SC is a relatively rare condition with an incidence of ~1 case per 100,000 individuals. It primarily affects adults between the ages of 30 and 50 years, although both infants and the elderly can also be affected (1,12,13). Earlier studies suggested that the male-to-female ratio of SC was 1.8:1, indicating a higher prevalence in males (12,13). However, other studies suggest that this ratio may range from 2:1 to 4:1 (14). Notably, in areas such as the temporomandibular joint, hands and wrists, the incidence in females may be higher compared with males (15). Furthermore, due to the often-insidious symptoms of SC, the average time to diagnosis is ~5 years (15). However, with advancements in imaging technology, the detection rate of SC has markedly increased over the years (8). The higher incidence of SC in adults may be associated with long-term joint stress and a history of trauma, while the rarity of SC in children may be related to protective mechanisms during skeletal development (14). Additionally, PSC and SSC exhibit notable differences in epidemiology. PSC is generally more common and has a higher recurrence rate, whereas SSC is primarily associated with osteoarthritis or joint injuries, being relatively rare and often confused with primary diseases (9–11,16). Extraglenoid SC is rare, typically presenting as a painless mass and there is no notable trend associated with sex or age in these cases (14).

The recurrence rate of SC ranges from 0–31%, with the recurrence rate being lower when loose body removal and synovectomy are carried out via arthroscopy (~7.1%) (17,18). However, if the synovectomy is incomplete, the recurrence rate may rise to 20–30% (19). PSC has an increased recurrence rate compared with SSC, suggesting that PSC may exhibit more biological activity (9–11). Multiple recurrences may increase the risk of transformation into SS. Overall, the risk of malignant transformation in SC is low, typically ~5% (20). However, a study has reported a malignant transformation rate of ≤11.1% in hip joint SC cases (21), although this value may be lower in actual clinical practice due to limited follow-up times. Malignant transformation in SC is typically observed in cases with a disease duration of >5 years or in recurrent cases. Symptoms such as pain, swelling and local destruction may occur, and certain patients may exhibit cartilage matrix calcification and nuclear atypia, which resemble the features of low-grade SS (14). Compared with SSC, PSC carries a higher risk of malignant transformation, and gene fusions such as FN1-ACVR2A and chromosomal abnormalities have been detected in certain cases (22). However, to the best of our knowledge, there are currently no clear predictive markers for malignant transformation, emphasizing the need for long-term follow-up and biological assessments.

In summary, SC has a low incidence, delayed diagnosis and a higher prevalence in males. The recurrence rate of PSC is higher than that of SSC, with stronger biological activity, which may increase the risk of malignancy. The overall malignancy rate of SC is low, but cases with long-term recurrence may have potential for malignant transformation. Currently, epidemiological data on SC are limited and the mechanisms of malignancy remain unclear, with no effective predictive indicators. Further research is required on its pathogenesis, diagnostic methods and long-term prognosis.

Occurrence of SC involves multiple signaling pathways, with the Hedgehog, FGF9/FGFR3 and TGF-β pathways being considered the most key (28–30) (Fig. 4). Overactivation of the Hedgehog signaling pathway induces abnormal proliferation of synovial cells and promotes their differentiation into chondrocytes. A study has shown that elevated expression of PTC1 and GLI1 genes in PSC patient tissues suggests that the Hedgehog signaling pathway may carry out a pivotal role in SC pathogenesis (28). Furthermore, the FGF9/FGFR3 pathway promotes chondrification of synovial cells through the abnormal activation of the MAPK/ERK signaling axis, accelerating disease progression. The notably elevated FGF9 levels in tissues of patients with PSC further corroborate this mechanism (29). The abnormal activation of the TGF-β signaling pathway also carries out a significant role in the pathogenesis of SC, as TGF-β1 promotes synovial cell proliferation and cartilage matrix formation via both Smad-dependent and independent pathways, exacerbating disease progression (30). In addition to these pathways, TGF-β3, FGF2 and IL-6 may also contribute to SC development (31,32,34). Although these signaling pathway abnormalities have been confirmed, their specific roles in different stages and subtypes of SC require further investigation (28–32,34).

