Imaging of Synovial Tumors and Tumor-like Conditions (Medical Radiology) 3031336348, 9783031336348

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Medical Radiology · Diagnostic Imaging Series Editors: Hans-Ulrich Kauczor · Paul M. Parizel · Wilfred C.G. Peh

Filip M. Vanhoenacker Mohamed Fethi Ladeb   Editors

Imaging of Synovial Tumors and Tumor-like Conditions

Medical Radiology

Diagnostic Imaging Series Editors Hans-Ulrich Kauczor Paul M. Parizel Wilfred C. G. Peh

The book series Medical Radiology  – Diagnostic Imaging provides accurate and up-to-date overviews about the latest advances in the rapidly evolving field of diagnostic imaging and interventional radiology. Each volume is conceived as a practical and clinically useful reference book and is developed under the direction of an experienced editor, who is a world-renowned specialist in the field. Book chapters are written by expert authors in the field and are richly illustrated with high quality figures, tables and graphs. Editors and authors are committed to provide detailed and coherent information in a readily accessible and easy-to-understand format, directly applicable to daily practice. Medical Radiology  – Diagnostic Imaging covers all organ systems and addresses all modern imaging techniques and image-guided treatment modalities, as well as hot topics in management, workflow, and quality and safety issues in radiology and imaging. The judicious choice of relevant topics, the careful selection of expert editors and authors, and the emphasis on providing practically useful information, contribute to the wide appeal and ongoing success of the series. The series is indexed in Scopus.

Filip M. Vanhoenacker Mohamed Fethi Ladeb Editors

Imaging of Synovial Tumors and Tumor-like Conditions

Editors Filip M. Vanhoenacker Department of Radiology AZ Sint-Maarten Mechelen Mechelen, Belgium

Mohamed Fethi Ladeb Department of Radiology MT Kassab Institute of Orthopaedics Tunis, Tunisia

ISSN 0942-5373     ISSN 2197-4187 (electronic) Medical Radiology ISSN 2731-4677     ISSN 2731-4685 (electronic) Diagnostic Imaging ISBN 978-3-031-33634-8    ISBN 978-3-031-33635-5 (eBook) https://doi.org/10.1007/978-3-031-33635-5 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

It was indeed a great honor when professor Mohamed Fethi Ladeb asked me last year to co-edit a book on “Tumor and Tumor-like Conditions of the Synovium.” However, I asked him for some time to think, because the topic seemed to be very specific and might be considered a niche in the imaging of soft tissue tumors. Very soon after, I became very enthusiastic, as I realized that there is a very wide spectrum of diseases that may affect the synovium and the subject has not been covered so extensively before in other monographs or books. Together, we exchanged plans for the contents of the book and the concept was made within a very short period. This book contains five major parts. The first part is related to basic sciences and provides a comprehensive overview of the normal anatomy and histology of the synovium. Part II provides an up-to-date review of the current classification, pathology, genetics, and molecular biology of tumors of the synovium. Part III emphasizes the value of each imaging modality used for diagnosis, evaluation of the disease extent, follow-up, and monitoring of treatment. Part IV provides a systematic overview of the imaging features of the different tumor and tumor-like conditions of the synovium. Finally, Part V provides insights into the current treatment of these diseases. We are very grateful that the series editors of Medical Radiology-­ Diagnostic Imaging (Springer) professor Wilfred Peh and professor Paul Parizel entrusted us with the task to edit this book. We have been very fortunate to work with very talented and outstanding experts in the field of musculoskeletal imaging from the school of Tunis, Antwerp, and Ghent, supplemented by excellent contributions from highly esteemed researchers from the UK, France, Poland, and Singapore. We also thank the late Professor Arthur M. De Schepper who was regarded as the pope of “Imaging of Soft Tissue Tumors” for his mentorship during our early career in musculoskeletal (MSK) radiology and particularly in imaging of MSK tumors. We are also deeply indebted to the technicians and colleagues in our respective departments for providing us with high-quality images. We would like to express our special thanks to Springer-Verlag for the opportunity allowing us to edit this book. A special word of thanks goes to Professor Annemiek Snoeckx. Annemiek was one of my former residents and I am very proud that she now holds the position of chairperson of the Department of Radiology at Antwerp University Hospital. Last but not least, we want to thank our families for their constant support while we were working on this amazing project.

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Preface

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We hope that this work becomes a valuable and practical resource for graduated clinical radiologists, orthopedic surgeons, oncologists, pathologists as well as residents and researchers of these disciplines. We hope you enjoy reading it. Mechelen, Belgium Tunis, Tunisia  July 2022

Filip M. Vanhoenacker Mohamed Fethi Ladeb

Contents

Part I Anatomy and Histology of the Synovium Normal Anatomy and Histology ������������������������������������������������������������   3 Annelies Kerckhofs and Vasiliki Siozopoulou Part II Classification, Pathology, Genetics and Molecular Biology  Classification of Synovial Tumors According to WHO 2020���������������  15 Annelies Kerckhofs and Vasiliki Siozopoulou  Pathology, Genetics, and Molecular Biology ����������������������������������������  21 Vasiliki Siozopoulou Part III Imaging Modalities  Ultrasound of Synovial Tumors and Tumorlike Conditions����������������  47 Mohamed Chaabouni, Mohamed Fethi Ladeb, and Mouna Chelli Bouaziz Radiography and CT in Synovial Tumors and Tumorlike Conditions������������������������������������������������������������������������������������������������  61 Kirran Khalid, Radhesh Lalam, and Simranjeet Kaur Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions����������������������������������������������������������������������  79 A. R. Goossens, F. M. Vanhoenacker, and K. L. Verstraete  PET/CT in Synovial Tumors and Tumor-Like Conditions������������������ 105 Sarah K. Ceyssens Diagnostic Algorithm of Synovial Tumors and Tumor-Like Conditions �������������������������������������������������������������������������� 117 Eline De Smet and Filip Vanhoenacker

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Part IV Imaging of Synovial Tumors and Tumor-­Like Conditions of the Synovium Synovial Chondromatosis������������������������������������������������������������������������ 123 Guillaume J. M. Vangrinsven and Filip M. Vanhoenacker Tenosynovial Giant Cell Tumor�������������������������������������������������������������� 139 Hend Riahi, Mohamed Fethi Ladeb, and Mouna Chelli Bouaziz Lipoma Arborescens�������������������������������������������������������������������������������� 155 Mouna Chelli Bouaziz, Mohamed Fethi Ladeb, and Hend Riahi Synovial Hemangioma ���������������������������������������������������������������������������� 163 Mouna Chelli Bouaziz, Mohamed Fethi Ladeb, and Hend Riahi Synovial Chondrosarcoma���������������������������������������������������������������������� 173 Emna Labbène and Mohamed Fethi Ladeb  Synovial Metastasis and Lymphoma������������������������������������������������������ 181 Emna Labbène, Mouna Chelli Bouaziz, and Mohamed Fethi Ladeb Synovial Amyloidosis ������������������������������������������������������������������������������ 187 Youssef Boulil, François Glowacki, Ralph Abou Diwan, Huda Khizindar, and Anne Cotten  Synovial Cysts, Ganglion Cysts, and Bursae ���������������������������������������� 199 Filip M. Vanhoenacker  Mimics of Synovial Tumors Due to Trauma and Inflammation���������� 217 Magdalena Posadzy and Filip Vanhoenacker  Mimics of Synovial Tumors Due to Chronic Infection ������������������������ 241 Yet Yen Yan and Wilfred C. G. Peh Part V Treatment of Synovial Tumors and Tumor-­Like Conditions of the Synovium Surgical Treatment���������������������������������������������������������������������������������� 269 A. Van Beeck and Jozef Michielsen Nonsurgical Treatment���������������������������������������������������������������������������� 277 A. Van Beeck and J. Michielsen

Contents

Part I Anatomy and Histology of the Synovium

Normal Anatomy and Histology Annelies Kerckhofs and Vasiliki Siozopoulou

Contents

Abstract

1

Introduction

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2 2.1 2.2 2.3

Gross Anatomy and Function The Joints The Synovial Joint The Synovial Fluid

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3 3.1 3.2 3.3

Histology of the Synovium The Synovial Membrane Synoviocytes Subintima

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4 4.1 4.2

Function of the Normal Synovium Homeostasis of the Joint Cytokine Production

10 10 10

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Key Points

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References

A. Kerckhofs Department of Pathology, University Hospital Antwerp, Edegem, Belgium V. Siozopoulou (*) Department of Pathology, Cliniques Universitaires de Saint-Luc, Brussels, Belgium e-mail: [email protected]

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The synovium or synovial membrane is a distinct and rather complex structure that lines joints, tendons, fat pads, articular disks, and bursae. Its role is to maintain homeostasis. Its function and histomorphological aspect depend largely on the location and the particular joint. Synovium is found in synovial diarthrotic joints, where it namely forms the inner layer of the joint capsule. Histologically, the synovial membrane consists of two layers, a cellular intimal layer and a more fibrous subintimal layer. The intimal layer faces the articular space. Its main function is to produce and absorb the synovial fluid. The intima is composed of two types of cells, type A and type B synoviocytes. Type A cells serve as macrophages and are responsible for the phagocytosis of debris in the joint space. Type B synoviocytes are more dominantly present in the synovium and produce numerous extracellular matrix proteins, especially hyaluronic acid. The function of the subintimal layer, which is broad and contains blood vessels, nerves, and fibroblasts, is not yet fully understood. Synovium can be a site of development for a variety of benign, intermediate, and malignant tumors.

Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_407, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 12 April 2023

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A. Kerckhofs and V. Siozopoulou

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1

Introduction

Synovium is a distinct and specialized structure of the human body, and its main role is to maintain homeostasis of the synovial joints and the tendons. It is also called synovial stratum, synovial membrane, or stratum synoviale. The synovial membrane forms the lining of joint, bursae, and tendons. Its anatomy and histomorphology largely depend on the location and the type of function of the particular joint.

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Gross Anatomy and Function

2.1

The Joints

The ends of contiguous bones in combination with their adjacent soft tissue components, ligaments, tendons, cartilage, and synovium serve as a functioning unit: the joint (Mils 2020). Joints can be subdivided into categories depending on their function or their structure (Fig. 1). According to their functional properties, joints can be classified into three main types, which depends on their range of motion (Gordon Betts et  al. 2022). The diarthrotic joint is the most common type. It is also called movable joint and consists of two movable bone ends that form an Fig. 1 Classification of joints according to their function or their structure. (Created with BioRender)

articulate unit. The end surfaces of the bones in this type of joints are covered by a thin layer of cartilaginous tissue. The two bones that consist of this joint are held together by ligaments. This type of joint is also characterized by the presence of a synovial membrane (Mils 2020). Examples are the joints of the fingers, toes, hip, knee, elbow, and shoulder. The second and third types are the amphiarthrosis and the synarthrosis. The amphiarthrosis is a single movable joint, and it allows only partial movement; example of this type is the intervertebral disks. The synarthrosis is an immobile or otherwise called fixed joint, which does not allow any movement. Example of this type is the skull, where the bones form a firm structure in order to protect the brain. These two last types of joints are not covered by synovium and are therefore not discussed further. On the other hand, joints when classified according to their structure can be subdivided into three categories (Gordon Betts et al. 2022). A fibrous joint is made of bones that are immobile toward one another. They are linked by dense connective tissue without the presence of a joint cavity. For example, the bones of the skull form a fibrous joint. Cartilaginous joints, as the name suggests, are lined by cartilage, which can be either of fibrocartilaginous or hyaline type. The movement of this type of joint is limited. The

Normal Anatomy and Histology

pubic symphysis and the sternoclavicular joint are two examples of this type. The last and most common structural type of joint is the synovial joint. The main function of this joint is to maintain stability during its movement. It promotes a free and painless movement of the articular surfaces without impediment as well as an equitable distribution of load across the joints (Mils 2020).

2.2 The Synovial Joint The functional properties of a joint are associated with the architectural structure. As such, a synovial joint is a movable diarthrotic joint that bridges two bones together. The distal ends of these two bones are called the epiphysis (Gordon Betts et  al. 2022). The epiphyses of the bones involved in a joint do not touch one another but are connected through the joint capsule and its surrounding structures. At the epiphyseal sites of the bone rests a thin layer of hyaline cartilage. This serves as a cushion that prevents the bones from crushing into each other, especially when the joint endures considerable pressure, as for instance by jumping or running. Around the joint is located the joint capsule, which role is to maintain the joint stable. It consists of two layers: the inner layer which represents the synovial membrane and links the terminal ends of the bone through their respective hyaline cartilage. This layer mainly consists of a loose fibrous connective tissue. The second layer or the outer layer (stratum fibrosum) is the fibrous membrane and

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is made of a firmly dense connective tissue. This outer layer protects the joint and holds it together (Iwanaga et al. 2000). Figure 2 depicts the architecture of a synovial joint and its different compartments. While synovial membranes are always found in synovial joints, they can also be present in fat pads, articular disks, bursae, and tendon sheaths. Intra-articular fat pads are structures of closely packed adipose cells that are surrounded by a synovial lining. The function of fat pads is still not fully understood, though, in combination with the synovial cells, it may play an important role in the pathogenesis and progression of various pathologies, such as osteoarthritis (Greif et al. 2020). Apart from the fibrous capsule around the joint, articular disks or menisci, that can be seen within several joints, also promote the joint stability and allow a more even distribution of forces between the articulating surfaces (Chen et  al. 2017). They are made of a thin plate of fibrocartilage that is also lined by a layer of synoviocytes. They serve as a shock absorber especially at weight-bearing joints. The tendon sheath is a special layer of synovium that surrounds the tendons of the body (Doyle 1989). This protective synovial layer reduces friction and ensures mobility of the tendon and the joint. Finally, bursae are small subcutaneous or subtendinous bags filled with synovial fluid (Hirji et  al. 2011). They are found nearby synovial joints and function as a protective cushion

Fig. 2  A synovial joint and its compartments. (Created with BioRender)

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between bone structures and ligaments, tendons, and muscles. They reduce friction by providing extra lubrication and thereby supporting the articular joint.

2.3 The Synovial Fluid Inside the synovial joint (the articular cavity) circulates the synovial fluid (Mils 2020; Gordon Betts et al. 2022). This fluid is a viscous filtrate of plasma and hyaluronic acid. The fluid lubricates and feeds the articular cartilage with nutrients. Since the articular cartilage is an avascular structure, these nutrients are provided by the synovial fluid. When there is an increase in pressure affecting the joint, synovial fluid is pressed out of the synovial membrane and into the articular cavity to nourish the cartilage and greases the synovial joint. When the pressure reduces, the fluid will gradually decrease and flow away. This tidal movement of the synovial fluid provides a homeostatic equilibrium within the joint space.

3 Histology of the Synovium 3.1 The Synovial Membrane The inner layer of the joint capsule is called synovial membrane (Fig. 2). This is further subdivided into two specific layers, more particularly the cellular intimal layer and the fibrous subintimal layer (Smith 2011). The cellular intimal layer lies against the joint cavity and faces the articular space. It constitutes a smooth surface with occasional microvilli and plicae. These promote a broad range of motion and large absorption capacity to support the contact with the synovial fluid that is circulated within the joint cavity. The intimal layer is composed of intimal cells, also called the synoviocytes. Their main role is on the one hand to produce and on the other hand to absorb the synovial fluid from the joint cavity. They form a discontinuous layer leaving open spaces between the cells, through which the joint cavity focally directly communicates with the subintimal layer.

A. Kerckhofs and V. Siozopoulou

In general, epithelial cell layers rest on a basal cell membrane, which is not the case in synovium that lacks a basal membrane. This is probably due to its ectodermal derivation. Therefore, the intimal layer stands in close contact with the underlying interstitium/subintima. This promotes the exchange of solvents between the joint cavity and blood vessels that are located in the interstitium. The subintimal layer is less cellular than the intimal. It consists of loose fibroadipose and connective tissue that shows a rich vascularization with blood and lymphatic vessels (Fig.  3). The stroma contains also fibroblasts as well as inflammatory cells such as macrophages and mast cells. The subintimal layer can show a broad variety of architectural forms, depending on the local mechanical factors and the nature of the underlying tissue. Joints that are susceptible to high mechanical pressures present with a rather flattened hypocellular synovial membrane. Joints that endure less pressure display a redundant synovial membrane that is wider and rich in cellularity (Iwanaga et al. 2000; Zhang et al. 2020). The transition between the intima and subintima layer is no sharp. Beneath the intima, there can be an indistinct layer of type I collagen fibers that form a thin, indistinct layer, but in most cases, this is not recognizable under the light microscope. The synovial membrane can be subdivided into three main types (Smith 2011) that show different morphological features. The first and most common type is the areolar synovium. This type is defined by a relatively broad cellular intimal layer that covers an underlying richly vascularized loose connective tissue (subintima) with lymphatic vessels, blood vessels, and nerve fibers lying deep in the subintima (Smith et  al. 2003) (Fig. 4). This type is characterized by a surface area covered by plicae or villi that promotes the exchange of solvents. Beneath this areolar synovial membrane are located the tendon and the ligament of the joint or periosteum of the bones. The second type is the adipose synovium that can be found in fat pads. In this type of synovial membrane, the intimal layer is flattened and consists of only one layer of cells. The subintima is

Normal Anatomy and Histology

Fig. 3  (HE, 10×) Synovial membrane of the knee joint. The tissue is lined by a thin layer of synoviocytes (green arrow). The intima consists mainly of fibroblastic cells

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(blue arrow). In the subintima, there are blood vessels (red arrow)

Fig. 4  The histology of synovium. Synovium shows two layers: the intima and the subintima. The intima is mainly characterized by the presence of synoviocytes. The subintima is usually formed by fibroblasts. In the subintima circulate inflammatory cells. Therein are also blood vessels and nerves. (Created with BioRender)

less fibrous and rather adipocyte-rich with a vast capillary network (Fig.  5). Lastly, the fibrous synovium is characterized by a dense, fibrous-­ rich subintimal layer lined by a thin cellular intima. This type can be found in small joints, such as finger and foot joints (Smith 2011). Interestingly, besides the differences in morphology, each type displays also difference in the thickness of the intima and the subintima.

Inside the synovial joint (the articular cavity) circulates the synovial fluid (Gordon Betts et al. 2022; Mils 2020) (Fig. 3). This fluid is a viscous filtrate of plasma and hyaluronic acid. The fluid lubricates and feeds the articular cartilage with nutrients. Since the articular cartilage is an avascular structure, these nutrients are provided by the synovial fluid. When there is an increase in pressure affecting the joint, synovial fluid is

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A. Kerckhofs and V. Siozopoulou

Fig. 5  (HE, 10×) Synovial membrane with synoviocytes on the top (green arrows). The red arrow illustrates capillaries. In the subintima, we found many adipocytes (blue arrows)

pressed out of the synovial membrane and into the articular cavity to nourish the cartilage and greases the synovial joint. When the pressure reduces, the fluid will gradually decrease and flow away. This tidal movement of the synovial fluid provides a homeostatic equilibrium within the joint space.

3.2 Synoviocytes Till now, there is no consensus regarding the origin of synovial lining cells or synoviocytes. The embryologic origin of the synovial lining arises from the mesenchyme of the primordial skeletal blastema. It is derived from the bone marrow and undergoes maturation in the intimal layer (Henderson and Pettipher 1985). Electron microscopic studies have revealed that the intimal layer of the synovial membrane mainly consists of two cell types, type A and B synoviocytes. They are typically arranged in one to three cells thick layers and form an epithelium-like unit. As already mentioned, this distinct epithelium-like unit of synovium is discontinuous and does not lie on a basement membrane as other types of epithelial structures. The synoviocytes vary in size, shape, orientation, and number and can sometimes look pleiomorphic (Fig. 6).

Type A synovial cells (Fig. 7) can be compared to hepatic Kupffer cells; they serve as local macrophages that are responsible for the active phagocytosis of cellular debris in the joint space. The phagocytosis or pinocytosis can take place through special structures on the surface and within the cells such as microfilopodia and a prominent Golgi apparatus. The filopodia extent upward and form a ramifying network of overlapping processes devoid of junctional attachments. Apart from this function, type A cells also represent antigen-presenting cell. These cells are therefore in close contact to the joint cavity (Saraiva 2021). They express numerous cell surface markers of the monocyte-macrophage lineage, including CD11b, CD68, and CD14 (Athanasou and Quinn 1991). Histologically, type A cells are characterized by a dense nucleus, numerous Golgi structures, and scanty, rough endoplasmic reticulum (Henderson and Pettipher 1985). Type B synoviocytes (Fig.  7), also called fibroblast-like cells, are the dominant cell type in the synovial membrane. These cells have ovoid open nuclei and long cytoplasmic processes that circumferentially surround the nucleus. They present with a remarkable endoplasmic reticulum with regular ribosomes and cytoplasmic processes, which are broader and contain organelles, in contrast to type A cells. They do not present

Normal Anatomy and Histology

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Fig. 6  (HE, 60×) Synoviocytes or synovial cells as seen under the microscope. They form a four-cell layer on the top of the synovium. Under the light microscope, there is no distinction between type A and type B synoviocytes

Fig. 7  Types of synoviocytes (or synovial cells). On the left: type B synoviocytes. On the right: type A synoviocytes. (Created with BioRender)

with prominent filopodia as do type A cells. Type B cells synthesize numerous extracellular matrix proteins, including hyaluronan (hyaluronic acid), collagen, fibronectin, and laminin (Henderson and Pettipher 1985). Hyaluronan, a glycosaminoglycan, serves as a lubricant to maintain hydration of the joints. These cells also express numerous adhesion molecules, such as integrins, CD44 and CD55, that are markers of fibroblasts, as well as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule (ICAM)-1 (Saraiva 2021; Scanzello and Goldring 2012; O’Connell 2000; Smith et  al. 2003; Edwards 1995).

Both type A and type B synoviocytes are embedded in a collagen-rich extracellular matrix with pools of amorphous ground substance. This matrix contains collagen types III, IV, V, and VI; laminin; fibronectin; and proteoglycans (Revell et al. 1995; Ashhurst et al. 1991). Cells that contain features of both type A and type B have been described and have variously been termed as intermediate. The exact origin of type A and B cells is up for discussion in literature. They may represent cells of distinct origin and lineage or may be phenotypic variants of the same cell type. The presence of an intermediate cell type, with electron microscopic features

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common to both type A and B cells, has been used as an argument in favor of the latter hypothesis. The origin of synoviocytes is interesting since they are major effector cells in the joint damage that occurs in rheumatoid arthritis. Synoviocytes do not have a specific, pathognomonic immunohistochemical profile. Both types stain for vimentin and CD68. Vimentin is a constituent of the intermediate filament family of proteins and is expressed in normal mesenchymal cells as well as in tumors arising from these cells (Satelli and Li 2011). It is not exclusively expressed in synoviocytes; hence, it cannot be used as a marker of synovial differentiation. CD68 or cluster of differentiation 68 is a protein expressed in cells with monocyte lineage like macrophages (Holness and Simmons 1993). Synoviocytes do not express markers of myofibroblastic differentiation like smooth muscle actin (SMA) or desmin, nor epithelial markers like keratins or markers that support hematopoietic cell differentiation like CD45. Hence, the recognition of synovium and synoviocytes relies mainly on morphology.

3.3 Subintima Besides fibroblasts, blood vessels, and nerves, inflammatory cells may also be found in the subintimal tissue. These inflammatory cells are mainly lymphocytes, both from T-cell and from B-cell lineage (Smith et  al. 2003; Singh et  al. 2004). The role of these cells in the synovial membrane is unclear, yet it is thought that they may circulate through the normal synovium.

4 Function of the Normal Synovium 4.1 Homeostasis of the Joint The synovial membrane is formed in this particular way that it serves different functions, all to maintain a homeostasis of the synovial joint. To allow continuous movement of the joints, the synovial membrane must inhibit adhesion. The

A. Kerckhofs and V. Siozopoulou

most important factor in this process is the production of hyaluronic acid and lubricin by the intimal fibroblasts or type B synoviocytes. These fibroblasts also inhibit the formation of fibrin and therefore scarring. Another factor that serves the homeostasis of the joint cavity is the synovial fluid. This viscous and glycoprotein-rich fluid lubricates the cartilage and reduces the stress performed on the joint during exercise. It serves as a synovial cushion that is highly dependent on the presence of hyaluronic acid. When the joint cavity contains a generous amount of synovial fluid, the mechanical stress on the intimal fibroblasts will be reduced with the result of a downgrading of the hyaluronic acid. Homeostasis is thereby preserved.

4.2 Cytokine Production Normal synovial tissue can produce pro-­ inflammatory cytokines, like interleukins (IL), mainly IL-1 and IL-6 (Smith et al. 2003). Their role is to suppress any inflammatory process that may take place in the synovium. Receptor activator of nuclear factor kappa-Β ligand (RANKL) is an osteoclast differentiation factor that belongs to the tumor necrosis factor (TNF) (Anderson et al. 1997). RANKL controls bone regeneration and remodeling (Hanada et  al. 2011; Wada et  al. 2006). The expression of RANKL in synovial fibroblast and inflammatory cells is rather low and is thought to be responsible for the formation of osteoclasts and erosions during inflammatory arthritis (Danks et al. 2016).

5 Key Points • The synovial membrane, also called synovium or stratum synoviale, forms the lining of joints, bursae, fat pads, tendons, and articular disks. • Its function is to maintain the homeostasis of the synovial joint by production of the hyaluronic fluid. • The histomorphology of synovium is rather complex and not fully understood.

Normal Anatomy and Histology

• The synovial membrane is made out of two layers: a cellular intimal layer and a fibrous subintimal layer. • The intimal layer is composed of type A and type B synoviocytes. • The subintimal layer contains blood vessels, nerves, and inflammatory cells of which the function is rather unclear.

References Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L (1997) A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature 390(6656):175–179. https://doi.org/10.1038/36593 Ashhurst DE, Bland YS, Levick JR (1991) An immunohistochemical study of the collagens of rabbit synovial interstitium. J Rheumatol 18(11):1669–1672 Athanasou NA, Quinn J (1991) Immunocytochemical analysis of human synovial lining cells: phenotypic relation to other marrow derived cells. Ann Rheum Dis 50(5):311–315. https://doi.org/10.1136/ard.50.5.311 Betts JG, Young KA, Wise JA, Johnson E, Poe B, Kruse DH, Korol O, Johnson JE, Womble M, DeSaix P (2022) Anatomy and physiology, 2nd edn. OpenStax Chen S, Fu P, Wu H, Pei M (2017) Meniscus, articular cartilage and nucleus pulposus: a comparative review of cartilage-like tissues in anatomy, development and function. Cell Tissue Res 370(1):53–70. https://doi. org/10.1007/s00441-­017-­2613-­0 Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H (2016) RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann Rheum Dis 75(6):1187–1195. https://doi. org/10.1136/annrheumdis-­2014-­207137 Doyle JR (1989) Anatomy of the flexor tendon sheath and pulley system: a current review. J Hand Surg Am 14(2 Pt 2):349–351. https://doi. org/10.1016/0363-­5023(89)90110-­x Edwards JC (1995) Synovial intimal fibroblasts. Ann Rheum Dis 54(5):395–397. https://doi.org/10.1136/ ard.54.5.395 Greif DN, Kouroupis D, Murdock CJ, Griswold AJ, Kaplan LD, Best TM, Correa D (2020) Infrapatellar fat pad/ synovium complex in early-stage knee osteoarthritis: potential new target and source of therapeutic mesenchymal stem/stromal cells. Front Bioeng Biotechnol 8:860. https://doi.org/10.3389/fbioe.2020.00860 Hanada R, Hanada T, Sigl V, Schramek D, Penninger JM (2011) RANKL/RANK-beyond bones. J Mol

11 Med (Berl) 89(7):647–656. https://doi.org/10.1007/ s00109-­011-­0749-­z Henderson B, Pettipher ER (1985) The synovial lining cell: biology and pathobiology. Semin Arthritis Rheum 15(1):1–32. https://doi. org/10.1016/0049-­0172(85)90007-­1 Hirji Z, Hunjun JS, Choudur HN (2011) Imaging of the bursae. J Clin Imaging Sci 1:22. https://doi. org/10.4103/2156-­7514.80374 Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81(6):1607–1613 Iwanaga T, Shikichi M, Kitamura H, Yanase H, Nozawa-­ Inoue K (2000) Morphology and functional roles of synoviocytes in the joint. Arch Histol Cytol 63(1):17– 31. https://doi.org/10.1679/aohc.63.17 Mils SE (2020) Histology for pathologists, 5th edn. Wolters Kluwer India Pvt Ltd O’Connell JX (2000) Pathology of the synovium. Am J Clin Pathol 114(5):773–784. https://doi.org/10.1309/ LWW3-­5XK0-­FKG9-­HDRK Revell PA, al-Saffar N, Fish S, Osei D (1995) Extracellular matrix of the synovial intimal cell layer. Ann Rheum Dis 54(5):404–407. https://doi.org/10.1136/ ard.54.5.404 Saraiva F (2021) Ultrasound-guided synovial biopsy: a review. Front Med (Lausanne) 8:632224. https://doi. org/10.3389/fmed.2021.632224 Satelli A, Li S (2011) Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci 68(18):3033–3046. https://doi.org/10.1007/ s00018-­011-­0735-­1 Scanzello CR, Goldring SR (2012) The role of synovitis in osteoarthritis pathogenesis. Bone 51(2):249–257. https://doi.org/10.1016/j.bone.2012.02.012 Singh JA, Arayssi T, Duray P, Schumacher HR (2004) Immunohistochemistry of normal human knee synovium: a quantitative study. Ann Rheum Dis 63(7):785–790. https://doi.org/10.1136/ ard.2003.013383 Smith MD (2011) The normal synovium. Open Rheumatol J 5:100–106. https://doi. org/10.2174/1874312901105010100 Smith MD, Barg E, Weedon H, Papengelis V, Smeets T, Tak PP, Kraan M, Coleman M, Ahern MJ (2003) Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints. Ann Rheum Dis 62(4):303–307. https:// doi.org/10.1136/ard.62.4.303 Wada T, Nakashima T, Hiroshi N, Penninger JM (2006) RANKL-RANK signaling in osteoclastogenesis and bone disease. Trends Mol Med 12(1):17–25. https:// doi.org/10.1016/j.molmed.2005.11.007 Zhang H, Cai D, Bai X (2020) Macrophages regulate the progression of osteoarthritis. Osteoarthr Cartil 28(5):555–561. https://doi.org/10.1016/j. joca.2020.01.007

Part II Classification, Pathology, Genetics and Molecular Biology

Classification of Synovial Tumors According to WHO 2020 Annelies Kerckhofs and Vasiliki Siozopoulou

Contents

Abstract

1

Introduction

16

2

World Health Organization Classification

16

3

Grading

17

4

Redefinition and Reclassification

17

5

Key Points

18

References

A. Kerckhofs Department of Pathology, University Hospital Antwerp, Edegem, Belgium V. Siozopoulou (*) Department of Pathology, Cliniques Universitaires de Saint-Luc, Brussels, Belgium e-mail: [email protected]

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The synovium or synovial membrane can be a primary site of development of various tumor types. These tumors can be benign or malignant. While benign tumors behave in an indolent manner, malignant tumors show high metastatic potential and can therefore be lethal for the patients. The latest editions of the World Health Organization (WHO) classification for soft tissue and bone tumors initiated also the intermediate category, where tumors are neither indolent nor frankly malignant. In this category, tumors can be locally aggressive or can rarely metastasize, but the metastatic potential is in this case rather low. For the soft tissue tumors, grade and stage are better predictors of disease outcome than the histologic type. On the other hand, grading of bone tumors is very difficult to assess, giving their degree of heterogeneity in combination with the rarity of these neoplasms. Therefore, histologic (sub)type is in these cases a better prognostic marker. The only true synovial tumors are the fibroma of the tendon sheath and the tenosynovial giant cell tumor. In very rare instances, synovium can also be the primer site of involvement for a variety of soft tissue and bone tumors, either benign, intermediate, or malignant.

Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_408, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 22 April 2023

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1 Introduction The synovial membrane can give rise to neoplastic proliferations, both benign and malignant. Pure synovial tumors are rare, but a variety of mesenchymal tumors can present in the synovium. Non-tumoral conditions such as sarcoidosis, granuloma, synovitis, or gouty arthritis can also cause neoplastic proliferations within the synovium. Although these tumors and proliferative processes often demonstrate overlapping clinical presentations, they present with characteristic pathologic and molecular features, which facilitate accurate diagnosis. Multidisciplinary approach is the gold standard for a precise differentiation between these disease entities, leading to correct treatment choices for each patient separately.

2 World Health Organization Classification The World Health Organization for soft tissue (STS) and bone tumors (BT) divides these entities into four major categories in terms of their biological potential (WHO classification of Tumours Editorial Board 2020). The first category includes benign tumors. Benign mesenchymal neoplasms occur locally and are almost always cured by complete excision. For some tumors, full excision may not be possible, for instance due to their anatomical location, and in such cases, the lesion may recur locally. Even in these cases, it does not grow in a disruptive manner. The metastatic potential is not a feature of tumors in this category. Benign tumor of the synovium is fibroma of the tendon sheath. The second and third categories comprise the intermediate tumors. Intermediate tumors that are locally aggressive have the tendency to grow in an infiltrative and disruptive manner, making their total resection a difficult task. These lesions are therefore better treated with wide surgical resection, which, however, can lead to unfavorable aesthetic issues and/or functional disabilities. In

A. Kerckhofs and V. Siozopoulou

addition to the local aggressiveness, intermediate, rarely metastasizing tumors can give rise to metastatic disease. This metastatic potential does not exceed 2% in most reported cases. Prototype of a synovial tumor that belongs to the intermediate category is the tenosynovial giant cell tumor (localized and diffuse type). The tumors of the malignant category display a high tendency to disseminate to other organs. The 5-year survival rate for metastatic sarcomas in general is less than 16% (Bessen et al. 2019). Some tumors can vary in their morphology from low to high grade within the same tumor, or a tumor with an initial low-grade morphology may develop a more aggressive, high-grade phenotype. Malignant tumors of the synovium are exceedingly rare; to this category belongs the malignant variant of the tenosynovial giant cell tumor. Table 1 summarizes the tumors that can arise in the synovium, according to their behavior. Although primary tumors deriving from the synovial membrane are rare, other mesenchymal tumors can also arise within the synovium. Such tumors are synovial nodular fasciitis, synovial chondromatosis, synovial lipoma, synovial hemangioma, and synovial chondrosarcoma. Table 1  Benign, intermediate, and malignant tumors that arise in synovium Benign tumors arising in synovium Soft tissue tumors Fibroma of the tendon sheath Synovial nodular fasciitis Synovial hemangioma Synovial lipoma Intermediate tumors arising in synovium (locally aggressive or rarely metastasizing) Soft tissue tumors Tenosynovial giant cell tumor, localized and diffuse type Bone tumors Synovial chondromatosis Malignant tumors arising in synovium Soft tissue tumors Tenosynovial giant cell tumor, malignant type Synovial sarcoma Bone tumors Synovial chondrosarcoma

Classification of Synovial Tumors According to WHO 2020

3 Grading Benign and intermediate tumors display in the majority of the cases a favorable prognosis. On the other hand, malignant neoplasms of the synovium can behave in an aggressive manner. Thus, for malignant STS, the histologic grade and the stage are better predictors of disease outcome than the histologic type. Among the different grading systems, the most accepted to predict metastatic potential is the Federation Francaise des Centres de Lutte Contre le Cancer (FNCLCC) (Coindre et  al. 2001), at least for STS in adults. The FNCLCC takes three parameters into account; these are cell differentiation, necrosis, and mitotic activity. Each parameter is subject to a three-point score from 1 up to 3 (for the differentiation and the mitotic count) or from 0 up to 2 (for the presence and extent of necrosis), while the sum of these scores provides the grade of each tumor ranging from 1 up to 3. Tumors that are defined as grade 1 have the most favorable while grade 3 tumors the least favorable prognosis. Despite the fact that this is the most widely used grading system for the STS, also recommended from the College of American Pathologists (CAP) and the American Joint Committee on Cancer (AJCC) (Rubin et  al. 2010b), its main weakness is the lack of definition of cell differentiation, since for many tumors the differentiation line remains unknown (Deyrup and Weiss 2006). In contrast to STS, BTs are in general not graded. Bone tumors are very heterogenous making standardization of grading system very difficult to assess. For this tumor category, histological subtype determines the clinical behavior and thus also the grade (Rubin et al. 2010a; Mangham and Athanasou 2011).

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4 Redefinition and Reclassification Given the difficulty of defining the line of differentiation for many tumors, in recent years, effort has been made in order to characterize their molecular profiles. Consequently, the latest version of the WHO has adopted molecular classification into different soft tissue and bone tumors, which in some instances has led to redefinition of categories but also tumor types within the categories. In terms of synovium, synovial sarcoma is thought to be a tumor arising from synovium because of its tendency to occur around the joint of the knee, hence its name. With the advance of molecular science, it has been proven that the vast majority of synovial sarcomas have a unique t(X;18)(p11.2;q11.2) translocation that results in the fusion of the gene SYT on chromosome 18 to three closely related genes, namely SSX1, SSX2, and SSX4, on the X chromosome (Clark et  al. 1994; Crew et  al. 1995; Skytting et  al. 1999). Despite this molecular definition, the cell of origin of synovial sarcoma remains unknown. As such, its nomenclature is a misnomer since. We have described a primary cardiac synovial sarcoma of the interatrial septum (De Hous et  al. 2018), which emphasizes the fact that it can arise laterally anywhere in the human body. Intra-­ articular synovial sarcomas are exceedingly rare. Lipoma arborescens is an uncommon pseudotumoral synovial lesion. It presents with a villous proliferation of the synovial membrane and infiltration of the subsynovial tissue with adipose cells (Davies and Blewitt 2005) (Fig.  1a, b). Although previously described as a tumoral condition, the etiology is unknown, thought to be associated with trauma, degenerative joint dis-

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a

b

Fig. 1 (a) (HE, 0.5×): Synovial membrane with obvious villous appearance. (b) (HE, 2×): On higher magnification, we see replacement of the subintimal layer through adipose tissue (cells with clear cytoplasm)

ease, or chronic arthritis (Singh 2020). Nowadays, it is considered as a hyperplastic lesion and is not a WHO diagnosis.

5 Key Points • Synovium can be the site of development of a variety of soft tissue and bone tumors. • According to the WHO classification schemes, these tumors can be subdivided into four categories: the benign, the intermediate locally aggressive, the intermediate rarely metastasizing, and the malignant.

• For soft tissue tumors, grade and stage are the best prognostic factors. • For bone tumor, histologic (sub)type is the best prognostic factor.

