Synonyms

• DDLPS
• dediff LPS

Category

Soft tissue

Behaviour

Malignant

Grade

High

Gender

Male

Tissue of Origin

Adipose

Epidemiology

• 20% of all liposarcomas
• Peak incidence in 6th–7th decades
• Slight Male predominance
• Can arise de novo or from well-differentiated liposarcoma

Clinical Features

• Large, often painless retroperitoneal mass
• Abdominal discomfort, constipation, urinary symptoms
• Peripheral extremity form: large deep soft tissue mass
• Weight loss and fatigue with large tumours

Location

• Retroperitoneum (75%)
• Deep extremity (tHigh)
• Spermatic cord (paratesticular)
• Other deep sites

Imaging

• Large heterogeneous mass with fatty and non-fatty components
• Fat-containing well-differentiated component adjacent to non-fatty dedifferentiated nodule
• CT: Adipose density component + solid enhancing mass
• MRI: may show transition from fat-signal to heterogeneous High-grade component

Pathology

• Non-adipocytic High-grade sarcoma (resembling MFH/UPS or myxofibrosarcoma) adjacent to WDLPS/ATLPS
• Abrupt transition between components
• MDM2 and CDK4 amplification (12q13-15) in both components
• MDM2, CDK4 IHC positive

Genetics

• MDM2 amplification - present in >95% (also in WDLPS)
• CDK4 amplification - co-amplified with MDM2
• FISH for MDM2 is gold-standard confirmation
• 12q13-15 amplification (supernumerary ring or giant marker chromosomes)

Treatment

• Wide surgical resection - often challenging in retroperitoneum
• Re-resection for recurrence
• Chemotherapy (doxorubicin/ifosfamide) - modest activity
• CDK4/6 inhibitors - clinical trials ongoing
• MDM2 inhibitors - clinical trials

Prognosis

• 5-year survival 40–50%
• High local recurrence rate in retroperitoneum (40–60%)
• Distant metastasis in 20–30%
• Retroperitoneal location associated with worse prognosis than extremity

Key Points

• MDM2 FISH is diagnostic - essential for all lipomatous tumours in retroperitoneum
• Retroperitoneal location prevents adequate margins - leading cause of death from local recurrence
• CDK4/6 inhibitors (palbociclib) showing activity in clinical trials
• De novo DDLPS (no WDLPS component seen) still harbours MDM2 amplification

Workup - Blood Tests

• FBC, U&E, LFTs - pre-operative and pre-systemic therapy baseline
• LDH - baseline

Workup - Local Imaging

• CT chest/abdomen/pelvis - first-line; fat + non-fat components in retroperitoneal mass
• MRI primary site - better soft tissue characterisation; identifies transition to dedifferentiated component

Workup - Biopsy

• Core needle biopsy - must sample non-fatty (dedifferentiated) component
• MDM2 FISH - amplification confirms DDLPS/WDLPS (gold standard)
• CDK4 and MDM2 IHC - positive in both components
• Histology: High-grade non-adipocytic sarcoma adjacent to or replacing well-differentiated lipomatous area

Workup - Staging

• CT chest/abdomen/pelvis - metastases (20–30% at presentation in High-grade disease)
• CT abdomen essential for retroperitoneal primary to assess organ involvement

Follow-up Summary

• NHS/LSESN: High-grade soft tissue sarcoma - standard intensive Follow-up protocol
• Years 1–2: 3–4 monthly clinical review + CXR; CT chest/abdomen/pelvis every 3–4 months (retroperitoneal primary)
• MRI primary site at 3 months post-op then 6-monthly for 2 years
• Years 3–5: 6-monthly clinical review; CT chest/abdomen/pelvis 6-monthly
• Years 6–10: Annual clinical review; CT chest/abdomen/pelvis annually
• Retroperitoneal DDLPS: local recurrence is dominant mode of failure - CT abdomen essential at every review
• CDK4/6 inhibitor or MDM2 inhibitor trial patients: routine toxicity monitoring at each visit
• Discharge at 10 years with documented self-monitoring advice