Estudo histopatológico de gastrectomias totais de portadores de mutações de CDH1

Entre as síndromes genéticas associadas a um risco aumentado de carcinoma gástrico, o carcinoma hereditário difuso do estômago (CHDE), causado por alterações germinativas do gene CDH1, caracteriza-se pelo desenvolvimento multigeracional de carcinoma difuso do estômago e carcinoma lobular da mama. A gastroscopia tem uma acuidade diagnóstica limitada para a identificação de lesões neoplásicas precoces e a gastrectomia total (GT) constitui atualmente o tratamento de escolha para os portadores assintomáticos de mutações do gene CDH1. Com o intuito de compreender melhor a história natural desta síndrome e o impacto das alterações histopatológicas na orientação clínica dos doentes, os autores deste estudo realizaram uma revisão exaustiva da literatura, centrada nas gastrectomias totais realizadas em indivíduos assintomáticos com CHDE. Globalmente, foram analisadas as GTs de 174 portadores assintomáticos de mutações do gene CDH1. Os resultados deste estudo demonstraram que o exame histológico da totalidade da mucosa gástrica constitui o gold standard para a identificação de focos de cancro em GTs realizadas no contexto de CHDE, devendo ser realizado por patologistas com experiência nesta síndrome para garantir a acuidade de diagnóstico. Esta abordagem fornecerá informação relevante para um melhor seguimento dos doentes com CHDE, particularmente no que se refere ao tempo ideal para a realização de GT.

Autores e Afiliações:
Rocha JP 1, Gullo I 2,3,4,5, Wen X 4,5,6, Devezas V 7,8,9, Baptista M 7,8,9, Oliveira C 3,4,5, Carneiro F 2,3,4,5

1 Local Health Unit of Matosinhos, Matosinhos, Portugal.

2 Department of Pathology, Centro Hospitalar de São João (CHSJ), Porto, Portugal.

3 Department of Pathology, FMUP, Porto, Portugal.

4 Institute of Molecular Pathology and Immunology at the University of Porto (Ipatimup), Porto, Portugal.

5 Institute for Research Innovation in Health (i3S), University of Porto, Porto, Portugal.

6 Department of Pathology, Centro Hospitalar Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Portugal.

7 Department of General Surgery, CHSJ, Porto, Portugal.

8 Department of General Surgery, FMUP, Porto, Portugal.

9 General Surgery, High Risk Consultation of Digestive Tumours, CHSJ, Porto, Portugal.

Abstract:
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome characterised by multigenerational diffuse gastric cancer, and is mainly caused by germline alterations in the CDH1 gene. Currently, endoscopy has limited diagnostic accuracy, and total gastrectomy (TG) is the treatment of choice for asymptomatic CDH1 carriers. In this study, we aimed to obtain a better understanding of HDGC syndrome by exploring the histopathological findings of TG specimens from asymptomatic HDGC patients. A comprehensive literature review was carried out, searching for TGs performed in asymptomatic HDGC patients. Fourteen unpublished cases, analysed in our institution, were also included. The series encompassed 174 CDH1 carriers. Preoperative endoscopic biopsies were positive in 28.3%. A macroscopic lesion was apparent in 11.7% of TGs. Histopathological analysis revealed intraepithelial lesions and/or intramucosal signet ring cell carcinoma in 87.9% of TGs. When we explored the type of protocol used for handling the specimens, we found that microscopic cancer foci were detected in 95.3% of TGs when a total-embedding protocol (assessment of the totality of gastric mucosa) was applied, and only in 62.5% when no specific protocol was used (P < 0.001). Helicobacter pylori infection was found in 23.4% cases. In conclusion, a thorough histopathological examination of gastric mucosa remains the gold standard for detection of cancer foci in HDGC gastrectomy specimens, requiring experienced pathologists for an accurate diagnosis. A better understanding of the natural history of HDGC will enable better clinical management of HDGC patients, particularly regarding the optimal timing for the performance of TG.

Revista: Histopathology, Volume 73, Issue 6, December 2018, Pages 878-886

Link: https://onlinelibrary.wiley.com/doi/abs/10.1111/his.13715