➢ Synovial chondromatosis is a rare, benign condition of unknown etiology in which the synovium undergoes metaplasia leading to cartilaginous nodules that ultimately break free, mineralize, and even ossify.
➢ The most commonly involved joint is the knee.
➢ Patients may be asymptomatic or may present with pain, swelling, and limited range of motion.
➢ Plain radiographs can be diagnostic and mineralized nodules are pathognomonic.
➢ Recommended treatment involves arthroscopic or open removal of loose bodies with or without a synovectomy to prevent further articular and periarticular destruction and to relieve symptoms.
Synovial chondromatosis (SC) is an uncommon, benign condition that was first described in 1558 in the knee by Ambrose Paré1 and in 1813 as intra-articular loose bodies arising from subsynovial tissues by Laennac2,3. It is characterized by synovial formation of cartilaginous or osteochondral bodies4-8, which are typically intra-articular but may also be extra-articular9. Extra-articular cases typically involve tenosynovial structures10. SC is also known as synovial osteochondromatosis, synovial chondrosis, Reichel syndrome11, or synovial chondrometaplasia4. All orthopaedists should be able to recognize SC as most orthopaedic surgeons, regardless of subspecialty, will encounter this pathology and it can frequently mimic other joint conditions. It has a relatively nonspecific presentation and, if symptomatic, presents with symptoms of insidious onset such as decreased range of motion, pain, swelling, crepitus, or locking of the knee2,4-6,12,13. It is commonly encountered as an incidental finding. Diagnosis is consequently often delayed, with an average time from symptom onset to diagnosis of five years2. Spontaneous regression, although uncommon, has been reported but often requires several years from onset to resolution of symptoms5,7,13-15. Therefore, prompt diagnosis and treatment will assist in avoiding secondary pathology, including intra-articular or periarticular destruction and chronic pain4,6,7.
SC, including both primary and secondary types, is an uncommon arthropathy4,6,14,16 that typically affects diarthrodial, weight-bearing joints of individuals thirty to sixty years of age2,4-6,9,14. The exact incidence is unknown, but it has been reported as 1.8 per million individuals per year in England2. SC affects males 1.8 to three times more commonly than females2,4,5,16-18 and occurs bilaterally 10% of the time. To date, SC has been reported in at least thirty-three different locations8, with the following locations in descending order of frequency: knee (70%), hip (20%), shoulder, elbow, ankle, and wrist2,6,9,14,18-20. In general, the larger that a joint is and the more weight that it bears, the greater potential that it has for the development of SC. SC has also been reported in intervertebral facet joints16, the temporomandibular joint, and a variety of tenosynovial locations10,21.
The pathogenesis of SC involves the development of cartilaginous foci in synovial membranes, including the lining of synovial joints, bursae, and tendon sheaths6,7,14. SC may be considered metaplastic7,14 as it passes through a sequence of events typical for metaplasia and lacks atypia or invasion. However, some authors consider SC a neoplastic condition because clonal chromosomal changes have been associated with SC17,22-24. To date, no specific chromosomal abnormality has been identified in SC, but chromosome 6 aberrations have been observed in five (62%) of eight cases17,22-24.
The foci of SC initially develop as sessile cartilaginous bodies, meaning that they remain in contact with the subjacent synovium. As the synovial attachment becomes increasingly peduncular, they break loose to form intra-articular or periarticular loose bodies7,16. The majority of loose bodies are produced at the transitional zone between the synovium and articular cartilage; this is hypothesized to be due to the high density of pluripotent stem cells localized to this area6,25. Two-thirds26 of these foci undergo endochondral ossification while the rest of these bodies remain nonossified27. Once free, the loose bodies obtain nutrition from synovial fluid and continue to grow16. The loose bodies can also reattach to synovium, or they can be reabsorbed16. Although the loose bodies typically occur within the synovium-lined spaces including joints, bursae, or tendon sheaths6,7,10,14,28,29, extra-articular involvement can occur if loose bodies escape through the joint capsule into the tendon sheath or bursa4,16 or if they form in the tendon sheath or bursa primarily10,29.