The development of SC is associated with its inflammatory microenvironment (Fig. 5). A study has shown that IL-6 and VEGF-A levels are considerably elevated in the synovial fluid of patients with SC, where IL-6 enhances inflammation via the JAK/STAT signaling pathway and VEGF-A promotes angiogenesis, potentially leading to chronic inflammation and accelerating disease progression (31). In patients with PSC, an increase in CD68+ synovial macrophages and human leukocyte antigen-DR-positive cells indicates that immune dysregulation carries out a key role in the pathogenesis of PSC (35). At the molecular level, the co-expression of COL3A1 and CD90 synergistically promotes the synthesis of glycosaminoglycans and COL2A1, enhancing chondrocyte migration and proliferation. These molecules contribute to the pathogenesis of SC through immune and metabolic pathways and may serve as potential diagnostic markers to distinguish PSC from SSC (36). Additionally, the overlapping expression of biomarkers such as PCNA, CD90, CD105, IGF-1 and TGF-β1 in PSC cartilage nodules highlights the complex interactions between cell proliferation, mesenchymal stem cells and cartilage formation (37). Elevated expression of BMP-2 and BMP-4 in SC lesions further supports their key role in chondrification (38), while overexpression of C-erbB-2 in certain PSC tissue samples may be associated with synovial cell proliferation and disruptions in signaling pathways (39). Moreover, abnormal proliferation of CD34+ progenitor cells, in conjunction with TWIST1, TGF-β1 and Harmane, may promote osteogenic differentiation, accelerating chondrification and calcification processes (40). Synovial hyperplasia, angiogenesis and proteoglycan deposition are key pathological features of SC lesions (31). By contrast, the inflammatory microenvironment in SSC is primarily driven by joint damage, with its inflammatory state closely associated with the progression of the primary disease. Furthermore, synovial macrophages, through M1/M2 polarization, carry out a key role in cartilage degradation and regeneration. M1 macrophages promote inflammation and cartilage degradation, while M2 macrophages support cartilage repair and regeneration (35).

Mechanical stress carries out a key role in the pathogenesis of SSC (Fig. 5). Prolonged mechanical stress can induce synovial cell proliferation and promote chondrification through the regulation of CD105 and CD90 (33,41). Moreover, mechanical stimulation may further enhance the expression of pro-inflammatory factors such as TNF-α and IL-1β, promoting synovial cell proliferation and chondrification (31). Under mechanical stress, synovial stem cells may differentiate into chondrocytes, ultimately leading to SC lesions. Patients with SSC often exhibit subchondral bone sclerosis, joint space narrowing and osteophyte formation in affected areas, suggesting that SSC may be an adaptive proliferative response of the synovium to prolonged mechanical stress (41).

Overall, PSC is primarily driven by signaling pathway abnormalities, while SSC is more influenced by inflammation and mechanical stress. Factors such as IL-6 and VEGF-A may promote disease progression, but the specific roles of these mechanisms in the disease process require further clarification. To the best of our knowledge, there is currently no unified pathogenic model and future research should focus on in-depth exploration of these mechanisms and their key regulatory factors. A deeper understanding of the pathogenesis of SC will provide theoretical support for clinical molecular biological diagnosis and targeted drug therapy.

SC manifests with a range of clinical symptoms. The most common include persistent joint pain, typically rated between 5 and 7 on the VAS scale, which intensifies as the disease progresses (3,8,9). With SC, 75–85% of patients experience mechanical dysfunctions, such as joint popping, locking and a reduced range of motion, often associated with intra-articular loose bodies. A total of 85–90% of patients present with recurrent joint swelling and increased local skin temperature, indicating an inflammatory response. In patients with a disease duration >3 years, nerve compression symptoms (such as numbness in the branches of the trigeminal nerve) and secondary osteoarthritis may develop. These symptoms not only reflect the severity of the disease but also provide key clues for clinical diagnosis and management (3,8,9). They offer clinicians essential insights to assess the severity of the disease and progression. In practice, doctors typically devise personalized treatment plans based on both the patient's subjective symptoms and imaging results.

The clinical presentation of early-stage SC is characterized by a lack of specificity, which poses considerable difficulties for accurate diagnosis. Ultrasonography (US), x-ray, computed tomography (CT), magnetic resonance imaging (MRI) and pathological examinations form a diagnostic system that progresses from basic to advanced methods, complementing each other. Among these, MRI is regarded as the most optimal imaging modality, capable of thoroughly evaluating synovial lesions and surrounding tissue involvement. However, pathological examination remains the definitive diagnostic tool (42). Furthermore, other diagnostic methods have become increasingly important in diagnosing SC.

