Surgical Pathology of Prostate & Seminal Vesicles 9780849348044, 0849348048

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Surgical Pathology of Prostate and Seminal Vesicles Author

Joseph Kovi, M.D., F.R.C.Path., F.C.A.P. Professor Department of Pathology Howard University College of Medicine Washington, D.C.

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No claim to original U.S. Government works ISBN 13: 978-0-8493-4804-4 (hbk) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials orthe consequences oftheir use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming. and recording, or in any information storage or retrieval system, without written permission from the publishers. for permtsswn to photocopy or use material electronically from this work, please access www. copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Visit the Taylor & Francis Web site at http://www. taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Library of Congress Card Number 88-8181 LIBRARY OF CONGRESS Library of Congress Cataloging-in-Publication Data

Kovi, Joseph. Surgical pathology of prostate and seminal vesicles I author, Joseph Kovi. p. em. Includes bibliographies and index. ISBN 0-8493-4804-8 I. Prostate gland-Diseases. 2. Seminal vesicles-Diseases. 3. Pathology, Surgical. I.. Title. [DNLM: I. Pathology. Surgical. 2. Prostate-pathology. 3. Prostatic Diseases-pathology. 4. Seminal Vesiclespathology. WJ 750 K88s] RC899.K68 1989 616.6'5-dcl9 DNLM/DLC for Library of Congress 88-8181

CJP

THE AUTHOR Joseph Kovi, M.D., F.R.C. Path., F.C.A.P., is Professor, Departments of Pathology and Oncology, Howard University College of Medicine, Washington, D.C. Professor Kovi received his M.D. degree from the College of Medicine, University of Budapest, Hungary, in 1953. After having completed his residency in pathology at Roswell Park Memorial Institute, Buffalo, NY, he became a Diplomate of the American Board of Pathology in 1967. Dr. Kovi has been on the faculty of Howard University College of Medicine since 1970. In 1979, he spent his sabbatical leave as a Visiting Professor in Virology at the Department of Molecular Carcinogenesis and Virology, M. D. Anderson Hospital and Tumor Institute, Houston, Texas. Dr. Kovi was a founder member of the College of Pathologists of Great Britain. He is presently a fellow of the Royal College of Pathologists, College of American Pathologists, American Society of Clinical Pathologists, and a member of the International Academy of Pathology and the Electron Microscopy Society of America. Dr. Kovi has published more than 70 research papers and has been the principal investigator or co-investigator of research grants from the National Cancer Institute.

ACKNOWLEDGMENTS I am deeply indebted to Mrs. Elizabeth Kovi for proofreading the manuscript. Typing and editing of the text was done by Mr. Ati Kovi. This work could not have been accomplished without the support of the Cooperative Prostatic Research Group, Howard University College of Medicine, Washington, D.C. Members ofthis group were B.S. Ahluwalia, Ph.D.; E. B. Attah, M.B., F.R.C.P.C., F.R.C.Path. (Calabar, Nigeria); E. C. Christian, M.D., F.R.C.Path. (Accra, Ghana); Mitchell Edson, M.D. (Washington Hospital Center, Washington, D.C.); J. P. Enterline, M.S. (The Johns Hopkins Oncology Center, Baltimore); Jay Herson, Ph.D.; Martin Heshmat, M.D., Ph.D., Dr.PH.; Aaron G. Jackson, M.D.; Marvin A. Jackson, M.D.; George W. Jones, Ph.D.; Lalita Kaul, Ph.D.; Joseph Kovi, M.D.; Nkposong, M.D., F.R.C.S. (Ibadan, Nigeria); S. L. Perry, M.D. (D.C. General Hospital, Washington, D.C.); M.S. Rao, Ph.D.; and A. 0. Williams, M.D., F.R.C.P., F.R.C.Path. (Ibadan, Nigeria). The photomicrographs, unless otherwise specified, were taken from microscopic sections prepared by the Surgical Pathology Laboratory, Howard University Hospital. Mr. Jeffrey Fearing was responsible for printing of negatives taken by the author. The line drawings were made by Mrs. Naida W. Page, medical artist. Illustrative roentgenograms were kindly provided by Harry C. Press, Jr., M.D., F.A.C.R., Howard University Hospital. The cooperation of Ms. Sandy Pearlman, Director of Editing, Design, and Production; Ms. Anita Hetzler, Senior Coordinating Editor; and the staff of the photographic department of CRC Press, Inc., is gratefully acknowledged. The author was supported in part by U.S. Public Health Service grants CA-15448, CA-26679, and CA-2667904 from the National Prostatic Cancer Project, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Dedicated to Dr. F. K. Mostofi and associates, Dr. Charles J. Davis, Jr., and Dr. I. A. Sesterhenn, Armed Forces Institute of Pathology, Washington, D.C.

