LIPOSARCOMA
Malignant Adipocytic Tumor | Most Common Adult Sarcoma | Variable Prognosis by Subtype
WHO Histological Classification
Critical Must-Knows
- Most common soft tissue sarcoma in adults (24% of all sarcomas)
- Well-differentiated liposarcoma (atypical lipomatous tumor) has excellent prognosis in extremity
- MDM2 amplification distinguishes well-differentiated liposarcoma from lipoma
- Dedifferentiated liposarcoma has high metastatic potential (15-30%)
- Wide excision with negative margins is cornerstone of treatment
Examiner's Pearls
- "Atypical lipomatous tumor and well-differentiated liposarcoma are same entity, different names by location
- "Myxoid liposarcoma is radiosensitive unlike other sarcomas
- "Retroperitoneal liposarcomas have worse prognosis than extremity due to margins
- "Round cell variant of myxoid has worse prognosis and higher metastatic rate
Clinical Imaging
Imaging Gallery
Critical Liposarcoma Exam Points
Histological Subtypes and Prognosis
Well-differentiated (best), myxoid (intermediate), dedifferentiated/pleomorphic (worst) - Subtype determines prognosis and treatment. Five-year survival ranges from 80% for well-differentiated extremity lesions to 30% for pleomorphic.
Molecular Diagnostics
MDM2 amplification for well-differentiated, FUS-DDIT3 fusion for myxoid - Molecular testing is diagnostic. MDM2 positive distinguishes atypical lipomatous tumor from benign lipoma. FUS-DDIT3 confirms myxoid subtype.
Surgical Margins
Wide excision with 1-2cm margins - Margin status is most important prognostic factor. Positive margins lead to 30-50% local recurrence. Re-excision mandatory if margins positive.
Adjuvant Therapy
Radiation for high-grade, chemotherapy for dedifferentiated/pleomorphic - Myxoid liposarcoma is uniquely radiosensitive. Doxorubicin-based chemotherapy for high-grade subtypes.
WDMPLiposarcoma WHO Subtypes (Prognosis Order)
Memory Hook:WDMP - prognosis goes from Well (best) to Pleomorphic (worst) in alphabetical order!
Overview and Epidemiology
Liposarcoma is the most common soft tissue sarcoma in adults, accounting for 20-24% of all adult sarcomas. Unlike lipoma (benign adipocytic tumor), liposarcoma demonstrates malignant potential with capacity for local recurrence and distant metastasis. The tumor arises from primitive mesenchymal cells rather than mature adipocytes, explaining its variable differentiation and behavior.
Nomenclature Distinction
Atypical lipomatous tumor (ALT) versus well-differentiated liposarcoma (WDLS): These are the SAME entity. Extremity/superficial lesions are called ALT due to negligible metastatic potential. Deep-seated retroperitoneal lesions are called WDLS due to higher recurrence risk from incomplete excision. Both show MDM2 amplification.
Demographics
- Age: Peak 50-65 years (median 55)
- Gender: Slight male predominance (M:F 1.2:1)
- Location: 75% extremity or trunk, 25% retroperitoneum
- Hereditary: Rare Li-Fraumeni syndrome cases
Location Distribution
- Extremity: 60% (thigh most common)
- Retroperitoneum: 20% (worse prognosis)
- Trunk: 15%
- Head/neck: 5% (rare)
Pathophysiology and Anatomy
Anatomical Distribution
Liposarcomas arise from mesenchymal precursors and can develop in any location with adipose tissue. Location significantly impacts surgical approach and prognosis.
