Leiomyosarcoma

Leiomyosarcoma is a malignant smooth muscle tumor and makes up 10 to 20% of soft tissue sarcomas. Common sites are the uterus, retroperitoneum, inferior vena cava, limbs, skin and subcutis, and the gastrointestinal tract. Peak age is 50 to 70 years. Risk factors are prior radiotherapy, retinoblastoma (germline RB1 mutation), Li-Fraumeni syndrome, and Epstein-Barr virus infection in immunocompromised patients (HIV, transplant recipients).

Grade is based on differentiation, mitotic count and necrosis. Biology: loss of TP53, RB1 and PTEN, and complex karyotype. Spread is hematogenous, to the lung and liver. Lymph node metastases are uncommon. Outcomes: 5-year survival 60 to 70% for localized extremity disease, 30 to 50% for retroperitoneal tumors, and about 40% for stage I uterine disease. Complications: local recurrence, distant metastases, organ obstruction, and for caval tumors, venous outflow obstruction.

• A painless, enlarging deep mass in an extremity or the trunk
• Retroperitoneal: abdominal distension, early satiety, back pain, leg edema and weight loss
• Uterine: abnormal vaginal bleeding and a rapidly growing pelvic mass
• Caval: leg edema, ascites and hepatic dysfunction
• Cutaneous: a firm dermal nodule that may ulcerate
• Red flags: rapid growth, size over 5 cm, deep location, pain, new respiratory symptoms

1. MRI (extremity, pelvis) or CT with contrast (retroperitoneum, abdomen): a heterogeneous mass with necrosis and variable enhancement. MR or CT angiography for a caval tumor.
2. Core needle biopsy before treatment (image-guided, with a coaxial approach, and planned along the future surgical tract). Histology: spindle cells with blunt-ended nuclei, positive for desmin, smooth muscle actin and h-caldesmon. Ki-67 and mitotic count for grade.
3. Staging: CT chest, and CT abdomen and pelvis. PET-CT in selected patients.
4. Uterine tumors: endometrial sampling is often non-diagnostic, and LDH may be raised.
5. Genetics: germline testing in young patients and in those with a family history.

Differentials: leiomyoma variants, gastrointestinal stromal tumor, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, carcinosarcoma, metastasis.

• Surgery: wide resection with negative margins (a 1 to 2 cm margin in extremity tumors, or an anatomical barrier such as fascia). Retroperitoneal tumors: en bloc resection with adjacent organs. Uterine tumors: total hysterectomy without morcellation, with oophorectomy at the surgeon's discretion. Caval tumors: resection with reconstruction using a graft.
• Prophylaxis: cefazolin 2 g IV before incision (3 g if over 120 kg), and enoxaparin 40 mg SC daily for 28 days after major cancer surgery.
• Radiotherapy: 50 Gy in 25 fractions before or after surgery for high-grade extremity tumors and close margins, and selected retroperitoneal tumors.
• Advanced or metastatic disease:
  • Doxorubicin 75 mg/m2 IV every 21 days for 6 cycles (maximum cumulative dose 450 to 550 mg/m2, with echocardiogram before treatment and after 300 mg/m2), with or without dacarbazine 800 to 1000 mg/m2 IV.
  • Gemcitabine 900 mg/m2 IV on days 1 and 8 with docetaxel 75 mg/m2 IV on day 8, every 21 days, with filgrastim.
  • Trabectedin 1.5 mg/m2 IV over 24 hours every 21 days after anthracycline (premedicate with dexamethasone 4 mg orally twice daily for 3 days, check liver tests and creatine kinase before each cycle).
  • Eribulin 1.4 mg/m2 IV on days 1 and 8 every 21 days, or pazopanib 800 mg orally once daily (monitor blood pressure and liver tests).
• Metastasectomy for isolated resectable lung metastases.

Follow-up: MRI or CT of the primary site and CT chest every 3 to 4 months for 2 to 3 years, every 6 months to year 5, then yearly. Counsel on late recurrence, which is common in this tumor.