Gastric mixed large cell neuroendocrine-adenosquamous carcinoma with heterogenous MSH6 loss in Lynch syndrome

• Published in: Human Pathology Reports Vol. 26; p. 300579
• Main Authors: Dawley, Jillian C., Haroon Ahmad, Y., Riall, Taylor S., Sun, Belinda L.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2021; Elsevier
• Subjects: DNA mismatch repair gene; Gastric cancer; Lynch Syndrome; Mixed neuroendocrine-adenosquamous carcinoma; Lynch Syndrome; DNA mismatch repair gene; Gastric cancer; Mixed neuroendocrine-adenosquamous carcinoma
• ISSN: 2772-736X; 2772-736X
• DOI: 10.1016/j.hpr.2021.300579

Lynch syndrome (LS) is the most common hereditary gastrointestinal cancer predisposition syndrome and is caused by mutations in DNA mismatch repair (MMR) genes. Deficiency of MMR proteins manifests as the microsatellite instability-high (MSI-H) phenotype. Gastric cancer is the second most common non-gynecological LS-associated malignancy, and LS-associated gastric cancer is most commonly adenocarcinoma of the intestinal type. Neuroendocrine carcinoma and adenosquamous carcinoma each account for less than 1% of all gastric cancers. Herein, we report a case of an 80-year-old male with history of remote colon cancer and melanoma presenting with a gastric cancer shown to be mixed large cell neuroendocrine-adenosquamous carcinoma. In addition, this mixed carcinoma showed complete loss of MSH6 in the adenosquamous component but intact MSH6 expression in the large cell neuroendocrine carcinoma component. Genetic analysis showed germline mutation of MSH6 gene confirming Lynch Syndrome in this patient.