Comprehensive genomic profiling-guided treatment selection in appendiceal adenocarcinoma with discordant mismatch repair findings: a case report and literature review
Year: 2026
Type: preprint
Study design: Case Report
Abstract: Background Appendiceal adenocarcinoma is rare, and systemic treatment is often extrapolated from colorectal cancer. Discordance between mismatch repair (MMR) immunohistochemistry and microsatellite instability (MSI) or tumor mutational burden (TMB) testing can complicate treatment selection, particularly in rare gastrointestinal cancers. We report a case in which comprehensive genomic profiling (CGP) helped interpret discordant MMR findings and guide subsequent treatment. Case presentation: A 25-year-old woman presented with advanced appendiceal signet-ring cell adenocarcinoma with bilateral ovarian metastases and peritoneal dissemination. MMR immunohistochemistry showed loss of MLH1/PMS2 expression, whereas MSI testing and tumor-normal paired CGP showed microsatellite-stable disease and low TMB. Nivolumab plus ipilimumab was not effective, and ascites persisted after mFOLFOX6 alone. CGP revealed RAS / BRAF V600E wild-type and HER2-negative status without apparent major anti-EGFR resistance-associated alterations, and also identified a germline TP53 pathogenic variant consistent with Li-Fraumeni syndrome. After panitumumab was added to mFOLFOX6, the patient achieved a marked clinical improvement and a partial response, with sustained disease control at the time of writing. Conclusions This case suggests that MMR protein loss on immunohistochemistry alone may not define the dominant therapeutic biology of a tumor when MSI and TMB results are discordant. Integrating MMR immunohistochemistry, MSI status, TMB, and CGP may support treatment selection in rare gastrointestinal cancers and may reveal clinically important germline findings.
Source: Research Square
Institutions: University of Toyama, Toyama University Hospital
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204554743