toughness and resistance of sialoliths to shockwave lithotripsy. The increased obstruction caused by sialoliths will allow greater ascent by microbes, and bacteria at the surface of sialoliths may become incorporated into the growing sialolith and calcified. However, if a sialolith causes complete obstruction, the process may end as a symptomless sialolith in a very fibrosed duct with completely atrophic remnants of gland and little or no inflammation.

Conclusion Sialolithiasis is relatively frequent and a nationwide population-based investigation in Denmark found the incidence to be between 7.27 and 14.10 per 100,000 population per year.28 The paradigm shift in the management of sialadenitis and sialolithiasis to a conservative approach is paralleled by the increased understanding of the pathogenesis of sialolithiasis that informs the management of the condition (Fig. 10.10).

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Lymphoepithelial sialadenitis in Sjögren's

• Fig. 10.10

 

Pathogenesis of chronic sialadenitis and sialolithiasis.

CHAPTER 10  Pathogenesis of Salivary Calculi

KEY POINTS • Sialolithiasis is secondary to chronic sialadenitis. • Sialomicroliths accumulate when there is secretory inactivity and may eventually lead to chronic obstructive sialadenitis. • Any form of chronic sialadenitis or partial obstruction can lead to sialolithiasis. • Good salivary secretory activity and a diet with a reasonable content of phytate are likely to be prophylactic against sialolithiasis.

References 1. Harrison JD. Natural history of chronic sialadenitis and sialolithiasis. In: Nahlieli O, Iro H, McGurk M, Zenk J, editors. Modern management preserving the salivary glands. Herzeliya: Isradon; 2007. p. 93–135. 2. Harrison JD. Causes, natural history, and incidence of salivary stones and obstructions. Otolaryngol Clin North Am 2009; 42:927–47. 3. Küttner H. Ueber entzündliche Tumoren der SubmaxillarSpeicheldrüse [On the inflammatory tumors of the submandibular salivary gland]. Beitr Klin Chir 1896;15:815–28. 4. Küttner H. Speichelsteine [salivary stones]. In: Garrè C, Küttner H, Lexer E, editors. Handbuch der praktischen Chirurgie [Handbook of practical surgery], vol. 1. 6th ed. Chirurgie des Kopfes [Surgery of the head]. Stuttgart: Ferdinand Enke; 1926. p. 929–35. 5. Harrison JD, Epivatianos A, Bhatia SN. Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases. Histopathology 1997; 31:237–51. 6. Triantafyllou A, Harrison JD, Garrett JR. Production of salivary microlithiasis in cats by parasympathectomy: light and electron microscopy. Int J Exp Pathol 1993;74:103–12. 7. Triantafyllou A, Harrison JD, Garrett JR. Microliths in the parotid of ferret investigated by electron microscopy and microanalysis. Int J Exp Pathol 2009;90:439–47. 8. Canzi P, Occhini A, Pagella F, et al. Sialendoscopy in juvenile recurrent parotitis: a review of the literature. Acta Otorhinolaryngol Ital 2013;33:367–73. 9. Su YX, Lao XM, Zheng GS, et al. Sialoendoscopic management of submandibular gland obstruction caused by intraglandular foreign body. Oral Surg Oral Med Oral Pathol Oral Radiol 2012; 114:e17–21. 10. Xie L, Zheng L, Yu C, et al. Foreign body induced sialolithiasis treated by sialoendoscopic intervention. J Craniofac Surg 2014;25:1372–5. 11. De Luca R, Trodella M, Vicidomini A, et al. Endoscopic management of salivary gland obstructive diseases in patients with Sjögren’s syndrome. J Craniomaxillofac Surg 2015;43:1643–9.

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12. De Luca R, Vicidomini A, Trodella M, et al. Sialoendoscopy: a viable treatment for I131 induced sialoadenitis. Br J Oral Maxillofac Surg 2014;52:641–6. 13. Harrison JD, Rodriguez-Justo M. Commentary on IgG4-related sialadenitis: Mikulicz’s disease, Küttner’s tumour, and eponymy. Histopathology 2011;58:1164–6. 14. Harrison JD, Rodriguez-Justo M. IgG4-related sialadenitis is rare: histopathological investigation of 129 cases of chronic submandibular sialadenitis. Histopathology 2013;63:96–102. 15. Gallo A, Capaccio P, Benazzo M, et al. Outcomes of interventional sialendoscopy for obstructive salivary gland disorders: an Italian multicentre study. Acta Otorhinolaryngol Ital 2016;36:479–85. 16. Capaccio P, Torretta S, Di Pasquale D, et al. The role of interventional sialendoscopy and intraductal steroid therapy in patients with recurrent sine causa sialadenitis: a prospective cross-sectional study. Clin Otolaryngol 2017;42:148–55. 17. Jokela J, Haapaniemi A, Mäkitie A, Saarinen R. Sialendoscopy in treatment of adult chronic recurrent parotitis without sialolithiasis. Eur Arch Otorhinolaryngol 2018;275:775–81. 18. Sigismund PE, Zenk J, Koch M, et al. Nearly 3,000 salivary stones: some clinical and epidemiologic aspects. Laryngoscope 2015;125:1879–82. 19. Huoh KC, Eisele DW. Etiologic factors in sialolithiasis. Otolaryngol Head Neck Surg 2011;145:935–9. 20. Yiu AJ, Kalejaiye A, Amdur RL, et al. Association of serum electrolytes and smoking with salivary gland stone formation. Int J Oral Maxillofac Surg 2016;45:764–8. 21. Hung SH, Huang HM, Lee HC, et al. A population-based study on the association between chronic periodontitis and sialolithiasis. Laryngoscope 2016;126:847–50. 22. Hung SH, Lin HC, Su CH, Chung SD. Association of sialolithiasis with cholelithiasis: a population-based study. Head Neck 2016;38:560–3. 23. Wu CC, Hung SH, Lin HC, et al. Sialolithiasis is associated with nephrolithiasis: a case-control study. Acta Otolaryngol 2016;136:497–500. 24. Schrøder S, Homøe P, Wagner N, et al. Does drinking water influence hospital-admitted sialolithiasis on an epidemiological level in Denmark? BMJ Open 2015;5:e007385. 25. Schrøder SA, Homøe P, Wagner N, Bardow A. Does saliva composition affect the formation of sialolithiasis? J Laryngol Otol 2017;131:162–7. 26. Li Y, Reid DG, Bazin D, et  al. Solid state NMR of salivary calculi: proline-rich salivary proteins, citrate, polysaccharides, lipids, and organic–mineral interactions. C R Chimie 2016;19:1665–71. 27. Nolasco P, Anjos AJ, Aquino Marques JM, et al. Structure and growth of sialoliths: computed microtomography and electron microscopy investigation of 30 specimens. Microsc Microanal 2013;19:1190–203. 28. Schrøder SA, Andersson M, Wohlfahrt J, et al. Incidence of sialolithiasis in Denmark: a nationwide population-based register study. Eur Arch Otorhinolaryngol 2017;274:1975–81.

11 

Conventional Surgery for Salivary Inflammatory Diseases EUGENE N. MYERS

Introduction Chronic sialadenitis is the most common benign disease of the major salivary glands and is usually the result of obstruction of salivary flow due to calculi, strictures, or both. Chronic sialadenitis, particularly in the parotid gland, may also be associated with Sjögren syndrome, sarcoidosis, and other forms of granulomatous sialadenitis.1 In the pre-antibiotic era, the treatment of chronic and recurrent sialadenitis consisted of adequate hydration, sialagogues, warm compresses, and massage of the affected area. In those cases caused by distal intraductal calculi, the papilla of the duct was incised and the calculus removed, with immediate relief. However, many of these patients later developed recurrent calculi, chronic sialadenitis, ductal stenosis, and fistulous tracts leading to the skin. In these cases, the gland was excised. Even now, when more conservative management fails, surgical excision of the gland is the mainstay of effective treatment.2 The introduction of techniques such as sialendoscopy,3 extracorporeal shockwave lithotripsy,4 and a combination of sialendoscopy and external surgery5 (Fig. 11.1) has fundamentally changed the therapeutic approach to chronic sialadenitis and ushered in the era of organ preservation. Zenk et al.6 described a series of 1154 patients who underwent sialendoscopy in the diagnosis and treatment of sialolithiasis. Using sialendoscopy with extraction of the calculi or in combination with transoral removal of the calculus, only 4% of their patients required removal of the submandibular gland. Likewise, only 4% of their patients eventually required parotidectomy. Marchal5 described a combined transfacial endoscopic technique to extract large calculi, calculi adherent to the duct, intraparenchymal calculi inaccessible to the endoscope, or following failed attempts at calculi removal with other procedures. While conservative measures as described above are usually effective in controlling the acute exacerbations of this disease, conventional surgery may become necessary when they fail and the infections become too frequent or too severe for episodic treatment.7 For instance, we 92

described a series of patients with chronic sialadenitis, some of whose underlying problem was Sjögren disease.8 The clinical course of these patients was characterized by recurrent parotiditis, which required multiple admissions to the hospital for treatment with intravenous antibiotics. Some of these patients also developed abscesses and one patient developed an abscess with a cutaneous fistula. My indications for surgery in patients with chronic parotitis are: frequent episodes of parotiditis, recurrent parotiditis requiring hospitalization for intravenous antibiotics and for patients who develop complications such as abscess or fistula formation. The indications for excision of the submandibular gland for chronic sialadenitis are similar.

Total Parotidectomy for Sialadenitis A modified Blair incision is drawn with a skin marker (Fig. 11.2A). A 2-0 silk suture is placed in the earlobe. The skin incision is made with a Colorado tip electrocautery. Once the elevation of the skin flap is complete, hemostasis is obtained and the edges of the skin flap are sewn to the drape (see Chapters 35.1 and 47.1). Some patients will have had spontaneous extrusion of a calculus through the skin surrounding the gland or have a fistulous tract present. An elliptical incision surrounding the tract or calculus is made in the direction of relaxed skin tension lines. The tract is then dissected down through the platysma muscle down to the gland. Blunt and sharp dissection is carried out along the sternocliedomastoid muscle (SCM) toward the mastoid tip. The greater auricular nerve is identified and transected. The mastoid tip is palpated, completing identification of the first landmark for the facial nerve (Fig. 11.2B). The posterior belly of the digastric muscle is skeletonized. Skin hooks are inserted to retract the preauricular soft tissue. The perichondrium of the external auditory meatus (EAM) is then incised and the end of the scalpel handle is inserted along the anterior aspect of the EAM. The main trunk of the facial nerve is usually found 1–2 cm anterior and inferior to the cartilaginous pointer (Fig. 11.3). Since

CHAPTER 11  Conventional Surgery for Salivary Inflammatory Diseases

Keywords Salivary Gland Inflammatory Diseases Sialadenitis Conventional Surgery Parotidectomy Submandibular Gland Resection

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CHAPTER 11  Conventional Surgery for Salivary Inflammatory Diseases

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Tympanomastoid suture Cartilaginous pointer

Facial nerve Mastoid process Digastric

• Fig. 11.1

  A combined transfacial-endoscopic technique is useful in extracting calculi inaccessible to the endoscope. (With permission from Marchal F. Removal of calculi in salivary ducts that cannot be removed by sialendoscopy. In: Myers EN, Ferris RL, eds. Salivary gland disorders. New York: Springer; 2007, p. 151).

A

B • Fig. 11.2  (A) A modified Blair incision is used. The superior and inferior limbs of the incision are incorporated into natural skin folds. The curved part of the incision is hidden by the auricle. (B) The greater auricular nerve is identified and the parotid gland is dissected free of the sternocleidomastoid muscle up to the mastoid tip. ((A) With permission from Galati L. Superficial parotidectomy. In: Myers EN, Snyderman CH, eds. Operative otolaryngology – head and neck surgery, 3rd edn., Vol. 1. New York: Elsevier; 2018, Fig. 92.1A.)

• Fig. 11.3  The landmarks used to identify the main trunk of the facial nerve.

the nerve exits between the mastoid tip and the boney EAM, I prefer to palpate the boney EAM deep to the pointer for greater accuracy. The main trunk of the facial nerve is a deep structure which is very constant as it exits the stylomastoid foramen and enters the parotid gland. In children, the nerve, while identified as described above, is more superficial because of the smaller size of the child. It has been suggested that in cases of chronic parotid sialadenitis, it would be safer to identify a peripheral branch of the nerve and dissect it retrograde to the main trunk, thinking that the area of the main trunk would be obliterated by infection-induced scar tissue. The parotid gland is encased in the parotid-masseteric fascia derived from the superficial layer of the deep cervical fascia, which prevents the infection in the gland from involving the area of the stylomastoid foramen, making dissection in the area very safe and the position of the nerve quite predictable. An exception to this is in the case of a previous superficial parotidectomy during which this area has been dissected. Even in the midst of infection and fibrosis, by staying in the proper plane, the nerve can be dissected free. The dissection continues anteriorly along the branches of the upper and lower divisions (Fig. 11.4A). The tissue resting on the masseter muscle between the upper and lower divisions constitutes the deep lobe of the parotid gland. Anatomically, there is not an official deep lobe of the gland, so this distinction is left to the imagination and experience of the surgeon. The deep lobe is dissected sharply off of the masseter muscle by mobilizing the facial nerve when necessary and keeping the deep lobe attached to the superficial lobe, if possible (Fig. 11.4B). At the anterior border of the masseter muscle Stenson’s duct will be identified. Dissection is carried along the duct until the buccal mucosa is identified. An incision is made in the buccal mucosa and the papilla is excised in continuity with the entire specimen (Fig. 11.4C). All tissue which looks like parotid tissue should then be identified and removed. Doing so often means elevating

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A

Internal maxillary vessels

Superficial temporal vessels

in a field compromised by chronic infection and fibrosis is not a easy one. The wound in the buccal mucosa is closed with 3-0 chromic catgut sutures, meticulous hemostasis is obtained and the wound irrigated. A hemovac drain is inserted and prior to closing the wound, all branches of the nerve are stimulated. If the nerves are anatomically intact but do not stimulate briskly, function will return, possibly more slowly. The wound is closed in layers using 6-0 fast absorbing catgut for the skin, since those do not require removal. The risk of injury to the facial nerve is a significant consideration for a surgeon who is offering definitive therapy for chronic infection of the parotid gland. In my own series,8 5/14 patients undergoing total parotidectomy experienced some degree of immediate postoperative facial weakness (one or more branches) which resolved within a few weeks, except in one patient whose weakness resolved over 3 months.

Excision of the Submandibular Gland for Chronic Sialadenitis External carotid artery

B

Retromandibular vein

C • Fig. 11.4

  (A) The branches of the facial nerve are identified and preserved. (B) The deep lobe is removed – mobilizing the branches of the facial nerve as necessary. (C) Total parotidectomy, including superficial and deep lobes and the entire Stensen’s duct with the impacted calculus. ((B) With permission from Moore EJ, Olson KD. Total parotidectomy. In: Myers EN, Ferris RL, eds. Salivary gland disorders. New York: Springer; 2007, p. 262.)

various branches of the facial nerve. There is a certain risk in doing this, but there is also a risk in not doing so, because there is a substantial rate of recurrence when partial surgery is done. I have had the experience of re-operating on several patients who have had previous partial surgery, and working

A 3- to 4-cm incision is made in a natural skin fold using a Colorado tip electrocautery to prevent bleeding from the skin edges, and carried stepwise down to the platysma muscle. The skin flaps are initially undermined using a No. 15 Bard Parker blade. The undermining should extend superiorly to the inferior border of the mandible and to the level of the hyoid bone inferiorly. Self-retaining retractors are then placed (see Chapters 35.2 and 47.2). Some patients will have had spontaneous extrusion of a calculus through the skin surrounding the gland or have a fistulous tract present. An elliptical incision surrounding the tract or calculus is made in the direction of relaxed skin tension lines. The tract is then dissected down through the platysma muscle down to the gland. A transverse incision is made sharply at the inferior aspect of the gland since the marginal mandibular branch of the facial nerve is found deep to the platysma muscle and the superficial layer of the deep cervical fascia (Fig. 11.5). The posterior belly of the digastric muscle is skeletonized. The inferior aspect of the gland is now identified, and a plane is developed between the platysma muscle and the superficial layer of deep cervical fascia. Fibrosis from chronic sialadenitis is often encountered. Dissection is enhanced by placing a Babcock clamp on the inferior aspect of the gland and exerting traction in an inferior direction. Double skin hooks are placed in the superior edge of the muscle and dissection carried superiorly. The marginal branch of the facial nerve will be incorporated into this flap as it is elevated superiorly. In cases where there is extensive fibrosis, a hand-held nerve stimulator may be useful in identifying the nerve. The facial artery is then palpated at the mandibular notch to identify its location. The facial artery and vein are ligated and transected (Fig. 11.6). The silk suture is left long

CHAPTER 11  Conventional Surgery for Salivary Inflammatory Diseases

Marginal mandibular nerve crossing facial vein

• Fig. 11.5  The marginal mandibular branch of the facial nerve is visible deep to the superficial layer of deep cervical fascia. (With permission from Fraioli RE. Excision of the submandibular gland. In: Myers E, Snyderman CH, eds. Operative otolaryngology – head and neck surgery, 3rd edn., Vol. 1. New York: Elsevier; 2018, Fig. 91.2.)

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The posterior border of the mylohyoid muscle is identified and skeletonized, as dissection is carried out anteriorly. An Army-Navy retractor is used to retract the muscle anteriorly. Wharton’s duct is now identified and dissected free from the soft tissue. The surgical assistant then places a finger into the oral cavity and exerts downward pressure on the floor of the mouth. Complete dissection of the duct is then completed up to the mucosa of the floor of the mouth where the duct is then clamped, ligated, transected, and the specimen removed. This thorough dissection of the duct prevents the possibility of retained calculi in a duct remnant, which may lead to subsequent infection. During the dissection, any fistulous tracts and/or calculi impacted in the skin are included in the specimen and removed with the gland. Meticulous hemostasis is obtained and the wound is thoroughly irrigated. A hemovac drain is placed in the submandibular triangle and sewn to the skin at the point of exit in the posterior aspect of the incision and attached to suction. The wound is then closed in layers using 6-0 fast absorbing catgut in the skin. The potential major complication of this surgery is injury to the marginal mandibular branch of the facial nerve. This may result in weakness of the lower lip, which is usually temporary but may in some cases be permanent.

Discussion

• Fig. 11.6

  The mandibular branch of the facial nerve is transposed out of the surgical field by ligating the superficial branch of the facial artery and clamping the long end of the suture to the drape. (With permission from Fraioli RE. Excision of the submandibular gland. In: Myers E, Snyderman CH, eds. Operative otolaryngology – head and neck surgery, 3rd edn. New York: Elsevier; 2018, p. 610.)

and fixed to the drape. This maneuver protects the mandibular branch of the facial nerve. The entire gland is now exposed and dissection using a blunt tip iris scissor is carried out in a plane between the fascia and the gland. The gland is mobilized and by retracting it anteriorly, and the posterior belly of the digastric muscle inferiorly, the deep aspect of the facial artery is identified, clamped, divided, and doubly ligated using 2-0 silk suture. Ligating the artery allows for mobilization of the gland. Dissection is continued anteriorly and deep in order to identify the lingual nerve and the hypoglossal nerve on the floor of the submandibular triangle. The branch of the lingual nerve at the submaxillary ganglia is clamped using a curved mosquito hemostat, transected and doubly ligated using 2-0 silk suture. This maneuver is made necessary by the presence of an artery, which accompanies the nerve. The hypoglossal nerve is located more superiorly in the submandibular triangle and may or may not be identified.

Disorders of the salivary glands are uncommon and when they do occur, experience in managing the process is diluted over a range of disciplines. The result is that traditional views go unchallenged and are recast, unchanged from one textbook to another.7 Excision of the submandibular gland as described provides excellent results in relieving the vexing symptoms of chronic sialadenitis. My only change in the technique described in most textbooks is the dissection of Wharton’s duct up to the mucosa of the floor of the mouth, which is important in preventing subsequent infection in a duct remnant with undetected calculi. Total parotidectomy with facial nerve dissection is an effective procedure for complete elimination of chronic sialadenitis of the parotid gland and prevention of recurrent infection.8 Total parotidectomy gives superior results since removing the deep lobe and surrounding tissue decreases the possibility of recurrent infections. Sharma’s7 review of the literature indicated that some patients with parotid sialadenitis respond to conservative management with systemic antibiotics, tympanic neurectomy, ligation of Stensen’s duct, sialogogues, and massage of the gland. There was a high rate of failure using these measures and many of these patients were subject to surgery for the removal of what was thought to be, but later proved not to be universally true, non-functional glands. The concept of organ preservation became popular in the 1990s with the use of advances in technology, including extracorporeal shockwave lithotripsy described by Iro et al.4 and sialendoscopy, which was introduced in Europe by

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radiologist Phillipe Katz,9 and advanced by Marchal et al.3 and Zenk et al.6 However, patients who fail these measures require removal of the infected gland. Moody et al.10 pointed out that, while superficial parotidectomy has apparently become the standard of care for patients with chronic and recurrent parotid sialadenitis, in this series, the disease recurred only in those patients who had a superficial parotidectomy. Another area of controversy involves whether or not to include the entire Stensen’s duct with the superficial parotidectomy. Amin et al.11 reviewed their series of 23 consecutive superficial parotidectomies with preservation of Stensen’s duct and concluded that this was a safe and effective technique with minimal long-term complications. However, Zhang et al.12 reported their series of patients in whom superficial parotidectomy was carried out. In 13 of their patients, Stenson’s duct was completely removed while, in four cases, the distal portion of the duct was preserved. One of the patients developed an infection in the duct remnant and was subsequently cured by complete removal of the duct. When conservative measures, including sialendoscopy, fail to control chronic and recurrent sialadenitis, conventional surgery is indicated. In order to prevent recurrent infection, surgery should be completed as described above. This philosophy and the meticulous surgical techniques will provide good results in elimination of chronic sialadenitis.