TABLE OF CONTENTS SECTION A: PROST ATE GLAND Chapter I Introduction ............................................................................................................................ 3 I. Embryology .................................................................................................................... 3 II. Anatomy ......................................................................................................................... 3 III. Histology ........................................................................................................................ 5 IV. Diagnostic Immunohistochemistry of Prostate .............................................................. 7 A. Prostate-Specific Acid Phosphatase (PSAP) ........................................................ 7 I. Methods of Measurement of Serum Acid Phosphatase .............................. 8 a. Enzymatic Assays .............................................................................. 8 b. Immunoassays for Prostatic Acid Phosphatase ................................. 8 2. PSAP Immunohistochemistry ..................................................................... 9 3. Interpretation of Immunoperoxidase Staining ............................................ 9 4. Normal Prostate Stained for PSAP ........................................................... 10 5. Immunoperoxidase Staining for PSAP in BNH ........................................ 12 6. PSAP Immunoperoxidase Staining for Identification of Prostatic Carcinoma .............................................................................. 13 7. PSAP Immunoreactivity in Selected Entities ............................................ 17 a. "Endometrial" Adenocarcinoma of Prostatic Urethra ..................... 17 b. Immunoreactivity of Skeletal Metastases ........................................ 17 c. Detection of Viable Tumor Cells following Radiation Treatment of Prostatic Carcinoma ................................................... 17 d. Interpretation of Immunoperoxidase Reaction in a Small Tissue Sample .................................................................................. 18 e. Differential Diagnosis of a Monotonous Cellular Infiltrate of Single Cell Type in a Prostatic Needle Biopsy ........................... 18 f. False-Positive Immunostaining for PSAP ....................................... 18 g. Negative PSAP Immunostaining in Primary Carcinoma of Prostate ........................................................................................ 18 h. Immunoperoxidase Staining for Differential Diagnosis of Malignant Neoplasms Involving the Prostate Gland ................................................................................. 19 8. Discrepancy between Serum and Tissue PSAP Findings ......................... 19 9. Utilization of Immunoperoxidase Technique for PSAP in Aspiration Biopsy Cytology (ABC) ...................................................... 20 B. Prostate-Specific Antigen (PSA) ........................................................................ 20 I. Relationship between Tumor Differentiation and PSA Immunoreactivity ...................................................................................... 20 2. False-Positive Reaction with Polyclonal Antibodies to PSAP ................. 22 3. Nonimmunoreaction Elements in Surgical Specimens of the Prostate Gland ........................................................................................... 22 4. Prognostic Implications of Immunohistochemical Localization of PSA and PSAP ...................................................................................... 22 V. Fine Needle Aspiration Biopsy of the Prostate Gland ................................................. 22 A. History of Fine Needle Aspiration of Prostate ................................................... 22 B. Aspiration Biopsy Cytology (ABC) ................................................................... 23 1. Benign Nodular Hyperplasia (BNH) ......................................................... 23

2. 3. 4.

C. D. E.

Prostatitis ................................................................................................... 23 Adenocarcinoma of Prostate ..................................................................... 25 Aspiration Biopsy Cytology (ABC) Grading of Adenocarcinoma of Prostate ..................................................................... 27 5. Diagnostic Accuracy of Fine Needle Aspiration (FNA) Biopsy ............................................................................................ 28 Advantages of FNA Biopsy ................................................................................ 28 Complications of FNA ........................................................................................ 29 Pitfalls of ABC ................................................................................................... 29