| Location | Frequency | Anatomical Considerations | Prognosis Impact |
|---|---|---|---|
| Thigh (anterior/posterior) | 40% | Deep compartments, femoral vessels/nerve proximity | Best prognosis, limb salvage greater than 95% |
| Retroperitoneum | 20% | Large at diagnosis, organ displacement, IVC/aorta adjacent | Worse prognosis, 40% recurrence |
| Trunk/shoulder | 15% | Variable depth, chest/abdominal wall | Intermediate prognosis |
| Arm/forearm | 15% | Smaller compartments, neurovascular proximity | Good, smaller tumors |
| Head/neck | 5% | Rare, complex anatomy | Variable by site |
Tumor Biology
Cellular Origin
- Arises from mesenchymal stem cells (not mature adipocytes)
- Clonal chromosomal aberrations (MDM2, FUS-DDIT3)
- Variable differentiation determines subtype
- Can dedifferentiate over time (worse prognosis)
Compartmental Spread
- Respects fascial boundaries initially
- Intramuscular spread along muscle fibers
- Eventually breaks through compartments
- Retroperitoneal tumors infiltrate adjacent organs
Classification Systems
WHO 2020 Classification of Liposarcoma
| Subtype | Frequency | Key Features | Molecular Marker | 5-Year Survival |
|---|---|---|---|---|
| Well-differentiated (ALT) | 40-45% | Mature fat with atypical cells, thick septa | MDM2/CDK4 amplification | 80-90% (extremity) |
| Dedifferentiated | 10-15% | High-grade non-lipogenic within well-diff | MDM2+ with high-grade areas | 30-40% |
| Myxoid | 25-30% | Myxoid matrix, lipoblasts, arborizing vessels | FUS-DDIT3 fusion | 70% |
| Round cell (high-grade myxoid) | 5% | greater than 5% round cells in myxoid background | FUS-DDIT3 fusion | 40% |
| Pleomorphic | 5-10% | High-grade, pleomorphic lipoblasts | Complex karyotype | 30% |
Classification determines treatment approach all prognosis.
Histology and Molecular Pathology
WHO Classification (2020)
The WHO classifies liposarcoma into four main subtypes based on histological and molecular features. This classification has direct prognostic and therapeutic implications.
| Subtype | Frequency | Molecular Marker | 5-Year Survival |
|---|---|---|---|
| Well-differentiated (ALT) | 40-45% | MDM2/CDK4 amplification | 80-90% (extremity) |
| Myxoid/Round cell | 30-35% | FUS-DDIT3 fusion (t12;16) | 70% (myxoid), 30% (round cell) |
| Dedifferentiated | 10-15% | MDM2+ with high-grade areas | 30-40% |
| Pleomorphic | 5-10% | Complex karyotype, no specific marker | 30% |
Molecular Diagnostics
Well-Differentiated Liposarcoma
MDM2 amplification is the diagnostic hallmark of well-differentiated and dedifferentiated liposarcoma.
Testing methods:
- FISH (fluorescence in situ hybridization): Gold standard
- Immunohistochemistry: Screening tool (MDM2 and CDK4 overexpression)
- Next-generation sequencing: Can detect amplification
Clinical significance:
- Positive MDM2 confirms diagnosis (distinguishes from lipoma)
- Negative MDM2 excludes well-differentiated/dedifferentiated subtype
- Helps guide surgical planning (wide margins required)
MDM2 testing is essential for any deep or large fatty tumor to distinguish benign lipoma from atypical lipomatous tumor.
Pathology Pitfalls
Diagnostic errors to avoid:
- Pleomorphic lipoma (benign with bizarre nuclei) versus pleomorphic liposarcoma: MDM2 negative in benign variant
- Spindle cell lipoma versus spindle cell liposarcoma: Clinical and molecular distinction essential
- Myxoid liposarcoma versus myxofibrosarcoma: FUS-DDIT3 testing differentiates
- Well-differentiated liposarcoma versus lipoma: MDM2 amplification is key
MFMolecular Markers for Liposarcoma Diagnosis
Memory Hook:MF = Molecular Fingerprints - MDM2 for Well-differentiated, FUS for myxoiD!
