Clinical History: A 51-year-old male presents with slowly progressive swelling, loss of range of motion and intermittent locking of the right knee. What are the findings? What is your diagnosis?
Findings
Diagnosis
Primary Synovial Chondromatosis (Reichel Syndrome)
Introduction
Synovial chondromatosis is a rare, monoarticular benign process characterized by hyaline cartilaginous bodies proliferating in subsynovial tissue and detaching as a collection of numerous chondral bodies in a joint or less commonly in bursae or tendon sheaths. 70-95% of the bodies undergo mineralization and may eventually undergo ossification. It is typically a self-limiting process, however, it may recur locally and rarely undergo malignant transformation. Imaging plays a key role in the diagnosis and management as the clinical presentation is non-specific and laboratory tests do not exist. Pathology may simulate chondrosarcoma making the MRI characteristic features vital to the correct diagnosis and management of these patients. 1,2,3,4
Epidemiology and Pathogenesis
Primary synovial chondromatosis preferentially affects one joint with predilection for large joints such as the knee, hip, elbow or shoulder. However, it can be seen in any joint, tendon or bursa. It tends to affect males more frequently than females by greater than 2:1 and most commonly in the third to fifth decades. Several case reports describe synovial chondromatosis occurring in children. 1,2,5,6
Three phases of synovial chondromatosis have been described though progression through each phase has not been established. The phase at diagnosis is virtually non-diagnostic without histopathologic correlation. The first phase is the active formation of hyaline cartilaginous bodies within the synovium with no loose intra-articular bodies. The second phase is a combination of both synovial cartilaginous proliferation and shedding of intra-articular loose bodies. The third phase is the complete shedding of numerous intra-articular cartilaginous bodies and no active synovial proliferation. MRI findings are variable though three distinct patterns that correspond to the phase of pathology have been described. The most frequently reported pattern corresponds to phase two pathology followed by phase one and phase three. 1,2,5
The molecular basis of the disease is unclear though high levels of BMP-2 and BMP-4 have been isolated from diseased synovium and loose bodies. Fibroblastic growth factors 2 and 3 and chromosome 6 abnormalities have been found in cases of primary synovial chondromatosis and may also play a factor in metaplasia. These growth factors and cytogenetic abnormalities have not been found in secondary synovial chondromatosis. 1,7,8
On gross pathology, the synovial bodies tend to range from 2.0 mm to 10 mm in size and are composed of a chalky yellow material consisting of calcification, endochondral ossification or both (Figure 4). Bodies undergo ossification via vascular invasion and endochondral bone formation. Microscopically the hyaline bodies demonstrate greater cellularity than articular cartilage and are clustered rather than evenly distributed. The cells exhibit considerable size range and nuclear chromaticity. Many have atypical features and occasional mitoses can be seen (Figure 5). These atypical features are common findings for this benign disease and thus correlation with characteristic imaging features and clinical presentation is essential for accurately diagnosing this benign condition. 7
Secondary synovial chondromatosis is more common than the primary form and presents in the setting of chronic pathology of the joint either secondary to a mechanical or an arthritic process leading to formation of loose chondral bodies. It is more commonly seen in the knee, hip or shoulder in the setting of osteoarthritis, trauma, inflammation, osteonecrosis or neuropathy and found in patients who are older than patients with primary disease. The bodies arise from loose hyaline cartilage implanting in synovium and inducing synovial metaplasia. The subsequent metaplastic chondral bodies that accumulate in the joint tend to be fewer in number and more variable and larger in size suggesting various times of origin. Several concentric rings of calcification may be seen in secondary synovial bodies as opposed to the more typical ‘ring and arc’ pattern of chondroid calcification seen in primary synovial chondromatosis. 1,2,4
On gross and histologic pathology, the bodies are nodular and bosselated and may contain the osteo-articular fragment that incited the metaplasia. They are composed of reactive and metaplastic features between hyaline and fibrocartilage. Histologically, they are uniform in cellularity and laminar in arrangement as opposed to the clustered appearance seen in primary synovial chondromatosis (Figure 6). They rarely demonstrate atypia or mitotic activity. The primary and secondary forms of synovial chondromatosis are easily differentiated by histopathology. 7
The incidence of synovial chondrosarcoma in the setting of synovial chondromatosis is rare with reported incidence ranging from 1% and most recently reported up to 6.4% 9, and only reported in intra-articular cases. The majority of cases of synovial chondromatosis are self-limiting with case reports of spontaneous resolution. Following synovectomy, the incidence of recurrence in primary synovial chondromatosis is reported as high as 23%. In those patients who present with recurrence, differentiating from a malignant transformation can be difficult. The degree of atypia found in synovial chondromatosis can equal or exceed the atypia found in low and intermediate grade chondrosarcoma making histology not always helpful. To date, there are no reliable immune or histochemical markers that differentiate the two pathologies, therefore, imaging and clinical characteristics play a crucial role. Any patient presenting with an aggressive or debilitating recurrence and/or MRI demonstrating aggressive features of permeative or invasive bone erosions should be regarded as suspicious for malignant transformation to chondrosarcoma. Chondrosarcoma is generally treated by amputation and despite aggressive therapy, up to 56% of patients demonstrate lung metastases as reported in a series by Bertoni et al. 9 Radiation and chemotherapy are ineffective in treating chondrosarcoma and primary synovial chondromatosis. 1,9,10,11,12
