Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases
Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases
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DOI：
10.1038/s41379-019-0264-2
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发表时间：
2019-08-01
期刊：
影响因子：
7.5
通讯作者：
Nakamura, Shigeo
中科院分区：
文献类型：
--
作者：
Satou, Akira;Tabata, Tetsuya;Nakamura, Shigeo
在WHO分类中，蛋氨酸相关淋巴组织增生性疾病被归类为“其他免疫缺陷相关淋巴组织增生性疾病”。蛋氨酸相关淋巴增生性疾病主要是B细胞淋巴增生性疾病或霍奇金淋巴瘤类型，而T细胞淋巴增生性疾病相对罕见（4-8%）。到目前为止，仅详细描述了少数与甲氨蝶呤相关的T细胞淋巴增生性疾病。由于罕见，蛋氨酸相关的T细胞淋巴增生性疾病尚未得到很好的研究，其临床病理特征是未知的。对28例甲氨蝶呤相关性T淋巴细胞增生性疾病进行回顾性分析。组织学及免疫化学分型：血管免疫母细胞性T细胞淋巴瘤19例，外周T细胞淋巴瘤NOS 6例，CD 8（+）细胞毒性T细胞淋巴瘤3例。28例CD 8（+）细胞毒性T细胞淋巴瘤中仅有1例EB病毒阳性。其余27例肿瘤细胞EB病毒阴性，24例（89%）检出散在EB病毒感染的B细胞，提示患者免疫缺陷状态导致EB病毒再激活。在诊断为甲氨蝶呤相关的T细胞淋巴增生性疾病后，26例患者立即停用甲氨蝶呤。20例（77%）病例出现自发消退。与甲氨蝶呤相关的B细胞淋巴增殖性疾病相比，甲氨蝶呤相关的T细胞淋巴增殖性疾病患者的男性比例（p = 0.035）和B症状的存在（p = 0.036）显著更高，EB病毒（+）肿瘤细胞的比例更低（p < 0.001）。尽管差异不显着，但甲氨蝶呤相关T细胞淋巴增生性疾病也有更频繁的自发消退（p = 0.061）。总之，蛋氨酸相关T细胞淋巴增殖性疾病分为三种主要类型：血管免疫母细胞性T细胞淋巴瘤、外周T细胞淋巴瘤、NOS和CD 8（+）细胞毒性T细胞淋巴瘤。血管免疫母细胞性T细胞淋巴瘤最常见。甲氨蝶呤相关性T细胞淋巴增生性疾病的特点是甲氨蝶呤停药后自发消退率高。EB病毒阳性在甲氨蝶呤相关的T细胞淋巴增生性疾病中相对罕见，明显低于甲氨蝶呤相关的B细胞淋巴增生性疾病，提示不同的发病机制。
Methotrexate-associated lymphoproliferative disorders are categorized as "other immunodeficiency-associated lymphoproliferative disorders in the WHO classification. Methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorders or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4-8%). Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far. Because of the rarity, methotrexate-associated T-cell lymphoproliferative disorder has not been well studied and its clinicopathological characteristics are unknown. A total of 28 cases of methotrexate-associated T-cell lymphoproliferative disorders were retrospectively analyzed. Histologically and immunohistochemically, they were divided into three main types: angioimmunoblastic T-cell lymphoma (n = 19), peripheral T-cell lymphoma, NOS (n = 6), and CD8(+) cytotoxic T-cell lymphoma (n = 3). Among the 28 cases, only one CD8(+) cytotoxic T-cell lymphoma case was Epstein-Barr virus-positive. The other 27 cases were negative for Epstein-Barr virus on tumor cells, but scattered Epstein-Barr virus-infected B-cells were detected in 24 cases (89%), implying the reactivation of Epstein-Barr virus caused by immunodeficient status of the patients. After the diagnosis of methotrexate-associated T-cell lymphoproliferative disorder, methotrexate was immediately withdrawn in 26 cases. Twenty (77%) cases presented with spontaneous regression. Compared to methotrexate-associated B-cell lymphoproliferative disorder, patients with methotrexate-associated T-cell lymphoproliferative disorder had a significantly higher proportion of males (p = 0.035) and presence of B-symptoms (p = 0.036), and lower proportion of Epstein-Barr virus(+) tumor cells (p < 0.001). Although the difference was not significant, the methotrexate-associated T-cell lymphoproliferative disorder also had more frequent spontaneous regression (p = 0.061). In conclusion, methotrexate-associated T-cell lymphoproliferative disorder was divided into three main types: angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, NOS, and CD8(+) cytotoxic T-cell lymphoma. Angioimmunoblastic T-cell lymphoma was the most common type. Methotrexate-associated T-cell lymphoproliferative disorder was characterized by a high rate of spontaneous regression after methotrexate cessation. Epstein-Barr virus positivity was relatively rare in methotrexate-associated T-cell lymphoproliferative disorder, significantly less frequent than methotrexate-associated B-cell lymphoproliferative disorder, suggesting different pathogenesis.