New Insights in Histogenetic Pathways of Gastric Cancer

Abstract

The aim of this paper was to describe 3 possible histogenetic pathways for poorly cohesive (diffuse) carcinomas and 2 for intestinal-type gastric carcinomas (GCs), which might influence the behavior of GC. In the present observational study, 102 patients with early (n = 50) and advanced GCs (n = 52) were evaluated, and the histogenetic background was analyzed. All of the cases were sporadic GCs. For particular aspects, Maspin, E-cadherin, and SLUG immunostains were performed. For our final conclusions, the results were correlated with literature data. In early stages, poorly cohesive carcinomas can display 3 histogenetic pathways, with particular molecular behaviors: "carcinoma with intraepithelial pagetoid onset" (with or without a switch from E-cadherin to SLUG positivity), "carcinoma with early lymphatic invasion" (carcinoma limited to mucosa but with carcinomatosis of the lymph vessels from subjacent layers), and "microglandular-type poorly cohesive carcinoma" (the onset is similar with adenocarcinoma but abrupt dedifferentiation can be seen in the submucosa, with persistence of a dual component in the deep layers). The intestinal type carcinoma can be developed on the background of superficially located dysplasia ("classic adenocarcinoma") or in the submucosal heterotopic mucosa ("adenocarcinoma arising from the mucosal infolding in the submucosa"). Based on personal observations correlated with literature data, 5 histopathogenetic pathways are proposed with specific denominations. Each of them can partially explain the aberrant behavior of early gastric cancer.

FIGURE 1

Carcinoma with intraepithelial pagetoid onset—the stepwise evolution.

FIGURE 2

Carcinoma with early lymphatic invasion is limited to the mucosa but presents carcinomatosis of the lymph vessels (^∗) in submucosa and muscularis propria (A, B). Inside the intramucosal lymph vessels (^∗), Maspin (C), and E-cadherin expression is kept (D).

FIGURE 3

Microglandular-type poorly cohesive carcinoma presents intramucosal tubular architecture (A–C), with well-defined buddings (B,C), and diffuse growth with small glands in the muscularis propria (D–F).

FIGURE 4

Classic tubular carcinoma presents a stepwise evolution from dysplasia to carcinoma, with progressive acquirement of Maspin positivity.

FIGURE 5

In the gastric submucosa, low power view (A,B) shows a round mucosal island surrounding by muscularis mucosae, with normal covering mucosa. A higher power view (C) shows no dysplastic or tumor cells but adenocarcinomas can originate from this mucosal infolding in the submucosal layer. In this case, the protruded lesion was endoscopically resected, in a 74-year-old men.