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Langerhans cell sarcoma
Langerhans cell sarcoma
Clinical features Langerhans cell sarcoma (LCS) (malignant histiocytosis X, malignant Langerhans cell tumor) is a very rare high-grade neoplasm with overtly malignant features.1โ4 Almost all reported cases are in adults, with a median age of 39 years (range, 10โ72 years) and female predilection.1โ4 Skin and underlying soft tissue are most commonly involved. However, LCS is often high stage at presentation (44% stage III/IV), and there is frequent multiorgan involvement with spread to lymph nodes, lungs, liver, spleen, and bone.1,3โ8 Skin lesions may manifest as generalized papules and nodules at
presentation, but more often acral sites (particularly the leg) are affected by a single tumor nodule. Twenty-two percent of cases are primarily nodal, and hepatosplenomegaly and pancytopenia may be seen in 22% and 11% of cases, respectively.1 A leukemic phase has also been described in two cases, although the phenotype of the circulating cells in the most recent report was not that of Langerhans cells.9,10 Prognosis is poor with >50% mortality, although occasional cases have a more favorable prognosis.1,11
Pathogenesis and histologic features The pathogenesis of LCS is largely unknown. Cases may arise de novo but have also been described in patients with Langerhans cell histiocytosis as well as in association with other hematological malignancies, including B-lymphoblastic leukemia, follicular lymphoma, CLL, and hairy cell leukemia.12โ17 A clonal relationship has been demonstrated in such situations and BRAF mutation has also been identified in a sporadic case.13,15,16,18
1495 Indeterminate dendritic cell tumor
eosinophilic cytoplasm reminiscent of the โground glassโ cells of RH are evident.5 In contrast to LCH, abundant reticulin fibers are present in CSH, surrounding either individual cells or groups of cells, and PAS-positive cytoplasmic inclusions are frequently seen.5,16,25 The latter may include punctate and ring forms representing glycogen or diffuse cytoplasmic staining indicating the presence of neutral glycosaminoglycans.5
Immunohistochemically, the infiltrate is indistinguishable from LCH, and tumor cells are positive for S100 protein, CD1a, CD4, and HLA-DR.1
Ultrastructurally, in addition to Birbeck granules (present in 10โ25% of cells), tumor cells contain myelin-like dense bodies and, less often, phagolysosomes filled with laminated membranous debris and paracrystalline material.1,2,5,6 The latter do not appear to have been described in LCH.
Tumor cells are malignant with pleomorphic nuclei containing clumped chromatin and prominent nucleoli.1,7,11 There is often little to suggest a Langerhans cell origin, although some cells may possess complex nuclear grooves similar to those seen in LCH cells. Mitotic figures are numerous (>50 per 10 HPFs).4 Scattered eosinophils and occasional small lymphocytes may be present.1,8,19
Ultrastructural or phenotypic evidence of Langerhans cell differentiation must be confirmed. Electron microscopy may reveal Birbeck granules and the immunophenotype is usually identical to that seen in Langerhans cell histiocytosis, although staining for individual markers may be focal and patchy.1,4 Immunoglobulin and T-cell receptor genes are Germline except in cases related to other lymphomas.13,15,16,20
Differential diagnosis In view of the histologic and immunohistochemical similarities, distinction of CSH from multisystem LCH depends on the absence of severe systemic involvement and regression of lesions in the former condition.