US is primarily used for early screening and postoperative monitoring. It can detect synovial thickening, effusion and free bodies and dynamically assess the activity of the lesions (7,42). However, US has limited sensitivity for detecting non-calcified lesions and is inadequate in accurately determining the size and number of cartilage nodules, particularly in deep joints such as the hip, thus limiting its role in final diagnosis (14).

X-ray remains the first choice for imaging in SC, effectively screening for lesions and providing preliminary staging information (14). The typical X-ray features of PSC include multiple spherical or ring-shaped calcifications within the joint cavity, while SSC typically involves calcification patterns that are irregular and may overlap with osteoarthritis calcifications, complicating the diagnosis (7,42). Additionally, x-ray is less sensitive for detecting extra-articular SC and soft tissue calcifications may be misdiagnosed as tendon calcifications. Non-calcified SC or early-stage cases may appear normal on x-rays, necessitating further evaluation with CT or MRI (43).

CT carries out a key role in the early diagnosis of SC, especially in evaluating fine calcifications and bone destruction (7). The high resolution of CT allows clear visualization of small calcification points, ring-like calcifications and bone erosion, making it suitable for complex lesions or cases involving bone destruction (42,44). Furthermore, the multi-planar reconstruction function of CT helps analyze the relationship between calcified nodules, bone, synovium and soft tissues, which is especially advantageous in areas such as the hip, shoulder and ankle (44,45). However, CT is less effective for assessing synovial thickening and non-calcified cartilage nodules and MRI remains necessary for further analysis (7,45).

MRI is considered the gold standard for imaging diagnosis of SC, as it provides a comprehensive assessment of lesion extent, free body characteristics, soft tissue involvement and potential malignant transformation risks (7,46). MRI can detect non-calcified free bodies and clearly visualize synovial proliferation and cartilage matrix structure, demonstrating excellent diagnostic capability for both PSC, SSC and extra-articular SC (8). Compared with x-ray and CT, MRI offers considerable advantages in early detection of lesions, synovial activity assessment and postoperative follow-up (39). A study by Kramer et al (47) categorized the MRI presentation of SC into three patterns: Type A, typical calcified type, high T2 signal with focal low-signal areas, corresponding to Milgram Stage II; Type B, non-calcified type, high T2 signal without focal low-signal areas, corresponding to Milgram Stage I; and Type C, advanced ossification type, high signal intensity areas resembling fat, indicating cartilage matrix enrichment or malignant potential. This classification aids in determining the disease stage and selecting the most appropriate treatment (Table II). Additionally, MRI can help distinguish SC from SS, PVNS and other lesions, improving diagnostic accuracy (48). In early-stage SC, extra-articular SC and suspected malignant cases, the diagnostic value of MRI is irreplaceable. However, the high cost and longer examination time may necessitate complementary CT or X-ray evaluations for certain cases.

Although imaging carries out a key role in diagnosing SC, the final diagnosis depends on pathological analysis, which includes gross pathological and microscopic evaluations (29). Gross pathology in PSC typically reveals multiple translucent blue-white cartilage nodules with smooth surfaces; by contrast, SSC presents as localized cartilaginous metaplasia accompanied by chronic synovial inflammation and fibrosis (49,50). Microscopic examination of PSC reveals abundant undifferentiated chondrocytes within the synovium, rich matrix and uniform cellular arrangement, while SSC exhibits inflammatory cell infiltration, cartilage fragment deposition and fibrous tissue proliferation (49,50).

In pathological diagnosis, the gene fusion of FN1-ACVR2A and the overexpression of C-erbB-2 protein can indicate the clonal proliferation characteristics of PSC (22,38). This biomarker has considerable clinical value: In terms of diagnosis, the sensitivity of FN1-ACVR2A fusion for identifying SS is 92%, and the specificity is 100% (22); in terms of prognosis, patients with positive fusion have a 2.3-fold increased risk of recurrence, and the overexpression of C-erbB-2 is negatively associated with chemotherapy response (38). In terms of treatment, patients with positive fusion are recommended to undergo extensive synovectomy and extended follow-up for ≥5 years, while those with negative fusion can undergo local resection combined with routine 3-year follow-up (22,38). Although FN1-ACVR2A has not been included in the diagnostic criteria for malignancy, its status should be noted in the pathological report and integrated with imaging and clinical manifestations for risk-stratification management (23).

