Microsatellite instability in pancreatic and ampullary carcinomas: histology, molecular pathology, and clinical implications

Hum Pathol. 2023 Feb:132:176-182. doi: 10.1016/j.humpath.2022.06.009. Epub 2022 Jun 14.


Microsatellite instability (MSI)/defective DNA mismatch repair (dMMR) represents an important molecular alteration with diagnostic, prognostic, and predictive value. The increasing interest toward this genetic alteration is given to the high response rate of MSI/dMMR tumors to immunotherapy. There are different cancers in the periampullary region that can harbor MSI/dMMR, and significant morphological-molecular correlates should be acknowledged in this district: (1) pancreatic ductal adenocarcinoma (PDAC): in this tumor category, the prevalence of MSI/dMMR is about 1-2%, and medullary and colloid variants are the most typically involved; (2) ampullary adenocarcinoma: here the prevalence of MSI/dMMR is up to 18%, and in this neoplastic group, MSI/dMMR is more commonly found in the intestinal subtype; (3) pancreatic acinar cell carcinoma: here the prevalence of MSI/dMMR is up to 14%; and (4) pancreatic and ampullary neuroendocrine carcinoma: in this tumor category, the prevalence of MSI/dMMR is up to 5-8%, and this molecular alteration should be assessed also in cases of mixed neuroendocrine-non-neuroendocrine neoplasms. Given the clinical importance of MSI/dMMR and its not-negligible prevalence among the different carcinomas arising in this district, its assessment should become part of the routine diagnostic workflow at least for the most typical histotypes. The test of choice is represented by immunohistochemistry for PDAC and ampullary carcinomas, and by direct molecular analyses including MSI-based polymerase chain reaction and next-generation sequencing for acinar cell and neuroendocrine carcinomas.

Keywords: AVC; MSI; Microsatellite; Mismatch; PDAC; Pancreatic ductal adenocarcinoma; dMMR.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Ampulla of Vater* / pathology
  • Carcinoma, Pancreatic Ductal* / pathology
  • Colorectal Neoplasms* / genetics
  • DNA Mismatch Repair
  • Humans
  • Microsatellite Instability
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Pathology, Molecular