Leiomyosarcoma



Leiomyosarcoma


Elizabeth A. Montgomery, MD





Key Facts


Terminology



  • Malignant neoplasm composed of cells exhibiting smooth muscle differentiation


Etiology/Pathogenesis



  • Epstein-Barr virus-associated in immunosuppressed patients


Clinical Issues



  • Retroperitoneal and inferior vena cava lesions more common in women


  • Deep soft tissue mass, often asymptomatic in extremities


  • Retroperitoneum most common site


  • Site and stage dependent as per other sarcoma types


  • Surgical excision


  • Rare: 10-15% of extremity sarcomas


  • Most common sarcoma type if uterine examples are included


Microscopic Pathology



  • Perpendicularly oriented fascicles of spindle cells


  • Brightly eosinophilic cytoplasm


  • Blunt-ended nuclei


  • Nuclear atypia


Ancillary Tests



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



    • Some cases label with keratins


Top Differential Diagnoses



  • Gastrointestinal stromal tumor (in gastrointestinal tract)


  • Fibromatosis (in most sites)






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.


TERMINOLOGY


Abbreviations



  • Leiomyosarcoma (LMS)


Definitions



  • Malignant neoplasm composed of cells exhibiting smooth muscle differentiation


ETIOLOGY/PATHOGENESIS


Infectious Agents



  • Epstein-Barr virus associated in immunosuppressed patients


  • Occasional examples associated with radiation


CLINICAL ISSUES


Epidemiology



  • 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


Presentation



  • 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


Treatment



  • Surgical excision



    • Radiation


    • Chemotherapy


Prognosis



  • 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


MICROSCOPIC PATHOLOGY


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


ANCILLARY TESTS


Immunohistochemistry



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



    • Some cases label with keratins


Cytogenetics



  • Complex variable karyotypes


  • No characteristic translocation, mutation, or fusion product known

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

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