Review Question - QID 214050

Colony-stimulating factor 1 (CSF1) overexpression has been linked to the growth and development of pigmented villonodular synovitis (PVNS).

PVNS is an idiopathic monoarticular neoplastic synovial disease. Three predominant types of PVNS are known; localized (intra-articular or classic form),diffuse (extra-articular extension), and giant cell tumor of tendon sheath occurring along tendon sheaths of hands and feet. This condition is most commonly managed with surgical synovectomy. Unfortunately, local recurrence is common, and degenerative changes and joint destruction often occur. Early clinical trials using colony-stimulating factor 1 receptor (CSF1R) inhibitors (ex. Imatinib) are promising.

Tap et al. reviewed the expression of the CSF1 gene and the CSF1R. Investigating a selective CSF1R inhibitor, PLX3397, they found that patients with tenosynovial giant-cell tumors had a partial response and 7 patients had stable disease. They concluded that treatment of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients.

Gelhorn et al. reviewed tenosynovial giant cell tumor treated pharmacologically. They note the influence of CSF1R-bearing macrophages recruited to the tumor by genetic elevation of CSF1 activity leading to joint destruction. They report trends of improvement in both pain and stiffness over time and concluded that they have identified content-valid patient-reported outcome measures.

Figure A is the intraoperative image demonstrating brownish inflamed synovium suggestive of PVNS

Incorrect Answers:
Answers 1&2: Ubiquitin-specific protease 6 fusion genes have been linked to aneurysmal bone cysts and more recently to nodular fasciitis.
Answer 4: PVNS is driven by overexpression of colony-stimulating factor 1 (CSF-1).
Answer 5: Mouse double minute-2 homolog has been associated with the development of low-grade and parosteal osteosarcoma as well as atypical lipomatous tumors.