Familial Intraductal Papillary Mucinous Neoplasm Associated With the Germline MSH6 Missense Variant and Progression of Pancreatic cancer.

IF 1.7 4区医学 Q3 GASTROENTEROLOGY & HEPATOLOGY

Pancreas Pub Date : 2024-07-01 Epub Date: 2024-02-24 DOI:10.1097/MPA.0000000000002313

Koji Tezuka, Mitsunori Yamakawa, Ryoko Murakami, Ichiro Hirai, Ryo Toya, Akihiko Suzuki, Hiroshi Kawamura, Yuki Miyano, Hidenori Sato, Fuyuhiko Motoi

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引用次数: 0

Abstract

Objectives: Intraductal papillary mucinous neoplasm (IPMN) in individuals with at least one first-degree relative with IPMN is defined as familial IPMN. However, few studies have reported on familial IPMN, its clinical characteristics, or the associated genetic factors.

Materials and methods: We report the case of a 58-year-old woman with multifocal IPMN and a mural nodule in the pancreatic body. The patient underwent a distal pancreatectomy and developed pancreatic head cancer 1 year and 6 months postoperatively. The patient had a family history of multifocal IPMN in her father. Therefore, a genetic predisposition to IPMN and pancreatic cancer was suspected. The patient was analyzed for germline variants, and the resected IPMN was subjected to immunohistochemical and somatic variant analyses.

Results: Next-generation sequencing revealed a heterozygous germline missense variant in exon 5 of MSH6 (c.3197A>G; Tyr1066Cys). The pathogenicity of this variant of uncertain significance was suspected based on multiple in silico analyses, and the same MSH6 variant was identified in the patient's father's colonic adenoma. The mural nodule in the pancreatic body was pathologically diagnosed as a high-grade IPMN with ossification and somatic KRAS and PIK3CA variants.

Conclusions: This case revealed a possible genetic factor for familial IPMN development and presented interesting clinicopathological findings.

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家族性导管内乳头状黏液性肿瘤与种系MSH6缺失性变异和胰腺癌进展有关

目的：至少有一名一级亲属患有导管内乳头状粘液瘤（IPMN）的个体被定义为家族性 IPMN。然而，关于家族性 IPMN、其临床特征或相关遗传因素的研究报道却很少：我们报告了一例 58 岁女性的病例，她患有多灶性 IPMN 和胰腺体壁结节。患者接受了胰腺远端切除术，术后 1 年 6 个月发展为胰头癌。患者的父亲有多灶性 IPMN 家族史。因此，她被怀疑患有 IPMN 和胰腺癌遗传倾向。对患者进行了种系变异分析，并对切除的 IPMN 进行了免疫组化和体细胞变异分析：结果：新一代测序发现，MSH6第5外显子存在一个杂合子种系错义变异（c.3197A>G；Tyr1066Cys）。根据多项硅学分析，怀疑该变异具有不确定的致病性，而且在患者父亲的结肠腺瘤中也发现了相同的MSH6变异。胰腺体壁结节经病理诊断为高级别IPMN，伴骨化及体细胞KRAS和PIK3CA变异：该病例揭示了家族性 IPMN 发病的可能遗传因素，并展示了有趣的临床病理结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pancreas 医学-胃肠肝病学

CiteScore

4.70

自引率

3.40%

发文量

289

审稿时长

1 months

期刊介绍： Pancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.