Case Report: Medullary carcinoma of the pancreas with MLH1 promoter hypermethylation, induced deficient mismatch repair, successfully treated with an immune checkpoint inhibitor
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 <i>MLH1</i> mutation was; hypermethylation of the <i>MLH1</i> 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 <i>MLH1</i> promoter hypermethylation, effectively treated with an ICI.
Authors
- Kazuhiro Miwa (ORCID: https://orcid.org/0009-0000-8943-5956)
- Akihiro Nishiyama (ORCID: https://orcid.org/0000-0002-4805-9787)
- Yoshiaki Nakamura (ORCID: https://orcid.org/0000-0002-5241-6855)
- Dai Inoue
- Atsushi Watanabe (ORCID: https://orcid.org/0000-0002-4181-8111)
- Hiroshi Kotani (ORCID: https://orcid.org/0000-0002-6001-0636)
- Fumihito Toshima (ORCID: https://orcid.org/0000-0003-2609-8985)
- Shinji Takeuchi (ORCID: https://orcid.org/0000-0002-3779-1454)
- Hiroyuki Sakaguchi
- Kunio Miyake (ORCID: https://orcid.org/0000-0001-9196-2229)
- Takayuki Yoshino (ORCID: https://orcid.org/0000-0002-0489-4756)
- Kenji Notohara (ORCID: https://orcid.org/0000-0001-5618-1312)
- Takao Fujisawa (ORCID: https://orcid.org/0000-0002-9196-9436)
- Koushiro Ohtsubo (ORCID: https://orcid.org/0000-0002-4490-4306)
- Seiji Yano
- Toshifumi Gabata (ORCID: https://orcid.org/0000-0002-9413-3431)
- Hiroko Ikeda (ORCID: https://orcid.org/0000-0001-7105-6376)
- Kaname Yamashita
- Shigeki Sato (ORCID: https://orcid.org/0009-0001-7753-4559)
Institutions
- Kurashiki Central Hospital (JP)
- Kanazawa University Hospital (JP)
- Kanazawa Medical University Hospital (JP)
- National Cancer Center Hospital East (JP)
- University of Yamanashi (JP)
- Komatsu (Japan) (JP)
Publication Details
- Journal
- Frontiers in Oncology
- Published
- 2025-03-27
- DOI
- https://doi.org/10.3389/fonc.2025.1551038
- Citations
- 1
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 1.05