Clinical Assessment
History
Presenting Symptoms
- Painless mass: Most common (70-80%)
- Growing mass: Noticed over months
- Pain: 20-30% (compression of nerves/vessels)
- Functional impairment: Large masses affecting movement
Red Flags for High-Grade
- Rapid growth: Over weeks to months
- Systemic symptoms: Weight loss, malaise
- Large size: Greater than 10cm
- Deep location: Retroperitoneal or intramuscular
Physical Examination
Examination Approach
Observe:
- Size (measure in cm)
- Location (superficial vs deep)
- Skin changes (rare except for large tumors)
- Asymmetry of limb
Assess:
- Consistency (firm to hard; unlike soft lipomas)
- Mobility (deep lesions fixed to fascia/muscle)
- Tenderness (usually non-tender)
- Fixation to skin or deep structures
Document:
- Distal pulses
- Sensory and motor function
- Nerve compression signs
- Vascular compression (venous congestion)
Palpate regional lymph nodes (nodal metastasis rare in sarcomas but check baseline)
Lymph node involvement uncommon in liposarcoma (less than 5% except for myxoid round cell variant).
Investigations and Staging
Imaging Protocol
MRI (Investigation of Choice)
MRI is the gold standard for local staging of soft tissue sarcomas.
Protocol:
- T1-weighted: Anatomical detail, fat signal
- T2-weighted with fat suppression: Tumor extent, edema
- Post-contrast T1 with fat suppression: Enhancement pattern
- Include entire muscle compartment plus joint above and below
Features of Liposarcoma:
| Subtype | MRI Characteristics |
|---|---|
| Well-differentiated | Predominantly fat signal with thick septa (greater than 2mm), nodular areas |
| Dedifferentiated | Mixed fat and solid enhancing areas (high-grade component) |
| Myxoid | High T2 signal (myxoid matrix), minimal fat, lacy enhancement |
| Pleomorphic | Heterogeneous, minimal fat, irregular enhancement, necrosis |
MRI guides biopsy planning and surgical approach.
Biopsy
Biopsy Principles for Sarcoma
Critical rules:
- Core needle biopsy (14-16 gauge) is preferred over incisional biopsy
- Biopsy tract must be excisable at definitive surgery (plan incision)
- Avoid contaminating neurovascular structures or adjacent compartments
- Request MDM2 or FUS-DDIT3 testing on biopsy specimen
- Never perform excisional biopsy for suspected sarcoma (risks seeding, inadequate margins)
Referral to sarcoma center before biopsy is ideal for optimal outcomes.
Staging System
AJCC 8th Edition Staging (Extremity/Trunk)
| Stage | Grade | Size/Depth | 5-Year Survival |
|---|---|---|---|
| IA | Low (G1) | Superficial or deep, any size | 90% |
| IB | Low (G1) | Deep, greater than 5cm | 80% |
| II | Low (G1) | Deep, greater than 10cm | 75% |
| IIIA | High (G2-3) | Superficial/deep, under 5cm | 60% |
| IIIB | High (G2-3) | Deep, 5-10cm or greater than 10cm | 50% |
| IV | Any | Metastatic disease | 15-20% |
MBCPMLiposarcoma Staging Workup
Memory Hook:MBCPM = Must Be Checked Pre-Management - complete staging before surgery!