Chapter 2 Endocrinology ...................................................................................................................... 3 I I. Hormonal Regulation of Prostatic Growth ................................................................... 31 II. Molecular Mechanism of Androgen Action ................................................................. 31 III. The "DHT Thesis" ....................................................................................................... 31 IV. Age-Related Changes of Steroid Hormone .................................................................. 32 Chapter 3 Atrophy ................................................................................................................................. 33 I. Histologic Forms of Atrophy ....................................................................................... 33 A. Simple Atrophy ................................................................................................... 33 B. Sclerotic Atrophy ................................................................................................ 33 II. The Role of Apoptosis in Prostatic Atrophy ................................................................ 33 III. Postatrophic Hyperplasia .............................................................................................. 35 A. Lobular Hyperplasia ........................................................................................... 36 B. Hyperplasia Associated with Sclerotic Atrophy ................................................. 36 IV. Secondary Hyperplasia ................................................................................................. 38 Chapter4 Prostatic Calculi ................................................................................................................... 39 I. Endogenous Prostatic Stones ....................................................................................... 39 A. Anatomical Location of Prostatic Corpora ......................................................... 39 B. Composition of Endogenous Prostatic Calculi ................................................... 40 II. Exogenous Prostatic Stones ......................................................................................... 40 III. Predisposing Factors in Calculous Disease of Prostate ................................................ 41 IV. Prostatic Calculi and Recurrent Prostatitis ................................................................... 41 V. The Role of Calcinuria in the Formation of Prostatic Stones ..................................... .41 VI. Ochronosis and Prostatic Stones .................................................................................. 41 VII. Symptoms and Diagnosis ............................................................................................. 41 Chapter 5 Prostatic Infarction .............................................................................................................. 43 Predisposing Condition .......................................................................................................... 43 Etiology and Pathogenesis ..................................................................................................... 43 Gross Findings ....................................................................................................................... 43 Histology ................................................................................................................................ 43 Incidence of Squamous Metaplasia ....................................................................................... 44 Clinical Manifestations of Infarction ..................................................................................... 45 Significance ........................................................................................................................... 45

Chapter 6 Melanotic Lesions of the Prostate ....................................................................................... 47 Blue Nevus of the Prostate ..................................................................................................... 47 Epithelial Melanosis of the Prostate ...................................................................................... 47 Malignant Melanoma of the Prostate ..................................................................................... 50 Chapter 7 Prostatitis .............................................................................................................................. 53 I. Acute Bacterial Prostatitis ............................................................................................ 53 A. Histology ............................................................................................................. 53 B. Clinical Manifestations ....................................................................................... 53 II. Chronic Bacterial ......................................................................................................... 55 A. Histology ............................................................................................................. 55 B. Clinical Manifestations ....................................................................................... 55 C. Diagnosis ............................................................................................................ 57 III. Nonbacterial Prostatitis ................................................................................................ 57 A. Definition ............................................................................................................ 57 B. Incidence ............................................................................................................. 58 C. Etiology ............................................................................................................... 58 D. Pathology ............................................................................................................ 58 E. Clinical Manifestations ....................................................................................... 58 F. Diagnosis ............................................................................................................ 58 IV. Prostatodynia ................................................................................................................ 58 Granulomatous Prostatitis ...................................................................................................... 58 I. Noneosinophilic Granulomatous Prostatitis ................................................................. 59 A. Pathogenesis ....................................................................................................... 59 B. Histology ............................................................................................................. 59 C. Clinical Manifestations ....................................................................................... 59 D. Diagnosis ............................................................................................................ 59 E. Significance of Granulomatous Prostatitis ......................................................... 59 II. Eosinophilic Granulomatous Prostatitis ....................................................................... 61 A. Histology ............................................................................................................. 61 B. Pathomechanism of Granulomatous Formation ................................................. 62 C. Clinical Manifestation ........................................................................................ 63 III. Necrotizing Prostatic Granuloma- A Sequel to Previous Operation ........................ 63 A. Etiology ............................................................................................................... 64 B. Histology ............................................................................................................. 64 C. Significance ........................................................................................................ 65 D. Differential Diagnosis of Necrotizing Prostatic Granuloma .............................. 65 E. Clinical Manifestations ....................................................................................... 65 Malakoplakia ......................................................................................................................... 65 A. Incidence ............................................................................................................. 66 B. Pathogenesis ....................................................................................................... 66 C. Histology ............................................................................................................. 66 D. Ultrastructure ...................................................................................................... 66 E. Clinical Manifestations ....................................................................................... 68 F. Significance ........................................................................................................ 68 Tuberculous Prostatitis ......................................................................................................... 68 A. Pathogenesis ....................................................................................................... 68 B. Histology ............................................................................................................. 69 C. Clinical Manifestations ....................................................................................... 69

D.

Differential Diagnosis ......................................................................................... 69

Chapter 8 Mycotic Infections and Parasitic Diseases ......................................................................... 71 Deep (Systemic) Candidiasis ................................................................................................. 71 Major Deep Mycoses ............................................................................................................. 71 I. Blastomycosis ............................................................................................................... 71 A. Incidence ............................................................................................................. 71 B. Histology ............................................................................................................. 71 C. Clinical Manifestations ....................................................................................... 73 II. Cryptococcosis ............................................................................................................. 73 A. Definition ............................................................................................................ 73 B. Etiologic Agent ................................................................................................... 73 C. Organ Involvement ............................................................................................. 73 D. Cryptococcal Prostatitis ...................................................................................... 73 E. Histology ............................................................................................................. 73 F. Clinical Manifestations ....................................................................................... 74 III. Coccidioidomycosis ..................................................................................................... 74 A. Definition ............................................................................................................ 74 B. Geographic Distribution ..................................................................................... 74 C. Organ Involvement ............................................................................................. 74 D. Pathogenic Organism .......................................................................................... 75 E. Coccidioidomycotic Prostatitis ........................................................................... 75 F. Histology ............................................................................................................. 75 G. Clinical Manifestations ....................................................................................... 75 IV. Paracoccidioidomycosis and Histoplasmosis ............................................................... 76 Parasitic Diseases Involving the Prostate and Seminal Vesicles ........................................... 76 I. Schistosomiasis (Bilharziasis) ...................................................................................... 76 A. Definition ............................................................................................................ 76 B. History ................................................................................................................ 76 C. Geographic Distribution ..................................................................................... 76 D. Incidence ............................................................................................................. 76 E. Infective Parasites ............................................................................................... 76 F. Life Cycle of S. haematobium ............................................................................ 76 G. Genitourinary Involvement ................................................................................. 77 H. Histology ............................................................................................................. 77 I. Inactive Genitourinary Schistosomiasis ............................................................. 78 J. Schistosomiasis of the Seminal Vesicles ............................................................ 78 K. Clinical Manifestations ....................................................................................... 79 L. Diagnosis ............................................................................................................ 79 M. Schistosomiasis and Carcinoma of Prostate ....................................................... 79 II. Trichomoniasis ............................................................................................................. 79 A. Histology ............................................................................................................. 79 B. Clinical Manifestations and Diagnosis ............................................................... 80 III. Echinococcosis ............................................................................................................. 80 A. Histology ............................................................................................................. 82 B. Clinical Manifestations ....................................................................................... 82 Chapter 9 Basal Cell Hyperplasia (Basal Cell Adenoma) .................................................................. 83 I. The Basal Cell .............................................................................................................. 83

II.

III. IV.

A. Structure .............................................................................................................. 83 B. Histochemistry and DNA Synthesis ................................................................... 83 C. Electron Microscopy ........................................................................................... 83 D. Physiologic Function of the Basal Cell .............................................................. 83 Basal Cell Hyperplasia ................................................................................................. 84 A. Histology ............................................................................................................. 84 B. Clinical Manifestations ....................................................................................... 88 Basal Cell Adenoma (Adenoid Basal-Cell Tumor) ...................................................... 88 A. Histology ............................................................................................................. 88 Basal Cell Hyperplasia and Adenocarcinoma of Prostate ............................................ 88

Chapter 10 Benign Nodular Hyperplasia (BNH) .................................................................................. 91 I. Epidemiology ............................................................................................................... 91 A. Age Incidence ..................................................................................................... 91 B. Geographic Distribution ..................................................................................... 91 C. Interracial Incidence ........................................................................................... 93 II. Etiology ........................................................................................................................ 93 A. The Role of Testes in BNH ................................................................................ 94 B. Testosterone (T) .................................................................................................. 94 C. DHT .................................................................................................................... 94 D. Risk Factors ........................................................................................................ 95 III. Histogenesis ................................................................................................................. 95 A. Epithelial Origin of BNH .................................................................................... 96 B. Dual Origin of BNH ........................................................................................... 97 C. Site of Origin ...................................................................................................... 97 D. Stereologicl Analysis of BPH ............................................................................. 97 IV. Pathology ...................................................................................................................... 97 A. Gross Features .................................................................................................... 97 B. Microscopic Appearances of BNH ..................................................................... 97 C. Microscopic Categorization of Nodular Hyperplasia ......................................... 98 D. Secretory Activity of Hyperplastic Glands ....................................................... 105 E. The Glandular Epithelium ................................................................................ 106 F. Epithelial Cell Growth ...................................................................................... 107 G. Secondary Changes in Nodules ........................................................................ 107 V. Histologic Effects of Orchiectomy and Estrogens in BNH ........................................ 107 VI. Effects of Cauterization in Tissue Fragments Obtained by Transurethral Resection of the Prostate (TURP) .............................................................................. 108 VII. Ultrastructure .............................................................................................................. 108 VIII. Pathophysiology ......................................................................................................... 109 IX. Clinical Manifestanons .............................................................................................. 110 X. Treatment and Handling of Surgically Removed Specimens .................................... 111 XI. BNH and Carcinoma of Prostate ................................................................................ 112 Chapter 11 Atypical Hyperplasia of the Prostate ............................................................................... 115 I. Atypical Small Acinar Hyperplasia ............................................................................ 115 A. Growth Pattern .................................................................................................. 117 B. Mode of Spread ................................................................................................. 117 C. Comparison to Normal Ducts ........................................................................... 120 D. Variation of Glandular Patterns within a Microscopic Field ............................ 120

