Han Bogyeong, Kim Sehui, Koh Jiwon, Bae Jeong Mo, Yun Hongseok, Jeon Yoon Kyung
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Center for Precision Medicine, Seoul National University Hospital, Seoul, Korea.
J Pathol Transl Med. 2022 Mar;56(2):92-96. doi: 10.4132/jptm.2021.10.15. Epub 2021 Nov 16.
Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status has been approved as a tissue-agnostic biomarker for immune checkpoint inhibitor therapy in patients with solid tumors. We report the case of an MSI-H/dMMR diffuse large B-cell lymphoma (DLBCL) identified by targeted gene sequencing (TGS). A 90-year-old female who presented with vaginal bleeding and a large mass in the upper vagina was diagnosed with germinal center-B-cell-like DLBCL, which recurred at the uterine cervix at 9 months after chemotherapy. Based on TGS of 121 lymphoma-related genes and the LymphGen algorithm, the tumor was classified genetically as DLBCL of EZB subtype. Mutations in multiple genes, including frequent frameshift mutations, were detected by TGS and further suggested MSI. The MSI-H/dMMR and loss of MLH1 and PMS2 expression were determined in MSI-fragment analysis, MSI real-time polymerase chain reaction, and immunohistochemical tests. This case demonstrates the potential diagnostic and therapeutic utility of lymphoma panel sequencing for DLBCL with MSI-H/dMMR.
微卫星高度不稳定/错配修复缺陷（MSI-H/dMMR）状态已被批准作为实体瘤患者免疫检查点抑制剂治疗的一种不依赖组织的生物标志物。我们报告了一例通过靶向基因测序（TGS）鉴定的MSI-H/dMMR弥漫性大B细胞淋巴瘤（DLBCL）病例。一名90岁女性因阴道出血和阴道上段巨大肿物就诊，被诊断为生发中心B细胞样DLBCL，化疗9个月后在子宫颈复发。基于121个淋巴瘤相关基因的TGS和LymphGen算法，该肿瘤在基因上被分类为EZB亚型的DLBCL。通过TGS检测到多个基因的突变，包括频繁的移码突变，进一步提示为MSI。在MSI片段分析、MSI实时聚合酶链反应和免疫组织化学检测中确定了MSI-H/dMMR以及MLH1和PMS2表达缺失。该病例证明了淋巴瘤基因panel测序对MSI-H/dMMR的DLBCL的潜在诊断和治疗价值。
