Felgar R E, Salhany K E, Macon W R, Pietra G G, Kinney M C
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA.
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.
间变性大细胞淋巴瘤（ALCL）是一组异质性的CD30 +大细胞淋巴瘤；最具特征性的类型具有T或无细胞表型，常表达上皮膜抗原（EMA）和细胞溶解性淋巴细胞标志物，且常具有非随机的t(2;5)(p23;q35)染色体易位。我们研究了22例（19例T细胞型、1例无细胞型、2例B细胞型）ALCL，包括4例原发性皮肤ALCL（PC-ALCL），检测其TIA-1、细胞毒性T淋巴细胞（CTL）或自然杀伤（NK）细胞相关抗原CD4、CD8、βF1、TCRδ1、CD56和CD57、ALCL相关抗原p80和EMA以及霍奇金病相关标志物CD15的表达情况，以更好地明确这些标志物与组织学亚型、原发部位及患者临床特征之间的关系。在20例（60%）T或无细胞型ALCL中，有12例可见TIA-1表达，呈胞质颗粒状分布。超微结构研究显示，细胞毒性型颗粒（致密核心型、多囊泡型和中间型）在免疫金标记时TIA-1定位于颗粒上。TIA-1染色与年轻患者年龄（≤32岁，P <.05）及EMA表达（P <.05）密切相关。排除4例PC-ALCL病例后，在所有T细胞型病例中，TIA-1染色也与p80表达相关（P <.05）。3例CD15 +病例TIA-1阴性。在所有形态学亚型（2例小细胞变异型中的2例、4例单形性变异型中的3例、14例多形性变异型中的7例）及原发性肿瘤部位（14例淋巴结型中的6例、4例原发性皮肤型中的2例、2例骨型中的2例、2例软组织型中的2例）的T或无细胞型ALCL中均可见TIA-1表达。在所有亚群中均可见TIA-1 +颗粒：6例CD4 + ALCL中的5例、2例CD8 + ALCL中的1例、8例CD56 + ALCL中的4例、2例CD57 + ALCL中的1例。值得注意的是，10例T或无细胞型ALCL中有4例表达γδ T细胞受体（TCR），而10例T或无细胞型ALCL中只有1例αβ TCR +；5例未检测到TCR。4例γδ TCR + ALCL中有3例表达TIA-1，1例αβ TCR + ALCL表达TIA-1。这些数据支持大多数T或无细胞型ALCL具有细胞毒性淋巴细胞表型，并提示部分T细胞型ALCL来源于细胞溶解性CD4 + T细胞、γδ T细胞或NK样（CD56 +或CD57 +）T细胞。