Primary SC represents SC that occurs in an otherwise normal joint. In primary SC, also known as idiopathic SC, there is no clear link to trauma, synovial irritation, genetics, or infection. Generally, when compared with secondary SC, primary SC occurs at an earlier age (third or fourth decade of life) and is relatively rare16. More commonly, secondary SC is encountered, meaning that it occurs in a joint with a disease and/or an intra-articular process that leads to joint destruction and synovitis, typically in patients in their fifth or sixth decade of life16,17,29. Examples of these processes include osteoarthritis, traumatic injury, osteochondritis dissecans, Charcot joint (neuropathic) arthropathy, or advanced osteonecrosis16,29. Additionally, secondary SC may result from a single substantial traumatic event or from the mechanical stimulation caused by repetitive trauma6,13-16. Primary SC often has small, round, loose bodies that are uniform in size30, whereas secondary SC is characterized by loose bodies that tend to have greater variability in size4,16. The precise role of degenerative changes predisposing major joints to secondary SC is unknown. In fact, in some patients regarded as having secondary SC, it may be the case that the SC started prior to joint degeneration and the presence of loose bodies led to subsequent joint degeneration.
Despite the lack of agreement about whether the origin of SC is neoplastic or metaplastic, there is a small risk of malignant transformation to chondrosarcoma31. Transformation is very rare and is associated with recurrence despite initial treatment8,18,32. It is uncommon for untreated SC to progress to chondrosarcoma. Exactly how rare this occurrence is cannot be determined. Evans et al. reviewed a large orthopaedic oncology database to evaluate the rate of SC transforming to chondrosarcoma2. Of seventy-eight patients with primary SC, five developed malignant transformation to chondrosarcoma. Although these numbers yield a 6.4% rate of malignant transformation, the actual rate is most likely much lower, given the large number of patients who are either not diagnosed or not referred to an academic institution2. The mean age when diagnosed with primary SC was twenty-eight years and the time from original diagnosis to malignant transformation was twenty years (range, 2.5 to thirty-nine years)2. Galat et al. reported a retrospective review from 1970 to 2006 of eight patients diagnosed with SC of the foot and ankle33. They reported recurrence in three of the eight patients, with subsequent malignant transformation into chondrosarcoma in two (25%)33. Distinguishing SC from chondrosarcoma can be a diagnostic dilemma for the pathologist. It is also a dilemma for the clinician, as the more reliable indicators of malignancy (Fig. 1)—such as osseous invasion, permeation, and destructive growth across joints—are also late developments in the disease progression. We continue to stress the importance of recurrence (especially multiple episodes of recurrence) as a sign that should prompt consideration of malignant transformation. Factors such as lesion size, lesion number, and rate of change do not correlate with malignancy.
In 1977, Milgram described SC as a self-limiting disease with three phases from onset to resolution34. The three stages of SC were based on gross and pathologic findings from thirty cases of SC15,34. Stage-I disease represents an active, inflammatory intrasynovial process without loose bodies; patients present with localized joint pain and swelling (or may be asymptomatic). Stage-II disease involves active synovial proliferation with so-called transitional loose bodies, which are bodies that are in transition from a pedunculated process to a free loose body. Because of the loose bodies, patients often present with mechanical symptoms and decreased range of motion. Stage-III disease is characterized by the presence of multiple loose bodies with minimal synovial disease and minimal inflammation and may be thought of as a quiescent stage of the disease with no ongoing metaplasia5,6,29. Patients with Stage-III disease are the most likely to be asymptomatic as the loose bodies, not the metaplastic synovium, are the primary cause of the presenting mechanical symptoms. This classification system has limited practical value to the treating clinician but is useful to know as it recapitulates the pathologic progression of the disease.
History and Physical Examination
Patients with SC may be asymptomatic, or they may present with decreased range of motion, swelling, recurrent effusions, pain, crepitus, or locking4-6,12,15. Patients may also have mechanical pain (clicking or grating of the joint), a palpable mass, and joint-line tenderness16. They less commonly will report instability, joint effusions, or evidence of compromise of surrounding neurovascular structures16.
The natural history of SC tends to be chronic and progressive. Delayed diagnosis or late presentation may result in the most common long-term sequela of unrecognized SC: irreversible cartilaginous erosions about the joint4,5,35. Early diagnosis and rapid treatment can prevent this and other types of secondary joint pathology, including mechanical symptoms, adjacent tendon degeneration (e.g., rotator cuff tears in shoulders with SC), and chronic pain4,6,7,16,36. Physical disability is more commonly associated with SC of the hip and elbow16.
