Tenosynovial Giant Cell Tumour (PVNS / GCT-TS)

Gradient-echo MRI is the critical sequence for TGCT. Haemosiderin causes magnetic susceptibility artefact that produces dramatic signal loss (blooming) on GRE sequences. This is absent on standard spin-echo T1 and T2. If you suspect TGCT and the MRI protocol does not include GRE, request it specifically. The blooming artefact is the imaging equivalent of Prussian blue staining on histology — it proves haemosiderin is present.

A common viva follow-up is "how does the pathologist confirm it, and how is it told apart from giant cell tumour of bone or a sarcoma?" The key is to separate the two cell populations:

• The neoplastic large mononuclear (dendritic-like) cells: these carry the CSF1 rearrangement and are the diagnostic population. They are typically desmin positive (a dendritic-cell pattern, not smooth-muscle) and clusterin positive; a subset express CD163/CD68. CSF1 over-expression can be shown by in-situ hybridisation, and CSF1 rearrangement by FISH in difficult cases.
• The recruited reactive cells (the bulk): small mononuclear histiocytes and osteoclast-like multinucleated giant cells that are CD68 / CD163 positive (macrophage markers), plus haemosiderin-laden macrophages (Prussian blue positive) and foam (xanthoma) cells.
• Telling it apart: from giant cell tumour of bone (the giant cells look identical, but GCT of bone is centred in epiphyseal bone and carries the H3F3A G34W mutation, not a CSF1 rearrangement); from synovial sarcoma (monophasic spindle cells, SS18-SSX / t(X;18), TLE1 positive); and benign TGCT lacks the marked atypia, atypical mitoses and necrosis of a malignant lesion.

Exam point: TGCT shows a CSF1-driven desmin/clusterin-positive dendritic neoplastic cell within a reactive population of CD68/CD163-positive macrophages, osteoclast-like giant cells and haemosiderin - and the differentiating molecular tests are H3F3A (GCT of bone) and SS18-SSX (synovial sarcoma).

Best prognosis: Localised type, first-time excision, complete margins, digit location

Poor prognosis: Diffuse type, extra-articular extension, multiple prior recurrences, hip or ankle location (harder to access for complete synovectomy)

Key concept: TGCT does not metastasise — it is a locally aggressive neoplasm. However, the morbidity comes from local destruction, functional impairment, and the morbidity of repeated surgical interventions.

Q: What is the molecular driver of TGCT and what is its mechanism? A: CSF1 overexpression due to a translocation (most commonly t(1;2)(p13;q35)) that fuses CSF1 to the COL6A3 promoter. The neoplastic cells (small minority) overexpress CSF1, which recruits CSF1R-expressing macrophages (the bulk of the tumour). This paracrine recruitment mechanism is the basis for CSF1R-targeted therapy with pexidartinib.

Q: What MRI finding is pathognomonic for TGCT? A: Blooming artefact on gradient-echo (GRE) sequences. Haemosiderin within the proliferative synovium causes magnetic susceptibility artefact, producing dramatic signal loss on GRE that appears larger and darker than on spin-echo sequences. The synovium is low signal on both T1 and T2-weighted images. This triad (low T1, low T2, blooming GRE) is characteristic.

Q: How do localised and diffuse TGCT differ in behaviour and management? A: Localised TGCT (formerly GCT of tendon sheath): well-circumscribed digital nodule, marginal excision, 5-15 percent recurrence. Diffuse TGCT (formerly PVNS): infiltrative synovial proliferation of large joints, combined anterior and posterior synovectomy, 20-50 percent recurrence. Pexidartinib is reserved for unresectable diffuse disease.

Q: When is pexidartinib indicated and what monitoring is required? A: Symptomatic diffuse TGCT not amenable to surgical improvement. It is a CSF1R tyrosine-kinase inhibitor that blocks macrophage recruitment. Monitoring requires LFTs at baseline, weekly for the first 2 months, then monthly due to a black-box warning for hepatotoxicity. It is suppressive, not curative — tumour regrows if discontinued.

Q: A 30-year-old presents with recurrent bloody knee aspirates. Name three differential diagnoses and the key discriminator for each. A: Diffuse TGCT — MRI blooming artefact, monoarticular. Haemophiliac arthropathy — polyarticular, known bleeding disorder. Synovial chondromatosis — radiodense loose bodies on X-ray, T2-bright cartilage nodules. Synovial sarcoma — aggressive imaging features, heterogeneous enhancement, often extra-articular.

Q: What is the main driver of recurrence in diffuse TGCT and how is it minimised? A: Incomplete synovectomy — leaving residual disease in the posterior compartment is the most common cause of recurrence in knee TGCT. A combined anterior and posterior synovectomy reduces recurrence from approximately 50 percent (anterior only) to approximately 20-30 percent (combined approach). Adjuvant radiotherapy may be considered for multiply recurrent or high-risk cases.