References Bessen T, Caughey GE, Shakib S, Potter JA, Reid J, Farshid G, Roder D, Neuhaus SJ (2019) A population-­ based study of soft tissue sarcoma incidence and survival in Australia: an analysis of 26,970 cases. Cancer Epidemiol 63:101590. https://doi.org/10.1016/j. canep.2019.101590 Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM, Gusterson BA, Cooper CS (1994) Identification

Classification of Synovial Tumors According to WHO 2020 of novel genes, SYT and SSX, involved in the t(X;18) (p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 7(4):502–508. https://doi. org/10.1038/ng0894-­502 Coindre JM, Terrier P, Guillou L, Le Doussal V, Collin F, Ranchere D, Sastre X, Vilain MO, Bonichon F, N’Guyen Bui B (2001) Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer 91(10):1914–1926. https://doi. org/10.1002/1097-­0142(20010515)91:103.0.co;2-­3 Crew AJ, Clark J, Fisher C, Gill S, Grimer R, Chand A, Shipley J, Gusterson BA, Cooper CS (1995) Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppelassociated box in human synovial sarcoma. EMBO J 14(10):2333–2340 Davies AP, Blewitt N (2005) Lipoma arborescens of the knee. Knee 12(5):394–396. https://doi.org/10.1016/j. knee.2005.01.003 De Hous N, Paelinck B, Van den Brande J, Siozopoulou V, Laga S (2018) Primary cardiac synovial sarcoma of the interatrial septum. J Card Surg 33(7):391–392. https://doi.org/10.1111/jocs.13733 Deyrup AT, Weiss SW (2006) Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world. Histopathology 48(1):42–50. https://doi. org/10.1111/j.1365-­2559.2005.02288.x

19 Mangham DC, Athanasou NA (2011) Guidelines for histopathological specimen examination and diagnostic reporting of primary bone tumours. Clin Sarcoma Res 1(1):6. https://doi.org/10.1186/2045-­3329-­1-­6 Rubin BP, Antonescu CR, Gannon FH, Hunt JL, Inwards CY, Klein MJ, Kneisl JS, Montag AG, Peabody TD, Reith JD, Rosenberg AE, Krausz T, Members of the Cancer Committee CoAP (2010a) Protocol for the examination of specimens from patients with tumors of bone. Arch Pathol Lab Med 134(4):e1–e7. https:// doi.org/10.1043/1543-­2165-­134.4.e1 Rubin BP, Cooper K, Fletcher CD, Folpe AL, Gannon FH, Hunt JL, Lazar AJ, Montag AG, Peabody TD, Pollock RE, Reith JD, Qualman SJ, Rosenberg AE, Weiss SW, Krausz T, Members of the Cancer Committee CoAP (2010b) Protocol for the examination of specimens from patients with tumors of soft tissue. Arch Pathol Lab Med 134(4):e31–e39. https:// doi.org/10.1043/1543-­2165-­134.4.e31 Singh C (2020) Lipoma arborescens. PathologyOutlinescom. https://www.pathologyoutlines.com/topic/softtissueadiposelipomaarb.html Skytting B, Nilsson G, Brodin B, Xie Y, Lundeberg J, Uhlen M, Larsson O (1999) A novel fusion gene, SYT-SSX4, in synovial sarcoma. J Natl Cancer Inst 91(11):974–975. https://doi.org/10.1093/ jnci/91.11.974 WHO classification of Tumours Editorial Board (2020) WHO classification of tumours. Soft tissue and bone tumours, WHO classification of tumours, vol 3, 5th edn. IARC Publications, Lyon, France

Pathology, Genetics, and Molecular Biology Vasiliki Siozopoulou

Contents

Abstract

1

Introduction

22

2 2.1

Fibroma of the Tendon Sheath Genetics and Molecular Biology

22 24

3 3.1

Synovial (Intra-articular) Nodular Fasciitis Genetics and Molecular Biology

25 26

4 4.1

Synovial Hemangioma Genetics and Molecular Biology

27 28

5 5.1

Synovial Lipoma Genetics and Molecular Biology

28 28

6 6.1

Synovial Chondromatosis Genetics and Molecular Biology

29 30

7 7.1

Synovial Sarcoma Genetics and Molecular Biology

30 31

8 8.1

Tenosynovial Giant Cell Tumor Genetics and Molecular Biology

31 35

9 9.1

Synovial Chondrosarcoma Genetics and Molecular Biology

36 36

10

Other Very Rare Mesenchymal Tumors Arising in Synovium

37

11

Lymphomas

37

12

Metastatic Disease in the Synovium

37

13

Key Points

38

References

38

The synovial membrane is a limited space in the human body, yet therein can arise a variety of benign, intermediate, and malignant soft tissue and bone tumors. Each of these tumors shows different and in some instances unique histomorphologic features that help to recognize and differentiate them from other tumor types. Their molecular profile has also been extensively analyzed, and specific driver ontogenetic mechanisms have been described, establishing their neoplastic nature. The only true primary neoplasms of the synovium are fibroma of the tendon sheath and tenosynovial giant cell tumor. In very rare instances, other tumor types can also primarily arise in synovium, presumably from cells that are located or circulated within the synovial membrane, like endothelial cells, adipose cells, and cells of lymphopoietic origin. Synovium can also be a site of metastatic disease involvement. In all instances, a multidisciplinary team approach where history, clinical, radiological, and pathological image, accompanied by molecular testing, will be discussed is the key to the correct diagnosis.

V. Siozopoulou (*) Department of Pathology, Cliniques Universitaires de Saint-Luc, Brussels, Belgium e-mail: [email protected] Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_409, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 22 April 2023

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V. Siozopoulou

22 Table 1 Molecular alterations of lesions arise in synovium

Mechanism Gene rearrangements and fusions

Structural abnormalities

1 Introduction Despite the fact that synovial tumors arise within the same limited space, they vary in terms of their pathological features as well as their genetics and molecular biology. In this chapter, we will discuss each tumor that can arise in the synovium according to their nature—benign, intermediate, and malignant— as discussed in the chapter “Classification of Synovial Tumors According to WHO 2020”, with emphasis on their molecular profile. The molecular aspects of the tumor that are discussed in this chapter are summarized in Table 1.

2 Fibroma of the Tendon Sheath Synovium is the connective tissue that lines the structures in the joints. A tendon sheath is a subtype of synovium that specifically lines tendons (Cohen and Kaplan 1987).

Molecular alteration t(2;11)(q31-32;q12) t(9;11)(p24;q13-14) t(4;10)(p16-q24;q22) USP6 rearrangements with different fusion partners USP6-MYH9 USP6-COL1A1 FN1-ACVR2A FN1-NFATc2 FN1-ACVR2A KMT2A-BCOR SYTT-SSX1 SYT-SSX2 SYT-SSX4 CSF1-FN1 CSF1-COL6A3 CSF1-KCNMA1 CSF1-S100A10 NIPBL-ERG FN1-ROS1 YAP1-MAML2 12q13-q15 16q21 Loss of material in 13q Ring chromosomes

Tumor type Fibroma of the tendon sheath

Synovial nodular fasciitis Synovial chondromatosis Synovial chondrosarcoma Synovial sarcoma

Tenosynovial giant cell tumor

Lipoma

Fibroma of the tendon sheath is a benign soft tissue tumor. There is no malignant counterpart. It consists of a fibroblastic/myofibroblastic proliferation that is typically attached to a tendon. It may occur throughout the human body but has a predilection for the palmar aspect of the wrist and the hand (Chung and Enzinger 1979), while intra-articular locations at the elbow, knee, and ankle joints have also been rarely reported (Park et  al. 2011; Kundangar et al. 2011; Ciatti and Mariani 2009). In their vast majority, these tumors affect adults between 20 and 50  years old while they infrequently occur in children (Shibayama et al. 2020). Due to their benign nature, they grow very slow reaching up to 3 cm. On macroscopy, the lesions are lobulated, well circumscribed, and firm (Fig. 1). The microscopy reveals a spindle cell morphology (Fig.  2). The cells are slender; the nucleus has pointed ends, mainly without a nucleolus, and is embedded in abundant eosinophilic cytoplasm with undistinctive cytoplasmic borders. Sometimes, degenerative, pleiomorphic cells can be present. Still,

Pathology, Genetics, and Molecular Biology

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Fig. 1  Overview of a fibroma of the tendon sheath. The lesion is well circumscribed and is covered by a thin fibrous capsule (blue arrow). The lesion is in close proximity with the tendon (yellow arrows) (HE, 2×)

Fig. 2  Closer view of Fig. 1 shows a proliferation of spindle cells without nuclear pleiomorphism. Between the tumor cells, one can find collagen fibers (circle) (HE, 10×)

mitotic activity is not a feature, neither is necrosis. The cellularity of the neoplasm varies. Most cases are paucicellular and contain dense collagen matrix with scattered slit-like vessels. Some lesions are more cellular, usually at the periphery. Changes like osseous and chondroid metaplasia or even cystic and myxoid degeneration have also been described (WHO Classification of Tumours Editorial Board 2020).

The diagnosis is usually based on the morphology in correlation with the clinical and microscopical image (firm circumscribed lesion attached to the tendon), while ancillary techniques like immunohistochemistry are in most cases not warranted. Immunohistochemically, the cells may express smooth muscle actin (SMA) while myogenic markers like desmin and muscle-­ specific actin are negative.

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The differential diagnosis encompasses tenosynovial giant cell tumor (TSGCT) (localized type), synovial nodular fasciitis, and desmoplastic fibroblastoma. Tenosynovial giant cell tumor shows monomorphous rounded cells next to giant cells and can contain iron pigmentation. Nodular fasciitis displays a feathery growing pattern, usually with obvious red blood extravasation and a lymphocytic infiltrate throughout the lesion. Both entities will be discussed in detail in the following sections. Desmoplastic fibroblastoma can share morphologic features with fibroma of the tendon sheath. Both represent fibroblastic/myofibroblastic proliferations, and on molecular level, these two entities seem to share same genetic events (Nakayama et  al. 2021b). Still the localization differs as desmoplastic fibroblastoma primarily arises in the subcutaneous tissue of the upper extremities. Moreover, they display strong nuclear positivity for the immunohistochemical staining against FOSL1, a protein coding gene, while desmoplastic fibromas are herewith negative. Although a benign lesion, fibroma of the tendon sheath can recur after surgery in 5–10% of the cases. It has been suggested that the recurrence rate is probably underestimated because of the short-term follow-up and could be diminished with more aggressive surgical excisions (Ludke et al. 2020). Fig. 3 Schematic representation of a translocation. This happens when a piece of one chromosome breaks off and attaches to another chromosome

V. Siozopoulou

2.1 Genetics and Molecular Biology Genetic investigation of fibromas of the tendon sheath was first conducted in order to determine whether the tumors represent a reactive fibrosing process or whether they are neoplastic. To date, only few genetic alterations have been reported. In all cases, it concerns a translocation and mainly evolves chromosome 11 (Dal Cin et  al. 1998; Nishio et al. 2014). A translocation occurs when a piece of one chromosome breaks off and attaches to another chromosome (Fig.  3). The first case that was published showed a t(2;11) (q31-32;q12) rearrangement (Dal Cin et  al. 1998), while many years later, another report presented a t(9;11)(p24;q13-14) translocation (Nishio et  al. 2014). Lately, a rearrangement involving genes 4 and 10 was described t(4;10) (p16-q24;q22) (Rubinstein et  al. 2019). As of yet, the clinical relevance of this translocation is unknown. Cytogenetic studies have demonstrated the presence of 11q12 rearrangements and an identical t(2;11)(q31;q12) translocation in desmoplastic fibroblastoma (Nakayama et al. 2021b), which can show morphological similarities with fibroma of the tendon sheath. Some cellular types of fibromas of the tendon sheath seem to harbor fusions of the USP6 gene

Pathology, Genetics, and Molecular Biology

(Pizem et al. 2021; Mantilla et al. 2021; Eisenberg et al. 2021; Carter et al. 2016). Tumors with these fusions tend to be more cellular. There are many different fusion partners described. These fusions are well known by nodular fasciitis (Pizem et al. 2021; Eisenberg et  al. 2021; Nakayama et  al. 2021a), raising the question of whether any of these tumors actually represent the case of synovial nodular fasciitis. Despite the effort to genetically characterize the fibromas of the tendon sheath, the etiology of the tumors remains unknown.

3 Synovial (Intra-articular) Nodular Fasciitis Nodular fasciitis is a fibroblastic/myofibroblastic proliferation with a benign course. In the majority of the cases, it arises in the fascia and extends into the subcutaneous fat tissue. Most common involved locations are upper extremities, trunk, and head and neck area. In rare occasions, it can occur in the skin or even intravascularly (WHO Classification of Tumours Editorial Board 2020). Intra-articular nodular fasciitis is a very uncommon event, and occurrence in such cases may lead to misdiagnosis (Wang et al. 2019; Hornick and Fletcher 2006). To date, less than 30 cases have been reported in the English literature

25

(Yamamoto et  al. 2001; Hornick and Fletcher 2006; Ladermann et al. 2008; Hagino et al. 2010; Matsuzaki et al. 2012; Harish et al. 2011; Strazar et  al. 2013, 2021; Ko et  al. 2013; Gans et  al. 2014; Chan et  al. 2014; Miyama et  al. 2021; Choughri et al. 2019; Nakamura et al. 2019; Igrec et al. 2020). The joints of the elbow, the finger, the shoulder, and the hip have been reported as sites of appearance, but still the most common involved is the knee joint. It is a very fast-­growing lesion with a median of 4 months prior to surgery (Wang et al. 2019) and depending on the location can reach from 2 up to 5  cm before starting to give clinical symptoms. Individuals are slightly younger than in “common” nodular fasciitis, with a median of 26 years. The pathological findings are those of nodular vasculitis at any other site. The lesion is usually well circumscribed (Fig. 4), but it is never encapsulated. A focal infiltrative growth pattern may be seen. It consists of plump spindle cells with bland ovoid nuclei. Mitotic activity is usually present, and depending on the time of duration, it can be very prominent, but atypical mitotic figures are not a sign. The cells are typically growing in a loose, “feather-­ like” or “culture-like” pattern. Cystic degeneration and myxoid changes are also described. Thick collagen bundles can be seen in between the tumor cells. The lesion displays a lympho-

Fig. 4  Example of an extra-articular nodular fasciitis; the intra-articular cases show the same morphology. The lesion is well circumscribed (HE, 5×)

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V. Siozopoulou

Fig. 5  Closer view of Fig. 4. The lesion shows a rather low cellularity with obvious myxoid changes (yellow arrow) and extravasation of red blood cells (blue arrow).

The lesion presented a USP6 translocation, as shown by molecular techniques (FISH) (HE, 20×)

cytic infiltration, often with histiocytes and giant cells, but plasma cells are not a feature. Very often, extravasation of red blood cells can be observed, which in some instances can be prominent (Fig. 5). The lesion does not show pathognomonic immunohistochemical patterns; thus, immunohistochemistry is usually not needed to confirm the diagnosis, but rather to exclude other entities. Hence, SMA can be positive, and in some instances also cluster of differentiation 68 (CD68) which is expressed in cells with monocytic lineage. Desmin is rarely reported, but the expression pattern is rather focal. Immunohistochemical markers with a more specific differentiation line have not been described. The differential diagnosis contains other tumors arising in the joints, such as fibroma of the tendon sheath, synovial chondromatosis, and tenosynovial giant cell tumor, as well as lesions arising outside synovium that resample morphologically nodular fasciitis, such as desmoid fibromatosis. Desmoid fibromatosis has a more infiltrative growth pattern with lymphoid aggregates at the periphery of the lesion (Siozopoulou et  al. 2019) and has a distinctive immunohistochemical profile. Namely, it shows a nuclear positivity for beta-catenin, which correlates with

activating mutations of the Wnt signaling pathway (Amini Nik et al. 2005). Given its inflamed phenotype, nodular fasciitis can sometimes clinically misinterpret as inflammatory arthritis or lymphoma; however, the pathology of these lesions is distinct. (Intra-articular) nodular fasciitis is a benign and self-limiting tumoral growth. The therapy is surgical excision with no recurrences up to date (Wang et al. 2019).

3.1 Genetics and Molecular Biology Nodular fasciitis was considered a reactive lesion, given its benign course despite its rapid growth and based on the fact that in some cases it was reported after injury. Recently, chromosomal alterations resulting in a fusion of the USP6 gene, which is located on the p13.2 region of the chromosome 17, have been described in nearly all cases. USP6 is a deubiquitinating protease, which plays a role in cell trafficking, protein degradation, signaling pathway, and inflammation (WHO Classification of Tumours Editorial Board 2020). A fusion can be a result of a chromosomal translocation, deletion,

Pathology, Genetics, and Molecular Biology

or inversion leading to a chimeric protein, which in some instances can be oncogenic. Accordingly, cases of intra-articular nodular fasciitis that have been screened with molecular techniques demonstrated the same findings. In the vast majority of the cases (five reported cases), the fusion partner is the MYH9 gene (22q12.3), which provides instructions for making myosin-9 protein (Simons et  al. 1991; Miyama et  al. 2021; Igrec et  al. 2020; Strazar et  al. 2021). One case presented COL1A1 as fusion partner (Strazar et al. 2021). This gene is located at the long arm of the chromosome 17 (17q21.3-22.1) and provides instructions for making part of a large molecule called type I collagen (Greco et al. 1998). There is doubt if some fibromas of the tendon sheath with cellular morphology displaying USP6 fusions represent in fact intra-articular nodular fasciitis.

4 Synovial Hemangioma Synovial hemangioma is a very rare entity arising in any synovium-lined surface, including joints, bursae, and tendon sheath (Greenspan and Grainger 2018). Among these, the joint of the

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knee is the predilection site. The average age of presentation differs in various studies ranging from 12.4 to 25  years (Muramatsu et  al. 2019; Devaney et al. 1993). Hemangioma is the result of proliferation of endothelial cells, i.e., cells that line blood vessels of any size. Synovial hemangiomas are subject to various classifications. According to their pathological appearance, they are classified into capillary, cavernous, mixed, and venous (Devaney et al. 1993). This classification however does not have a prognostic value (Muramatsu et al. 2019). Based on their anatomic site, synovial hemangiomas are subdivided into circumscribed (usually cavernous type) and diffuse (usually capillary type), where the latter is infiltrative into the surrounding tissues. Another classification scheme divides the tumors into patellofemoral joint, popliteal, and diffuse types (Muramatsu et al. 2019). The former represents the circumscribed lesions, the latter the diffuse lesions, while the popliteal is juxta-articular. Synovial hemangiomas arise from the mesenchymal tissue of the subsynovial layer. It shows a proliferation of blood vessels of variable sizes, lined by one layer of not atypical endothelial cells (Fig. 6). Reactive endothelial atypia may be present, but true pleiomorphism or increased

Fig. 6  Synovial hemangioma displays a proliferation of synovial layer, which is covered by synovial lining (green blood vessels (red arrow) lined by one layer of non-­ arrow) (HE, 20×) atypical endothelial cells. The lesion is located in the sub-

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mitotic activity is not a feature. In some instances, thrombi can be present in the lumen of the vessels. Between the proliferating blood vessels, there is variable amount of adipose or fibrous tissue, while the overlying synovium can be ­ hyperplastic (Greenspan and Grainger 2018). The clinical differential diagnosis includes inflammatory processes such as rheumatoid arthritis, but also neoplastic diseases as synovial chondromatosis and tenosynovial giant cell tumor. Still, from a pathologic point of view, these entities can easily be excluded given their dissimilar morphology. Purely morphologically, one should exclude angiosarcoma; however, primary angiosarcomas of the synovium are not reported to date. The prognosis of these lesions is excellent, with surgery being the gold standard, without reported recurrences.

4.1 Genetics and Molecular Biology Synovial hemangiomas are not (yet) genetically described. Hence, there are discrepancies about the pathogenesis of these lesions, whether they represent true neoplasm, malformations, or hamartomas (Dalmonte et  al. 2012; Kroner and Fruensgaard 1989).

5 Synovial Lipoma While lipoma is one of the most frequent benign mesenchymal tumors that arise anywhere in the human body (Marui et  al. 2002), true intra-­ articular synovial lipomas are rare and only limited number of cases have been reported in the literature. They show a predilection for the knee joint (Kheok and Ong 2017), yet limited cases have been reported in other joints (Poorteman et  al. 2015; Margheritini et  al. 1998; Pavithra et al. 2014). The age range varies, but it mostly affects middle-age adults. The lesion is benign and is asymptomatic unless it gets very large (Dalla Rosa and Nogales Zafra 2019).

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The morphology of the intra-articular lipomas is identical to the lipomas arising elsewhere in the human body. They form a nodule that is surrounded by a thin, distinct fibrous capsule. The lesion is well defined and does not show infiltrative borders (Kheok and Ong 2017). Histology reveals a lesion consisting of numerous medium-sized, unilocular adipose cells. The cells show discrete variation in shape and size. Adipose cells accumulate fat droplets into their cytoplasm, which pushes the nucleus away. This is why the nucleus in these cells is located at the periphery of the cell. Although the cytoplasm contains large amount of fat, under the microscope, it looks clear and empty. This is due to the extraction of the fat during the process of fixation. In some cases, the lesion can be separated in large nodules by thin fibrous septa. These display a low cellularity and show no atypia. The lesion also contains thin-walled blood vessels. Figure 7 depicts the microscopy of a lipoma. While recognition of fat tissue is straightforward under the microscope, the diagnosis of an intra-articular lipoma is not easy, based solely on histomorphology. The main differential diagnosis is a lipoma arborescens. This is a non-tumoral, reactive lesion that has a villous appearance, in contrast to lipoma which is well circumscribed (Kheok and Ong 2017; Dalla Rosa and Nogales Zafra 2019).

5.1 Genetics and Molecular Biology The molecular biology of the true intra-articular lipomas has not been a subject of research. In general, lipomas show three major cytogenetic patterns (Sreekantaiah et al. 1991; Bartuma et al. 2007; Billing et al. 2008). The first are the structural rearrangements, mainly of chromosome bands 12q13-q15 in two-thirds of the cases and less common of 6p21. The second is loss of material of the short arm on chromosome 13 (13q). The third shows supernumerary ring chromosomes. In some instances, combination of these abnormalities has been described.

Pathology, Genetics, and Molecular Biology

Fig. 7  Microscopic view of a lipoma. There is proliferation of adipose cells with very little variation in size. Under the microscope, the cytoplasm looks empty, but

6 Synovial Chondromatosis

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this is due to fixation procedure. The nucleus is usually pushed at the periphery of the cell (blue arrow). Fibrous septa may also be present (yellow arrow) (HE, 10×)

periarticular loose bodies (Jung et  al. 2007). It has been suggested that the majority of loose Primary synovial chondromatosis is a rather bodies are produced at the transitional zone infrequent, locally aggressive tumor arising in between the synovium and articular cartilage the synovial membrane of the joints, bursae, and given the high density of stem cells in this area tendon sheath (Hermann et al. 1995). It can arise (Tokis et  al. 2007). The nodules have a smooth within the joint space, in the subsynovial tissue, and regular surface. As already discussed, a numor extra-articular. When the lesion appears extra-­ ber of the nodules will undergo calcification or articular, it is called tenosynovial chondromato- ossification. Microscopically, the nodules consist sis. The neoplasm affects mostly adults. Many of a chondroid matrix, wherein chondrocytes are different locations have been assigned, with the present forming clusters, and are surrounded by majority of the neoplasm appearing in the knee synovial tissue. Although chondrocytes may (70%), followed by the hip (20%), shoulder, present some degree of atypia, nuclear pleiomorelbow, ankle, and wrist (Neumann et  al. 2016). phism and loss of chondrocyte clustering are not These extra-articular lesions show a strong predi- features of benign lesions and infiltration of adjalection for the joints of the hand and the feet cent bone should raise suspicion of malignancy (Bertoni et al. 1991). (Fetsch et al. 2003). Immunohistochemistry is not applicable in Cartilaginous nodules may be subject to calcification or ossification (Davis et al. 1998), hence this context. Synovial chondromatosis, sometimes also the term osteochondromatosis. However, this referred to as secondary chondromatosis, should nomenclature is currently not recommended anybe distinguished from multiple osteochondral more (WHO Classification of Tumours Editorial loose bodies. Loose bodies are small fragments Board 2020). of cartilage or bone that move freely in joint fluid, The lesion starts as sessile cartilaginous nodular proliferation, which remains in contact with or synovium. They result from injury and inflamthe subjacent synovium. As the lesion becomes matory or degenerative conditions of the joint. The disease is benign, but lesions can recur in multinodular, the nodules detach from the synovium membrane to form intra-articular or up to 20% of the cases (Neumann et  al. 2016).

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The recurrence rates for the tenosynovial chondromatosis are much higher (Fetsch et al. 2003). Malignant transformation has also been reported and will be discussed further in this chapter.

6.1 Genetics and Molecular Biology Synovial chondromatosis has been considered as a metaplastic process. In recent years, the neoplastic nature of the lesions has been confirmed through molecular studies that demonstrated the presence of gene fusions. The most commonly involved genes are the fibronectin 1 (FN1) and the activin receptor 2A (ACVR2A). FN1 resides at the long arm of chromosome 2 and plays a role in adhesion of cells in the extracellular matrix (Pankov and Yamada 2002). ACVR2A encodes for an activin type 2 receptor protein. This protein acts as a receptor for activin A and bone morphogenic proteins 4 and 6 (Donaldson et  al. 1992). An FN1-ACVR2A (or an ACVR2A-FN1) fusion has been discovered in nearly 70% of synovial chondromatosis cases (Totoki et  al. 2014; Amary et al. 2019; Agaram et al. 2020). It is however unclear which gene alterations drive oncogenesis. In the study of Agaram et al. (2020), a novel FN1-NFATc2 has been described in 1 out of 27 cases where molecular analysis was done. NFATc2 resides on the long arm of chromosome 20 and is a member of the nuclear factor of activated T-cell family.

7 Synovial Sarcoma Synovial sarcoma is one of the most common soft tissue tumors, which mainly affects children and young adults reaching up to 15% of the soft tissue sarcomas in this age population (Sultan et al. 2009). The majority arise around the joints of the large bones, like the knee joint, which was initially thought to be from synovial origin, hence its name. Years later, a novel t(X;18)(p11.2;q11.2) translocation has been reported in nearly all tumors with morphology of synovial sarcoma (Clark et al. 1994; Crew et al. 1995). This discov-

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ery made clear that the tumor does not arise from the synovial membrane, but still the cell of origin remains unknown. Synovial sarcomas can arise everywhere in the human body, while intra-­ articular localization is extremely rare. A limited number of cases have been published in the English literature (Asiri et  al. 2020; Al-Mohrej et  al. 2020; Nakamura et  al. 2018; Cao et  al. 2021). Nevertheless, the morphology and microscopy of the lesion are the same regardless of the localization. Macroscopically, the lesions show a firm, soft cut surface with a white-to-tan color. Areas with myxoid appearance may also be seen (Evans 1980). Microscopically, the tumors present with to phenotypes (WHO Classification of Tumours Editorial Board 2020). The majority are monophasic (almost two-thirds of the cases), and the rest are biphasic. Monophasic synovial sarcomas display a proliferation of small spindle cells, with a fascicular growth pattern. Despite the high grade of the tumor, the spindle cells show a bland morphology with only little variation in shape and size. The cells have an elongated, hyperchromatic nucleus with indistinguishable nucleoli. The nuclear-to-cytoplasmic ratio is high, and the cytoplasm is inconspicuous while the nucleus stands out, giving the cells a dark blue appearance. The mitotic rate is usually high. In biphasic synovial sarcoma, next to the spindle cell, there is a second component. The cells here form tubular or glandular structures, like the structures found on adenocarcinomas. The cells are cuboidal or columnar and form one cell layer, while the lumen of the tubules or glands contains mucinous material. These cells have more cytoplasm than the spindle cells and hence display a more eosinophilic appearance. In some cases, this component can dominate, and in these cases, the differential diagnosis from a metastatic adenocarcinoma can be challenging. Still, in synovial sarcomas, there will always be a small spindle cell component. The tumor contains many blood vessels with a staghorn growth pattern resembling hemangiopericytoma. Calcification and ossification have

Pathology, Genetics, and Molecular Biology

also been described (Milchgrub et  al. 1993). Cases with poor differentiation may be difficult to be diagnosed, for which ancillary techniques might be required (Jobbagy et al. 2022). On immunohistochemistry, synovial sarcomas show expression of epithelial membrane antigen (EMA) in the majority of the cases. Both epithelial and spindle cell components can express EMA. Cytokeratin markers can also be expressed, but in less frequency than the EMA, especially in monophasic or poorly differentiated types (Pelmus et al. 2002). Spindle cells may express CD99, CD34, or SMA, but these immunohistochemical markers are not pathognomonic. Transducer-like enhancer of split 1 (TLE1) is overexpressed in synovial sarcomas (Foo et  al. 2011). Nevertheless, a small subset of malignant peripheral nerve sheath tumors and solitary fibrous tumors show limited staining for TLE1, making this marker non-pathognomonic (Foo et al. 2011). The prognosis of the tumor largely depends on the tumor stage at presentation, tumor size, the French Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) tumor grade, as well as the extent of areas of dedifferentiation (Guillou et al. 2004; ten Heuvel et al. 2009; Krieg et al. 2011; Bergh et al. 1999). Metastatic locations predominantly include lung, bone, and regional lymph nodes. The tumor can have late recurrences after 5  years of initial diagnosis, as such long-term follow-up is recommended (Krieg et al. 2011).

7.1 Genetics and Molecular Biology Synovial sarcomas are characterized by a unique translocation between chromosomes X and 18 (t(X;18)). Namely, the translocation takes place between the SYT gene located on the short arm of chromosome 18 (18q11) and the SSX1, SSX2, or less frequently SSX4 genes, all of which are located on the long arm of chromosome X (Xp11). This translocation results in a chimeric gene between the SYT gene and one of the SSX genes (SYT-SSX1, SYT-SSX2, or SYT-SSX4,

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respectively). It has been shown that SYT-SSX1 translocation is mostly correlated with a biphasic phenotype, while SYT-SSX2 with a monophasic (Kawai et  al. 1998). Moreover, tumors with a SYT-SSX1 translocation have a more complex karyotype and these patients display worst clinical outcome than those with a SYT-SSX2 translocation (dos Santos et  al. 2001; Panagopoulos et al. 2001).

8 Tenosynovial Giant Cell Tumor Tenosynovial giant cell tumors (TGCTs) are the only tumors that show true synovial differentiation. They arise from the synovium of joints, bursae, and tendon sheaths (WHO Classification of Tumours Editorial Board 2020). There are two types, the localized and the diffuse one, which differ in terms of location, size, macroscopic appearance, and biological behavior; however, genetically and histopathologically, they are indistinguishable. Localized TGCTs are circumscribed and maybe surrounded by a fibrous capsule (Fig. 8). They predominantly arise in the hand, especially in the finger, in close proximity to synovium. They present as a slow-growing, painless mass, while local recurrence after surgical excision is seen only in a minority of cases. Diffuse TGCTs are mainly extra-articular lesions but may also show intra-articular involvement (Fig.  9). As the term indicates, they grow diffusely with poorly circumscribed borders. The predominant site of involvement is the joint of the knee (Ottaviani et al. 2011). The lesions present with pain, swelling, or restriction of joint movement. Due to its diffuse growth, complete surgical excision is difficult to assess. As a result, the tumor shows high frequency of local recurrence, which might lead to destruction and functional loss of the joint. TGCTs of both types affect mainly young to middle-aged adults. The microscopic appearance of both types is similar (Mastboom et  al. 2019). The tumor is composed of polymorphous cell population con-

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a

b

Fig. 8 (a) Localized-type tenosynovial giant cell tumor (TGCT). The lesion is well circumscribed (HE, 1×). (b) Localized-type TGCT. The lesion shows a nodular growth pattern (HE, 5×)

sisting of (1) mononuclear cells, (2) osteoclastlike (multinucleated) giant cells, and (3) foamy histiocytes. Another characteristic of these tumors is the presence of hemosiderin depositions and a collagenized stroma (WHO Classification of Tumours Editorial Board 2020; Shankar 2021; Wang and Cui 2022). The mononuclear cells can display either a small size or a large epithelioid appearance. These cells are round and have an eccentrically located nucleus. The larger epithelioid cells have in addition a prominent nucleolus as well as intracytoplasmic hemosiderin deposition. The proportion of the different neoplastic cell population differs from

case to case. Mitotic activity may be seen, especially in the large epithelioid mononuclear cells. Necrosis is also reported (WHO Classification of Tumours Editorial Board 2020). Nevertheless, high mitotic rate and necrosis, in the right histopathologic and clinical concept, should raise suspicion of malignant transformation (Al-Ibraheemi et al. 2019; Vougiouklakis et al. 2020). Figures 10, 11, 12, and 13 display the different cell types in cases of localized and diffuse TGCT. As already mentioned, the morphologic distinction between the localized and the diffuse form of the TGCT is very difficult if not impossible. Localized tumors are well circumscribed.

Pathology, Genetics, and Molecular Biology

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Fig. 9  Diffuse-type TGCT. The lesion has indistinctive borders, infiltrating the adjacent adipose tissue (yellow arrow) (HE, 5×)

Fig. 10 Mononuclear cells in a localized type of TGCT. The cells are rounded with little eosinophilic cytoplasm and a smooth nucleus with indistinct nucleolus.

Some larger mononuclear cells contain hemosiderin around the periphery of these large cells (blue arrow) (HE, 40×)

Tumors of the diffuse type present with villonodular hyperplasia showing papillary projections of the synovium. Localized tumors in general contain more osteoclast-like giant cells than diffuse growing tumors, yet in both cases, these cells may be limited or even absent. Hence, no specific proportion of cells has been described, which correlates with one type more than the other.

TGCTs belong to the so-called fibrohistiocytic tumors. Hence, cells express immunohistochemical markers of histiocytic differentiation, such as CD68 and cluster of differentiation 163 (CD163). They also express cluster of differentiation 45 (CD45), a marker of nucleated hematopoietic cell origin (Fenu and Maracaja 2022). Large epithelioid mononucleated cells may show expression for desmin (Fenu and Maracaja 2022).

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Fig. 11  Adjacent to the mononuclear cells (blue arrow), there are also osteoclast-like giant cells (yellow arrow). These cells are big and contain numerous nucleoli. The

green arrows depict some mitotic figures. This can be a finding in a localized TGCT; still the mitosis is not numerous, neither atypical (HE, 20×)

Fig. 12  This is a case of a diffuse TGCT with many foam macrophages (green arrow) (HE, 10×)

The prognosis of TGCTs is different depending on the type. Localized tumors are benign, although they can recur. On the other hand, diffuse TGCTs belong to the locally aggressive and rarely metastasizing tumor category according to the WHO classification system. Atypical forms and malignant transformation of TGCTs have also been reported. Atypical TGCTs have more prominent cellularity with the presence of spindle cells and an increased

mitotic activity, but with a rather low ki67 proliferation index (less than 5%). The nuclei are hyperchromatic and/or enlarged. Symplastic and myxoid change can also be a feature (Vougiouklakis et al. 2020). Genetic characteristics of atypical TGCTs are also different from the typical TGCTs. The malignant transformation is always associated with areas of a typical TGCT.  The areas with malignant morphology display high cellu-

Pathology, Genetics, and Molecular Biology

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Fig. 13  Closer magnification of the previous figure. The macrophages display a foamy cytoplasm (blue arrow) with a centrally located, small nucleus (HE, 20×)

larity, nuclear pleiomorphism, increased mitotic activity with a mean of 18 mitosis per 10 high-­ power fields, and geographic necrosis. The cells show loss of expression of the histiocytic markers CD68 and CD163. Desmin in the large epithelioid cells may also be lost (O’Connell et al. 2000; Al-Ibraheemi et al. 2019). Malignant transformation is related to high metastatic rates and disease-­ associated deaths.

receptor, CSF1 promotes survival, proliferation, and differentiation of monocytes, macrophages, and osteoclasts (Mastboom et al. 2019). This may lead to tumorigenesis. Thus, it is suggested that neoplastic cells that overexpress CSF1 attract abnormal CSF1R-expressing macrophages. Further investigation revealed that the CSF1 overexpression is not always the result of a CSF1 translocation while an additional S100 calcium-­ binding protein A10 (S100A10) translocation partner has been discovered, which replaces the 8.1 Genetics and Molecular 3′ untranslated region (UTR) of the CSF1 with a Biology sequence from the 3′ end of the S100A10 gene (Panagopoulos et al. 2014). While the majority of typic and malignant TGCTs of the localized and diffuse type are characterized by a recurrent translocation that evolves TGCTs show translocation of the 1p13 involvthe p13 region of the chromosome 1, where ing the CSF1 gene (Al-Ibraheemi et  al. 2019), colony-­stimulating factor 1 (CSF1) gene is local- so-­ called atypical TGCTs present with nonized. The most common translocation partner is CSF1 fusions (Vougiouklakis et  al. 2020). In the 2q37, involving the collagen type VI alpha 3 this category, three novel fusions, namely chain (COL6A3) gene, which leads to a CSF1-­ NIPBL-ERG, FN1-ROS1, and YAP1-MAML2, COL6A3 chimeric (West et al. 2006). Other less have been established in equal amount of cases. frequent translocation patterns are the 5q22-31, This may suggest that these fusions are associ11q11-12, and 8q21-22 (Nilsson et al. 2002). ated with more aggressive morphological and The excessive CSF1 secretion attracts inflam- clinical features; still to our knowledge, they matory cells that express the CSF1 receptor have not yet been described in TGCTs with (CSF1R) (West et  al. 2006). By binding to its malignant transformation.

