CYTOTOXIC-CELL ANTIGEN EXPRESSION IN ANAPLASTIC LARGE-CELL LYMPHOMAS OF T-CELL AND NULL-CELL TYPE AND HODGKINS-DISEASE - EVIDENCE FOR DISTINCT CELLULAR-ORIGIN

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 thes e tumors represent a single entity or several, and what the exact cell origin, is controversial. Recently, granzyme B, a cytotoxic granule c omponent, was reported in a small percentage of ALCL, suggesting that some cases may originate from cytotoxic lymphocytes. To further invest igate this possibility, we performed an immunohistochemical study of 3 3 ALCLs of T- and null-cell type, using monoclonal antibodies to cytot oxic cell-associated antigens, including CD8, CD56, CD57, and the cyto toxic granular proteins perforin and TIA-1. In addition, CD4 expressio n was also evaluated. ALCL cases included 27 classical systemic forms and variants, 3 primary cutaneous (PC) forms, and 3 acquired immunodef iciency syndrome-associated forms. Cytotoxic antigen expression was al so studied in 51 cases of Hodgkin's disease (HD) and 17 large B-cell l ymphomas (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 anti gen 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 protein s in the absence of lineage specific markers, and one case expressed b oth T-cell- and natural killer cell-like markers. These 7 cases (21%) were placed into a phenotypic category of cytotoxic lymphocytes of uns pecified subtype. Twenty-four percent (8 cases) of ALCLs were cytotoxi c granule protein negative. All but one of these displayed a T-cell ph enotype. Cytotoxic granule protein expression did not correlate with t he presence of the NPM-ALK fusion transcript. Only 10% of the 51 HD ca ses were found to be TIA-1(+), and none expressed perforin. Cytotoxic antigen expression was absent in LBCL. The expression of cytotoxic gra nule proteins in the majority of ALCL implies a cytotoxic lymphocyte p henotype 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 anti bodies used to distinguish ALCL, HD, and anaplastic LBCL. This is a US government work. There are no restrictions on its use.