Leiomyosarcoma: Soft Tissue Sarcoma of Smooth Muscle — Overview, Diagnosis & Treatment Options | MyMedicPlus

Leiomyosarcoma (LMS) is a malignant smooth muscle tumor representing 5-10% of all soft tissue sarcomas. Common primary sites include the uterus (most common, approximately 40% of all LMS), retroperitoneum, large blood vessels (IVC, femoral vein), and extremities. Approximately 2,000 new US cases are diagnosed annually. Uterine LMS accounts for 1-2% of all uterine malignancies but causes 25-35% of uterine cancer deaths due to its aggressive behavior.

Most LMS cases are sporadic without identifiable cause. Prior radiation therapy to the pelvis increases the risk of radiation-induced sarcoma, including LMS, with a latency period of 5-30 years. Li-Fraumeni syndrome (TP53 germline mutation) predisposes to sarcomas including LMS. Tamoxifen use has been associated with an increased risk of uterine sarcomas. IDH mutations and PTEN deletions are common somatic events. ATRX mutations are present in approximately 25% of LMS and associated with alternative lengthening of telomeres (ALT). No environmental or dietary risk factors are firmly established.

Uterine LMS presents with abnormal uterine bleeding, pelvic pain or pressure, rapid uterine enlargement, and postmenopausal uterine mass. Retroperitoneal LMS causes diffuse abdominal or back pain, an enlarging abdominal mass, and gastrointestinal or urinary symptoms from compression of adjacent structures. Extremity LMS presents as a deep enlarging soft tissue mass, which may be painless initially. Constitutional symptoms (weight loss, fatigue) indicate advanced or metastatic disease. Large tumors may compress adjacent neurovascular structures.

MRI with gadolinium is the preferred imaging modality for local staging, delineating tumor borders, vascular involvement, and compartmentalization. CT of chest, abdomen, and pelvis evaluates for pulmonary and hepatic metastases. Core needle biopsy in the resection plane provides tissue for FNCLCC grade, smooth muscle actin, desmin, and h-caldesmon immunohistochemistry. Molecular testing for ATRX, IDH1/2, and TP53 aids diagnosis and may predict behavior. AJCC 8th edition soft tissue sarcoma TNM staging applies. FDG-PET may be used for assessing treatment response and detecting metastases.

Wide surgical excision with negative margins (R0 resection) is the primary treatment. Uterine LMS: total hysterectomy plus bilateral salpingo-oophorectomy (BSO); lymphadenectomy does not improve survival. Perioperative radiation is considered for high-risk retroperitoneal or extremity LMS. Adjuvant chemotherapy for high-risk LMS (doxorubicin plus ifosfamide or gemcitabine plus docetaxel for uterine LMS) is used based on institutional practice but without definitive Level 1 evidence. Metastatic LMS: doxorubicin monotherapy or in combination; gemcitabine plus docetaxel (particularly for uterine LMS); trabectedin; eribulin; pazopanib; dacarbazine.

Five-year overall survival: localized extremity LMS approximately 50-70%; retroperitoneal LMS approximately 30-40% (due to difficulty achieving R0 margins); uterine LMS localized approximately 40-55%, advanced approximately 10-25%. High FNCLCC grade and retroperitoneal location are the strongest adverse prognostic factors. Approximately 50-70% of patients with localized high-grade LMS develop distant metastases within 2-3 years. Selected patients with isolated pulmonary metastases may benefit from metastatectomy, with 2-year post-resection survival of approximately 25-30%.

No established prevention strategy exists for sporadic LMS. Unnecessary pelvic radiation should be avoided to minimize radiation-induced sarcoma risk. Patients with Li-Fraumeni syndrome (TP53 germline mutation) require annual whole-body MRI surveillance. The rare risk that a uterine mass is LMS (approximately 1 in 2,000) does not justify prophylactic hysterectomy for all fibroids, but rapid growth or atypical features should prompt investigation. Power morcellation should be avoided in presumed myomectomy or hysterectomy for fibroids due to the risk of disseminating occult uterine sarcoma.