Although the alteration of the 9p24.1 chromosome locus and PD-L1 overexpression is found in nodular sclerosis classic Hodgkin lymphoma, whether these aberrations occur in CHL and Hodgkin-like lesion (HLL) of methotrexate-associated lymphoproliferative disorder (MTX-CHL and MTX-HLL) is unknown. We compared the clinicopathologic features, the genomic status of the 9p24.1 locus and PD-L1 expression in a series of 34 patients including 17 with Epstein-Barr virus-positive de novo CHL, 7 with MTX-CHL, 10 with MTX-HLL using an immunofluorescence in situ hybridization method and immunohistochemistry. The proportions of cells with 9p24.1 genetic alteration in CD30-positive Hodgkin/Reed-Sternberg cells of de novo CHL, MTX-CHL and MTX-HLL were 55%, 68%, and 24%, respectively. The positive rates of PD-L1 measured by immunohistochemical H-scores of de novo CHL, MTX-CHL and MTX-HLL were 142±38, 157±75, and 70±42, respectively. Alteration of the 9p24.1 gene and expression of PD-L1 protein were correlated with all 3 diseases (correlation coefficient, 0.731). Both alteration of the 9p24.1 gene and overexpression of PD-L1 protein were observed in Epstein-Barr virus-positive de novo CHL and MTX-CHL but not in MTX-HLL. In conclusion, MTX-CHL has similar pathogenesis-like de novo CHL, but MTX-HLL seems to be a different disease from de novo CHL and MTX-CHL.

中文翻译：

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9p24.1 基因改变和 PD-L1 表达是新发和甲氨蝶呤相关 Epstein-Barr 病毒阳性霍奇金淋巴瘤的特征，但不是甲氨蝶呤相关霍奇金样病变的特征。

尽管在结节性硬化经典霍奇金淋巴瘤中发现了 9p24.1 染色体基因座的改变和 PD-L1 过表达，但这些异常是否发生在甲氨蝶呤相关淋巴组织增生性疾病（MTX-CHL 和 MTX）的 CHL 和霍奇金样病变（HLL）中-HLL) 未知。我们比较了 34 名患者的临床病理学特征、9p24.1 基因座的基因组状态和 PD-L1 表达，其中 17 名 Epstein-Barr 病毒阳性新发 CHL，7 名 MTX-CHL，10 名 MTX-HLL使用免疫荧光原位杂交方法和免疫组织化学。从头 CHL、MTX-CHL 和 MTX-HLL 的 CD30 阳性 Hodgkin/Reed-Sternberg 细胞中具有 9p24.1 基因改变的细胞比例分别为 55%、68% 和 24%。从头 CHL 的免疫组化 H 评分测量的 PD-L1 的阳性率，MTX-CHL 和 MTX-HLL 分别为 142±38、157±75 和 70±42。9p24.1基因的改变和PD-L1蛋白的表达与所有3种疾病相关（相关系数，0.731）。在 Epstein-Barr 病毒阳性的新发 CHL 和 MTX-CHL 中观察到 9p24.1 基因的改变和 PD-L1 蛋白的过表达，但在 MTX-HLL 中未观察到。综上所述，MTX-CHL 的发病机制与新生 CHL 相似，但 MTX-HLL 似乎是不同于新生 CHL 和 MTX-CHL 的疾病。