Langerhans Cell Sarcoma



Langerhans Cell Sarcoma


Sa A. Wang, MD





Key Facts


Terminology



  • Neoplastic proliferation of Langerhans cells with overtly malignant cytologic features


Clinical Issues



  • LCS most often presents as de novo mass



    • Subset of cases can progress from antecedent Langerhans cell histiocytosis (LCH)


  • Skin & soft tissue are most commonly involved sites



    • ˜ 20% of patients present with lymphadenopathy


    • Multiorgan involvement is common


  • Many patients with LCS have clinically aggressive disease



    • Mortality rate is ˜ 50%


    • Death often within 2 years


Microscopic Pathology



  • LCS tends to resemble other types of sarcoma



    • Overtly malignant cytologic features


    • High mitotic rate (> 50 mitosis/10 HPF)


    • Large areas of coagulative necrosis


    • Few neoplastic cells show characteristic cytologic features of Langerhans cells


  • IHC and ultrastructure similar to LCH



    • CD1a(+), S100 protein(+), langerin(+)


    • Birbeck granules


Top Differential Diagnoses



  • Langerhans cell histiocytosis


  • Interdigitating dendritic sarcoma


  • Follicular dendritic cell sarcoma


  • Histiocytic sarcoma







Langerhans cell sarcoma replacing lymph node parenchyma in a 61-year-old man. Uninvolved lymph node is at the bottom left of the field. This neoplasm presented de novo.






Langerhans cell sarcoma involving lymph node. This field shows neoplastic cells with irregular nuclear contours and abundant cytoplasm. Mitotic figures are numerous.


TERMINOLOGY


Abbreviations



  • Langerhans cell sarcoma (LCS)


Synonyms



  • Dendritic/histiocytic sarcoma, Langerhans cell type


  • Malignant histiocytosis X


  • Malignant Langerhans cell tumor


Definitions



  • Neoplastic proliferation of overtly malignant Langerhans cells


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Rare


  • Age



    • Median: 46 years (range: 10-81 years)


  • Gender



    • Female predominance; M:F ratio = 1:2


Site



  • Skin and soft tissue are most commonly involved sites


  • Multiorgan involvement is common



    • Lymph nodes, lung, liver, spleen, bone, gallbladder, brain, intestines, pancreas


  • Primary lymph node involvement in ˜ 20% of patients


Presentation



  • Langerhans cell sarcoma usually arises de novo


  • Rare cases of LCS progress from antecedent Langerhans cell histiocytosis (LCH)



    • Rare case reports


  • Most patients present with extranodal mass without other symptoms



    • ˜ 40% of patients have stage III or IV disease


    • ˜ 20% have hepatosplenomegaly


    • ˜ 10% have pancytopenia; often associated with bone marrow involvement


  • Systemic symptoms in subset of patients



    • Fatigue, night sweats, weight loss


Treatment



  • Surgical excision, if resectable, is best approach


  • Chemotherapy and radiation therapy for disseminated disease



    • Often poor response


Prognosis



  • Clinically aggressive neoplasm



    • Many patients show progressive disease


    • ˜ 50% mortality rate; many patients die within 2 years


IMAGE FINDINGS


General Features



  • CT and MR



    • Mass lesion


    • Often show multifocal or disseminated disease


  • Positron emission tomography (PET)



    • Abnormal utilization of isotope


MICROSCOPIC PATHOLOGY


Histologic Features



  • Skin and soft tissue



    • Resembles other types of sarcoma


    • Diffuse pattern


    • Neoplastic cells are overtly malignant



      • Pleomorphic cells with prominent nucleoli and clumped chromatin


      • Mitotic rate often high; up to > 50 mitoses/10 high-power fields


      • Atypical mitotic figures may present



      • Neoplastic cells can have moderate or abundant cytoplasm, ± foamy or vacuolated


