Definition:
- A rare, usually benign but locally aggressive neoplasm of the synovium, tendon sheaths, and bursae.
- Characterized by CSF1 (colony-stimulating factor 1) gene overexpression, which recruits macrophages and leads to tumor proliferation.
Epidemiology:
- Rare: incidence ~1.8 cases per million/year.
- Typically affects young to middle-aged adults (20–50 yrs).
- Knee and hip are the most commonly involved joints.
Types:
- Localized TGCT
- Involves tendon sheath or small area.
- Often in hands/fingers.
- Easier to surgically remove; lower recurrence risk.
- Diffuse TGCT (PVNS)
- Involves entire synovium.
- Often in larger joints (knee, hip, ankle).
- High recurrence after surgery; more disabling.
Clinical Presentation:
- Joint pain, swelling, stiffness.
- Decreased range of motion.
- Sometimes recurrent hemarthrosis.
Diagnosis:
- MRI is preferred imaging (shows synovial thickening and hemosiderin deposits).
- Confirmed by biopsy/histology (giant cells, hemosiderin-laden macrophages).
Treatment Options:
- Localized TGCT: Surgery (usually curative).
- Diffuse TGCT: Surgery + synovectomy, but high recurrence rates.
- Unresectable or recurrent TGCT:
- Pexidartinib (Turalio®) – FDA approved (2019) for symptomatic TGCT not amenable to surgery.
- Dose: 400 mg PO twice daily with a low-fat meal.
- MOA: CSF1R inhibitor, blocks CSF1 signaling.
- Boxed warning: Hepatotoxicity (requires REMS).
- Common AEs: ↑LFTs, hair color changes, fatigue, nausea, edema.
- Other CSF1R inhibitors (investigational): cabiralizumab, emactuzumab.
- Radiation (rare, used in refractory cases).
- Pexidartinib (Turalio®) – FDA approved (2019) for symptomatic TGCT not amenable to surgery.
Monitoring (esp. for pharmacists):
- LFTs (frequent during first 3 months with pexidartinib).
- CBC, renal function.
- Dermatologic and GI monitoring.
Pharmacist high-yield point: TGCT is generally benign but disabling due to joint damage. Systemic therapy (pexidartinib) is reserved for symptomatic, unresectable, or recurrent diffuse TGCT, with close liver monitoring due to hepatotoxicity.