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 investigation.