II. III.

IV.

E. Individual Gland Structure ............................................................................... 120 F. Proclivity of Glands Toward Convolution ....................................................... 122 G. Corpora Amylacea within Acini ....................................................................... 122 H. Glandular Secretion .......................................................................................... 122 I. Cell Necrosis ..................................................................................................... 123 J. Luminal Border of Acini .................................................................................. 123 K. Configuration of Epithelial Cells ...................................................................... 123 L. Lumen-to-Gland-Wall Ratio ............................................................................. l24 M. Epithelial Cell Cytoplasm ................................................................................. 124 N. Position of Nuclei within the Epithelium ......................................................... 124 0. Nuclear Patterns ................................................................................................ 124 P. Nucleoli ............................................................................................................. l26 Large Acinar ("Intraductal") Atypical Hyperplasia ................................................... 126 Atypical Cribriform Hyperplasia ............................................................................... 128 A. Association of Atypical Hyperplasia and Carcinoma of Prostate .................... 130 B. Spatial Relationship between Atypical Hyperplasia and Prostatic Carcinoma .......................................................................................... 132 C. Association of Atypical Hyperplasia and Multicentric Carcinoma .................. 132 D. Cell Kinetic Findings in Atypical Hyperplasia and Prostatic Carcinoma ........ 133 E. AH and Age ...................................................................................................... 133 Phyllodes Type of Atypical Hyperplasia ................................................................... 133

Chapter 12 Tumors of the Prostatic Urethra, Periurethral Ducts, and Cowper's Glands ............. 135 Benign Tumors and Tumor-Like Lesions ............................................................................ 136 I. Polypoid Urethritis ..................................................................................................... 136 A. Definition .......................................................................................................... 136 B. Microscopic Findings ....................................................................................... 136 II. Fibroepithelial Polyp .................................................................................................. 136 A. Definition .......................................................................................................... 136 B. Histogenesis ...................................................................................................... 137 C. Gross Findings .................................................................................................. 137 D. Histology ........................................................................................................... 137 E. Clinical Manifestations ..................................................................................... 137 III. Urethral Polyp with Prostatic Type Epithelium ......................................................... 138 A. Definition .......................................................................................................... 138 B. Histogenesis ...................................................................................................... 138 C. Histology ........................................................................................................... 138 D. Histochemistry .................................................................................................. 138 E. Ultrastructure .................................................................................................... 139 F. Clinical Manifestations ..................................................................................... 139 IV. Nephrogenic Adenoma of Prostatic Urethra .............................................................. 140 A. Definition .......................................................................................................... 140 B. Etiology and Histogenesis ................................................................................ 140 C. Histology ........................................................................................................... 140 D. Clinical Manifestations ..................................................................................... 140 E. Microscopic Differential Diagnosis of Nephrogenic Adenoma and Well-Differentiated Adenocarcinoma of Prostate ............................................ 141 Malignant Tumors ................................................................................................................ 142 I. Transitional Cell Carcinoma ...................................................................................... 142 A. Histogenesis ...................................................................................................... 142

B.

Histology ........................................................................................................... 143 Differential Diagnosis of Poorly Differentiated Transitional Cell Carcinoma and Adenocarcinoma of Prostate ................................................... 146 D. Clinical Manifestations ..................................................................................... 146 Squamous Cell Carcinoma ......................................................................................... 147 A. Incidence ........................................................................................................... 147 B. Histogenesis ...................................................................................................... 147 C. Histology ........................................................................................................... 148 D. Spindle Cell Carcinoma (Squamous Cell Carcinoma Variant) ........................ 148 E. Clinical Manifestations ..................................................................................... 149 Adenosquamous Carcinoma ....................................................................................... 149 Adenocarcinoma of Ductal Origin ............................................................................. 150 A. Incidence ........................................................................................................... 150 B. Histology ........................................................................................................... 150 C. Adenocarcinoma of the Primary Ducts ............................................................. 150 D. Adenocarcinoma of the Secondary Ducts ......................................................... 150 E. Ductal Adenocarcinoma with Papillary and Glandular Patterns (So-Called "Endometrial Carcinoma") ............................................................. 150 F. Clinical Manifestations ..................................................................................... 154 Adenocarcinoma of Cowper's Glands ....................................................................... 154 A. Histology ........................................................................................................... 154 B. Clinical Manifestations ..................................................................................... 154 C.

