Hereditary Diffuse Gastric Cancer: Diagnosis and Management Vanessa Blair, Iain Martin, David Shaw, Ingrid Winship, Dale Kerr, Julie Arnold, Pauline Harawira, Maybelle McLeod, Susan Parry, Amanda Charlton, Michael Findlay, Brian Cox, Bostjan Humar, Helen More, Parry Guilford  Clinical Gastroenterology and Hepatology  Volume 4, Issue 3, Pages 262-275 (March 2006) DOI: 10.1016/j.cgh.2005.12.003 Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 1 Case T (family A). Gastric carcinoma (at 49 y) and metachronous bilateral lobular breast carcinoma (at 43 and 49 y). (A) White-light gastroscopy: 14-mm nodule, anterior wall, proximal antrum, biopsy examination showed SRC carcinoma. (B) Gastric pathology mapping (see Figure 2 for method) showed 18 foci of SRC carcinoma. The macroscopic T2 lesion was located at the body–antrum transitional zone and invaded the muscularis propria; the remaining 17 microscopic T1a foci were confined to the lamina propria. (C–E) Gastric T2 carcinoma: (C) SRCs invade the mucosa and submucosa; (D) higher magnification of box in C shows classic SRC morphology (arrows); (E) ABPAS stain showing a diffuse pattern of invasion of muscularis propria by poorly differentiated adenocarcinoma. (F, G) Lobular breast carcinoma: (F) atypical lobular hyperplasia (with atypical cells partly involving acini of lobule), (G) invasive lobular carcinoma cells in single files and loosely cohesive clusters. (H) E-cadherin immunohistochemistry: invasive lobular carcinoma cells are negative (arrow), epithelial cells of normal lobules are positive (brown staining). Clinical Gastroenterology and Hepatology 2006 4, 262-275DOI: (10.1016/j.cgh.2005.12.003) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 2 Stomach pathology map of case E (family A), a 16-year-old male. Gastrectomy performed after the sole biopsy specimen from a 3-mm pale lesion detected at his first surveillance chromogastroscopy showed carcinoma. Mucosal zones are indicated by translucent colors (see Charlton et al25 for methods). Black circles are SRC carcinoma foci, to scale, except foci less than 1 mm, which are shown arbitrarily as 1 mm. Mapping revealed 15 foci of carcinoma. Only 2 foci were greater than 1 mm in size: a 3.3-mm focus in the transitional zone and a 2.1-mm focus in the proximal antrum. Inset: typical microscopic focus of carcinoma in HDGC: SRCs infiltrate between gastric pits in the superficial lamina propria. Clinical Gastroenterology and Hepatology 2006 4, 262-275DOI: (10.1016/j.cgh.2005.12.003) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions

Figure 3 Flow chart showing the recommended procedures for the diagnosis and management of HDGC. Clinical Gastroenterology and Hepatology 2006 4, 262-275DOI: (10.1016/j.cgh.2005.12.003) Copyright © 2006 American Gastroenterological Association Institute Terms and Conditions