Synovial chondromatosis can usually be diagnosed on radiographs. Because the pathologic diagnosis can be confusing (as will be discussed later), it is important to recognize this condition radiographically. Radiographs will demonstrate multifocal, spheroidal, articular or periarticular calcific densities, which are pathognomonic of SC16. Often they have densely calcified outer borders with radiolucent centers16 characteristic of Stage-II and III disease. Although radiographs can be utilized to make the diagnosis, caution should be used in excluding this diagnosis because approximately 20% of SC cases do not present with calcifications because mineralization is time-dependent30. Nonmineralized nodules may appear as a vague fullness in the joint or bursa, or even mimic an effusion16. Additionally, clinical symptoms can precede the development of calcifications by months to years, which is another reason not to exclude the diagnosis on the basis of radiographs7. Typically, serial radiographs are used to evaluate for recurrence or degenerative changes after treatment4,27.
Cross-sectional imaging such as magnetic resonance imaging (MRI) and computed tomography (CT) can be useful in confirming the diagnosis in the early stages of the disease (namely the premineralization phase)4,6,7. In T1-weighted MRI sequences, loose bodies display a low signal intensity (but higher than that of muscle) (Fig. 2). In T2-weighted imaging sequences, loose bodies have a high signal intensity typical of the high water content of cartilage4. Areas of mineralization are hypointense on all routine MRI sequences, and they can be best seen on CT. In addition to evaluating the characteristics of loose bodies, MRI and CT are useful in evaluating the joint as well as involvement of adjacent structures. Cross-sectional imaging will typically give an accurate assessment of the extent of the disease, whereas radiographs may often underestimate the full extent.
The differential diagnosis includes any condition that results in intra-articular loose bodies or synovial proliferation. This includes, but is not limited to, crystal deposition disease (tendinosis calcarea), osteocartilaginous loose bodies, osteochondritis dissecans, neurotrophic arthritis, rheumatoid arthritis, degenerative arthritis, tuberculous arthritis, osteochondral fractures, soft-tissue tumors, and other benign synovial disorders such as synovial hemangioma, lipoma arborescens, and pigmented villonodular synovitis (PVNS)4,6,9,14,16.
Glistening, gray-white polypoid cartilaginous nodules characterize SC16. Nodules can be highly variable in size and may even coalesce to form a solid mass16, which has been termed “tumefactive” SC, in reference to the swollen appearance of the affected joint26 (Fig. 3). Tumefactive SC may be confused with sarcoma both radiographically (Fig. 4) and pathologically. As noted previously, nodules found in secondary SC may be larger, more irregularly shaped, and fewer in number compared with those found in primary SC16,30. Grossly, the synovium will appear thickened and hyperemic and can have a cobblestone appearance16.
Microscopic examination often reveals well-demarcated cartilaginous nodules. Loose and attached nodules have similar appearance, and the cartilage can be hyaline or myxoid16. The degrees of calcification and ossification are variable16. There may be endochondral ossification as well as synovial proliferation. SC can be confused with chondrosarcoma because of its hypercellularity, nuclear crowding, and nuclear atypia32. For this reason, it is difficult for a pathologist to render a correct diagnosis without the context of lesion location and imaging.
Treatment and Outcomes
Synovial chondromatosis has a highly variable natural history, and its treatment should be tailored to suit each patient. Because SC can be self-limiting, conservative management with nonsteroidal anti-inflammatory drugs (NSAIDs), activity modification, and cryotherapy9 can be considered. Conservative management can be used for pain and swelling; however, this would not be sufficient for decreased range of motion or locking symptoms. This treatment path carries the risk of articular damage from loose bodies as they become larger and ossify. For definitive resolution of the primary synovial chondromatosis, the only effective treatment is surgical removal of loose bodies with or without a synovectomy16,35. The necessity of a synovectomy is a matter of debate that warrants its own discussion.
