Introduction and Definition
Giant cell rich tumors can be classified according to their site of origin; bone, soft tissue, synovium or tendon sheath. Those that arise from synovium, tendon sheath or bursa are now classified into localized (nodular tenosynovitis) or diffuse (PVNS). WHO has classified the localized form as Giant cell tumor of tendon sheath and the diffuse type as Diffuse type GCT (Dt-GCT) or PVNS.
Pigmented villonodular synovitis is a benign but locally aggressive synovial tumor. It may affect the joints, tendon sheaths or bursae. There are two types; diffuse and localized nodular types. In the diffuse form entire synovium is involved and in the localized form a portion of the synovium is affected.
It was first described by Chassaignac in 1852. Simon first described the localized form in 1865 and the diffuse form was first described by Moser in 1909. It was reported in different names as synovial xanthoma, synovial endothelioma etc and in 1941, Jaffe, Lichtenstein and Sutro identified them as variants of the same entity.
Both are giant cell tumors that express an osteoclast like antigenic phenotype with calcitonin receptors. The giant cells are thought to be formed from macrophage precursors by a RANKL (Receptor activator of nuclear factor κβ ligand) dependent mechanism like the GCT of bone. Tumors are driven by over expression of Macrophage colony stimulating factor 1 (M-CSF1). In 30-60% M-CSF overexpression results from a t(1;2)translocation, which fuses M-CSF gene on chromosome 1p13 to the collagen 6A3 (COL6A3) gene on chromosome 2q35. M-CSF1 is expressed by few tumor cells but they attract other neoplastic cells to express M-CSF1 by a paracrine effect called landscape effect.
Localized type is most commonly seen in the hand and the diffuse form most frequently seen in the knee. It is most commonly seen in the third and fourth decades and both sexes are equally affected. Incidence is 1.8 per million per year. It is almost always monoarticular. 80% of diffuse type presents in the knee followed by hip (15%) and ankle (5%). Few multifocal cases has been reported and all of them in children.
Etiology is unknown; reactive hyperplasia, inflammatory origin and neoplastic process are suspected to be the cause. An association of PVNS with LEOPARD syndrome (lentiginosis, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, genital abnormalities, growth retardation, and sensorineural deafness) and Noonan-Like/multiple giant-cell lesion syndrome has been reported.
It presents as an intermittently painful and swollen joint. There may be recurrent swelling with spontaneous hemarthrosis. Usual age group is 20-50 years and peak incidence is in 21-30 year group. Duration of symptoms is likely to be 2-3 years and is slowly progressive.
The findings on imaging studies vary depending on the site. Soft tissue swelling is the main finding in the knee, but in joints with tight joint capsule like hip, periarticular erosions and cysts can be demonstrated. Bone mineralization is normal and joint space is normal till the advanced stage sets in. Lack of periarticular osteopenia can be helpful in differentiating it from inflammatory arthritis. In the hand, a soft tissue mass with erosions can be found. CT scans will show the hemosiderin deposits along with cysts and help delineating the extent of disease. MRI shows effusion with synovial hypertrophy with scattered areas of low signal density in both T1 and T2 sequences (blooming effect) due to hemosiderin deposits. Marked enhancement on T1 is seen after administration of gadolinium. Although similar findings can be seen in hemophilia and rheumatoid arthritis, with clinical correlation these findings are considered to be highly suggestive of PVNS. Other MRI differential diagnoses include amyloid arthropathy, synovial haemagioma and desmoid type fibromatosis.
Aspiration of the synovial fluid will usually yield hemorrhagic or serosanguinous fluid. Synovial fluid has high cholesterol content. Pathologic findings are well described by the name of the disease. On gross examination, synovium has a mossy or shaggy carpet appearance due to synovial hypertrophy with coarse villi, fine fronds with nodularity and heavy pigmentation which range from dark yellow to chocolate brown, due to hemosiderin deposits. Cut surface has a variegated pink grey appearance with flecks of yellow and brown areas. Nodular form shows a pedunculated firm nodule. Microscopic examination shows subsynovial mononuclear histiocytic reaction with the presence of few scattered giant cells, sheets of small ovoid or spindle shaped cells and a rich vascular plexus. Mitotic figures are common. With time, the cellularity decrease and fibrosis increases. Pathologically differential diagnoses include hemosiderotic synovitis, rheumatoid arthritis and synovial chondromatosis.
Treatment is by arthroscopic or open total synoviectomy and the rate of local recurrence is 45%. Arthroscopic excision has high risk of incomplete excision, hence open excision is preferred. Open excision is associated with prolonged hospitalization and significant morbidity and the incidence of joint stiffness is as high as 24%. Total joint arthroplasty may be required in case of extensive joint destruction but failure rate of 22% has been reported. Adjunct radiotherapy may be useful in case of recurrence, but is controversial. Intra-articular injection of yttrium-90 labeled colloid can be used for radiosynoviectomy. External beam radiation is used for unresectable tumors or as adjuvant therapy in partial resections. Characterization of molecular mechanism of PVNS has led to the development of neo-adjuvant targeted chemotherapy using systemic chemotherapy using tyrosine kinase inhibitors like imatinib or related compounds.
Copyright @Dr Rajesh Purushothaman, Associate Professor, Government Medical College, Kozhikode, Kerala, India