Management
Treatment Algorithm
Treatment Decision Matrix
| Subtype/Stage | Primary Treatment | Adjuvant Therapy | Prognosis |
|---|---|---|---|
| Well-differentiated, extremity | Wide excision (1-2cm margins) | None (low grade) | Excellent (80-90% 5-year) |
| Myxoid, localized | Wide excision | Radiation (radiosensitive) | Good (70% 5-year) |
| Dedifferentiated/pleomorphic | Wide excision | Radiation + chemotherapy | Poor (30-40% 5-year) |
| Retroperitoneal (any grade) | Complete resection + organs | Radiation (consider preop) | Variable (50% 5-year) |
Surgical Management
Extremity Liposarcoma Resection
Goal: Complete excision with negative margins (R0 resection)
Margin definition:
- Negative margin: Greater than 1mm clear tissue
- Wide margin: 1-2cm of normal tissue (goal for extremity sarcomas)
- Marginal: Tumor capsule or pseudocapsule (inadequate)
- Intralesional: Tumor violation (unacceptable)
Surgical Principles
- Review MRI with radiology and surgical team
- Identify neurovascular structures at risk
- Plan incision along biopsy tract (excise entire tract)
- Mark margins on skin based on MRI
- Excise biopsy tract en bloc with tumor
- Dissect along fascial planes (preserve compartment barriers)
- Achieve 1-2cm margin in all dimensions if feasible
- Protect critical neurovascular structures (accept closer margins if necessary)
- Remove tumor with surrounding cuff of normal tissue
- Mark specimen margins with sutures for pathologist
- Send frozen section if margin status uncertain
- Document neurovascular preservation
- Soft tissue coverage: Primary closure, flap, skin graft
- Functional reconstruction: Tendon transfers if muscle resected
- Drain placement for large dead spaces
- Limb salvage in over 95% of extremity sarcomas
Reconstruction planning is essential before resection.
Adjuvant Radiotherapy
| Indication | Timing | Dose | Benefit |
|---|---|---|---|
| High-grade extremity sarcoma | Preoperative or postoperative | 50 Gy (preop) or 60-66 Gy (postop) | Reduces local recurrence from 30% to 10% |
| Myxoid liposarcoma | Postoperative (radiosensitive) | 50-60 Gy | Excellent local control, superior to other subtypes |
| Positive margins (R1) | Postoperative | 66 Gy to margin | Improves local control but re-excision preferred |
| Retroperitoneal sarcoma | Preoperative (consider) | 50-50.4 Gy | Controversial benefit, reduces tumor size |
Myxoid Liposarcoma Radiosensitivity
Myxoid liposarcoma is uniquely radiosensitive among soft tissue sarcomas. Radiotherapy produces excellent local control and may achieve near-complete pathological response. This is attributed to FUS-DDIT3 fusion affecting DNA repair mechanisms. Radiation is standard adjuvant therapy for myxoid subtype.
Chemotherapy
Indications:
- High-grade liposarcoma (dedifferentiated, pleomorphic, round cell myxoid)
- Metastatic disease
- Neoadjuvant for large/unresectable tumors
Regimens:
- Doxorubicin + ifosfamide: Standard first-line (response rate 25-30%)
- Trabectedin: Active in myxoid liposarcoma (response rate 50% for myxoid subtype)
- Eribulin: Second-line option for dedifferentiated liposarcoma
Well-differentiated liposarcoma does not respond to chemotherapy.
Prognosis and Surveillance
Prognostic Factors
| Factor | Favorable | Unfavorable |
|---|---|---|
| Histological subtype | Well-differentiated, myxoid | Dedifferentiated, pleomorphic, round cell |
| Tumor size | Less than 5cm | Greater than 10cm |
| Tumor depth | Superficial | Deep (subfascial) |
| Margin status | Negative (R0) | Positive (R1/R2) |
| Location | Extremity | Retroperitoneum |
| Grade | Low (G1) | High (G2-3) |
Surveillance Protocol
Follow-Up Schedule
- Clinical examination
- MRI of primary site every 6 months
- CT chest every 6 months (high-grade subtypes)
- Clinical examination
- MRI primary site annually
- CT chest annually (high-grade subtypes)
- Clinical examination
- Imaging as clinically indicated
- Well-differentiated may recur late (10+ years)
Surveillance continues indefinitely for well-differentiated/dedifferentiated due to late recurrence risk.