The Role of Synovectomy
It may seem intuitive that synovectomy would be a useful adjunct for a synovially based process; however, at present there is little conclusive evidence that supports performing a complete synovectomy in conjunction with surgical removal of loose bodies4. Earlier literature supported the idea that total synovectomy offers no clear advantage compared with simply removing loose bodies37-40. In 1989, Dorfmann et al. reported that thirty-one of thirty-two knees with SC were treated solely with removal of loose bodies39. No synovectomies were performed, and only three of these patients required a second procedure. Those authors concluded that the most important prognostic factor is the condition of the femoral and tibial cartilage and that the treatment of choice for SC is arthroscopic removal of loose bodies alone. In 1990, Shpitzer et al. reported on thirty-one patients treated for SC40. Twelve of the thirty-one had a synovectomy in conjunction with loose body removal, sixteen had loose body removal only, and three had more radical surgery (two total hip replacements and one resection arthroplasty). Twenty-six of these patients were available for follow-up at an average of six years and four months. Those authors ultimately concluded that the results of removal of loose bodies were no different from those of synovectomy in conjunction with loose body removal40.
Others believe that synovectomy is helpful in preventing recurrence41-44. Those authors support synovectomy in conjunction with loose body removal with the goal of removing inflamed synovium, which is thought to have persistent metaplastic activity. Synovium with evidence of chondrometaplasia is thought to lead to a high risk of recurrence16,41. Ogilvie-Harris and Saleh performed a retrospective cohort study of thirteen patients with SC of the knee in which five were treated with loose body removal alone and eight were treated with loose body removal and arthroscopic total synovectomy41. At approximately one year of follow-up, three of five treated with loose body removal alone experienced recurrence41. Those three patients were then treated with arthroscopic synovectomy and had no subsequent recurrences. In contrast, none of the eight patients who had a total synovectomy experienced a recurrence41. These research results favor total synovectomy in addition to removal of loose bodies and support the idea that arthroscopic synovectomy is an adequate treatment for recurrence in situations in which no synovectomy was performed41. This study was not blinded or randomized and did not test the efficacy of a limited synovectomy; as with all studies of SC, the study was also limited by the small number of patients included41. Likewise, Schoeniger et al. reported no recurrence of SC in a case series of hips with SC treated with synovectomy using an anterior dislocation technique43. According to Marchie et al., patients with SC of the hip may be managed with arthroscopic partial synovectomy27. This can be effective, especially in patients without substantial cartilage disease, but the recurrence rate at sixty-four months of follow-up was reported to be seven (24%) of twenty-nine27. In a series of fifty-three patients, Maurice et al. showed that arthroscopy had a recurrence rate of 11.5% following loose body removal alone44.
In summary, the rate of recurrence with loose body removal alone has been reported as 3% to 60%39,41,44. The rate of local recurrence with total synovectomy is unknown, but it has been reported as low as zero of eight41. In this review we have attempted to separate, as much as possible, the discussion of whether or not to perform synovectomy from that of whether to perform arthroscopic or open treatment; however, these issues are often intertwined and difficult to analyze separately.
Open Versus Arthroscopic Treatment
It is debatable whether or not arthroscopic treatment of SC offers better visualization of joints compared with open treatment4,9. However, in general, arthroscopic management of SC results in lower morbidity, earlier return to function, a shorter rehabilitation course, decreased postoperative pain, and earlier active range of motion compared with open management4-6,9,28,44,45. Coolican and Dandy reported that eighteen patients who underwent arthroscopic treatment for SC of the knee had no loss of range of motion postoperatively46. However, four of these eighteen patients experienced recurrence of SC46. Additionally, Murphy et al. reported that 41% of thirty-two patients who underwent open synovectomy experienced moderate to severe loss of range of motion42.
Of note, comparable recurrence rates (0% to 31%) have been reported after open and arthroscopic treatment of SC of the shoulder and knee2,4,27,44,46-49. Several authors endorse arthroscopic management of synovial chondromatosis27,45,49-52. In 2008, Boyer and Dorfmann published one of the largest case series on SC of the hip, involving 111 patients who were managed with arthroscopy and followed for a mean of 78.6 months (range, twelve to 196 months)51. Forty-two (37.8%) of these patients subsequently required open surgery, and more than one arthroscopic surgery was necessary in twenty-three patients (20.7%). They concluded that hip arthroscopy was beneficial for patients with SC of the hip, as sixty-three (56.8%) of these 111 patients had excellent or good outcomes51. In 2014, de Sa et al. performed a systematic review that included 197 patients and showed a recurrence rate of 7.1% in hips with SC treated arthroscopically with loose body removal and synovectomy49.