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9 Synovial Chondrosarcoma While conventional chondrosarcoma is the second most common malignant neoplasm arising in the bones, synovial chondrosarcoma is exceedingly rare. The lesion can arise de novo, but the majority of them arise in the context of a synovial chondromatosis. Accordingly, the lesions are classified into three categories: (1) arising in patient previously diagnosed with synovial chondromatosis but without the presence of the benign counterpart at the time of malignancy, (2) arising in patients without known history of synovial chondromatosis but with simultaneous existence of the benign counterpart, and (3) arising de novo (no previous history or simultaneous presence of synovial chondromatosis) (Gambarotti et  al. 2020). The vast majority, almost 80%, have evidence of preexisting synovial chondromatosis (Urwin et al. 2019; Evans et al. 2014; Gambarotti et  al. 2020), while 60% represent malignant transformation from benign lesion, and 20% are de novo (Gambarotti et  al. 2020). Malignant transformation of a synovial chondromatosis is referred from 1% to 10% (Davis et  al. 1998; Wittkop et  al. 2002; Evans et  al. 2014; Bhadra et al. 2007). The tumor arises mostly in the knee joint, followed by the hip and the shoulder, but other locations like the ankle have also been reported (Gambarotti et al. 2020). The clinical feature may suggest synovial chondromatosis; still in cases of multiple and/or rapid recurrences after complete excision or by increased pain, this should raise the suspicion for malignant transformation (Zamora et al. 2009; Ng et al. 2017; Evans et al. 2014; McCarthy et  al. 2016; Goldman and Lichtenstein 1964; Jonckheere et  al. 2014; Schlachter et al. 2011). The pathology of a de novo chondrosarcoma is similar to that of the conventional type and shows chondroid matrix with increased cellularity and atypia of the chondrocytes with enlarged nuclei and/or binucleation and myxoid degeneration of the matrix. Direct contact to the bone, bone erosion, and extensive invasion of surrounded tissues are also described (Gambarotti et  al. 2020). In cases of a preexisting synovial

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chondromatosis, the features that favor malignant transformation are loss of clustering of the chondrocytes with increased cellularity at the periphery of the nodules, myxoid changes of the stroma, and permeation of trabecular bone in a “filling­up” pattern (Bertoni et al. 1991; Gambarotti et al. 2020). Conventional chondrosarcoma is subject to a tertiary grading system ranging from 1 to 3, where 1 is the less aggressive and 3 the most aggressive lesions. On histology, the higher the grade, the more increased the cellularity, nuclear atypia/hyperchromasia/size, mitotic activity, and myxoid changes, wherein cells show dedifferentiation into more spindle cell mor­ phology (WHO Classification of Tumours Editorial Board 2020). The tumor can demonstrate different grades, but the area with the highest grade determines the lesion. In case of malignant transformation of a synovial chondromatosis, the secondary chondrosarcoma is also classified according to the tertiary grading system (Evans et  al. 2014). However, grade 1 (or low-grade) chondrosarcomas may be very difficult to differentiate from synovial chondromatosis (Urwin et al. 2019). The median time of the first diagnosis of synovial chondromatosis to malignant transformation is 20 years (Evans et al. 2014). The prognosis of the lesion depends widely on their grade (Campanacci et  al. 2008). Tumors that are high grade display high recurrence rate reaching 50% (Gambarotti et  al. 2020) and increased risk for metastatic disease, most common in the lungs. However, other investigations refer that secondary synovial chondrosarcoma has worse prognosis than the conventional type, which is attributed to the location within the joint, delayed recognition, and subsequent inappropriate previous treatments (Biazzo and Confalonieri 2016).

9.1 Genetics and Molecular Biology Synovial chondrosarcomas display the same genetic alterations as synovial chondromatosis. This indicates that genetics is not a good

Pathology, Genetics, and Molecular Biology

surrogate to differentiate benign from malignant tumors. A novel KMT2A-BCOR fusion has been described in a dedifferentiated synovial chondrosarcoma. KMT2A gene resides on chromosome 11 at q23 and encodes for an enzyme with transcriptional role, regulating gene expression during early development. BCL6 corepressor (BCOR) is a gene that encodes the BCL-6 corepressor protein and resides on the Xp11.4. BCOR is also fusion partner in other malignant sarcomas, most known in a subject of undifferentiated small round cell sarcomas as well as in Ewing-­like sarcomas (Cohen-Gogo et al. 2014). Isocitrate dehydrogenase (IDH) mutation is prevalent in cartilaginous tumors including chondrosarcoma (Vuong et  al. 2021). However, this could not be proven in cases of synovial chondrosarcomas (Gambarotti et al. 2020).

10 Other Very Rare Mesenchymal Tumors Arising in Synovium The only primary synovial tumor is the fibroma of the tendon sheath and the tenosynovial giant cell tumor. Other tumor types can also primarily be localized intra-articularly, as described previously in this chapter; still these tumors do not arise from the synovial membrane. In this chapter, we described some of those with a more frequent intra-articular occurrence. However, several tumor types that have been published in the literature are isolated cases. Some examples of this category of isolated cases are neurofibromatosis in patients with Recklinghausen’s disease (Lassoued Ferjani et al. 2021), leiomyoma (Khezami et al. 2021), angioleiomyoma (Cao et  al. 2018; Fukawa et  al. 2014; Thung et  al. 2017), inflammatory myofibroblastic tumor (Pineda-Diaz et  al. 2021), Ewing’s sarcoma (LiBrizzi et  al. 2022; McGirr and Edmonds 1984), and osteosarcoma (LiBrizzi et  al. 2022). Nevertheless, it is not clear if these cases involve synovial membrane or other intra-­articular structures, for instance the ligaments.

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11 Lymphomas Besides the soft tissue tumors, the synovial membrane can in rare instances be involved by lymphoma. This involvement is usually secondary, but primary lymphomas have also been described. A primary synovial lymphoma should be considered only in the absence of lymph node or systemic disease. The diagnosis remains challenging, because the majority of the patients with an intra-­ articular lymphoma that involves the synovium present with clinical features of rheumatoid arthritis (Birlik et  al. 2004; Cosatti et  al. 2016; Noguchi et al. 2008). A link between active rheumatoid arthritis and synovial lymphoma has also been suggested (Visser et  al. 2012; Dias and Isenberg 2011; Baecklund et  al. 2006b). The lymphomas that primarily involve the synovium are non-Hodgkin and diffuse large B-cell lymphomas (DLBCLs), either of the germinal center (GC)-like or the non-GC-like phenotype. DLBCLs associated with rheumatoid arthritis are usually of the non-GC-like phenotype (Baecklund et  al. 2006a). DLBCLs are associated with chronic inflammation, whether it concerns the synovium or another location in the body, and may also be due to an EBV infection (Cheuk et al. 2005).

12 Metastatic Disease in the Synovium Synovium is a very rare site of metastatic disease. Tumors that metastasize in synovium can be either of epithelial or mesenchymal origin or lymphomas and melanomas (Thompson et  al. 1996). Adenocarcinoma has been encountered as the most common type of synovial metastasis (Levine et al. 2013; Ryu et al. 2010). On microscopic basis, the differential diagnosis of an adenocarcinoma should be straightforward, unless the tumor is poorly differentiated or in cases of sarcomatoid differentiation. In these cases, ancillary immunohistochemistry to establish the epithelial origin, together with an appropriate history and the knowledge of a primary tumor elsewhere in the body, will lead to the cor-

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rect diagnosis. Metastasis of a melanoma should always be considered, especially in cases of an undifferentiated tumor, even if the tumor shows no pigmentation. Again here, the right clinical information accompanied by immunohistochemical and/or molecular tests is the key to the diagnosis. Given that lymphomas and mesenchymal tumors can primarily involve the synovium, comprehensive clinical examination and clinical history of the patient play an important role to exclude or confirm metastasis.

13 Key Points • Synovial tumors are rare. • True synovial tumors are fibroma of the tendon sheath and tenosynovial giant cell tumor. • Other tumor types can also primarily arise in the synovium, presumably from non-synovial cells that are located within the synovial membrane (like endothelial or adipose cells). • Molecular classification can help in the recognition and differentiation of tumors arising in synovium. • Synovium can be the site of metastatic disease involvement. • Multidisciplinary team approach is the key to the correct diagnosis.

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42 rheumatoid arthritis]. Nihon Kokyuki Gakkai Zasshi 46(2):131–135 O’Connell JX, Wehrli BM, Nielsen GP, Rosenberg AE (2000) Giant cell tumors of soft tissue: a clinicopathologic study of 18 benign and malignant tumors. Am J Surg Pathol 24(3):386–395. https://doi. org/10.1097/00000478-­200003000-­00007 Ottaviani S, Ayral X, Dougados M, Gossec L (2011) Pigmented villonodular synovitis: a retrospective single-­center study of 122 cases and review of the literature. Semin Arthritis Rheum 40(6):539–546. https://doi.org/10.1016/j.semarthrit.2010.07.005 Panagopoulos I, Mertens F, Isaksson M, Limon J, Gustafson P, Skytting B, Akerman M, Sciot R, Dal Cin P, Samson I, Iliszko M, Ryoe J, Debiec-Rychter M, Szadowska A, Brosjo O, Larsson O, Rydholm A, Mandahl N (2001) Clinical impact of molecular and cytogenetic findings in synovial sarcoma. Genes Chromosomes Cancer 31(4):362–372. https://doi. org/10.1002/gcc.1155 Panagopoulos I, Brandal P, Gorunova L, Bjerkehagen B, Heim S (2014) Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors. Int J Oncol 44(5):1425– 1432. https://doi.org/10.3892/ijo.2014.2326 Pankov R, Yamada KM (2002) Fibronectin at a glance. J Cell Sci 115(Pt 20):3861–3863. https://doi. org/10.1242/jcs.00059 Park SY, Jin SP, Yeom B, Kim SW, Cho SY, Lee JH (2011) Multiple fibromas of tendon sheath: unusual presentation. Ann Dermatol 23(Suppl 1):S45–S47. https://doi. org/10.5021/ad.2011.23.S1.S45 Pavithra P, Arundhathi S, Kodandaswamy CR (2014) Intra articular synovial lipoma of the right tarsometatarsal joint—a rare case report. J Clin Diagn Res 8(7):FD03– FD04. https://doi.org/10.7860/JCDR/2014/9311.4540 Pelmus M, Guillou L, Hostein I, Sierankowski G, Lussan C, Coindre JM (2002) Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol 26(11):1434–1440. https:// doi.org/10.1097/00000478-­200211000-­00005 Pineda-Diaz J, Solar I, Hershkovitz D, Drukman I, Sher O (2021) Intraarticular inflammatory myofibroblastic tumor of the left knee with ALK-CARS fusion detected with archer fusionplex sarcoma NGS panel: case report and literature review. Int J Surg Pathol 29(2):216–222. https://doi.org/10.1177/1066896920937770 Pizem J, Matjasic A, Zupan A, Luzar B, Sekoranja D, Dimnik K (2021) Fibroma of tendon sheath is defined by a USP6 gene fusion-morphologic and molecular reappraisal of the entity. Mod Pathol 34(10):1876– 1888. https://doi.org/10.1038/s41379-­021-­00836-­4 Poorteman L, Declercq H, Natens P, Wetzels K, Vanhoenacker F (2015) Intra-articular synovial lipoma of the knee joint. BJR Case Rep 1(2):20150061. https://doi.org/10.1259/bjrcr.20150061 Rubinstein A, Fitzhugh V, Ahmed I, Vosbikian M (2019) A case of 14-year-old male with fibroma of tendon sheath of the hand with novel chromosomal transloca-

V. Siozopoulou tion 4;10. Case Rep Orthop 2019:3514013. https://doi. org/10.1155/2019/3514013 Ryu K, Masui F, Saito S, Marumo K (2010) Chronic arthritis of the knee due to synovial metastasis Schlachter TR, Wu Q, Matlyuk-Urman Z (2011) AIRP best cases in radiologic-pathologic correlation: synovial chondrosarcoma. Radiographics 31(7):1883– 1888. https://doi.org/10.1148/rg.317105210 Shibayama H, Matsui Y, Kawamura D, Urita A, Ishii C, Kamishima T, Nishida M, Shimizu A, Iwasaki N (2020) Fibroma of tendon sheath of the hand in a 3-year-old boy: a case report. BMC Musculoskelet Disord 21(1):732. https://doi.org/10.1186/ s12891-­020-­03728-­x Simons M, Wang M, McBride OW, Kawamoto S, Yamakawa K, Gdula D, Adelstein RS, Weir L (1991) Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. Circ Res 69(2):530–539. https://doi.org/10.1161/01. res.69.2.530 Siozopoulou V, Marcq E, Jacobs J, Zwaenepoel K, Hermans C, Brauns J, Pauwels S, Huysentruyt C, Lammens M, Somville J, Smits E, Pauwels P (2019) Desmoid tumors display a strong immune infiltration at the tumor margins and no PD-L1-driven immune suppression. Cancer Immunol Immunother 68(10):1573–1583. https://doi.org/10.1007/ s00262-­019-­02390-­0 Sreekantaiah C, Leong SP, Karakousis CP, McGee DL, Rappaport WD, Villar HV, Neal D, Fleming S, Wankel A, Herrington PN et al (1991) Cytogenetic profile of 109 lipomas. Cancer Res 51(1):422–433 Strazar K, Drobnic M, Zupanc O, Jovic V, Pizem J (2013) Intraarticular nodular fasciitis of the hip. Arch Orthop Trauma Surg 133(4):537–540. https://doi.org/10.1007/ s00402-­013-­1682-­0 Strazar K, Sekoranja D, Matjasic A, Zupan A, Snoj Z, Martincic D, Pizem J (2021) Intraarticular nodular fasciitis-detection of USP6 gene fusions in three cases by targeted RNA sequencing. Virchows Arch 478(6):1117–1124. https://doi.org/10.1007/ s00428-­020-­02991-­6 Sultan I, Rodriguez-Galindo C, Saab R, Yasir S, Casanova M, Ferrari A (2009) Comparing children and adults with synovial sarcoma in the surveillance, epidemiology, and end results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115(15):3537–3547. https://doi.org/10.1002/cncr.24424 ten Heuvel SE, Hoekstra HJ, Bastiaannet E, Suurmeijer AJ (2009) The classic prognostic factors tumor stage, tumor size, and tumor grade are the strongest predictors of outcome in synovial sarcoma: no role for SSX fusion type or ezrin expression. Appl Immunohistochem Mol Morphol 17(3):189–195. https://doi.org/10.1097/PAI.0b013e31818a6f5c Thompson KS, Reyes CV, Jensen J, Gattuso P, Sacks R (1996) Synovial metastasis: diagnosis by fine-needle aspiration cytologic investigation. Diagn Cytopathol 15(4):334–337. https://doi.org/10.1002/(SICI)1097-­ 0339(199611)15:43.0.CO;2-­P

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43 Med 10(13):4415–4423. https://doi.org/10.1002/ cam4.4019 Wang J, Cui J (2022) Tenosynovial giant cell tumor, localized type. https://www.pathologyoutlines.com/topic/ softtissuegctlocal.html. Wang W, Huang Y, Wang C, Hong J, Ma C, Lin N, Ye Z, Yan S, Wu H (2019) Intra-articular nodular fasciitis: a rare lesion case report and an updated review of the literature. BMC Musculoskelet Disord 20(1):5. https:// doi.org/10.1186/s12891-­018-­2375-­1 West RB, Rubin BP, Miller MA, Subramanian S, Kaygusuz G, Montgomery K, Zhu S, Marinelli RJ, De Luca A, Downs-Kelly E, Goldblum JR, Corless CL, Brown PO, Gilks CB, Nielsen TO, Huntsman D, van de Rijn M (2006) A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. Proc Natl Acad Sci U S A 103(3):690–695. https://doi. org/10.1073/pnas.0507321103 WHO Classification of Tumours Editorial Board (2020) WHO classification of tumours. Soft tissue and bone Tumours, vol 3, 5th edn. IARC Publications, Lyon Wittkop B, Davies AM, Mangham DC (2002) Primary synovial chondromatosis and synovial chondrosarcoma: a pictorial review. Eur Radiol 12(8):2112–2119. https://doi.org/10.1007/s00330-­002-­1318-­1 Yamamoto T, Nagira K, Noda M, Kurosaka M (2001) Intra-articular nodular fasciitis. Arthroscopy 17(9):E38. https://doi.org/10.1053/jars.2001.26919 Zamora EE, Mansor A, Vanel D, Errani C, Mercuri M, Picci P, Alberghini M (2009) Synovial chondrosarcoma: report of two cases and literature review. Eur J Radiol 72(1):38–43. https://doi.org/10.1016/j. ejrad.2009.05.029

Part III Imaging Modalities

Ultrasound of Synovial Tumors and Tumorlike Conditions Mohamed Chaabouni, Mohamed Fethi Ladeb , and Mouna Chelli Bouaziz

Contents

Abstract

1

Generalities

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2

Ultrasound-Guided Synovial Biopsy

48

3

Tenosynovial Giant Cell Tumor

49

4

Primary Synovial Chondromatosis

50

5

Lipoma Arborescens

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6

Synovial Hemangioma

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Synovial Chondrosarcoma

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8 8.1 8.2

Intra- and Periarticular Cysts Synovial Cysts Mucoid or Ganglion Cysts

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9

Conclusion

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10

Key Points

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References

58

The synovial membrane is prone to metaplasia and proliferation that is often benign, with extremely rare malignancy. Clinical presentation is nonspecific, and ultrasound, combined with radiography, is the first-line imaging technique. It detects synovial proliferation, effusion, and bone erosion with high sensitivity. It also guides biopsy, compensating for its low specificity. We review the ultrasound features of the main synovial tumors and tumorlike conditions, with a focus on the unique findings that enable a confident diagnosis or a limited differential diagnosis, and the ultrasound-guided synovial biopsy technique.

Abbreviations M. Chaabouni (*) · M. F. Ladeb · M. Chelli Bouaziz Department of Radiology, MT Kassab Institute of Orthopaedics, Tunis, Tunisia Faculty of Medicine of Tunis, Tunis-El Manar University, Tunis, Tunisia e-mail: [email protected]; fethiladeb@ hotmail.fr; [email protected]

LA PSC TGCT UGSB US

Lipoma arborescens Primary synovial chondromatosis Tenosynovial giant cell tumor Ultrasound-guided synovial biopsy Ultrasound

Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_410, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 12 April 2023

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48

1 Generalities

M. Chaabouni et al.

UGSB has several advantages when compared to arthroscopic biopsy. It can be safely and sucSynovial tumors and tumorlike conditions are cessfully performed on both large and small rare, mainly affecting one joint and sometimes joints and is less expensive, less invasive, and arising from a tendon sheath or a bursa. Their widely available (Johnsson and Najm 2021; diagnosis is difficult and delayed due to their Lazarou et al. 2019). UGSB has high sensitivity (97%) and specinonspecific clinical presentation and examinaficity (100%) for the diagnosis of synovial tumors tion, with often normal radiographs. Ultrasound (US) is widely used as a first-level (Sitt et al. 2017). Careful planning of the biopsy in a multidiscimodality in the diagnosis of many synovial tumors and tumorlike conditions. US is more plinary consultation meeting regarding the indiaccessible than MRI, inexpensive, fast, and well cation, technique, and choice of biopsy path is mandatory (Junaid et al. 2021). tolerated. The technique of UGSB is similar to High-resolution US has a spatial resolution US-guided biopsy of any soft tissue tumors (Sitt identical to or higher than that of MRI. et al. 2017). High-resolution linear transducers with a Major contraindications to UGSB are skin broad bandwidth frequency are generally used for superficial joints. Color and power Doppler infection, coagulation disorders, or anticoagulant are valuable in differentiating synovial thicken- therapy as well as noncollaborating patient ing from joint effusion and cysts from vascular- (Saraiva 2021). The biopsy is performed under sterile conized lesions. ditions. The US probe is covered with a sterile US is very sensitive to the detection of synoplastic sleeve and either sterile gel or chlorhexvial proliferation, joint effusion, and bone eroidine may be used as a contact medium sion in both large and small joints. Joint effusion is anechoic compressible and between the probe and the skin (Lazarou et al. 2015). devoid of Doppler signal. A local anesthetic is injected into the soft tisSynovial proliferation appears as a non-­ compressible echogenic tissue within a joint. Its sues up to the joint capsule. The needle caliber varies depending on the vascular pattern can be assessed using Doppler size of the joint. For large joints, a suitable US. coaxial outer needle may be used in addition The most important limitation of US lies in its to the 14 or 16G biopsy needle to facilitate limited field of view and depth of penetration, thus potentially resulting in an incomplete evalu- multiple tissue sampling from one needle penetration. For small joints, a 16G biopsy ation of the joint cavity. US has a low specificity in determining the needle is used without a coaxial sheath. The cause of synovial proliferation since considerable needle is introduced as parallel as possible to overlap exists in the US appearances of different the probe. Any fluid aspirated before synovial biopsy synovial tumors as well as infection and inflamshould be sent for microbial and cytological analmation (Sitt et al. 2017). ysis. Multiple needle passages are necessary in The specificity of US can be improved by most cases to obtain a sufficient amount of tumor ultrasound-guided synovial biopsy (UGSB). material for all pathological and bacteriological studies (Sitt et al. 2017). The biopsied specimens are immediately fixed 2 Ultrasound-Guided Synovial in a 4% formaldehyde solution for up to 24 h and Biopsy embedded in paraffin. Fine needle aspiration represents an excellent UGSB is safe, reliable, and well tolerated by patients alternative to exfoliative cytology or histology and can be performed in large and small joints as (Dodd and Major 2002; Iyer et al. 2003). well as bursae and tendon sheaths (Saraiva 2021).

Ultrasound of Synovial Tumors and Tumorlike Conditions

Patients are advised to rest the biopsied joint for 48 h after the procedure. Adverse events are uncommon and usually mild and transient: vasovagal reaction, ligament, muscle, tendon and nerve lesion, hemarthrosis, and skin or joint infection.

3

Tenosynovial Giant Cell Tumor

Tenosynovial giant cell tumor (TGCT) is a family of lesions usually involving the joint synovium, bursae, and tendon sheath. TGCT includes two subtypes, localized and diffuse, that are histologically similar but have disparate clinical and imaging features. Diffuse forms are most commonly intra-articular masses that mainly involve large joints. The localized type consists of a small well-circumscribed mass and

a

49

may be either intra- or extra-articular. It most commonly involves the hands and feet (Dundar et al. 2020). These tumor types were previously classified as pigmented villonodular synovitis or giant cell tumor of the tendon sheath. In the most recent version of the World Health Organization classification, TGCT has been suggested to replace both designations (de Saint Aubain Somerhausen and van de Rijn 2013). In diffuse TGCT, US depicts hypoechoic wellvascularized synovial proliferation of variable thickness. The presence of small intense echoes within the synovium has a good diagnostic value (Fig.  1). Joint fluid effusion is common. Loculation of joint fluid may be caused by synovial infolding. Bone erosions are less visible than in MRI. In extra-articular TGCT, US shows wellvascularized hypoechoic homogeneous or heter-

b

Fig. 1 Diffuse TGCT of the knee: longitudinal (a) and transverse (b) ultrasound images show echogenic proliferation of the synovium with multiple small intense echoes (arrows) within the thickened synovium (“starry sky” appearance)

M. Chaabouni et al.

50

ogenous mass intimately related to the tendon (Fig. 2). There are also pseudo-cystic, nonvascular, or diffuse forms that may be confused with tenosynovitis (Fig.  3) (Ladeb et  al. 2020). The features of localized intra-articular TGCT are similar to those seen in diffuse intra-articular TGCT.

Fig. 2 Localized extra-articular TGCT of the flexor tendon sheath of the right third finger: Ultrasound shows a hypoechoic mass intimately related to the flexor tendons, containing multiple punctiform intense echoes (arrows)

a

Fig. 3 Diffuse extra-articular TGCT of the flexor tendon sheath of the right fifth finger: Ultrasound in longitudinal (a) and transverse (b) images shows diffuse thickening of

4

Primary Synovial Chondromatosis

Primary synovial chondromatosis (PSC) is a rare metaplasia of the synovium leading to the formation of cartilaginous loose bodies (chondromas) that can ossify (osteochondromas). The pathogenesis of synovial chondromatosis is still controversial. The hypothesis of a benign neoplasia of the synovium put forward by Jaffe is the most commonly accepted (Jaffe 1958). It typically affects men in the third to fifth decades of life. The knee is affected in 50–65% of cases, followed by the hip, the elbow, the shoulder, and the ankle. Involvement of a tendon sheath or bursa is possible (Murphey et al. 2007). PSC is revealed by mechanical pain, joint swelling, and limitation of joint mobility or locking (Staals 2020). Radiographs do not show chondromas, but indirect signs may suggest their presence: periarticular opacity, bone erosions, and widening of the joint space. Osteochondromas present as

b

the flexor tendon sheath with peritendinous fluid effusion mimicking tenosynovitis. Note the fine intralesional echoes that help to suggest the correct diagnosis (arrows)

Ultrasound of Synovial Tumors and Tumorlike Conditions

multiple arciform or rarely punctiform calcifications identical in size and shape (Levine et  al. 2016). Both the cartilaginous and calcified nodules can be identified by US.  Nodules may form an acoustic shadow if calcified. Due to its dynamic scanning ability, US can differentiate freely moving bodies from nodules embedded in the synovium (Bargiela 2010). Bone erosions can be detected by US, but less frequently documented than with CT or MRI (Garner and Bestic 2013).

5

Lipoma Arborescens

Lipoma arborescens (LA) is a rare intra-articular tumorlike lesion characterized by a diffuse villous proliferation of the synovial tissue with fatty deposits under the synovial membrane.

a

51

The pathophysiology is still unclear, but LA is thought to be a reactive process, secondary to chronic inflammation or repetitive trauma. It has been observed in patients aged between 9 and 68 years, with equal predominance in men and women. All joints may be affected, and the knee is the most frequently involved. Bilateral and polyarticular involvement is possible (Sanamandra and Ong 2014). Clinical, radiographic, and US findings are usually not specific but may be suggestive of the diagnosis. US shows a hyperechoic villous synovial fringe pliable with compression and associated with joint effusion (Fig. 4a, b) (Garner and Bestic 2013). CT or even better MRI confirms the diagnosis of lipoma in the presence of fat in the synovial villi (Fig. 4c) (Huang et al. 2021).

c

b

Fig. 4 Lipoma arborescens of the knee: (a) Ultrasound shows hyperechoic villous synovial fringes with intraarticular effusion. (b) The fringes are pliable to compres-

sion by the probe. (c) Sagittal MRI T1-WI: thickened synovial fringes with fatty signal in the suprapatellar recess

M. Chaabouni et al.

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a

b

Fig. 5 Synovial hemangioma of the knee. (a) Ultrasound shows a vascularized intra-articular mass with heterogeneous echogenicity. (b) MRI sagittal T1-WI: the lesion

has a heterogeneous signal, containing a fatty component (T1 hypersignal) and a vascular component (T1 hyposignal) (arrows)

6

MRI is the technique of choice to confirm the diagnosis and to determine the extent of the lesion (Fig. 5b) (Levine et al. 2016).

Synovial Hemangioma

Synovial hemangioma (SH) is a rare benign vascular proliferation that occurs in 60% of cases in the knee and 30% of cases in the elbow. Most cases are observed in children. SH is asymptomatic in 75% of cases; otherwise, it is revealed by pain, joint swelling, or recurrent hemarthrosis (Cotten et al. 2006). SH appears on US as a vascular heterogeneous hypoechoic mass (Fig.  5a). Phleboliths are uncommon and are found in only 38% of cases (Garcia and Bianchi 2003). They appear as hyperechoic bands or spots with posterior acoustic shadowing, diffusely distributed within the mass. Identification of vessels depends on their size and flow within the lesion (Afonso and Mascarenhas 2015).

7

Synovial Chondrosarcoma

Synovial chondrosarcoma is an exceptional tumor that arises from the articular synovium. It most often affects men between 40 and 70 years of age. The most affected joint is the knee (47.7%), followed by the hip (34.3%) and the ankle (5.9%). This tumor occurs de novo (19%) or complicates primary synovial chondromatosis (81%) (Biazzo and Confalonieri 2016). US shows a synovial mass that may contain calcifications (Fig. 6).

Ultrasound of Synovial Tumors and Tumorlike Conditions

a

53

b

Fig. 6 Synovial chondrosarcoma of the knee. (a) Radiograph shows a dense soft tissue swelling posterior to the distal femur (arrow) containing fine cartilaginous-type

calcifications. (b) Ultrasound shows a hypoechoic mass (arrows) in the popliteal fossa, with polylobed contours and intralesional calcifications

8

The distinction between synovial cysts and ganglion cysts is not always straightforward. The content of a synovial cyst may be viscous, similar to that of a ganglion cyst, whereas the contents of a ganglion cyst may be close to synovial fluid. The wall of a ganglion cyst may be progressively covered with a synovial-type epithelium. This distinction is of no practical importance, since the symptomatology and treatment of these cysts depend essentially on their location and possible communication with the joint (Baron 2015).

Intra- and Periarticular Cysts

Intra- and periarticular cysts are common in clinical practice. They include synovial cysts and mucoid or ganglion cysts. Synovial cysts correspond to a herniation of the synovial membrane through the joint capsule due to increased intra-articular pressure or abnormal distension of a bursa that communicates with the adjacent joint. These cysts contain normal synovial fluid and are bounded by a fibrous wall lined with synovial cells (Baron 2015). Ganglion cysts are fluid collections containing a viscous colorless or xanthochromatic substance and limited by a fibrous wall, lined with pseudosynovial cells. Communication of cysts with the joint cavity is inconstant. The pathogenesis of ganglion cysts is controversial. The synovial theory is the most commonly accepted. The cyst results from leakage of articular fluid through a more or less long breach around which a fibroconjunctival tissue may develop (Diard et al. 1999).

8.1

Synovial Cysts

Synovial cysts are found in decreasing order of frequency in the knee, hip, wrist, etc. Popliteal cysts are the most common cystic knee lesions. In adults, they are secondary to meniscus or ligament injuries, gonarthrosis, or inflammatory arthritis. Popliteal cysts in children occur between 3 and 10 years of age and are almost always primary (Diard et al. 1999).

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8.2.1

Fig. 7 Popliteal (baker’s) cyst. Ultrasound reveals an anechoic mass in the popliteal fossa that communicates with the joint space via an opening (arrow) between the medial head of the gastrocnemius and the semimembranosus tendons

Uncomplicated popliteal cysts are usually asymptomatic but may be revealed by a more or less painful swelling of the popliteal fossa. The pain, when present, is due to the causative arthropathy or a complication: rupture, vascular compression, or infection. US reveals an anechoic mass, sometimes partitioned, with posterior enhancement of the echoes (Fig. 7). The contents become echogenic in case of bleeding or infection. Loose bodies may be seen within the cyst. The cyst wall is thin, unless there is underlying inflammatory arthritis. US is well suited to evaluate communication of the cyst with the joint (Fig. 7) and to assess its relationship to the neurovascular bundle. It also looks for intraarticular fluid effusion and synovial thickening. Rupture of the cyst results in an intermuscular and/or subcutaneous fluid collection (Marin et al. 2006).

8.2

Intra-articular Ganglion Cysts

8.2.1.1 Meniscal Cysts Meniscal cysts are rare, with an estimated incidence of 1–8%. The medial meniscus is affected with the same frequency as the lateral meniscus (Anderson et al. 2010). The pathophysiology of meniscal cysts is controversial. A degenerative origin is the most accepted. These cysts would be due to an accumulation of articular fluid through a meniscal fissure. When the fissure reaches the base of the meniscus, the cyst may extend posteriorly, laterally between the deep and superficial bundles of the medial collateral ligament, or anteriorly into Hoffa’s fat pad (Marin et al. 2006). Meniscal cysts are seen in middle-aged patients who present with joint pain and subcutaneous swelling variable in size with joint movement (Lantz and Singer 1990). US is sensitive for detection of meniscal cysts. It shows the cyst as an anechoic formation attached to the involved meniscus (Fig. 8), but it is less sensitive than MRI in the diagnosis of meniscal tear (Marin et al. 2006).

Mucoid or Ganglion Cysts

There are several types of ganglion cysts; according to their location, we may distinguish: – Intra-articular cysts which are intracapsular and intra- or extrasynovial – Intra-spongious or subperiosteal cysts – Para-articular cysts which can be juxtaarticular, intramuscular, intraneural, or intraarterial (Baron 2015)

Fig. 8 Meniscal cyst: ultrasound of the lateral meniscus: anechoic mass attached to the fissured meniscus (arrows)

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8.2.1.2 Cruciate Ligament Cysts Cruciate ligament cysts are rare with reported incidence ranging from 0.1% to 1%. They most commonly involve the anterior cruciate ligament (Vaishya et al. 2017). These cysts are thought to result from mucoid degeneration of the ligament from traumatic origin (degenerative theory) or passage under the effect of the local pressure of the joint fluid through a fine opening (synovial theory) (Diard et al. 1999). The cysts clinically present as popliteal or posterolateral pain, which is aggravated by effort and knee flexion (Vaishya et al. 2017). US identifies only the posteriorly located cysts, which form multiloculated anechoic collections. The relationship of the cyst with the popliteal artery must be studied to rule out the diagnosis of arterial cystic adventitial disease. MRI better shows deeply located cysts inaccessible to US (Mao et al. 2012).

8.2.2.1 Spinoglenoid Notch Cyst The spinoglenoid notch cyst is caused by the passage of joint fluid into the spinoglenoid notch through a fissure in the glenoid labrum. This cyst can lead to atrophy of the infraspinatus muscle by compression of the suprascapular nerve (Lee et al. 2007). US clearly shows the cyst (Fig. 10) and may guide aspiration in case of compressive neuropathy (Wee and Wu 2018). MRI confirms the diagnosis of a cyst and assesses the degree of fatty transformation of the infraspinatus muscle. CT or MR arthrography is best suited to document the underlying labrum tear.

8.2.1.3 Hoffa’s Fat Pad Cysts Hoffa’s fat pad cysts are rare with only few cases reported in the literature (Goyal et al. 2019). They are usually asymptomatic but may be responsible for anterior knee pain that increases with extension. US confirms the diagnosis of a

8.2.2.2 Intraneural Cyst The etiology of intraneural cysts has been controversial, and the articular (synovial) theory is the most plausible (Desy et al. 2016). Intraneural cysts most frequently involve the common fibular nerve.

a

cyst (Fig. 9), but it is less effective than MRI for final diagnosis and differential diagnosis (Marin et al. 2006).

8.2.2

Extra-articular Ganglion Cyst

b

Fig. 9 Hoffa’s fat pad cyst. Sagittal (a) and axial (b) ultrasound images show an anechoic mass in Hoffa’s fat pad, deep to the patellar ligament (arrows)

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a

b

Fig. 10 Spinoglenoid notch cyst. (a) Axial ultrasound showing an anechoic cyst occupying the infraspinatus fossa, adjacent to the spinoglenoid notch (arrow). (b) Sagittal PD FS MR image confirms the diagnosis. Due to

a wider field of view, MRI may allow a precise evaluation of the local extent of large lesion. (Image courtesy of Dr. Bouaziz N)

It is usually seen in middle-aged patients and is revealed by pain and a sensory-motor neurological deficit (Desy et al. 2016). Ultrasound shows enlargement of the nerve and intraneural cyst formation extending along the long axis of the nerve (Fig.  11). Communication of the cyst with the articular cavity is inconstantly visible. Distinguishing between an intraneural cyst and a proximal tibiofibular cyst can be difficult. Surgical treatment requires an MRI scan to determine the extension of the cyst and its relationship with neighboring structures (Marin et al. 2006).

The popliteal artery is the most affected site, and the patients are predominantly middle-aged men without arterial disease history (Desy and Spinner 2014). Duplex US scan shows an anechoic lesion in the arterial wall without intralesional color Doppler signal, unlike the arterial lumen (Fig. 12). It also enables to assess the vascular lumen stenosis and damping of the downstream flows. MRI reveals cystic joint connections more frequently (Affes et al. 2022).

8.2.2.3 Cystic Adventitial Disease Adventitial cysts develop in the arterial wall between the media and the adventitia. The etiology remains debated and is most likely due to communication with a neighboring joint through adventitial dissection of an articular vascular branch (Spinner et al. 2013).

8.2.2.4 Subperiosteal Cyst A subperiosteal cyst is located on the metaphyses and diaphyses of long bones. It appears on US as a hypo- or anechoic juxtacortical mass that erodes the cortex and raises the periosteum, which appears as a thin hyperechoic shell (Fig. 13). The differential diagnosis is subperiosteal hematoma and subperiosteal abscess.

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a

b

c

Fig. 11 Intraneural cyst. Longitudinal (a) and transverse (b) ultrasound images show an oblong anechoic mass, dissociating the nerve fibers. (c) Intraoperative image

a

b

Fig. 12 Ultrasound images: (a) Anechoic lesion in the popliteal artery wall (star) without intralesional color Doppler signal (b), responsible for moderate stenosis of the lumen. (Image courtesy of Dr. Affes M)

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a

b

c

Fig. 13 Subperiosteal mucoid cyst of the tibia. (a) Radiograph shows a soft tissue opacity (star) with external cortical erosion (arrow). (b, c) Ultrasound shows a juxta-

osseous mass, with anechoic content lifting the periosteum at its poles (c)

9

• US has a low specificity in synovial tumors and tumorlike conditions, and MRI is often needed to support the diagnosis. • UGSB is a safe, available, and specific tool in synovial tumors and tumorlike conditions.

Conclusion

US is a sensitive but not very specific technique for the diagnosis of synovial tumors and tumorlike conditions. US-guided joint puncture or synovial biopsy can compensate for its low specificity. MRI is in most cases essential to better characterize these tumors and study their extension.

10

Key Points

• US is highly sensitive in the detection of synovial tumors and tumorlike conditions. • Some unique US findings enable a confident diagnosis or a limited differential diagnosis.