Surgical Technique
Extremity Liposarcoma Excision - Step by Step
Surgical Protocol for Wide Excision
Preparation:
- Review MRI with surgical and radiology team
- Mark tumor extent on skin with MRI guidance
- Identify biopsy tract for en bloc excision
- Plan incision, reconstruction, and contingency for vessels/nerves
Setup:
- Position for optimal access to entire tumor
- Tourniquet for extremity lesions (bloodless field)
- Wide skin flaps to visualize compartment fully
- Identify and protect major neurovascular structures
Excision:
- Excise biopsy tract with tumor (contaminated tissue)
- Dissect along fascial planes with 1-2cm margins
- Accept closer margins on critical structures (vessels, nerves, bone)
- Frozen section if margin uncertain (intraoperative pathology)
Orientation and submission:
- Orient specimen with sutures (superior, lateral, deep)
- Ink margins if concerned about specific areas
- Send to pathology fresh for molecular testing if needed
- Document margin distances from critical structures
Closure options:
- Primary closure if tension-free
- Local flaps or skin grafts for large defects
- Vascular repair if sacrifice was necessary
- Drain placement for dead space management
Limb salvage achieved in greater than 95% of extremity sarcomas.
Intraoperative Considerations
Positive Margin Management
If frozen section shows positive margin:
- Re-excise immediately if feasible
- Document location for postoperative radiation boost
- Accept closer margin on vessels/nerves (radiation can cover)
- Do NOT compromise limb function for marginal gains
Critical Structure Decisions
When approaching nerve/vessel:
- Preserve if 1mm or more margin achievable
- Sacrifice if tumor encases structure
- Vascular reconstruction possible
- Nerve sacrifice: document for rehab planning
Complications
Perioperative Complications
| Complication | Incidence | Risk Factors | Management |
|---|---|---|---|
| Local recurrence | 10% (R0) to 50% (R1) | Positive margins, high grade, retroperitoneal | Re-excision ± radiation, MDT review |
| Distant metastases | 10-30% (high-grade) | Dedifferentiated, pleomorphic, round cell | Systemic chemotherapy, palliative care |
| Wound complications | 10-20% | Preoperative radiation, large resection | VAC therapy, debridement, flap coverage |
| Nerve injury | 5-10% | Proximity to major nerves, sacrifice | Physiotherapy, tendon transfers, orthotics |
| DVT/PE | 5-10% | Lower extremity surgery, prolonged immobility | Prophylaxis, early mobilization, anticoagulation |
Late Complications
Chronic Lymphedema
Risk factors:
- Groin/axillary dissection
- Postoperative radiotherapy
- Extensive resection
Management: Compression, lymphatic massage, elevation
Radiation Fibrosis
Effects:
- Skin changes (telangiectasia, thinning)
- Muscle/fascia fibrosis
- Joint stiffness
- Secondary malignancy (rare, 1%)
Prevention: Preoperative RT has lower fibrosis than postoperative
Postoperative Care
Standard Recovery Protocol
Postoperative Management
Inpatient care:
- Wound monitoring (flap viability, drainage)
- DVT prophylaxis (mechanical + pharmacological)
- Pain management (multimodal analgesia)
- Early mobilization with physiotherapy
Ward care:
- Drain management (remove when less than 30ml/24h)
- Wound assessment (infection, dehiscence)
- Progressive mobilization
- Discharge planning when mobile and wound stable
Clinic review:
- Wound check, suture removal
- Final histology and margin review
- MDT discussion of adjuvant therapy
- Radiation planning if indicated
If indicated:
- Radiotherapy (50-66 Gy over 5-7 weeks)
- Chemotherapy for high-grade (doxorubicin-based)
- Continue physiotherapy during adjuvant treatment
Treatment completion marks start of surveillance phase.
Functional Rehabilitation
| Scenario | Rehabilitation Focus | Expected Outcome |
|---|---|---|
| Standard excision (muscle sparing) | ROM, strengthening, return to activity | Full function 6-12 weeks |
| Muscle resection (single muscle) | Compensatory strengthening, gait training | Good function with adaptation |
| Nerve sacrifice (femoral, sciatic) | Orthotics, tendon transfers, gait retraining | Functional ambulation achievable |
| Post-radiation complications | Gentle ROM, lymphedema management | Variable, may require intensive therapy |
Australian Context
Sarcoma Service Referral
Australian sarcoma centers:
- Peter MacCallum Cancer Centre (VIC)
- Royal Prince Alfred Hospital (NSW)
- Princess Alexandra Hospital (QLD)
- Royal Perth Hospital (WA)
Referral indication: Any suspected soft tissue sarcoma should be referred BEFORE biopsy.