KEY POINTS • Conventional surgery is indicated in patients who have failed conservative management, including sialendoscopy for chronic sialadenitis. • Conventional surgery for chronic sialadenitis of the submandibular gland includes excision of the gland, including the entire Wharton’s duct. • Conventional surgery for chronic sialadenitis of the parotid gland includes total parotidectomy, including the entire Stensen’s duct. • Identification of the important anatomic landmarks is fundamental to success. • Facial nerve monitoring is required in total parotidectomy to help with identification of the facial nerve and its branches. • A thorough discussion of the risks and benefits of the surgery must take place between the operating surgeon and the patient and their family.

References 1. Fox PC, Hong CH, Brun AG, Brennan MT. Diagnosis and management of autoimmune salivary gland disorders. In: Myers EN, Ferris RL, editors. Salivary gland disorders. New York: Springer; 2007. p. 201–19. 2. Vashishta R, Gillespie MB. Salivary endoscopy for idiopathic chronic sialadenitis. Laryngoscope 2013;123:3016–20. 3. Marchal F, Dulguerov P, Lehmann W. Interventional sialendoscopy. N Engl J Med 1999;341:1242–3. 4. Iro H, Schneider HT, Födra C, et al. Shockwave lithotripsy of salivary duct stones. Lancet 1992;339:1333–6. 5. Marchal F. Removal of calculi or strictures in salivary ducts that cannot be removed by sialendoscopy in salivary gland disorders. In: Myers EN, Ferris RL, editors. Salivary gland disorders. New York: Springer; 2007. p. 149–58. 6. Zenk J, Koch M, Klintworth N, et al. Sialendoscopy in the diagnosis and treatment of sialolithiasis: a study on more than 1000 patients. Otolaryngol Head Neck Surg 2012;147:858–63. 7. Sharma R. Superficial parotidectomy for chronic parotid sialadenitis. Int J Oral Maxillofac Surg 2013;42:129–32. 8. Arriaga MA, Myers EN. The surgical management of chronic parotitis. Laryngoscope 1990;100:1270–5. 9. Katz P. [New treatment method for salivary lithiasis]. Rev Laryng Oto Rhinol (Bord) 1993;114:379–82. 10. Moody AB, Avery CME, Walsh S, et al. Surgical management of chronic parotid disease. Br J Oral Maxillofac Surg 2000;38:620–2. 11. Amin MA, Bailey BMW, Patel SR. Clinical and radiological evidence to support superficial parotidectomy as the treatment of choice for chronic parotid sialadenitis: a retrospective study. Br J Oral Maxillofac Surg 2001;39:348–52. 12. Zhang L, Guo CB, Huang MX, et al. Parotidectomy for treatment of chronic obstructive parotiditis. Clin J Dental Res 2007; 10:36–40.

12 

Salivary Duct Anatomy for Sialendoscopy YVES SABAN, TEVFIK SÖZEN, PETER PALHAZI, AND ROBERTO POLSELLI

Stensen’s Parotid Salivary Duct Description The secretions of the parotid gland are transported to the oral cavity via the Stensen’s duct. Embedded in the division of the parotid-masseteric-buccinator fascia, it arises from the anterior surface of the gland and is ~5 cm long. It runs anteriorly superficial to the masseter muscle and over its anterior border, passing around the buccal space and the Bichat’s deep buccal fat pad, like a tie around the neck. It then traverses the buccopharyngeal fascia and the buccinator muscle. The duct then pierces the buccinator, moving medially just under the buccal mucosa. It opens out into the oral cavity near the second upper molar tooth. The relationship with buccinator ensures that ballooning of the duct does not occur during blowing. Landmarking the Stensen’s parotid duct and the MacGregor patch is performed using the “magic finger” technique. The horizontal finger is applied on the zygomatic arch caudal border, while the vertical finger is just following the masseter muscle anterior border. Where the fingers cross is the MacGregor patch that corresponds to the transverse facial pedicle, including the Stensen’s duct, the buccal branches of the facial nerve, and the longitudinal branch of the transverse facial artery (Figs. 12.1–12.4).

Segmentation of Stensen’s Parotid Duct 1. Masseteric and glandular fixed posterior portion: embedded in the deep facial fascia division that corresponds to the parotid-masseteric fascia, the Stensen’s duct is fixed over the masseter muscle (Figs. 12.5, 12.6). 2. Duct knee: the duct, still in the fascia, becomes mobile; angle of the masseter: this knee may correspond to a friction zone between the fixed and mobile segments, that may create a stricture (Fig. 12.7). This angle is difficult to pass with endoscopes. 98

• Fig. 12.1

 

Landmarking Stensen’s parotid duct with the MacGregor

patch.

3. Buccal mobile anterior portion over the buccal space and over Bichat’s deep buccal fat pad. To straighten the duct and to pass the knee, it is mandatory to stretch the buccinator muscle anteriorly and laterally, so that the sialendoscope may pass the duct masseteric angle and enter the fixed masseteric and glandular portion (Fig. 12.8). 4. Buccinator muscular portion. 5. Papilla and submucosal intrabuccal portion. Many stenosis can be observed in this segment, leading to papillotomies or to direct access to the next segment through a surgical approach.

CHAPTER 12  Salivary Duct Anatomy for Sialendoscopy

Keywords Salivary Duct Sialendoscopy Stensen’s Duct Parotid Duct

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CHAPTER 12  Salivary Duct Anatomy for Sialendoscopy

• Fig. 12.2

• Fig. 12.3

 

Landmarking Stensen’s duct.

  Facial transverse pedicle Stensen’s duct, green marker; facial nerve buccal branches, black markers. Between the black markers is the transverse facial artery terminal branch.

99

• Fig. 12.4  Close up of facial transverse pedicle Stensen’s duct, green marker; facial nerve buccal branches, black markers. Between the black markers is the transverse facial artery terminal branch.

•

Fig. 12.5  Masseteric and glandular fixed posterior portion of Stensen’s duct.

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• Fig. 12.6

  Close up view of the masseteric and glandular fixed posterior portion of Stensen’s duct.

• Fig. 12.8

  To straighten the duct and to pass the knee, it is mandatory to stretch the buccinator muscle anteriorly and laterally, so that the sialendoscope may pass the duct masseteric angle.

Main Anatomic Relationships: the Buccal Triangle The parotid duct crosses the buccal space, before entering the oral cavity. The borders are: posteriorly, the masseter muscle anterior border; superomedially, the zygomaticus major muscle; inferiorly, the platysma muscle superior border or the mandible. Anatomic elements cross this space: (1) transverse facial pedicle containing the Stensen’s duct, the longitudinal branch of the facial transverse artery, and the buccal branches of the facial nerve; (2) the facial vein is straight and oblique from the inner canthus to the mandibular notch (junction mandible caudal border/masseter anterior border) where the facial vascular pedicle is crossing the mandible.

• Fig. 12.7

 

Duct knee: the duct, still in the fascia, becomes mobile.

13 

Sialendoscopy: Getting Started DAVID M. COGNETTI

Introduction The applications of sialendoscopy continue to increase. Whether in isolation or as an accessory to more invasive techniques, sialendoscopy has expanded gland-sparing options for the management of non-neoplastic salivary disorders. Appropriately, this has caused an increased interest in the use of sialendoscopy by physicians and patients alike. As with the implementation of any new technology, it is important that surgeons who are seeking to incorporate sialendoscopy into their practice do so in a manner that is both safe and efficient. The goal of this chapter is to provide advice for the novice sialendoscopist to optimize success during the learning curve of adoption. Traditional approaches to obstructive and chronic sialadenitis are limited in number and effectiveness. Conservative measures, such as medical management and/or ductal expansion with dilation or sialodochoplasty, typically result in undertreatment as they do not address the underlying source and often result in ongoing symptoms. Gland excision, on the other hand, typically results in overtreatment by removing physiologically functional tissue and carries with it associated surgical risks. Sialendoscopy offers several advantages over traditional approaches and can be used for both diagnostic and therapeutic purposes.1 By allowing endoscopic access to the salivary ductal system, sialendoscopy has expanded the minimally invasive options for the management of salivary gland disorders.2 This is evident not only by the increasing interest in the technique, but also by a demonstrable drop in the number of salivary gland excisions when it is utilized.3,4 Proper knowledge and preparation are critical to the success of sialendoscopy. This chapter offers recommendations to those who are getting started in the incorporation of sialendoscopy into their practice.

Training It is strongly encouraged that any surgeon new to sialendoscopy takes a formal course prior to initiation in practice. Specific advantages of a formal course include didactic introduction to techniques and concepts, hands-on experience with the equipment, and access to expert instruction

and counseling. Courses for both beginner and advanced sialendoscopists are available in Europe, Canada, and the United States. Animal and cadaveric models allow surgeons to increase familiarity with techniques prior to intervention on patients. When available, a visit to observe an experienced sialendoscopist performing live surgery further enhances a beginner’s understanding of the set-up and steps of sialendoscopy by providing real world exposure that cannot be mimicked in a laboratory. Proctorship or direct availability of an experienced mentor for phone consultation during one’s first few cases helps to cover any subtleties that may not have been appreciated during the formal training. After performing some cases, additional education through return to a formal course, study of published resources, and attendance of panels and lectures at national meetings, will be enhanced by the perspective gained from an early experience in sialendoscopy. Interest groups and formal sections for sialendoscopy have been developed within North American societies, such as the American Academy of Otolaryngology and the American Head and Neck Society, in addition to the European Salivary Gland Society (ESGS), now the international Multidisciplinary Salivary Gland Society (MSGS). These offer further online and in person opportunities to seek counsel and share ideas. Finally, it is important that the training and preparation extend beyond the surgeon. Intraoperative nurses and anesthesiologists should be educated regarding sialendoscopy and issues pertinent to their roles prior to embarking on a case. The personnel responsible for the sterilization of the endoscopes must be educated on proper handling to minimize preventable damage and associated costs.

Anatomy As with any surgical procedure, a thorough understanding of the anatomy is critical for a successful outcome. While the locations of the Wharton’s (Fig. 13.1) and Stensen’s (Fig. 13.2) papillae are familiar to most and visibly obvious, knowledge of the subtleties of how their ducts course can be the difference between a positive and frustrating result. The course of the ducts and their relationship to surrounding structures becomes more important during 101

CHAPTER 13  Sialendoscopy: Getting Started

Keywords Sialendoscopy Training Equipment Anesthesia Duct Access Complications

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• Fig. 13.1  Wharton’s papilla – located in the anterior floor of mouth posterior to the mandibular incisor teeth. • Fig. 13.3  Floor of mouth anatomy in a patient after sublingual gland excision demonstrating the relationship of the submandibular duct crossing the lingual nerve.

Equipment

• Fig. 13.2

  Stensen’s papilla – located in the buccal mucosa opposite the second maxillary molar.

interventional approaches that require incisions and dissection through adjacent tissue. Deep floor of mouth and deep buccal anatomy is rarely encountered in routine practice, and transoral and transcutaneous approaches to these areas result in different perspectives of the same structures. As such, nonendoscopic intervention requires a 3-dimensional understanding of the anatomy, especially with regards to the relationship of the ducts with the lingual and buccal nerves (Fig. 13.3). Not only does in-depth knowledge of anatomy facilitate localization and removal of stones, but it also prevents damage to these adjacent nerves. Submandibular duct stones are most commonly located in the proximal duct as it crosses under the lingual nerve (Video 13.1). Finally, due to a small potential for complication requiring immediate intervention, it is advised that all surgeons performing sialendoscopy have the competence to proceed with gland excision as a salvage procedure.

Much of the equipment used during sialendoscopy is fragile and expensive. Due to this, the acquisition of equipment is often the biggest hurdle for the adoption of sialendoscopy into practice. In addition to the endoscopes, there are an increasing number of accessory tools that aid with access, intervention, and stenting. Familiarity with these accessory tools will optimize the beginner’s experience and outcomes. The supplier of the sialendoscopes has developed a rental program to support institutions during the initiation process. Utilization of rental agreements and limitation of purchases to the most necessary accessories are advised until experience and case volume justify expansion. Fortunately, much of the supporting equipment required for sialendoscopy is already available to most surgeons, such as camera, light source, loupes, mouth gag, and irrigation system. Other common medical equipment can be repurposed to aid during sialendoscopy, such as the use of an angiocatheter for ductal access or stent. Due to the fragility and cost, proper handling and care of the sialendoscopes is stressed and proactive management of a chain of custody through the sterilization process is encouraged.

Case Set-Up Location/Anesthesia Sialendoscopy can be performed under local anesthesia, monitored anesthesia care, or general anesthesia, and in a range of locations including office, surgery center, and hospital setting.1,5–7 Factors that influence the level of anesthesia include patient preference, surgeon preference, and the anticipated degree of intervention. Diagnostic and purely endoscopic procedures favor local sedation, while concern for patient cooperation, surgeon inexperience, and difficult anatomy or complex procedures favor general anesthesia.5,6

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• Fig. 13.5

A

  Set-up of the Mayo stand limited to dilators and essential instruments to minimize risk of damage to endoscope. Note the endoscope’s handle is supported by a rolled towel to minimize risk of damage to the endoscopic portion.

B • Fig. 13.4  Positioning of the video tower and Mayo stand in (A) an awake patient undergoing sialendoscopy with head of bed upright and directed towards the anesthesiology team, and in (B) an anesthetized patient with bed flat and head of bed directed away from the anesthesiology team.

When performed under local ± sedation, the patient is kept in the seated position and any sedation is lightly titrated to keep the patient alert and cooperative. When general anesthesia is utilized, some favor nasal intubation. However, nasal intubation is typically not necessary for parotid procedures and unilateral submandibular interventions.

Room/Equipment Room set-up should be configured to facilitate viewing of the television monitor by the surgeon and assistants (Fig. 13.4). This is typically positioned near the head of the patient. An instrument tray created specifically for sialendoscopy procedures is encouraged to ensure proper instrumentation is available. A Mayo stand (Fig. 13.5) is utilized for the endoscope and dilators, while a backtable (Fig. 13.6) houses additional instrumentation to minimize clutter

• Fig. 13.6  Arrangement of the backtable, which houses any additional instruments.

around the fragile endoscope. Disposable accessories are kept unopened but immediately available during the procedure (Fig. 13.7). It is important to white balance, focus, and orient the camera to the scope prior to introduction into the patient. If the camera and scope are not in line, then navigation of the duct will prove impossible (Fig. 13.8). The light source is kept to the minimum needed to illuminate the view, which is typically around 30%. The scope is handed directly and deliberately between operating room personnel to minimize risk of damage and placed on the table with its handpiece on a rolled towel to prevent pressure on the endoscopic shaft (Fig. 13.5).

Ductal Access Ductal access can be challenging for the beginner sialendoscopist. While training models and cadavers may help,8 they do not sufficiently mimic the pliability of live human tissue. The duct should be accessed with the smallest dilator

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and then serially dilated with sequentially increasing sizes.7 With experience, ductal access times can be as short as 3–4 min.9 When access is challenging, various adjunct and alternative methods have been described including methylene blue staining,10 guidewire placement and dilation with Seldinger technique,11 papillotomy,7 and limited distal sialodochotomy.12

Case Selection Learning Curve Many groups have demonstrated a definable learning curve with sialendoscopy. With experience, likelihood of failure of cannulation,13 duration of case,13–15 percentage of cases performed under anesthesia,14,16 and the number of gland excisions have all been shown to decrease.3 In Denmark, the national rate of gland excisions was shown to have decreased after the introduction of sialendoscopy.4 While some of these measures represent improvements in familiarity and skill of the surgeons, many practiced sialendoscopists would advise that the refinement of case selection that comes with experience has a bigger impact. Fortunately, much literature exists that can be used to predict outcomes and best approaches for novices who are still in the learning curve. A thorough understanding of the indications and limitations of sialendoscopy will help guide both the surgeon’s and patient’s expectations. When early in the learning curve, surgeons should favor diagnostic and less challenging interventions and should have a low threshold to perform the procedures under general anesthesia.

Treatment Algorithms • Fig. 13.7

Disposable accessories stored in a mobile tower to facilitate availability during cases.

•

 

Fig. 13.8  Orientation of the light source of the endoscope 180 degrees from the button pad of the camera. This ensures proper orientation of view when the endoscope is held in the proper position with the irrigation channel up and light source down.

Many studies have reported outcomes, including large studies of over 1000 and 5000 patients with sialolithiasis, that can be used to guide case selection.17,18 In addition to stones, sialendoscopy has been described in the diagnosis and management of many other salivary disorders.19 These include ductal stenosis,20,21 radioactive iodine induced sialadenitis,22,23 juvenile recurrent parotitis,24 and acute masseteric bend.25 When evaluating cases of sialolithiasis, ~75% will occur in the submandibular gland and 25% will occur in the parotid gland.17,18 A very small percentage of stones have been reported in the sublingual duct/gland.26 Ductal cannulation can be more difficult for the Wharton’s duct in comparison with Stensen’s duct.9 The submandibular duct, on the other hand, tends to be easier to navigate than the parotid duct due to its larger size and straighter course. Although parotid stones tend to be on average smaller in size, parotid interventions tend to have a lower success rate compared with submandibular interventions, likely due to anatomic differences.3,17 It should be noted that purely endoscopic removal is achieved in the minority of cases, with combined transoral and transfacial techniques often required.27,28 Algorithms exist to help guide the approach for both parotid and submandibular stones.1,2,17,29 These

CHAPTER 13  Sialendoscopy: Getting Started

tend to be based on the size of the stone and its location along the duct. The success of endoscopic removal decreases with increasing size of stone and distances from the papilla.30 The length of the minor axis of a stone has been shown to significantly correlate with treatment outcome for purely endoscopic intervention, whereas the length of the major axis has not (Video 13.2).31 The orientation and shape of the stone has also been suggested to predict success.32 For parotid stones, location in relation to the masseter muscle can be used to guide the type of intervention and expectation of endoscopic visualization.33–35 Finally, in addition to size and mobility of stones, duration of patient symptoms may also predict likelihood of purely endoscopic removal.36

Imaging There are several imaging options for the work-up and management of patients with salivary disorders. Often, patients referred for sialendoscopy arrive with imaging already performed. Computed tomography (CT) tends to be the most common and has been shown to have high specificity and sensitivity in the detection of stones.37 Traditional iodinated sialography offers excellent visualization of ductal anatomy, but is less frequently utilized due to the technical burden. Compared with CT, the visualization of stones is poor on magnetic resonance (MR) imaging, but visualization of the ductal system is improved, especially in MR sialography (Fig. 13.9).38 While the sensitivity and negative predictive value of ultrasound have been described as low for sialolithiasis,37,39 surgeon-performed ultrasound has been described to predict sialendoscopy findings with greater accuracy.40,41 Combining surgeon-performed ultrasound with transoral

A

palpation, a technique described as sonopalpation, further increases the sensitivity and specificity over ultrasound alone.42 For beginners who are not experienced in ultrasound, CT is recommended for all sialolithiasis cases. MR imaging is recommended for inflammatory cases.

Patient-Reported Outcomes In addition to the technical outcomes on which the above described treatment algorithms are based, there is a burgeoning body of data on patient-reported outcomes. The University of California, San Francisco (UCSF) has developed a survey called the Chronic Obstructive Sialadenitis Symptoms (COSS) questionnaire to assess symptomatic outcomes in an objective manner.43 In line with a study that showed that parotid cases were more likely to require additional interventions,3 the USCF groups found that patients with parotid interventions had higher post-sialendoscopy COSS scores than patients with submandibular interventions, indicating higher persistent symptoms. Patients who underwent interventions for stones versus non-stone disease had significantly lower COSS scores, indicating the symptom resolution is more likely in the treatment of stones. Symptom relief after sialendoscopy for non-stone disease can be seen in as low as half of patients.44 A similar study investigating quality of life after gland-preserving surgery found that almost 90% of patients have symptom improvement but almost 50% continue to have some level of persistent symptoms.45 In this study and in another study, patients with stones also had significantly higher symptom relief and perceived benefit, respectively.45,46

B • Fig. 13.9

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  (A) CT and (B) MR of a patient with a parotid duct stone. Note the improved visualization of the stone on CT versus improved visualization of ductal ectasia on MR.