References Affes M, Chaabouni M, Attia M et  al (2022) Cystic adventitial disease of the popliteal artery with unusual spontaneous regression: a case report with literature review. Clin Case Rep 10:e05757 Afonso D, Mascarenhas V (2015) Imaging techniques for the diagnosis of soft tissue tumors. Rep Med Imaging 8:63–70 Anderson JJ, Connor GF, Helms CA (2010) New observations on meniscal cysts. Skelet Radiol 39:1187–1191

Ultrasound of Synovial Tumors and Tumorlike Conditions Bargiela A (2010) Utilidad de la ecografíaenelestudio de la enfermedadsinovial [The usefulness of ultrasonography in synovial disease]. Radiologia 52:301–378 Baron D (2015) Kystes synoviaux. EMC Appareil Locomoteur 10:1–13 [Article 15-154-A-10] Biazzo A, Confalonieri N (2016) Synovial chondrosarcoma. Ann Transl Med 4:280 Cotten A, Dabbeche C, Vieillard MH (2006) Tumeurs et pseudotumeurs synoviales du genou. Rev Rhum 73:593–602 de Saint Aubain Somerhausen NS, van de Rijn M (2013) Tenosynovial giant cell tumor: localized type, diffuse type. In: Fletcher C, Bridge J, Hogendoorn P, Martens F (eds) World Health Organization classification of tumours of soft tissue and bone. IARC Press, Lyon Desy NM, Spinner RJ (2014) The etiology and management of cystic adventitial disease. J Vasc Surg 60:235–245 Desy NM, Wang H, Elshiekh MA et  al (2016) Intraneural ganglion cysts: a systematic review and reinterpretation of the world’s literature. J Neurosurg 125:615–630 Diard F, Chateil JF, Hauger O (1999) Kystes synoviaux et kystes mucoïdes articulaires, para-articulaires et intra-­ osseux. J Radiol 80:679–696 Dodd LG, Major NM (2002) Fine-needle aspiration cytology of articular and periarticularlesions. Cancer 96:157–165 Dundar A, Young JR, Wenger DE et  al (2020) Unusual manifestations of diffuse-type tenosynovial giant cell tumor in two patients: importance of radiologic-­ pathologic correlation. Skelet Radiol 49:483–489 Garcia J, Bianchi S (2003) Tumeurs synoviales du genou. Rev Med Suisse 2444:1404–1410 Garner HW, Bestic JM (2013) Benign synovial tumors and proliferative processes. Semin Musculoskelet Radiol 17:177–188 Goyal R, Chopra R, Singh S et al (2019) Ganglion cyst of Hoffa’s fat pad of knee-a rare cause of knee pain and swelling-a case report and literature review. J Clin Orthop Trauma 10:S215–S217 Huang Y, Liu H, Wang Y et  al (2021) Imaging features of lipoma arborescens. Acta Radiol. https://doi. org/10.1177/02841851211027388 Iyer VK, Kapila K, Verma K (2003) Fine-needle aspiration cytology of giant cell tumor of tendon sheath. DiagnCytopathol 29:105–110 Jaffe HL (1958) Synovial chondromatosis and other benign articular tumors. In: Tumor and tumorous conditions of the bone and joints. Lea & Febiger, Philadelphia, pp 558–566 Johnsson H, Najm A (2021) Synovial biopsies in clinical practice and research: current developments and perspectives. Clin Rheumatol 40:2593–2600 Junaid SE, Bilal S, Saifuddin A (2021) Suspected intra-­ articular soft-tissue tumours and tumour-like lesions:

59 performance of image-guided core needle biopsy. Eur J Radiol 135:109469 Ladeb MF, Chelli Bouaziz M, Riahi H et  al (2020) Echographie des tumeurs et pseudo-tumeurs synoviales. In: Actualités en échographie de l’appareil locomoteur tome 16. Sauramps Medical, Montpellier. ISBN: 9791030302400 Lantz B, Singer KM (1990) Meniscal cysts. Clin Sports Med 9:707–725 Lazarou I, D’Agostino MA, Naredo E et  al (2015) Ultrasound-guided synovial biopsy: a systematic review according to the OMERACT filter and recommendations for minimal reporting standards in clinical studies. Rheumatology (Oxford) 54:1867–1875 Lazarou I, Kelly SG, Meric de Bellefon L (2019) Ultrasound-guided synovial biopsies of wrists, metacarpophalangeal, metatarsophalangeal, interphalangeal joints, and tendon sheaths. Front Med (Lausanne) 6:2 Lee BC, Yegappan M, Thiagarajan P (2007) Suprascapular nerve neuropathy secondary to spinoglenoid notch ganglion cyst: case reports and review of literature. Ann Acad Med Singap 36:1032–1035 Levine BD, Motamedi K, Seeger LL (2016) Synovial tumors and proliferative diseases. Rheum Dis Clin N Am 42:753–768 Mao Y, Dong Q, Wang Y (2012) Ganglion cysts of the cruciate ligaments: a series of 31 cases and review of the literature. BMC Musculoskelet Disord 13:137 Marin F, Albert JD, Jrad Z et al (2006) Imagerie des kystes synoviaux et mucoïdes du genou de l’adulte. Rev Rhum 73:633–641 Murphey MD, Vidal JA, Fanburg-Smith JC et  al (2007) Imaging of synovial chondromatosis with radiologic-­ pathologic correlation. Radiographics 27:1465–1488 Sanamandra SK, Ong KO (2014) Lipoma arborescens. Singap Med J 55:5–10 Saraiva F (2021) Ultrasound-guided synovial biopsy: a review. Front Med (Lausanne) 8:632224 Sitt JC, Griffith JF, Lai FM et al (2017) Ultrasound-guided synovial Tru-cut biopsy: indications, technique, and outcome in 111 cases. Eur Radiol 27:2002–2010 Spinner RJ, Desy NM, Agarwal G et al (2013) Evidence to support that adventitial cysts, analogous to intraneural ganglion cysts, are also joint-connected. Clin Anat 26:267–281 Staals EL (2020) Synovial chondromatosis. In: Diagnosis of musculoskeletal tumors and tumor-like conditions. Springer, Cham Vaishya R, Esin Issa A, Agarwal A et al (2017) Anterior cruciate ligament ganglion cyst and mucoid degeneration: a review. Cureus 9:e1682 Wee TC, Wu CH (2018) Ultrasound-guided aspiration of a paralabral cyst at the spinoglenoid notch with suprascapular nerve compressive neuropathy. J Med Ultrasound 26:166–167

Radiography and CT in Synovial Tumors and Tumorlike Conditions Kirran Khalid, Radhesh Lalam, and Simranjeet Kaur

Contents 1

Introduction

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2 2.1 2.2 2.3

Techniques Radiography Computed Tomography (CT) Dual-Energy Computed Tomography (DECT)

62 62 63 63

3 3.1 3.2 3.3 3.4

Anatomical Considerations Synovial Joints Periarticular Fat Planes Tendons Bursae

64 64 64 64 65

4

Anatomical Considerations of Some Common Synovial Joints Shoulder Elbow Hip Knee

65 65 66 67 68

4.1 4.2 4.3 4.4

4.5

Ankle

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5 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 5.9 5.10 5.11 5.12

Pathological Considerations Synovial Hemangioma Juxta-Articular Myxoma Lipoma Arborescens TSGCT Primary Synovial Chondromatosis Synovial Chondrosarcoma Synovial Metastasis BCP Crystal Deposition Disease CPPD Gout Arthritides Tuberculosis (TB)

70 71 71 71 71 72 73 73 73 75 75 76 77

6

Conclusion

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7

Key Points

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References

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K. Khalid · R. Lalam (*) · S. Kaur Department of Musculoskeletal Radiology, Robert Jones and Agnus Hunt Orthopaedic Hospital (RJAH), Oswestry, UK e-mail: [email protected]; [email protected]; [email protected] Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_411, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 18 April 2023

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Abstract

Synovial tumors and tumorlike conditions may arise from or extend into any synovial lined structure such as joints, bursae, and tendon sheaths. Radiography and CT play an important role in the workup of musculoskeletal pathologies. Although MRI is the gold standard for assessing the synovium, changes in radiographic densities are ready discernable on radiography and CT, which can alert the radiologist, prompting further investigation to eliminate a sinister cause and on the other hand to dismiss a non-sinister pathology avoiding further unnecessary investigations and most importantly patient reassurance. Fat planes and bursae are routinely visualized on radiography and CT and provide anatomical landmarks, where the pathology may be arising from or extending into, with CT providing higher resolution and more specific anatomical boundaries. The aim of the chapter is to discuss the radiographic and CT (DECT where relevant) appearances of synovial tumors and tumorlike conditions and highlight key imaging differentials where pathologies overlap in their imaging features.

joint pathology is suspected as they are inexpensive, quick, and readily available. Magnetic resonance imaging (MRI) is the imaging modality of choice for investigating the synovium membrane, as the synovium is readily seen and confidently characterized for components such as fat, cartilage, and hemosiderin (Larbi et al. 2016) and will be discussed in a subsequent chapter.

2 Techniques Over the past century, musculoskeletal radiology has progressed from bone-only radiography to a dedicated subspecialty heavily dependent on imaging, particularly radiography and cross-­ sectional imaging (Geijer et al. 2021).

2.1 Radiography

Radiography is a two-dimensional representation of a three-dimensional structure, and at least two orthogonal views are obtained to each other for accurate localization of an abnormality, usually anteroposterior and lateral. The basic principle behind image formation in plain radiography is the attenuation of the X-ray beam by the various structures, and this depends on the radiodensity and composition of the tissues the beam is tra1 Introduction versing through. The five main radiographic densities are metal, bone, soft tissue/fluid, fat, and Radiography and CT play an essential role in the air. A structure is only appreciable on a radioearly detection of synovial disease and their management, and are key in preventing irreversible graph, if there is a relative difference in the radiodensity between itself and the surrounding joint damage (Turan et al. 2017). The aim of this chapter is to provide an in-­ tissues. If the structure in question is adjacent to depth knowledge in aiding the diagnosis of syno- a tissue of a different radiodensity, like fat or air, vial tumors and tumorlike conditions on radiography will provide excellent contrast radiography and CT, as well as what to expect to resolution. Radiographs are invaluable for assessing the see using these modalities. This should equip the radiologist with knowledge in image interpreta- bone and joints; soft tissue and capsular struction and managing various musculoskeletal con- tures are of low radiodensity, and therefore less ditions, not limited to synovial tumors and well defined; nevertheless, they can still be tumorlike conditions. These modalities usually appreciated and assessed. The appreciation of form part of the primary investigations when a different radiodensities allows non-touch

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Table 1  Overview of radiographic and CT findings in synovial pathology Bone density Normal

Joint space Preserved

Erosions Frequent— marginal

Juxta articular myxoma Lipoma arborescens Primary synovial chondromatosis

Normal

Preserved

Normal

Effusion Frequent— dense due to hemosiderin

Rare

Calcification Infrequent— presence of phleboliths is pathognomonic Infrequent

Rare

Rare

Normal

Preserved or co existent OA Preserved → wide

Infrequent— marginal

TSGCT

Normal

Preserved

Frequent— marginal

Frequent— punctate, rings and arc No

Frequent— lucent Frequent

Synovial chondrosarcoma CPPD

Normal

Bone destruction

Osteopenia

Preserved until destruction Narrowing

Gout

Normal

Preserved

Frequent— punched out, sclerotic margins, overhanging edges

Synovial haemangioma

Late

lesions to be safely classified and the patient reassured. Differentiating between synovial chondromatosis and TSGCT for example can be made using ­ radiography and computed tomography (CT) alone, based on the presence of mineralization. Many image findings on radiography and CT (Sheldon et al. 2005) can be helpful in the early detection of a sinister pathology, which requires further investigations and imaging modalities. Not only is radiography inexpensive and readily available, but also forms part of the primary investigations for patients with suspected synovial and joint disease. Sound anatomical knowledge and appreciation of the normal anatomical boundaries allow the radiologist to identify where the abnormality may be arising from as well as the extent of the pathology.

2.2 Computed Tomography (CT) CT is based on the principle that radiodensity of a tissue can be measured by calculating the atten-

Frequent—rings and arc Frequent—linear, delicate, stratified Frequent— amorphous, cloudy

Rare

Frequent— dense due to hemosiderin Frequent Infrequent Frequent

uation coefficient. An X-ray tube takes a series of X-ray images from different angles; using a complex mathematical algorithm and computer processing, a cross-sectional image with exquisite anatomical detail is produced. Low-dose musculoskeletal CT is widely used and achieves an effective dose comparable to that of conventional radiography with added detail relating to soft tissues. Faint calcification may not be readily discernable on radiographs but is better depicted on CT. Table 1 shows the radiographic and CT findings in synovial pathology.

2.3 Dual-Energy Computed Tomography (DECT) Recent developments in CT include DECT, also known as spectral imaging. This allows characterization of tissues based on their relative absorption of X-rays during simultaneous image acquisition at different photon energy levels (typically 80 and 140 kVp) (Johnson et al. 2007). The

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difference in the attenuation of the X-ray beam is related to the atomic weight number and electron density of the tissue being examined. Early scanners employed a single-source and single-­ detector machine setup, utilizing an X-ray source capable of alternating between two peak voltages (“kV switching”) (Johnson 2012). Current machine setups, known as dual-source DECT scanners, are capable of simultaneous image acquisition at two different photon energy levels by utilizing two separate X-ray tubes and detectors placed between 90° and 95° apart (Flohr et al. 2006). An important application of DECT is its ability to detect urate crystals with high specificity in the case of gout. DECT provides a color-coded representation and quantification of tophus without the need for invasive synovial fluid or tissue sampling. Urate crystals are usually radiodense and have a higher mean CT value compared to adjacent soft tissues, allowing discrimination between the adjacent tissues and accurate identification of the urate crystals (Christiansen et al. 2020; Geijer et al. 2021). DECT can also be used to detect calcium in calcium pyrophosphate dihydrate deposition disease (CPPD) (Tanikawa et al. 2018) as well as in analyzing collagenous (tendons and ligaments) structures owing to the presence of dense side chains within collagen molecules obviating the need for CT arthrography (Johnson and Fink 2011). Using tissue decomposition algorithms, the tendons or ligaments can be color coded and fused to the conventional grayscale CT images, which allow precise localization (Mallinson et al. 2016).

3 Anatomical Considerations Knowledge of articular anatomy, joint boundaries, capsular attachments, and normal soft tissue/ fat planes provides the radiologist with confidence in reaching an appropriate differential diagnosis for intra/extra-articular tumors and tumorlike conditions. Joints have complex anatomy: adjacent or contiguous bursae, tendinous attachments, and various joint recesses. Disease processes affect-

ing the synovium can either arise from or extend into the abovementioned synovial tissues, thereby stressing the importance of anatomical knowledge.

3.1 Synovial Joints Unlike cartilaginous and fibrous joints, synovial joints are unique because of the presence of a fluid-filled space, the joint cavity. The articulating surfaces of a synovial joint are lined by smooth hyaline cartilage. The boundaries of the joint cavity are formed by the articular capsule, a fibrous connective tissue that attaches to the bone at the interface where the articular cartilage finishes and anatomically allows appreciation of the boundaries within which a synovial tumor or tumorlike condition can arise. The inner surface of the articular capsule is lined by a synovial membrane, which secretes synovial fluid; this acts as a lubricant between the opposing bones within joint cavity allowing for smooth movement, minimal friction, and increased mobility. The articular cartilage is relatively avascular, and the synovial fluid provides a source of nourishment.

3.2 Periarticular Fat Planes Periarticular soft tissues in the form of fat planes (fat pads) are located around joints. Normal fat planes are well defined and distinct. Although a small synovial tumor or tumorlike condition may not be readily discernable on a radiograph, displacement or obscuration of the relevant fat planes should prompt the radiologist to an underlying synovial pathological process.

3.3 Tendons Tendons are tough bands of connective tissue, connecting muscles to bones, and allow for the stabilization of the joint. The tendon is enveloped by further layers of connective tissue termed the tendon sheath, which is lined by synovium. The

Radiography and CT in Synovial Tumors and Tumorlike Conditions

synovium within the tendon sheath shares the same cellular and histological characteristics to that found in synovial joints. The synovial fluid provides nourishment to the tendon as well as provides a low-friction environment, allowing smooth gliding of the tendon, which in return reduces wear and tear. Pathology in and around the tendons, as in the case of calcific tendinopathy, can present as an increased density on radiographs; soft tissue swelling or calcification can be mistaken for a tumor, and MRI is often necessary for better characterization. On radiographs, tendons are difficult to appreciate with confidence, but an understanding of their anatomical location can help raise the suspicion that a tumor may be tendon related, especially in the periarticular location, or dismiss a benign finding. CT provides better delineation of a suspected tumor or tumorlike condition arising from or involving the tendons. Some tendons like the popliteus, flexor hallucis longus, and long head of biceps tendons communicate with the joint cavity allowing a joint-related pathology as well as tumors and tumorlike conditions to potentially extend into any of these tendons via the joint communication.

3.4 Bursae Bursae are extra-articular fluid-filled, small sacs found between a tendon or muscle and adjacent bony prominence and may communicate with the joint. Bursae perform the role of a cushion by reducing tension and wear and tear and allow low resistance movements, at an interface where pressure is being generated. Bursae can be either adventitious or native (anatomical). The most prevalent bursae, the native bursae, are lined with a synovium and are located at predictable anatomical locations. Knowledge of the normal bursae and their location can help distinguish them from a potential disease process. Bursae may or may not communicate with the joint and when they do in the case of a native bursa the bursal pathology results

65

from a synovial process and reflects an intra-­ articular process, such as a joint effusion, synovial hypertrophy, or intra-articular loose bodies (Ruangchaijatuporn et al. 2017).

4 Anatomical Considerations of Some Common Synovial Joints Outlined below are the anatomical considerations: capsular attachments, tendons, bursae, and fat planes for some common joints affected by synovial tumors and tumorlike conditions. These joints and the structures mentioned can potentially be seen on radiography and of course in much more detail using CT.

4.1 Shoulder Articular capsule: Glenohumeral joint has a loose articular capsule (Rugg et  al. 2018), which wraps around the anatomic neck of the humerus extending to the rim of the glenoid fossa (Chang et al. 2021). Fat planes: This can be identified as a linear radiolucency deep to the deltoid muscle, extending between the greater tuberosity laterally and the acromion medially, and is a representation of the extrasynovial fat which lines the subacromial-subdeltoid (SASD) bursa. In the case of calcific tendonitis, rheumatoid arthritis (Mitchell et  al. 1988), and massive rotator cuff tears, the fat plane can be obliterated and a radiodense focus may be seen. Tendons: The long head of biceps (LHB) tendon is intra-articular but extrasynovial; the tendon sheath is lined with synovium, and it communicates with the joint (Morris et  al. 2014); therefore, an intra-articular disease process can extend into the LHB tendon sheath or arise from it and then extend into the joint. Therefore, synovial tumors and tumorlike conditions should be considered when differential radiodensities or loose bodies are

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observed on radiography or CT; for example, synovial chondromatosis originating from the joint can be seen tracking along the LHB tendon sheath confirming the articular relationship. Bursae: Clinically, the most significant bursae around the shoulder are the SASD (two confluent bursae), subcoracoid, and subscapular bursae. Normally, there is no communication between the SASD bursa and the joint cavity. In the event of rotator cuff tear, the bursa can communicate with the glenohumeral joint. It is this bursa that when distended is apparent on the frontal radiograph. Basic calcium phosphate (BCP) crystal deposition disease, formerly known as hydroxyapatite deposition disease (HADD) and calcific tendinopathy, may also be bursal related and can be seen as a radiodensity on radiography and CT. Albeit rare, amyloidosis has a predilection for the SASD bursa. Normally, there is no communication between the subcoracoid bursa and the joint cavity; communication with the SASD bursa is seen in 50% of patients (Meraj et al. 2014; Schraner and Major 1999), which can potentially allow communication between the bursa and joint cavity via the SASD bursa if the rotator cuff is incompetent. The subscapular bursa communicates with the joint via openings between the

a

b

Fig. 1 Elbow radiographs of three different patients. Lateral projection. (a) Normal anterior fat plane (white arrows). (b) Elevation of the anterior fat plane and presence of the posterior fat plane in keeping with an intra-

superior and middle glenohumeral ligaments, and therefore, intra-articular disease process can extend into the bursa or arise from it.

4.2

Elbow

Articular capsule: Anteriorly, the capsule attaches to the coronoid process and radial fossa of the humerus. The articular capsule extends just beyond the medial and lateral joint lines, except for at the medial and lateral epicondyles, at the origin of the common extensor and flexor tendons. Fat planes: There are two fat planes in the elbow, best assessed on the lateral radiograph and sagittal CT.  The physiological anterior fat plane is seen as a “teardrop” configuration in the normal flexed elbow, and its presence is deemed normal (Fig.  1a). Diffuse synovial disease, a tumor or tumorlike condition as well as a joint effusion whether secondary to infection, inflammation, or joint disease, can displace and elevate the normal anterior fat plane assuming a “sail” configuration. The posterior fat plane is hidden within olecranon fossa; the presence of the posterior fat plane is always deemed pathological (Fig.  1b), suggestive of similar pathologies which cause an elevated anterior fat plane.

c

articular pathology (black arrows). (c) Distension of the olecranon bursa with radiodense contents in keeping with gout (dashed lines)

Radiography and CT in Synovial Tumors and Tumorlike Conditions

Bursae: There are two bursae around the elbow joint: the bicipitoradial and olecranon bursae. The bicipitoradial bursa does not communicate with the joint. Although the common pathology here is usually secondary to overuse injury or distal biceps tendinosis, radiographically the appearances may present as a mass. Calcification in the region of the distal biceps tendon attachment suggestive of calcific tendinopathy, or ill definition of the proximal radius suggestive of an effusion, should prompt further investigation of the joint to exclude a synovial tumor or tumorlike condition. The olecranon bursa is superficial and located in the subcutaneous tissues overlying the olecranon. Gout has a propensity for this bursa as well as the prepatellar bursa, where cloud-like radiodense material characteristic of tophus can be readily appreciated on radiography (Fig. 1c) and CT. In the event of the tophus located adjacent to bone, a cortical erosion is often seen (Ruangchaijatuporn et  al. 2017).

a

Fig. 2  Right hip radiograph. (a) Right hip radiograph demonstrates the normal appearances of the fat planes. (b) Same right radiograph with annotations demonstrating the fat planes (gluteus minimus (Gmin), gluteus medius

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4.3 Hip Articular capsule: Proximally, the articular capsule attaches to the acetabular margin and transverse acetabular ligament, whereas distally, the attachment is at the femoral neck. Fat planes: There are three periarticular fat planes around the hip (Fig. 2): obturator internus, iliopsoas, and gluteus. The obturator internus fat plane is medial to the obturator internus muscle. The iliopsoas fat plane is medial to the iliopsoas muscle. The gluteus fat plane is in between gluteus medius laterally and the gluteus minimus medially. Periarticular fat planes are not always symmetrical or readily discernable on radiographs. A disturbance in a fat plane is highly suggestive of an underlying pathology, but the absence of a fat plane does not exclude an underlying joint or synovial pathology. The iliopsoas fat plane is radiographically visible in a large percentage of patients and usually asymmetrical, routinely well defined on one side, and indistinct on the other side,

b

(Gmed), obturator (Obt), and iliopsoas (Ili) as well as bursae (blue ovoid shapes): trochanteric laterally and iliopsoas medially)

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assuming a neutral or “bulgy” configuration. The obturator internus fat planes, if radiographically present, are symmetrical. The gluteal fat planes are usually asymmetrical and vary in appearance. Tendons: There are many tendons around the hip with intimately related bursae. Bursae: The iliopsoas bursa (Fig. 2) is the largest bursa around the hip, located anterior to the joint capsule, and is present in 98% of hips. Through a gap between the iliofemoral and pubofemoral ligaments, the iliopsoas bursa may extend proximally to communicate with the joint space in 15% of normal hips, allowing the extension of intra-articular disease processes into the bursa, which may manifest as a mass in the ilioinguinal region. Primary disease processes involving the iliopsoas bursa include overuse injury, trauma, and rheumatoid arthritis of which all can be mistaken for a synovial tumor, tumorlike condition, or even a hernia. Radiologically, bursae at the greater trochanter can be seen deep to the gluteus minimus (subgluteus minimus), medius (subgluteus medius), and maximus (subgluteus maximus/trochanteric) muscles; bursitis here (commonly subgluteus minimus and medius) can lead to an effusion as well as soft tissue calcification, seen as distension of the bursa and altered density on radiography and even better delineated on CT.  Disease processes such as tuberculous (TB) infection and tenosynovial giant cell tumor (TSGCT) have a propensity for the subgluteus bursa (Ruangchaijatuporn et al. 2017).

4.4 Knee Various radiodensities are readily apparent around the knee joint and helpful in spotting an underlying disease process. The synovial membrane of the knee is the most extensive and can be subdivided into the central portion, suprapatellar synovial pouch, posterior femoral recesses, and subpopliteal recess.

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Articular capsule and tendons: The capsule surrounds the sides and posterior aspects of the knee joint. Behind the lateral tibial condyle, there is an opening which allows the popliteus tendon to emerge, and as a result communicates with the joint. Fat planes: On the lateral radiograph, with the knee mildly flexed, the suprapatellar recess creates a sharp vertical radiodense band between the anterior suprapatellar fat and pre-­femoral fat pad. This radiodense band is usually less than 5  mm but may be as thick as 10  mm (Fig. 3a, b). A disturbance in radiographic densities around these fat planes is suggestive of an effusion or an underling mass lesion (Fig. 3c, d). Loose bodies, synovial chondromatosis, and TSGCT are frequently encountered around the knee; these can be found in the joint cavity as well as in the bursae and recesses as they communicate with the joint. Bursae: There are many bursae around the knee which communicate with the joint cavity, allowing synovial tumors and tumorlike conditions to arise from there or extend into them. Calcific or ossific foci within the bursae are readily discernable on radiographs and CT and may be secondary to loose intra-articular bodies secondary to synovial chondromatosis or arthritis. The suprapatellar recess always communicates with the joint as well as with the medial and lateral joint recesses. Effusion, hemarthrosis, and synovial hypertrophy causing pathological bursal distension can be seen as a result of the communication with the joint (Ruangchaijatuporn et  al. 2017). Synovial chondromatosis although more commonly seen in the joint can easily extend into suprapatellar bursa (Walker et al. 2011) as can lipoma arborescens (Nisolle et  al. 1999). The popliteus bursa also communicates with the joint, and distension of the bursa is strongly associated with an intra-articular disease process, with some patients presenting with a mass in the posterolateral aspect of the knee. The gastrocnemius-semimembranosus bursa may also

Radiography and CT in Synovial Tumors and Tumorlike Conditions Fig. 3 Lateral knee schematic drawings and radiographs. (a, b) Normal collapsed suprapatellar recess between the suprapatellar and pre-femoral fat planes, seen as a radiodense band measuring between 5 and 10 mm (arrows). (c, d) There is obliteration of the suprapatellar and pre-femoral fat planes, seen as a thickened radiodense band with blurred margins (arrows), suggesting an intra-articular pathology

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c

b

d

communicate with the joint, but this is not always the case (Guerra et al. 1981; Lindgren and Willén 1977; Rauschning 1980; Calvisi and Zoccali 2016).

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Ankle

Articular capsule: Proximally, the capsule attaches to the articular surface of the medial and lateral malleoli and distally to the trochlear surface of the talus.

Tendons: Many tendons and their counterpart tendon sheaths are intimately associated with the ankle; the flexor hallucis longus communicates with the joint. Bursae and fat planes: There are two bursae around the ankle: the retrocalcaneal and retroAchilles bursae. The retrocalcaneal bursa is located between the Achilles tendon and posterior surface of the calcaneus (Fig.  4a, b). This potential space is lined with synovium and extends over both the Achilles tendon and the inferior aspect of the pre-Achilles

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a

b

Fig. 4 Lateral ankle. (a) Schematic diagram of the lateral ankle demonstrating the relationship of the anterior and posterior recesses (dashed lines), fat pad (yellow), and retrocalcaneal bursa (blue triangle). (b) Normal large radiolucent triangle representing Kager’s fat pad (white arrows). Boundaries of the normal anterior and posterior

(Kager’s) fat pad (Fig.  4a, b). This fat pad assumes a triangular configuration and is lucent with sharp but gently curving border on radiography. It is the disturbance in this sharp contour of the pre-Achilles fat pad which suggests an effusion or underlying pathology (Fig.  4c), and the same rationale applies for altered radiodensity in the region of the other ankle bursae. Further juxta-articular fat pads are intimately related to the anterior and posterior recesses and should be of fat density in normal circumstances and best seen on the lateral radiograph or sagittal CT plane. The anterior recess is intimately related to the neck of the talus. In the event where the anterior recess is distended, there will be loss/obscuration of the fat density resulting in the “teardrop” sign. Soft tissue density replacing the normal fat pads in either the anterior or the posterior recess can be secondary to a synovial tumor or tumorlike condition, and these changes are readily discernable on radiographs and better evaluated on CT (Ruangchaijatuporn et  al. 2017; Towbin et al. 1980).

c

ankles recess (dashed lines). (c) Increased radiodensity in the region of the Kager’s fat pad with resultant smaller visible radiolucent triangle (white arrows). Displacement of the anterior and posterior fat planes secondary to fullness in the anterior and posterior ankle recess (black arrows) suggestive of an intra-articular pathology

5

Pathological Considerations

In this section, the role of radiography and CT in the diagnosis of tumor and tumorlike conditions will be discussed. Synovial tumors can be grouped into (WHO 2020): • Benign—synovial hemangioma, juxtaarticular myxoma, and lipoma arborescens • Benign, locally aggressive—synovial chondromatosis and tenosynovial giant cell tumor • Malignant—synovial chondrosarcoma and synovial metastasis Conditions which may present as a tumorlike condition are not limited to and include BCP crystal deposition disease, CPPD, gout, amyloid arthropathy, rheumatoid arthritis, and tuberculous arthritis. As discussed previously, disturbance in the normal periarticular fat planes results in a change in radiographic density when compared with adjacent structures. It is this feature that can be readily observed on radiograph as well as on CT,

Radiography and CT in Synovial Tumors and Tumorlike Conditions

and these telltale signs allow some disease processes to be safely dismissed and potential concerning pathologies to be investigated. The difference in density usually accounts for the presence or absence of “something.” For example, the sharp vertical dense band created by the suprapatellar pouch would appear denser and thicker with blurred margins in the presence of a suprapatellar effusion, whereas the deposition of hemosiderin would appear even more dense. On radiography or CT, the soft tissues need to be interrogated for a relative radiodensity or radiolucency.

5.1 Synovial Hemangioma Synovial hemangioma is a vascular malformation seen arising from an intra-articular location, most commonly seen in the knees, elbow, and ankles. On radiography and CT, a joint effusion (usually dense, owing to hemosiderin content secondary to repetitive bleeds) and a nonspecific soft tissue mass are frequently encountered. Well-marginated pressure erosions are secondary to repetitive bleeds; phleboliths are rare but when seen are pathognomonic. Differential diagnosis includes TSGCT and hemophilic arthropathy and should be considered in view of a dense joint effusion, pressure erosions, and a dense soft tissue mass (no calcification) (Manaster 2016). Synovial hemangioma will be further discussed in the chapter “Synovial Hemangioma”.

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mass on radiographs. The soft tissue mass and radiodensity secondary to hemosiderin are also observed in TSGCT; however, the absence of a joint effusion and marginal erosions in juxtaarticular myxoma separates the two pathologies apart.

5.3 Lipoma Arborescens Lipoma arborescens is a tumorlike condition which manifests as a rare intra-articular lesion characterized by the replacement of synovial tissue with mature fat cells and is the only disease process discussed which manifests as a radiolucency within the joint space. Joint effusion is common as are coexistent degenerative changes readily discernable on radiography (Fig. 5) and CT. Erosions are infrequent (Larbi et al. 2016). Lipoma arborescens will be further discussed in the chapter “Lipoma Arborescens”.

5.4 TSGCT TSGCT can arise from either a synovial joint, tendon sheath, or bursa just like synovial chondromatosis, to be discussed next. Dense soft tissue swelling surrounding the joint secondary to hemosiderin deposition is a feature of TSGCT as

5.2 Juxta-Articular Myxoma Juxta-articular myxoma is a tumorlike condition which may present as a soft tissue mass with slightly increased density compared to the adjacent normal soft tissues. The tumorlike lesion may occur in close proximity to a large joint, usually the extremities. Juxta-articular myxomas microscopically resemble intramuscular ­myxomas. Areas of hemorrhage and hemosiderin give the appearance of a dense soft tissue

Fig. 5  Lipoma arborescens. Cross-table projection of the knee demonstrating space occupation in the suprapatellar recess with multiple radiolucent areas of fat within, as well as obscuration of the Hoffa’s fat pad in keeping with an intra-articular pathology

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Fig. 7  Primary synovial chondromatosis. Frontal radiograph of the left hip demonstrates innumerable, uniform, dense loose bodies with punctate, rings and arcs calcification in keeping with synovial chondromatosis

Fig. 6  TSGCT. Lateral foot radiograph: preserved bone density; marginal erosions of the anterior distal tibia and talar neck (black arrow); obliteration of the anterior and posterior ankle fat planes (dashed lines) secondary to a dense effusion and synovial proliferation. Obliteration of the Kager’s fat pad (*) revealing a smaller radiolucent triangle (white arrows)

is the lack of calcification (Fig. 6). There is better delineation of TSGCT on CT, where hypertrophic synovium is seen as a dense soft tissue mass (Larbi et al. 2016; Sheldon et al. 2005). Marginal pressure erosions on radiography are frequently seen in TSGCT. TSGCT will be further discussed in the chapter “Tenosynovial Giant Cell Tumor”.

5.5 Primary Synovial Chondromatosis TSGCT and non-calcific form of synovial chondromatosis share some imaging features. Hyaline cartilage nodules are formed from the periarticular synovium, tendon sheath, or bursa. The nodules may enlarge and detach from the synovium to form loose intra-articular bodies and continue to grow as they receive nourishment from the synovium, even when detached. Punctate calcification with rings and arcs is the hallmark for

chondroid-forming tumors, also known as chondroid matrix mineralization and seen in 70–95% of cases of synovial chondromatosis (Fig.  7). Radiographic findings will depend on the extent of ossification. On CT, in the absence of calcification, the non-mineralized nodules of synovial chondromatosis reflect the high water content of the cartilaginous tissue, which accounts for up to 25% of cases. Radiograph findings are likely to be nonspecific: soft tissue mass related to the joint (not as dense as TSGCT, as there is no hemosiderin content), extrinsic erosions in 20–25% of cases (less frequent when compared with TSGCT, but in less capacious joints, pressure erosions are more likely as a result of reduced capacity and the nodules/loose bodies may be pushed into an adjacent bursa or seen tracking along a tendon sheath), joint space widening followed by narrowing, and osteoarthritic changes. In the presence of extensive ossification, loose intra-articular bodies are seen and can either be fully ossified or demonstrate the classical rings and arcs pattern. The loose bodies are usually numerous and uniform in size. CT is also helpful in confirming the exact location of the loose bodies (Murphey et al. 2007). CT is superior to radiography for subtle calcification; approximately 33% of patients with synovial chondromatosis lack calcification on

Radiography and CT in Synovial Tumors and Tumorlike Conditions

CT, which can be mistaken for TSGCT (Murphey et al. 2007). Synovial chondromatosis will be further discussed in the chapter “Synovial Chondromatosis”. MRI is diagnostic in synovial chondromatosis and TSGCT, but CT arthrography is also helpful in demonstrating the location of the nodules/ loose bodies and can also depict the iso-­attenuated loose bodies within the joint, which have a similar density to that of synovial fluid and appear as multiple, uniform-sized filling defects, whereas random synovial based space occupation is seen in TSGCT.  Following intravenous contrast administration, there is typical peripheral and septal enhancement of the nodules/loose bodies in synovial chondromatosis, representing the fibrovascular septa and synovium, while the central nonenhancing areas represent the chondroid nodules. A focal or diffuse but homogenous enhancement is noted in TSGCT.

5.6 Synovial Chondrosarcoma Synovial chondrosarcoma most commonly involves the knee and hips. Malignant transformation of synovial chondromatosis to chondrosarcoma is reported between 1% and 10% (Bhadra et al. 2007; Davis et al. 1998; Wittkop et al. 2002). Radiological differentiation of synovial chondrosarcoma from synovial chondromatosis is often difficult and is dependent on the demonstration of bone destruction (Biazzo and Confalonieri 2016). Common features are the characteristic rings and arcs matrix mineralization, which is readily discernable on radiography and CT.  Radiography may demonstrate an increased density, secondary to an intra-articular mass, which may contain calcified bodies as well as bone erosions and bone destruction, best appreciated on CT (Fig.  8a–c). Chondrosarcoma may appear as de novo primary intra-articular tumors, although this is rare. Distinction between cases of primary chondromatosis, secondary chondrosarcomas arising from these, and rather rare primary synovial chondrosarcoma should be made with further imaging and tissue sampling (Sheldon et  al. 2005). Synovial chondrosarcoma will be discussed in detail in the chapter “Synovial Chondrosarcoma”.

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5.7 Synovial Metastasis Synovial metastasis is rare, and the radiographic and CT features are nonspecific. This will be further discussed in the chapter “Synovial Metastasis and Lymphoma”. Many tumorlike conditions that demonstrate calcification on radiography and CT may be mistaken for tumors. Most calcifications observed in our day-to-day practice are trivial, and some calcification can be an early indication of an unsuspected pathology. Many synovial tumors and tumorlike conditions may present with increased density in the form of calcification. Calcification is usually seen as a mineralized density, with an attenuation coefficient higher than soft tissues, but lower than bone. With CT, the Hounsfield unit (HU) for calcification varies, commonly between 100 and 400 HU, whereas the HU for bone is much higher (circa 700 and 1500 HU for trabecular and cortical bone, respectively) (Friere et  al. 2018). Calcification is usually apparent on radiographs, but CT is more sensitive in the detection and analysis of the calcification and provides insight into the location with respect to adjacent tissues. Calcifications have numerous appearances, locations, and etiologies. Employing a systematic approach will allow the image interpreter to narrow the differential diagnosis, which can in return minimize the triggering of further unnecessary investigations, referrals, and anxiety.

5.8 BCP Crystal Deposition Disease Soft tissue density changes, particularly around the shoulder joint, are frequently seen. Intra-­ tendon calcification in the form of amorphous, well-defined cloud-like calcification is classical, and the calcification may even be multiloculated, giving rise to a tumorlike appearance. Depending on the phase of the disease, the calcification may even migrate to the adjacent subacromial ­(subdeltoid) bursa as well as be seen in the periarticular region. These appearances are a result of hydroxyapatite accumulation in degenerative

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a

b

c

d

Fig. 8 Synovial chondrosarcoma. (a) Frontal right hip radiograph: Coxa profunda. Radiolucent foci (black arrow) in the femoral head and acetabulum in keeping with erosions. (b) Axial CT right hip: confirms the presence of subtle rings and arcs matrix mineralization (white

arrows) in keeping with synovial chondromatosis. (c, d). Axial CT and MRI right hip: destruction (*) of the acetabulum and tumor (white arrow) eroding the acetabulum and extending into the pelvis suggestive of synovial chondrosarcoma

and traumatized tendons. Mineralization not related to BCP crystal deposition disease in the form of degenerative enthesopathy must be differentiated from calcific tendinopathy, with the former showing no resolution in the calcification

formed, and with some progressing to coarser ossification. It is important to be aware of the anatomical considerations discussed earlier, in order to appreciate where the calcification is arising from.

Radiography and CT in Synovial Tumors and Tumorlike Conditions

5.9 CPPD CPPD has a tendency for intra-articular structures: hyaline cartilage, fibrocartilage, synovium, capsule, and ligaments. The knee, pubic symphysis, and wrist are most involved, as well as the spine in the case of crowned dens syndrome. In both the acute and chronic phases of CPPD, the deposits present as fine, linear, or punctate calcification, following the fibrillar architecture of the affected tissue (Omoumi et  al. 2016), whereas within the cartilage, they are seen to deposit in the middle layer giving rise to a linear pattern which is parallel to the subchondral bone, in contrast to gout which deposits on the surface of cartilage. CPPD may progress to severe arthropathy resembling osteoarthritis (OA), and radiographic features are helpful in differentiating between the two. In CPPD, the arthropathy is severe and progressive causing the formation of loose intra-­ articular bodies as well as marked subchondral cystic changes (Fig.  9). Non-weight-bearing

Fig. 9  CPPD. Frontal knee radiograph: joint space narrowing at the tibiofemoral joints (medial more than lateral), large subchondral cysts and erosions (black arrow), and lateral meniscus chondrocalcinosis (white arrow)

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joints can be equally affected as weight-bearing joints, which is atypical for OA.