Clinical Presentation
Symptoms are often insidious and gradually progress with duration to diagnosis on average of 5 years. Patients most commonly present with pain, followed by swelling, decreased range of motion, and locking of the joint and least commonly present with a palpable mass. They generally do not report acute trauma and do not exhibit signs of infection or illness. Presentation is non-specific and non-diagnostic. Most patients are sent for MRI for more sensitive and specific diagnosis. 1,2
MRI Imaging Characteristics
Depending on the phase of disease at the time of imaging, primary synovial chondromatosis can have a varied MRI appearance but with characteristic and specific diagnostic features. In the setting of synovial metaplasia with no mineralization of bodies, the radiographs may be unremarkable and MRI images demonstrate hyperintense T2 signal intra-articular masses which correspond to T1-weighted intermediate to hypointense masses without areas of internal signal void. The synovial masses will enhance intensely following IV contrast. During the second phase of disease, the synovial bodies are characteristically hyperintense on T2 and low to intermediate signal on T1 with central signal void from calcification or central fat and a low signal rim variably depending on the degree of mineralization. They demonstrate mild enhancement with a peripheral and septal pattern. The bodies tend to be more fusiform in shape. During phase three, there are numerous intra-articular bodies with varying degrees of mineralization characterized by central fat signal intensity with a dark rim from calcification. No synovial lobular masses are seen. 1,2,3,4
CT and x-rays help characterize mechanical erosions and evaluate mineralization of intra-articular bodies. At the time of presentation, up to 70% of patients have radiographically visible calcifications or ossifications. Bone erosions of variable size can be seen more often in joints with a tight capsule such as the hip and are reported in 20-50% of all cases. The calcifications found in primary synovial chondromatosis are the typical ‘ring and arc’ pattern of mineralization rather than concentric rings of calcification seen in secondary synovial chondromatosis. 1,2,3,4
MRI Diagnosis in Primary Synovial Chondromatosis
MRI Diagnosis in Primary versus Secondary Synovial Chondromatosis
Differentiating primary synovial chondromatosis from its more common secondary form may be difficult by MRI as secondary synovial chondromatosis generally presents in the setting of osteoarthritis, and long standing primary synovial chondromatosis predisposes to developing osteoarthritis.1 However, important differences frequently allow the diagnosis to be made.13
Differential Diagnosis on MRI
The bodies of synovial chondromatosis should not be confused for rice bodies which are found in the setting of chronic inflammation of synovium and described in several entities including chronic arthritis, MAI infection, sarcoidosis and most commonly in rheumatoid arthritis. Rice bodies are tiny, uniformly shaped and sized bodies composed of fibrin, which are hypointense on T2, intermediate in signal intensity on T1 and contain no mineralization. It is proposed that synovial cells undergo infarction, are shed into the joint, and become encased by fibrin over a period of time. Others theories suggest the fibrin accumulates in hypertrophied synovium and sheds off as fibrin bodies into the joint. 5,14,15
Synovial chondromatosis in the tendon sheath or bursa may be referred to as tenosynovial or bursal chondromatosis and is pathologically identical to intra-articular primary synovial chondromatosis. Tenosynovial or bursal chondromatosis most commonly affects adults over 20 years of age with the greatest number cases found in patients in their fifth decade of life. It most commonly affects males, however when diagnosed in older patients there is a female predominance. Extra-articular involvement is most commonly seen in the hands accounting for greater than 50% of cases, followed by feet and wrists. Patients generally present with a painless mass or mass with mild tenderness to palpation. In contrast to intra-articular disease, they seldom present with limited joint motion. 1,3,4,13,16,17
The primary differential diagnosis for bursal or tenosynovial chondromatosis is giant cell tumor of the tendon sheath (GCTTS). It presents as a slow growing painless mass most commonly found in the hand and is pathologically identical to PVNS. MRI shows low to intermediate signal on T1 and T2 weighted sequences due to the presence of hemosiderin. Calcifications are uncommon in GCTTS. 1,2,17,18
MR’s soft tissue resolution allows differentiation of synovial chondromatosis from other primary synovial pathologies which include pigmented villonodular synovitis (PVNS), hemosiderin arthrosis, nodular synovitis otherwise referred to as localized PVNS, lipoma arborescens and synovial hemangiomas. 1,2,3,4,18,19 PVNS is a benign proliferative synovial lesion, generally mono-articular and presenting in the 3rd to 4th decade of life. PVNS lesions tend to bleed, resulting in characteristic very dark signal hemosiderin deposits. The nodular masses in PVNS typically cause bone erosions, which is helpful in differentiating this disease from hemosiderin arthrosis. PVNS tends to have a more frond-like villous appearance. 1,2,3,4,17,18,19 Hemophilic or hemosiderin arthropathy leads to uniform dark signal thickening of the synovium without nodular masses, villous proliferation or erosions.