Medicare and PBS
Funding considerations:
- MRI and CT staging: Medicare rebateable
- MDM2/FISH testing: Available at sarcoma centers
- Trabectedin: PBS-listed for myxoid liposarcoma
- Radiation: Public hospital access, private options available
Medicolegal Considerations
Key documentation requirements:
- Pre-biopsy imaging and staging completed
- Biopsy performed by or in consultation with sarcoma team
- MDT discussion documented before definitive surgery
- Informed consent including recurrence risk, margin status, adjuvant therapy
- Surveillance plan documented at discharge
Common litigation issues:
- Excision of suspected lipoma without imaging/biopsy (missed liposarcoma)
- Inadequate margins requiring re-excision
- Failure to refer to sarcoma MDT
- Inadequate surveillance leading to late detection of recurrence
Evidence Base and Key Studies
Liposarcoma Epidemiology and Classification
- Liposarcoma accounts for 24% of all soft tissue sarcomas
- Well-differentiated subtype most common (40-45%)
- Extremity well-differentiated has better prognosis than retroperitoneal
- Dedifferentiated subtype has 15-30% distant metastasis rate
MDM2 Amplification in Atypical Lipomatous Tumor
- MDM2 amplification present in 95% of well-differentiated liposarcomas
- Absent in benign lipomas (100% specificity)
- FISH testing is gold standard for diagnosis
- Enables distinction of ALT from lipoma in difficult cases
Trabectedin in Myxoid Liposarcoma
- Trabectedin achieves 50% response rate in myxoid liposarcoma
- Superior efficacy compared to other sarcoma subtypes
- Mechanism: Targets FUS-DDIT3 fusion protein
- Approved for advanced myxoid liposarcoma in Europe/US
Radiotherapy in Myxoid Liposarcoma
- Myxoid liposarcoma more radiosensitive than other sarcomas
- Radiation achieves excellent local control (over 90%)
- Lower radiation doses effective compared to other subtypes
- Pathological complete response in 20% of cases
Margin Impact on Recurrence in Extremity Sarcoma
- Positive margins increase local recurrence from 10% to 30-50%
- Re-excision to achieve negative margins reduces recurrence
- Margin width (under 1mm vs greater than 1mm) significant
- Radiation can mitigate but not eliminate positive margin impact
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
Scenario 1: Deep Thigh Mass - Diagnosis and Staging
"A 55-year-old man presents with a 10cm deep mass in his thigh that has grown over 6 months. MRI shows a predominantly fatty mass with thick septations and some solid enhancing areas. What is your differential diagnosis and initial management?"
Scenario 2: Surgical Margins and Re-excision
"You excised a 12cm deep thigh mass thinking it was a lipoma. Histology returns as dedifferentiated liposarcoma with positive deep margin (tumor 1mm from fascia). The patient is 10 days post-op. How do you proceed?"
Scenario 3: Myxoid Liposarcoma Treatment Planning
"Biopsy of a 15cm calf mass confirms myxoid liposarcoma, FUS-DDIT3 positive. CT staging shows no metastases. The tumor is close to the tibial nerve. The MDT asks for your surgical plan. What do you propose?"
MCQ Practice Points
Histology Question
Q: What molecular marker distinguishes well-differentiated liposarcoma from benign lipoma? A: MDM2 amplification - MDM2 and CDK4 amplification detected by FISH is diagnostic for well-differentiated liposarcoma (atypical lipomatous tumor) and absent in benign lipoma. This testing is essential for any deep or large fatty tumor to guide surgical planning.