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References

• Fig. 13.10

  Extraluminal view after ductal perforation. Note the fascia stranding and submucosal fat.

Complications Complications from sialendoscopy assisted procedures can be as high as 25%, but fortunately, the vast majority are minor.47,48 Minor complications include infection, ductal perforation, lingual nerve paresis, and postoperative edema.3,47,48 These are typically conservatively managed and well tolerated by the patient. It is important to recognize ductal perforation when it occurs as aggressive insufflation can lead to extensive edema from extravasation of the saline from the duct (Fig. 13.10 and Video 13.3). In submandibular cases, the floor of mouth edema can lead to airway concerns. Long-term complications are rare and include strictures, ranulas, and recurrent stone formation.49 The most common instrument complication is breakage of the endoscope. It is recommended that a second endoscope always be on hand when performing sialendoscopy. Rare reported occurrences that require immediate salvage open surgery include ductal avulsion, basket entrapment within a patient, and laser tip fragmentation within a patient.47,48,50 Finally, malignancy has been reported to present as chronic sialadenitis and should be considered to avoid misdiagnosis.51,52

Conclusion Sialendoscopy has revolutionized the management of salivary disorders by expanding gland-sparing options for the treatment of obstructive and inflammatory conditions. As new users seek to add sialendoscopy to their armamentarium, there should be a focus on safety and efficacy. Learning from the experience of others via training courses, textbooks, videos, published literature, and direct consultation, aids in optimizing outcomes.

1. Witt RL, Iro H, Koch M, et al. Minimally invasive options for salivary calculi. Laryngoscope 2012;122(6):1306–11. 2. Marchal F, Dulguerov P. Sialolithiasis management: the state of the art. Arch Otolaryngol Head Neck Surg 2003;129(9):951–6. 3. Modest MC, Galinat L, Rabinowitz MR, et al. Learning progression in the use of sialendoscopy for sialolithiasis: effect on gland preservation. Otolaryngol Head Neck Surg 2014;151(2): 240–5. 4. Rasmussen ER, Lykke E, Wagner N, et al. The introduction of sialendoscopy has significantly contributed to a decreased number of excised salivary glands in Denmark. Eur Arch Otorhinolaryngol 2016;273(8):2223–30. 5. Jokela J, Haapaniemi A, Mäkitie A, Saarinen R. Sialendoscopy under local anaesthesia. Acta Otolaryngol 2017;137(3): 310–14. 6. Trujillo O, Drusin MA, Pagano PP, et al. Evaluation of monitored anesthesia care in sialendoscopy. JAMA Otolaryngol Head Neck Surg 2017;143(8):769–74. 7. Marchal F, Becker M, Dulguerov P, Lehmann W. Interventional sialendoscopy. Laryngoscope 2000;110(2 Pt 1):318–20. 8. Pascoto GR, Stamm AC, Lyra M. Sialendoscopy training: presentation of a realistic model. Int Arch Otorhinolaryngol 2017;21(1):17–20. 9. Kent DT, Walvekar RR, Schaitkin BM. Sialendoscopy: getting started, how long does it take? Laryngoscope 2016;126(5):1083–5. 10. Luers JC, Vent J, Beutner D. Methylene blue for easy and safe detection of salivary duct papilla in sialendoscopy. Otolaryngol Head Neck Surg 2008;139(3):466–7. 11. Chossegros C, Guyot L, Richard O, et al. A technical improvement in sialendoscopy to enter the salivary ducts. Laryngoscope 2006;116(5):842–4. 12. Chang JL, Eisele DW. Limited distal sialodochotomy to facilitate sialendoscopy of the submandibular duct. Laryngoscope 2013;123(5):1163–7. 13. Steck JH, Stabenow E, Volpi EM, Vasconcelos ECG. The learning progression of diagnostic sialendoscopy. Braz J Otorhinolaryngol 2016;82(2):170–6. 14. Hawat Al A, Vairel B, De Bonnecaze G, et al. Sialendoscopy learning curve: comparing our first and last 100 procedures. B-ENT 2015;11(4):281–5. 15. Luers JC, Damm M, Klussmann JP, Beutner D. The learning curve of sialendoscopy with modular sialendoscopes: a single surgeon’s experience. Arch Otolaryngol Head Neck Surg 2010;136(8):762–5. 16. Farneti P, Macrì G, Gramellini G, et al. Learning curve in diagnostic and interventional sialendoscopy for obstructive salivary diseases. Acta Otorhinolaryngol Ital 2015;35(5):325–31. 17. Zenk J, Koch M, Klintworth N, et al. Sialendoscopy in the diagnosis and treatment of sialolithiasis: a study on more than 1000 patients. Otolaryngol Head Neck Surg 2012;147(5):858–63. 18. Iro H, Zenk J, Escudier MP, et al. Outcome of minimally invasive management of salivary calculi in 4,691 patients. Laryngoscope 2009;119(2):263–8. 19. Erkul E, Gillespie MB. Sialendoscopy for non-stone disorders: the current evidence. Laryngoscope 2016;1(5):140–5. 20. Koch M, Iro H. Extended and treatment-oriented classification of parotid duct stenosis. Laryngoscope 2017;127(2):366–71. 21. Koch M, Künzel J, Iro H, et al. Long-term results and subjective outcome after gland-preserving treatment in parotid duct stenosis. Laryngoscope 2014;124(8):1813–18.

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22. Kim JW, Han GS, Lee SH, et al. Sialoendoscopic treatment for radioiodine induced sialadenitis. Laryngoscope 2007; 117(1):133–6. 23. Bomeli SR, Schaitkin B, Carrau RL, Walvekar RR. Interventional sialendoscopy for treatment of radioiodine-induced sialadenitis. Laryngoscope 2009;119(5):864–7. 24. Berta E, Angel G, Lagarde F, et al. Role of sialendoscopy in juvenile recurrent parotitis (JRP). Eur Ann Otorhinolaryngol Head Neck Dis 2017;134(6):405–7. 25. Reddy R, White DR, Gillespie MB. Obstructive parotitis secondary to an acute masseteric bend. ORL J Otorhinolaryngol Relat Spec 2012;74(1):12–15. 26. Goodstein L, Galinat L, Curry J, et al. Sialendoscopy for sublingual gland sialolithiasis. Ann Otol Rhinol Laryngol 2017;126(3):216–18. 27. Roland LT, Skillington SA, Ogden MA. Sialendoscopy-assisted transfacial removal of parotid sialoliths: a systematic review and meta-analysis. Laryngoscope 2017;127(11):2510–16. 28. Walvekar RR, Bomeli SR, Carrau RL, Schaitkin B. Combined approach technique for the management of large salivary stones. Laryngoscope 2009;119(6):1125–9. 29. Koch M, Zenk J, Iro H. Algorithms for treatment of salivary gland obstructions. Otolaryngol Clin North Am 2009;42(6):1173–92. 30. Cox D, Chan L, Veivers D. Prognostic factors for therapeutic sialendoscopy. J Laryngol Otol 2018;132(3):275–8. 31. Kondo N, Yoshihara T, Yamamura Y, et al. Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis: the minor axis of the sialolith is a regulative factor for the removal of sialoliths in the hilum of the submandibular gland using sialendoscopy alone. Auris Nasus Larynx 2018;45(4):772–6. 32. Walvekar RR, Carrau RL, Schaitkin B. Endoscopic sialolith removal: orientation and shape as predictors of success. Am J Otolaryngol 2009;30(3):153–6. 33. Galinat L, Curry J, Luginbuhl A, et al. Nonvisualization of sialoliths during sialendoscopy. Otolaryngol Head Neck Surg 2016;154(6):1019–22. 34. Kiringoda R, Eisele DW, Chang JL. A comparison of parotid imaging characteristics and sialendoscopic findings in obstructive salivary disorders. Laryngoscope 2014;124(12):2696–701. 35. Kondo N, Yoshihara T, Yamamura Y, et al. The landmark for removal of sialoliths using sialendoscopy alone in parotid gland sialolithiasis. Auris Nasus Larynx 2018;45(2):306–10. 36. Luers JC, Grosheva M, Reifferscheid V, et al. Sialendoscopy for sialolithiasis: early treatment, better outcome. Head Neck 2012;34(4):499–504. 37. Thomas WW, Douglas JE, Rassekh CH. Accuracy of ultrasonography and computed tomography in the evaluation of patients undergoing sialendoscopy for sialolithiasis. Otolaryngol Head Neck Surg 2017;156(5):834–9.

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38. Becker M, Marchal F, Becker CD, et al. Sialolithiasis and salivary ductal stenosis: diagnostic accuracy of MR sialography with a three-dimensional extended-phase conjugate-symmetry rapid spin-echo sequence. Radiology 2000;217(2):347–58. 39. Terraz S, Poletti PA, Dulguerov P, et al. How reliable is sonography in the assessment of sialolithiasis? AJR Am J Roentgenol 2013;201(1):W104–9. 40. Larson AR, Aubin-Pouliot A, Delagnes E, et al. Surgeonperformed ultrasound for chronic obstructive sialadenitis helps predict sialendoscopic findings and outcomes. Otolaryngol Head Neck Surg 2017;157(6):973–80. 41. Goncalves M, Mantsopoulos K, Schapher M, et al. Ultrasound supplemented by sialendoscopy: diagnostic value in sialolithiasis. Otolaryngol Head Neck Surg 2018;159(3):449–55. 42. Patel NJ, Hashemi S, Joshi AS. Sonopalpation: a novel application of ultrasound for detection of submandibular calculi. Otolaryngol Head Neck Surg 2014;151(5):770–5. 43. Aubin-Pouliot A, Delagnes EA, Eisele DW, et al. The Chronic Obstructive Sialadenitis Symptoms Questionnaire to assess sialendoscopy-assisted surgery. Laryngoscope 2016;126(1):93–9. 44. Delagnes EA, Aubin-Pouliot A, Zheng M, et al. Sialadenitis without sialolithiasis: prospective outcomes after sialendoscopyassisted salivary duct surgery. Laryngoscope 2017;127(5):1073–9. 45. Gillespie MB, O’Connell BP, Rawl JW, et al. Clinical and quality-of-life outcomes following gland-preserving surgery for chronic sialadenitis. Laryngoscope 2015;125(6):1340–4. 46. Meier BA, Holst R, Schousboe LP. Patient-perceived benefit of sialendoscopy as measured by the Glasgow Benefit Inventory. Laryngoscope 2015;125(8):1874–8. 47. Jokela J, Tapiovaara L, Lundberg M, et al. A prospective observational study of complications in 140 sialendoscopies. Otolaryngol Head Neck Surg 2018;159(4):650–5. 48. Walvekar RR, Razfar A, Carrau RL, Schaitkin B. Sialendoscopy and associated complications: a preliminary experience. Laryngoscope 2008;118(5):776–9. 49. Nahlieli O. Complications of sialendoscopy: personal experience, literature analysis, and suggestions. J Oral Maxillofac Surg 2015;73(1):75–80. 50. Goates AJ, Kung RW, Tracy CR, Hoffman HT. Intraductal laser fiber tip fracture and retrieval during sialendoscopic laser-assisted lithotripsy. Ann Otol Rhinol Laryngol 2017;126(11):774–7. 51. Bryant LM, Tassone P, Curry J, et al. Buccal space malignancy in the setting of chronic sialadenitis: a report of 2 cases. Ear Nose Throat J 2018;97(1–2):E12–14. 52. Nahlieli O. Advanced sialoendoscopy techniques, rare findings, and complications. Otolaryngol Clin North Am 2009; 42(6):1053–72.

14 

Types of Sialendoscopes and Accessories FRANCIS MARCHAL (14.1), FREDERIC FAURE (14.1), MICHAEL KOCH (14.2), HEINRICH IRO (14.2), MARK MCGURK (14.3), AND ROHAN R. WALVEKAR (14.4)

14.1  THE MARCHAL INSTRUMENTS Salivary Endoscopy Relies on Several Factors 1. The size of the papilla and the difficulty to pass the papilla without traumatizing it 2. The caliber of the ducts 3. The diameter of the scope 4. The quality of the scope (number of pixels) 5. The limitations of maneuvering the scope in the ductal system due to the anatomy (sharp angles) and to the scope (bendable or not) 6. The correct visibility in the ductal system (that depends both on the rinsing system and on the tightness of the papilla) as the duct is naturally collapsed, similar to the esophagus. The history of sialendoscopes and sialendoscopy has been closely related to these facts. Gundlach and colleagues, in 1990, developed the first flexible scope of 2.2  mm that had a fixed angled tip enabling 12 laser lithotripsy cases.1 The length and fragility of the scope hampered its development. Katz, in 1991, performed the first stone extraction via a basket next to a nude optic fiber of 0.5 mm.2 The poor vision, the lack of rinsing, and inability to direct both the basket and optic fiber hampered its development. Nahlieli and colleagues, in 1994, used a rigid optic fiber of 2.7 mm and baskets adjacent to the fiber on eight cases.3 There was a lack of a rinsing system and working channel, and this imposed a systematic marsupialization. We started using a 1.6 mm flexible endoscope (mobile tip) with a working channel for rinsing and inserting baskets in 1995.4,5 Although it was the first scope with both a rinsing and working channel, its fragility made its development impossible. In 1997, Nahlieli and Baruchin6 started developing an interventional “sialendoscope” based on two tubes of 108

1.3 mm with a large handle and rinsing system. Its diameter corresponded to the diameter of the ducts (Zenk et al.),7 and length limited its use. Our development of a specific “modular sialendoscope” occurred also in 1997.4,5,8 A line of diagnostic and interventional sheaths is adapted to thin optic fibers of 0.75 mm with working channels (WC) of 0.65 and 1.15 mm. A similar line for 1  mm optic fibers, with similar WC, a rinsing system around the optic fiber, and a beveled tip allowed progressive dilatation of the papilla (Fig. 14.1.1). The fibers are semiflexible, and they can follow any curve that has been previously applied to the sheaths, in order to explore sharp angled bifurcations. The first 100 cases were published in the New England Journal of Medicine (NEJM) in 1999.9 The noninvasive passage of the papilla being the limiting factor, we developed specific instruments to dilate the papilla atraumatically. We focused starting in 2001, teaching the technique in our European Sialendoscopy Training Center. The importance of papilla dilators, conic dilators, hollow dilators introduced over guidewires, as well as scissors and grasping and biopsy forceps (all instruments that were developed in collaboration with the Karl Storz Co., Tuttlingen, Germany) enabled a reproducible technique (Fig. 14.1.2). Regarding disposables, as there were no small diameter baskets and balloons, we developed baskets of three, four, and six wires (0.6 and 0.4 mm diameter) with and without tip as well as balloons (0.7 and 0.9 mm) microburrs and guidewires (0.38, 0.4, and 0.6 mm) fitting our sialendoscopes (Fig. 14.1.3), and looked for laser fibers of similar sizes, enabling endoscopic controlled intraductal lithotripsy of stones. Later in 1999, the Karl Storz Co. produced what we named the “all-in-one scopes,” including optics and light, rinsing channels (RC), and WC in a single tube. To be able to treat children and small ducts, as well as adults, we requested several diameters: 0.89 mm (WC or RC 0.25); 1.1 mm (WC 0.45, RC 0.25); 1.3 mm (WC 0.65, RC 0.25); and 1.6 mm (WC 0.8, RC 0.25).

CHAPTER 14  Types of Sialendoscopes and Accessories

Keywords Sialendoscope Accessories Modular Sialendoscope Interventional Sialendoscope Diagnostic Sialendoscope Sialo-Balloon Dilator

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• Fig. 14.1.1

  Marchal modular sialendoscope. Interventional sheaths and semi-rigid optic fibers (exist in two sizes: 0.75 and 1 mm). (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

A A B

C

B D C • Fig. 14.1.3

  Accessory instruments: (A) a tipless basket and balloon; (B) basket with tip; (C) guidewire. (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

E • Fig. 14.1.2

  Accessory instruments: (A) papilla dilators (from 0000 to 8); (B) conic dilator; (C) bougies (in five sizes); (D) grasping forceps; and (E) scissors. (©2018 Photo Courtesy of KARL STORZ EndoscopyAmerica, Inc.)

All the scopes have markings for each centimeter and a bent tip of 5°, as we have noticed that exploration of the ductal system requires a rigid bend of the tip of the scope (Fig. 14.1.4).8–48 Both systems, for 20 years, have been used to treat patients with salivary stones and strictures.8–51 Nahlieli and Baruchin52 later developed the same principle of a straight “sialoscope,” with disposable sheaths and a flexible optic fiber. In 2004, the Erlangen group using also

a similar sialoscope published their first 24 sialendoscopy cases.53 In 2007, the Karl Storz Co. developed, with the Erlangen group, similar sialendoscopes to our “all-in-one” scopes (0.89 mm, 1.1 mm, 1.6 mm) with a different material, nitinol, allowing total flexibility of the scope but no definite bending of its tip. Having used both systems for almost 20 years, the modular scope system appears, in our opinion, to be slightly less fragile, with a superior image quality due to an increase in pixels for an identical size. It is also more efficient to explore the entire ductal system due to the customizable bending of its tip and to dilate strictures with the beveled tip. This customization is impossible with “allin-one scopes”: Marchal models do have a fixed angle of 5°, which facilitates exploration but is not bendable, and the Erlangen scopes do not have a bent tip, as it is flexible but not bendable. It is important to say that all the scopes existing on the market (at time of writing) are extremely fragile. The

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fragility is not only linked with the tip of the endoscope but also with the cable, that contains the optic fibers and the light fibers. The sterilization process is one of the keys to its duration.

14.2  THE ERLANGEN SET Investigation of salivary ducts with endoscopes was first described by Königsberger in 1990 and Katz in 1990.54,55 These flexible endoscopes caused minimal trauma owing to their small diameter and flexibility. Image quality was unsatisfactory due to their poor optical properties and the absence of an irrigation channel in many instruments. Rigid endoscopes, derived from urology, were used later by Nahlieli et al.3 and provided better optical quality but caused greater trauma to the duct epithelium. To combine the advantages of both types, semirigid or semiflexible endoscopes were developed.9,10,52 These instruments have a smooth, flexible, atraumatic outer sheath (Table 14.2.1). Zenk et al. examined the diameters of the salivary duct in anatomic specimens. His study indicated that the parotid and submandibular ducts each had an average diameter of 1.5 mm. The parotid duct orifice had an average diameter of 0.5 mm, and the submandibular duct orifice measured 0.1–0.5 mm. It was concluded that sialendoscopes with an outer diameter of 0.7–1.7 mm should be suited for all the major salivary ducts.7 Erlangen sialendoscopes were developed based on our own clinical experience and basic research (Karl Storz; Fig. 14.2.1, Table 14.2.1).56 All the endoscopes can be sterilized with standard disinfectant solution or gas/plasma

A

B • Fig. 14.1.4

  Marchal “all-in-one” sialendoscopes of 0.89  mm, 1.1  mm, 1.3 mm, 1.6 mm, having all working channels (WC) and/or rinsing channels (RC). (A) Larger sialendoscopes of similar appearance: 1.1 mm (WC 0.45, RC 0.25); 1.3 mm (WC 0.65, RC 0.25); 1.6 mm (WC 0.8, RC 0.25). (B) Small sialendoscope of 0.89 mm (WC or RC 0.25). (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

A • Fig. 14.2.1

B

  Erlangen set of sialendoscopes with one diagnostic and two interventional sialendoscopes: (A) the 0.8 mm and the 1.6 mm sialendoscopes with forceps and microdrill suited for the latter; (B) the 1.1 mm sialendoscope with several instruments passing through its working channel. (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

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TABLE 14.2.1  History of the Development of the Sialendoscopes

Author (Year)

Sialendoscope (Type)

Sialendoscope (Diameter)

1. Channel (Diameter)

2. Channel (Diameter)

Königsberger (1990)

Flexible

–

–

–

Katz (1990), (1991)

Flexible

0.8 mm

–

–

Gundlach (1994)

Flexible

2.0 mm

0.6 mm

–

Nahlieli (1994)

Rigid

2.7 mm

–

–

Iro (1995)

Flexible

1.6 mm

0.6 mm

–

Ito (1996)

Flexible

1.5 mm

0.2 mm

–

Arzoz (1996)

Rigid

2.1 mm

1.0 mm

–

Marchal (1997)

Flexible

1.5 mm

0.5 mm

–

Yusua (1997)

Flexible Rigid

0.8 mm 1.8 mm

– –

– –

Nahlieli (1997)

Rigid Rigid

2.0 mm 2.5 mm

– 1.0 mm

– –

Marchal (1998)

Semiflexible Semiflexible

1.3 mm 2.67 mm2

0.8 mm 0.8 mm

– –

Nahlieli (1999)

Semiflexible Semiflexible

1.3 mm 2.3 mm × 1.3 mm

1.0 mm 1.0 mm

– yes

Iro (2000)

Semiflexible Semiflexible

1.1. mm 1.2 mm

0.4 mm 0.6 mm

– yes

Marchal (2001), (2002)

Semiflexible Semiflexible

1.3 mm 2.29 mm2

0.8 mm 0.8 mm

yes yes

Zenk (2004)

Semiflexible Semiflexible

1.1 mm 1.38 mm

0.4 mm 0.8 mm

yes yes

“Erlangen-Set” (2004–2007)

Semiflexible Semiflexible Semiflexible

0.8 mm 1.1 mm 1.6 mm

0.25 mm 0.45 mm 0.85 mm

– 0.25 mm 0.25 mm

sterilization. Sialendoscopes and instruments can be stored on a metal tray. The Erlangen set of sialendoscopes currently consists of three different sialendoscopes and includes specific features. The image transmission system has a resolution of 6000–10,000 pixels. The optical cable and telescope can be connected to a standard cold light source and video system. The sialendoscopes have 0° forward-view optics. The eyepiece is offset, has built-in fiberoptics, and is 140 cm long. The sialendoscopes have a specific designed handpiece suitable for economic handling of the device. The outer sheath of the endoscopes is made of nitinol to provide adequate flexibility. The useful length is at least 10 cm and markings are placed at 1 cm intervals along the outer sheath. The diameter for the sialendoscope for diagnostic purposes is 0.8 mm. The sheath contains the optical channel and one channel for irrigation with a diameter of 0.25 mm (Fig. 14.2.1A). The nitinol sheath provides flexibility to a nearly 90° angle. The set of endoscopes includes two

sialendoscopes for diagnostic and interventional purposes, which have a diameter of 1.1 and 1.6 mm. The 1.1 mm (Fig. 14.2.1B) sialendoscope has a working channel of 0.45 mm included within the sheath, which allows insertion of small instruments with adequate diameters like various baskets, microdrill or laser fiber. This sialendoscope can be bent to about 40–50°. The 1.6 mm sialendoscope permits larger instruments with a diameter of the working channel of 0.85 mm. The larger microdrill and various kinds of forceps (diameter 0.78 mm each) make more effective interventional therapy possible. The sheath is firmer so that flexibility is limited to about 30°. The different diameters and centimeter markers on the shaft of the sialendscopes are of particular importance in the diagnosis and classification of stenosis. These parameters are important for sialendoscopic-based classification of stenosis.57–59 The narrow duct orifice must allow entry of the endoscope, and generally this requires expanding the orifice with a dilator (Fig. 14.2.1B).