Nodular synovitis, also termed localized pigmented villonodular synovitis, is found in the knee and most commonly in the infrapatellar fat pad. Bodies tend to be ovoid or multilobular, intermediate to high signal on T1 and heterogeneous on T2. Imaging characteristics tend to mimic PVNS with areas of dark signal due to hemosiderin. In addition to being unifocal, nodular synovitis tends to grow outward in a more pedunculated fashion as compared to diffuse PVNS. 2,3,18,19
Lipomatosis arborescens is a benign villous proliferation of synovium replaced by mature fat cells and is a reactive response to chronic synovial irritation or inflammation. It is characterized on MRI by frond like proliferation of synovium projecting into the joint with signal on all pulse sequences consistent with fat. 2,19
Treatment
Primary synovial chondromatosis tends to be self-limiting, however it can cause severe damage to the joint and lead to osteoarthritis. Early removal of loose bodies in both primary and secondary forms of synovial chondromatosis is generally performed to relieve painful symptoms and to prevent further joint deterioration. 1,2
Synovectomy has generally been reserved for recurrent and persistent synovial metaplasia, however, determining the exact phase of the disease process is based on histologic correlation and therefore most physicians recommend excision of the bodies and synovectomy. Sufficient evidence supports arthroscopic removal of loose bodies with limited synovectomy as first-line surgical therapy. Synovectomy is not necessary in secondary forms of chondromatosis as recurrence is uncommon. Patients who are treated conservatively are generally treated with non-steroidal anti-inflammatories, activity modification, ultrasound and cryotherapy. 1,2,5
Conclusion
Primary synovial chondromatosis is a benign metaplastic process characterized by hyaline cartilage bodies proliferating in subsynovial tissues of the joint, bursa or tendon sheaths. Radiographic and MRI features are pathognomonic when characterized by a collection of numerous mineralized bodies of similar shape and size and seen with relative preservation of articular cartilage of the joint. Secondary synovial chondromatosis may be differentiated from its primary form by the accumulation of variable shape and size bodies, and fewer intra-articular bodies demonstrating concentric rings of calcification. Secondary synovial chondromatosis generally presents in the setting of underlying arthritis of the joint. Treatment of primary synovial chondromatosis most often consists of removal of loose bodies and synovectomy. Malignant transformation of primary synovial chondromatosis to chondrosarcoma is uncommon and can be difficult to distinguish from benign disease. The degree of atypia is similar in both primary disease and chondrosarcoma making pathology not always helpful. Aggressive and debilitating recurrence and/or MRI demonstrating permeative and invasive bone erosions should be regarded as malignant transformation. Understanding the pathology and recognizing the radiographic and MRI appearance of primary synovial chondromatosis and differentiating it from its secondary form and other common synovial pathologies are important in diagnosis and clinical management of these patients. 1,2,5,7
References
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- MRI Web Clinic — June 2013 Palmar Bursae and Flexor Tendon Sheaths of the Wrist and Hand Chad Mann, M.D., Shareef Riad, M.D., Donald Resnick, M.D. See more at: https://radsource.us/palmar-bursae-and-flexor-tendon-sheaths/#sthash.J2zqiOhz.dpuf ↩
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