The expression of TIA-1⁺ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30⁺ anaplastic large cell lymphomas (ALCL): Correlation with morphology, immunophenotype, ultrastructure, and clinical features

Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30⁺ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, βF1, TCRδ1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease-associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (≤32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15⁺ cases were TIA-1^-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue), TIA-1⁺ granules were seen in all subsets: 5 of 6 CD4⁺, 1 of 2 CD8⁺, 4 of 8 CD56⁺, and 1 of 2 CD57⁺ ALCL. Of note, 4 of 10 T or null cell ALCL expressed γδ T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was αβ TCR⁺; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 γδ TCR⁺ ALCL and 1 of 1 αβ TCR⁺ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4⁺ T cells, γδ T cells, or NK-like (CD56⁺ or CD57⁺) T cells.