When to Consider Lynch Syndrome in Non-Colon and Non-Endometrial Malignancies

Am Surg. 2023 May;89(5):1912-1922. doi: 10.1177/00031348211031835. Epub 2021 Jul 10.

Abstract

Lynch syndrome (LS) is a common genetic syndrome characterized by pathogenic mutations of DNA mismatch repair genes resulting in a hereditary predisposition to cancer. While typically associated with colonic and endometrial cancer, LS additionally influences the development of many other malignancies. The Amsterdam II and Revised Bethesda Guidelines are the established clinical criteria for diagnosing LS. These guidelines are based on the most general characteristics of LS and do not address specific characteristics of the less commonly LS-associated malignancies. For individuals that present initially with a non-colon and non-endometrial malignancy, recommendations and guidelines on when to consider screening for LS are limited. Therefore, it is essential that clinicians are familiar with distinct LS-associated patient- and tumor-specific characteristics, especially of the less common LS-associated cancers, so that LS's diagnosis is not missed. In this review article, we focus on extra-colonic and extra-endometrial LS-associated cancers, paying particular attention to any established or currently investigated cancer features that help raise suspicion for LS and potentially lead to its earlier diagnosis. This review will also discuss current guidelines specific to each LS-associated malignancy.

Keywords: lynch syndrome; special topics; surgical oncology.

Publication types

  • Review

MeSH terms

  • Colorectal Neoplasms, Hereditary Nonpolyposis* / diagnosis
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / pathology
  • Endometrial Neoplasms* / diagnosis
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Mutation