Metastatic mismatch repair deficient oesophageal squamous cell carcinoma leading to diagnosis of Lynch syndrome with a complete response to nivolumab treatment.

IF 3.1 3区医学 Q1 PATHOLOGY

Virchows Archiv Pub Date : 2025-09-19 DOI:10.1007/s00428-025-04269-1

H H Wang, G Kats-Ugurlu, R H Sijmons, J L Kluiver, S Z Commandeur-Jan, W Noordzij, B van Etten, J T M Plukker, G A P Hospers, D G Knapen

{"title":"Metastatic mismatch repair deficient oesophageal squamous cell carcinoma leading to diagnosis of Lynch syndrome with a complete response to nivolumab treatment.","authors":"H H Wang, G Kats-Ugurlu, R H Sijmons, J L Kluiver, S Z Commandeur-Jan, W Noordzij, B van Etten, J T M Plukker, G A P Hospers, D G Knapen","doi":"10.1007/s00428-025-04269-1","DOIUrl":null,"url":null,"abstract":"<p><p>A 59-year-old woman with two colorectal adenocarcinomas in 2015 and 2022 (both with loss of MSH2 and focal presence of MSH6 protein, thus MMR-deficient profile) had a variant of c.1012G > C p.(Gly338Arg) in the MSH2 gene, classified as Variant of Uncertain Significance (VUS) in 2023. That year, she was also diagnosed with oesophageal squamous cell carcinoma (ESCC), again MMR-deficient. Although uncommon, a proportion of ESCC can be MMR-deficient. The ESCC showed complete response to nivolumab. Genetic studies of the three tumours showed the same germline variant. During follow-up, the tumour board requested a reclassification of the VUS due to suspected Lynch syndrome. This time the genetic variant was classified as likely pathogenic, confirming Lynch syndrome in May 2025. This case highlights the importance of additional MMR profile evaluation in patients with multiple tumours, even if tumour types are unusual. Such evaluation may improve individual treatment and classification of syndrome-associated tumours.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-025-04269-1","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

A 59-year-old woman with two colorectal adenocarcinomas in 2015 and 2022 (both with loss of MSH2 and focal presence of MSH6 protein, thus MMR-deficient profile) had a variant of c.1012G > C p.(Gly338Arg) in the MSH2 gene, classified as Variant of Uncertain Significance (VUS) in 2023. That year, she was also diagnosed with oesophageal squamous cell carcinoma (ESCC), again MMR-deficient. Although uncommon, a proportion of ESCC can be MMR-deficient. The ESCC showed complete response to nivolumab. Genetic studies of the three tumours showed the same germline variant. During follow-up, the tumour board requested a reclassification of the VUS due to suspected Lynch syndrome. This time the genetic variant was classified as likely pathogenic, confirming Lynch syndrome in May 2025. This case highlights the importance of additional MMR profile evaluation in patients with multiple tumours, even if tumour types are unusual. Such evaluation may improve individual treatment and classification of syndrome-associated tumours.

查看原文本刊更多论文

转移性错配修复缺陷食管鳞状细胞癌导致Lynch综合征的诊断，对纳武单抗治疗完全有效。

一名在2015年和2022年患有两例结直肠癌的59岁女性（均伴有MSH2缺失和MSH6蛋白的局灶性存在，因此mmr缺陷谱）在MSH2基因中存在C . 1012g > C p.（Gly338Arg）变异，在2023年被归类为不确定意义变异（VUS）。同年，她也被诊断为食管鳞状细胞癌（ESCC），同样是mmr缺陷。虽然不常见，但一部分ESCC可能存在mmr缺陷。ESCC对纳武单抗显示完全缓解。对这三种肿瘤的遗传研究显示出相同的种系变异。在随访期间，肿瘤委员会要求对疑似Lynch综合征的VUS进行重新分类。这一次，该基因变异被归类为可能致病，并于2025年5月确认了林奇综合征。该病例强调了对多发性肿瘤患者进行额外MMR谱评估的重要性，即使肿瘤类型不寻常。这样的评价可以改善个体化治疗和综合征相关肿瘤的分类。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Virchows Archiv 医学-病理学

CiteScore

7.40

自引率

2.90%

发文量

204

审稿时长

4-8 weeks

期刊介绍： Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.