True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis

Five cases of true histiocytic lymphoma (THL) were analysed by immunophenotyping and immunoglobulin/T‐cell receptor genotyping. These cases showed striking morphologic diversity but a strong degree of immunophenotypic homogeneity. The malignant cells reacted with multiple histiocytic markers including CD11c (Ki‐M1, LeuM5), CD14, CD68 (Ki‐M6) and Ki‐M8; anti‐HLA‐DR and non‐specific esterase staining was also found in all cases. The malignant cells did not express monoclonal immunoglobulin and did not react with the B‐ or T‐cell monoclonal antibodies used except for those known to be cytoplasmically expressed in monocytes/histiocytes, such as CD4 and CD19; B‐ and T‐cell staining was otherwise limited to background small lymphocytes. By genotypic analysis, three cases showed rearrangements: one with Tβ, one with Tβ and immunoglobulin heavy chain (J_H) and one with both J_H and light chain: the remaining two cases retained their immunoglobulin and T‐cell receptor genes in germline configuration. The results not only suggest that certain subsets of the histiocyte/reticulum cell system may be capable of rearranging immunoglobulin or Tβ genes while simultaneously expressing multiple histiocytic surface antigens but also demonstrate the necessity of using multiple histiocytic‐specific monoclonal antibodies and cytochemical staining in diagnosing THL. Gene rearrangement studies must be interpreted in conjunction with immunophenotyping and morphology in the determination of cell lineage.