Update on Tenosynovial Giant Cell Tumor, an Inflammatory Arthritis With Neoplastic Features

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction and bone erosion. Even if many treatments were developed with success in the last decades, some patients fail to respond, and disease chronicity is still a burden. Mechanisms involved in such resistance may include molecular changes in stromal cells. Other explanations can come from observations of tenosynovial giant cell tumor (TGCT), first considered as an inflammatory arthritis, but with unusual neoplastic features. TGCT leads to synovium hypertrophy and hyperplasia with hemosiderin deposition. It affects young adults, resulting in secondary osteoarthritis and increased morbidity. TGCT shows clinical, histological and genetic similarities with RA but affecting a single joint. However, the monoclonality of some synoviocytes, the presence of translocations and rare metastases also suggest a neoplastic disease, with some features common with sarcoma. TGCT is more probably in an intermediate situation between an inflammatory and a neoplastic process, with a main involvement of the proinflammatory cytokine CSF-1/CSF1R signaling axis. The key treatment option is surgery. New treatments, derived from the RA and sarcoma fields, are emerging. The tyrosine kinase inhibitor pexidartinib was recently FDA-approved as the first drug for severe TGCT where surgery is not an option. Options directly targeting the excessive proliferation of synoviocytes are at a preclinical stage.

Invasion Patterns and Long-Term Clinical Outcomes of Diffuse Tenosynovial Giant Cell Tumor of the Ankle Joint

“…Postoperative radiotherapy was not performed in our patients because the patients did not want it, but it may be a treatment option for postoperative recurrence. The effects of several systemic therapies, including CSF-1 receptor monoclonal antibodies and tyrosine kinase inhibitors, have recently been investigated and are expected to be expanded for future indications [ 16 , 17 ].…”

Synoviocytes from pigmented villonodular synovitis are less sensitive to cadmium-induced cell death than synoviocytes from rheumatoid arthritis

“…Described for the first time in 1941, pigmented villonodular synovitis (PVNS), also known as tenosynovial giant cell tumor, is a rare articular disease characterized by an inflammatory synovitis with proliferation of synoviocytes and accumulation of large size monocyte-derived osteoclasts in the synovial tissue of joints 1 . Affecting mostly a single joint, PVNS usually affects young adults with an annual incidence of 1.8 cases out of one million 2 , 3 . The wide spectrum of clinical manifestations includes mainly pain, inflammation and joint swelling leading to a limitation of joint function 4 .…”

Novel CSF1R-positive tenosynovial giant cell tumor cell lines and their pexidartinib (PLX3397) and sotuletinib (BLZ945)-induced apoptosis

“…Consequently, the underlying cause of TGCTs can be targeted by inhibiting signaling between CSF1 and the CSF1 receptor (CSF1R) [ 8 , 9 ]. Research has shown that the monocyte–macrophage lineage marker CD68 stains synovial-lining cells; double staining revealed that CD68 is also expressed by TGCT cells that express CSF1 [ 10 ]. Other work found high CD68 expression levels in several tumor types, particularly TGCTs, compared with normal tissue samples [ 11 ].…”