Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management

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 Fourteen unpublished cases, analysed in our institution, were also included.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.

Hereditary Gastric and Breast Cancer Syndromes Related to CDH1 Germline Mutation: A Multidisciplinary Clinical Review

“…According to the data published in the current literature, the number of pT1a carcinoma foci found in total gastrectomy specimens from CDH1 carriers, ranged from 1 to 487 and the size varied from <0.1 mm to 16 mm. The number of cancer foci is significantly higher in specimens with previous positive endoscopic biopsies [23]. No correlation between the number, diameter, or location of the HDGC lesions and the age, gender, or CDH1 germline variant of the CDH1 carriers has been described so far.…”

“…Pathology data from over 170 total PTG in the setting of HDGC has been published until now [23]. Gross examination revealed HDGC lesions in only a minority of cases (11.7%), encompassing pale patches, nodules, and tiny ulcers/scars.…”

“…A recent review [23] demonstrated that when a thorough histopathological examination of the entire gastric mucosa was not performed, HDGC lesions were found in only 62.5% of the total gastrectomies. In contrast, when the whole gastric mucosa was examined according to total-embedding protocol, precursor lesions or invasive carcinoma foci were identified in almost all gastrectomy specimens (95.3%).…”

“…Foveolar hyperplasia and tufting of surface epithelium, focally with globoid change, is also a frequent finding and, in some areas, vacuolization of surface epithelium is very striking, however this does not seem to be a specific finding. Intestinal metaplasia and Helicobacter pylori infection were found in 22% and 23% of total gastrectomy specimens, respectively [23].…”

Hereditary gastric cancer. Indications of genetic study. When and to whom?

“…Esta tarea es consumidora de tiempo y el patólogo debe tener los recursos necesarios y la experiencia para realizarlo. Un estudio que compara el manejo estándar de análisis de piezas de GT vs un protocolo de evaluación completa de la mucosa describe un aumento en la identificación de focos de CG desde 60% a 95% 37 . En casos en que no se encuentran focos de CG se puede considerar la posibilidad de realizar una consulta en un centro con mas experiencia en HDGC 25 .…”