HISTIOCYTIC SARCOMAS AND MONOBLASTIC LEUKEMIAS - A CLINICAL, HISTOLOGIC, AND IMMUNOPHENOTYPICAL STUDY

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled ''ordinary'' tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11B, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigations.