Recent advances in the pathology of heritable gastric cancer syndromes

Autores da FMUP

• Irene Gullo

  Autor

• Maria De Fátima Machado Henriques Carneiro

  Autor

Participantes de fora da FMUP

• van der Post, RS

Unidades de investigação

• Patologia

Abstract

Despite the relative rarity of hereditary gastric cancer syndromes, the prompt recognition of their specific clinical features and histopathological characteristics is pivotal in offering patients the most appropriate treatment. In this article, we address the three major inherited syndromes that primarily affect the stomach: hereditary diffuse gastric cancer (HDGC), caused by germline variants in CDH1 and CTNNA1; gastric adenocarcinoma and proximal polyposis of the stomach, caused by germline mutations in promoter 1B of APC; and familial intestinal gastric cancer, which has a poorly defined genetic cause. The main focus will be on HDGC, in light of the recent publication of updated clinical practice guidelines and emerging concepts regarding HDGC histopathology. In particular, we describe the broad morphological spectrum of HDGC lesions, stressing the importance of recognising indolent and aggressive phenotypes. Moreover, we discuss the increased risk of gastric (pre)malignancies developing in patients with other well-defined hereditary cancer syndromes, such as familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis, Li-Fraumeni syndrome, and hereditary breast and ovarian cancer syndrome.

Keywords

• CDH1; CTNNA1; familial adenomatous polyposis; GAPPS; hereditary gastric cancer; Lynch syndrome; signet‐ ring cell carcinoma; stomach