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, 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.
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA.
R E
RE
Felgar
K E
KE
Salhany
W R
WR
Macon
G G
GG
Pietra
M C
MC
Kinney
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D002648:Child; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D018396:Mucin-1 / Q000096:biosynthesis; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis; D039102:Poly(A)-Binding Proteins; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011506:Proteins; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*; D000074019:T-Cell Intracellular Antigen-1
D015703:Antigens, CD; D008565:Membrane Proteins; D018396:Mucin-1; D015514:Oncogene Proteins, Fusion; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases