The American Journal of Surgical Pathology ( IF 5.6 ) Pub Date : 2022-03-01 , DOI: 10.1097/pas.0000000000001813 Julien Calvani 1, 2 , Laurence Gérard 3 , Jehane Fadlallah 3 , Elsa Poullot 4, 5 , Lionel Galicier 3 , Cyrielle Robe 4, 5 , Margaux Garzaro 2, 3 , Remi Bertinchamp 3 , David Boutboul 2, 3 , Wendy Cuccuini 6 , Jean-Michel Cayuela 2, 7 , Philippe Gaulard 4, 5 , Éric Oksenhendler 2, 3 , Véronique Meignin 1
Primary effusion lymphoma (PEL) is associated with human herpesvirus 8 and frequently with Epstein-Barr virus (EBV). We report here a single-center series of 19 human immunodeficiency virus–associated PELs, including 14 EBV+ and 5 EBV− PELs. The objectives were to describe the clinicopathologic features of PELs, with a focus on programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, to search for genetic alterations by targeted deep sequencing analysis, and to compare the features between EBV+ and EBV− cases. All the patients were male, and the median age at diagnosis was 47 years old (interquartile range: 40 to 56 y). Reflecting the terminal B-cell differentiation, immunophenotypic profiles showed low expression levels of B-cell markers, including CD19 (0/19), CD20 (1/19), CD79a (0/19), PAX5 (1/19), BOB1 (3/19), and OCT2 (4/19), contrasting with a common expression of CD38 (10/19), CD138 (7/19), and IRF4/MUM1 (18/19). We observed a frequent aberrant expression of T-cell markers, especially CD3 (10/19), and less frequently CD2 (2/19), CD4 (3/19), CD5 (1/19), and CD8 (0/19). Only 2 cases were PD-L1 positive on tumor cells and none PD-1 positive. With respect to immune cells, 3 samples tested positive for PD-L1 and 5 for PD-1. Our 36-gene lymphopanel revealed 7 distinct variants in 5/10 PELs, with either a single or 2 mutations per sample: B2M (n=2), CD58 (n=1), EP300 (n=1), TNFAIP3 (n=1), ARID1A (n=1), and TP53 (n=1). Finally, we did not observe any major clinical, pathologic, or immunohistochemical differences between EBV+ and EBV− PELs and the outcome was similar (2-y overall survival probability of 61.9% [95% confidence interval, 31.2-82.1] vs. 60.0% [95% confidence interval, 12.6-88.2], respectively, P=0.62).
中文翻译:
19 种 HIV 感染者原发性渗出性淋巴瘤的综合临床病理学和分子研究
原发性渗出性淋巴瘤 (PEL) 与人类疱疹病毒 8 型相关,并且经常与 Epstein-Barr 病毒 (EBV) 相关。我们在此报告了 19 种人类免疫缺陷病毒相关 PEL 的单中心系列,其中包括 14 种 EBV +和 5 种 EBV - PEL。目的是描述 PEL 的临床病理特征,重点关注程序性细胞死亡蛋白 1 (PD-1)/程序性死亡配体 1 (PD-L1) 的表达,通过靶向深度测序分析寻找遗传改变,以及比较 EBV +和 EBV -病例之间的特征。所有患者均为男性,诊断时的中位年龄为 47 岁(四分位距:40 至 56 岁)。免疫表型图谱反映了 B 细胞终末分化,显示 B 细胞标记物的表达水平较低,包括 CD19 (0/19)、CD20 (1/19)、CD79a (0/19)、PAX5 (1/19)、BOB1 (3/19) 和 OCT2 (4/19),与 CD38 (10/19)、CD138 (7/19) 和 IRF4/MUM1 (18/19) 的常见表达形成对比。我们观察到 T 细胞标记物频繁出现异常表达,尤其是 CD3 (10/19),较少出现 CD2 (2/19)、CD4 (3/19)、CD5 (1/19) 和 CD8 (0/19) )。仅2例肿瘤细胞PD-L1阳性,无PD-1阳性。免疫细胞方面,3个样本的PD-L1检测呈阳性,5个样本的PD-1检测呈阳性。我们的 36 基因淋巴组在 5/10 PEL 中显示了 7 个不同的变异,每个样本有一个或 2 个突变:B2M (n=2)、CD58 (n=1)、EP300 (n=1)、TNFAIP3 (n= 1)、ARID1A (n=1) 和TP53 (n=1)。最后,我们没有观察到 EBV +和 EBV − PEL 之间有任何重大的临床、病理或免疫组织化学差异,并且结果相似(2 年总生存概率为 61.9% [95% 置信区间,31.2-82.1] 对比 60.0) % [95% 置信区间,12.6-88.2],分别,P = 0.62)。