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A

C

B

D

• Fig. 14.2.2

  Instruments for interventional sialendoscopy: (A) basket with tip; (B) without tip; (C) biopsy forceps; and (D) grasping forceps within the working channel of the 1.6 mm sialendoscope. (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

Several wire baskets with a working length of 20 cm differ in size, tip, and handle. The smaller baskets have an outer diameter of 0.38 mm and four wires; the larger baskets are 0.78 mm and come with three, four, or six wires. They can have a handle by which the basket is opened and closed; alternatively, the basket is opened and closed passively when pulled back into the sheath. If the basket has a tip, it can be welded or twisted. Tipless baskets allow a more atraumatic removal of stones or fragments (Figs. 14.2.2B, 14.2.3). All baskets are useful for extracting stones, plaques, or foreign bodies; however, only those with a tip (Fig. 14.2.2A) can be used to open stenoses.60–65 The available microdrills measure 0.38  mm and 0.78  mm in diameter (Fig. 14.2.4). They can be used to fragment stones which are impacted or too large for primary basket extraction. The sharp edges of the microdrill are also useful for opening filiform or complete stenoses. The drill can restore an absent lumen or expand a small residual lumen to permit insertion of other instruments such as a wire basket, balloon, or stent.59–63,66 Two different types of forceps are available; both have a diameter of 0.78 mm. The grasping forceps is flexible and has a length of 30 cm (Fig. 14.2.2C,D). Both jaws are movable and have a scored grasping surface. Small stones or fragments can be extracted in this way. If its consistency is not too hard, a stone may also be fragmented to allow extraction of the fragments, and also removal of plaques or foreign bodies is possible.62 The biopsy forceps are suitable for small biopsies. Cleaning brushes are available to obtain cytology.67 The WC of both interventional sialendoscopes permit laser lithotripsy and pneumatic lithotripsy. The probes of

•

Fig. 14.2.3  Interventional sialendoscopes with a basket inserted through the working channel. A tipless basket is inserted into the working channel of the 1.6 mm sialendoscope, which can be maneuvered with a handpiece (top right). Note the cm markings on the nitilol scope. (©2018 Photo Courtesy of KARL STORZ Endoscopy-America, Inc.)

both pneumatic lithotripters available68,69 fit through the working channel of the 1.6 mm sialendoscope. Stent implantation can be performed with custom-made stents made from polyurethane and available in various sizes ranging from 4.5, 6F, and 9F. These stents fit over the shaft of the Erlangen sialendoscopes for sialendoscopic-controlled stent implantation (Fig. 14.2.5).59–63,66,70,71

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14.3  POLYDIAGNOST MICROENDOSCOPES Overview

A

B • Fig. 14.2.4

  The smaller and larger microdrill (A) and the larger microdrill within the working channel of the 1.6 mm sialendoscope (B).

• Fig. 14.2.5

  Sialendoscope with stent pulled over the shaft before endoscopic controlled stent implantation.

The Polydiagnost (Hallbergmoos, Germany) salivary microendoscope uses 6000 and 10,000 pixel fibers to transmit light into the duct system and take images. Endoscopes with 3000 pixel fibers are not adequate. The two microendoscopes commonly used for salivary endoscopy are the Polydiagnost and Storz systems. These endoscopes have a number of features in common. Both instruments are delicate and easily broken. Particular attention should be paid to the cleaning process, as in hospitals this is normally delegated to a third party that uses robust systems that frequently damage the instruments. The endoscopes are provided with a custom-made tray, which provides some degree of protection. Both companies provide a range of sialendoscopes, starting with ~0.7 mm diameter shaft, which has an irrigation but no working channel. It is used to inspect the duct system and is useful in narrow ducts. The next size bracket are scopes of 1.1–1.3 mm diameter. These scopes have both working and irrigation channels and normally pass easily down most submandibular or parotid duct systems. These are the workhorse of the sialendoscopist. Finally, the upper size range, 1.4–1.6  mm, has the advantage of a large working channel but on occasion, is difficult to pass along a parotid duct; however, it is usually accepted by the wider submandibular duct system. These two manufacturers make accessories such as baskets, balloons, and drills to fit their own instrument. The design of these two endoscopes is based on different principles. The Storz system comes as a complete unit with an optic at one end of the system and the endoscope at the other. It cannot be dismantled and if a larger bore endoscope is required, a second endoscope is required. In contrast, the Polydiagnost unit is modular in design. This makes it more flexible in terms of application. The same endoscope can accept a range of different diameter disposable shafts that pass over the optical fiber (i.e., 0.7, 1.1, or 1.6 mm). An additional advantage is that the shaft can be replaced by a needle to allow the endoscope to be inserted into joint spaces or root canal cavities. This is a very versatile endoscopic design. The 10,000-pixel images have more definition but the fiber is larger with a commensurate reduction in space within the working channel. This limits the range of instruments that can be passed down the working channel (including the intracorporeal lithotripter). The advantage offered by a wider working channel is greater than the improved optics provided by the 10,000-pixel fiber. The author prefers the 6000-pixel endoscope because of the versatility it offers. But if the endoscope is to be used only for inspection, then the 10,000-pixel fibers is superior. An intracorporeal lithotripter was introduced transiently to clinical practice. It was quite efficient at breaking calculi

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but the cost of regulation led to its withdrawal. It is likely to reappear in due course. The wire used to transfer shocks onto the stone has to pass down the endoscope and this is only possible with the large bore endoscope, i.e., 1.6 mm, and in the Polydiagnost system with the 6000-pixel fiber.

Polydiagnost Modular Endoscope The basic unit (Figs. 14.3.1, 14.3.2) consists of the cable with an optical section at one end onto which a light source can be fitted (adaptors allow any light source to suffice). At

• Fig. 14.3.1  The endoscope consists of a long length of optical fiber, with an optical connection at one end and exposed fiber at the other. The shifter and triple connector (coupler) join together and can be shifted up and down the metal shaft so the end of the optical fiber just protrudes from the end of the disposable shaft. (Courtesy/permission PolyDiagnost, Hallbergmoos, Germany.)

the other end, the thin flexible fiber is exposed. On to this is fitted a “Shifter”. It forms a watertight seal and shifts up and down the metal shaft holding the fiber. Once the correct position is decided upon, it is held in position with a small screw tightened by finger pressure. Then a three-way adaptor (coupler) is slipped onto the metal shaft and locked onto the Shifter by way of a Luer lock. The three-way adaptor allows the fiber to pass down one of the channels, and the others are for irrigation and a working channel. Finally, there is the choice of different diameter disposable shafts to pass over the exposed optical fiber. These attach to the front of the adaptor and the whole ensemble can be moved up and down the metal shaft by releasing the Shifter until the optical fiber just emerges from the end of the shaft. The advantage is that the shafts can be changed during a procedure without the need to have another whole endoscope system deployed. There are other designs of the threeway adapter that allow the endoscope to be used in the mouth for inspection of root canals and implant channels in the bone. The Polydiagnost system can also be used to inspect small joints such as the temporomandibular joint (TMJ). It is much less traumatic than current TMJ endoscope systems. These two endoscope systems (Storz and Polydiagnost) are rigid in design and unlike larger endoscopes, the end is fixed. This limits the application of these endoscopes principally to the main ducts of the two major salivary glands, although on occasion, second and third order ducts can be accessed. One of the advantages of the Polydiagnost system on selected cases is that the hollow disposable shaft can be bent slightly to negotiate a distal bend in the duct system. The flexible fiber accommodates this adaption of the shaft readily. It is helpful to place something in the shaft when bending it, otherwise it will kink.

KEY POINTS • Polydiagnost and Storz endoscopes systems work very well at negotiating the submandibular and parotid duct system and both produce good images. • Both are delicate and need to be handled carefully to avoid damage. • The Polydiagnost system is more versatile and has a wider application. • Storz has the supreme advantage of company reach worldwide.

14.4  SIALENDOSCOPY ACCESSORIES: COOK MEDICAL •

Fig. 14.3.2  An assembled endoscope. The optical fiber can be moved to occupy a side channel so that an instrument can run directly down the endoscope. The optical fiber is flexible. It should be remembered that if the light source is too powerful (which is usually the case on common theatre stacks) there is a whiteout within the duct and nothing can be seen. Normally the very lowest setting is required, especially for imaging the parotid duct. High settings transillimuinate through the skin and can be used to identify the parotid duct at open surgery. (Courtesy/permission PolyDiagnost, Hallbergmoos, Germany.)

The technical ability of the sialendoscopist to perform endoscopy and intervention within the salivary ducts is influenced by salivary ductal disease, anatomy, and available technology. The introduction of innovative accessories by Cook Medical (Bloomington, IN) influenced the course of salivary endoscopy as a treatment option for treating physicians. Here, we discuss accessories by Cook Medical and how they have influenced the procedure.

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• Fig. 14.4.1  Salivary access dilator with guidewire. (Illustration 2011 Lisa Clark; courtesy Cook Medical.)

• Fig. 14.4.2

Duct Access Using Salivary Access Dilators-Guidewire System

damage to the duct. There are several other uses of the Cook dilators such as being used as a catheter to infuse steroid within the duct; to serve as a guide to a hilar or ductal stone by digital palpation of the dilator; facilitating a combined approach cutdown using a Bovie (as the dilators are not metal); and also for mechanical dilation of ductal stenosis either under direct view, endoscopic control, or ultrasound guidance.

The most important contribution from the Cook Medical Group (“Cook”) has been the introduction of the disposable salivary access ductal dilator system with guidewire (Fig. 14.4.1). Although introduced primarily for management of the submandibular duct access, the system can be used for dilation of both submandibular and parotid ductal systems. The access to the duct has been the rate-limiting step to performing sialendoscopy. Until the introduction of the Cook dilators, access was possible using serial metal dilators, sialodochotomy, or use of metal dilators over a guidewire via Seldinger’s technique. Although the option of metal dilators over a guidewire for dilation of the ductal system was available, the latter was not ideal due to a small transition between the guidewire and the tip of the dilator. The Cook dilators were able to conform more closely to the guidewire, creating a smooth transition to the guidewire at the tip–guidewire interface and making dilation easy and rapid. The dilators range from a No. 4 dilator to No. 7. Usually, dilation to No.5 or 6 is adequate for the ductal system (especially parotid ductal system) and allows introduction of the 1.1 and 1.3 mm all-in-one sialendoscopes. Dilation to No. 7 allows introduction of the 1.6 mm sialendoscopes. The dilators must always be used over a guidewire to prevent ductal damage and perforation (Video 14.4.1). The dilators are best used after allowing the tips to rest in water. Once inserted, it is advised to allow the dilators to stay within the duct for 10–15 s to allow the duct to accommodate to the dilation before introducing the next size up. The guidewire provided has two tips: a “flexible” tip (nontraumatic), which is usually used for introduction into the duct; however, in cases of a difficult papilla, the “stiff” tip can serve as firmer metal dilator to help enter a slightly stenotic or floppy papilla. Once the papilla is visualized or accessed, the guidewire ends can be switched within the dilator to the flexible tip end to prevent inadvertent

  Kolenda access sheath in place with sialendoscopy being performed through the surgical access channel it maintains. (Illustration 2011 Lisa Clark; courtesy Cook Medical.)

Maintaining Ductal Access: Kolenda Access Sheath The Kolenda Access sheath is an indwelling operative sheath used in conjunction with the Cook dilators (Fig. 14.4.2). The Kolenda system comes in 5F–6F versions and can be used within the submandibular ductal system. There is also a parotid duct version of the system. Although not used frequently in this author’s practice, the goal of the system is to provide a stable operative view for endoscopic intervention for cases that involve multiple ductal entries; e.g., stone removal via fragmentation. The sheath can protect the ductal lumen in these cases. The sheath also allows introduction of a second instrument along an endoscope and the suction port on the sheath can be valuable in helping irrigate stone microfragments and ductal debris after stone management. The sheath can be trimmed and can be left in situ for short-term stenting but has the risk of migration into the duct or extrusion.

Intraductal Accessories: NGage, NCircle, Sialo-Balloon and SialoCath The NCircle and NGage Cook stone baskets are made with nitinol fibers. They are strong hard stone baskets that provide an option of grabbing intraductal stones with a traditional “fishing” technique or end-on with a front-facing

116 se c t i o n 3 116

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• Fig. 14.4.3

  Cook accessories for interventional sialendoscopy. (Illustration 2011 Lisa Clark; courtesy Cook Medical.)

mouth, respectively (Fig. 14.4.3). The NGage basket provides a unique open front-end capturing option that can be valuable in difficult-to-capture stones. The SialoCath is a flexible tip cannula that allows nontraumatic duct irrigation and can be valuable to irrigate steroid into a duct or clear debris. The Sialo-balloon is a 1 mm noncompressible balloon for dilation of ductal stenosis. Unfortunately, the caliber of the balloon does not allow it to be introduced into the sialendoscope; however, it can be used for dilation of stenosis either under direct visualization using the Kolenda Access sheath and a smaller endoscope, or under ultrasound visualization.

KEY POINTS • The Cook accessories have allowed a paradigm shift in the course of sialendoscopy, making the procedure more predictable. • They improve intraductal interventional capabilities.

References 1. Gundlach P, Scherer H, Hopf J, et al. Endoscopic-controlled laser lithotripsy of salivary calculi. In vitro studies and initial clinical use. HNO 1990;38(7):247–50. 2. Katz P. New therapy for sialolithiasis. Inf Dent 1991;73(43): 3975–9. 3. Nahlieli O, Neder A, Baruchin AM. Salivary gland endoscopy: a new technique for diagnosis and treatment of sialolithiasis. J Oral Maxillofac Surg 1994;52:1240–2. 4. Marchal F, Becker M, Kurt AM, et al. Lithiases salivaires: nouvelles orientations diagnostiques et thérapeutiques. Méd Hyg 1997;55:2064–9.

5. Marchal F, Dulguerov P, Becker M, et al. Traitement ambulatoire de la lithiase salivaire. Méd Hyg 1998;56:1961–2. 6. Nahlieli O, Baruchin AM. Sialoendoscopy: three years’ experience as a diagnostic and treatment modality. J Oral Maxillofac Surg 1997;55:912–20. 7. Zenk J, Hosemann WG, Iro H. Diameters of the main excretory ducts of the adult human submandibular and parotid gland: a histologic study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:576–80. 8. Marchal F, Dulguerov P, Guyot JP, Lehmann W. Sialendoscopie et lithotrypsie intracanalaire. ORL Nova 1999;8:262–4. 9. Marchal F, Dulguerov P, Lehmann W. Interventional sialendoscopy. N Engl J Med 1999;341:1242–3. 10. Marchal F, Becker M, Dulguerov P, Lehmann W. Interventional sialendoscopy. Laryngoscope 2000;110:318–20. 11. Becker M, Marchal F, Becker C, et al. MR-sialography using 3D-extended phase conjugate symmetry rapid spin echo (express) sequence: diagnostic accuracy for assessing sialolithiasis and salivary duct stenosis. Radiology 2000;217(2):347–58. 12. Marchal F, Dulguerov P. Approche diagnostique et thérapeutique des affections des glandes salivaires. Méd Hyg 2001;59: 1986–97. 13. Marchal F, Dulguerov P, Becker M, et al. Specificity of parotid sialendoscopy. Laryngoscope 2001;111:264–71. 14. Marchal F, Kurt AM, Lehmann W. Retrograde theory in sialolithiasis formation: role of an anatomical sphincter. Arch Otolaryngol Head Neck Surg 2001;15:11–13. 15. Marchal F, Kurt AM, Dulguerov P, et al. Histopathology of submandibular glands removed for sialolithiasis. Ann Otol Rhinol Laryngol 2001;110:464–9. 16. Marchal F, Dulguerov P, Becker M, et  al. Interventional sialendoscopy. In: Wackym P, Rice DH, Schaefer SD, editors. Minimally invasive surgery of the head, neck, and cranial base. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 416–26.

CHAPTER 14  Types of Sialendoscopes and Accessories

17. Marchal F, Dulguerov P, Becker M, et al. Submandibular diagnostic and interventional sialendoscopy: new procedures for ductal pathologies. Ann Otol Rhinol Laryngol 2002;111:27–35. 18. Marchal F, Dulguerov P. Sialolithiasis management: the state of the art. Arch Otolaryngol Head Neck Surg 2003;129:951–6. 19. Marchal F. Salivary gland endoscopy: new limits? Rev Stomatol Chir Maxillofac 2005;106:244–9. 20. Faure F, Boem A, Taffin C, et al. Diagnostic and interventional sialendoscopy. Rev Stomatol Chir Maxillofac 2005;106: 250–2. 21. Giger R, Mhawech P, Marchal F, et al. Mucoepidermoid carcinoma of Stensen’s duct. Head Neck 2005;27(9):829–33. 22. Faure F, Boem A, Taffin C, et al. Diagnostic and interventional sialendoscopy. Rev Stomatol Chir Maxillofac 2005;106(4):250–2. 23. Chossegros C, Guyot L, Richard O, et al. A technical improvement in sialendoscopy to enter the salivary ducts. Laryngoscope 2006;116(5):842–4. 24. Marchal F. A combined endoscopic and external approach for extraction of large stones with preservation of parotid and submandibular glands. Laryngoscope 2007;17:373–7. 25. Marchal F. The combined approach towards salivary stones. In: Myers E, Ferris R, editors. Salivary glands. Stuttgart: Thieme; 2007. 26. Marchal F, Bradley P. Sialolithiasis and sialendoscopy. In: Myers E, Ferris R, editors. Salivary glands. Stuttgart: Thieme; 2007. 27. Marchal F. Sialendoscopy. In: Myers E, Ferris R, editors. Salivary glands. Stuttgart: Thieme; 2007. 28. Faure F, Quenin S, Dulguerov P, et al. Pediatric salivary gland obstructive swelling: sialendoscopic approach. Laryngoscope 2007;117:1364–7. 29. Marchal F, Chossegros C, Faure F, et al. Salivary stones and stenosis. A comprehensive classification. Rev Stomatol Chir Maxillofac 2008;109:233–6. 30. Faure F, Froehlich P, Marchal F. Paediatric sialendoscopy. Curr Opin Otolaryngol Head Neck Surg 2008;16:60–3. 31. Quenin S, Plouin-Gaudon I, Marchal F, et al. Juvenile recurrent parotitis, a sialendoscopic approach. Arch Otolaryngol Head Neck Surg 2008;134(7):715–19. 32. Boehm A, Faure F, Dietz A. Sialendoscopy: diagnostic possibilities and therapeutic options. Laryngorhinootologie 2008; 87(5):317–21. 33. Wang S, Marchal F, Zou Z, et al. Classification and management of chronic sialoadenitis of the parotid gland. J Oral Rehabil 2009;36(1):2–8. 34. Marchal F, Chossegros C, Faure F, et al. Salivary stones and stenosis. A comprehensive classification. Rev Stomatol Chir Maxillofac 2009;110–16. 35. Marchal F. Sialendoscopy salivary glands. In: Bradley P, GuntinasLichius O, editors. Salivary Gland Disorders and Diseases: Diagnosis and Management. Stuttgart: Thieme; 2009. 36. Marchal F. Inflammatory and non inflammatory diseases of the salivary glands. In: Arnold W, Ganzer U, editors. European manual of ORL. Stuttgart: Thieme; 2009. 37. Martins-Carvalho C, Plouin-Gaudon I, Quenin S, et  al. Pediatric sialendoscopy: a 5-year experience at a single institution. Arch Otolaryngol Head Neck Surg 2010;136(1):33–6. 38. Al-Abri R, Marchal F. New era of endoscopic approach for sialolithiasis: silendoscopy. Sultan Qaboos Univ Med J 2010; 10(3):382–7. 39. Marchal F, Nahlieli O. Combined techniques for parotid duct pathologies. In: McGurk M, editor. Advances in salivary gland diseases. Oxford: OUP; 2010.

