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.
Synonyms
TGCT