Subtype Question
Q: Which liposarcoma subtype is most radiosensitive and why? A: Myxoid liposarcoma - This subtype shows unique radiosensitivity attributed to the FUS-DDIT3 fusion protein affecting DNA repair. Radiotherapy achieves excellent local control and may produce near-complete pathological response. This is the only soft tissue sarcoma subtype where radiation is more effective than others.
Prognosis Question
Q: What is the 5-year survival for extremity well-differentiated liposarcoma after complete excision? A: 80-90% - Extremity well-differentiated liposarcoma (atypical lipomatous tumor) has excellent prognosis with wide excision achieving negative margins. Metastatic potential is less than 2%. In contrast, retroperitoneal well-differentiated liposarcoma has worse prognosis (50% 5-year survival) due to difficulty achieving negative margins and higher recurrence rate.
Treatment Question
Q: What is the most important prognostic factor for local recurrence in liposarcoma? A: Surgical margin status - Negative margins (R0 resection) are associated with 10% local recurrence. Positive margins increase recurrence to 30-50%. Re-excision to achieve negative margins significantly improves local control and is mandatory if initial margins positive.
Molecular Question
Q: What chromosomal translocation is pathognomonic for myxoid liposarcoma? A: t(12;16) producing FUS-DDIT3 fusion - This translocation is present in 95% of myxoid liposarcomas. Alternative fusion EWSR1-DDIT3 from t(12;22) occurs in 5%. Detection by RT-PCR or FISH confirms diagnosis and has therapeutic implications (radiosensitivity, trabectedin efficacy).
LIPOSARCOMA
High-Yield Exam Summary
Key Epidemiology
- •Most common soft tissue sarcoma in adults (24% of all sarcomas)
- •Peak age 50-65 years, slight male predominance
- •75% extremity/trunk, 25% retroperitoneum
- •Incidence 2.5 per million per year
WHO Classification (Prognosis)
- •Well-differentiated (40-45%) = ALT = MDM2+ = 80-90% 5-year (extremity)
- •Myxoid (30-35%) = FUS-DDIT3 = radiosensitive = 70% 5-year
- •Dedifferentiated (10-15%) = MDM2+ with high-grade = 30-40% 5-year
- •Pleomorphic (5-10%) = poorest prognosis = 30% 5-year
Molecular Markers (MF Mnemonic)
- •MDM2 for Well-differentiated/dedifferentiated (FISH gold standard)
- •FUS-DDIT3 for Myxoid (t12;16 translocation)
- •MDM2 negative excludes well-differentiated/dedifferentiated
- •Round cell variant (greater than 5% round cells) worse prognosis
Staging Workup (MBCPM Mnemonic)
- •MRI of primary = local staging and surgical planning
- •Biopsy (core needle 14-16G) = never excisional biopsy
- •CT chest = rule out lung metastases
- •PET-CT if myxoid = FDG-avid subtype
- •MDT discussion = before definitive treatment
Surgical Principles
- •Wide excision with 1-2cm margins (R0 resection goal)
- •Excise biopsy tract en bloc with tumor
- •Positive margins mandate re-excision (within 2-4 weeks)
- •Limb salvage possible in over 95% extremity sarcomas
- •Retroperitoneal requires organ resection, accept close margins on vessels
Adjuvant Therapy
- •Radiotherapy for high-grade or close/positive margins (reduces recurrence 30% to 10%)
- •Myxoid subtype uniquely radiosensitive (preop RT 50 Gy)
- •Chemotherapy: Doxorubicin + ifosfamide for high-grade
- •Trabectedin highly active in myxoid subtype (50% response)
- •Well-differentiated does NOT respond to chemotherapy
Prognosis and Surveillance
- •5-year survival: Well-differentiated extremity 80-90%, myxoid 70%, dediff/pleo 30-40%
- •Positive margins increase local recurrence from 10% to 30-50%
- •Follow-up: Q3-4mo years 1-2, Q6mo years 3-5, annual after 5 years
- •MRI primary site and CT chest (high-grade) per schedule
- •Well-differentiated can recur late (10+ years) - indefinite surveillance