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Cytotoxic cell antigen expression in anaplastic large cell lymphomas of T-
and null-cell type and Hodgkin's disease: evidence for distinct cellular
origin
L Krenacs, A Wellmann, L Sorbara, AW Himmelmann, E Bagdi, ES Jaffe and M Raffeld
Hematopathology Section, National Cancer Institute, Bethesda, MD 20892,
USA.
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.
Volume 89,
Issue 3,
pp. 980-989,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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