Krenacs L, Wellmann A, Sorbara L, Himmelmann A W, Bagdi E, Jaffe E S, Raffeld M
Hematopathology Section, National Cancer Institute, Bethesda, MD 20892, USA.
Blood. 1997 Feb 1;89(3):980-9.
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.
间变性大细胞淋巴瘤（ALCL）由大细胞组成，这些细胞通常形态怪异，呈T细胞或裸细胞表型，表现出偏好的窦状生长模式且CD30持续阳性。这些肿瘤是代表单一实体还是多个实体，以及确切的细胞起源是什么，存在争议。最近，在一小部分ALCL中报道了细胞毒性颗粒成分颗粒酶B，这表明一些病例可能起源于细胞毒性淋巴细胞。为了进一步研究这种可能性，我们使用针对细胞毒性细胞相关抗原的单克隆抗体，包括CD8、CD56、CD57以及细胞毒性颗粒蛋白穿孔素和TIA-1，对33例T细胞和裸细胞型ALCL进行了免疫组织化学研究。此外，还评估了CD4表达。ALCL病例包括27例经典的系统性形式和变异型、3例原发性皮肤（PC）形式以及3例与获得性免疫缺陷综合征相关的形式。还对51例霍奇金淋巴瘤（HD）和17例具有间变性细胞形态和/或CD30阳性的大B细胞淋巴瘤（LBCL）进行了细胞毒性抗原表达研究。我们发现，76%的ALCL（代表除PC形式外的所有亚型）表达TIA-1、穿孔素或这两种蛋白。TIA-1和穿孔素的表达高度相关（P <.001）。根据其免疫表型特征，可以识别出细胞毒性抗原阳性和阴性的ALCL的几个亚型。55%的ALCL（33例中的18例）表现出与细胞毒性T细胞一致的免疫表型特征。6例在缺乏谱系特异性标志物的情况下表达细胞毒性颗粒蛋白，1例同时表达T细胞和自然杀伤细胞样标志物。这7例（21%）被归入未指定亚型的细胞毒性淋巴细胞表型类别。ALCL的24%（8例）细胞毒性颗粒蛋白阴性。除1例之外，所有这些都表现出T细胞表型。细胞毒性颗粒蛋白表达与NPM-ALK融合转录本的存在无关。在51例HD病例中，仅10%被发现TIA-1阳性，且无一例表达穿孔素。LBCL中无细胞毒性抗原表达。大多数ALCL中细胞毒性颗粒蛋白的表达意味着细胞毒性淋巴细胞表型，并表明大多数病例起源于具有细胞毒性潜力的淋巴细胞。此外，细胞毒性细胞相关蛋白的证明可能是对目前用于区分ALCL、HD和间变性LBCL的抗体组的有益补充。