5.10 Gout Tophus is a pathognomonic feature of chronic gout and presents as dense skin nodules, which can be mistaken for a tumorlike condition. Gouty tophi are usually fainter than the deposits seen with CPPD. The distribution of gout is usually within tendons, ligaments, and bursae, unlike CPPD which has a tendency for periarticular soft tissues: hyaline cartilage, fibrocartilage, synovium, capsule, and ligaments (Omoumi et al. 2016). Although gout deposits are not typically seen in cartilage, they can be observed in advanced disease, as can joint space narrowing. Radiographic signs of chronic gout include eccentric, asymmetric articular, juxta-articular, or periarticular soft tissue nodules corresponding to the tophi (Dalbeth et al. 2010). Bone erosions are typical of gout, have a sclerotic margin, and are present in the intra-articular or juxta-articular location with overhanging edges typically near the tophi. Bone density is usually preserved in gout (Omoumi et  al. 2016). Intra-osseous calcification secondary to the penetration of the calcified tophus has been described in severe cases and should not be confused with entities like enchondroma or bone infarcts (Resnick and Broderick 1981). As well as CPPD, differential diagnosis of gout includes rheumatoid arthritis (RA) and amyloid arthropathy. In the acute phase of gout, radiographs may be normal or may only show nonspecific findings: soft tissue swelling and joint effusion in which case ultrasound or CT may be more helpful. CT is more sensitive owing to its excellent resolution and high contrast and remains the modality of choice (Fig. 10a), and crystals can be differentiated based on their density, with CPPD crystals being denser than those found in gout (Omoumi et al. 2016). DECT provides a color-coded representation and quantification of tophus (Fig.  10b) without the necessity of identifying monosodium urate (MSU) crystals in synovial fluid or tissue aspirates (Christiansen et al. 2020). Gout will be further discussed in the chapter “Mimics of Synovial Tumors Due to Trauma and Inflammation”.

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a

Fig. 10  Gout. (a) Forefoot coronal CT: punched-out, marginal erosions (black arrows) with a sclerotic margin and radiodense tophi (white arrows). (b) Forefoot coronal

b

DECT: color-coded representation confirming monosodium urate crystals in the radiodense foci confirming gout

5.11 Arthritides Accumulation of amyloid in and around the joints in amyloid arthropathy is similar to gout. Involvement is bilateral, most frequently affecting the shoulders, hips, knees, and wrists. On radiography and CT, findings similar to gout can be observed: preserved joint space, joint effusion, juxta-articular increased density masses, and erosions. However, the presence of periarticular osteopenia and subchondral cystic changes differentiates amyloid arthropathy from gout (Sheldon et al. 2005). Joint amyloidosis will be further discussed in the chapter “Synovial Amyloidosis”. Rheumatoid arthritis primarily involves the synovial joints. It is thought that an inflammatory response results in hyperplastic and hypervascular synovium, called pannus, which can present as a tumorlike condition. Affected joints demonstrate soft tissue swelling, which is usually fusiform and periarticular and is a combination of edema, joint effusion, and tenosynovitis. The altered radiodensity as a result of the swelling can be an early sign on radiography. Other radiographic hallmarks of RA are marginal erosions (Fig. 11) seen in the

Fig. 11  Rheumatoid arthropathy. Shoulder radiograph: Periarticular osteopenia and marginal erosions (black arrows)

bare areas, frequently at the radial side of the metacarpophalangeal joints. Juxta-articular osteopenia progressing to generalized osteoporosis and symmetrical joint space narrowing is also observed on radiography. Osteoporosis and symmetrical joint space narrowing seen in RA are not features of gout. CT is not routinely used for the evaluation of RA, except in the

Radiography and CT in Synovial Tumors and Tumorlike Conditions

cases of spine and for preoperative assessment (Larbi et al. 2016). RA will be further discussed in the chapter “Mimics of Synovial Tumors Due to Trauma and Inflammation”.

5.12 Tuberculosis (TB) Half of the patients present with tenosynovitis, bursitis, and arthritis. Radiographic findings typically include monoarticular involvement, soft tissue swelling, and joint effusion appreciated as a change in soft tissue density, as well as periarticular osteopenia and marginal erosions. Joint space narrowing is seen later, owing to the preservation of the articular cartilage until late in the course of the disease. CT can be helpful in identifying periarticular abscesses, often encountered in TB arthritis (Sheldon et al. 2005). Many extrapulmonary radiographic features observed in TB overlap with RA, the distinguishing features being that TB is usually monoarticular whereas RA is polyarticular and that symmetrical joint space narrowing is an early feature of RA but a later feature of TB. Joint TB will be further discussed in the chapter “Mimics of Synovial Tumors Due to Chronic Infection”.

6 Conclusion Radiography and CT are readily available and inexpensive imaging modalities with radiography being employed as a first-line modality in the imaging of the musculoskeletal system. Both radiography and CT allow the evaluation of bone density, erosions, mineralization, and soft tissue masses to varying degrees, allowing the radiologist to readily compile a short list of plausible differential diagnosis.

7 Key Points • Synovial tumors and tumorlike conditions can arise from the joint and extend into other synovial lined structures such as bursae and tendon sheaths.

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• Radiography is inexpensive, readily available, and usually the first imaging modality performed in musculoskeletal radiology. • CT allows a 3D reconstruction of the 2D image, providing a superior image quality and better anatomical details for characterization and location of a tumor or tumorlike condition. • Good anatomical knowledge allows fat planes and bursae to be identified on radiography and CT; a disturbance or obscuration of these implies a synovial based pathology. • DECT allows color-coded representation of urate crystals without the need for invasive procedures. • MRI is the gold standard for assessing the synovium, but radiography, CT, and DECT are very helpful in the workup of synovial tumors and tumorlike conditions. Acknowledgments Thanks go to Mr. Andy Biggs, Medical Illustrations Department, RJAH.

References Bhadra A, Pollock R, Tirabosco RP, Skinner JAM, Cannon SR, Briggs TWR, Flanagan AM (2007) Primary tumours of the synovium—a report of four cases of malignant tumour. J Bone Joint Surgery Br 89:1504 Biazzo A, Confalonieri N (2016) Synovial chondrosarcoma. Ann Transl Med 4:280 Calvisi V, Zoccali C (2016) Arthroscopic patterns of the poster-medial aspect of the knee joint: classification of the gastrocnemius-semimembranosus gateway and its relationship with Baker’s cyst. Muscles Ligaments Tendons J 6:492–498 Chang L-R, Anand P, Varacallo M (2021) Anatomy, shoulder and upper limb, glenohumeral joint. In: StatPearls. StatPearls Publishing, Treasure Island, FL Christiansen S, Müller FC, Østergaard M, Slot O, Møller JM, Børgesen HF, Gosvig KK, Terslev L (2020) Dual-energy CT in gout patients: do all colour-coded lesions actually represent monosodium urate crystals? Arthritis Res Ther 22:212 Dalbeth N, Pool B, Gamble GD, Smith T, Callon KE, McQueen FM, Cornish J (2010) Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum 62:1549–1556 Davis R, Hamilton A, Biggart JD (1998) Primary synovial chondromatosis: a clinicopathologic review and assessment of malignant potential. Hum Pathol 29:683–688

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Flohr TG, McCollough CH, Bruder H, Petersilka M, Murphey M, Vidal JA, Fanburg-Smith JC, Gajewski DA (2007) Imaging of synovial chondromatosis with Gruber K, Süss C, Grasruck M, Stierstorfer K, Krauss radiologic-pathologic correlation. Radiographics B, Raupach R, Primak AN, Küttner A, Achenbach S, 21(5):1465 Becker C, Kopp A, Ohnesorge BM (2006) First performance evaluation of a dual-source CT (DSCT) sys- Nisolle JF, Blouard E, Baudrez V, Boutsen Y, De Cloedt P, Esselinckx W (1999) Subacromial-subdeltoid lipoma tem. Eur Radiol 16:256–268 arborescens associated with a rotator cuff tear. Skelet Friere V, Moser TP, Lepage-Saucier M (2018) Radiol 28:283–285 Radiological identification and analysis of soft tissue musculoskeletal calcifications. Insights Imaging Omoumi P, Zufferey P, Malghem J, So A (2016) Imaging in gout and other crystal-related arthropathies. Rheum 9:477–492 Dis Clin N Am 42:621–644 Geijer M, Inci F, Solidakis N, Szaro P, Al-Amiry B (2021) The development of musculoskeletal radiology for 100 Rauschning W (1980) Anatomy and function of the communication between knee joint and popliteal bursae. years as presented in the pages of Acta Radiologica. Ann Rheum Dis 39:354–358 Acta Radiol 62:1460–1472 Guerra J, Newell J, Resnick D, Danzig LA (1981) Resnick D, Broderick TW (1981) Intraosseous calcification in tophaceous gout. AJR Am J Roentgenol Gastrocnemio-semimembranosus bursal region of the 137:1157–1161 knee. Am J Roentgenol 136:593–596 Johnson TR (2012) Dual-energy CT: general principles. Ruangchaijatuporn T, Gaetke-Udager K, Jacobson JA, Yablon CM, Morag Y (2017) Ultrasound evaluation of AJR Am J Roentgenol 199:S3–S8 bursae: anatomy. Skelet Radiol 46:445–462 Johnson T, Fink C (2011) Dual energy CT in clinical practice. Springer Science & Business Media, Rugg CM, Hettrich CM, Ortiz S, Wolf BR, MOON Shoulder Instability Group, Zhang AL (2018) Berlin Surgical stabilization for first-time shoulder disloJohnson TR, Krauss B, Sedlmair M, Grasruck M, Bruder cators: a multicenter analysis. J Shoulder Elb Surg H, Morhard D, Fink C, Weckbach S, Lenhard M, 27:674–685 Schmidt B, Flohr T, Reiser MF, Becker CR (2007) Material differentiation by dual energy CT: initial Schraner AB, Major NM (1999) MR imaging of the subcoracoid bursa. AJR Am J Roentgenol experience. Eur Radiol 17:1510–1517 172:1567–1571 Larbi A, Viala P, Cyteval C, Snene F, Greffier J, Faruch M, Beregi J-P (2016) Imaging of tumors and tumor-­ Sheldon P, Forrester DM, Learch TJ (2005) Imaging of intrarticular masses. Radiographics 25:105–119 like lesions of the knee. Diagn Interv Imaging Tanikawa H, Ogawa R, Okuma K, Harato K, Niki Y, 97(7–8):767–777 Kobayashi S, Nagura T (2018) Detection of calcium Lindgren PG, Willén R (1977) Gastrocnemio-­ pyrophosphate dihydrate crystals in knee meniscus by semimembranosus bursa and its relation to the knee dual-energy computed tomography. J Orthop Surg Res joint: I.  Anatomy and histology. Acta Radiol Diagn 13:73 (Stockh) 18:497–512 Mallinson P, Coupal TM, McLaughlin PD, Nicolaou S, Towbin R, Dunbar JS, Towbin J, Clark R (1980) Teardrop sign: plain film recognition of ankle effusion. AJR Am Munk PL, Ouellette HA (2016) Dual-energy CT for J Roentgenol 134:985 the musculoskeletal system. Radiology 281(3):690 Manaster BJ (2016) Diagnostic imaging: musculoskeletal Turan A, Çeltikçi P, Tufan A, Öztürk MA (2017) Basic radiological assessment of the synovial diseases: picnon-traumatic disease, 2nd edn. Elsevier torial essay. Eur J Rheumatol 4:166–174 Meraj S, Bencardino JT, Steinbach L (2014) Imaging of cysts and bursae. Semin Musculoskelet Radiol Walker EA, Murphey MD, Fetsch JF (2011) Imaging characteristics of tenosynovial and bursal chondroma18:436–447 tosis. Skelet Radiol 40:317–325 Mitchell MJ, Causey G, Berthoty DP, Sartoris DJ, Resnick D (1988) Peribursal fat plane of the shoulder: WHO Classification of Tumours (2020) Soft tissue and bone tumours. International Agency for Research on anatomic study and clinical experience. Radiology Cancer, Lyon 168:699–704 Morris B, Byram IR, Lathrop RA, Dunn WR, Kuhn JE Wittkop B, Davies A, Mangham D (2002) Primary synovial chondromatosis and synovial chondrosarcoma: a (2014) Mapping the articular contact area of the long pictorial review. Eur Radiol 12:2112–2119 head of the biceps tendon on the humeral head. Anat Res Int 2014:814721

Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions A. R. Goossens, F. M. Vanhoenacker, and K. L. Verstraete

Contents 1 2 2.1 2.2 2.3 2.4 2.5 2.6 3 3.1 3.2 3.3

4

Field Strength, Coils, Matrix, and Imaging Planes

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Basic Sequences T1-Weighted Imaging (T1-WI) T2-Weighted Imaging (T2-WI) T2* Gradient Recalled Echo (T2* GRE) Value of Fat Suppression (fs) Sequences Fluid-Sensitive Sequences Gadolinium Contrast-Enhanced MRI

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Advanced MR Techniques Dynamic Contrast-Enhanced MRI (DCE-MRI) Diffusion MRI MR Spectroscopy

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Role of MRI in Characterization and Grading

Role of MRI in Evaluation of Lesion Extension 5.1 Size 5.2 Lesion Localization and Compartmental/ Extracompartmental Extension 5.3 Local Staging

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6.1 6.2

Role of MRI in Follow-Up After Treatment Follow-Up of Malignant Synovial Tumors Follow-Up of Benign Lesions

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Key Points

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References

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A. R. Goossens AZ Jan Palfijn Ghent and Ghent University Hospital, Ghent, Belgium e-mail: [email protected] K. L. Verstraete Ghent University, Ghent, Belgium e-mail: [email protected] F. M. Vanhoenacker (*) Department of Radiology, AZ Sint-Maarten Mechelen, Mechelen, Belgium Antwerp University Hospital, Faculty of Medicine and Health Sciences, University of Antwerp, Edegem, Belgium Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium Faculty of Medicine, University Leuven, Leuven, Belgium e-mail: [email protected] Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_427, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 30 April 2023

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Abstract

Due to its unparalleled soft tissue resolution and multiplanar imaging capability, MRI is the modality of choice for imaging synovial tumor and tumorlike lesions. The minimal hardware requirements, imaging protocol, and either basic or advanced MR sequences are described. For lesion characterization, four major groups can be distinguished based on the analysis of signal intensities on T1- and T2-weighted images. Furthermore, this chapter gives an overview on the role of MRI in grading and local staging and might serve as a guideline for suggesting a relevant differential diagnosis and prognosticating the probability or degree of malignancy of synovial tumors. MRI characteristics for some specific tumors are further described in the respective chapters of this book.

Abbreviations DCE-MRI Dynamic contrast-enhanced MRI FOV Field of view FS Fat suppressed FSE Fast spin echo GRE Gradient recalled echo MRI Magnetic resonance imaging SE Spin echo SI Signal intensity STIR Short tau inversion recovery TSGCT Tenosynovial giant cell tumor WI Weighted image

1 Field Strength, Coils, Matrix, and Imaging Planes The basic requirements of primary diagnosis of tumor and tumorlike conditions of the joint are similar to the imaging protocol of other soft tissue tumor and tumorlike conditions. A magnetic field strength of 1.5 Tesla (T) is considered a minimum requirement for the evaluation of synovial lesions. Currently, literature data on the value of MRI in the diagnosis of soft tissue

tumors are mostly based on the use of a magnet strength of 1.5 T. 1.5 T magnets are widely available, are known to provide good-quality images, and are useful for the evaluation of soft tissue tumors in daily practice. For more advanced imaging and multiparametric imaging, including proton nuclear MR spectroscopy, 3  T magnets may add additional information, but there is currently no evidence that this may alter clinical decision-making. Patient coils, field of view (FOV), and matrix size are three important parameters for optimizing spatial resolution and thus allowing markedly improved anatomic delineation of adjacent vessels, fascial planes, nerves, and other structures. Dedicated joint-specific multi-phased array coils are recommended. The FOV should be as large as necessary to image the entire lesion, peritumoral edema, and a layer of adjacent normal tissue. The use of at least one sequence with a large FOV may be used for initial detection or for detection of multifocality. Multiplicity, satellite lesion, and abnormal proximal lymph nodes should be described on these large FOV.  However, use of a large FOV results in a loss of spatial resolution. Therefore, a smaller FOV targeted to the lesion is recommended for detailed information (Brys 2017). The imaging matrix should be as high as achievable to demonstrate relevant morphologic features and anatomic detail. The matrix should be optimized to achieve high in-plane spatial resolution, high signal-to-noise ratio, and a reasonable examination time (e.g., 256, if possible 384, or even 512). To determine whether a lesion is confined to a single compartment and whether it is invading or encasing surrounding structures, axial planes are key. Indeed, as most anatomical compartments of the extremities are oriented longitudinally, the axial plane is usually the most important to assess the localization and local extent of a lesion. T1and T2-weighted images (WI) should be obtained in the axial plane at exactly the same location to allow image-by-image comparison. In addition, to reliably image nonpalpable masses, images should be obtained in a longitudinal plane, either sagittally or coronally, to define the extent of the lesion as anteroposteriorly or mediolaterally,

Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions

respectively, and to measure a lesion in three dimensions. It should be noted that for certain synovial tumor and tumorlike conditions, the primary imaging plane may differ; for example, for diffuse-type intra-articular TSGCT of the ankle and knee, the sagittal plane is often preferred, whereas the coronal plane provides the most valuable information for evaluation of diffuse-­ type intra-articular TSGCT of the shoulder.

2 Basic Sequences Due to its exquisite soft tissue contrast, MRI is currently regarded as the imaging technique of choice for detection and characterization of tumor and tumorlike conditions of the synovium, especially in large joints. Both spin-echo (SE) and fast spin-echo (FSE) sequences are feasible to achieve this goal. In small joints, such as the fingers, and superficially located cystic lesions, ultrasound may serve as an alternative (see the chapter “Ultrasound of Synovial Tumors and Tumorlike Conditions”).

2.1 T1-Weighted Imaging (T1-WI) 2.1.1 T1-WI Without Fat Suppression (Non-FS T1-WI) Non-FS T1-WI is typically used for accurate anatomical delineation in relation to intermuscular fat planes, fat surrounding neurovascular structures, subcutaneous fat, and fatty bone marrow (Amini et al. 2015; Brys 2017). On T1-WI without fat suppression, synovial tumor and tumor-­like lesions are generally iso- or hypointense to muscle and synovium, resulting in a high tumor-­to-­fat contrast but low tumor-to-muscle and tumor-to-synovium contrast. Exceptions are fatty tumors like lipoma arborescens and synovial lipoma, which are T1 hyperintense to muscle and synovium, thus showing a high tumor-to-muscle and tumor-tosynovium contrast. High-resolution axial images can be obtained first and precede the longitudinal imaging plane that best illustrates the relationship of the lesion with the synovium, bone, and vessels. As a baseline for fat suppression and/or contrast-

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enhanced studies and for surgical planning, nonFS T1-WI is an essential imaging sequence (Wu and Hochman 2009; Brys 2017).

2.1.2 T1-WI with Fat Suppression (FS T1-WI) FS helps to differentiate between hyperintense signal caused by fat or other T1 hyperintense substances, such as methemoglobin, mucoid tissue, proteinaceous fluid, and melanin (Wu and Hochman 2009; Grande et al. 2014; Brys 2017). Therefore, FS T1-WI is more useful in the characterization of synovial tumor or tumorlike conditions which are hyperintense on non-FS T1-WI rather than lesions which are iso- or hypointense to muscle on non-FS T1-WI.  Fat-containing lesions, such as synovial lipoma and lipoma arborescens, will be hyperintense on non-FS T1-WI, but will become hypointense on FS T1-WI. On the contrary, a post-traumatic hemorrhagic mass containing methemoglobin will be hyperintense signal on both non-FS and FS T1-WI (Wu and Hochman 2009).

2.2 T2-Weighted Imaging (T2-WI) T2-weighted sequence without fat saturation can offer additional morphological information useful for narrowing the differential diagnosis. T2 hypointense signal can be caused by evolving blood products (hemosiderin), flowing blood, calcifications, crystalline deposits, and collagenous fibrous tissue (Finkelstein et  al. 2021). As mentioned before, T1- and T2-weighted acquisitions could be obtained in the axial plane at exactly the same location to allow image-by-­ image comparison. Note that, if visible, the synovial membrane has high signal intensity on T2-WI (Burke et al. 2019).

2.3 T2* Gradient Recalled Echo (T2* GRE) Gradient recalled echo (GRE) imaging sequences are indispensable for the evaluation of hemosiderin-­ containing lesions. Hemosiderin

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deposition causes a local magnetic susceptibility effect that shows low signal intensity on T2* gradient echo imaging as compared with that on T2-WI. This effect is referred to as blooming and can be observed in  localized and diffuse-type tenosynovial giant cell tumors (TSGCTs) (Fig.  1), (synovial) hemangioma, hemophilic arthropathy, and chronic hematomas (Narváez

et al. 2001; Wu and Hochman 2009; Garner and Bestic 2013; Mallinson et  al. 2014; Kransdorf and Murphey 2016; Levine et al. 2016). Calcified nodules in chondromatosis may also cause blooming. Therefore, correlation with radiographs or CT is required as presence of calcifications argues against TSGCT and favors the diagnosis of chondromatosis.

a

b

c

d

Fig. 1 Intra-articular diffuse-type tenosynovial giant cell tumor of the knee, previously designated as pigmented villonodular synovitis. (a) Sagittal T1-WI; (b) sagittal FS T1-WI; (c) sagittal FS proton density-WI; (d) sagittal T2* gradient recalled echo. Both T1-WIs show two TSGCT foci of low SI to muscle: one arises in the infrapatellar fat

pad, and the other causes pressure erosion in the tibia (arrows, a and b). The proton density-WI illustrates associated bone marrow edema surrounding the pressure erosion (arrowheads, c). Blooming is seen on T2* GRE, a local magnetic susceptibility artifact caused by the presence of hemosiderin (asterisks, d)

Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions

2.4 Value of Fat Suppression (fs) Sequences When using fat suppression for the characterization of synovial lesions, the aim is to maximize tumor conspicuity, to confirm or exclude the presence of intralesional fat and for further characterization of lesions of high signal intensity on nonfat T1-WI. There are different methods of fat suppression. Short tau inversion recovery (STIR) is a fat suppression based on nulling of tissues with an appropriate T1 relaxation time (Mirowitz et al. 1994). This nonselective nature may lead to suppressing of nonfatty- or gadoliniumenhanced tissues along with fat, and fatty tissues might not be fully suppressed as expected. Therefore, STIR should not be used for tumor characterization (Ma 2008; Wu and Hochman 2009; Amini et al. 2015). Dixon and spectral fat saturation are chemical shift-based techniques that exploit the different precession frequency of water and fat molecules. Dixon and spectral fat saturation both selectively decrease the signal intensity of fat, while other hyperintense tissues remain hyperintense (Mirowitz et  al. 1994; Grande et al. 2014). Dixon offers robust and homogeneous fat suppression and works well on both 1.5 T and 3 T machines while having a minimal impact on areas of high magnetic susceptibility like metallic implants (Grande et al. 2014). Spectral fat saturation, also known as “fat sat,” yields better results at 3 T than at 1.5 T near the isocenter and has a shorter scan time than Dixon, but is susceptible to inhomogeneities in the magnetic field as sometimes seen at the edges of the examined body part (Grande et  al. 2014; Amini et  al. 2015). Both chemical shift-based techniques are adequate for tissue characterization. Hybrid FS techniques such as spectral presaturation with inversion recovery (SPIR) and spectral attenuated inversion recovery (SPAIR) combine a chemical shift with an inversion delay. There are no significant scan time differences. As with fat sat, these techniques are preferably per-

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formed on higher field strength and may also show heterogeneous fat suppression at the edges of the FOV.  In contrast to Dixon, SPIR and SPAIR are rather sensitive to metal artifacts (Grande et al. 2014). However, an imaging protocol using solely FS sequences must be avoided for two reasons. Firstly, the signal intensity of a lesion can appear vastly different on an FS image compared to the corresponding non-FS T1- or T2-weighted image; hence, it would be unreliable to describe the signal characteristics of a lesion solely based on FS sequences (Wu and Hochman 2009). Secondly, in surgical planning, identification of anatomical fat planes is crucial for local staging purposes. Suppression of the high signal intensity of fat results in obscuring fat planes, which is a major disadvantage for treatment planning (Brys 2017). Suppression of high signal intensity of fat on FS T1-WI results in the so-called rescaling effect, a redistribution of gray-level intensities leading to a more efficient use of the dynamic range for display for tissue contrast (Helms 1999). This is useful for tumor characterization, as minor differences in signal intensity between tissues on non-FS imaging get magnified and thus signal inhomogeneity or subtle gadolinium enhancement is better evaluated (Gielen et al. 2003; Brys 2017). The rationale of the rescaling effect is important to understand, for example when evaluating gadolinium uptake by comparison of FS-enhanced T1- to non-FS precontrast T1-WI. An intralesional high signal intensity in the lesion on FS-enhanced T1-WI may result from two variables, either due to contrast enhancement or due to dynamic range redistribution, and hence misinterpretation might occur (Fig. 2) (Helms 1999). As a rule of thumb, when gadolinium-enhanced imaging is performed, we recommend the use of pre- and postcontrast T1-WI with identical imaging parameters for evaluation of the degree of enhancement. In ­addition, subtraction of the pre- and postcontrast FS T1-WI is mandatory for more precise evaluation of enhancement.

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a

b

c

Fig. 2 Diffuse-type tenosynovial giant cell tumor of the left ankle. (a) Axial T1-WI; (b) axial T2-WI; (c) axial FS T1-WI after gadolinium contrast administration. Notice an intra-articular lesion of heterogeneous signal and low signal foci to muscle both on T1- and T2-WI (a, b). After

gadolinium contrast administration, moderate and heterogeneous enhancement is seen (c). However, without a comparable precontrast FS T1-WI, it is impossible to appreciate whether the high signal on c (arrow) is due to contrast enhancement or due to rescaling effect

2.5

contrast T1-WI is subtracted from identical postcontrast T1-WI during post-processing. The following conditions must be met: both T1-WIs have the exact same imaging parameters, and patients are installed with intravenous access prior to examination and cannot change positions in between acquisitions (Chung et  al. 2009). Contrast-enhancing sequences may be omitted when the suspected synovial lesion is clearly characterized without contrast, such as in synovial or ganglion cyst, or a benign simple lipoma. We recommend the use of intravenous gadolinium contrast administration for three reasons. Firstly, it is generally accepted that the use of postcontrast MR imaging is superior for visualization of the synovium (Chung et  al. 2009; Burke et al. 2019), as the anatomical relationship of the synovial membrane to the lesion is pivotal for precise characterization and evaluation of local lesion extent. Secondly, contrast-enhanced MR is essential for the decision whether to perform a biopsy. A benign finding like synovial hemangioma does not require biopsy. When in doubt, planning of biopsy site should be well considered. The area

Fluid-Sensitive Sequences

Reactive peritumoral edema might contain miniscule satellite tumoral lesions. The usage of fluid-sensitive sequences is required for maximizing tumor and peritumoral edema conspicuity in contrast to suppressed fat and muscles. In the imaging of soft tissue tumor and tumorlike lesions, FS T2-WI is most often used as a side-toside comparison with non-FS T2-WI.  A viable alternative, especially in large joints, is in the use of FS proton density-weighted images. The advantage is a better signal-to-noise ratio (Kransdorf and Murphey 2016), at the expense of less pronounced tissue contrast of edema within the soft tissues and bone marrow.

2.6

Gadolinium ContrastEnhanced MRI

Gadolinium uptake can be assessed by visual comparison of (non-)FS T1-WI with (non-)FS contrast-enhanced T1-WI.  However, we recommend the use of subtraction image, in which pre-

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showing the most intense enhancement on static enhanced MRI can be used to identify the most suitable location of vascularized tumor and subsequently increase the yield of biopsy (Verstraete et al. 1994; Verstraete and Lang 2000; Mallinson et al. 2014; Kransdorf and Murphey 2016; Brys 2017; Bruno et al. 2019). Thirdly, surgical planning for iso- to hypointense tumor and tumorlike lesions to muscle is most often based on static non-FS-enhanced T1-WI. Since enhancement can decrease tumor-­ to-­ fat contrast, preoperative evaluation for lipoma arborescens or synovial lipoma is preferred on non-FS precontrast T1-WI. Benefits of dynamic contrast-enhanced MRI are discussed in Sect. 3.1. The role of direct MRI arthrography for the evaluation of synovial lesions is limited. Noncalcified loose bodies can be demonstrated as intra-articular filling defects that are outlined by contrast material (Chung et  al. 2009). Nonspecific nodular synovial thickening may be seen in other tumor and tumorlike conditions of the synovium.

3 Advanced MR Techniques 3.1 Dynamic Contrast-Enhanced MRI (DCE-MRI) DCE-MRI involves rapid acquisition of sequential images within the first three minutes during and after intravenous administration of gadolinium contrast. DCE-MRI prioritizes a high temporal resolution (e.g., one series of images per 3 s or less) and moderate spatial resolution (e.g., matrix 192  ×  192) to observe and quantify contrast enhancement over time. On the contrary, in static contrast-enhanced MRI, tissues are imaged in high spatial resolution for greater anatomic detail in at least two imaging planes when gadolinium contrast is in an equilibrium state between blood and interstitial space (Verstraete et al. 2017). Injection of gadolinium contrast should be done in a standardized way as repeated examina-

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tions over time (weeks, months) are considered (monitor effect chemotherapy, preoperative evaluation, …). Bolus injection (0.2  ml/kg) at an injection rate of 3–5 ml/s in the right antecubital vein is followed by a 20 ml saline flush. In single-­ slice DCE-MRI, thorough evaluation of precontrast T1- and T2-weighted images should be performed to select one imaging plane, which will include a representative part of the lesion, muscle tissue—as a reference—and an artery to evaluate the time of onset enhancement in various parts of the lesion. In multislice DCE-MRI, the whole volume of the tumor should be covered. Generally, no fat suppression techniques are used in DCE-MRI as fat tissue is adequately suppressed in subtraction and first-pass image post-processing (Verstraete et al. 2017). The extracellular distribution of gadolinium contrast among blood plasma and interstitial spaces is essentially divided into three phases. During the first pass of the bolus, when the concentration gradient of gadolinium contrast is the highest between intravascular and interstitial space, fast diffusion occurs and lesional contrast enhancement is determined by tissue vascularization (number of vessels), tissue perfusion (local capillary resistance), and capillary permeability. At the equilibrium phase, in which maximum contrast enhancement is shown, gadolinium contrast reaches an equal concentration between blood and interstitial space. Time interval to equilibrium depends on the size of the interstitium. After contrast injection, the first pass generally lasts for about 7–15 s while the time interval for equilibrium phase may vary from less than 20  s in lesions with small interstitial space to 3–5 min in tissues with a larger interstitial space. During the washout phase, gadolinium contrast is progressively washed out from the interstitial space as the intravascular concentration reduces. Only in highly vascular lesions with small interstitial space, early washout occurs within the first minutes after bolus injection (Verstraete et  al. 1994, 2017; Verstraete and Lang 2000). Contrast enhancement in DCE-MRI can be evaluated qualitatively, semiquantitatively, and

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quantitatively. Post-processing subtraction images in which precontrast images are subtracted from all subsequent images allows for the detection of discrete, early, and small enhancing areas, while high signals from fat and hemorrhage are nullified (Verstraete et al. 1994, 2017; Verstraete and Lang 2000). This technique provides quick information on vascularization and perfusion of a lesion, which can help to characterize a lesion, to indicate the best biopsy site, or to detect residual tumoral tissue. Another option is post-processing so-called slope images in which the steepest slope of each pixel’s TIC is calculated. Subsequently, a single new “first-pass image” with the same matrix can be composed (Verstraete et al. 2017). The latter provides information of tissue vascularization, perfusion capillary permeability, and composition of interstitial space. As an example, for tumor characterization, the early arterial phase enhancement and overall highest slope values have been seen in synovial sarcoma and may help to differentiate from most benign lesions, such as low slope values in synovial chondromatosis (Verstraete et  al. 2017; Ashikyan et al. 2019). Depicting tissue vascularization with DCE-MRI for monitoring the response to chemotherapy and for detecting residual/recurrent tumor after therapy is discussed in Sect. 6.1.

3.2 Diffusion MRI Diffusion MR measures the random Brownian motion of water molecules within a voxel of tissue. The diffusion characteristics of a single volume represent the combined diffusion of water molecules in cellular spaces (extracellular, intracellular, transcellular) and in intravascular fluid. The b-value reflects the diffusion force and diffusion weighting of the image. Diffusion information is extracted from tissue by using a conventional T2-WI (b-value  =  0  s/mm2) with diffusion gradients in different directions to filter the signal from highly mobile water molecules

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and to improve the detection of diffusion and mobility. To measure the tissue’s complete diffusion profile, and to improve interpretation accuracy, b-values of the diffusion gradient are evaluated. Practically, at least two different b-­values are generally used (0; 600; 1000 s/mm2) (Costa et al. 2011). Diffusion MRI can be performed qualitatively by using diffusion-weighted sequences such as diffusion-weighted imaging (DWI), echoplanar imaging (EPI), and steady-state free precession (SSFP) imaging (Baur and Reiser 2000), in which diffusion is evaluated by signal intensity on low and high b-value. Diffusion can be quantified by calculating the apparent diffusion coefficient (ADC) of each pixel in an ROI, which is displayed on ADC maps. Diffusion restriction occurs in highly cellular tissues or in tissues with excessive cellular swelling, showing high signal intensity on diffusion-weighted sequences and low signal intensity on ADC (Baur and Reiser 2000). Malignant tumors typically show greater cellularity and thus more water molecule restriction. However, for tumoral lesions, it is important to understand that ADC depends on water molecule diffusion in the extracellular tumor compartment, but also on the degree of tumor perfusion (van Rijswijk et al. 2002). For this reason, hyperperfused but not necessarily malignant tumors, such as localized tenosynovial giant cell tumor, might show intravoxel incoherent motion with low ADC values that becomes more apparent at low b-values (Ashikyan et  al. 2019). To avoid this, perfusion might be corrected for in perfusion-­insensitive ADC value (PIADC) (van Rijswijk et al. 2002; Verstraete et al. 2017; Bruno et al. 2019). The role of diffusion MRI for tumor and tumorlike conditions of the synovium is unclear. In combination with standard MRI modalities, it might be useful for lesion characterization. For example, cystic tumor and tumorlike lesions, such as ganglion cysts, exhibit less water molecule motion restriction compared to solid masses or cellular tumors (Verstraete et  al. 2017).

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Concerning tumor grading, lower ADC values are seen in (more) malignant soft tissue tumors. However, due to a broad overlap of ADC values between benign and malignant tumors, especially in myxoid lesions, we do not recommend the use of diffusion MR for tumor grading (Messina et al. 2020). In contrast, diffusion MR is proven to differentiate between abscesses, hematomas, and necrotic tumors which might be difficult on conventional MRI (Costa et al. 2011). The combination of DCE-MRI and diffusion MRI for detection of postoperative recurrence/residual synovial sarcoma has been suggested in a recent study (Eldaly et al. 2018) (see Sect. 6.1).

3.3 MR Spectroscopy MR spectroscopy allows tissue to be characterized based on the presence and concentration of metabolic constituents, which can be translated into pixel intensity maps based on the relative signal from a certain metabolite (water, creatine, lipids, choline, …) (Verstraete et al. 2017; Bruno et al. 2019). It has been proven feasible for characterizing musculoskeletal tumors (Fayad et  al. 2006) and additional information such as bone invasion and tissue destruction (Doganay et  al. 2011). However, due to the low number of studies on the value of choline MR spectroscopy (Bruno et  al. 2019) and overall low specificity findings (Teixeira et  al. 2017), we currently do not recommend the use of MR spectroscopy specifically for the evaluation of synovial tumor and tumorlike conditions.