II.

III. IV.

V.

Chapter 13 Adenocarcinoma of Prostate ............................................................................................. 155 I. Incidence and Mortality ............................................................................................. 155 A. Time Trends ...................................................................................................... 155 B. U.S. Black and White Comparison ................................................................... 155 C. U.S. Indians, Hispanics, and Orientals ............................................................. 157 D. Regional Variation of Prostate Cancer in the U.S ............................................ 157 E. International Comparisons ................................................................................ 157 F. Migratory Patterns ............................................................................................ 157 II. Etiology (Risk Factors) .............................................................................................. 157 A. Age .................................................................................................................... 157 B. Familial Factors ................................................................................................ 158 C. Sexual Factors ................................................................................................... 160 D. Hormonal Factors ............................................................................................. 160 E. Latent Carcinoma .............................................................................................. 161 F. Religion ............................................................................................................. 162 G. Diet ................................................................................................................... 162 H. Socioeconomic Status ....................................................................................... 163 I. Occupation ....................................................................................................... 163 J. Benign Nodular Hyperplasia (BNH) ................................................................ 163 K. Venereal Infection ............................................................................................ 163 III. Histogenesis and Evolution ........................................................................................ 164 A. Site of Origin .................................................................................................... 164 B. Precursor Lesions .............................................................................................. 164 1. Glandular Atrophy .................................................................................. 164 2. Derivation from Persisting Youthful-Appearing Glands ........................ 164 3. Atypical Hyperplasia ............................................................................... 165 C. Carcinoma Arising in AH ................................................................................. 166

D. E.

IV.

V.

VI.

Cytogenesis ....................................................................................................... 166 Categorization of Prostatic Carcinoma ............................................................. 166 1. Latent Carcinoma .................................................................................... 166 2. Incidental Carcinoma .............................................................................. 166 3. Occult Carcinoma ................................................................................... 167 4. Clinical Carcinoma ................................................................................. 167 Pathology .................................................................................................................... 167 A. Small Acinar Adenocarcinoma ......................................................................... 168 1. Growth Pattern ........................................................................................ 168 2. Peri glandular Stroma Propria .................................................................. 169 3. Stromal Invasion ..................................................................................... 170 4. Structural Uniformity .............................................................................. 172 5. Epithelial Lining ..................................................................................... 172 6. The Neoplastic Cell ................................................................................. 175 7. Nucleus .................................................................................................... l75 8. Nucleolus ................................................................................................ 175 9. Acinar Lumen ......................................................................................... 177 10. Mitosis ..................................................................................................... 178 11. Apoptosis ................................................................................................ 178 12. Small Acinar Adenocarcinoma Variants ................................................. 179 B. Large Acinar Adenocarcinoma ......................................................................... 179 C. Cribriform Adenocarcinoma ............................................................................. 183 D. Solid/ Trabecular Adenocarcinoma .................................................................. 187 E. Poorly Differentiated ("Undifferentiated") Adenocarcinoma .......................... 187 Grading ....................................................................................................................... 195 A. Mostofi (Armed Forces Institute of Pathology) System ................................... 195 B. Gleason (VA CUR G) Grading System .............................................................. 196 1. Critique of the Gleason System .............................................................. 197 C. The Gaeta Grading System ............................................................................... 197 D. Mayo Clinic Grading System ........................................................................... 198 E. M. D. Anderson Hospital (MDAH) Grading System ....................................... 198 F. University of Freiburg Grading System ........................................................... 199 G. Limitations of Grading ..................................................................................... 199 1. Histologic Heterogeneity of Prostatic Carcinoma .................................. 199 2. Progression of Tumors ............................................................................ 200 3. Reliability of Predictions ........................................................................ 200 H. New Methods of Grading ................................................................................. 201 I. Grading in Needle Aspiration Biopsy ............................................................... 201 Spread ......................................................................................................................... 201 A. Intraprostatic Growth ........................................................................................ 201 1. Stromal Invasion ..................................................................................... 202 2. Vascular Invasion .................................................................................... 202 3. Lymphatic Dissemination ....................................................................... 202 4. Intraductal Spread ................................................................................... 202 B. Incidental Carcinoma ........................................................................................ 203 C. Local Extension ................................................................................................ 207 I. Capsular Invasion .................................................................................... 207 2. Seminal Vesicle Invasion ........................................................................ 208 3. Rectal Invasion ........................................................................................ 208 D. Lymphatic Spread ............................................................................................. 209 E. Hematogenous Metastases ................................................................................ 211