117

40. Walvekar RR, Marchal F. Ear, nose, and throat manifestations of Sjögren’s syndrome. In: Ramos-Casals M, Stone JH, Moutsopoulos HM, editors. Sjögren’s syndrome. London: Springer-Verlag; 2012. 41. Meyer A, Delas B, Hibon R, et al. Sialendoscopy: a new diagnostic and therapeutic tool. Eur Ann Otorhinolaryngol Head Neck Dis 2013;130(2):61–5. 42. Durbec M, Dinkel E, Vigier S, et al. Thulium laser sialendoscopy for parotid and submandibular sialolithiasis. Lasers Surg Med 2012;44(10):783–6. 43. Sabot JF, Gustin MP, Delahougue K, et al. Analytical investigation of salivary calculi by mid-infrared spectroscopy. Analyst 2012;137(9):2095–100. 44. Terraz S, Poletti PA, Dulguerov P, et al. How reliable is sonography in the assessment of sialolithiasis? AJR Am J Roentgenol 2013;201(1):W104–9. 45. Marchal F. A combined endoscopic and external approach for extraction of large stones with preservation of parotid and submandibular glands. Laryngoscope 2015;125(11):2430. 46. Marchal F, Becker M, Dulguerov P, Lehmann W. Interventional sialendoscopy. Laryngoscope 2015;125(11):2427–9. 47. Ardekian L, Klein H, Al Abri R, Marchal F. Sialendoscopy for the diagnosis and treatment of juvenile recurrent parotitis. Rev Stomatol Chir Maxillofac Chir Orale 2014;115:17–21. 48. Ardekian L, Klein H, Araydy S, Marchal F. The use of sialendoscopy for the treatment of multiple salivary gland stones. J Oral Maxillofac Surg 2014;72:89–95. 49. Pezier T, Prasad S, Marchal F. Towards an international database of benign salivary disease: management of salivary gland disorders by sialendoscopy: a systematic review. Br J Oral Maxillofac Surg 2016;54(8):968–9. 50. Prasad S, Pezier T, Faure F, Marchal F. Sialendoscopy: what is it and what is its awareness? Eur Arch Otorhinolaryngol 2016;273(10):3249–53. 51. Jouan R, Picot E, Hermann R, et al. Sialendoscopy for sialolithiasis in children:4–8 years follow-up. Br J Oral Maxillofac Surg 2018;56(2):120–3. 52. Nahlieli O, Baruchin AM. Endoscopic technique for the diagnosis and treatment of obstructive salivary gland diseases. J Oral Maxillofac Surg 1999;57:1394–401. 53. Zenk J, Koch M, Bozzato A, Iro H. Sialoscopy – Initial experiences with a new endoscope. Br J Oral Maxillofac Surg 2004; 42(4):293–8. 54. Königsberger R, Feyh J, Goetz A, et al. Endoscopic controlled laser lithotripsy in the treatment of sialolithiasis. Laryngorhinootologie 1990;69:322–3. 55. Katz P. New method of examination of the salivary glands: the fiberscope. Inf Dent 1990;72:785–6. 56. Iro H, Zenk J, Koch M, Bozzato A. The Erlangen salivary gland project – part 1: sialendoscopy in obstructive diseases of the major salivary glands. Tuttlingen: Endo-Press; 2008. 57. Koch M, Iro H, Zenk J. Sialendoscopy-based diagnosis and classification of parotid duct stenoses. Laryngoscope 2009; 119:1696–703. 58. Koch M, Iro H. Extended and treatment-oriented classification of parotid duct stenosis. Laryngoscope 2017;127:366– 71. 59. Koch M, Iro H. Salivary duct stenosis: diagnosis and treatment. Acta Otorhinolaryngol Ital 2017;37:132–41. 60. Koch M, Zenk J, Iro H. Diagnostic and interventional sialoscopy in obstructive diseases of the salivary glands. HNO 2008; 56:139–44.

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61. Koch M, Iro H, Zenk J. Role of sialoscopy in the treatment of Stensen’s duct strictures. Ann Otol Rhinol Laryngol 2008;117:271–8. 62. Koch M, Zenk J, Iro H. Algorithms for treatment of salivary gland obstructions. Otolaryngol Clin North Am 2009;42:1173–92. 63. Koch M, Iro H, Kunzel J, et al. Diagnosis and gland-preserving minimally invasive therapy for Wharton’s duct stenoses. Laryngoscope 2012;122:552–8. 64. Zenk J, Koch M, Klintworth N, et al. Sialendoscopy in the diagnosis and treatment of sialolithiasis: a study on more than 1000 patients. Otolaryngol Head Neck Surg 2012;147:858–63. 65. Capaccio P, Torretta S, Pignataro L, Koch M. Salivary lithotripsy in the era of sialendoscopy. Acta Otorhinolaryngol Ital 2017;37:113–21. 66. Koch M, Iro H, Klintworth N, et al. Results of minimally invasive gland-preserving treatment in different types of parotid duct stenosis. Arch Otolaryngol Head Neck Surg 2012;138:804–10. 67. Chatziavramidis A, Konstantinidis I, Boglou K, Constantinidis J. Cytology sampling by sialendoscopy: how we do it. Br J Oral Maxillofac Surg 2013;51(8):e314–16.

68. Koch M, Mantsopoulos K, Schapher M, et al. Intraductal pneumatic lithotripsy for salivary stones with the StoneBreaker: preliminary experience. Laryngoscope 2016;126:1545–50. 69. Serbetci E, Celikoyar MM, Altundag A. Sialendoscopic pneumatic lithotripsy for salivary calculi: a new technique and a long-term clinical experience. Otolaryngol Head Neck Surg 2017;157:906–8. 70. Koch M, Bozzato A, Iro H, Zenk J. Combined endoscopic and transcutaneous approach for parotid gland sialolithiasis: indications, technique, and results. Otolaryngol Head Neck Surg 2010;142:98–103. 71. Koch M, Iro H, Zenk J. Combined endoscopic-transcutaneous surgery in parotid gland sialolithiasis and other ductal diseases: reporting medium- to long-term objective and patients’ subjective outcomes. Eur Arch Otorhinolaryngol 2013;270:1933–40.

15 

Management of the Submandibular Duct Papilla and Other Approaches to Salivary Ducts PAULINE POUZOULET, NICOLAS GRAILLON, JEAN MARC FOLETTI, MARC-KEVIN LE ROUX, AND CYRILLE CHOSSEGROS

Introduction Papilla crossing is one of the key points for sialendoscopy, especially in submandibular sialendoscopy. After the papilla has been crossed, the sialendoscopy can begin. Instead of papilla crossing, other approaches to the salivary duct may also be needed. For example, the retropapillary approach can replace the papillary crossing when this crossing is not feasible. However, when the lithiasis removal procedure is over, the surgeon must check for the absence of remaining lithiasis in combined approaches procedures; in such cases, a retrograde approach to the duct is helpful (Fig. 15.1). Usual papillary crossing is performed with probes of increasing diameter, as described by Marchal et al.1 In 20% of cases, usual papillary crossing does not work,2 giving place to another papilla crossing technique – the guided puncture technique.3

Anterior Approaches to the Duct Papillary Approach The Classic Marchal Technique The progressive papilla dilatation is performed with lacrimal or salivary probes of diameters from 0000 to 6.1 The main difficulty is that after each salivary duct probe change, the surgeon goes out of the papilla and can lose the papilla entrance. At each step of the dilatation, it becomes more and more difficult to find and enter the papilla again.

The Chossegros Guided Puncture Technique After the smaller probe 0000 insertion and removal, the probe is directly replaced by a 0.6 mm guidewire, which is nearly the same diameter as the 0000 probe.2 This guide measures 50 cm long. The surgeon must take care not to

enter too deeply into the duct, to avoid posterior lithiasis migration. After the guide is in place, a center-drilled bougie is inserted on it, allowing a slow and progressive dilatation of the papilla (Fig. 15.2). Several diameters of bougies are available and the authors recommend starting with the 1 mm bougie, following with the 1.5 mm diameter bougie (and in rare cases, the 2.0 mm). The bougie penetrates the duct by its conic end. When the cylindric part of the bougie enters the duct easily, the papilla diameter is similar to the diameter of the bougie and to the diameter of the sialendoscope. To facilitate entering the duct, the authors recommend leaving the guidewire in the duct. The bougie is removed and the guidewire is inserted into the working channel of the sialendoscope (Fig. 15.3). This technique reduces the operative time and the percentage of papilla entrance failure, especially for the submandibular sialendoscopy.

The Nahlieli Papillotomy The duct is opened on a 0000 probe.4 This technique is easier to perform but is not as minimally invasive. The authors believe it can create fibrous tissues with a risk of stenosis.

Retropapillary Approach The Aldosari and Chang Retropapillary Approach The retropapillary approach is an alternative approach that is needed when it is impossible to cannulate the papilla. After infiltration, a 10 mm long incision is made in the mucosa, 5 mm behind the papilla.5,6 The dissection permits the identification of the duct and the sialodochotomy is performed partially through the wall of the anterior third of the duct, with a 5 mm incision. The sialendoscope is introduced (Fig. 15.4). The edges of the incision can be sutured to the floor of mouth mucosa, creating a new ductal opening (a “neo-ostium”). No stent is needed. 119

CHAPTER 15  Management of the Submandibular Duct Papilla and Other Approaches to Salivary Ducts

Keywords Submandibular Duct Wharton’s Duct Papilla Retropapillary

119.e1

120 se c t i o n 3 120

Diagnostic Sialendoscopy

Retrograde approach and irrigation

Retropapillary approach (usual or fast) Papillary approach

Submandibular gland Hilum

Papilla Anterior third

Middle third Posterior third

• Fig. 15.1

 

Salivary duct

The different approaches to the salivary ducts.

All-in-one Storz 1.3 mm sialendoscope Bougie

Guidewire Guidewire

• Fig. 15.2

The guidewire is in the left submandibular duct and a center-drilled “bougie” is inserted over the guidewire, through the papilla.  

The Pouzoulet Retropapillary Approach After infiltration, the duct is punctured just 5 mm behind the papilla with a 21 G needle. A saline solution is injected through this puncture. The issue of the solution through the papilla confirms the intraductal position of the catheter. A guidewire is gently inserted into the catheter and dilatation can be conducted with a bougie, and then with the sialendoscope, allowing the sialendoscopy (Fig. 15.5).

The Avignon Posterior Approach The transoral approach for submandibular calculi has been described by Benazzou et al.7 When the lithiasis is removed, the surgeon must check for the absence of remaining calculi

• Fig. 15.3

  After the bougie is removed, the “all-in-one” Storz Marchal sialendoscope is inserted on to the guidewire to enter the left submandibular duct.

in the anterior part of the duct, between the lithiasis and the papilla, which can occur in ~10% of cases. This absence of remaining lithiasis can be evaluated with the help of a sialendoscope or with an irrigation of the duct. This irrigation is classically performed through the papilla with the plastic part of a 20 G catheter inserted on a 0000 probe. This is not always feasible, and in such failures, a retrograde irrigation can be performed, with an angled ear aspiration canula. The angled ear aspiration canula is inserted though the hilar area of Wharton’s duct where a previous incision was performed to remove the lithiasis (Fig. 15.6). The issue of the solution through the papilla ensures the permeability of the duct. No complementary sialendoscopy is needed in most cases. Wharton’s duct is then sutured to the mucosa as in normal procedure.

CHAPTER 15  Management of the Submandibular Duct Papilla and Other Approaches to Salivary Ducts

121

Ear aspiration cannula Wharton’s duct Saline solution flow through the papilla

Papilla

• Fig. 15.4

  A salivary crest incision is made 5 mm behind the papilla. This incision is 10 mm long and the Wharton’s duct is dissected. The duct is infiltrated with a saline solution that flows out of the papilla. A cut-down on the needle opens the duct. The sialendoscope can be inserted through the ductal incision.

Guidewire 21 gauge needle

• Fig. 15.5

  The procedure is initiated with a 21 G needle puncture in the Wharton’s duct. A saline filled syringe is connected to the needle. When the saline solution flows out of the papilla, it confirms the needle is in the ductal lumen. The 0.6 mm guidewire can be inserted in the needle to catheterize the duct. Then the needle is removed and replaced by the “bougie”, if needed, and then by the sialendoscope (as described for the previous procedures).

Parotid Gland The Stensen’s Duct Papilla Approach This approach is generally less complex, even though the Stensen’s duct diameter is narrower than the Wharton’s duct diameter. In cases of anterior one-third (distal) stenosis, the transoral technique can be used, as described by Foletti et al.8

• Fig. 15.6  Retrograde irrigation with saline solution. The saline solution going out of the Wharton’s papilla can be seen, confirming there is good ductal permeability after removing the hilar lithiasis.

References 1. Marchal F, Dulguerov P, Lehmann W. Interventional sialendoscopy. N Engl J Med 1999;341:1242–3. 2. Chossegros C, Guyot L, Richard O, et al. A technical improvement in sialendoscopy to enter the salivary ducts. Laryngoscope 2006;116:842–4. 3. Foletti JM, Graillon N, Avignon S, et al. Salivary calculi removal by minimally invasive techniques: a decision tree based on the diameter of the calculi and their position in the excretory duct. J Oral Maxillofac Surg 2018;76:112–18. 4. Nahlieli O, Shacham R, Bar T, Eliav E. Endoscopic mechanical retrieval of sialoliths. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:396–402. 5. Aldosari B, Chossegros C, Stroumsa R. Wharton’s duct retropapillary approach. J Oral Maxillofac Surg 2014;72:1124.e1–e2. 6. Chang JL, Eisele DW. Limited distal sialodochotomy to facilitate sialendoscopy of the submandibular duct. Laryngoscope 2013; 123:1163–7. 7. Benazzou S, Salles F, Cheynet F, et al. Transoral removal of submandibular hilar calculi. Rev Stomatol Chir Maxillofac 2008; 109:163–6. 8. Foletti JM, Chossegros C, Salles F, Guyot L. Transoral approach for Stensen’s duct lithiasis. Laryngoscope 2011;121:1893–5.

16 

Operative Techniques With Diagnostic Sialendoscopy OLIVIER ABBOUD

Introduction Diagnostic sialendoscopy is fundamental in the assessment and the treatment of salivary gland ductal pathology. Because of this diagnostic modality, the main duct, secondary, and tertiary branches can practically all be explored and evaluated.1 Diagnostic sialendoscopy can either be done as a single procedure or it can be incorporated in a more complex surgery involving combined or purely endoscopic approaches.1 Diagnostic sialendoscopy must not be viewed as a minor part of a surgery performed only at the beginning of these combined or purely endoscopic procedures. It is a dynamic tool during the different parts of the surgery. For example, after removing a submandibular hilar stone transorally, it is paramount to proceed with a proximal endoscopy to evaluate for residual stones or stenosis that need to be addressed. The purpose of this chapter is to: (1) help distinguish the gross and subtle differences between inflammatory salivary gland disorders evaluated with diagnostic sialendoscopy; (2) offer technical maneuvers to improve the chances of correct diagnosis; and (3) assess and predict the chances of success of interventional sialendoscopy.

Choosing the Appropriate Endoscope for Diagnostic Sialendoscopy All sialendoscopes can adequately perform diagnostic sialendoscopy. It is important to understand the advantages and disadvantages of each endoscope. Endoscopes are roughly divided into two categories: the all-in-one system (Marchal and Erlangen sets, Karl Storz, Tuttlingen, Germany)2 and the modular system (Marchal Modular set, Karl Storz).2 The former has integrated rinsing and operating channels (the operating channel is absent in the endoscopes that have a diameter 5 or fixed 5.6 (1–17)

85.1

10 /7–26)

84.5

89% 63

6.6 (2–33)

11 (7–25)

Free of Stones and Symptoms

Stone Diameter (mm)

TABLE 18.1  Results of Studies in More Than 2100 Patients

10

17.8

14.4

16 residual 16 primary failure

17

11.2

19

8 32

Residual Fragments or Symptoms (%)

5

3.4

n.a.

4.6

n.a.

0.6

n.a

1.2

0.6 transient

0

4.6 hilar

0 1 12

10.7

4.6

0.6

3.2 transient 2.4 permanent

5.6 4 symptoms without stone

n.a.

n.a.

11.2 (persistent or recurrent)

n.a.

0.8

Recurrence (%)

0

6% (tingling)

2.1/transient

1.2

0.5/0.8

Lingual Nerve Injuries (%)

0.7

0

0

0

1.2

0.9

Ranula (%)

1.9 0

5

1.2

1.6

Stenoses (%)

(4% of 186) 1.9

1.5

1.2

3 5

Gland Removal (%)

37.5 (3–87)

31.2 (10.7–51.7)

54.8 (12.8– 113.6)

3

28 (4–62)

12

52

12

Follow-Up (Months)

CHAPTER 18  Submandibular Gland Sialendoscopy-Assisted Transoral Technique

143

144 se c t i o n 4 144

Interventional Sialendoscopy for Stones

• Fig. 18.20

  Marsupialization of the stonebed. The needle is guided from the duct mucosa (blue arrow) through the mucosa of the floor of the mouth (green arrow).

at least 12 months of follow-up reveals a success rate between 76% and 90% depending on the stone location and number of stones. Authors who differentiate between distal and proximal duct stones find a higher rate of success, up to 100% for distal concrements.19,21 For stones within the hilum or attached to the parenchyma, the success rate is 84–90%. The more challenging stones are those in the hilar region attached to the parenchyma of the submandibular gland or patients with multiple stones. The recurrence of obstructive symptoms have a significantly higher rate in proximal stones and also in multiple stones. In the case of a partially removed stone (typically in large adherent parenchymal stones that are soft and tend to break during the procedure), there can be a return of symptoms. Other factors such as gender, age, size of stones, and palpability of stones are not related to the development of recurrent obstructive symptoms.29 Early sequelae are swelling, edema, pain, and tingling of the tongue that might occur in up to 74%26 and resolves within the first weeks after the surgical procedure. Injuries of the lingual nerve are reported in up to 3.2% permanently and 2.4% transiently. Most of the authors report around 1% or less. In these cases no other therapy is possible. Because of the anatomic proximity of stone and lingual nerve, the risk of an injury is higher for hilar stones.29 The development of a ranula after a transoral procedure is reported as between 0% and 1.9%. The more the lingual gland is left laterally and minimally dissected, the less the chance for generating a ranula.19,21 Obstructive symptoms after stone removal can be originated by residual or recurrent stones, but also by duct stenosis. There is still an ongoing discussion whether it is useful to create a neo-ostium with sialodochoplasty within the floor of the mouth or not. Postoperative stenosis, reported between 0% and 5%, occurs regardless of applied technique.19–21,24,26,28,29 Roh and Park,30 in a prospective randomized study of 28 patients with and 26 without a sialodochoplasty, found no difference in symptom recurrence and recovery of salivary gland function within 6 months. Woo et al.,31 in a prospective study of 28 patients after transoral removal of stones without sialodochoplasty, found

that 79% recovered with a normal duct size, 14% developed saccular dilatation, and 3% (1 duct) showed a partial stenosis by sialography. Using a stent, described by Nahlieli et al.,21 is not routinely necessary and not reported by other publications. The authors perform a sialodochoplasty, sometimes >2 cm, to reduce the distance between the floor of the mouth and a hilar or parenchymal opening; a “submandibulotomy”. Control of salivary flow in the direct postoperative course is easier to assess and it does not harm the patient. Submandibulectomy after a transoral procedure is significantly more frequent in hilar or multiple stones.32 Long-term success is ~90%, with the rate of secondary submandibulectomy ~5%. Residual fragments causing obstructions may be treated by transoral stone removal or other techniques including intra- or extracorporeal lithotripsy. Residual fragments may have minimal symptoms with no indication for further treatment or gland removal.

