CASE REPORT article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
This article is part of the Research TopicPrecision Medicine and Targeted Therapies in Gastrointestinal and Genitourinary Solid TumorsView all 29 articles
A Case Report and Literature Review of Duodenal Adenocarcinoma with Complete Loss of Mismatch Repair Proteins
Provisionally accepted
- 1Department of Pathology, Daping Hospital, Army Medical University, chongqing, China
- 2Department of Radiology, Daping Hospital, Army Medical University, chongqing, China
- 3Department of Nuclear Medicine, Daping Hospital, Army Medical University, chongqing, China
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Background: Deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) phenotype holds significant prognostic and therapeutic implications in gastrointestinal cancers. While typically characterized by loss of specific MMR protein pairs, the concomitant loss of all four MMR proteins (MLH1, PMS2, MSH2, MSH6) is scarcely documented, with molecularly confirmed cases being exceptionally rare. Case Presentation: We presented a case of duodenal adenocarcinoma whose contrast-enhanced 64-row CT and PET/CT demonstrated characteristic features highly suspicious for malignancy. Subsequently, the patient underwent duodenal resection. Histopathology showed moderately differentiated adenocarcinoma invading the subserosa and immunohistochemical staining revealed MLH1, PMS2, MSH2 and MSH6 were completely lost in tumor cells. Molecular profiling confirmed MSI-H status, high tumor mutational burden (TMB-H), MLH1 promoter hypermethylation and somatic mutations in MSH2 and MSH6 genes, but without pathogenic germline variants. Conclusion: We represent a molecularly validated case of dMMR duodenal adenocarcinoma, suggesting a somatic molecular pathogenesis distinct from classic intestinal cancer. The findings highlight the critical importance of comprehensive molecular characterization in rare tumors, as accurate identification of these phenotypes are important for optimal treatment selection, particularly immune checkpoint inhibitor therapies for gastrointestinal malignancies.
Keywords: Duodenal adenocarcinoma, High microsatellite instability, Mismatch repair deficiency, somatic mutation, Tumor mutational burden
Received: 19 Nov 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Jie, feng, yuan, mi, yi and shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: wang qiu shi
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