VII. Staging ........................................................................................................................ 213 A. Staging Procedures ........................................................................................... 213 B. Staging Systems ................................................................................................ 215 VIII. Clinical Manifestations .............................................................................................. 217 A. Symptoms and Signs ......................................................................................... 217 B. Diagnosis .......................................................................................................... 218 I. Core Needle Biopsy ................................................................................ 218 2. Transurethral Resection of the Prostate (TURP) .................................... 218 3. Fine Needle Aspiration ........................................................................... 218 4. Flow Cytometry ...................................................................................... 219 5. Bone Scans .............................................................................................. 219 6. Tumor Markers ....................................................................................... 219 IX. Treatment ................................................................................................................... 220 A. Transurethral Resection of Prostate .................................................................. 220 B. Radical Prostatectomy ...................................................................................... 220 C. Radiation Therapy ............................................................................................ 221 I. External-Beam Megavoltage Irradiation ................................................. 221 2. Interstitial Irradiation .............................................................................. 221 3. Combined Interstitiai'"'Gold ("0.0 l ). However, when the severity of age-related changes was compared in either American or African black men with carcinoma and with no carcinoma, no significant differences were detected. In particular, no significant association between sclerotic atrophy and early prostatic carcinoma was found in this study. Sclerotic atrophy was less severe in black men from Washington, D.C., with invasive cancer than with no cancer (p >0.05). This study supported the notion that prostatic carcinoma does not originate from atrophic glands.

IV. SECONDARY HYPERPLASIA Secondary hyperplasia must be distinguished from postatrophic hyperplasia. Secondary hyperplasia is slightly more common in the outer prostate than in the inner prostate. In secondary hyperplasia the periglandular stroma exhibits considerable fibrous replacement of the smooth muscle fibers. The acini may be widely separated by delicate connective tissue bands. 17•18•142 The pathognomic change in this lesion is segmental intraacinar proliferation of the epithelium in an otherwise atrophic gland. The proliferating epithelial cells form papillary infoldings, the individual cells are tall columnar, the nuclei moderately enlarged, and the cytoplasm is clear (Figure 35). Secondary hyperplasia probably represents a renewed (secondary) growth of the epithelial cells following involution. 155

39 Chapter4

PROST A TIC CALCULI The first report of prostatic calculi was by Marcellus Donatus, 156 who in 1586 noted a case in which the patient was only able to pass some watery fluid at intercourse. The patient was found to have a calculus which obstructed the prostatic secretions. 156- 159 In 1619 Fabricius Bartholetus 160 reported a patient with complete urinary retention, "who had a calculus formed of retained spermatozoa about the vesical neck". The prostatic concretions were called corpora amyloidea by Virchow in 1852. 158 •161 The concretions gave a similar reaction to iodine and methyl violet as amyloid substances. In his textbook, Diseases of the Prostate, published in 1861, Sir Henry Thompson 62 devotes an entire chapter to prostatic concretions. He found these small bodies extensively distributed throughout the gland, and designated them, "corpora amylacea". Impregnation by calcium phosphate and carbonate gradually transformed the corpora amylacea to prostatic calculi. Apart from man, prostatic corpora amylacea also occurs in lagomorphs, boars, deer, and insectivores. 15 x Age incidence: All investigators reported a positive association between prostatic calculi and age. 157 · 158 •163 - 165 Concretions are rare in children, uncommon below age 30, and increase in number after age 40. Thomas and Robert, 157 in 1927, reviewed 305 cases of prostatic calcification. The ages were obtainable actually only for 280 patients. The greatest number of cases occurred in the 5th decade, viz., 73 (26% ), and the 4th, 5th, and 6th decades together accounted for more than 70% of cases. In a recent study, a statistically significant association was found between calcification and age in Jlack men from Washington, D.C.; Ibadan, Nigeria; and Accra, Ghana. 163 Prostatic stones can be divided into two types: primary or "endogenous" and secondary or "exogenous". Primary calculi are those that developed from prostatic secretions. Secondary stones are composed mainly of constituents of urine. 157 · 164- 168