KEY POINTS • At least 90% of the patients have no further symptoms at the follow-up and 5 mm in diameter or a patent duct is lacking, the transfacial approach is required (see Chapter 20).

Complications of Sialendoscopy Pure endoscopic interventions may produce several complications. Gland swelling, strictures, perforations (false track), and avulsion of the salivary duct, are the main endoscopyrelated complications in the parotid cases. The endoscopyrelated complications are rare and of different origin in comparison with the traditional surgery complications.19,20 For example, neurologic complications are minimal when pure sialendoscopy is involved, specifically for the parotid, facial palsy/paralysis, or Frey syndrome will not occur.20 Transient facial nerve weakness is remotely possible if perforation of the duct occurs. Excessive postoperative parotid gland swelling following sialendosopy usually occurs because of obstruction of the main salivary duct, perforation of the duct, or excessive irrigation.20–22 Such gland swelling usually resolves in approximately 24–48 h.23,24 The treatment of postoperative stricture is covered in Chapters 27 and 28. The perforation (false route) of the salivary duct can occur near the orifice of the duct because of separation of the ductal wall from the oral mucosa. It can happen during sialendoscopic mechanical intraductal procedures such as stone removal and stricture dilation.21,25 The endoscopic identification of this pathology is possible, but the ductal structures of the lumen may be overlooked. Avulsion of the duct occurs when an operating surgeon fixes a calculus in the wire basket and then tries to remove it from the duct. If the traction is excessive, an avulsion can occur. This complication

is rare. Another sign is the excessive swelling in the region of a perforation due to the leakage of the irrigation solution into the surrounding tissue. Last, failure of the extraction instrument such as a broken wire basket is an extremely rare complication.26 Sigismund and colleagues, in an analysis of nearly 3000 salivary stones,27 concluded that, due to their location and smaller diameter, parotid stones in some cases can be treated using only a mini-invasive endoscopic technique, while submandibular calculi more often require a combined approach.

KEY POINTS • About 5–20% of the stones are found in the parotid gland. • The ability to extract a calculus via the endoscopic transoral technique is based on the location, on the diameter of the stone, and the diameter of the ductal lumen. • Pure endoscopic intraductal technique is suitable for approximately 30% of all salivary calculi. • Endoscopically stone removal is carried out using a basket, miniforceps, hydrostatic pressure, or intracorporeal lithotripsy.

References 1. Huoh KC, Eisele DW. Etiologic factors in sialolithiasis. Otolaryngol Head Neck Surg 2011;145:935–9. 2. Grases F, Santiago C, Simonet BM, Costa-Bauza A. Sialolithiasis: mechanism of calculi formation and etiologic factors. Clin Chim Acta 2003;33:131–6. 3. Zenk J, Zikarsky B, Hosemann WG, Iro H. The diameter of the Stenon and Wharton ducts. Significance for diagnosis and therapy. HNO 1998;46(12):980–5.

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4. Zhang YQ, Ye X, Liu DG, et al. Endoscopy-assisted sialodochoplasty for the treatment of severe sialoduct stenosis. Beijing Da Xue Bao Yi Xue Ban 2018;50(1):160–4. 5. Marchal F. Sialendoscopy. In: Myers E, editor. Salivary gland disorders. Berlin: Springer; 2007. p. 127–48. 6. PolyDiagnost. Catalogue, version 2.6. Hallbergmoos: PolyDiagnost; 2015. 7. Karl Storz – Endoskope. Oral and maxillofacial surgery. Highlights 2016. Karl Storz; 2016. 8. PolyDiagnost. Operation manual: Semi-rigid optics. PolyDiagnost; 2015. 9. Thomas WW, Douglas JE, Rassekh CH. Accuracy of ultrasonography and computed tomography in the evaluation of patients undergoing sialendoscopy for sialolithiasis. Otolaryngol Head Neck Surg 2017;156(5):834–9. 10. Schwarz D, Kabbasch C, Scheer M, et al. Comparative analysis of sialendoscopy, sonography, and CBCT in the detection of sialolithiasis. Laryngoscope 2015;125(5):1098–101. 11. Carta F, Farneti P, Cantore S, et al. Sialendoscopy for salivary stones: principles, technical skills and therapeutic experience. Acta Otorhinolaryngol Ital 2017;37(2):102–12, 1. 12. Matsushita N, Iguchi H, Wada T, et al. A clinical study of malignant tumors of Stensen’s duct. Acta Otolaryngol 2015; 135(3):290–4. 13. Jouan R, Picot E, Hermann R, et al. Sialendoscopy for sialolithiasis in children: 4–8 years follow up. Br J Oral Maxillofac Surg 2018;56(2):120–3. 14. Gallo A, Capaccio P, Benazzo M, et al. Outcomes of interventional sialendoscopy for obstructive salivary gland disorders: an Italian multicentre study. Acta Otorhinolaryngol Ital 2016; 36(6):479–85, 1. 15. Jokela J, Haapaniemi A, Mäkitie A, Saarinen R. Sialendoscopy under local anaesthesia. Acta Otolaryngol 2017;137(3):310–14. 16. Rotnágl J, Zavázalová Š, Vorobiov O, Astl J. Sialendoscopy and combined minimally invasive treatment for large parotid stones. Biomed Res Int 2016;2016:1354202.

17. Samani M, Hills AJ, Holden AM, et al. Minimally-invasive surgery in the management of symptomatic parotid stones. Br J Oral Maxillofac Surg 2016;54(4):438–42. 18. Foletti JM, Graillon N, Avignon S, et al. Salivary calculi removal by minimally invasive techniques: a decision tree based on the diameter of the calculi and their position in the excretory duct. J Oral Maxillofac Surg 2018;76(1):112–18. 19. Lari N, Chossegros C, Thiery G, et al. Sialendoscopy of the salivary glands. Rev Stomatol Chir Maxillofac 2008;109(3):167–71. 20. Nahlieli O, Shacham R, Zagury A, et al. The ductal stretching technique–endoscopic assisted technique for submandibular stones. Laryngoscope 2007;117(6):1031–5. 21. Witt RL, Iro H, Koch M, et al. Minimally invasive options for salivary calculi. Laryngoscope 2012;122(6):1306–11. 22. Iwai T, Matsui Y, Yamagishi M, et al. Simple technique for dilatation of the papilla in sialoendoscopy. J Oral Maxillofac Surg 2009;67(3):681–2. 23. Kroll T, Finkensieper M, Sharma SJ, et al. Short-term outcome and patient satisfaction after sialendoscopy. Eur Arch Otorhinolaryngol 2013;270(11):2939–45. 50-–1007/s–1007/s00405500–10. 24. Nahlieli O, Droma EB, Eliav E, et al. Salivary gland injury subsequent to implant surgery. Int J Oral Maxillofac Implants 2008;23(3):556–60. 25. Escudier MP. The development of salivary lithotripsy: its role in the management of salivary calculi department of oral medicine. London: University of London; 2008. 26. Capaccio P, Gaffuri M, Torretta S, Pignataro L. Sialendoscopyassisted transfacial surgery for the removal of an iatrogenic foreign body in Stensen’s duct: a stone and broken wire basket. J Laryngol Otol 2016;130(5):501–5. 27. Sigismund PE, Zenk J, Koch M, et al. Nearly 3,000 salivary stones: some clinical and epidemiologic aspects. Laryngoscope 2015;125(8):1879–82.

20 

Parotid Gland Proximal Stones, Combined Transoral and External Approach URBAN GEISTHOFF

Introduction Patients with stones of the parotid gland and its duct were usually treated by partial parotidectomy in previous years. Extracorporeal shock wave lithotripsy reduced the number of surgeries but is not generally available and is successful in only about two-thirds of cases. Today, sialendoscopy has led to a new, transoral approach. Smaller stones can be extracted with sialendoscopy and a basket. Larger stones can potentially be treated with extracorporeal shock wave lithotripsy or intraductal laser lithotripsy prior to sialendoscopic extraction. Intraductal laser lithotripsy is possible with working channels of only 0.4 mm. Therefore, it is often possible to reach the stone with the endoscope. However, intraductal laser lithotripsy is time consuming. Mechanical methods such as intraductal pneumatic lithotripsy are dependent on larger working channels and intraductal pneumatic lithotripsy is precluded if the ducts are narrow. An additional approach uses sialendoscopy and/or ultrasonography as navigation methods to guide a minimallyinvasive transcutaneous intervention.1 The first description of this type of approach was probably the use of a probe inserted into the duct for mechanical localization of the stone.2 Currently, this type of surgical approach is usually addressed by the term “combined approach”.

Combined Transoral and External Approach Combined approaches can be further categorized depending on the stone localization technique (sialendoscopic, ultrasonographic) and the type of incision (direct, posterior/ parotidectomy).1 The method used for localization depends on various factors: availability of instruments; acquaintance of the

surgeon with the methods; duct diameter and tortuosity; and localization of the stone. In rare cases, stones can be palpated either from the outside or with a blunt probe through the papilla of Stensen’s duct. In these cases, neither ultrasound nor endoscopy are necessary for localization. However, sialendoscopy and ultrasound, in these cases, can add information by ensuring that no further stones remain. Some stones cannot be reached by sialendoscopy. In these cases, ultrasonography is a remaining alternative.1 The selection of the incision also depends on various factors, including location of the stone, age, and gender of the patient.1,3 If the risk of a visible scar is paramount, a posterior approach, as used for parotidectomy, is preferred. This is usually possible as the skin is very flexible. However, for anterior located stones, the amount of skin preparation necessary, risk of nerve trauma (both sensory and motor), and duration of surgery might increase.

Combined Transfacial Incision Approach The direct incision technique is illustrated in the following example: A 48-year-old male patient had several stones identified sonographically in Stensen’s duct about 2.5 cm anterior of the gland. Different therapeutic options including extracorporeal shock wave lithotripsy and intraductal lithotripsy were discussed with the patient. He chose a combined approach including a direct incision above the stone. The position of the stone was marked by transillumination using sialendoscopy (Figs. 20.1, 20.2). Using facial nerve monitoring, an incision was performed directly above the stones along the relaxed skin tension lines. Judiciously, the tissue was divided. It was possible to identify the buccal branch of the facial nerve with the operating microscope. The facial nerve branch was confirmed by neural stimulation with a nerve integrity monitoring probe (Fig. 20.3). The light of the microscope was dimmed intermittently 153

CHAPTER 20  Parotid Gland Proximal Stones, Combined Transoral and External Approach

Keywords Parotid Duct Stensen’s Duct Stone Sialolithiasis External Approach Transoral

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• Fig. 20.1

  The position of the stone is marked by transillumination using sialendoscopy.

• Fig. 20.2

 

Stone visualized with a sialendoscope.

• Fig. 20.3  Transverse facial incision with identification of the facial nerve utilizing a nerve integrity monitoring probe.

• Fig. 20.4

  Ambient light is reduced and the stone is visualized from the sialendoscopic light source.

• Fig. 20.5  The facial nerve branch is dissected from the underlying duct.

to confirm the exact position of the stone (Fig. 20.4). The stone was located deep to the facial nerve branch. The facial nerve branch is meticulously separated from surrounding tissue and carefully mobilized cranial to the duct (Fig. 20.5). With the duct visible, it was incised with a 15 blade and the sialodochotomy was enlarged using fine plastic scissors. Stones were extracted with a blunt hook (Fig. 20.6). Fig. 20.6 also shows the tip of the sialendoscope inside the duct. Multiple stones were retrieved. The sialendoscope confirmed that no further stones remained inside the duct system. A drain was attached to the tip of the endoscope (Fig. 20.7) and the endoscope was withdrawn intraorally. The duct was closed using 5-0 resorbable sutures. Subsequently, the overlying soft tissue and the skin were closed. The sialodrain was sutured to the buccal mucosa (Fig. 20.8). This technique has since progressed, and currently the authors seldom insert drains because sialodrains

CHAPTER 20  Parotid Gland Proximal Stones, Combined Transoral and External Approach

155

• Fig. 20.9

  Ultrasound of a proximal Stensen’s duct stone. sd, salivary duct; pg, parotid gland; mm, masseter muscle; mand, mandible.

• Fig. 20.6

  Stones are extracted with a blunt hook. The tip of the endoscope can be visualized.

are usually not necessary and may even block the flow of saliva.

Combined Parotidectomy-Like Posterior Approach

• Fig. 20.7

• Fig. 20.8

 

 

Placement of a sialodrain.

Suture of the sialodrain to the intraoral buccal mucosa.

The second case is an example of a posterior parotidectomylike skin incision. It has different indications. In a 58-year-old male, a stone was posterior to the masseter muscle inside the intraparenchymal part of Stensen’s duct (Fig. 20.9). Endoscopically, it was difficult to reach the stone. The stone was within a secondary duct behind a stenosis (Video 20.1). It was barely possible to reach it with a thin diagnostic sialendoscope. The authors discussed with the patient extracorporeal shock wave lithotripsy versus a combined approach. He chose the latter. The stone position was marked by transillumination of the sialendoscope. A small skin flap was raised as with partial parotidectomy (Fig. 20.10). The parotid was carefully dissected and ultimately the duct became visible directly deep to a buccal branch of the facial nerve (Fig. 20.11). The duct was opened and the stone extracted (Fig. 20.12). The sialendoscope was used to make sure that no additional stones remained. A drain was placed (Fig. 20.13) and the duct was closed with a 5-0 Polyglactin 910 (Vicryl) suture (Fig. 20.14). If the stone cannot be reached by an endoscope, ultrasound is a useful technique to localize the stone. The stone is visualized by ultrasound. The stone is marked with two perpendicular needles. The procedure is performed in the same way as described above. The position of the needles can change during the surgery; therefore intraoperative control of the needle position is recommended. Combined approaches are usually performed under general anesthesia. This also allows the use of facial nerve monitoring. However, these techniques have also been described under local anesthesia.1 A recent review and metaanalysis4 stated that the success rate for combined approaches for stones of the parotid gland is about 99%; the complication rate was low (6%).

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• Fig. 20.12

 

Duct incision performed and stone extracted.

• Fig. 20.10

  Parotidectomy-like incision with transillumination of the location of the stone with sialendoscope.

• Fig. 20.13

 

Sialodrain placed.

• Fig. 20.11  Stensen’s duct in close approximation to a buccal branch of the facial nerve.

• Fig. 20.14

 

Suture closure of the duct.

CHAPTER 20  Parotid Gland Proximal Stones, Combined Transoral and External Approach

157

Conclusion

References

Combined approaches are safe and effective surgeries to treat parotid stones.

1. Nahlieli O, London D, Zagury A, Eliav E. Combined approach to impacted parotid stones. J Oral Maxillofac Surg 2002;60(12): 1418–23. 2. Baurmash H, Dechiara SC. Extraoral parotid sialolithotomy. J Oral Maxillofac Surg 1991;49(2):127–32. 3. Foletti JM, Graillon N, Avignon S, et al. Salivary calculi removal by minimally invasive techniques: a decision tree based on the diameter of the calculi and their position in the excretory duct. J Oral Maxillofac Surg 2018;76(1):112–18. 4. Roland LT, Skillington SA, Ogden MA. Sialendoscopy-assisted transfacial removal of parotid sialoliths: a systematic review and meta-analysis. Laryngoscope 2017;127(11):2510–16.

KEY POINTS • Parotid stones can be removed by an open approach using either sialendoscopy or ultrasound for localization. • The technique is especially helpful for stones too large for sialendoscopy extraction and when lithotripsy is not possible.

21 

Interventional Sialendoscopy for Stones: Robotic Approaches CHRISTOPHER H. RASSEKH

Transoral Robotic Surgery for Submandibular Sialolithiasis Transoral robotic surgery (TORS) was invented at the University of Pennsylvania1 and subsequently Food and Drug Administration (FDA) approved in 2009.2 Transoral surgery of the submandibular gland for tumors and inflammatory disease has not been popular because access to the hilum is difficult. TORS has been utilized in the author’s institution to allow better visualization for transoral submandibular gland excision, primarily for neoplasms. This remains a challenging operation. Sialendoscopy has been combined with transoral access to the posterior oral cavity to allow management of hilar stones. Walvekar first reported using TORS for a submandibular megalith,3 and Razavi et al. have provided a series of patients4 using TORS in combined approaches for hilar stones. TORS is now utilized for hilar stones in two different ways. The author has termed these approaches “TORSsialo” and “Sialo-TORS-sialo”. In the former, TORS is done immediately and then followed by sialendoscopy for stones that are easily palpated, usually larger, most commonly single stones and is the more commonly performed operation. The Sialo-TORS-sialo approach is utilized for situations when evaluation of the duct and stone prior to doing the combined approach is needed.

TORS-Sialo Nasal intubation with general anesthesia and muscle relaxant is used. The robot is draped and the monopolar cautery arm is placed on the ipsilateral side. A Maryland dissector is placed on the contralateral side. The 0° camera is used. A Jennings mouth gag is placed with the handle on the contralateral side. Two side arms for self-retaining retractors are used and a sweetheart is placed on the contralateral side to retract the tongue away. A cheek retractor is placed on the ipsilateral side. These two retractors reduce head movement. An alternative is to attach one of the side arms directly to 158

the Jennings mouth gag and retract the tongue with sutures. The retraction of the tongue is dynamic and is facilitated by the bedside assistant. An incision is made in the floor of mouth and, if needed for exposure, the inferior aspect of the tonsillar pillar. This is a paralingual approach and occasionally a lower parapharyngeal space approach is helpful for challenging stones. The monopolar cautery is set at 10 Watts (W). The cutting pedal is used to make the incision, preserving adequate mucosa laterally to allow closure. Small vessels can be cauterized either using monopolar on low setting or by the assistant with bipolar. The lingual nerve is identified as is the posterior aspect of the sublingual gland. Usually the mylohyoid can be seen after careful blunt dissection. The triangle formed by the posterior border of the sublingual gland, the lingual nerve, and the mylohyoid/ mandible is then inspected. The lingual nerve usually must be gently retracted medially but in rare cases, when the stone is very large and bulging medially, the duct can be opened medial to the lingual nerve and the nerve remains lateral to the dissection of the duct. Occasionally, when there has been severe sialadenitis, the nerve will be very adherent to the duct in the exact area where the duct needs to be incised. The nerve may require additional mobilization and only performed if absolutely necessary. The assistant will use two suctions: one will retract the sublingual gland anteriorly and one will retract the mylohyoid laterally. The surgeon will carefully place the Maryland dissector just lateral to the lingual nerve and the spatula tip cautery can bluntly dissect until the duct is outlined. Once the position of the stone is identified, a second assistant provides upward pressure from the neck to facilitate incision in the duct. The incision in the duct can be carried out with monopolar cautery, again emphasizing the need to use a very low wattage (10 W). The incision is extended as needed to allow removal of the stone without fragmenting the stone and avoiding dissection except on the superficial aspect of the duct. In some cases, the stone may be quite adherent to the duct wall. In such cases, the bedside assistant may utilize a cottle elevator to gently dissect the stone out of the duct. In this situation, the robotic arms now serve as a retractor. The approach is

CHAPTER 21  Interventional Sialendoscopy for Stones: Robotic Approaches

Keywords Sialendoscopy Robotic Stone Sialolithiasis TORS

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CHAPTER 21  Interventional Sialendoscopy for Stones: Robotic Approaches

modular, in that sometimes the surgeon at the console is removing the stone and sometimes the assistant is doing so and the console surgeon is assisting. Once the stone is removed, the duct is explored through the wound to look for any fragments and irrigation is performed. Then, a conventional sialendoscopy procedure is performed ideally via the normal papilla. Generally, a 1.3 mm all-in-one sialendoscope is then used to inspect the duct and if any additional fragments of stone are seen, these are removed by irrigation or by basket retrieval (Video 21.1). Caution is advised in basket retrieval as it is possible for the basket to catch on the edge of the previously opened duct, which could result in avulsion of the duct when retrieving the basket with the stone. For this reason, if the patient is felt to have small stones in addition to a larger hilar stone, Sialo-TORS-sialo is preferred to get these stones out prior to performing the hilar duct incision (Video 21.2).

