Synonyms

• Congenital fibrosarcoma
• ETV6-NTRK3 fibrosarcoma

Category

Soft tissue

Behaviour

Malignant

Grade

Low

Gender

Both equally

Tissue of Origin

Fibrous

Epidemiology

• Most common soft tissue sarcoma in infants (<2 years)
• Presents at birth or within first year of life
• ETV6-NTRK3 fusion is the defining molecular event

Clinical Features

• Large soft tissue mass present at birth or early infancy
• Rapidly enlarging lesion
• Skin discolouration over tumour
• Rarely causes systemic symptoms

Location

• Distal extremities (forearm, hand, foot, leg) most common
• Trunk and retroperitoneum
• Head and neck

Imaging

• Large, often poorly defined soft tissue mass
• Variable heterogeneity with areas of necrosis on MRI
• CT: large soft tissue mass without significant calcification
• Vascularity may be prominent on Doppler ultrasound

Pathology

• Highly cellular spindle cell sarcoma in herringBone or fascicular pattern
• ETV6-NTRK3 fusion gene diagnostic
• NTRK3 (TrkC) expression by IHC
• High mitotic rate but favourable biology in infants

Genetics

• ETV6-NTRK3 fusion (t(12;15)(p13;q25)) - present in >90%
• This translocation is diagnostic
• Shared with congenital cellular mesoblastic nephroma (same fusion)
• NTRK inhibitors Highly effective (larotrectinib, entrectinib)

Treatment

• Chemotherapy: VAC-based regimens - High response rate
• Surgery after chemotherapy downstaging - limb-preserving surgery possible
• NTRK inhibitors (larotrectinib, entrectinib): transformative therapy for NTRK3 fusion
• Wide excision when feasible

Prognosis

• Excellent prognosis - 5-year survival >80% even with metastatic disease in infants
• Dramatically better prognosis than adult fibrosarcoma
• NTRK inhibitors produce durable responses
• Spontaneous regression reported

Key Points

• ETV6-NTRK3 fusion defines infantile fibrosarcoma - shared with mesoblastic nephroma
• NTRK inhibitors are transformative - larotrectinib has 75% response rate in TRK fusion-positive tumours
• Prognosis far better than adult fibrosarcoma despite aggressive histology
• Active surveillance/watch-and-wait being explored for very young infants

Workup - Blood Tests

FBC, U&E, LFTs - baseline if systemic therapy planned

Workup - Local Imaging

MRI primary site - local staging; assess soft tissue extent

Workup - Biopsy

• Core needle biopsy - confirm diagnosis
• IHC: p53+, Ki67 High, SMA and desmin negative
• ETV6-NTRK3 FISH (t(12;15)(p13;q25)) - diagnostic in 90%
• Histology: spindle cell sarcoma with storiform pattern

Workup - Staging

CT chest - pulmonary metastases

Workup - Other

• Paediatric oncology MDT mandatory
• ETV6-NTRK3 fusion alLows targeted therapy (TRK inhibitors like larotrectinib)
• Often responsive to chemotherapy/targeted therapy

Follow-up Summary

• Years 1–2: 3–4 monthly clinical review + CXR; MRI primary site at 3 months post-op then 6-monthly
• CT chest every 3–4 months for first 2 years (pulmonary metastasis is primary concern)
• Years 3–5: 6-monthly clinical review + CXR; CT chest 6-monthly
• Years 6–10: Annual clinical review + CXR; CT chest annually
• Immunotherapy or targeted therapy patients: routine toxicity monitoring at each visit
• Discharge at 10 years with documented self-monitoring advice