Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease

摘要: Background and Aims The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little known about progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails detect early lesions, risk-reducing/prophylactic total gastrectomy (PTG) only curative approach. We present an HDGC family with early-onset disease in which clinical histologic findings provided insight into understanding different Methods proband was diagnosed at age 18 years metastatic DGC. CDH1 genetic testing identified a pathogenic, germline variant (c.1901C>T, p.Ala634Val). Thirty members were tested, 15 carriers identified. Results Six had PTG, negative preoperative workup. proband's 14-year-old sister youngest patient, reported date, have PTG after biopsy sampling. Intramucosal foci detected all specimens (1-33). In contrast "indolent" phenotype these foci, DGC showed pleomorphic cells, absent E-cadherin expression, increased proliferation (Ki-67 index), activation oncogenic events (p53, pSrc pStat3 overexpression). All Helicobacter pylori gastritis. Cag-A–positive strains specimens, except sister. Conclusions heterogeneous regarding behavior, endoscopic findings, histopathologic features, immunophenotypic/molecular profile. presence bizarre, cells suggestive advanced should prompt intervention. involvement full multidisciplinary team essential management patients.