Synonyms

• MFH
• undifferentiated pleomorphic sarcoma

Category

Bone and soft tissue

Behaviour

Malignant

Grade

High

Gender

Male

Tissue of Origin

Fibrous

Epidemiology

• Now largely reclassified as undifferentiated pleomorphic sarcoma (UPS)
• Peak incidence in 5th–7th decades
• Slight Male predominance
• May arise de novo or secondary to prior irradiation or Bone infarct

Clinical Features

• Painful enlarging mass
• Rapid growth
• Pathological fracture common in Bone MFH
• Constitutional symptoms (weight loss, fatigue) in advanced disease

Location

• Metaphysis of long Bones (distal femur, proximal tibia) for Bone MFH
• Extremities (tHigh most common) for soft tissue MFH
• Retroperitoneum

Imaging

• Aggressive permeative lytic lesion with cortical destruction
• Soft tissue mass extension common
• No tumour matrix mineralisation
• MRI: heterogeneous signal with areas of necrosis

Pathology

• High-grade pleomorphic spindle cell sarcoma
• Storiform growth pattern with marked nuclear atypia
• Numerous atypical mitoses
• Areas of necrosis common

Genetics

• Complex karyotype with multiple chromosomal gains and losses
• No specific defining mutation
• MDM2 amplification may be present

Treatment

• Wide surgical resection with negative margins
• Neoadjuvant and adjuvant chemotherapy (doxorubicin/ifosfamide-based)
• Radiotherapy for unresectable or margin-positive disease

Prognosis

• 5-year survival approximately 50–60% for localised disease
• Metastasis to lungs in 40% of cases
• Poor prognosis with positive margins or metastatic disease

Key Points

• Now considered largely synonymous with undifferentiated pleomorphic sarcoma per WHO 2020
• Must rule out other pleomorphic sarcomas with differentiation (dedifferentiated liposarcoma, etc.)
• MDM2 FISH and immunohistochemistry helpful to exclude dedifferentiated liposarcoma

Workup - Blood Tests

• FBC, U&E, LFTs, Bone profile (if Bone) - baseline and pre-chemotherapy
• LDH - elevated in advanced disease
• Coagulation screen - pre-operative

Workup - Local Imaging

• Plain radiograph (Bone MFH)
• MRI primary site with gadolinium

Workup - Biopsy

• Core needle biopsy at sarcoma centre - en bloc excision of tract
• Histology: storiform pleomorphic sarcoma with High-grade atypia
• Comprehensive IHC + molecular testing to exclude other pleomorphic sarcomas (DDLPS, pleomorphic liposarcoma)
• MDM2 FISH - to exclude dedifferentiated liposarcoma

Workup - Staging

• CT chest/abdomen/pelvis - pulmonary and visceral metastases
• PET-CT - increasingly used for staging

Follow-up Summary

• Year 1: Post-operative visit within first 6 weeks; 3–4 monthly clinical examination and CXR; image prosthesis at 6 months and 1 year
• Year 2: 3–4 monthly clinical examination and CXR; image prosthesis annually
• Years 3–4: 6-monthly clinical examination and CXR; image prosthesis annually
• Years 5–10: Annual clinical examination and CXR; image prosthesis annually
• Discharge at 10 years after surgery