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

Hum Pathol. 1999 Feb;30(2):228-36. doi: 10.1016/s0046-8177(99)90281-2.


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, betaF1, TCRdelta1, 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 (< or = 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 gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta 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, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / biosynthesis*
  • Child
  • Female
  • Humans
  • Immunophenotyping
  • Infant
  • Lymphoma, Large-Cell, Anaplastic / metabolism*
  • Lymphoma, Large-Cell, Anaplastic / pathology
  • Lymphoma, Large-Cell, Anaplastic / ultrastructure
  • Male
  • Membrane Proteins / biosynthesis*
  • Microscopy, Immunoelectron
  • Middle Aged
  • Mucin-1 / biosynthesis
  • Oncogene Proteins, Fusion / biosynthesis
  • Poly(A)-Binding Proteins
  • Protein-Tyrosine Kinases / biosynthesis
  • Proteins*
  • RNA-Binding Proteins / biosynthesis*
  • Receptors, Antigen, T-Cell / biosynthesis*
  • T-Cell Intracellular Antigen-1


  • Antigens, CD
  • Membrane Proteins
  • Mucin-1
  • Oncogene Proteins, Fusion
  • Poly(A)-Binding Proteins
  • Proteins
  • RNA-Binding Proteins
  • Receptors, Antigen, T-Cell
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • p80(NPM-ALK) protein
  • Protein-Tyrosine Kinases