Solitary Fibrous Tumour

Solitary fibrous tumour is a fibroblastic neoplasm of intermediate, rarely metastasising behaviour characterised by an NAB2::STAT6 gene fusion from a 12q13 inversion and nuclear STAT6 expression. The terms haemangiopericytoma and localised fibrous tumour of the pleura describe the same entity.

It makes up under 2% of soft tissue tumours. Median age is 50 to 60, and it occurs at any site: pleura (about 30%), meninges, retroperitoneum and pelvis, limbs, head and neck and orbit.

Rarely, tumours secrete insulin like growth factor 2 (IGF-II) and cause non-islet-cell tumour hypoglycaemia, and some cause hypertrophic osteoarthropathy.

Pathophysiology. The fusion converts NAB2 into an activator of EGR1-driven transcription, with STAT6 nuclear translocation. IGF2 overexpression explains hypoglycaemia. TERT promoter mutation and TP53 alterations mark dedifferentiated tumours.

Histology. Patternless cellular and collagenous areas of bland spindle cells with staghorn (branching) vessels. CD34 is positive in most, and STAT6 nuclear staining is highly sensitive and specific. Dedifferentiated tumours show high grade sarcoma with loss of CD34.

Risk stratification. Age 55 or over, size (under 5 cm, 5 to 10 cm, 10 to 15 cm, 15 cm or more), 4 or more mitoses in 10 high power fields and necrosis of 10% or more define low, intermediate and high risk of metastasis.

Behaviour. About 10% to 30% metastasise (lung, liver, bone, brain), and relapse can occur more than 10 years after surgery. Intracranial and retroperitoneal tumours recur more often.

• Often asymptomatic, found incidentally on imaging as a large well circumscribed mass.
• Mass effect: cough, dyspnoea and chest pain (pleural), headache and focal deficit (meningeal), abdominal or pelvic symptoms, proptosis (orbital).
• Hypoglycaemia (fasting, early morning): sweating, confusion, seizures.
• Digital clubbing and joint pain (hypertrophic osteoarthropathy).

Red flags.

• Neuroglycopenic symptoms (confusion, seizure, loss of consciousness) with low glucose.
• Haemothorax or haemorrhage into a large tumour.
• Pleural effusion with a rapidly enlarging mass.

• CT or MRI: well defined, hypervascular mass with heterogeneous enhancement, flow voids and necrosis in large tumours. Intracranial tumours are dural based.
• Core biopsy with STAT6 and CD34 immunohistochemistry. Confirm with NAB2::STAT6 by RT-PCR or sequencing in difficult cases.
• Staging with CT of chest, abdomen and pelvis (liver and lung metastases) and MRI brain for symptoms.
• Hypoglycaemia workup during a fast: low insulin, low C-peptide and low beta hydroxybutyrate with low glucose, low IGF-I, and a high IGF-II to IGF-I ratio (over 10).
• Embolisation planning angiography for hypervascular tumours.

Differential diagnosis.

• Synovial sarcoma and malignant peripheral nerve sheath tumour
• Dedifferentiated liposarcoma
• Mesothelioma and metastatic tumours to the pleura
• Meningioma and schwannoma
• Gastrointestinal stromal tumour and desmoid type fibromatosis
• Spindle cell lipoma and myofibroma

Surgery. Complete resection with negative margins is curative for most. Preoperative embolisation reduces bleeding in hypervascular tumours.

Radiotherapy. Postoperative 50 to 60 Gy for high risk features, positive margins, intracranial or retroperitoneal tumours, and for unresectable disease.

Hypoglycaemia. Resection cures it. Until then:

• Dextrose: 10% dextrose 150 to 250 mL IV over 15 minutes, repeated until glucose is over 4 mmol/L, then 10% dextrose infusion titrated to glucose; maximum set by fluid balance; monitoring: capillary glucose every 15 minutes until stable then hourly, electrolytes, fluid status; adjustment: caution in heart failure and kidney impairment, with regular feeding (complex carbohydrate overnight) when out of hospital.

Metastatic or unresectable disease.

• Pazopanib: 800 mg orally once daily on an empty stomach until progression; maximum 800 mg daily; monitoring: liver tests at baseline, weeks 3, 5, 7 and 9, then months 3 and 4 and as needed, blood pressure at each visit, ECG and electrolytes, thyroid function, proteinuria; adjustment: reduce in 200 mg steps for toxicity, 200 mg daily in moderate hepatic impairment (bilirubin over 1.5 to 3 times the upper limit), avoid in severe impairment, stop for ALT over 8 times the upper limit, avoid strong CYP3A4 inhibitors.
• Temozolomide with bevacizumab: temozolomide 150 mg/m2 orally daily on days 1 to 7 and 15 to 21 of a 28-day cycle, with bevacizumab 5 mg/kg IV on days 8 and 22, until progression; maximum temozolomide 150 mg/m2 daily and bevacizumab 5 mg/kg each dose; monitoring: FBC (day 21 and before each cycle), liver tests, blood pressure, proteinuria; adjustment: reduce temozolomide by one dose level (about 25%) for grade 3 to 4 haematological toxicity, hold bevacizumab for uncontrolled hypertension, proteinuria of 2 g or more in 24 hours or bleeding, caution when creatinine clearance is under 36 mL/min, stop bevacizumab 4 weeks before elective surgery. Activity is highest in this subtype, with response assessed by density change on CT.
• Doxorubicin has low activity, except in dedifferentiated tumours.
• Resection or stereotactic radiotherapy of oligometastases.

Monitoring. CT or MRI every 3 to 6 months for 2 years, then every 6 to 12 months, with long term follow up for over 10 years.

Referral and escalation.

• Sarcoma centre referral for tumours over 5 cm, retroperitoneal tumours or any with high risk features.
• Neurosurgery for intracranial tumours, thoracic surgery for pleural tumours.
• Urgent admission for symptomatic hypoglycaemia.

Special groups.

• Older adults: high risk scoring applies at 55 years or more.
• Orbital and intracranial tumours need specialist surgery, and postoperative radiotherapy is used more often.