Another point of contention is the effectiveness of complete compared with subtotal synovectomy. In 2006, Lim et al. reported a retrospective review of twenty-one patients with SC of the hip35. Thirteen of the patients underwent loose body removal and synovectomy by means of arthrotomy (incomplete synovectomy), and the remaining eight underwent loose body removal and synovectomy by means of anterior dislocation (complete synovectomy). At four years of follow-up, the mean Harris hip score had improved from 58 to 91 and there was no difference between the two cohorts. They reported a recurrence in two of the thirteen patients who had undergone arthrotomy and zero of the eight who had undergone anterior dislocation. Although the complication rate was higher in the dislocation cohort (one of the eight had osteonecrosis of the femoral head, one had avulsion of the lesser trochanter, and one had femoral nerve palsy), they concluded that incomplete synovectomy resulted in a greater rate of recurrence35. Both approaches relieve symptoms, but one must weigh the lower recurrence rate with complete synovectomy against the higher surgical risk35.
Treatment of Malignant Transformation
Treatment of malignant disease depends on obtaining an accurate diagnosis. Most cases that transform do so into low-grade chondrosarcoma, but transformation into intermediate and high-grade chondrosarcoma has also been reported. Core needle biopsies or incisional biopsies are acceptable. However, the biopsy tract should be resected during definitive surgical management, and referral to an orthopaedic oncologist prior to biopsy is therefore recommended. Because synovial chondromatosis involves a joint, that joint will be contaminated with tumor in the case of malignant transformation. For this reason, extra-articular resection of the joint (meaning resection of the joint without ever entering it) is often required.
The Authors’ Preferred Treatment
Arthroscopic treatment is preferred for the majority of cases, given the excellent intra-articular visualization and minimally invasive approach. However, in cases of tumefactive SC or those with such extensive size and/or number of loose bodies that arthroscopic removal would be tedious or ineffective, open excision is preferred. Additionally, the surgical approach is location-dependent; we would not recommend arthroscopic treatment for very small joints such as the sternoclavicular joint, or for areas such as the posterior aspect of the knee. Although we recognize the active debate and recognize that synovectomy may not confer an additional advantage, we routinely perform a synovectomy as it facilitates intra-articular visualization, allows for removal of sessile lesions, and does not add substantially to the case time, complications, or complexity. With regard to the extent of synovectomy, we perform as complete a synovectomy as possible, but we do not extend the exposure (or convert from an arthroscopic to an open procedure) in order to increase the extent of the synovectomy. For example, a patient with synovial chondromatosis of the hip treated at our institution would undergo arthroscopic removal of loose bodies and arthroscopic synovectomy. He or she would not undergo open arthrotomy and surgical hip dislocation purely to facilitate a total synovectomy.
SC is a rare, benign condition of unknown etiology in which the synovium undergoes focal metaplasia leading to cartilaginous nodules that ultimately break free, mineralize, and even ossify. The most commonly involved joint is the knee, followed by the hip. Patients may be asymptomatic but can present most commonly with pain, swelling, and limited range of motion that can be debilitating. Radiographs can be diagnostic and mineralized nodules are pathognomonic30. MRI and CT can confirm the diagnosis. Malignant transformation to chondrosarcoma is rare, but clinicians should be aware of the potential for this, especially in recurrent or atypical cases. Recommended treatment involves surgical removal of loose bodies as soon as possible to prevent further articular and periarticular destruction and to relieve symptoms. To date, inconclusive evidence exists as to whether a synovectomy should be performed in conjunction with loose body removal. Although arthroscopic and open treatments have similar recurrence rates, arthroscopic treatment of SC is associated with less morbidity.
Source of Funding: There was no external funding source for the production of this manuscript.
Investigation performed at the Department of Orthopaedic Surgery, Duke University Medical Center, Durham, North Carolina
Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, one or more of the authors has had another relationship, or has engaged in another activity, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.
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