Histiocytic Sarcomas and Monoblastic Leukemias:A Clinical, Histologic, and Immunophenotypical Study

Abstract

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.

Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163

“…[18][19][20] Hemophagocytosis, a feature previously felt to be important in the diagnosis, may be present but is nonspecific 29,54,55 and frequently is not prominent in bona fide cases. 1,17,19,20,41,51 Likewise, this feature was inconspicuous in all but one of our cases. The importance of immunophenotypic studies in the diagnosis of histiocytic neoplasms has been emphasized.…”

“…Although light microscopy alone is unreliable in establishing the diagnosis, the cases in the current study and review of literature describe similar histologic features consisting of discohesive large cells with pleomorphic nuclei and abundant cytoplasm. 2,13,17,20,28,41,[50][51][52][53] Malignant cytologic features with evidence of tissue invasion or destruction were constant findings in this study and are necessarily present in order to distinguish from benign histiocytic proliferations. [18][19][20] Hemophagocytosis, a feature previously felt to be important in the diagnosis, may be present but is nonspecific 29,54,55 and frequently is not prominent in bona fide cases.…”

“…The importance of immunophenotypic studies in the diagnosis of histiocytic neoplasms has been emphasized. 13,17,51 However, establishing histiocytic lineage by special stains has historically been elusive. Markers once thought to be specific for histiocytic differentiation, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, lysozyme, and KP1, have been shown to have low specificity and may be positive in a wide variety of neoplasms, including a significant percentage of non-Hodgkin lymphomas.…”

“…[12][13][14][15][16][17] This diagnostic challenge is further complicated as it is necessary to distinguish HS from other histiocytic processes, both benign and malignant, to include the hemophagocytic syndrome, [18][19][20] malignant histiocytosis, 10,[18][19][20][21] and monocytic leukemia. 17,19 The diagnosis of HS relies predominantly on the verification of histiocytic lineage and the exclusion of other, poorly differentiated, large cell malignancies (ie lymphoma, carcinoma, melanoma) by way of extensive immunophenotypic investigation. Fulfilling these conditions, particularly establishing histiocytic differentiation, has been problematic due to a high incidence of crossreactivity of many immunohistochemical antibodies originally believed to be specific for histiocytes.…”

Histiocytic/Dendritic Cell Transformation of B-Cell Neoplasms: Pathologic Evidence of Lineage Conversion in Differentiated Hematolymphoid Malignancies

“…9 Fraser et al, 14 in a study of a case of CLL/SLL transformed to IDCS, demonstrated altered expression of transcription factors, including PU.1 and C/EBPa, in IDCS, suggesting their possible role in this lineage conversion. Expression of p53 protein has been previously reported in sporadic cases of HS, 28 but its role in lineage conversion from B-cell lymphoma to H/DS is currently unknown. Future studies may focus on genetic changes and gene expression profiles in secondary H/DS in comparison with primary B-cell neoplasms and secondary DLBCL as well as de novo H/DS in order to elucidate the molecular mechanism of this unusual clinicopathologic phenomenon.…”