4 Role of MRI in Characterization and Grading The ultimate aim of tumoral imaging is predicting a specific histologic diagnosis or suggesting a relevant differential diagnosis and prognosticating the probability or degree of malignancy. MRI

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serves as the most important imaging technique for tissue characterization and grading of tumor and tumorlike conditions of the synovium, although the final diagnosis is made by the pathologist. Besides age and location, careful consideration of morphology, signal intensity on different MR sequences, and contrast enhancement are key in tissue characterization. Table  1 summarizes these imaging parameters in relation to the most common synovial tumor and tumorlike lesions, which are further described in the respective chapters. Morphology is particularly helpful in the prediction of a tissue-specific diagnosis. Morphological signs, such as soap bubble/cauliflower appearance in lipoma arborescens (Fig. 3), or serpiginous/bunch-of-grapes appearance of synovial hemangioma (Fig.  4), or moniliform appearance of synovial–ganglion cyst can be distinctive. Localized tenosynovial giant cell tumor and ganglion cyst have a very-well-defined border, while diffuse tenosynovial giant cell tumor has an ill-defined border. Intra-articular nodules are found in synovial chondromatosis (Fig.  5) and amyloid arthropathy (Narváez et  al. 2001; Garner and Bestic 2013; Levine et  al. 2016; Vanhoenacker and De Schepper 2017). Similar to other soft tissue tumors, when analyzing signal intensities (SI) on T1-WI and T2-WI, essentially four major groups can be distinguished in synovial tumor and tumorlike conditions (Vanhoenacker and De Schepper 2017): Group I: High SI to muscle on T1-WI and intermediate SI on T2-WI are seen in synovial lipoma and lipoma arborescens with suppression of high SI on FS sequences (Fig.  3) (Narváez et al. 2001). On the contrary, a melanin-­containing melanoma shows no signal drop on fat-­suppressed imaging (Wu and Hochman 2009). Therefore, correct interpretation should rely on the meticulous analysis of all pulse sequences, including FS imaging. Group II: Combination of intermediate SI on T1-WI and high SI on T2-WI is uncommon in

Similar to synovial chondromatosis Destructive, inflammatory arthritis Sinus tract formation

SI signal intensity to muscle

Synovial chondrosarcoma Tuberculous arthropathy

Well-defined mass with heterogeneous SI

Intra-articular nodule(s)

Amyloid arthropathy Synovial sarcoma

Variable SI on T1-WI, intermediate to low SI on T2-WI Heterogeneous Complications mostly include high SI on T2-WI (periarticular abscess, bursitis, osteomyelitis, sinus tract)

Similar to synovial chondromatosis

Increased lesion conspicuity Increased lesion conspicuity

Increased lesion conspicuity Increased lesion conspicuity

Surrounding synovium may contain hemosiderin

Increased lesion conspicuity

Serpiginous morphology Fluid-fluid levels

Synovial hemangioma

Low to intermediate SI on T1-WI, high-SI on T2-WI 15–20% show signal void by calcifications on T2-WI Low SI on T1-WI, low to intermediate on T2-WI Low SI on T1-WI, heterogeneous intermediate on T2-WI Special scenario: triple signal on T2

Calcified nodules may cause blooming

Increased lesion conspicuity

SI might vary according to Kramer stage

Only in hemorrhagic component Only in hemorrhagic component

No hemosiderin deposition Only in hemorrhagic component

Low and may demonstrate blooming

Increased lesion conspicuity

Low SI on T1-WI, low SI on T2-WI

Well defined for localized type Ill-defined for diffuse type Intra-articular nodules

Ganglion– synovial cyst

Localized-type and diffuse-type tenosynovial giant cell tumor Synovial chondromatosis

T2* GRE No hemosiderin deposition No hemosiderin deposition No hemosiderin deposition

Fat sat Suppression of fat signal Suppression of fat signal Increased lesion conspicuity

T1-WI and T2-WI Fat signal intensity: high SI on T1and intermediate SI T2-WI Fat signal intensity: high SI on T1and intermediate SI on T2-WI Low SI on T1-WI, high SI on T2-WI

Morphology Soap bubble appearance Cauliflower appearance Well-defined mass Moniliform appearance Well-defined mass with homogeneous SI

Tumor and tumorlike Lipoma arborescens Synovial lipoma

Table 1  Imaging parameters of tumor and tumorlike conditions of the synovium

Heterogeneous enhancement Enhancement of the erosion’s rim and the synovium Heterogeneous enhancement

Mild, peripheral enhancement Marked and heterogeneous enhancement

Peripheral enhancement Ring-and-arc enhancement Diffuse enhancement

Absent or peripheral rim enhancement Moderate, heterogeneous enhancement

Absent

Contrast enhancement pattern Absent

Chapter “Synovial Amyloidosis” Chapters “Surgical Treatment” and “Nonsurgical Treatment” Chapter “Synovial Chondrosarcoma” Chapter “Mimics of Synovial Tumors Due to Chronic Infection”

Chapter “Synovial Hemangioma”

Chapter “Synovial Chondromatosis”

See chapter for more detailed description Chapter “Lipoma Arborescens” Chapter “Lipoma Arborescens” Chapter “Synovial Cysts, Ganglion Cysts, and Bursae” Chapter “Tenosynovial Giant Cell Tumor”

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Fig. 3 Lipoma arborescens in the suprapatellar recess of the right knee. (a) Sagittal T1-WI; (b) sagittal FS T2-WI; (c) axial FS T2-WI. Notice a frond-like synovial prolifera-

tion showing high SI similar to subcutaneous fat on T1-WI with suppression of the fat on fat-suppressed T2-WI (arrows, a–c)

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Fig. 4 Synovial hemangioma of the knee. Axial (a) and sagittal FS proton density-WI (b). The synovial hemangioma originates from the suprapatellar fat pad, a typical

location for this lesion (arrows). The lesion has a bunchof-grape morphology (a, b)

synovial tumors, but this may be seen in synovial hemangioma/vascular malformation. Group III: A low SI on T1-WI and high SI on T2-WI are seen in cystic lesions such as synovial and ganglion cyst (Figs. 6 and 7) and in the proliferative initial stage of synovial chondromatosis and synovial chondrosarcoma (Doepfer and Meurer 2015; Levine et al. 2016). Group IV: Low to intermediate SI on T1-WI and low SI on T2-WI may correspond to hemosiderin in old hematomas, localizedtype and diffuse-type tenosynovial giant cell tumor (Fig.  2), amyloid arthropathy, hemophilic arthropathy, and synovial hemangioma complicated by bleeding (Garner and Bestic 2013; Doepfer and Meurer 2015; Levine et al. 2016). Furthermore, when describing signal intensities on T2-WI, it is important to analyze the lesion’s homogeneity. In synovial sarcoma, a het-

erogeneous “triple signal” can be seen on T2-WI consisting of a mixture of cystic, hemorrhagic, and solid components (Fig.  8) (Doepfer and Meurer 2015). Of note, the presence of signal void can be seen either due to high flow in highflow vascular malformation or due to the presence of intralesional phleboliths in low-flow vascular malformations/hemangioma, and due to calcifications in the second stage of synovial chondromatosis (Fig.  9) (Kramer et  al. 1993; Levine et al. 2016) and in the so-called synovial sarcoma (Narváez et al. 2001). Contrast enhancement is typically absent in ganglion cyst (Fig.  6), moderate to marked in tenosynovial giant cell tumors (Fig.  10), and marked and heterogeneous in malignant tumors (Figs. 8 and 11) (Garner and Bestic 2013; Levine et al. 2016). Ring-and-arc enhancement is seen in synovial chondroid lesions (Fig.  11) (Brassens et al. 2010).

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Fig. 5 Secondary synovial chondromatosis. (a) Sagittal T1-WI; (b) sagittal FS T2-WI; (c) coronal FS T2-WI. Loose bodies of different sizes are found posteri-

orly at the knee joint (arrows, a, b). The coronal images show the underlying osteoarthritis (arrowheads, c) indicating secondary chondromatosis

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Fig. 6 Multilocular synovial cyst at the carpal tunnel at the level of the distal carpal row deeply located to the flexor tendons. (a) Axial T1-WI; (b) axial FS T2-WI. The

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lesion is of low SI on T1-WI and high SI on T2-WI, in keeping with fluid content (arrows, a, b)

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Fig. 7 (a, b) Ganglion cyst adjacent to the medial aspect of the distal tibia. (a) Coronal FS T2-WI; (b) axial FS T1-WI after intravenous administration of gadolinium contrast. The patient presented with an asymptomatic

swelling of the medial lower leg. A homogeneous lesion of high SI on FS T2-WI and absent contrast enhancement is seen (arrows, a, b)

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Fig. 8  Synovial sarcoma of the thigh. (a) Axial T1-WI; (b) axial FS T1-WI; (c) axial T2-WI; (d) gadolinium-­ enhanced axial T1-WI.  Axial T1-WI shows a heterogeneous mass at the posterior compartment of the right thigh. Note the presence of intralesional areas of high signal intensity, corresponding to subacute hemorrhage (dotted arrows, a). The persistent high signal intensity foci on

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FS T1-WI confirm the presence of methemoglobin (arrowheads, b). A triple signal with high (black arrow), intermediate (white arrow), and low SI areas (gray arrow) is seen on axial T2-WI (c) with marked, peripheral enhancement of the solid part of the lesion after administration of gadolinium contrast (asterisks, d)

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Fig. 9 Primary synovial chondromatosis (Kramer stage 2) of the wrist. (a) Conventional radiograph; (b) coronal gradient-echo image; (c) coronal FS T2-WI; (d) sagittal FS T2-WI. Notice the presence of multiple calcified loose bodies (arrow, a). These nodules are of heterogeneously

b

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low signal on gradient-echo imaging with subtle blooming (b). The low signal intense foci on all pulse sequences (b–d) can be attributed to calcifications (a). Note also a well-described pressure erosion on the pisiform bone without associated bone marrow edema (dotted arrow, d)

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Fig. 10 Diffuse-type tenosynovial giant cell tumor of the left ankle. (a) Sagittal FS proton density-WI; (b) axial subtraction image of FS T1-WI before and after gadolinium contrast. Notice a lesion in the posterior recess of the

tibiotalar joint with overall intermediate signal and subtle intralesional foci of low signal (arrow, a). Marked contrast enhancement is seen (arrowheads, b)

Grading consists of differentiation between benign and malignant tumors and definition of malignancy grade. In synovial proliferative disorders, malignant tumors are far outnumbered by benign tumors; intra-articular tumors are almost always benign. Most useful MR parameters that suggest malignancy of a synovial lesion are large size (more than 5 cm), inhomogeneity on (all) MR sequences, intralesional hemorrhage or necrosis, invasion in adjacent bones and neurovascular bundles, and extracompartmental extension (Chung et  al. 2012;

Vanhoenacker and De Schepper 2017; Whitehouse and Kirwadi 2017). For example, differentiating primary synovial chondromatosis and synovial chondrosarcoma might be difficult on imaging, but cortical destruction with bone marrow invasion (rather than pressure erosions), inhomogeneity on all pulse sequences, multiple recurrences, and rapid increase of size of lesion and extra-articular extension are imaging findings that strongly suggest malignant transformation (Fig.  11) (Garner and Bestic 2013; Levine et al. 2016).

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Fig. 11 Immunohistochemically confirmed malignant transformation into a synovial chondrosarcoma. (a) Sagittal T1-WI; (b) sagittal FS T2-WI; (c) axial T1-WI; (d) axial FS T2-WI; (e) axial FS gadolinium-enhanced T1-WI. Multiple intra-articular loose bodies located posterolaterally at the knee joint in a patient with primary synovial chondromatosis (arrowheads, a, b). The axial images show a heterogeneous mass with intermediate to

e

high SI to muscle on T1-WI and mixed SI on T2-WI (arrows, c, d). Tumor size >5 cm and lesion inhomogeneity are suggestive of a malignant chondrosarcoma. No cortical destruction or extracompartmental extension is observed. Gadolinium-enhanced images show ring-andarc enhancement of the synovial chondromatosis indicating the chondroid nature (e)

Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions

5 Role of MRI in Evaluation of Lesion Extension 5.1 Size As most anatomical compartments of the extremities are oriented longitudinally, MRI protocol should include axial images and at least one longitudinal plane to measure a lesion in three dimensions. Peritumoral edema is considered an integral part of the lesion and should therefore be included in the measurement. The size criterion of lesion size more than 5 cm as a malignant feature is arbitrary, as a substantial amount of malignant soft tissue tumors will be found at less than 5 cm in diameter and may not exceed this diameter for months or years. However, if this criterion is met in a malignant lesion, prognosis is significantly worse (Grimer 2006; Whitehouse and Kirwadi 2017). For the so-called synovial sarcoma, an almost linear correlation is seen between increasing size and incidence of metastases at diagnosis (Grimer 2006).

5.2 Lesion Localization and Compartmental/ Extracompartmental Extension As for all soft tissue tumors, location of synovial lesions has little value in differentiating benign from malignant lesions. Determining whether the tumor extension is compartmental or ­extracompartmental is important for local staging. Generally, five compartments are described: the skin, subcutaneous fat, bone, para-osseous space, and joint spaces. Extracompartmental spaces include the groin, popliteal fossa, ankle and dorsum of the foot for the lower limb, and the periclavicular region, axilla, cubital fossa, wrist, and dorsum of the hand for the upper extremity (Anderson et al. 1999; Gielen 2017). Most synovial tumor and tumorlike lesions are compartmental and arise in large joints (knee, hip, shoulder) and to a lesser extent in smaller

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joints. The knee is most involved and is the primary site of pathology for most benign intra-­ articular lesions. Lipoma arborescens typically originates in the suprapatellar recess (Fig.  3). Synovial hemangioma has the same preferred location but is commonly associated with overlying periarticular or extracompartmental soft tissue hemangioma (Fig.  4) (Garner and Bestic 2013; Levine et al. 2016). For localized-type and diffuse-type intra-articular TSGCT, previously termed localized nodular synovitis (LNS) and pigmented villonodular synovitis (PVNS), respectively (Choi and Ro 2021), consecutive extension into the infrapatellar fat pad and suprapatellar recess is typically seen, and diffuse-type TSGCT can extend beyond the joint capsule and into the bone marrow (see Sect. 5.3) (Levine et  al. 2016). Extracompartmentally located lesions in the popliteal fossa are mostly of cystic nature (e.g., baker’s cyst, synovial or ganglion cyst, meniscal cysts). Other examples of lesions in the popliteal fossa include diffuse-type TSGCT and aneurysms of the popliteal artery. Ganglion cysts most often occur in and around the hand and wrist, but any joint may be involved (Vanhoenacker and De Schepper 2017). At diagnosis, malignant tumor often involves two or more compartments. It should be emphasized that synovial sarcoma, which has no relationship with synovial tissue and originates from mesenchymal cells, occurs far more common extra-articularly and periarticularly rather than intra-articularly, in which case the foot, ankle, and knee are sites of predilection (Fig. 7) (Levine et al. 2016).

5.3 Local Staging Local staging is important for surgical treatment when sufficient radicality is in balance with postoperative functionality of the joint. In addition to tumor size and precise location, information on bone marrow involvement or cortical destruction, neurovascular encasement, and extension within the joint and abnormal proximal/regional lymph

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nodes should be carefully described. Edema and blood resulting from biopsy can be difficult to differentiate from tumor and peritumoral edema. Therefore, local staging by MRI should always be performed before biopsy.

5.3.1 Bone (Marrow) Involvement MR imaging is highly accurate to demonstrate osseous invasion and the extent of bone marrow invasion. Where fluid-sensitive sequences are most sensitive to detect reactive bone marrow edema caused by tumoral invasion, T1-WI best appreciates cortical destruction and the extent of bone marrow invasion by showing bone marrow replacement (Palmer et al. 2020). Signal alternations of cortical and medullary bone on fluid-­ sensitive sequences at the contact zone with a malignant lesion are suspicious for osseous invasion. However, if merely close contact between tumor and bone occurs without osseous signal changes, it should not be interpreted as bone invasion. This has important consequences for the surgical approach of malignant lesions. For example, in the so-called synovial sarcoma, if there is mere contact of the tumor with bone surface without bone marrow alterations on fluid-­ sensitive sequences, it might be sufficient to remove periosteum together with the sarcoma to obtain an adequate surgical margin. In contrary, resection of the involved bone and soft tissue is mandatory in case of marrow invasion (Elias et al. 2003; Holzapfel et al. 2015). It should be noted that a number of locally aggressive benign lesions may cause bone erosion and reactive bone marrow edema, which should not be misinterpreted as a sign of malignancy. Synovial chondromatosis often causes extrinsic erosions of the bone secondary to mechanical pressure exerted by intrasynovial chondromas, so-called pressure erosions (Fig. 8). Similar pressure erosions are found in amyloid arthropathy (Khoo et  al. 2018) and diffuse-type intra-articular TSGCT.  In the latter condition, these erosions might be so deep that it simulates bone marrow invasion and a more aggressive process (Fig. 12).

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Gout is another lesion of benign biological behavior that typically shows well-defined erosions with overhanging sclerotic edges, so-called rat bite erosions (Sheldon et al. 2005).

5.3.2 Lymph Node Involvement For detection of abnormal regional lymph nodes, we suggest the use of at least one sequence with a large FOV, which is also useful for the evaluation of multiplicity and satellite lesions in case of malignant synovial lesions. The size of the FOV depends on the examined joint. In patients with synovial sarcoma, lymph node metastasis has been reported in more than 10% at diagnosis compared to an overall prevalence of 1–3% in soft tissue sarcoma (Johannesmeyer et  al. 2013; Sherman et  al. 2014; Wörtler 2017). However, a recent review from Jacobs et al. (2018) in a series of 885 synovial sarcomas stated that the proportion of patients with lymph node metastasis was not higher compared to the overall soft tissue sarcoma population, respectively, 4.1% and 5.3%. For synovial sarcoma, regional lymph node involvement is a relatively rare finding but represents the strongest prognostic factor excluding distant metastasis (Johannesmeyer et  al. 2013). For synovial chondrosarcoma, regional lymph node metastasis has also been described (Bertoni et al. 1991). The presence of regional lymphadenopathy and focal synovial proliferation should raise suspicion for lymphoma, even though synovial involvement by lymphoma is extremely rare (Kelsey 2021). In general, regional lymph node involvement does not occur in benign synovial tumors and should raise suspicion for malignant synovial lesions. A number of pseudotumoral conditions of the synovium may be associated with lymphadenopathy. Typical examples consist of septic arthritis or Lyme disease and other inflammatory conditions, such as gout, pseudogout, rheumatoid arthritis, and severe osteoarthritis (Fig.  13) (Çalgüneri et al. 2003; Burke et al. 2019).

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Fig. 12 Intra-articular diffuse-type tenosynovial giant cell tumor of the left hip. (a) Conventional radiograph; (b) coronal T1-WI; (c) coronal T2-WI; a well-circumscribed osteolytic lesion is seen in the proximal femur (a). MR

imaging confirms the well-delineated but heterogeneous lesion that is partially located in the joint and causes a huge erosion of the femoral neck (b). There is no surrounding bone marrow edema (c)

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Fig. 13 Rheumatoid arthritis with lymph node involvement in the popliteal fossa. (a) Sagittal T1-WI; (b) sagittal FS T2-WI.  Synovial hyperemia including joint effusion

and synovial thickening (arrows) and enlarged lymph nodes in the popliteal fossa (arrowheads) are nonspecific findings for inflammatory/infectious diseases

6

is optional and may be valuable for differentiation of local recurrence in synovial sarcoma. For follow-up for benign synovial lesions, we suggest to only use the basic sequences with contrast enhancement as recommended by the ESSR guidelines.

Role of MRI in Follow-Up After Treatment

The recommended protocol by the European Society of Musculoskeletal Radiology (ESSR) guidelines for follow-up of soft tissue sarcoma includes T1-WI and a fluid-sensitive FS sequence parallel to the long axis of the tumor as well as axial FS proton density- or FS T2-WI.  Gadolinium-enhanced sequences should be performed in two planes and compared to precontrast sequences with the same parameters (Noebauer-Huhmann et al. 2015). We also suggest the use of dynamic contrastenhanced MRI (DCE-MRI) for the evaluation of treatment response during/after neoadjuvant chemotherapy and postoperatively of malignant soft tissue tumors. Diffusion MRI

6.1

Follow-Up of Malignant Synovial Tumors

Optimal follow-up of patients with malignant synovial tumors requires three DCE-MRI examinations: before biopsy, during chemotherapy, and for preoperative planning at the end of neoadjuvant chemotherapy (Verstraete and Lang 2000).

Magnetic Resonance Imaging of Synovial Tumor and Tumorlike Conditions

For systematic therapy, conventionally, RECIST (Response Evaluation Criteria in Solid Tumors) criteria are used for the evaluation of treatment response based on the longest dimension of the lesion(s) (van Persijn Van Meerten et al. 2010). However, for synovial sarcoma, evaluation size is not an optimal parameter as lesion growth may be due to nonneoplastic intralesional hemorrhage. Good treatment response has been defined as a decrease in size with formation of macroscopic necrosis of more than 90%. Static gadolinium-enhanced MRI is unable to differentiate enhancing, residual viable tumor, and post-­ therapy changes such as fibrosis/granulation tissue. Therefore, DCE-MRI is recommended and has shown to be accurate in synovial sarcoma (Verstraete et al. 1994; Verstraete and Lang 2000; Noebauer-Huhmann et al. 2020). Currently, there is no evidence-based consensus about the follow-up interval by imaging sarcoma patients. We suggest clinical examination, locoregional MRI, and non-contrast CT scan of the chest every 3 months for up to the third year after first treatment, thereafter every 6  months until the fifth year, and finally annually from the fifth year up to 10 years. Detection of local malignant recurrences and differentiation from post-therapeutic can be done by DCE-MRI, diffusion MRI, or a combination of both (Verstraete et al. 2017; Eldaly et al. 2018). The combination of absence of hyperintense T2 signal, no sharp delineation of the lesion, and absence of architectural distortion of the “texture” or “feathering” pattern of muscles on FS T2-WI is very sensitive (±99%) to exclude local recurrence of synovial sarcoma. Additionally, PET/CT can be used (Noebauer-Huhmann et al. 2020).

6.2 Follow-Up of Benign Lesions For locoregional follow-up interval of benign synovial lesions, we recommend a different approach for lesions that do often recur and those with low recurrence rate.

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Frequently recurring lesions include intra-­ articular diffuse-type TSGCT (up to 68% after 5 years and increasing by time), synovial chondromatosis (rarely after synovectomy, but up to 23% in case of surgical debulking), and synovial hemangioma (particularly common in diffuse-­ type synovial hemangioma that requires wide-­open excision) (Narváez et  al. 2001; Verspoor et al. 2014). For this group, we suggest a regular clinical follow-up interval of 6 months to 1 year by MRI follow-up in case of recurrent symptoms. In addition, conventional radiography every 6  months is recommended to exclude calcifications (which could indicate recurrent synovial hemangioma or chondromatosis) or pressure erosions (in case of suspected intra-articular diffuse-­type TSGCT or synovial chondromatosis). One should keep in mind that malignant transformation into synovial chondrosarcoma may occur in 1–5% of patients with synovial chondromatosis. Worsening or refractory pain in patients with synovial chondromatosis warrants further evaluation by MRI imaging (Urwin et al. 2019). For other benign lesions such as synovial cysts, recurrence rates after surgery are low. Follow-up MRI is indicated in case of clinical suspicion of recurrence.

7 Key Points • The recommended minimal imaging protocol includes a combination of T1-WI, T2-WI, and a fluid-sensitive sequence. Although axial imaging is usually the primary imaging plane for soft tissue tumors in general, this may be different for synovial tumor and tumorlike conditions; for example, for diffuse TSGCT of the ankle and knee, the sagittal plane is often preferred. The choice of the additional imaging planes depends on the location of the lesion. Spectral fat suppression is preferred over inversion recovery unless metal artifact is present.

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• The anatomical relationship with the synovial membrane is pivotal for precise characterization and evaluation of local lesion extent of tumor and tumorlike conditions of the synovium. For this reason, we recommend the use of gadolinium contrast imaging. In addition to the relationship with the synovium, it is important to report the contrast of the lesion to the muscle or fat. • Although gradient-echo imaging is not part of the routine imaging protocol of soft tissue tumors, T2* imaging should be performed whenever the lesion is suspicious for containing hemosiderin such as TSGCT. • For local staging, an optimal protocol also includes one large field-of-view (FOV) image. In addition to tumor size and precise location, information on bone marrow involvement (versus bone erosion), neurovascular encasement, extension within the joint, and abnormal proximal/regional lymph nodes should be carefully described. Local staging should always precede biopsy. • Administration of gadolinium contrast is recommended, and subtraction images of pre- and postcontrast should be performed. Dynamic contrast enhancement may be helpful in the evaluation of lesion vascularization. Pretreatment dynamic contrast enhancement MR studies are useful as a baseline for followup MR scans to monitor response to treatment. Dynamic contrast-­enhanced MRI (DCE-MRI) is mandatory for the evaluation of treatment response of malignant synovial lesions during/ after neoadjuvant chemotherapy and postoperatively.

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104 Teixeira PAG, Ledrich M, Kauffmann F et  al (2017) Qualitative 3-T proton MR spectroscopy for the characterization of musculoskeletal neoplasms: update on diagnostic performance and indications. Am J Roentgenol 208:1312–1319. https://doi.org/10.2214/ AJR.16.17285 Urwin JW, Cooper K, Sebro R (2019) Malignant transformation of recurrent synovial chondromatosis: a case report and review. Cureus 11:5839. https://doi. org/10.7759/CUREUS.5839 van Persijn Van Meerten EL, Gelderblom H, Bloem JL (2010) RECIST revised: implications for the radiologist. A review article on the modified RECIST guideline. Eur Radiol 20:1456–1467. https://doi. org/10.1007/S00330-­009-­1685-­Y van Rijswijk CSP, Kunz P, Hogendoorn PCW et al (2002) Diffusion-weighted MRI in the characterization of soft-tissue tumors. J Magn Reson Imaging 15:302– 307. https://doi.org/10.1002/JMRI.10061 Vanhoenacker FM, De Schepper AM (2017) Grading and tissue-specific diagnosis. In: Vanhoenacker FM, Parizel PM, Gielen J (eds) Imaging of soft tissue tumors. Springer International Publishing, pp 161–179 Verspoor FGM, Zee AAG, Hannink G et  al (2014) Long-term follow-up results of primary and recurrent pigmented villonodular synovitis. Rheumatology

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PET/CT in Synovial Tumors and Tumor-Like Conditions Sarah K. Ceyssens

Contents

Abstract

1

Introduction

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2 2.1 2.2 2.3

Differential Diagnosis of a Primary Mass Rheumatoid Arthritis Tumor-Like Conditions Tumors

106 106 107 107

3

Conclusion

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4

Key Points

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References

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S. K. Ceyssens (*) Department of Nuclear Medicine, Antwerp University Hospital, Edegem, Belgium e-mail: [email protected]

Accurate differentiation between a benign or malignant tumor is crucial to define the best therapeutic strategy. Besides the confirmation of the diagnosis of a malignancy, it is essential to know the exact histology and grading of the primary tumor. Consequently, the approach to a patient with a mass suspicious of a malignancy usually starts with a biopsy. By identifying the most metabolically active portion of a tumor mass, 18F-FDG-PET-CT can guide biopsy toward the most aggressive zone. In rheumatoid arthritis, 18F-FDG PET can be used to assess disease activity in the affected joints, to reveal extra-articular manifestations (e.g., subcutaneous rheumatoid nodule, vasculitis, rheumatoid lung disease, pericarditis, and pleuritis) and to monitor response to treatment. In case of other benign synovial masses, the role of 18F-FDG PET is rather limited. In the diagnostic work up of sarcoma, the strength of 18F-FDG PET-CT lies in its ability to detect metastases outside the standard fieldof-view of CT and MRI, and in the exclusion of disease in equivocal results on conventional imaging. With regard to treatment monitoring in sarcoma, 18F-FDG PET seems promising, with a good correlation between an early and significant decline in metabolic activity and response to therapy. Although further studies are necessary, recent studies suggest a role for

Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_421, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 12 April 2023

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the use of 18F-FDG PET for detection of local recurrence of STS, particularly when combining the metabolic information of PET and the excellent soft tissue contrast of MRI in an integrated 18F-FDG PET/MRI. Additionally, 18F-FDG uptake in high grade sarcoma on pretreatment scan is an independent predictor for overall and disease-free survival.

1 Introduction

S. K. Ceyssens

tion or monitoring of specific changes which are not associated with or which precede the anatomical changes. Combining the anatomical information of CT or MRI and the metabolic information of PET improves diagnostic accuracy, provides surgery and radiation therapy planning and can guide biopsies by merging the anatomic and metabolic information in one single procedure. Still, studies are required to evaluate the impact of combining these imaging techniques on the overall diagnostic performance in sarcoma in general.

Positron Emission Tomography (PET) can reveal 2 Differential Diagnosis the biodistribution of small quantities of positron-­ of a Primary Mass emitting radiopharmaceuticals (i.e., tracers). PET uses radioisotopes of natural elements, oxygen- Several disorders can affect the synovium and 15, carbon-11, nitrogen-13, and fluorine-18. can be either localized or systemic. According to ­ These radioisotopes can be easily incorporated the underlying etiology, they can be classified as into physiologic compounds in the human body inflammatory (e.g., rheumatoid arthritis), infecwithout disrupting their characteristics (“physio- tious (infectious arthritis), degenerative (osteoarlogic labelling”) (Jones 1996). thritis), traumatic disease (posttraumatic The most commonly used tracer in PET is the synovitis, hemophilic arthropathy), tumors glucose analogue Fluorine-18-labeled 2-fluoro-­ (synovial hemangioma, synovial sarcoma), or 2-deoxy-d-glucose, [18F]FDG, in which a tumor-like conditions (pigmented villonodular hydroxyl group in the 2-position is replaced by a synovitis, synovial chondromatosis, lipoma arbopositron-emitting 18F.  After malignant transfor- rescens) (Larbi et al. 2016; Sriram et al. 2012). mation, an increased expression of glucose transIncreased 18F-FDG uptake is not specific for porter proteins and an up-regulation of hexokinase cancer cells. It is also seen in neutrophils, eosinoactivity are seen. Just like glucose, [18F]FDG is phils, macrophages, and proliferating fibroblasts, transported into the cell by the glucose trans- sometimes even more intense than in malignant porter proteins and once intracellular rapidly cells (Kubota et al. 1992). Therefore, an increased phosphorylated to [18F]FDG-6-phosphate. Yet, FDG-uptake can also be seen in some inflammathe latter is—in contrast to glucose-6-­tory conditions, being the most common cause of phosphate—not a substrate for the glucose phos- a false positive FDG-signal (Yamada et al. 1995), phate isomerase and thus cannot be converted to as well as infectious foci (e.g., infectious arthrithe fructose analogue. Since most tumors have a tis) (Pijl et al. 2020). low phosphatase activity, the negatively charged [18F]FDG-6-phosphate will accumulate in the cell, resulting in the so-called metabolic trapping 2.1 Rheumatoid Arthritis and an increased signal in cancer cells compared to non-malignant tissue (Warburg et al. 1931). Rheumatoid arthritis (RA) is a chronic progresSince PET relies on the detection of metabolic sively destructive and symmetric inflammation of alterations, these examinations yield data inde- multiple joints giving rise to synovitis. RA first pendently of structural features as provided by affects the synovium, resulting in synovial prolifcomputed tomography (CT) and magnetic reso- eration and inflammatory changes, causing high nance imaging (MRI), and therefore allow detec- 18F-FDG uptake. Several studies have demon-

PET/CT in Synovial Tumors and Tumor-Like Conditions

strated that 18F-FDG uptake may be used to assess the activity of synovial inflammation in the affected joints. This imaging technique can also reveal extra-articular manifestations (e.g. subcutaneous rheumatoid nodules, vasculitis, rheumatoid lung disease, pericarditis, and pleuritis), of which the latter four have been linked to an increased mortality compared with patients with RA in general (Sollini et al. 2016). 18F-FDG PET is not only useful for the detection, but also for monitoring of response to therapy. Early decrease in 18F-FDG uptake has been shown to correlate well with clinical activity parameters such as disease activity score (DAS)–28, C-reactive protein, and erythrocyte sedimentation rate and clinical outcome at week 12 of triple combination oral DMARD (methotrexate, sulfasalazine, hydroxychloroquine and low-dose glucocorticoids) therapy (Roivainen et al. 2013).

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there is a villous lipomatous proliferation of the synovium, usually involving the suprapatellar pouch of the knee joint.

2.3 Tumors 2.3.1 Synovial Hemangioma To the best of my knowledge there is no literature on the use of 18F-FDG PET/CT in this rare benign vascular malformation.

2.3.2 Synovial Sarcoma Synovial sarcoma (SS) accounts for about 8–10% of all soft tissue sarcoma (Mastrangelo et  al. 2012). Often they present as large masses, typically in deep soft tissues. Although SS can occur at almost every anatomic site, they most commonly do in the extremities, mainly the lower extremities (usually around the knee) (Thway and Fisher 2014). Although in general considered 2.2 Tumor-Like Conditions as a high-grade tumor, with an overall 5-year survival in adults of 50–60% and a 5-year metastatic 2.2.1 Tenosynovial Giant Cell Tumor/ disease free survival ranging between 40% and Pigmented Villonodular 60%, also cases with a more indolent course are Synovitis described (Stacchiotti and Van Tine 2018). Tenosynovial giant cell tumor, of which the intra-­ With regard to the characterization and gradarticular diffuse type was previously designated ing of soft tissue masses in general, the accumuas Pigmented villous nodular synovitis (PVNS) lation of 18F-FDG in cells has been shown to be is an rare benign proliferative process. It is char- proportional to the rate of glucose metabolism acterized by focal or diffuse hyperplasia of syno- with a strong correlation between maximum vial villi affecting the synovial joints, tendon tracer uptake (SUV, Standardized Uptake Value) sheaths and bursa membranes. The knees and and mitotic count, but also with the presence of hips are the most common locations of tumor necrosis. 18F-FDG-uptake has been demPVNS. Due to the high 18F-FDG uptake, PVNS onstrated to correlate well with the histological lesions can mimic malignancy on 18F-FDG PET/ grade, with a significant higher uptake in interCT (Broski et al. 2016; Nguyen 2007). mediate/high grade soft tissue sarcomas compared to low grade tumors using a SUV higher 2.2.2 Synovial Chondromatosis than 2.0 as cut-off (sensitivity and specificity To the best of my knowledge there is no literature 87% and 79% for SUV >2.0 and 70% and 87% on the use of 18F-FDG PET/CT in this uncommon for SUV >3.0), although there was some overlap. benign disorder of the synovial membrane of False negative results can be seen in some low-­ joints, tendon sheaths or bursae. grade sarcomas, while false positive findings were seen in inflammatory lesions or lesions with 2.2.3 Lipoma Arborescens high cellularity (e.g. giant cell tumor) (Ioannidis To the best of my knowledge there is no literature and Lau 2003). on the use of 18F-FDG PET/CT in this chronic, Considering other factors such as the differslowly progressive intra-articular lesion in which ence in reaching peak activity concentration (a

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steady increase in FDG-uptake with a peak activity at approximately 4  h is seen in high grade malignant lesions versus a peak within 30  min followed by a washout in benign lesions) (Chen et al. 2020; Ferner et al. 2000; Lodge et al. 1999), or the uptake pattern (high-grade lesions tend to show a more heterogeneous pattern whereas low-­ grade sarcoma display a more homogeneous uptake) can help to distinguish intermediate/ high-grade lesions from low-grade/benign lesions. However, adequate discrimination between low-grade tumors and benign lesions by 18 F-FDG PET remains difficult (Lucas et  al. 1999; Mayerhoefer et al. 2008). In addition to confirmation of malignancy, it is essential to know the exact histology and grading of the primary tumor to define the best therapeutic strategy. The main role of the current imaging modalities is to tell apart patients with typically benign disease, in whom further invasive staging can be omitted, and patients with a suspected malignancy, who should be referred for biopsy. In many situations core-needle biopsies are accepted as an proper alternative to open biopsy in the evaluation of a musculoskeletal mass. However, since sarcomas tend to be heterogeneous and contain areas of necrosis, there is a risk of sampling error and underestimating true tumor grade (Domanski et al. 2005). Additionally, with a risk of redo-biopsy (in 15–20% of cases) and complications (20%), it is logical that there is a growing interest in using imaging modalities to guide biopsies towards the biologically most active zone (Lucas et al. 1999). 18F-FDG-PET is giving information on biological activity of different tumoral parts and on intratumoral heterogeneity, reflected as areas of high and low tracer uptake (Rakheja et al. 2012). By identifying the metabolically most active portion of a tumor mass, 18F-FDG-PET can guide biopsy to that tumoral part most likely to contain tumor tissue of the highest grade present. 2.3.2.1  Evaluation of Disease Extent As a consequence of its clear, detailed images of soft tissues, MRI is the imaging modality of choice to evaluate the local extent of the primary tumor in the different anatomical compartments

S. K. Ceyssens

surrounding the tumor like muscles, fat, blood vessels, nerves, tendons and synovial tissues. Nearly 20% of all patients with a synovial sarcoma will have metastatic disease at initial diagnosis, 75% of the metastases arising in lungs (76%) or lymph nodes (20%) (Palmerini et  al. 2009). Studies have shown a higher specificity for 18 F-FDG PET-CT compared to conventional imaging modalities (CIMs) in the detection of lung lesions (96% compared to 87%) but a lower sensitivity (80% compared to 93%), presumably as a result of a combination of factors such as lung lesions with a size below the limits of resolution of 18F-FDG-PET (i.e. 4–5 mm), partial volume effects and breathing motion (Quartuccio et al. 2013; Roberge et al. 2012). High resolution CT remains the most sensitive imaging modality to detect lung metastases, although it was shown to be only cost-effective in patients with high-­ grade T2-lesions or T2 extremity lesions (Porter et  al. 2002). The higher specificity of 18F-FDG PET-CT emphasizes the complementary roles of these imaging modalities in the assessment of lung lesions. In these same studies 18F-FDG PET was found to be superior to imaging modalities including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy in the detection of lymph node involvement (sensitivity, 95% for PET versus 25% for CIMs, respectively) as well as bone lesions (sensitivity, 90% versus 57%, respectively) (London et  al. 2012; Völker et  al. 2007). With regard to the detection of lymph node metastases, the power of 18 F-FDG PET exists in its ability to show tumoral involvement in normal-sized nodes and to exclude disease in reactively enlarged nodes (Dwamena et al. 1999). In view of the fact that lymphatic spread is not uncommon in case of SS (Palmerini et al. 2009), it is possible that with the growing use of 18F-FDG PET-CT, the prevalence of detectable lymph node metastases may even increase. Several groups reported a high sensitivity and accuracy of 18F-FDG-PET, 18F-FDG-PET-CT and/or subsequent MRI for PET-MRI fusion for the detection of liver metastases in different kinds

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a

b

Fig. 1  A 71-year-old woman with a mass on the medial side of the left knee was referred for a 18FDG PET-CT (a) initial staging showing an intense 18FDG uptake in the

mass, (b) follow-up after surgery and radiotherapy (60 Gy) showing local tumor response

of tumors (Beiderwellen et al. 2015; Donati et al. 2010; Reiner et  al. 2014). Despite this, liver metastases are usually visualized on the abdominal CT performed to evaluate the primary intra-­ abdominal mass. To the best of my knowledge, no specific literature is available on the accuracy of 18F-FDG PET for the detection of liver metastases in SS.  Since clinical experience with 18F-­ FDG PET/MRI is still limited, its role in the evaluation off SS still needs to be defined. In summary, the main power of 18F-FDG PET and 18F-FDG-PET-CT lies in the ability to screen the entire patient for distant metastases without significantly increasing the radiation burden. The key role of 18F-FDG-PET-CT, lies largely in detecting metastases at unexpected sites, outside the standard field-of-view of CT and MRI, and in the exclusion of disease in equivocal results on conventional imaging (Nair and Basu 2005; Upadhyay et al. 2020). Although further studies are required, preliminary clinical experiences with 18F-FDG PET/MRI seem promising. The main advantages of combining the anatomical information of MRI and the metabolic information of PET lies in joining the strength of the T staging equal to that of an MR alone, comple-

mented by the power of N and M staging from the PET component (Partovi et al. 2014) (Fig. 1). 2.3.2.2  Evaluation of Response to Treatment The purpose of therapy monitoring is to assess chemosensitivity, i.e. to distinguish accurately responders from non-responders. The ultimate goal is to adapt the therapy to the information provided: treatment can be continued in responders, whereas therapy can be switched in case of non-response. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria are widely used in oncology clinical trials. In the RECIST criteria partial response is defined as a decrease of at least 30% in the sum of diameters of the target lesions, with the baseline sum of diameters as reference (Arbuck et al. 2009). However, evaluation of tumor response by volume changes, especially in STS, has been demonstrated to be unreliable (Ceresoli et  al. 2007; Goffin et  al. 2005; Stacchiotti et  al. 2009). Firstly, in ill-­ defined lesions like bone, bowel and peritoneal lesions correct measurement of tumor dimensions can be challenging. Secondly, chemother-

