Synonyms

ASPS

Category

Soft tissue

Behaviour

Malignant

Grade

High

Gender

Female

Tissue of Origin

Unknown (possible muscle/Neural crest origin)

Epidemiology

• Rare, 0.5–1% of soft tissue sarcomas
• Peak incidence in adolescents and young adults (15–35 years)
• Slow-growing despite High-grade histology

Clinical Features

• Painless Slowly-growing deep soft tissue mass
• Often large at presentation due to indolent course
• Pulsatile mass or prominent vessels may be evident
• Brain metastases can present as neurological symptoms

Location

• Lower extremity (tHigh) in adults - most common
• Head and neck (tongue, orbit) in children
• Upper extremity
• Rarely trunk or retroperitoneum

Imaging

• Well-defined hyperVascular mass on CT/MRI
• Prominent internal and peripheral fLow voids on MRI (fLow vessels)
• Avid FDG uptake on PET-CT
• May show lung and brain metastases at presentation

Pathology

• Organoid/alveolar pattern with large polygonal cells
• PAS-positive diastase-resistant crystals (pathognomonic)
• TFE3 nuclear expression by immunohistochemistry
• ASPSCR1-TFE3 fusion gene

Genetics

• ASPSCR1-TFE3 fusion (der(17)t(X;17)(p11;q25))
• Unbalanced translocation always present
• TFE3 FISH/IHC confirmatory

Treatment

• Wide surgical resection
• Sunitinib - most active single agent
• Cediranib - High response rates in metastatic disease
• Immunotherapy (PD-1 inhibitors) showing activity

Prognosis

• Indolent course but High rate of metastasis (lungs, bone, brain)
• 5-year survival 60% for localised disease
• Late metastasis common (>10 years after resection)
• Brain metastases associated with very poor outcome

Key Points

• Deceptively Slow-growing despite High-grade histology and metastatic propensity
• TFE3 rearrangement is diagnostic
• PAS-positive crystals pathognomonic but not always seen
• Long-term surveillance required - late metastasis well recognised

Workup - Blood Tests

FBC, U&E, LFTs - baseline and pre-chemotherapy

Workup - Local Imaging

MRI with contrast of primary site

Workup - Biopsy

• Core needle biopsy - confirm diagnosis
• IHC: TFE3+, PAX8 Variable, CD34+, CD31+ (periVascular)
• ASPSCR1-TFE3 FISH (t(X;17)(p11;q25)) - diagnostic in 100%
• Histology: nested architecture with characteristic alveolar/organoid pattern

Workup - Staging

• CT chest/abdomen/pelvis - metastatic disease (lungs and brain characteristic)
• MRI brain - brain metastases common
• PET-CT

Workup - Other

MDT review with sarcoma specialist centre

Follow-up Summary

• Post-operative review at 6 weeks
• Year 1–2: 3–4 monthly clinical review; CT chest, total body PET scan as per LSESN protocol for ASPS
• Years 3–5: 6-monthly clinical review + CXR; CT chest/abdomen/pelvis annually
• Years 6–10: Annual clinical review + imaging; continue annual CT chest and brain MRI if clinically indicated
• Beyond 10 years: Continue surveillance - late metastasis (lung, Bone, brain) well recognised >10 years post-resection
• Specific LSESN note: ASPS listed as requiring CT chest + total body PET scan at staging and for surveillance due to High metastatic rate
• Red flags: new neurological symptoms (brain mets), respiratory symptoms, new Bone pain
• Propensity for late metastasis - requires EXTENDED Follow-up beyond 10 years