AUTHOR=Ohtsubo Koushiro , Sato Shigeki , Sakaguchi Hiroyuki , Kotani Hiroshi , Nishiyama Akihiro , Yamashita Kaname , Yano Seiji , Toshima Fumihito , Inoue Dai , Gabata Toshifumi , Ikeda Hiroko , Watanabe Atsushi , Notohara Kenji , Fujisawa Takao , Nakamura Yoshiaki , Yoshino Takayuki , Miyake Kunio , Miwa Kazuhiro , Takeuchi Shinji 

TITLE=Case Report: Medullary carcinoma of the pancreas with MLH1 promoter hypermethylation, induced deficient mismatch repair, successfully treated with an immune checkpoint inhibitor

JOURNAL=Frontiers in Oncology

VOLUME=Volume 15 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1551038

DOI=10.3389/fonc.2025.1551038

ISSN=2234-943X

ABSTRACT=We report the case of a 75-year-old woman with a pancreatic body mass. Pathological findings from endoscopic ultrasonography-guided fine-needle aspiration revealed medullary carcinoma of the pancreas (MCP). Deficient mismatch repair (dMMR) and high microsatellite instability (MSI-H) were identified through immunohistochemistry and next generation sequencing, respectively. While immunohistochemistry suggested MLH1 abnormality, no MLH1 mutation was; hypermethylation of the MLH1 promoter was later confirmed via bisulfite sequencing. The patient initially received nab-paclitaxel plus gemcitabine, achieving tumor shrinkage. Upon tumor regrowth, she was treated with the anti-programmed cell death-1 immune checkpoint inhibitor (ICI) pembrolizumab, which resulted in significant tumor reduction. This is the first case report of MCP with dMMR/MSI-H due to MLH1 promoter hypermethylation, effectively treated with an ICI.