159

A

Sialo-TORS-Sialo The technique of Sialo-TORS-sialo is quite similar to TORS-sialo (Video 21.2). The main situations are when the stone cannot be easily palpated and additional localization of the stone within the duct is helpful. In such cases, if a stone can be grasped with a basket, even if it cannot be removed, the basket can be used to help identify the position of the stone during TORS and can also provide some retraction if the duct needs to be “stretched” (pulled distally) to access stones that are smaller and very posterior/ lateral to the lingual nerve. In addition, as mentioned, it is preferable when there are multiple stones, especially when they are distal to the larger hilar stone (or if it is difficult to determine from computed tomography [CT] whether there is a single or multiple stones), it is safer and easier to remove these prior to making a hilar duct opening. Not only does this make avulsion of the duct less likely, it helps to avoid loss of the irrigation through the duct incision, making basket retrieval easier (Fig. 21.1). Subsequently, the TORS procedure is performed much as described in TORS-sialo. If a basket has trapped the stone, it will be delivered with the stone and then it can be opened to release the stone and then closed and removed from the duct and back through the papilla. In some cases where stones are too large for purely endoscopic removal, but too small to be palpated, sonopalpation (ultrasound-guided localization) can be used. The approach may need to be hybrid, especially when the space between the lingual nerve and mylohyoid is narrow due to the shape of the mandible or dentition.

Discussion The combined approach for hilar stones that are too large for purely endoscopic removal can be done without the use of the robot, and lithotripsy is an option for selected patients. However, options for lithotripsy are limited in the United States and submandibular stones are often very

B

C • Fig. 21.1

  (A) Sialo-TORS-sialo: a 1.3 mm endoscopic intraductal view of sialolith in hilum with the basket trapped. (B) Sialo-TORSsialo: exposure of lingual nerve, posterior aspect of sublingual gland, and mylohyoid muscle. Spatula tip cautery is in the center of the triangle preparing to incise the duct at the hilum of the gland. (C) Sialo-TORS-sialo: following incision of the duct, stone and basket are removed.

dense and difficult to break with a Ho:YAG laser. In general, stones >7 mm are not good candidates for lithotripsy. The author prefers TORS-sialo and Sialo-TORS-sialo for the combined approaches to the SMG hilum. The excellent 3D magnified optics allows for enhanced visualization of

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the lingual nerve. The author also believes that the fourhanded approach with the dynamic interaction of the surgeon and bedside assistant is facilitated. There are space limitations during combined approaches and it is very difficult for all members of the surgical team to see what is happening in this tight surgical space. It has also been found that the display on the monitor helps the surgical staff to understand what is happening, and has greatly facilitated teaching trainees how to perform the combined approach. The critical steps of the procedure can be performed very quickly once the technique is learned and in some cases, a very small incision is possible and the actual TORS portion of the operation can sometimes be as short as 5 min. The author recommends that surgeons be trained in the more conventional techniques and indications for TORS, prior to adopting this technique.

KEY POINTS • “TORS-sialo”: TORS is done immediately and then followed by sialendoscopy for stones that are easily palpated, usually larger, most commonly single stones, and is the more commonly performed operation. • Sialo-TORS-sialo approach (in which case a sialendoscopy is performed both before and after the TORS) is for situations when evaluation of the duct and stone prior to doing the combined approach is needed. • 3D magnified optics allows for enhanced visualization of the lingual nerve.

References 1. Weinstein GS, O’Malley BW Jr, Hockstein NG. Transoral robotic surgery: supraglottic laryngectomy in a canine model. Laryngoscope 2005;115:1315–19. 2. Weinstein GS, O’Malley BW Jr, Magnuson JS, et al. Transoral robotic surgery: a multicenter study to assess feasibility, safety, and surgical margins. Laryngoscope 2012;122:1701–7. 3. Walvekar RR, Tyler PD, Tammareddi N, Peters G. Roboticassisted transoral removal of a submandibular megalith. Laryngoscope 2011;121:534–7. 4. Razavi C, Pascheles C, Samara G, Marzouk M. Robot-assisted sialolithotomy with sialendoscopy for the management of large submandibular gland stones. Laryngoscope 2016;126:345–51.

22 

Laser Fragmentation of Salivary Stones ROBERT A. IRVINE

Introduction Laser Types and Mechanism of Action Several lasers have been studied and utilized in salivary stone lithotripsy. Zenk et al.1 have described in detail the development of laser stone fragmentation, including their research into stone fragmentation and duct wall effects of five different laser systems. Presently, the Holmium:YAG laser is the predominant system in use. Although some authors report a photoacoustic or shockwave mechanism of action, due to creation of a gas bubble and subsequent cavitation collapse, the mechanism of this laser is photothermal,2 resulting in stone vaporization. Schrötzlmair et al.3 measured the outcome of in vitro stone fragmentation of harvested submandibular stones, subjected to Ho:YAG laser settings of 0.5, 1.0, and 1.5 J per pulse, using a 200 µm fiber. They studied a variety of physical and radiologic parameters of the stones, including computed tomography (CT) stone density, but did not find any correlation with measured stone parameters.

Outcome Data Numerous papers have described outcomes of salivary stone fragmentation with the Holmium:YAG laser. Martellucci et al.4 described 16 patients with submandibular stones ranging between 5 and 8 mm in diameter. The stone location was not specified. All patients had a successful fragmentation. Three patients had residual symptoms; two were found to have retained stone fragments, which were removed at a subsequent procedure; and one patient had a stricture at the laser site, which was successfully dilated. There are case reports describing laser fragmentation and endoscopic removal of large submandibular stones, notably by Sun et al.,5 who successfully removed multiple large stones measuring up to 13 mm from the mid-ductal region of the submandibular duct, in a procedure exceeding 4 h in duration. A letter to the editor regarding this paper, by SahinYilmaz and Oysu,6 described their experience in attempting laser fragmentation of a 7 mm stone in the parotid duct in a patient who had refused a transfacial procedure. The procedure was terminated after a 2 h attempt at laser fragmentation, and subsequent investigations identified a

residual 4 mm stone. A second attempt at endoscopy found a dense stricture that could not be sufficiently dilated to access the remaining stone. Sionis et al.,7 reported on a series of patients undergoing sialendoscopy, including 15 patients who underwent Ho:YAG lithotripsy. There were eight submandibular and seven parotid patients, with stone sizes ranging from 4–15 mm. All stones were successfully fragmented and removed, except for one 15 mm stone in the submandibular gland, which underwent gland excision. One parotid patient had an intractable stenosis requiring parotidectomy. Carta et al.,8 described 16/21 cases that were successfully treated with a single laser procedure; 3/21 cases subsequently underwent gland excision, including 1/9 parotid stone patients, due to a parotid ductal stricture. Capaccio et al.9 have published a detailed study of the range of options for salivary lithotripsy, including extracorporeal and intracorporeal options. They suggest that stones 85%5,7,8,11,12,15,20, these make up only 15–20% of all stones. In over 80% of stones, prior fragmentation by intracorporeal shock wave lithotripsy (ISWL), extracorporeal shock wave lithotripsy (ESWL) is necessary or transoral duct surgery, or combined approaches has to be performed due to stone size, impaction, and location.1,4–8 ISWL is indicated for stones accessible with the sialendoscope with various methods of intraductal fragmentation available. If properly selected, these modalities can be applied with high success rates of more than 90%.1,6,7,11,12,14,20–23 The size of the stone is associated with impaction, the location may determine the accessibility of the stone with the sialendoscope, and the consistency pertains to method of fragmentation. Mechanical fragmentation can be achieved by microdrills or forceps of different sizes (0.38–0.78 mm). The stone is fragmented by shear, rotational, and pressure movements. It is generally suited only for stones with maximal size of 7–8 mm with a softer consistency.4,7,15,20,24,25 In laser lithotripsy (LT), the energy of the laser light is transmitted by a glass fiber directly onto the surface of stones in near contact and/or contact modus. The emitted energy causes vaporization and/or fragmentation. Stones, which are hard, hyaline stones with a high ratio of mineralization, are more suited for this kind of lithotripsy. Results after application of different laser types have been published for over 15 years.26–32,37,40 Acceptable results with constant success rates of >80% were reported with the use of the Ho:YAG laser.27–32 Different modifications of kinetic or ballistic lithotripsy are electrohydraulic lithotripsy (EHL), electrokinetic 164

lithotripsy (EKL), and pneumatic lithotripsy (PL). In all applications, the energy is transmitted to a probe resulting in kinetic energy, which is transmitted onto the surface of a stone causing fragmentation. All of these are associated with the potential disadvantage of mechanical trauma to the tissue (e.g., duct perforation) and propulsion of stones into the proximal/intraparenchymal duct system or into the periductal tissue.23,33,34,37 Although effective, risks and costs of EHL and EKL are not favored currently.9,11,12,14,21–23,35,38,39

Pneumatic Lithotripsy Alongside intraductal LT (see Chapter 22), intraductal pneumatic lithotripsy (IPL) represents the most effective method of ISWL. In IPL, gas, mostly CO2 gas, is the source of energy. The pneumatic energy is transmitted to a probe resulting in kinetic energy, which is transmitted onto the surface of a stone. Direct contact to the stone is necessary to cause fragmentation. The gas can be released out of a central connecting system or out of a cartridge. Several devices are used to perform IPL. Arzoz et al. treated 18 patients with sialolithiasis, nine of these with IPL (Lithoclast; EMS Swiss, Nyon, Switzerland).40 The overall success rate was 80%. The gland preservation rate was 89%. Serbetci and Sengor reported on the treatment of two patients with IPL (Calcusplit; Storz, Tuttlingen, Germany). In one of two cases, complete fragmentation and a stone-free state was achieved.24 At the beginning of 2015, a new device for the performance of IPL was introduced to fragment salivary stones (StoneBreaker; Cook Medical, Bloomington, IL, USA). It is a small and lightweight handheld device (Fig. 23.1). Due to the integrated gas cartridge, the device is independent from immobile gas resources. The pneumatic energy is released by a trigger mechanism and can be transmitted by an exchangeable nitinol probe (diameter 0.56 mm) under direct endoscopic control onto the surface of a stone. The application is, like all other methods of intraductal fragmentation, dependent on the accessibility of the stone with an adequate sialendoscope. In a recent publication,33

CHAPTER 23  Stone Fragmentation with Pneumatic Lithotripsy

Keywords Lithotripsy Pneumatic Stone Sialolithiasis Fragmentation

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CHAPTER 23  Stone Fragmentation with Pneumatic Lithotripsy

165

A

• Fig. 23.1

  (A) The StoneBreaker with the probe cap; the stability device with the nitinol probe and cartridge in place; the silicone tube connected to the exhaust valve. (B) During intraductal pneumatic lithotripsy: one person is maneuvering the sialendoscope and the probe, one person is holding the lithotripter in place and is operating the trigger, and another person is performing irrigation. (Permission for use granted by Cook Medical, Bloomington, Indiana.)

B

st

sd

mm pg m

44 patients with 49 stones were treated with this device (19 submandibular and 23 parotid glands; Figs. 23.2–23.4). In 40 patients, one stone was present; in three patients two stones; and in one case, three stones were treated. In 98%, complete fragmentation (96% of submandibular and

•

Fig. 23.2  The ultrasound image shows a stone of the parotid gland, 7 mm in size, located in the middle to proximal duct system. mm, masseter muscle; m, mandible; st, stone; sd, Stensen’s duct; pg, parotid gland.

100% of parotid stones) was achieved. Some 98% of the patients became stone-free (100% of submandibular and 95% of parotid glands). All patients became complaint-free. Complete success was achieved in 98% (100% submandibular and 95% parotid glands). In 100% of patients,

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A

B

C

D

E • Fig. 23.3

  (A) The probe on the surface of the stone after the start of lithotripsy. The stone after (B) partial and (C) complete fragmentation. (D) Basket extraction of a fragment. (E) After complete stone fragmentation and removal of all fragments there is slight maceration of the ductal wall.

CHAPTER 23  Stone Fragmentation with Pneumatic Lithotripsy

167

sd

pg

rmv

m

• Fig. 23.4

  The ultrasound image after treatment with the StoneBreaker shows stone-free state of the parotid gland. m, mandible; sd, Stensen’s duct; pg, parotid gland; rmv, retromandibular vein.

gland preservation was achieved. In five patients (11.4%), additional treatment methods were necessary to reach this success rate (in two patients, transoral duct surgery – all in submandibular glands; in three patients, ESWL was required – one submandibular and two parotid gland). The efficacy, duration, and number of procedures necessary to achieve successful treatment by this method appears similar to all other modalities of intraductal lithotripsy. It is dependent on the size and location of the stone, but also on the anatomic relationships of the salivary duct system.33 IPL is indicated for difficult sialolithiasis, e.g., in stones with difficult location and/or multiple stones. In difficult sialolithiasis, IPL has had very good results in combination with ESWL.41 Serbetci et al. reported results after treatment of stones with an alternative device (Vibrolith; Elmed LT Systems, Ankara, Turkey). This device has to be connected to a standard immobile gas source. The strikes can be triggered by a foot-operated switch. The number of shots delivered is tracked by a counter. The fragmentation is performed under sialendoscopic control with a 0.6–0.7-mm-wide, 35-cmlong probe that can be inserted through the working channel. A total of 34 stones were treated and 88% (30/34) were fragmented. Total stone removal was possible in 67.6% and partial stone removal in 20.6% of stones. Complete success was reported in 86.3%.42 In general, as in all methods of intraductal lithotripsy, the indication for IPL is best for difficult sialolithiasis. In submandibular glands, IPL is indicated in difficult impacted/ or no indication immobile posthilar stones, which are borderline candidates for extended transoral duct surgery. IPL may be indicated in all parotid stones requiring fragmentation that are accessible with a sialendoscope.4,33

KEY POINTS • Intraductal pneumatic lithotripsy is indicated for difficult sialolithiasis. • Intraductal laser lithotripsy and intraductal pneumatic lithotripsy represents the most effective methods of ISWL. • Success rates are higher than 90%.

References 1. Marchal F, Dulguerov P. Sialolithiasis management: the state of the art. Arch Otolaryngol Head Neck Surg 2003;129:951–6. 2. McGurk M, Escudier MP, Thomas BL, Brown JE. A revolution in the management of obstructive salivary gland disease. Dent Update 2006;33:28–36. 3. Capaccio P, Torretta S, Ottavian F, et al. Modern management of obstructive salivary diseases. Acta Otorhinolaryngol Ital 2007; 27:161–72. 4. Koch M, Zenk J, Iro H. Algorithms for treatment of salivary gland obstructions. Otolaryngol Clin North Am 2009;42:1173–92. 5. Iro H, Zenk J, Escudier MP, et al. Outcome of minimally invasive management of salivary calculi in 4,691 patients. Laryngoscope 2009;119:263–8. 6. Nahlieli O, Shacham R, Zaguri A. Combined external lithotripsy and endoscopic techniques for advanced sialolithiasis cases. J Oral Maxillofac Surg 2010;68:347–53. 7. Zenk J, Koch M, Klintworth N, et al. Sialendoscopy in the diagnosis and treatment of sialolithiasis: a study on more than 1000 patients. Otolaryngol Head Neck Surg 2012;147:858–63. 8. Witt RL, Iro H, Koch M, et al. Minimally invasive options for salivary calculi. Laryngoscope 2012;122:1306–11. 9. Nahlieli O, Baruchin AM. Endoscopic technique for the diagnosis and treatment of obstructive salivary gland diseases. J Oral Maxillofac Surg 1999;57:1394–402.

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10. Marchal F, Becker M, Dulguerov P, Lehmann W. Interventional sialendoscopy. Laryngoscope 2000;110:318–20. 11. Marchal F, Dulguerov P, Becker M, et al. Specificity of parotid sialendoscopy. Laryngoscope 2001;111:264–71. 12. Marchal F, Dulguerov P, Becker M, et al. Submandibular diagnostic and interventional sialendoscopy: new procedure for ductal disorders. Ann Otol Rhinol Laryngol 2002;111:27–35. 13. Zenk J, Koch M, Bozzato A, Iro H. Sialoscopy–initial experiences with a new endoscope. Br J Oral Maxillofac Surg 2004;42:293–8. 14. Nakayama E, Okamura K, Mitsuyasu T, et al. A newly developed interventional sialendoscope for a completely nonsurgical sialolithectomy using intracorporeal electrohydraulic lithotripsy. J Oral Maxillofac Surg 2007;65:1402–5. 15. Koch M, Zenk J, Iro H. Diagnostic and interventional sialoscopy in obstructive diseases of the salivary glands]. HNO 2008; 56:139–44. 16. Koch M, Iro H, Zenk J. Role of sialoscopy in the treatment of Stensen’s duct strictures. Ann Otol Rhinol Laryngol 2008; 117:271–8. 17. Geisthoff UW. Technology of sialendoscopy. Otolaryngol Clin North Am 2009;42:1001–28. 18. Nahlieli O, Iro H, McGurk M, Caldart M. Minimal invasive methods and procedures for the treatment of salivary gland sialolithiasis. In: Nahlieli O, Iro H, McGurk M, Zenk J, editors. Modern management preserving the salivary glands. Herzeliya (Israel): Isradon; 2007. p. 136–76. 19. Iro H, Zenk J, Koch M, Bozzato A. The Erlangen salivary gland project – part 1: sialendoscopy in obstructive diseases of the major salivary glands. Tuttlingen: Endo-Press; 2008. 20. Nahlieli O, Shacham R, Bar T, Eliav E. Endoscopic mechanical retrieval of sialoliths. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2003;95:396–402. 21. Konigsberger R, Feyh J, Goetz A, Kastenbauer E. Endoscopicallycontrolled electrohydraulic intracorporeal shock wave lithotripsy (EISL) of salivary stones. J Otolaryngol 1993;22:12–13. 22. Papadaki ME, McCain JP, Kim K, et al. Interventional sialoendoscopy: early clinical results. J Oral Maxillofac Surg 2008;66:954–62. 23. Modayil PC, Jacob V, Manjaly G, Watson G. Intracorporeal electrokinetic lithotripsy: an advancement in minimally invasive management of parotid duct calculus. J Laryngol Otol 2008;122:428–31. 24. Serbetci E, Sengor GA. Sialendoscopy: experience with the first 60 glands in Turkey and a literature review. Ann Otol Rhinol Laryngol 2010;119:155–64. 25. Chu DW, Chow TL, Lim BH, Kwok SP. Endoscopic management of submandibular sialolithiasis. Surg Endosc 2003;17:876–9. 26. Durbec M, Dinkel E, Vigier S, et al. Thulium-YAG laser sialendoscopy for parotid and submandibular sialolithiasis. Laser Surg Med 2012;44:783–6. 27. Martellucci S, Pagliuca G, de Vincentiis M, et al. Ho:Yag laser for sialolithiasis of Wharton’s duct. Otolaryngol Head Neck Surg 2013;148:770–4.

28. Sun YT, Lee KS, Hung SH, Su CH. Sialendoscopy with Holmium:YAG laser treatment for multiple large sialolithiases of the Wharton duct: a case report and literature review. J Oral Maxillofac Surg 2014;72:2491–6. 29. Sionis S, Caria RA, Trucas M, et al. Sialoendoscopy with and without holmium:YAG laser-assisted lithotripsy in the management of obstructive sialadenitis of major salivary glands. Br J Oral Maxillofac Surg 2014;52:58–62. 30. Phillips J, Withrow K. Outcomes of holmium laser-assisted lithotripsy with sialendoscopy in treatment of sialolithiasis. Otolaryngol Head Neck Surg 2014;150:962–7. 31. Su CH, Lee KS, Tseng TM, Hung SH. Endoscopic Holmium:YAG laser-assisted lithotripsy: a preliminary report. B-ENT 2015;11:57–61. 32. Schrotzlmair F, Muller M, Pongratz T, et al. Laser lithotripsy of salivary stones: correlation with physical and radiological parameters. Laser Surg Med 2015;47:342–9. 33. Koch M, Mantsopoulos K, Schapher M, et al. Intraductal pneumatic lithotripsy for salivary stones with the StoneBreaker: preliminary experience. Laryngoscope 2016;126:1545–50. 34. Iro H, Benzel W, Gode U, Zenk J. Pneumatic intracorporeal lithotripsy of salivary calculi. In vitro and animal experiment studies]. HNO 1995;43:172–6. 35. Bayar N, Kaymaz FF, Apan A, et al. Effects of electrohydraulic extracorporeal shock wave lithotripsy on submandibular gland in the rat: electron microscopic evaluation. Int J Pediatr Otorhinolaryngol 2002;63:223–33. 36. Katz P. New techniques for the treatment of salivary lithiasis: sialoendoscopy and extracorporal lithotripsy: 1773 cases]. Ann Otolaryngol Chir Cervicofac 2004;121:123–32. 37. Raif J, Vardi M, Nahlieli O, Gannot I. An Er:YAG laser endoscopic fiber delivery system for lithotripsy of salivary stones. Laser Surg Med 2006;38:580–7. 38. Iro H, Zenk J, Hosemann WG, Benzel W. [Electrohydraulic intracorporeal lithotripsy of salivary calculi. In vitro and animal experiment studies]. HNO 1993;41:389–95. 39. Pace CG, Hwang KG, Papadaki M, Troulis MJ. Interventional sialoendoscopy for treatment of obstructive sialadenitis. J Oral Maxillofac Surg 2014;72:2157–66. 40. Arzoz E, Santiago A, Esnal F, Palomero R. Endoscopic intracorporeal lithotripsy for sialolithiasis. J Oral Maxillofac Surg 1996;54:847–52. 41. Koch M, Schapher M, Mantsopoulos K, et al. Multimodal treatment in difficult sialolithiasis: role of extracorporeal shock-wave lithotripsy and intraductal pneumatic lithotripsy. Laryngoscope 2018;128(10):E332–8. 42. Serbetci E, Celikoyar MM, Altundag A. Sialendoscopic pneumatic lithotripsy for salivary calculi: a new technique and a longterm clinical experience. Otolaryngol Head Neck Surg 2017; 157:906–8.

