A 45-year-old woman has multiple pigmented villonodular synovitis (PVNS) nodules confirmed on MRI of the knee. The RANKL pathway drives osteoclast-mediated bone erosion in PVNS. Which targeted therapy is approved for unresectable or recurrent PVNS/tenosynovial giant cell tumour?
- A Pexidartinib (PLX3397) — CSF1R inhibitor ✓
- B Imatinib (anti-BCR-ABL)
- C Denosumab (anti-RANKL)
- D Pazopanib (anti-VEGFR)
Explanation
Tenosynovial giant cell tumour (TGCT/PVNS) is driven by CSF1 (colony-stimulating factor 1) gene overexpression, often due to chromosomal translocation, attracting CSF1R-expressing macrophages and osteoclasts. Pexidartinib (PLX3397) is a CSF1R tyrosine kinase inhibitor approved by the FDA in 2019 for symptomatic TGCT where surgery would result in severe morbidity. It targets the neoplastic stromal cells expressing the CSF1-CSF1R axis. Denosumab targets RANKL and is used in GCT of bone; imatinib and pazopanib target different receptor tyrosine kinases not central to TGCT pathogenesis.
Reference: Maheshwari Essential Orthopaedics, 6th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.