Elizabeth A. Montgomery, MD

Gross pathology photograph shows a leiomyosarcoma arising in association with a large deep vessel. This is a common presentation of leiomyosarcomas.

Hematoxylin & eosin shows a leiomyosarcoma associated with a large vein image. Note that the cytoplasm of the lesional cells is brightly eosinophilic, identical to that of the vein.



  • Leiomyosarcoma (LMS)


  • Malignant neoplasm composed of cells exhibiting smooth muscle differentiation


Infectious Agents

  • Epstein-Barr virus associated in immunosuppressed patients

  • Occasional examples associated with radiation



  • Incidence

    • Rare: 10-15% of extremity sarcomas

    • Most common overall sarcoma type if uterine and visceral examples are included

  • Age

    • Middle-aged adults

  • Gender

    • No gender preference overall

      • Retroperitoneal and inferior vena cava lesions more common in women


  • Deep soft tissue mass, often asymptomatic in extremities

    • Retroperitoneum most common site

      • Retroperitoneal lesions can be associated with abdominal pain

    • Vena cava examples often symptomatic

      • Upper portion: Budd-Chiari syndrome (hepatomegaly, jaundice, ascites)

      • Mid-portion: Renal obstruction

      • Lower portion: Lower extremity edema

  • Uterine examples considered separately with unique diagnostic criteria


  • Surgical excision

    • Radiation

    • Chemotherapy


  • Outcome depends on site and stage as per other sarcoma types

    • Lesions restricted to cutis essentially never metastasize

      • Some observers have advocated diagnosing them as “atypical smooth muscle tumors”

    • Subcutaneous lesions

      • Up to 1/3 of tumors metastasize

      • 10-20% of patients with subcutaneous lesion die of leiomyosarcoma

    • Retroperitoneum: About 80% of patients die of disease, typically with metastases

    • Bone: Metastases in up to 1/2 of patients

      • 5-year survival: 65%

    • Vena cava: 5- and 10-year survival: 50% and 30%, respectively

    • Head and neck

      • Few data available

      • Over 1/2 metastasize


Histologic Features

  • Perpendicularly oriented fascicles of spindle cells

  • Brightly eosinophilic cytoplasm

  • Blunt-ended nuclei

  • Nuclear atypia

  • Some examples are epithelioid

  • Any number of mitoses sufficient in subcutis, scrotal lesions, or deep soft tissue if nuclear atypia is present

  • In vulva, some observers offered > 5 mitosis per 10 HPF as “cutoff,” but recurrences reported in lesions with any mitotic activity

  • In uterus

    • Diffuse moderate to marked cytologic atypia and

    • Mitotic rate 10 or more mitoses per 10 HPFs and

    • Tumor cell necrosis

Predominant Pattern/Injury Type

  • Fascicular

Predominant Cell/Compartment Type

  • Mesenchymal, muscle, smooth

Variant and Special Forms

  • Myxoid leiomyosarcoma

    • Grossly gelatinous

    • Extensive myxoid change, but zones of typical leiomyosarcoma allow diagnosis

      • Express desmin and actin

      • Subset labels with keratin antibodies

    • Tends to be low grade

    • Clinicopathologic features otherwise as per typical leiomyosarcoma

  • Inflammatory leiomyosarcoma

    • Characterized by dense inflammation that masks underlying lesion

      • Histiocytes, xanthoma cells, lymphocytes, neutrophils

    • Areas of more typical morphology must be sought

    • Clinicopathologic features otherwise as per typical leiomyosarcoma

  • Pleomorphic leiomyosarcoma

    • Defined as pleomorphic areas in > 2/3 of tumor

      • Ordinary leiomyosarcomatous fascicular area covers < 1/3

    • More aggressive since higher grade

      • In 1 series, 65% of patients died of disease

    • Subset features osteoclast-like giant cells

  • Epstein-Barr-virus-associated leiomyosarcoma

    • a.k.a. Epstein-Barr-virus-associated smooth muscle tumors (EBV-SMT)

      • Regarded as “leiomyoma” and “leiomyosarcoma,” but term EBV-SMT may be more appropriate

      • Appearances are somewhat unique

      • Found in immunosuppressed patients

      • Frequently multifocal

      • Each tumor is unique molecular event; no clearcut metastases reported

    • Histologic features

      • Monomorphic, spindled, smooth muscle cells arranged in short intersecting fascicles

      • Subpopulation of more primitive round cells are either admixed with spindled cells or form discrete nodules

      • Variable lymphocytic infiltrate composed primarily of T cells

      • Mitotic activity variable (0-18 per 10 HPF)

      • Necrosis and myxoid change in some cases

      • All are EBV-encoded RNA (EBER) positive

      • All express SMA, desmin in ˜ 1/2

    • Reducing immunosuppression in transplant patients should be key treatment

      • Rapid tumor reduction following reduced immunosuppression reported, but some lesions persist

      • About 5% die of disease

    • Treatment is primarily surgical

    • Sirolimus (inhibitor of mTOR-associated protein pathway) effective in some lesions

  • Leiomyosarcoma with osteoclast-like giant cells

    • Same demographics as per typical leiomyosarcoma

    • Areas with same histology as per typical leiomyosarcoma

      • Reactive with smooth muscle markers: Actins and desmin

    • Areas with osteoclast-like giant cells

      • Some giant cells appear bland (like histiocytes), but others cytologically malignant

      • Benign-appearing osteoclast-like giant cells label with CD68 but not muscle markers

      • Cytologically malignant giant cells label with smooth muscle markers

    • No osteoid/matrix formation seen

  • Epithelioid leiomyosarcoma

    • Literature confounded because many epithelioid gastrointestinal stromal tumors (GIST) were termed epithelioid leiomyosarcoma in past

    • Found anywhere in body

    • Distinct epithelioid morphology but more nuclear atypia than gastrointestinal stromal tumors

    • Older studies reported actin(+), desmin(-) immunophenotype, but desmin labels most lesions using modern immunohistochemistry

      • Possible reflection of misdiagnosed GISTs

      • Less sensitive desmin antibodies in past



  • Label as per smooth muscle: Desmin, actin, calponin, caldesmon

    • Some cases label with keratins


  • Complex variable karyotypes

  • No characteristic translocation, mutation, or fusion product known

Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Leiomyosarcoma
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