I. ENDOGENOUS PROST A TIC STONES It was suggested first by Sir Henry Thompson 162 that prostatic calculi had developed from corpora amylacea through deposition of calcium salts. Perhaps the clearest pathological description of corpora amylacea was given by Moore. 169 He described the typical corpus as a smooth, round, light yellow-brown body with a diameter of approximately 250 J..Lm. This structure stained lightly with eosin and gave a brown reaction with iodine. The internal structure in its simplest form was either homogenous or delicately granular with or without a central core. Most of the corpora, however, revealed one or more concentric lines which divided the corpus into layers (Figure 36). The corpora amylacea consist of a mucoprotein matrix that is present in an acidic sulfated form. Neutral polysaccharides are also found in the matrix. This matrix is produced by the prostatic epithelium, and forms a round structure about which additional layers of matrix are being deposited. Gradually these bodies undergo calcification and give rise to prostatic calculi. 158

A. Anatomical Location of Prostatic Corpora Corpora amylacea and calculi are scattered throughout the entire prostate gland but are most common in the cephalic portion of the posterior lobe and within the larger ducts and acini of the laterallobes. 158 •169

· 40

Surgical Pathology of Prostate and Seminal Vesicles

FIGURE 36. Prostatic corpora amylaceae (psammoma bodies): round structures formed within the lumen of acini. Note concentric layering of corpora. (H & E stain. Original magnification x l25.)

B. Composition of Endogenous Prostatic Calculi Prostatic calculi may be formed by consolidation and calcification of preexisting corpora amylacea, or by direct calcification of precipitated glandular secretions. 164 In a recent study, 70 prostatic calculi were analyzed using crystallographic methods. 168 Crystallographic examination revealed that endogenous calculi had a compact nucleus and a peripheral zone composed of layers of apatite (mostly carboapatite), often mixed with layers of whitlockite and, Jess frequently, with other oxalic layers. With scanning electron microscopy and X-ray microanalysis, Vilches et al. 170 have identified two distinct types of endogenous prostatic stones. The first type of calculus had a lobular surface made up of small spheres. Microanalytically, it contained the following elements: Na, AI, Mg, S, P, Ca, and Zn. The highest peak corresponded to S. The second type of stone was polyfaceted with high peaks ofP and Ca. It was suggested that stones rich inS (the first type of calculi) could have originated from corpora amylacea. Type II calculi probably developed directly from prostatic secretions.

II. EXOGENOUS PROSTATIC STONES Calculi found in the prostatic urethra may have originated in the urinary bladder. Exogenous prostatic calculi are not true prostatic stones. These are composed predominantly of constituents of urine. 165 In their crystallographic study of prostatic calculi, Ramirez et al., 168 found in the exogenous stones an oxalic or uric nucleus which was surrounded by layers of apatite and whitlockite.

III. PREDISPOSING FACTORS IN CALCULOUS DISEASE OF PROSTATE Prostatic calculi have been reported in patients with nodular hyperplasia, carcinoma of the

41 prostate, and urethral stricture. 164• 171 The main predisposing factor in stone formation is benign nodular hyperplasia (BNH). 165 Compression and eventual obstruction of prostatic ducts result in stagnation of glandular secretions and stone formation.

IV. PROSTATIC CALCULI AND RECURRENT PROSTATITIS In patients with bacterial prostatitis, prostatic calculi can become infected. Bacteria embedded in the substance of calculi are a major source of recurrent urinary tract infections. To furnish evidence that prostatic stones are infected, the washed and crushed stones must be cultured for bacteria. Relapsing urinary tract infection caused by infected prostatic calculi can be cured only by surgical removal of stones. 165

V. THE ROLE OF HYPERCALCINURIA IN THE FORMATION OF PROST ATIC STONES It was reported that prostatic and urinary calculi, in the absence of other genitourinary diseases, are often related to hypercalcinuria. 159 In a recent study, the incidence of prostatic calcification in blacks in Washington, D.C. and selected African cities was examined by correlating necropsy specimen roentgenographs and pathologic findings. 163 The incidence of calcification in the prostate gland of black men from Washington, D.C.; Ibadan, Nigeria; and Accra, Ghana, West Africa, was assessed in a total of 874 prostate specimens. The frequency of calcification was significantly higher in the Washington, D.C., series than in the West African series in all age groups (p