    • Focal necrosis often present


    • Eosinophils are few or absent in background


  • Lymph nodes



    • LCS may show variety of patterns; often a mixture present



      • Diffuse effacement


      • Vaguely nodular


      • Sinusoidal involvement


  • Histologic clues to diagnosis of LCS



    • Neoplastic cells show irregular nuclear contours or nuclear grooves



      • Usually only small subset of neoplastic cells


      • Small areas where eosinophils are present in background


Cytologic Features



  • Very large cells with round or folded nuclei, ± prominent nucleoli, and abundant cytoplasm



    • Difficult diagnosis to establish without immunohistochemistry


ANCILLARY TESTS


Immunohistochemistry



  • CD1a(+), S100 protein(+), or langerin/CD207(+)



    • Expression can be focal or patchy


    • CD40(+), HLA-DR(+), vimentin(+/-)


    • CD56/NCAM(+)



      • CD56 is usually negative in LCH


    • CD31(+); CD31 is negative in normal Langerhans cells


    • CD68(+/-), CD45(+/-); when positive, CD68 and CD45 can be weak or variable


    • CD4(+/-); CD163(-/+)


    • Lysozyme(-/+); if positive, it is often in only a subset of cells


    • Fascin(-)


  • Follicular dendritic cell markers(-)



    • CD21, CD23, CD35, clusterin, etc.


Molecular Genetics



  • No evidence of immunoglobulin or T-cell receptor gene rearrangements


  • Very few cases assessed by human androgen-receptor assay (HUMARA) are reported


  • “Transdifferentiation” reported



    • LCS and B-lymphoblastic leukemia


Electron Microscopy



  • Birbeck granules are present


  • No evidence of



    • Desmosomes/junctional specialization


    • Interdigitating cell processes


DIFFERENTIAL DIAGNOSIS


Langerhans Cell Histiocytosis (LCH)



  • Langerhans cells have bland cytologic features



    • “Twisted towel” nuclei with nuclear grooves and open chromatin


  • Often many eosinophils in background



    • Some cases of LCH have eosinophilic microabscesses


  • Necrosis can be present; often associated with eosinophils


  • Variable number of macrophages and small lymphocytes in background



    • Multinucleated giant cells can be present


  • Clinical behavior of LCH can overlap with LCS



    • Some patients with LCH present with multiorgan involvement



      • Infants: Letterer-Siwe disease (disseminated)


      • Young children: Often unisystem multifocal disease


      • Patients with systemic involvement can have aggressive clinical course


  • Some cases of LCH can show appreciable mitotic rate



    • 10-20 mitosis/10 HPF, some cases can be up to 30 mitosis/10 HPF


  • Histologic features that distinguish LCS from LCH



    • Lesion looks like sarcoma



      • Overtly malignant cytologic features



      • Few neoplastic cells have features typical of Langerhans cells


      • Few eosinophils in background


      • Extensive coagulative necrosis


      • Extremely high mitotic rate, > 30/10 HPF


      • Atypical mitotic figures


      • LCS typically occurs in adults (unlike many LCH patients)


  • Immunophenotypic features may distinguish LCS from LCH



    • CD56 is positive in LCS but negative in LCH


    • Expression of markers of Langerhans cells is often patchy in LCS


Interdigitating Dendritic Sarcoma



  • Fascicles, storiform arrays, whorls growth pattern



    • This pattern may not be obvious in high-grade lesions


  • Neoplastic cells can be spindled or epithelioid


  • Immunohistochemistry



    • S100(+); can be patchy


    • CD11c(+), HLA-DR(+)


    • Vimentin(+), fascin(+)


    • CD4(+/-), CD45/LCA(+/-)


    • CD68(+/-), CD163(+/-)


    • CD15(-/+), lysozyme(-/+)


    • CD1a(-), langerin(-)


  • Electron microscopy (EM)



    • No Birbeck granules


Follicular Dendritic Cell Sarcoma

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Langerhans Cell Sarcoma

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