In addition to imaging and pathological examination, several auxiliary methods can aid in the diagnosis of SC. Electron microscopy can be used to observe the ultrastructural features of SC tissues, such as bone-cartilage differentiation, but its clinical application remains limited (51). Arthroscopy allows direct assessment of synovial proliferation and free bodies but is unable to precisely measure synovial thickness and the extent of soft tissue infiltration (10). Artificial intelligence (AI)-assisted diagnosis has shown promise in SC imaging analysis, particularly in using deep learning techniques to identify non-calcified SC, assess recurrence risks and predict malignant tendencies. However, this technology is still in the research phase and requires further validation before clinical implementation (52).

In summary, the diagnosis of SC should combine multiple diagnostic methods. US is useful for early screening and postoperative follow-up, while x-ray is the preferred method to identify calcified lesions, although non-calcified cases may be missed. CT can precisely assess calcification patterns and bone destruction, while MRI provides a comprehensive evaluation of synovial lesions, loose bodies and soft tissue involvement, making it suitable for early diagnosis and the assessment of malignancy. Definitive diagnosis still requires pathological analysis. The diagnosis of SC relies on a comprehensive evaluation of imaging and pathology, and AI-assisted diagnosis shows potential, but further research is needed for validation.

SC must be differentiated from all diseases that may cause intra-articular free bodies or synovial proliferation, including crystal deposition diseases (such as calcific tendinitis and hydroxyapatite deposition), osteochondral free bodies (such as osteochondritis dissecans), arthritis-related lesions (such as rheumatoid arthritis, degenerative arthritis and osteoarthritis), synovial proliferative diseases [such as pigmented villonodular synovitis (PVNS) or synovial hemangiomas], and other conditions (such as giant cell tumors of the tendon sheath, elbow joint tuberculosis, tumor-induced calcification and periarticular scleroderma) (27,53,54). The majority of these diseases can be distinguished through clinical presentation, imaging and pathological examination. However, the differential diagnosis between PSC and SS is particularly notable, as misdiagnosis can lead to unnecessary overtreatment, while failure to diagnose may delay treatment and compromise the outcome (52).

Imaging findings are the cornerstone for differentiating SC from SS (27). SC typically presents with cartilage nodules on the synovial surface, multiple free bodies in the joint and mild synovial thickening (2). By contrast, SS appears as an irregular soft tissue mass around the joint, with fewer free bodies (47). The calcification patterns in SC are typically ring-like, clustered or lobulated, which are characteristic of cartilage calcification (7,42). Conversely, SS presents as diffuse, patchy or punctate calcification with uneven distribution (52). SC lesions are generally confined to the synovium and rarely infiltrate deep tissues, whereas SS is more prone to invasion of muscles, nerves and blood vessels, with widespread edema and soft tissue infiltration visible on MRI (21,52). The degree of local tissue destruction also differs. SC shows mild bone erosion on the joint surface, with localized bone defects visible on CT and preserved bone cortex, while SS tends to cause bone destruction, periosteal reaction and marrow infiltration, indicating a higher degree of aggressiveness (7,21,52).

Histopathological examination further aids in distinguishing SC from SS. Microscopically, PSC shows translucent cartilage nodules with a regular arrangement of chondrocytes and few signs of atypia, necrosis or abnormal mitosis. By contrast, SS is characterized by high cellular density, disorganized arrangement of small round cells, active mitotic figures and may exhibit a biphasic pattern (epithelial-like and spindle cells) (42,55,56). Molecular markers can provide more definitive diagnostic evidence. In PSC, Bcl-2 protein expression is low, whereas SS shows high Bcl-2 expression. Additionally, SYT-SSX gene fusion [t (X;18)(p11.2; q11.2)] is a specific marker for SS, which is not present in SC (Table III) (55).

In summary, the typical imaging features of SC include loose bodies, multiple calcifications and localized synovial thickening, which are indicative of a benign mass, while SS is characterized by aggressive growth, soft tissue infiltration, bone destruction and specific gene fusions, suggesting malignancy. A combined approach of imaging, pathology and molecular testing can help improve diagnostic accuracy, reduce misdiagnosis and optimize clinical management. Although SC and SS show notable differences in imaging and molecular features, diagnosis remains challenging due to overlapping imaging characteristics with other diseases and the need for improved sensitivity and specificity of molecular markers. Future research should focus on optimizing the combined use of imaging diagnostics and molecular testing, as well as exploring the potential of AI-assisted diagnosis to enhance early diagnostic accuracy and efficiency.