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apy can induce pronounced tissue changes like necrosis and fibrosis. Therefore, a reduction in viable tumor cell fraction is not always associated with a reduction in volume. In rare cases, even an increase in dimensions can be seen due to necrosis, fibrosis of hemorrhage (Lucas et  al. 2008). Thirdly, volume changes are rather late events and therefore changes measured by anatomical imaging techniques are often not significant when performed earlier than 2–3 months after the start of treatment. In this way, patients might be exposed to expensive, ineffective and even toxic treatments during a prolonged period. It can even reduce the chance of a curative resection by postponing surgery in the neo-adjuvant setting. Finally, the goal of new anti-vascular and cytostatic agents is rather a stabilization of tumor growth than tumor shrinkage and therefore, no major volume changes are to be expected. In various tumors promising results for 18F-­ FDG PET in treatment monitoring were shown with a good correlation between an early and significant decline in metabolic activity and response to therapy, as well as a good correlation between the early decrease in 18F-FDG uptake and patient outcome (Juweid and Cheson 2006). Since 18F-­ FDG PET can differentiate between viable cells and necrotic or fibrotic inactive tissue, it allows accurate differentiation between responders and non-responders early after the start of treatment (Canellos 1988; Spaepen et al. 2001). When using 18F-FDG PET to assess treatment response a basal or pretherapeutic PET scan is mandatory, since evaluation of metabolic response is based on the change in 18 F-FDG uptake in the tumor in comparison to the basal study. Moreover, as mentioned before, some tumors show only slight 18F-­FDG uptake. In the latter case, 18F-FDG PET is not suitable response assessment, nor follow up. Several studies have evaluated whether changes in 18F-FDG uptake and size measured before and after neoadjuvant chemotherapy in high-grade soft-tissue sarcoma could accurately assess histopathologic response defined as ≥95% pathologic necrosis on the resected tumor. Quantitative 18F-FDG-PET outperforms the size-­ based criteria to distinguish responders from

S. K. Ceyssens

non-responders to neoadjuvant therapy. Using a 60% decrease in 18F-FDG uptake resulted in a sensitivity of 100% and specificity of 71% for PET, whereas for RECIST a sensitivity of 25% and specificity of 100% was seen (Evilevitch et al. 2008). Even after only one cycle of neoadjuvant chemotherapy in high grade STS histologic responders could be identified using a ≥35% reduction in 18F-FDG uptake (SUVpeak) as early metabolic response threshold (sensitivity 100% and specificity 67%). Since responders have to be identified with high sensitivity to avoid withholding potentially effective treatments to patients a high sensitivity is more important than a high specificity (Benz et  al. 2009). Although scarce, studies in the subgroup of synovial sarcoma show similar, promising results (Chang et al. 2015; Lisle et al. 2009). In conclusion, 18F-FDG PET seems promising in treatment monitoring. A good correlation was found between an early and significant decline in metabolic activity and response to therapy in different types of sarcoma and synovial sarcoma in particular. 2.3.2.3  Detection of Recurrence In a study of Palmerini 18% of all patients with a synovial sarcoma were documented with local recurrence during follow up, in 22.5% patients developed lung metastases and 4% had metastases at multiple sites (Palmerini et al. 2009). Main factors predicting local recurrence are positive surgical margins, whereas grade, size and tumor-­ node-­metastasis (TNM) stage predict the development of metastatic disease and overall survival (Stefanovski et al. 2002). If the intent is surgical control, early detection and treatment of local recurrence is desirable, even if this does not necessarily influence the final outcome of the patient. Due to its high contrast resolution, MRI still is the technique of choice in case of suspected local recurrence in the extremities. However, radiotherapy and chemotherapy induced changes (soft-tissue trabeculation, increased fatty marrow, focal marrow abnormalities, hemorrhage) can complicate the evaluation of the affected region. On the other hand, the use of an organized systematic

PET/CT in Synovial Tumors and Tumor-Like Conditions

approach and certain algorithms, can reduce the challenge (Garner et  al. 2009; Vanel et  al. 1998). Preliminary results for the use of 18F-PET-CT for detection of local recurrence of STS seem promising (Dancheva et  al. 2016), particularly when combining the metabolic information of 18 F-FDG PET and the excellent soft tissue contrast of MRI in an integrated 18F-FDG PET/ MRI. Erfanian and coworkers compared the diagnostic accuracy of PET/MRI and MRI alone for the detection of local recurrences of soft tissue sarcomas (STS) after initial surgical resection of the primary tumors. 18F-FDG PET/MRI was shown to be an excellent imaging technique with a higher sensitivity and negative predictive value as well as a higher diagnostic confidence for the detection of recurrent STS after resection when compared to MRI alone (Erfanian et  al. 2017) (Figs. 2 and 3). 2.3.2.4 Prognostic Value Although synovial sarcomas are generally considered as a high grade sarcoma, the biologic behavior in this group of tumors may vary (Bergh

a

b

Fig. 2 Same patient as Fig. 1 (a) initial staging showing no metastases, (b) follow-up after surgery and radiotherapy (60 Gy) showing lung metastases, (c) further follow-

111

et al. 1999). Several studies showed a strong correlation between maximum 18F-FDG uptake (SUV) and pathological grade, cellularity, mitotic activity, MIB labeling index, and p53 overexpression, all of these factors known to have prognostic value (Kubota et  al. 1992). Studies demonstrated that high 18F-FDG uptake in sarcoma on the pre-treatment PET is associated with a significant shorter disease free survival (DFS) (p  hip > shoulder > other joints Benign chondroid neoplasia of the synovium • Soft tissue mass • Uncalcified, calcified, or bone maturation • Joint space preservation or widening • Numerous nodules (>5) of similar size and shape • Pressure erosions • T1: Intermediate signal intensity • T2: High signal intensity • Calcified foci: Low signal on all sequence • Peripheral and septal enhancement

Secondary synovial chondromatosis • >Sixth decade • No gender difference • Any joint Growth of intra-articular loose cartilage secondary to joint damage • Uncalcified, calcified, or bone maturation • Joint space narrowing • Less nodules ( hip > ankle > other joints Benign neoplastic proliferation of the synovium • Soft tissue mass • No calcifications • Increased density due to hemosiderin • Pressure erosions, sometimes circumferential

• T1: Intermediate signal intensity • T2: Heterogeneous high and low signal intensity • Hemosiderin foci (often large areas): Low signal on all sequences and blooming artifacts on T2*-WI • Marked and diffuse enhancement

recurrence. Spontaneous regression has been reported but is considered unusual (Swan and Owens 1972). Historically, open arthrotomy has been the treatment of choice for PSC. However, it has now been replaced by arthroscopic treatment in the majority of cases resulting in shorter rehabilitation periods and better postsurgical range of motion (Coolican and Dandy 1989; Jiménez-­ Martín et  al. 2014; de Sa et  al. 2014). On the downside, some regions of the joint can be more difficult to investigate during arthroscopy (Ogilvie-Harris and Saleh 1994; Zhu et al. 2018). Conflicting data exist about the need for synovectomy after complete removal of the intra-articular bodies. Removal of all intra-articular loose bodies followed by partial or total synovectomy is currently the treatment of choice for Milgram phases I and II (Coolican and Dandy 1989; Lim et al. 2006; Murphy et al. 1962). When treating Milgram phase III, synovectomy remains controversial (Maurice et al. 1988; Ogilvie-Harris and

Synovial Chondromatosis

Saleh 1994; Zhu et al. 2018). In SSC, removal of all the loose bodies is performed without ­synovectomy. Arthroplasty can be performed in cases of PSC as well as SSC with severe joint damage (Houdek et al. 2017; Tibbo et al. 2018).

8.2 Recurrence After loose body removal and complete synovectomy, recurrence rates for intra-articular and tenosynovial PSC are 0–12% and 38%, respectively. But even after total arthroplasty, recurrence rates remain high (up to 20%) (Davis et al. 1998; Houdek et  al. 2017; Maurice et  al. 1988; Roulot and le Viet 1999; de Sa et  al. 2014). Reasons for recurrence include incomplete removal of intra-articular lesions and incomplete resection of the diseased synovium. Older age has been associated with higher recurrence rates in some small case series as well (de Sa et  al. 2014).

8.3 Malignant Transformation SChS may be primary or arise from preexisting PSC.  The rate of malignant transformation among patients with PSC ranges from 2.6% to 6.4% (Davis et  al. 1998; Evans et  al. 2014; McCarthy et al. 2016; Urwin et al. 2019). For the differential diagnosis with PSC, please see paragraph 7, “Differential Diagnosis” section, and for a more complete discussion of SChS, see chapter “Synovial Chondrosarcoma.”

9

Key Points

• PSC is a benign neoplastic disease originating in the synovial lining of joint, tendon sheaths, or bursae. • Radiography will show intra-articular calcification suggestive of PSC in up to 95% of cases.

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• The pattern-based classification by Kramer et al. is best suited for radiologic purposes. • MRI is the modality of choice for evaluating disease extension but also to exclude bone marrow invasion, suggestive of malignancy. • Clinical, radiologic, and histopathologic correlation is important to arrive at the correct diagnosis.

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136 review of rates and predisposing factors for recurrence. Arthroscopy 30:1499–1504.e2 Edeiken J, Edeiken BS, Ayala AG, Raymond AK, Murray JA, Guo S-Q (1994) Giant solitary synovial chondromatosis. Skelet Radiol 23:23–29. Available from: http://link.springer.com/10.1007/BF00203697 Evans S, Boffano M, Chaudhry S, Jeys L, Grimer R (2014) Synovial chondrosarcoma arising in synovial chondromatosis. Sarcoma 2014:647939 Felbel J, Gresser U, Lohmöller G, Zöllner N (1992) Familial synovial chondromatosis combined with dwarfism. Hum Genet 88(3):351–354. Available from: http://link.springer.com/10.1007/BF00197274 Fetsch JF, Vinh TN, Remotti F, Walker EA, Murphey MD, Sweet DE (2003) Tenosynovial (extraarticular) chondromatosis. Am J Surg Pathol 27(9):1260– 1268. Available from: http://journals.lww. com/00000478-­200309000-­00010 Flanagan A, Bloem J, Cates JMM, O’Donnell P (2020) WHO classification of tumours soft tissue and bone tumours, vol 3, 5th edn. IARC Press, Lyon, pp 368–369 Frankel DA, Bargiela A, Bouffard JA, Craig JG, Shirazi KK, van Holsbeeck MT (1998) Synovial joints: evaluation of intraarticular bodies with US1. Radiology 206:41–44. Available from: http://pubs.rsna.org/ doi/10.1148/radiology.206.1.9423649 Gill J, Tytherleigh-Strong G (2019) Osteochondritis dissecans with associated secondary chondromatosis in an adolescent shoulder. Shoulder Elbow 11(4):275–281 Hallam P, Ashwood N, Cobb J, Fazal A, Heatley W (2001) Malignant transformation in synovial chondromatosis of the knee? Knee 8:239 Hew S, Wong Bsc M, Salama S, Thoma A, Frcsc MD (2003) Synovial chondromatosis of the hand: three case reports and literature review. Can J Plast Surg 11:47–52. Available from: http://journals.sagepub. com/doi/10.1177/229255030301100109 Ho YY, Choueka J (2013) Synovial chondromatosis of the upper extremity. J Hand Surg 38(4):804–810 Houdek MT, Wyles CC, Rose PS, Stuart MJ, Sim FH, Taunton MJ (2017) High rate of local recurrence and complications following total knee arthroplasty in the setting of synovial chondromatosis. J Arthroplasty 32(7):2147–2150 Jamshidi K, Barbuto R, Shirazi R, Abolghasemian M (2015) A case report & literature review giant solitary synovial chondromatosis mimicking chondrosarcoma: report of a rare histologic presentation and literature review. Am J Orthop 44:E286–E290. Available from: www.amjorthopedics.com Jeffreys TE (1967) Synovial chondromatosis. J Bone Joint Surg Br 49(3):530–534. Available from: http://www. ncbi.nlm.nih.gov/pubmed/6037566 Jiménez-Martín A, Zurera-Carmona M, Santos-Yubero FJ, Pérez-Hidalgo S (2014) Arthroscopic treatment of synovial chondromatosis, an unusual cause of shoulder pain. Reumatol Clín (Eng Ed) 10(6):416–417 Kim SH, Hong SJ, Park JS, Cho JM, Kim EY, Ahn JM et al (2002) Idiopathic synovial osteochondromatosis of the hip: radiographic and MR appearances in 15

G. J. M. Vangrinsven and F. M. Vanhoenacker patients. Korean J Radiol 3(4):254. Available from: https://www.kjronline.org/DOIx.php?id=10.3348/ kjr.2002.3.4.254 Kramer J, Recht M, Deely DM, Schweitzer M, Pathria MN, Gentili A, Greenway G, Resnick D (1993) MRI appearance of idiopathic synovial osteochondromatosis. J Comput Assist Tomogr 17(5):772–776. Available from: http://journals.lww. com/00004728-­199309000-­00020 Lim S-J, Chung H-W, Choi Y-L, Moon Y-W, Seo J-G, Park Y-S (2006) Operative treatment of primary synovial osteochondromatosis of the hip. J Bone Joint Surg 88(11):2456–2464. Available from: http://journals. lww.com/00004623-­200611000-­00019 Matsumoto K, Sato T, Iwanari S, Kameoka S, Oki H, Komiyama K et  al (2013) The use of arthrography in the diagnosis of temporomandibular joint synovial chondromatosis. Dentomaxillofac Radiol 42(1):15388284 Maurice H, Crone M, Watt I (1988) Synovial chondromatosis. J Bone Joint Surg 70:807–811. Available from: https://online.boneandjoint.org.uk/ doi/10.1302/0301-­620X.70B5.3192585 McCarthy C, Anderson WJ, Vlychou M, Inagaki Y, Whitwell D, Gibbons CLMH et  al (2016) Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases. Skelet Radiol 45(6):755–762 McKee TC, Belair JA, Sobol K, Brown SA, Abraham J, Morrison W (2020) Efficacy of image-guided synovial biopsy. Skelet Radiol 49(6):921–928 McKenzie G, Raby N, Ritchie D (2008) A pictorial review of primary synovial osteochondromatosis. Eur Radiol 18:2662–2669 Milgram JW (1977) Synovial osteochondromatosis: a histopathological study of thirty cases. J Bone Joint Surg Am 59(6):792–801 Moss GD, Dishuk W (1984) Ultrasound diagnosis of osteochondromatosis of the popliteal fossa. J Clin Ultrasound 12(4):232–233. Available from: https:// onlinelibrary.wiley.com/doi/10.1002/jcu.1870120413 Murphey MD, Walker EA, Wilson AJ, Kransdorf MJ, Temple HT, Gannon FH (2003) Imaging of primary chondrosarcoma: radiologic-pathologic correlation. Radiographics 23:1245–1278 Murphey MD, Vidal JA, Fanburg-Smith JC, Gajewski DA (2007) Imaging of synovial chondromatosis with radiologic-pathologic correlation. Radiographics 27:1465–1488 Murphy FP, Dahlin DC, Sullivan CR (1962) Articular synovial chondromatosis. J Bone Joint Surg 44(1):77–86 Narváez JA, Narváez J, Aguilera C, de Lama E, Portabella F (2001) MR imaging of synovial tumors and tumor-­ like lesions. Eur Radiol 11(12):2549–2560 Neumann JA, Garrigues GE, Brigman BE, Eward WC (2016) Synovial chondromatosis. J Bone Joint Surg Rev 4:e2 Ng VY, Louie P, Punt S, Conrad EU (2017) Malignant transformation of synovial chondromatosis: a systematic review. Open Orthop J 11(1):517–524.

Synovial Chondromatosis Available from: https://openorthopaedicsjournal.com/ VOLUME/11/PAGE/517/ Norman A, Steiner GC (1986) Bone erosion in synovial chondromatosis. Radiology 161(3):749–752. Available from: http://pubs.rsna.org/doi/10.1148/ radiology.161.3.3786727 O’Connell J (2000) Pathology of the synovium. Am J Clin Pathol 114(5):773–784. Available from: https:// academic.oup.com/ajcp/article/114/5/773/1757978 Ogilvie-Harris DJ, Saleh K (1994) Generalized synovial chondromatosis of the knee: a comparison of removal of the loose bodies alone with arthroscopic synovectomy. Arthroscopy 10:166–170 Pai VR, van Holsbeeck M (1995) Synovial osteochondromatosis of the hip: role of sonography. J Clin Ultrasound 23:199–203. Available from: https:// onlinelibrary.wiley.com/doi/10.1002/jcu.1870230311 Patel MR, Desai SS (1985) Tenosynovial osteochondromatosis of the extensor tendon of a digit: case report and review of the literature. J Hand Surg 10(5):716–719 Pattee GA, Snyder SJ (1988) Synovial chondromatosis of the acromioclavicular joint. A case report. Clin Orthop Relat Res 233:205–207 Prager R, Mall J (1976) Arthrographic diagnosis of synovial chondromatosis. Am J Roentgenol 127(2):344– 346. Available from: http://www.ajronline.org/ doi/10.2214/ajr.127.2.344 Raf Sciot PDC (1998) Synovial chondromatosis clonal chromosome changes provide further evidence for a neoplastic disorder. Virchows Arch 433(2):189–191. Available from: http://link.springer.com/10.1007/ s004280050235 Roberts D, Miller TT, Erlanger SM (2004) Sonographic appearance of primary synovial chondromatosis of the knee. J Ultrasound Med 23:707–709. Available from: http://doi.wiley.com/10.7863/jum.2004.23.5.707 Roulot E, le Viet D (1999) Primary synovial osteochondromatosis of the hand and wrist. Report of a series of 21 cases and literature review. Revue du rhumatisme (Eng Ed) 66(5):256–266. Available from: http://www. ncbi.nlm.nih.gov/pubmed/10380257 Sergio G (1980) Skeletal radiology computed tomography feature of synovial osteochondromatosis case report. Skelet Radiol 5:219–222. Available from: http://link. springer.com/10.1007/BF00580593 Shanley DJ (1991) Synovial osteochondromatosis demonstrated on bone scan-correlation with CT and MRI. Clin Nucl Med 17(4):338–339. Available from: http://journals.lww.com/00003072-­199204000-­00021 Startzman A, Collins D, Carreira D (2016) A systematic literature review of synovial chondromatosis and pigmented villonodular synovitis of the hip. Physician Sportsmed 44:425–431

137 Swan EF, Owens WF (1972) Synovial chondrometaplasia: a case report with spontaneous regression and a review of the literature. South Med J 65(12):1496–1500 Tang B, Wang K, Wang H, Zheng G (2019) Radiological features of synovial chondromatosis affecting the temporomandibular joint: report of three cases. Oral Radiol 35(2):198–204 Testaverde L, Perrone A, Caporali L, Ermini A, Izzo L, D’Angeli I et al (2011) CT and MR findings in synovial chondromatosis of the temporo-mandibular joint: our experience and review of literature. Eur J Radiol 78(3):414–418 Tibbo ME, Wyles CC, Rose PS, Sim FH, Houdek MT, Taunton MJ (2018) Long-term outcome of hip arthroplasty in the setting of synovial chondromatosis. J Arthroplasty 33(7):2173–2176 Tins B, Cassar-Pullicino V (2003) Synovial osteochondromatosis in hereditary arthro-ophthalmopathy (Wagner-­ Stickler syndrome). Skelet Radiol 32(5):302–305 Trias A, Quintana O (1976) Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. Can J Surg 19(2):151 Urwin JW, Cooper K, Sebro R (2019) Malignant transformation of recurrent synovial chondromatosis: a case report and review. Cureus 11:e5839 Vanhoenacker FM, Parizel PM, Gielen JL (2017) In: Vanhoenacker FM, Parizel PM, Gielen JL (eds) Imaging of soft tissue tumors. Springer International Publishing, Cham. Available from: http://link.springer. com/10.1007/978-­3-­319-­46679-­8 Villacin AB, Brigham LN, Bullough PG (1979) Primary and secondary synovial chondrometaplasia. Hum Pathol 10(4):439–451. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0046817779800507 Wadhwa V, Cho G, Moore D, Pezeshk P, Coyner K, Chhabra A (2016) T2 black lesions on routine knee MRI: differential considerations. Eur Radiol 26:2387–2399 Walker EA, Murphey MD, Fetsch JF (2011) Imaging characteristics of tenosynovial and bursal chondromatosis. Skelet Radiol 40(3):317–325 Wittkop B, Davies AM, Mangham DC (2002) Primary synovial chondromatosis and synovial chondrosarcoma. Eur Radiol 12(8):2112–2119 Yao M, Chang C, Chen C, Chan W (2012) Synovial chondrosarcoma arising from synovial chondromatosis of the knee. J Belg Soc Radiol 95(6):360. Available from: http://www.jbsr.be/articles/abstract/10.5334/ jbr-­btr.723/ Zhu W, Wang W, Mao X, Chen Y (2018) Arthroscopic management of elbow synovial chondromatosis. Medicine (United States) 97(40):e12402

Tenosynovial Giant Cell Tumor Hend Riahi , Mohamed Fethi Ladeb , and Mouna Chelli Bouaziz

Contents

Abstract

1

Introduction

140

2

Epidemiology

140

3

Pathogenesis

140

4

Clinical Presentation

140

5 5.1

Pathologic Features Diffuse Tenosynovial Giant Cell Tumor Localized Tenosynovial Giant Cell Tumor

141

141

6 6.1 6.2 6.3 6.4 6.5 6.6

Imaging Radiography Ultrasound CT Arthrography CT MRI FDG PET/CT

143 143 144 146 147 147 150

7 7.1

Differential Diagnosis Diffuse Tenosynovial Giant Cell Tumor Localized Tenosynovial Giant Cell Tumor

150

151

8

Diagnosis

151

9

Treatment

151

10

Key Points

152

5.2

7.2

References

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150

Tenosynovial giant cell tumor is a family of lesions usually involving the joint, bursae, and/or tendon sheath synovia. Tenosynovial giant cell tumor includes two subtypes, localized and diffuse, that are histologically similar, but have disparate clinical and imaging features. Diffuse tenosynovial giant cell tumor most frequently affects the large joints, while localized forms involve the hand or wrist. Radiography shows nonspecific features such as maintained joint space, joint effusion, and extrinsic erosion on both sides of the joint space. MR imaging demonstrates the disease extent and depicts the blooming artifact from hemosiderin deposition. Diagnosis always requires MRI, and often histologic confirmation is needed. Indications and modalities of treatment are discussed according to symptomatology, progression, and location.

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H. Riahi (*) · M. F. Ladeb · M. Chelli Bouaziz Department of Radiology, Institut Mohamed Kassab d’orthopédie, Manouba, Tunisia e-mail: [email protected]; [email protected]; [email protected] Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_415, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 12 April 2023

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Abbreviations CT DTGCT

Computed tomography Diffuse tenosynovial giant cell tumor FDG PET/CT Fluorodeoxyglucose-positron emission computed tomography LTGCT Localized tenosynovial giant cell tumor MRI Magnetic resonance imaging TGCT Tenosynovial giant cell tumor

1 Introduction Tenosynovial giant cell tumor (TGCT) is a family of lesions usually involving the joint, bursae, and/ or tendon sheath synovia. TGCT includes two subtypes, localized and diffuse, that are histologically similar, but have disparate clinical and imaging features. Diffuse forms (DTGCT) are most commonly intra-articular masses that mainly involve the large joints. The localized type (LTGCT) consists of a small well-­circumscribed mass and may be either intra- or, most frequently, extra-articular. It most commonly involves the hands and feet (Dundar et al. 2020). While these tumor types were previously designated as pigmented villonodular synovitis or giant cell tumor of the tendon sheath, the most recent version of the World Health Organization classification (2020) recommends to replace the term pigmented villonodular synovitis (de Saint Aubain Somerhausen and van de Rijn 2013).

The localized extra-articular form of the disease accounts for 1.6–3.9% of all benign soft tissue masses, whereas the diffuse intra-articular form represents 0.9% (Myers and Masi 1980; Enzinger and Weiss 2008). Patients are most commonly in the third to fifth decades of life and a little earlier for the diffuse form. DTGCT occurs with equal frequency in both sexes, whereas LTGCT has a mild female predilection (1.5–2.1:1) (Kempson et  al. 2001; Kransdorf and Murphey 2006; Hughes et  al. 1995; Dorfman and Czerniak 1998; Flandry and Hughston 1987).

3 Pathogenesis The pathogenesis of TGCT has been poorly understood. It has historically been attributed to either an inflammatory process; repeated hemorrhage into the joint, perhaps related to an occult synovial hemangioma or repetitive mild trauma; or a disorder of lipid metabolism (Murphey et al. 2008). More recently, TGCT was found to be a clonal neoplastic process associated with specific genetic changes, frequently due to a specific translocation: t(1;2) CSF1:COL6A3. There is also typically a reactive component with proliferation and recruitment of colony-stimulating factor 1 receptor (CSF1R)-expressing cells including macrophages, giant cells, and osteoclasts, in what is known as the “paracrine landscape effect” (West et al. 2006).

4 Clinical Presentation 2 Epidemiology

DTGCT most frequently affects the large joints, The average annual incidence has been estimated with the knee involved in 66–80% of cases to be 9.2 and 1.8 cases per one million population (Schwartz et al. 1989; Sharma et al. 2007). The hip is the second most affected joint, for the LTGCT and DTGCT forms of the disease, accounting for 4–16% of cases (Kempson et al. respectively (Myers and Masi 1980). Localized disease represents 77% of TGCT 2001; Kransdorf and Murphey 2006). Other affected joints include the ankle, shoulcases. The tenosynovial form is the most comder, and elbow in decreasing order of frequency. mon and accounts for 23%. Localized intra-­ Rarely affected locations are apophyseal joints of articular involvement represents 6% of all cases the spine, small joints of the hands or feet, sacroof TGCT.

Tenosynovial Giant Cell Tumor

iliac joint, subtalar joints, and temporomandibular joint (Bemporad et  al. 1999; Furlong et  al. 2003). LTGCT most commonly involves the hand or wrist (65–89% of cases), specifically the index and long fingers. The volar aspect of the hand is affected approximately twice as often as the dorsal aspect. The next most common site of localized extra-articular disease is the foot and ankle, which account for 5–15% of lesions (Kransdorf and Murphey 2006; Hughes et al. 1995; Dorfman and Czerniak 1998). Other locations comprise, very rarely, hip or elbow (Ushijima et al. 1986). Localized intra-articular involvement of TGCT almost exclusively involves the knee (Myers and Masi 1980). Common clinical symptoms associated with DTGCT are pain (79–90% of cases), swelling (72–79%), and joint dysfunction (26–28%). Extra-articular LTGCT most frequently manifests clinically with a soft tissue mass (83–99% of cases) and pain (22–71%) (Kempson et  al. 2001; Kransdorf and Murphey 2006; Hughes et al. 1995; Dorfman and Czerniak 1998; Flandry and Hughston 1987). The duration of symptoms ranges widely from 1 to 120  months, with a mean duration of 15  months for diffuse forms and 19  months for localized disease (Myers and Masi 1980). DTGCT lesions may demonstrate intermittent, fluctuating symptoms with slow overall progression (Baker et al. 1989). A history of trauma has been found in 44–53% of patients (Murphey et al. 2008).

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5.1 Diffuse Tenosynovial Giant Cell Tumor Tumors range in size from 0.7 to 10  cm. Giant cell tumors are well-circumscribed, mostly solid, nodular mass with fleshy, reddish-brown or gray cut surface. There is no collagenous pseudo-­ capsule (Goldman and DiCarlo 1988) (Fig. 1). The articular cartilage is usually preserved but, particularly in the hip, it may show brown-­ green discoloration and damage resulting in a peeled off appearance of the superficial layers. Occasionally, the proliferating synovial tissue creeps in the subchondral bone dissecting the articular cartilage (Campanacci 1999).

5.2 Localized Tenosynovial Giant Cell Tumor It generally manifests as a circumscribed, lobulated, cauliflower-like, nodular soft tissue mass that is attached to the tendon sheath or that resides within a known bursal site. Lesion size typically ranges from 0.5 to 4.0 cm in greatest dimension (Fig.  2). Cut sections demonstrate pink-gray tumors with mottled brown or yellow, depending

5 Pathologic Features The histologic pattern of DTGCT is almost pathognomic, but it may also be seen as an incidental finding in the synovium of patients having osteoarthritis or rheumatoid arthritis (Vigorita 1984). The gross pathologic appearance of DTGCT varies, depending on the location and type of disease.

Fig. 1  Photograph from knee arthroscopy demonstrates brownish villonodular fronds. (Courtesy of Pr Ben Amor H)

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Fig. 2  Photograph shows a well-circumscribed, lobulated localized TGCT with a tan-yellow cut surface. (Courtesy of Pr Tarhouni L)

Fig. 3  Microscopic image of TGCT (original magnification ×80 H. E. stain): the synovium is composed of fingerlike fibrous stroma with large numbers of foamy macrophages; note the hemosiderin deposits (arrow). (Courtesy of Pr Jaafoura H)

on the amount of xanthoma cells or hemosiderin. At microscopic analysis, LTGCT disease typically reveals a multinodular, well-delineated process embedded in a dense, partially collagenous pseudo-capsule (Kempson et al. 2001). The microscopic presentation shows a mixture of histio-fibroblastic and capillary proliferation, villous production and/or clefts lined by synovial cells, macrophages containing hemosiderin, lipid-laden (foam or xanthoma) cells, multinucleated giant cells, modest and sparse chronic inflammatory cell component, and variability toward fibro-hyaline maturations (Figs. 3 and 4). In rare cases, chondroid or osteoid metaplasia with associated calcification is seen (Murphey et al. 2008). Cytogenetic aberrations may be seen in the majority cases of TGCT.  The most consistent genetic rearrangement in both localized and diffuse types of TGCT is in chromosome 1p11-13, a site for CSF-1 gene, which most commonly fuses to COL6a3 on chromosome 2q35 (Murphey et al. 2008). The reasons for the development of bone erosion remain controversial: Chung and Janes (1965) reported that the hyperplastic villonodular tissue with joint effusions causes increased intra-­ articular pressure, resulting in compression of the articular cartilage and bony cortex. Scott (1968)

Fig. 4  Microscopic image of TGCT (original magnification ×80 H. E. stain): hemosiderin deposits in the macrophage’s cytoplasm. (Courtesy of Pr Jaafoura H)

suggests that the synovium infiltrates deep into the bone by the vasa vasorum pathway, causing bone encroaching and bone atrophy due to compressive forces resulting in a cyst-like bone destruction. More recently, Ofluoglu showed that proteolytic enzymes expressed by the giant cells within the lesion may contribute to these osseous changes (Ofluoglu 2006). Malignant transformation is extremely rare but has been reported in the literature (Kim et al. 2000).

Tenosynovial Giant Cell Tumor

6 Imaging 6.1 Radiography 6.1.1 Diffuse Tenosynovial Giant Cell Tumor Radiography is normal in 25% of patients (Schvartzman et al. 2015). The joint space is preserved until late after the onset of the disease. Joint effusion may even cause widening of the joint space. The joint effusion may occasionally appear as a dense soft tissue swelling (Figs.  5 and 6) (Garner et al. 2008). Bone mineralization is normal, and hypertrophic spurring is absent (Garner et al. 2008). In large joints such as the knee with a large capacity of expansion, bone erosion is rarely seen (25% of cases) (Fig. 2), except in the later stages. On the contrary, in joints with a tight joint space, such as the hip (Fig. 6), ankle, elbow, and wrist, bone erosion is frequently seen (90% of cases) (Llauger et al. 1999). These erosions are ubiquitary, typically occur nearby the synovial insertion at both sides of the joint, and are delineated by a thin sclerotic rim of sclerosis (Fig. 7).

Fig. 5 Diffuse tenosynovial giant cell tumor, lateral radiograph of ankle shows hyperdense joint effusion (asterisks)

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Calcification is rare (6%) (Hughes et al. 1995) and should suggest an alternative diagnosis (Lindenbaum and Hunt 1977).

Fig. 6 Diffuse tenosynovial giant cell tumor, lateral radiograph of knee demonstrates posterior soft tissue mass (arrows) and bone erosion (arrowhead)

Fig. 7  Diffuse tenosynovial giant cell tumor, AP radiograph of the right hip shows joint space narrowing and multiple erosions (asterisk)

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Periosteal reaction may be seen in 8% of cases (Karasick and Karasick 1992).

6.1.2 Localized Tenosynovial Giant Cell Tumor 6.1.2.1  Extra-articular Form Radiographs in LTGCT (bursitis and tendon sheath) are normal in up to 20% of cases (Kransdorf and Murphey 2006; Carpintero et al. 2007). A nonspecific soft tissue mass is seen in 50–70% of cases (Fig. 8). Osseous abnormalities are present in 15–25% of cases, with extrinsic

erosion being the most common osseous abnormality, seen in 9–25% of cases (Abdelwahab et al. 2002; Karasick and Karasick 1992). 6.1.2.2  Intra-articular Form Radiographs appear normal in most cases (Myers and Masi 1980; Huang et al. 2003). In knee, an area of soft tissue opacity replacing the normal region of adipose tissue in the Hoffa’s fat pad may be seen (Fig.  9) (Murphey et al. 2008). Myers and Masi (1980) reported extrinsic erosion of bone in 20% of their cases involving the knee. Periosteal reaction is seen in 8% of cases and calcifications in 6% (Murphey et al. 2008).

6.2 Ultrasound 6.2.1 Diffuse Tenosynovial Giant Cell Tumor Sonographic features are nonspecific and may be seen in other causes of synovitis. US may show heterogenous intra-articular masses and thickened hypoechoic hypertrophic synovial fronds (Fig. 10) (Sullivan et al. 2020). The presence within the synovium of small intense echoes may be useful to suggest the diagnosis (Fig. 11) (Ladeb et al. 2020). Other findings include loculated joint effusion and presence of complex heterogeneous echoic masses. Bone erosions may be seen on ultrasound (Murphey et al. 2008). Power Doppler typically shows increased flow in the synovial masses with a relatively increased flow in the periphery of the synovial capsule (Lin et al. 1999). 6.2.2 Localized Tenosynovial Giant Cell Tumor

Fig. 8  Localized extra-articular tenosynovial giant cell tumor of a flexor tendon sheath of the middle finger lateral radiograph shows soft tissue swelling on the palmar aspect of the finger with cortical erosion of P2 (arrowhead)

6.2.2.1  Extra-articular Form LTGCT has been reported as being either hypoechoic (Middleton et  al. 2004; Martinoli et al. 1999) or hyperechoic (Peh et al. 2001). The borders of the lesions are clear in most cases. The mass has an intimate relationship with

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b

Fig. 9 Localized tenosynovial giant cell tumor, lateral radiograph of knee (a) demonstrates joint effusion and focal mass (asterisk) well seen on sagittal gradient-echo T2* MR image (arrow) (b)

Fig. 10 Diffuse tenosynovial giant cell tumor, longitudinal sonogram of anterior recess of ankle shows marked synovial thickening (arrows) with several pockets of fluid (asterisks) representing loculated joint effusion

the associated involved tendon, but it does not move with the tendon during dynamic sonography (Fig.  12). Doppler imaging commonly reveals increased blood flow (Murphey et  al. 2008) (Fig. 13). There are also nonvascularized pseudo-cystic forms or diffuse forms which may be confused with tenosynovitis (Ladeb et  al. 2020) (Fig. 14).

Fig. 11 Diffuse tenosynovial giant cell tumor, longitudinal sonogram of anterior recess of knee shows synovial thickening with several small intense echoes (arrowheads)

6.2.2.2 Intra-articular Form Localized intra-articular involvement has features similar to those seen in diffuse disease except for its focal appearance (Murphey et al. 2008).

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6.3

CT Arthrography

Nodular synovial thickening of TGCT can appear as filling defects within the joint. These findings are similar to those seen with synovial osteochondromatosis or rheumatoid arthritis (rice bodies) (Dorwart et al. 1984).

Fig. 12 Localized tenosynovial giant cell tumor, longitudinal sonogram. Hypoechoic nodule along the course of the flexor tendons with hyperechoic spots (arrowheads)

a

Fig. 13 Localized extra-articular tenosynovial giant cell tumor of a flexor tendon sheath of the middle finger; longitudinal sonograph shows a well-defined ovoid homoge-

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Fig. 14 Localized tenosynovial giant cell tumor, (a) longitudinal and (b) axial sonogram diffuse thickening of the flexor tendon sheath (arrows) and small intense echoes

b

neously hypoechoic lesion (a). There are a few peripheral flow signals (b)

b

(arrowheads) associated with a peritendinous fluid effusion (asterisk)

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6.4

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CT

6.4.2

6.4.1

Diffuse Tenosynovial Giant Cell Tumor CT features are similar to radiographic findings, but CT can further demonstrate synovial thickening and quantify the density of the lesion (Jelinek et al. 1989). Its attenuation may be slightly increased compared to that of muscle (38–66 HU) (Lang and Yuan 2015), a finding that reflects hemosiderin deposition as seen in 29% of seven cases described by Jelinek et al. (1989) (Fig. 15). However, synovial thickening is also frequently associated with low-attenuation joint effusion. CT does not only define the size and shape of the soft tissue mass, but it is also useful for the evaluation of changes of both sides of the joint (Le et al. 2014). CT is more sensitive than MRI for accurately defining the extent of bone erosion and subchondral cysts. However, the imaging features lack specificity (Lang and Yuan 2015). On dual-energy CT (DECT), spectral analysis with two materials (calcium and iron) shows an X-ray attenuation characteristic of iron (Becce et al. 2015).

a

b

Fig. 15 Diffuse tenosynovial giant cell tumor of the tibiofibular joint. (a) Lateral radiograph of the left knee demonstrating bone erosion (arrowhead) and increased density of the posterior compartments (arrow). (b) Axial T2-WI

Localized Tenosynovial Giant Cell Tumor

6.4.2.1 Extra-articular Form Computed tomography may show areas of high attenuation in the soft tissue mass as a result of hemosiderin deposition. Contrast enhancement is typically seen, due to its hypervascular nature (Peh et al. 2001). 6.4.2.2 Intra-articular Form This subtype presents as a nonspecific welldefined soft tissue mass with attenuation similar to that of adjacent muscle due to the more variable amount of hemosiderin in these lesions, compared with diffuse TGCT (Murphey et  al. 2008; Kransdorf and Murphey 2006).