24 

Extracorporeal Lithotripsy MICHAEL KOCH AND HEINRICH IRO

Background and Indication Treatment of sialolithiasis is currently achieved by a minimally invasive gland-preserving therapy regime. The observation by van den Akker and Busemann-Sokole that salivary gland function completely recovers after stone removal1 later was confirmed by others.2 In >80% of stones, fragmentation is necessary because of the size, impaction, and location. Of all stones in the submandibular, 80–85% and 75–80% in the parotid gland can be treated by transoral duct surgery and/or interventional sialendoscopy, including intraductal lithotripsy, which are methods of choice. However, 10–15% of stones in the submandibular gland and 20–25% in the parotid gland are not accessible with sialendoscopy but can be treated by extracorporeal shock wave lithotripsy (ESWL).3–9 The first successful fragmentation of a salivary stone in the parotid gland by ESWL was reported by Iro et al. in 1989.10

Shock Waves, Devices, and Procedures in Extracorporeal Shock Wave Lithotripsy In contrast to high-frequency ultrasound waves, which are characterized by a sinusoidal pressure course with successive compression and tensile phases, low-frequency acoustic shock waves are characterized by an extremely short time increment (10–100 ns), a short pulse duration (80% of patients.

28 

Parotid Gland Intraoral/External Combined Approaches for Strictures MICHAEL KOCH AND HEINRICH IRO

Introduction Salivary duct stenosis is a relatively rare pathologic condition. Of the stenosis cases, 70–75% are located in the parotid duct system.1,2 Salivary duct stenosis is the second most common cause of obstruction in the parotid gland, representing 15–25% of cases1–7 and making up 50–90% of cases of unclear duct dilation or gland swelling.5,8 Parotid stenosis can be associated with various conditions/ diseases; however, chronic (recurrent) parotitis may be the only cause. Stenosis develops in up to 13% of patients after prior surgery of the gland or the duct system, and is associated with sialolithiasis in over 15% of cases, which complicates treatment.1,2,5,7,9–19 Parotid duct stenosis is classified into inflammatory, fibrous, megaduct, duct anomalyassociated stenosis, and pure fibrous fixed stenosis without duct anomaly.20–22 Stenosis can be treated with success rates of >90% by a sialendoscopic minimally invasive and gland-preserving therapy, with good short- and long-term outcome. The success rates of the procedures are >80%, with improvement of symptoms reported in 70–90%, and gland preservation in 90–100% (see Chapter 27).3,5,8,14,17,19,21,23–32 Not all stenosis can be treated by sialendoscopic means. High-grade stenosis with complete duct obstruction and scarring can be managed only by more invasive surgical means. High-grade stenosis can occur after surgical procedures of the cheek region, Stensen’s duct itself, or after abscess formation due to sialolithiasis or in combination with other diseases. Almost all patients presenting with stenosis report a history of longstanding duct obstruction and excretion of murky and thick, sometimes jelly-like secretion. The gland function in many of these cases is compromised, reducing the chance of successful outcome.14,21,27 Stenosis associated with duct anomalies represent another group that may require more invasive measures to achieve a successful outcome. The grade of the stenosis with duct anomalies is generally mild to moderate; however, it can also be high-grade or nearly complete. This kind of stenosis is often complicated by kinking with an associated megaduct, in particular in the distal duct region.20–22,33–42

Diagnostic Work-Up and General Preoperative Considerations Although interventional sialendoscopy is the first choice in the treatment of ductal stenosis, transoral duct surgery or a combination of sialendoscopy and transcutaneous approaches may be the only treatment alternatives to ablation of the function of the gland or its resection.43 Meticulous diagnostic work-up is needed to assess if transoral or combined surgery is possible. Diagnostic information should include the course of the duct and the exact location of the stenosis and the nature of the surrounding tissue. The presence of a megaduct is an important precondition to successful transoral duct surgery, as it will allow marsupialization of the proximal duct to the oral mucosa more readily. If no megaduct is present, the chance for a successful outcome decreases. Ultrasound, magnetic resonance (MR)-sialography, conventional sialography, and computed tomography (CT) or cone beam-CT with sialography are the diagnostic imaging tools that can all contribute to a more precise characterization of stenosis (see Chapter 3).2,5,39,41,42,44–47 The duct itself, the surrounding tissues, and their relationship to the duct system can be determined by CT with sialography, MRsialography,39,41,42,44–49 or by ultrasound.5,14,21,22,26,27,42,46,50,51 In papillary stenosis and/or distal duct stenosis, ultrasound can used to measure the length of the stenosis, the distance from the oral mucosa to the most distal visible lumen, and the diameter of the duct lumen proximal to the stenosis, which are important criteria that help to indicate or to abandon transoral duct surgery (Fig. 28.1). In papillary or prepapillary and distal duct stenosis, the distance between the oral mucosa to the most distal visible duct lumen should not exceed 15 mm, because suturing of the duct to the oral mucosa may not be possible or only possible with a higher risk of complications due to increased tension. Creation of any neo-ostium must be performed without any tension in order to avoid re-stenosis. The ductal lumen proximal to the stenosis can be measured also by ultrasound. A megaduct with a duct diameter exceeding 5 or even 10 mm represents a favorable situation, because it offers an adequate lumen to 191

CHAPTER 28  Parotid Gland Intraoral/External Combined Approaches for Strictures

Keywords Stricture Stenosis Parotid Duct Intraoral Combined

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bfp ds

om bm

mm

m

• Fig. 28.1  (A) Ultrasound (US) in papillary distal stenosis with formation of a megaduct. Dilation of Stensen’s duct (8.3 mm) with tendency to form a megaduct, no lumen visible distally (white arrow), which indicates the proximal end of the stenosis. The distance from this point to the oral mucosa was measured at 8.4 mm. (B) US in papillary stenosis associated with megaduct and ductal anomaly. Massive dilation of ds, in particular in the distal duct system (12.6 mm) with no lumen visible distally (white arrow), which indicates the proximal end of the possible stenosis. The echo-rich structure within the ductal lumen indicates a web or duct kinking (green arrow). The distance from this point to the oral mucosa was measured at 12.4 mm. Thickness of the bm was measured to be 3.4 mm. ds, Stensen’s duct; mm, masseter muscle; m, mandible; om, oral mucosa; bm, buccinator muscle; bfp, buccal fat pad.

A

bfp ds bm

mm om

B

allow suturing of the pre-stenotic duct to the oral mucosa with creation of a wide neo-ostium and is one important precondition to perform successful transoral duct surgery in parotid gland duct stenosis (Figs. 28.2, 28.3). In complete stenosis, the sialendoscope cannot be inserted into the duct system primarily but it is important to perform stent implantation, indicated in virtually all cases.1,3,5,11,14,20,22,52

sialodochoplasty with duct reinsertion, and duct ligation. High failure rates exceeding 50% with the above techniques have been described.10,16,50,55–58 All methods of transoral duct surgery described here are restricted to the premasseteric distal duct system.

Treatment

In complete and extended papillotomy, the incision is performed through all layers of the papilla, namely oral mucosa, the whole periductal musculature, and the inner mucosal lining. Stent implantation is mandatory in this procedure and the stent should stay for at least 12 weeks to allow development of a stable scar (Fig. 28.2). Due to the impaired tissue quality within the involved ductal area, characterized by scarring and/or maceration, in most cases marsupialization cannot be performed adequately. Beyond that, the advantages of a larger lumen provided by the presence of a megaduct cannot be used to create

In general, one of the essential prerequisites for any successful treatment, independent of the method chosen, is adequate gland function. If an impaired gland does not recover, the use of almost any approach may not be successful.25,29,53,54

Methods of Transoral Duct Surgery Various invasive surgical procedures in the distal duct system have been described, such as papillotomy or meatotomy,

(Extended) Papillotomy

CHAPTER 28  Parotid Gland Intraoral/External Combined Approaches for Strictures

B

A

C • Fig. 28.2

  Distal duct slitting/incision in papillary stenosis. (A) Short stenosis with residual lumen at or very near to the papilla (arrow). (B) Duct incision is performed through all layers of the scarred and stenotic part of the duct. Because no marsupialization can be performed, stent implantation is mandatory. (C) Situation after the stent (arrow) was positioned within the duct system. 1, buccinator muscle; 2, masseter muscle; 3, Stensen’s duct.

A

B • Fig. 28.3

  Distal duct slitting/incision in papillary stenosis. (A) Incomplete high-grade stenosis at the papilla, endoscopic view showing tissue maceration. (B) Situation after extended slitting through the papilla and the prepapillary distal duct and after stent implantation.

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a wide neo-ostium. This procedure is associated with a higher risk of development of a re-stenosis, even with stent implantation.14,21,43,50 Cohen et al. reported recurrences after papillotomy and revision-papillotomy, with stent implantation for 2 weeks and 3 weeks, respectively. They emphasized that complete marsupialization is mandatory to achieve successful outcome.50 In our patients, this technique is carried out very rarely in patients presenting with a papillary stenosis in combination with sialolithiasis and stone extraction (Fig. 28.3). These patients present with completely scarred papillary stenosis.14 If at all, this technique should be deployed only in very exceptional situations and does not represent a routine primary treatment option.

A semicircular incision is performed ~5 mm adjacent to the scarred papilla (Fig. 28.4). The megaduct is prepared by careful dissection and freed from the buccal fat pad and the buccinator muscle. The opening of the duct can be made in a horizontal (alternatively also or vertical) direction, depending on the presentation. After adequate dissection of the duct, the incision is sutured to the surrounding oral mucosa with 4-0–6-0 resorbable sutures. The resulting neo-ostium is created by a “duct side wall to mucosa” – anastomosis (Fig. 28.5). This technique was described for stenosis with megaduct with and without associated duct anomalies.14,21,34,38,40,41,43,50 It is used in complete fibrotic stenosis with high inflammatory activity within the gland. Complete marsupialization by suturing the oral mucosa to the ductal epithelium must be performed to avoid recurrences.14,21,50 Stent implantation is indicated in almost every case. This technique is also indicated with stenosis associated with megaduct and duct anomalies, but without significant inflammation.34,38,40,41 The technique is for stenosis located in the papillary, prepapillary, or most distal region. In cases of a location more proximal, with a distance to the oral mucosa/ostium exceeding 15 mm, there is an increasing risk that marsupialization with creation of a tension-free neo-ostium may not be possible.14,21,43

Retropapillary Ductal Incision With Creation of Ductal Neo-Ostium In case of a short (50% of PAs; much less so in 12q14-15 region (10–15%).35 No genetic alteration has been identified in RPA in contrast to PA that brings it a step closer to carcinogenesis. While some groups have seen a persistence of PLAG1 and HMGA2 in carcinoma ex pleomorphic adenoma (CXPA), others have reported the absence of PLAG1 as a hallmark of malignant transformation; perhaps testing methodology plays a role in this discrepancy.36,37 Chromosomal gains, amplifications, gene fusions, and translocations in 8q, 12q, and loss in 17p are promoters of malignant transformation.37,38 Additionally, presence of HER2 (40%, mostly in SDCA) and EGFR (44%, both myoepithelial and SDCA) amplifications in CXPA are correlated with a poor outcome, while dual presence (23%) is indicative of a very aggressive subgroup. However, they also serve as targets for immunotherapy.

KEY POINTS • Pleomorphic adenoma’s name is derived from the presence of both epithelial and mesenchymal components. • Pseudopodia is less common in submandibular pleomorphic adenoma. • Minimizing capsular exposure and, when possible, getting a generous margin of healthy salivary tissue is highly recommended.

34.2  WARTHIN TUMOR Warthin tumor (WT), also known as papillary cystadenoma lymphomatosum or adenolymphoma, was first described by Aldred Warthin in 1929, in two cases.39 WT is the second most common benign tumor of the parotid gland,40,41 although it was reported the most common benign tumor in a series from Singapore.42 It has been associated with male gender and smoking and reported as multicentric in approximately 25% and bilateral in up to 15% of the cases.40,43,44 An increase in the incidence of WT in women was noted, possibly in association with an increased incidence of smoking.45 The vast majority of WTs occur in the parotid gland, although extra-parotid lesions have also been described.46,47 Incidence of WT is uncommon in the pediatric population.48 Localization of WT in the parotid gland has rarely been discussed. Occurrence of WT in the deep lobe of the gland was found to be 4%,49 3.7%,40 rare in a bi-institutional study of 122 patients,50 to non-existent in a study of 183 WT patients (Fig. 34.2.1).49 The deep lobe of the parotid is considered to account for 20% of the glandular tissue, with a similar proportion of lymph nodes. Presumably, a similar proportion of superficial vs deep lobe WT could be anticipated. The reason for the tumor to be limited almost

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uniformly to the superficial lobe is unknown but could presumably be related to the etiology of this elusive entity. This localization of the tumor was suggested as an additional common characteristic of WT.50 There is a great geographic and ethnic variability in the worldwide occurrence of WT. It is common in the Asian population51 but rare in Blacks.52 A significant number of our WT patients are from Jewish-Iraqi origin and the great majority are from the Iraqi-Syrian-Turkish region.50 WT is a rare occurrence in the African population,53,54 despite salivary gland tumors being a significant health problem in that continent.53 The etiology and pathogenesis of WT is still unclear, with some evidence that even challenges its neoplastic nature by arguing in favor of it being a developmental abnormality, or is the result of an autoimmune reaction.43,55–57 The authors reported formerly on familial occurrence of WT58 and, while it is classically considered to be a non-genetic disease, recently we identified four siblings (two males and two females) with bilateral WT in a single inbred family. Moreover, >10 cases of WT were identified within that same inbred cohort, suggesting possible recessive heredity of tumor predilection. Homozygosity mapping identified a possible genomic locus for a disease-associated gene, and relevant potential disease-causing mutations within this locus, identified through next generation sequencing, are currently being evaluated by our team. On gross pathologic examination, WT are usually encapsulated masses with a smooth or lobulated surface. Papillary cysts are commonly found on sectioning and contain mucoid, brown fluid. Solid gray tissue encapsulates white nodules of lymphoid tissue. Microscopically (Figs. 34.2.2–34.2.4), the combination of papillae of eosinophilic epithelia that project into cystic spaces and lymphoid matrix is a distinct and pathognomonic histologic feature. The typical cystic lining is arranged in two cell layers of even rows. The apical or luminar tall columnar and basal cuboidal cells contain small dark nuclei and abundant granular pink cytoplasm (oncocytes). The granular eosinophilia of oncocytes is due to abundant mitochondria present in the cytoplasm.59 The histology of WT includes both an oncocytic epithelial component forming cystic spaces with papillary appearance and lymphoid stroma. These microscopic features may suggest that WT originates in salivary parenchyma inclusions trapped in the intra- and periglandular lymph nodes of the parotid gland.60 The diagnosis of WT can be established by patient history, clinical examination, imaging, and cytology. Patients with WT usually present with an asymptomatic, slowgrowing mass in the superficial lobe of the parotid gland, often at the angle of the mandible (Fig. 34.2.5). Occasionally, patients may present with swelling, pain, and other inflammatory-like manifestations that may be secondary to an immunologic response. As was recently described, the evaluation of WT includes ultrasound-guided fine needle aspiration (FNA) with cytology characterized by the triad of oncocytes, lymphoid cells, and a proteinaceous background. The impact and importance of FNA in WT has

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Yu et al., China, 1998

Colella et al., Italy, 2010

0% in the Deep Lobe (n=183)

4% in the Deep Lobe (n=71)

Chumlam et al., Brazil, 2013 3.7% in the Deep Lobe (n=108)

Sagiv et al., 2017 99.2% in the Superficial Lobe (n=124)

• Fig. 34.2.1

 

Distribution of WT in the superficial vs deep lobe of the parotid gland.

• Fig. 34.2.2

• Fig. 34.2.3  Low power magnification depicting Warthin tumor’s histologic features; normal parotid tissue is noted inferiorly. (H&E ×2)

been widely discussed61–63 and is valuable in the diagnosis of WT both in its high sensitivity and high positive predictive value and for the implications of establishing a definite diagnosis prior to considering surgery. Though highly accurate, FNA cytology may often falsely diagnose oncocytoma, lymphoma, squamous cell carcinoma, and may also be nondiagnostic. Also, although uncommon, FNA in WT may lead to infection in much higher incidence than in other parotid tumors64 and while this does not negate its common use, it should be taken into consideration. Frozen section

was reported to have 100% accuracy rates.65 The uncommon incidence of WT in the deep lobe and in light of false-positive rates of FNA, re-evaluating a lesion in the deep lobe of the gland with FNA cytology of WT was suggested.50 Imaging may be of value in WT, not only in defining location and extent of disease but also as an aid in establishing diagnosis. Rassekh et al.66 analyzed positron emission tomography (PET) CT findings in WT patients when followed for malignant disease. Their study specifically

  Low power magnification depicting Warthin tumor’s histologic features. (H&E ×2)

CHAPTER 34  Benign Tumors

• Fig. 34.2.4

 

High magnification of Warthin tumor. (H&E ×40)

A

decisional algorithm for the preoperative diagnosis of WT utilizing standardized MRI with conventional sequences and functional sequences. Using the algorithm, sensitivity and specificity were 80–96% and 85–100%, respectively for two readers. The authors conclude that the specificity of the technique is sufficient to avoid surgery if a parotid gland tumor presents all the MRI characteristics of WT. Schwalje et al.69 evaluated growth characteristics of WT in 24 patients. WT appear to have an approximate average doubling time of 9 years but can have a wide range of growth rates, with many cases showing a reduction in size. The authors conclude that either conservative management or surgical resection could be supported by these data, depending on the current size of the tumor, appearance, symptoms, and the age, health, and wishes of the patient.69 Malignant transformation of WT was reported in sporadic cases70,71 and overall reported to be as low as 0.3%.41 With the above considerations, management of WT has evolved. While in the past the majority of patients were referred for surgery, there are currently many proponents suggesting observation only. This approach is now accepted, not only in patients with comorbidities but also in young and healthy individuals wishing to avoid surgery altogether.61 In those that do undergo surgery, in the presence of reliable FNA results, minimally invasive procedures can be implemented.65 A conservative surgical approach via extracapsular dissection of the tumor has been suggested,72 although others suggest superficial parotidectomy or partial superficial parotidectomy to be the procedure of choice. Even in recurrent cases of WT as described by Witt and Nicolai,73 being a metachronous occurrence of a new focus, or residual incomplete excision of all primary multicentric foci of WT, the surgical approach could be modified. They suggest selected cases can be observed while conservative surgical management can include partial superficial parotidectomy or even extracapsular dissection. In conclusion, WT is a common benign lesion of, mostly, the parotid gland. It is associated with the male gender and smoking and rarely harbors malignant features. There is a wide genetic and geographic variability and the exact mechanism of its development is yet to be defined. Surgery may be obviated and when performed, a limited procedure may suffice.

B • Fig. 34.2.5

  (A) Classic MRI features of a large Warthin tumor of the right gland (coronal view). (B) Classic MRI features of a large Warthin tumor of the right gland (axial view).

characterized clinical features, SPECT-CT, and FNA findings in these patients that can help reinforce the diagnosis of WT and thus facilitate management. Magnetic resonance imaging (MRI) was found to be more useful in the evaluation of WT than Tc-99m pertechnetate scintigraphy.67 Espinoza et al.68 assessed the added value of a

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KEY POINTS • Warthin tumor is the second most common benign tumor of the parotid gland. • It is associated with male gender and smoking. • It may be multicentric and bilateral. • Etiology-pathogenesis are not yet defined. • FNA and imaging are valuable in establishing diagnosis. • In recent years a more conservative treatment approach has been adopted. • Watchful waiting is a viable alternative to surgery in cases with a well-established diagnosis.

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34.3  OTHER BENIGN TUMORS Introduction Benign salivary tumors other than PA and WT represent 10% of benign salivary tumors; approximately 5% corresponding to myoepitheliomas and 3–4% to basal cell adenomas. Oncocytoma corresponds to approximately 0.5% and ductal papilloma to 0.2%. Sebaceous and nonsebaceous lymphadenomas, canalicular adenomas, and sebaceous adenomas are rare and account for