title: Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T- and null-cell type and Hodgkin's disease: evidence for distinct cellular origin.
abstract: Anaplastic large cell lymphoma (ALCL) is composed of large, frequently bizarre, cells of T- or null-cell phenotype that show a preferential sinusoidal growth pattern and consistent CD30 positivity. Whether these tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule component, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further investigate this possibility, we performed an immunohistochemical study of 33 ALCLs of T- and null-cell type, using monoclonal antibodies to cytotoxic cell-associated antigens, including CD8, CD56, CD57, and the cytotoxic granular proteins perforin and TIA-1. In addition, CD4 expression was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodeficiency syndrome-associated forms. Cytotoxic antigen expression was also studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell lymphomas (LBCLs) with anaplastic cytomorphology and/ or CD30 positivity. We found that 76% of ALCLs, representing all subtypes except the PC forms, expressed either TIA-1, perforin, or both proteins. Expression of TIA-1 and perforin were highly correlated (P < .001). On the basis of their immunophenotypic profiles, several subtypes of cytotoxic antigen positive and negative ALCL could be recognized. Fifty-five percent of ALCLs (18 of 33) displayed an immunophenotypic profile consistent with cytotoxic T cells. Six cases expressed cytotoxic granular proteins in the absence of lineage specific markers, and one case expressed both T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of unspecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxic granule protein negative. All but one of these displayed a T-cell phenotype. Cytotoxic granule protein expression did not correlate with the presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD cases were found to be TIA-1+, and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic granule proteins in the majority of ALCL implies a cytotoxic lymphocyte phenotype and suggests that most cases originate from lymphocytes with cytotoxic potential. Furthermore, the demonstration of cytotoxic cell related proteins may be a useful addition to the current panel of antibodies used to distinguish ALCL, HD, and anaplastic LBCL.
authors.affiliation: Hematopathology Section, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: L
authors.initials: L
authors.lastname: Krenacs
authors.forename: A
authors.initials: A
authors.lastname: Wellmann
authors.forename: L
authors.initials: L
authors.lastname: Sorbara
authors.forename: A W
authors.initials: AW
authors.lastname: Himmelmann
authors.forename: E
authors.initials: E
authors.lastname: Bagdi
authors.forename: E S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: M
authors.initials: M
authors.lastname: Raffeld
mesh_terms: D000293:Adolescent; D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D018959:CD57 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D019002:CD56 Antigen; D018959:CD57 Antigens; D016827:CD8 Antigens; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D054353:Perforin