6.5

MRI

6.5.1

Diffuse Tenosynovial Giant Cell Tumor MR imaging shows characteristic features of a heterogeneous, diffuse, synovially based, plaque-like thickening that is often associated with nodularity (Fig. 16).

c

shows a synovial thickening with low signal intensity (arrow). (c) Axial CT shows hyperdense synovial thickening with bone erosions (arrowheads)

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a

b

c

Fig. 16 Diffuse tenosynovial giant cell tumor in the hip; (a) coronal STIR, (b) axial T2*, and (c, d) coronal T1-WI show synovial thickening (asterisk) about the hip, with

a

b

d

blooming on gradient-echo sequence and high signal intensity in the mass on STIR sequence

c

Fig. 17 Diffuse tenosynovial giant cell tumor of the knee. (a) Sagittal fat-sat DP, (b) sagittal gradient-echo, and axial T1-WI show hypointense synovial thickening

(arrows). The blooming artifact is more prominent, with the gradient-echo sequence. (c) T1-WI shows the fatty areas (arrowheads)

MRI may reflect the different tissue components within the lesions, including hemosiderin, fibrous and fatty tissue, and bone marrow edema (Lang and Yuan 2015) (Fig. 17). The lesions are pigmented due to the presence of hemosiderin and lipoids. The iron ion in hemosiderin contains five unpaired electrons, leading to a nonhomogeneous local magnetic field. This results in low signal on both pulse sequences, which is even more pronounced on T2* gradient recalled echo (Roguski et  al. 2014; Flipo et  al. 1993). However, the signal may vary according

to the presence of fibrous and fatty tissue, and the different cellular and cystic components of the lesion (Lang and Yuan 2015). On short inversion time inversion recovery (STIR) sequence, the lesion may show diffuse increased signal intensity throughout the lesion, despite low signal intensity on T2-weighted images (WI) which may be caused by the edematous component of the inflammatory synovitis predominating over the signal effect of hemosiderin deposition (Lin et al. 1999) (Fig. 16).

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Entrapped fronds of perisynovial fat lead to areas of intermixed high signal intensity on T1-WI. This remains—however—an uncommon finding (Bravo et al. 1996) (Fig. 17). Associated joint effusion is common, particularly in large joints such as the knee, but the effusion is generally surrounded by thickened synovial rinds of hemosiderin-laden tissue. Enhancement of DTGCT is common after intravenous administration of gadolinium contrast, although the extent of enhancement varies (Murphey et al. 2008). Additional MRI findings are intralesional septations (67%), bone erosion or subchondral cyst formation (62% of cases), articular cartilaginous defects (31%), and edema in the adjacent bone or soft tissue (23%) (Hughes et al. 1995). The signal intensity of the lytic subchondral lesions varies along with the presence of fluid, soft tissue, or hemosiderin (Llauger et al. 2000). MRI is the modality of choice to depict and define the intra-articular and, particularly, extraarticular disease extent in order to guide complete surgical excision (Murphey et al. 2008) (Fig. 18).

a

b

Fig. 18 Diffuse tenosynovial giant cell tumor of the hip. (a) Coronal T1 WI, (b) axial gradient-echo T2*, and (c) axial T1-weighted fat-suppressed postcontrast images show femoral head erosions (arrowheads) and synovial

6.5.2

Localized Tenosynovial Giant Cell Tumor

6.5.2.1 Extra-articular Form MRI typically shows a well-defined lobulated mass adjacent to or enveloping a tendon. Characteristically, the mass reveals decreased signal intensity on T1-WI and usually low signal on T2-WI.  LTGCT demonstrates granular and separated hypointensity on PD-WI.  Generally, this hypointensity is scattered or located at the periphery of the lesion. Blooming artifact may occur with gradient-echo T2* sequences. There may be areas of low signal and high signal on T2-WI due to the presence of hemosiderin and fluid, respectively. Uniform mild to marked enhancement can be seen post-intravenous gadolinium contrast administration (Ge et  al. 2019) (Fig. 19). Bone erosion is seen in 14% of giant cell tumors of the tendon sheath (Ge et al. 2019). Localized TGCT in bursae is similar to DTGCT (Fig. 20).

c

thickening (asterisks) about the hip, with blooming on (b). The involvement extends superiorly to the iliopsoas bursa (arrows in c)

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a

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Fig. 19 Localized TGCT of a flexor tendon sheath of the index finger. (a) Axial T1-WI precontrast, (b) axial T1-WI postcontrast, and (c) axial gradient-echo T2* MR images

a

c

show soft tissue mass (arrow) at the volar aspect of the flexor tendon with several tiny internal low-signal foci (blooming) on T2* and peripheral enhancement (b)

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Fig. 20 Localized extra-articular tenosynovial giant cell tumor in pes anserinus bursa. (a) Axial T2-WI, (b) sagittal fat-suppressed proton-density WI, and (c) axial gradientecho T2* images reveal a high signal intensity collection

of fluid within the bursa (a, b), hypointense synovial thickening (arrows) with blooming artifact on the gradient-echo sequence (arrow in c)

6.5.2.2 Intra-articular Form MRI findings in localized and diffuse TGCT may be similar in many respects, reflecting the marked histologic overlap between the two varieties of lesion (Hughes et al. 1995).

demonstrate response to certain focal and systemic cancer therapies, and, therefore, response to therapy does not indicate malignancy (White et al. 2016).

6.6

FDG PET/CT

At FDG PET, all subtypes of TGCT may show moderate-to-intense FDG activity, which may mimic metastatic disease, especially with the localized forms. In addition, FDG activity may vary over time without treatment and TGCT may

7

Differential Diagnosis

7.1

Diffuse Tenosynovial Giant Cell Tumor

Although synovial hemangioma (see Chapter Synovial Hemangioma) and hemophiliac arthropathy may show similar MR imaging findings

Tenosynovial Giant Cell Tumor

(caused by repetitive intra-­articular hemorrhage and synovial hemosiderin deposition), DTGCT can be distinguished from these conditions because it is not associated with either serpentine vascular channels (hemangioma) or a clinical history of hemophilia (Murphey et al. 2008). Lipoma arborescens contains a large amount of fat and does not usually contain hemosiderin (see Chapter Lipoma Arborescens). In case of multiple subchondral cysts, the differential diagnosis includes degenerative joint disease, hemophilia, tuberculosis, amyloidosis, and synovial chondromatosis (Bhimani and Wenz 2001). Degenerative joint disease usually exhibits subchondral cysts in weight-bearing regions compared to DTGCT.  Synovial chondromatosis typically shows punctate calcifications or osteochondral fragments inside the joint and may cause pressure erosions (see Chapter Synovial Chondromatosis).

7.2 Localized Tenosynovial Giant Cell Tumor Differential diagnosis of localized TGCT includes ganglia and uncalcified synovial chondromatosis (Bhimani and Wenz 2001). Hypervascular soft tissue mass may represent soft tissue sarcoma (Young-in et al. 1998).

8 Diagnosis Joint aspiration may reveal a blood-stained synovial fluid. However, joint aspiration does not always reveal a hemarthrosis nor does it provide a direct tissue diagnosis (Bhimani and Wenz 2001). When interpreted in the clinical context, fine needle aspiration cytology may render a correct preoperative diagnosis of DTGCT (Gupta and Mishra 2002). Synovial biopsy usually reveals the definitive diagnosis. The biopsy can be performed either arthroscopically or via open arthrotomy, depending on the location and extent of involvement.

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Joint arthroscopy can be used for either diagnostic or therapeutic purpose (Muscolo et al. 2000). Ultrasound-guided needle biopsy of synovium is an increasingly performed procedure with a high diagnostic yield (Sitt et al. 2016). Ultrasound-guided needle biopsy may be performed with a portal-and-forceps or a semiautomatic guillotine-type biopsy needle approach. Procedures are both safe and well tolerated by patients. Ultrasound-guided biopsy retrieves high-quality tissue with good RNA yield from both small and large joints (Lazarou et al. 2015).

9 Treatment Treatment options include surgical resection, radiation therapy, pharmaceutical modulation of the disease, or a combination of these approaches (Schwartz et  al. 1989; Shabat et  al. 2002; Wu et al. 2007). Surgical excision is the preferred method of treatment. However, the long-term success rate of surgery for DTGCT, as with other tumorous lesions, depends on the ability to resect the disease completely. Diffuse intra-articular involvement is more difficult to eradicate with surgical resection alone, and adjunct therapies may be used. Synovectomy may be performed with either an arthroscopic or an open arthrotomy technique (Vastel et al. 2005). Radiation therapy may be used as the primary treatment for DTGCT, but it is best used to augment surgery following the incomplete resection of disease (O’Sullivan et al. 1995). The recurrence rate for localized disease is generally lower than that for DTGCT and ranges from 8% to 56% (Bravo et al. 1996). It is hard to distinguish between residual disease and recurrence in a previously unaffected synovial membrane. However, it should be remembered that the functional results of treatment may be satisfactory, in spite of recurrence (Rydholm 1998). Medical treatment was very recently proposed, based on developing targeted therapies and identifying the molecular mechanisms under-

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lying TGCT. Anti-TNF alpha was the first medical treatment to be described. However, the most encouraging early results were reported with imatinib, a tyrosine kinase inhibitor (Cassier et al. 2012). More recently, Cassier et al. have reported tolerance and efficacy for a monoclonal antibody inhibiting CSF1 receptors, which are overexpressed in TSGCT (Cassier et al. 2015).

10 Key Points • TGCT is a benign entity, with relatively nonspecific symptomatology and slow progression. • Radiography shows nonspecific features such as preserved joint space, joint effusion, and extrinsic erosion on both sides of the joint space. • CT reveals a nonspecific hyperdense synovial thickening and optimally depicts the bone erosion. • MR imaging demonstrates precisely the disease extent and depicts the blooming artifact from hemosiderin deposition. • Diagnosis always requires MRI and often histologic confirmation. The decision to treat the patient and the choice for the treatment option depend on the symptomatology, progression, and location.

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153 Llauger J, Palmer J, Roson N et al (1999) Pigmented villonodular synovitis and giant cell tumors of the tendon sheath: radiologic and pathologic features. AJR Am J Roentgenol 172:1087–1091 Llauger J, Palmer J, Rosón N, Bagué S, Camins A, Cremades R (2000) Nonseptic monoarthritis: imaging features with clinical and histopathologic correlation. Radiographics 20 Spec No:S263–S278. https://doi. org/10.1148/radiographics.20.suppl_1.g00oc13s263. PMID: 11046178 Martinoli C, Bianchi S, Derchi LE (1999) Tendon and nerve sonography. Radiol Clin North Am 37:691–711 Middleton WD, Patel V, Teefey SA, Boyer MI (2004) Giant cell tumors of the tendon sheath: analysis of sonographic findings. AJR Am J Roentgenol 183:337–339 Murphey MD, Rhee JH, Lewis RB, Fanburg-Smith JC, Flemming DJ, Walker EA (2008) Pigmented villonodular synovitis: radiologic-pathologic correlation. Radiographics 28(5):1493–1518 Muscolo DL, Makino A, Costa-Paz M, Ayerza M (2000) Magnetic resonance imaging evaluation and arthroscopic resection of localized pigmented villonodular synovitis of the knee. Orthopedics 23:367–369 Myers BW, Masi AT (1980) Pigmented villonodular synovitis and tenosynovitis: a clinical epidemiologic study of 166 cases and literature review. Medicine (Baltimore) 59:223–238 O’Sullivan B, Cummings B, Catton C et  al (1995) Outcome following radiation treatment for high-risk pigmented villonodular synovitis. Int J Radiat Oncol Biol Phys 32:777–786 Ofluoglu O (2006) Pigmented villonodular synovitis. Orthop Clin North Am 37:23–33 Peh WC, Wong Y, Shek TW, Ip WY (2001) Giant cell tumour of the tendon sheath of the hand: a pictorial essay. Australas Radiol 45:274–280 Roguski M, Safain MG, Zerris VA et al (2014) Pigmented villonodular synovitis of the thoracic spine. J Clin Neurosci 21:1679–1685 Rydholm U (1998) How I do it: pigmented villonodular synovitis. Acta Orthop Scand 69:203–210 Schvartzman P, Carrozza V, Pascual T, Mazza L, Odesser M, San Román JL (2015) Radiological features of pigmented villonodular synovitis and giant cell tumor of the tendon sheath. Rev Argent Radiol 79(1):4–11 Schwartz HS, Unni KK, Pritchard DJ (1989) Pigmented villonodular synovitis: a retrospective review of affected large joints. Clin Orthop Relat Res 247:243–255 Scott PM (1968) Bone lesions in pigmented villonodular synovitis. J Bone Joint Surg Br 50:306–311 Shabat S, Kollender Y, Merimsky O et al (2002) The use of surgery and yttrium 90 in the management of extensive and diffuse pigmented villonodular synovitis of large joints. Rheumatology (Oxford) 41:1113–1118 Sharma H, Rana B, Mahendra A, Jane MJ, Reid R (2007) Outcome of 17 pigmented villonodular synovitis (PVNS) of the knee at 6 years mean follow-up. Knee 14:390–394

154 Sitt JC, Griffith JF, Wong P (2016) Ultrasound-guided synovial biopsy. Br J Radiol 89(1057):20150363 Sullivan CJ, Eustace SJ, Kavanagh EC (2020) Pigmented villonodular synovitis of the hip joint: three cases demonstrating characteristic MRI features. Radiol Case Rep 15(8):1335–1338. https://doi.org/10.1016/j. radcr.2020.05.067. PMID: 32617126; PMCID: PMC7322487 Ushijima M, Hashimoto H, Tsuneyoshi M, Enjoli M (1986) Giant cell tumor of the tendon sheath (nodular tenosynovitis). A study of 207 cases to compare the large joint group with common digit group. Cancer 57:875–884 Vastel L, Lambert P, De Pinieux G, Charrois O, Kerboull M, Courpied JP (2005) Surgical treatment of pigmented villonodular synovitis of the hip. J Bone Joint Surg Am 87:1019–1024 Vigorita VI (1984) Pigmented villonodular synovitis-­ like lesions in association with rare cases of rheumatoid arthritis, osteonecrosis and advanced

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Lipoma Arborescens Mouna Chelli Bouaziz, Mohamed Fethi Ladeb , and Hend Riahi

Contents

Abstract

1

Introduction

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2

Epidemiology

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3

Pathophysiology

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4

Pathology

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5

Clinical Findings

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6

Imaging

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7

Differential Diagnosis

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Treatment

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9

Synovial Lipoma

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10

Key Points

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References

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Lipoma arborescens (LA) is a rare intraarticular tumorlike lesion characterized by a diffuse villous proliferation of the synovial tissue with fatty deposits under the synovial membrane. All joints may be affected, but the knee is the most frequently involved. Bilateral and polyarticular involvement are possible. The pathophysiology is unclear, but LA is thought to be a reactive process, secondary to chronic inflammation or repetitive trauma. Clinical, radiographic, and ultrasonographic findings are usually not specific but may be suggestive of the diagnosis. MRI remains the imaging modality of choice, and it is usually sufficient to confirm the diagnosis.

M. Chelli Bouaziz · M. F. Ladeb (*) · H. Riahi Department of Radiology, MT Kassab Institute of Orthopaedics, Tunis, Tunisia Faculty of Medicine of Tunis, Tunis-El Manar University, Tunis, Tunisia e-mail: [email protected]; [email protected]; [email protected]

Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_416, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 18 April 2023

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Abbreviations CT LA MRI TGCT

Computed tomography Lipoma arborescens Magnetic resonance imaging Tenosynovial giant cell tumor

1 Introduction Lipoma arborescens (LA), also known as villous lipomatous proliferation of the synovial membrane, is a rare intra-articular disorder described for the first time by Arzimanoglu in 1957. This tumorlike lesion is characterized by a diffuse villous proliferation of the synovial tissue in a branching or arbor-like pattern, with fatty deposits under the synovial membrane resulting from the replacement of subsynovial tissue by mature adipocytes and fibrous tissue (Larbi et al. 2016; Adelani et  al. 2008; Nevins and Tenfelde 2020). Some authors consider the term “lipoma” to be a misnomer, as there is no focal mass, and suggest to use the term “synovial lipomatosis,” more appropriate for this condition (Greenspan and Grainger 2018). LA is thought to be a reactive, nonneoplastic process, although this has not been proven. However, most cases are associated with OA (Nielsen et al. 2011). Although all joints may be affected, this lesion is usually found in the suprapatellar recess. The diagnosis is usually delayed due to its rare occurrence, its benign nature, and insidious clinical signs (Kamran et al. 2015).

2 Epidemiology Lipoma arborescens is rare, consisting of less than 1% of all lipomatous lesions. Affected patients are typically in the fifth through seventh decades, but cases have been reported in patients as young as 9 years of age. Cases in children are exceedingly rare, with less than 15 cases reported. Males and females appear to be equally affected although a slight male predominance

has recently been suggested (Adelani et  al. 2008; Kalia et  al. 2018; Nevins and Tenfelde 2020).

3 Pathophysiology The etiology of LA is still unknown. The most accepted hypothesis for its development involves proliferation of the synovial tissue and subsequent adipose differentiation of the hypertrophied synovium secondary to chronic inflammation or repetitive trauma. Indeed, LA has been associated in many cases with trauma, diabetes mellitus, rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, which supports the hypothesis of an inflammatory etiology (Greenspan and Grainger 2018; Kalia et al. 2018; Kamran et  al. 2015; Beyth and Safran 2016). This nonspecific reaction to chronic inflammation is also supported by the histologic finding of mononuclear cellular infiltrate in the overlying synovial membrane (Adelani et  al. 2008; Benegas et al. 2015). Some authors suggested that the involvement of multiple joints, especially in young patients, may be linked to systemic conditions, specifically to fat metabolism disorders (Kamran et al. 2015; Beyth and Safran 2016). However, although the majority of cases of lipoma arborescens are likely secondary, cases with massive intra-articular proliferation of frond-like fat, which occur without any known etiological factors, raise the possibility of a distinct primary form of the disease. Some authors suggest that adolescent patients present an idiopathic primary form of the disease, whereas older individuals and young and older adults exhibit a secondary process (Beyth and Safran 2016; Howe and Wenger 2013).

4 Pathology Grossly, the entire synovium has a yellowish appearance. The synovial fringes are distinctly thickened and nodular or finger-shaped and fatty

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in appearance. On cross section, the subsynovial connective tissue is replaced by abundant adipose tissue (Fig.  1) (Greenspan and Grainger 2018; Nielsen et al. 2011). Minor degrees of fatty infiltration of synovial space are normal in certain parts of the synovial membrane, particularly in the knee joint.

Fig. 1 Macroscopic appearance of lipoma arborescens. The image in the right lower quadrant is an enlarged view. (Courtesy Pr H Jaafoura)

a

Fig. 2 Microscopic appearance of LA. (a) Synovial fringes, distinctly thickened and fatty in appearance (arrowheads) (hematoxylin and eosin stain, original magnification ×80). (b) Vascular congestion (asterisk), hyper-

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Similarly, slight nodular thickening is a nonspecific finding in the synovium of osteoarthritic joints (Nielsen et al. 2011). Microscopically (Fig.  2), synovial villi are occupied by mature adipose tissue. The subsynovial compartment is filled by mature white adipocytes. Vascular congestion is often observed. The surface synovial cells typically appear reactive and hyperplastic. There may also be moderate infiltration of mononuclear inflammatory cells underlying synovial membrane and also perivascular focal infiltrate. Osseous and chondroid metaplasia can occur (Greenspan and Grainger 2018; Benegas et  al. 2015; Nielsen et al. 2011). Synovial fluid is usually acellular, sometimes moderately inflammatory or hemorrhagic (Kamran et al. 2015; Garnaoui et al. 2018). Some authors have suggested that the neoplastic transformation occurs at the multipotential undifferentiated mesenchymal cellular level that later differentiates to lipoblasts, chondroblasts, and/or osteoblasts. They presume that this may lead to differentiation of both adipose and osseous/chondroid tissues simultaneously (Kim et al. 2013).

b

plastic synovial membrane (arrow), and perivascular infiltration of lymphocytes (arrowheads) (hematoxylin and eosin stain, original magnification ×80). (Courtesy Pr H Jaafoura)

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It has also been suggested that synovial chondromatosis is yet another form of the synovial reaction and supported their theory by the coincidence of the two conditions in two cases, as well as the similar age distribution of the two conditions (Beyth and Safran 2016).

5 Clinical Findings Lipoma arborescens may have a monoarticular or a polyarticular involvement. The knee joint and particularly the suprapatellar pouch are the most frequently affected sites. Involvement of other joints, such as the shoulder, hip, wrist, elbow, and ankle, has been sporadically reported as well as sporadic reports of extra-articular sites like synovial sheaths of tendons, bicipitoradial, and subdeltoid bursa (Greenspan and Grainger 2018; Adelani et  al. 2008; Kamran et  al. 2015; Kalia et  al. 2018; Kord Valeshabad et  al. 2018). Extension into a baker’s cyst and bursal involvement outside of a joint is rare (Levine et al. 2016). Bilateral involvement of the knees, hips, wrists, ankles, and bursae has been reported, accounting for less than 20% of cases (Garnaoui et al. 2018; Kalia et al. 2018). Polyarticular LA is exceedingly rare (Greenspan and Grainger 2018; Santiago et  al. 2009; Siva et al. 2002; Mohammad et al. 2016; Bejia et al. 2005). The clinical course of LA is insidious. Patient typically presents with slowly progressive swelling of the joint with limited range of motion, locking, functional impairment, and recurrent effusions for several months to years. Pain may be present or not, typically mechanical. Clinical symptoms may simulate a chronic osteoarthritis or oligoarthritis with insidious and nonspecific symptoms and may result in the apprehension of a potential malignancy. Physical examination shows a prominent suprapatellar pouch and joint effusion. Rarely, a soft tissue mass may be identified on palpation. Aspirated synovial fluid is usually normal. Laboratory tests are unhelpful (Greenspan and Grainger 2018; Sheldon et al. 2005; Kalia et al. 2018; Nevins and Tenfelde 2020).

6 Imaging Radiographs often show joint fullness with an increased soft tissue opacity, and frequently associated nonspecific bone erosion and osteoarthritic changes. In favorable cases, the diagnosis of LA can be suspected when radiolucent areas suggestive of fat are observed in the joint space (Fig. 3). Furthermore, radiographs are useful in narrowing the differential diagnosis, which includes TGCT, synovial hemangioma, synovial lipoma, and synovial chondromatosis (Bejia et  al. 2005; Sheldon et al. 2005; Adelani et al. 2008; Nielsen et al. 2011). Ultrasound (US) shows the villous character of the mass, which typically presents as a synovial based hyperechoic frond-like proliferation frequently associated with a joint effusion (Fig. 4) (Larbi et al. 2016). The mass is compressible with dynamic manipulation of the ultrasound probe, which suggests its pliable nature (Kamran et al. 2015). The differential diagnosis on US includes inflammatory synovitis, gout, and synovial chondromatosis (Ladeb et al. 2019).

Fig. 3  Lateral radiograph of the knee joint: Soft tissue opacity of the suprapatellar pouch containing radiolucent areas suggestive of fat (arrows)

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Computed tomography (CT) typically demonstrates a villous synovial mass of low density similar to fat, commonly associated with joint effusion. The mass shows no enhancement after intravenous contrast administration (Bejia et al. 2005). Although the lesion has a characteristic appearance on ultrasound, magnetic resonance imaging (MRI) remains the imaging modality of choice when the diagnosis is suspected and it is usually sufficient to make the diagnosis (Bejia et al. 2005; Greenspan and Grainger 2018; Larbi et al. 2016). It typically shows a subsynovial frond-like proliferation with arborescent architecture. The

Fig. 4 LA of the knee: US shows synovial based frondlike hyperechoic projections into the suprapatellar pouch (arrow), associated with joint effusion

a

b

Fig. 5 LA of the knee in an adult patient. Sagittal MRI T1-weighted image (WI) (a), sagittal T2-WI (b), coronal fat-suppressed proton density image (c), and sagittal fatsuppressed T1-WI after intravenous administration of

signal intensity of this mass is similar to fat on all pulse sequences (high T1 and T2 signals), with suppression of the signal on fat-saturated and STIR sequences (Fig. 5). Well-demarcated subsynovial masses may also be present. Some authors suggest that a mass-like subsynovial fat may occur in “de novo” LA, whereas villous lipomatous synovial proliferation with or without a mass-like subsynovial fatty deposit is usually associated with a history of trauma and/or chronic inflammatory diseases (Narváez et al. 2001). Associated joint effusion is frequent. Chemical shift artifacts may be observed at the fat-fluid interface within the joint. Magnetic susceptibility effects associated with hemosiderin are absent (Bejia et al. 2005; Adelani et al. 2008; Sheldon et al. 2005). Erosive changes of the underlying bone related to associated synovitis rarely occur. With intravenous gadolinium contrast administration, the synovium may enhance while the fatty villi projections do not enhance (Levine et al. 2016). LA shows similar characteristics in adults and pediatric patients, although adults have been reported to more commonly present with associated conditions in the knee (Fig. 6). Common associated findings on MRI in adults include joint effusion (100%), degenerative changes (87%), meniscal tear (72%), synovial cysts (38%), bone erosions (25%), chondromato-

c

d

gadolinium contrast (d). Synovial thickening with proliferation of the synovial tissue and fatty deposits (arrows). After contrast administration, the thickened synovium enhances but the fatty deposits (arrow) do not

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a

b

Fig. 6 LA of the knee in a young adult: axial (a) and sagittal (b) T1-WI showing villous proliferation of the synovium being of high signal on T1-WI (arrows) associated with joint effusion (asterisk)

sis (13%), patellar subluxation (6%), and discoid meniscus (3%) (Nevins and Tenfelde 2020).

7

Differential Diagnosis

TGCT contains intralesional areas of low intensity on T1- and T2-weighted MRI and may show blooming artifact on T2*-WI (see chapter “Tenosynovial Giant Cell Tumor”). Synovial hemangioma is of low signal on T1-weighted images (WI), high signal on T2-WI, and characteristic hypointense linear fibrous septa (see chapter “Synovial Hemangioma”). However, contrast enhancement of the synovium is not helpful to distinguish TGCT from SH because it may be observed in both conditions. Synovial chondromatosis is associated with loose body formation, which is not seen in lipoma arborescens. Although characteristic imaging findings can lead to a fairly confident diagnosis, biopsy is required for definitive diagnosis (see chapter “Synovial Chondromatosis”). This can be done arthroscopically (Adelani et al. 2008).

8

Treatment

Intra-articular steroid injection may result in temporary relief of symptoms. However, definitive treatment is based on synovectomy (Levine et al. 2016). Timely synovectomy is strongly recommended, if not mandatory. Some authors stated that primary LA of the knee may induce early osteoarthritis if prompt synovectomy was not performed (Natera et al. 2015). The severity of osteoarthritis seems to be correlated with disease duration. However, the cause-and-effect relationship between LA and OA remains unclear. It is not known if osteoarthritis exacerbates fat deposition or if fat deposition exacerbates osteoarthritis (Suzuki and Ehara 2019; Poorteman et al. 2015). A recent systematic review showed that arthroscopic synovectomy had an overall success rate of 95%. Most patients experience favorable outcomes. Recurrence occurs in less than 3% of cases. The etiology of recurrence remains unknown but

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is thought to be related to incomplete synovectomy (Nevins and Tenfelde 2020).

9 Synovial Lipoma Synovial lipoma is a discrete benign fatty mass arising within the joint with signal intensity similar to fat on MRI, as opposed to the villous appearance seen with lipoma arborescens. Synovial lipomas are exceedingly rare, accounting for less than 1% of all lipomas with only a few cases reported in the English literature. Seventy-five percent of synovial lipomas are located in the knee and tend to be infrapatellar, whereas lipoma arborescens has a predilection for the suprapatellar pouch. Unlike lipoma arborescens, synovial lipomas are not thought to be related to underlying joint pathology or trauma. Sporadic cases of synovial lipoma of the hip joint and lumbar facet have been reported. Synovial lipomas may present with pain, mechanical symptoms (locking of the knee, trigger finger), or neurologic symptoms (carpal tunnel syndrome). Tendon rupture in association with a lipoma of the tendon sheath has been reported. Lipomas of the tendon sheath most often occur in the wrist and hand, most commonly in young patients (15–35  years), without sex predilection. Lipomas of the tendon sheath may be bilateral in about half of the cases and are typically symmetrical in distribution. Synovial lipomas are typically small, solitary, round, or oval masses that may demonstrate a vascular pedicle. Tumors are pathologically identical to the more common extra-articular lipomas, composed of mature adipose cells covered by a thin fibrous layer and invested by normal synovial cells. The imaging appearance of synovial lipoma mimics that of a typical superficial or deep soft tissue lipoma. Radiographs may reveal a mass of lower density than surrounding soft tissues consistent with a fatty composition. Although rare, metaplastic ossification and bony erosions have

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been described in association with intra-articular lipoma. CT demonstrates a well-defined intra-articular mass of fat attenuation. MRI features are typical of a fatty lesion, with high signal intensity on both T1- and T2-weighted sequences and suppression of signal on fat-saturated sequences. Intra-articular lipomas may also demonstrate internal fluid signal intensity, which is believed to represent mucoid degeneration. Resection of synovial lipomas, either arthroscopically or by open techniques, is curative in the vast majority of cases. Intra-articular lipomas should be differentiated from other more common lipomatous entities such as lipoma arborescens or Hoffa’s disease. In cases where a discrete fatty mass is clearly evident within a joint or along a tendon sheath, the diagnosis of synovial lipoma can be made with confidence (Garner and Bestic 2013; Kim et al. 2018; Lui and Lee 2015).

10 Key Points • Lipoma arborescens is a rare intra-articular tumorlike lesion of unknown etiology characterized by a diffuse villous proliferation of the synovial tissue with fatty deposits under the synovial membrane. • All joints and synovial lined spaces may be affected. Bilateral and polyarticular involvement is possible. • Clinical, radiographic, and ultrasonographic findings are usually not specific but may be suggestive of the diagnosis. • MRI remains the imaging modality of choice, and it is usually sufficient to confirm the diagnosis.

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162 Benegas E, Neto AA, Teodoro DS, da Silva MV, de Oliveira AM, Filippi RZ, de Santis PF (2015) Lipoma arborescens: rare case of rotator cuff tear associated with the presence of lipoma arborescens in the subacromial-subdeltoid and glenohumeral bursa. Rev Bras Ortop 47:517–520 Beyth S, Safran O (2016) Synovial lipomatosis of the glenohumeral joint. Case Rep Orthop 2016:4170923 Garnaoui H, Rahmi A, Messoudi A, Rafaoui A, Rafai M, Garch A, Elkhiraoui H, Benayad S, Belhaj S (2018) Intra-articular lipoma arborescens of the knee: a report of two cases with bilateral localization. Int J Surg Case Rep 51:224–227 Garner HW, Bestic JM (2013) Benign synovial tumors and proliferative processes. Semin Musculoskelet Radiol 17:177–178 Greenspan A, Grainger AJ (2018) Articular abnormalities that may mimic arthritis. J Ultrason 18:212–223 Howe BM, Wenger DE (2013) Lipoma arborescens: comparison of typical and atypical disease presentations. Clin Radiol 68:1220–1226 Kalia V, Daher O, Garvin G, Chhibber S, Shepherd J (2018) Synchronous bilateral lipoma arborescens of bicipitoradial bursa—a rare entity. Skeletal Radiol 47:1425–1429 Kamran F, Kavin K, Vijay S, Shivanand G (2015) Bilateral lipoma arborescens with osteoarthritis knee: case report and literature review. J Clin Orthop Trauma 6:131–136 Kim RS, Kim YT, Choi JM, Shin SH, Kim YJ, Kim L (2013) Lipoma arborescens associated with osseous/ chondroid differentiation in subdeltoid bursa. Int J Shoulder Surg 7:116–119 Kim S, Lee GY, Ha YC (2018) An intra-articular synovial lipoma of the hip, possibly causing osteoarthritis: a case report and review of the literature. Skeletal Radiol 47:717–721 Kord Valeshabad A, De La Vara D, Shamim E, Alsadi A, Xie KL (2018) Lipoma arborescens of the bicipitoradial bursa. Skeletal Radiol 47:549–551 Ladeb MF, Chelli Bouaziz M, Riahi H, Mechri M (2019) Echographie des tumeurs et des pseudotumeurs synoviales. In: Actualités en échographie de l’appareil locomoteur, vol 16. Sauramps Médical

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Synovial Hemangioma Mouna Chelli Bouaziz , Mohamed Fethi Ladeb , and Hend Riahi

Contents

Abstract

1

Introduction

164

2

Clinical Findings

164

3

Pathology

165

4 4.1 4.2 4.3

165 165 166

4.4

Imaging Radiography Ultrasound Arthrography Computed Tomography and Angiography Magnetic Resonance Imaging

166 168

5

Differential Diagnosis

171

6

Treatment

171

7

Key Points

172

References

172

Synovial hemangioma (SH) is a rare benign vascular proliferation, of unknown etiology, arising on the synovial membrane. It may be localized, pedunculated, or diffuse. Based on the predominant type of vessel, SH may be venous, venolymphatic, lymphatic, or arteriovenous. Most cases are observed in children, adolescents, and young adults with a female predilection. Clinical findings are usually not specific and cause misdiagnosis and/or diagnostic delay. MRI frequently shows pathognomonic findings suggestive of hemangioma. The vascular nature of the lesion is usually clearly evident on CT angiography and angio-MRI.

M. Chelli Bouaziz · M. F. Ladeb (*) · H. Riahi Department of Radiology, MT Kassab Institute of Orthopaedics, Tunis, Tunisia Faculty of Medicine of Tunis, Tunis-El Manar University, Tunis, Tunisia e-mail: [email protected]; [email protected]; [email protected] Med Radiol Diagn Imaging (2023) https://doi.org/10.1007/174_2023_417, © The Author(s), under exclusive license to Springer Nature Switzerland AG Published Online: 12 April 2023

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Abbreviations

2 Clinical Findings

AVM CT MRI SH TGCT

The average age of onset of a synovial hemangioma is 12 years old (De Gori et al. 2014). Most cases of synovial hemangioma are observed in children, adolescents (60% of cases), and young adults with a female predilection (Garner and Bestic 2013; Adelani et al. 2008). The knee is the most common joint affected (60% of cases), but SH may also be found in the elbow, wrist, and ankle as well as tendon sheaths. When located at the knee, most lesions involve the suprapatellar recess. Almost all patients are symptomatic. In most cases, they present with symptoms such as recurrent pain, limping, and spontaneous swelling of the joint due to hemarthroses. Limited range of motion, as well as joint stiffness, may also be observed, typically long-standing and in the absence of trauma (Guler et al. 2015). In approximately 40% of the cases, SH is associated with an overlying subcutaneous or deep soft tissue hemangioma (Levine et al. 2016; Narváez et al. 2001; Adelani et al. 2008). Misdiagnosis which is common and subsequent diagnostic delay may lead to poor clinical outcome due to recurrent hemarthrosis with progressive arthropathy (Larbi et  al. 2016; Kim et al. 2011; Garner and Bestic 2013; Sheldon et al. 2005; Adelani et al. 2008). Physical examination typically shows pain with joint movement, decreased range of motion, joint effusion, and occasionally quadriceps atrophy and a palpable mass. Signs mimicking meniscal tear or discoid meniscus such as clicking on the McMurray test have also been described in SH. Synovial hemangioma may be an isolated condition involving one or more joints, or it may occur as part of a systemic disease, such as Maffucci syndrome or von Hippel-Lindau syndrome (Adelani et al. 2008).

Arteriovenous malformation Computed tomography Magnetic resonance imaging Synovial hemangioma Tenosynovial giant cell tumor

1 Introduction Synovial hemangioma (SH) is a rare tumorlike lesion, consisting of a benign vascular proliferation, arising from a synovial lined surface, including the joints, bursae, and tendon sheaths. This entity was first described by Bouchut in 1856 (Ares-Rodriguez et  al. 2008; Tahmasbi et  al. 2014). The etiology of synovial hemangioma is still unknown, although such lesions most likely represent a congenital vascular malformation. Trauma has also been proposed as a possible etiologic factor, but the relationship has not been validated. The lesion may be localized, pedunculated, or more frequently diffuse, involving the entire synovial membrane (Larbi et  al. 2016; Adelani et  al. 2008; Levine et  al. 2016; Garner and Bestic 2013). Less than 1% of all hemangiomas are synovial. Intra-articular vascular lesions involving the synovium are more appropriately termed vascular malformations. They are classified by the predominant type of vessel observed at histologic examination and may be venous, venolymphatic, lymphatic, or arteriovenous (AVM) (Kim et  al. 2011; Narváez et al. 2001; Guler et al. 2015). This rare entity (with less than 200 cases reported) is often misdiagnosed. A correct preoperative diagnosis has been estimated to be made in only 22% of cases, frequently after a very long diagnostic delay (Adelani et al. 2008; Greenspan and Grainger 2018).

Synovial Hemangioma

165

3 Pathology Definitive diagnosis is based on the histopathological findings (De Gori et  al. 2014). Synovial hemangioma is a vascular proliferation originating in the subsynovial layer mesenchyme of the synovium. It may contain variable amounts of adipose, fibrous, and muscle tissue, as well as thrombi in the vessels (Greenspan et al. 1995). Based on their site of origin, soft tissue hemangiomas are categorized as cutaneous, subcutaneous, intramuscular, or synovial subtypes. An alternative classification is also used, taking into account the nature and size of the vessels predominating within the hemangioma, as capillary, venous, cavernous (large vessel), mixed, and arteriovenous (Greenspan et  al. 1995). SH is most commonly cavernous, with an edematous, myxoid, or hyalinized matrix separating individual thin-wall vessels. The adjacent synovium may contain variable amounts of hemosiderin. This finding may sometimes be quite prominent and grossly resemble tenosynovial giant cell tumor (TGCT) (Garner and Bestic 2013; Sheldon et al. 2005). Grossly, it appears as a lobulated soft, brown, doughy mass with overlying villous synovium that is often stained mahogany brown due to hemosiderin deposition. When the lesion is completely intra-articular, it is usually well circumscribed and apparently encapsulated, attached to the synovial membrane by a pedicle of variable size. On microscopic examination, the lesion exhibits arborizing vascular channels of different sizes (Fig.  1) and hyperplastic overlying synovium, which may show abundant hemosiderin deposits in chronic cases with repeated hemarthrosis (Greenspan and Grainger 2018; Greenspan et al. 1995).

Fig. 1 Microscopic appearance of SH.  Original magnification ×80, hematoxylin eosin staining. Arborizing vascular channels of different sizes (arrowheads) with hyperplastic overlying synovium (arrow). (Courtesy Prof H. Jaafoura)

4 Imaging 4.1 Radiography Until recently, synovial hemangiomas were evaluated by a combination of conventional radiography, arthrography, angiography, and contrast-enhanced CT (Greenspan and Grainger 2018). Radiographs are normal in approximately 50% of cases. Otherwise, they could show a localized swelling with or without a joint effusion, an illdefined soft tissue mass (Fig. 2), a periosteal reaction (5  cm, neoadjuvant chemoradiotherapy should be considered. • Immune therapy can stabilize disease in synovial sarcoma. • Tenosynovial giant cell tumors: in local types resection remains first choice. In diffuse type resection is still the primary treatment option, often in association with radiotherapy. • Tenosynovial giant cell tumors diffuse type can be stabilized or decreased in volume with the use of targeted therapy.

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