Liposarcoma

Liposarcoma is a malignant tumor of adipocytic differentiation and makes up 15 to 20% of soft tissue sarcomas. It is the most common retroperitoneal sarcoma. Peak age is 50 to 65 years, except myxoid liposarcoma, which peaks at 30 to 50 years.

Subtypes

• Well-differentiated (atypical lipomatous tumor): MDM2 and CDK4 amplification, no metastatic potential in the limbs, but local recurrence and dedifferentiation in the retroperitoneum
• Dedifferentiated: a high-grade non-lipogenic component with metastatic potential in about 15 to 20%
• Myxoid and round cell: FUS-DDIT3 fusion from t(12;16), thigh, metastases to bone, soft tissue and retroperitoneum, radiosensitive
• Pleomorphic: aggressive, with a high metastatic rate

The 5-year survival is about 90% for well-differentiated tumors in the extremities, 45 to 60% for dedifferentiated, 80 to 90% for myxoid and about 60% for pleomorphic. Retroperitoneal disease recurs locally in over half. Complications: local recurrence, distant spread, and compression of kidneys, ureters and bowel.

• A painless, slowly enlarging deep mass over months to years
• Retroperitoneal: abdominal fullness, early satiety, pain, weight loss, and urinary or bowel symptoms
• Myxoid: a thigh mass, with possible extension into the retroperitoneum or bone pain from metastases
• Red flags: rapid growth, size over 10 cm, firm non-lipomatous areas, pain, neurovascular symptoms

1. MRI with gadolinium (extremity): a fatty mass with thick septa and non-fatty nodular enhancing areas. CT with contrast (retroperitoneum): fat attenuation with enhancing soft tissue components.
2. Core biopsy (image-guided) when imaging suggests sarcoma, and in any fatty mass that is deep, over 10 cm, or has non-fatty nodules. MDM2 FISH distinguishes well-differentiated liposarcoma from lipoma.
3. Molecular tests: FUS-DDIT3 for myxoid tumors.
4. Staging: CT chest, and spine and bone MRI for myxoid tumors because they metastasize to bone and extrapulmonary sites.

Differentials: lipoma, hibernoma, angiomyolipoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, renal and adrenal masses.

• Surgery: wide excision with negative margins. Retroperitoneal tumors: en bloc compartmental resection, including the kidney, colon or other involved organs when the tumor is adherent. Well-differentiated limb tumors: marginal excision is acceptable.
• Prophylaxis: cefazolin 2 g IV before incision (3 g if over 120 kg), and enoxaparin 40 mg SC daily for 28 days after major abdominal cancer surgery.
• Radiotherapy: preoperative 50.4 Gy in 28 fractions for extremity tumors of intermediate and high grade (a reduced dose of 36 Gy can be used for myxoid tumors), and selected retroperitoneal tumors.
• Chemotherapy for high-grade, advanced or myxoid disease:
  • Doxorubicin 75 mg/m2 IV every 21 days for 6 cycles, with ifosfamide 9 g/m2 over 3 days (with mesna at 100% of the ifosfamide dose in divided IV doses) when a high response rate is needed. Check cardiac function, creatinine and neurotoxicity (ifosfamide encephalopathy treated with methylene blue 50 mg IV every 6 hours), and monitor for hemorrhagic cystitis.
  • Trabectedin 1.5 mg/m2 IV over 24 hours every 21 days (very effective in myxoid disease), with dexamethasone premedication and checks of liver tests and creatine kinase.
  • Eribulin 1.4 mg/m2 IV on days 1 and 8 every 21 days, with filgrastim as needed.
• Metastatic myxoid disease: radiotherapy to bone and soft tissue deposits.

Follow-up: retroperitoneal tumors with CT every 3 to 4 months for 2 years, then every 6 months to year 5. Extremity tumors need MRI and chest imaging. Well-differentiated disease needs long-term follow-up since recurrence can occur after 10 years.