True Histiocytic Lymphoma: A Morphologic, Immunohistochemical, and Molecular Genetic Study of 13 Cases

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Abstract

We describe the morphologic, immunohistologic, and genotypic characteristics of 13 cases of true histiocytic lymphomas. Six cases presented with primary gastrointestinal involvement, five with lymphadenopathy, the other sites involved being the bone marrow and the skin. The neoplastic cells displayed large abundant eosinophilic cytoplasm, occasionally vacuolated with folded or bizarre-shaped nuclei with prominent nucleoli. Mitotic figures were numerous. Multinucleated cells were common. The pattern of growth was usually diffuse and noncohesive. Spindle cell sarcoma-like areas were evident in five cases, with a prominent foam cell component in four cases. All cases expressed histiocyte-associated markers (CD68, lysozyme, α-1-antitrypsin), CD45 or CD45RO, and were negative for CD1a, epithelial, and B- and T-cell lineage-specific markers. Reactivity for S-100 was observed in a variable proportion of cells in 11 cases. The proliferation fraction varied from 3 to 88%. Genotypic analysis for T-cell receptor or immunoglobulin gene rearrangement demonstrated a germline configuration in all cases. We demonstrate that true histiocytic lymphoma is a rare distinctive pathologic entity that may be defined by immunohistochemical criteria and that recognition among histiocytic disorders is important for clinical and prognosis reasons.

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