The cause is unknown and may be related to trauma, inflammation, genetic factors and disorders of cholesterol metabolism. Some believe it is due to impaired lipid metabolism, others believe it is the result of massive proliferation of osteoclasts due to bone destruction, others believe it is due to synovial cell hyperplasia and highly dilated capillaries, resulting in the formation of villi or nodular protrusions on the synovial surface due to high synovial hyperplasia and dilated capillary filling, in addition to clinical observations that nodular lesions are highly prone to recurrence when surgical excision is incomplete, and there are Cases of malignant transformation due to multiple surgical recurrences have been reported.
Several studies have discussed the importance of genetic factors in the development of giant cell tumours of the tendon sheath. The presence of chromosome 7 trisomy is associated with giant cell tumours of the tendon sheath (chromosome 7 trisomy is associated with a variety of tumour conditions). Infiltration of histiocytes, macrophages and plasma cells supports the possibility of an inflammatory origin, and increased activity of epidermal growth factor (EGFR) and the growth factor PDGF (encoded by the c-erb B oncogene on chromosome 7) may also contribute to the inflammatory lesions caused by synovitis.
Trauma appears to be an important cause, with approximately 1 in 4 to 1 in 2 cases having a history of trauma, or trauma that exacerbates symptoms and progression of the disease; it also tends to occur in weight-bearing and injury-prone joints of the lower limbs, particularly the knee and hip, and less commonly the upper limbs.