Gastric Carcinoma

Overview
  • The vast majority of gastric malignancies are adenocarcinomas which display two morphological variants, intestinal and diffuse, which appear to derive from different cells of origin and display distinct pathogeneses, morphologies, and prognoses.
Cell of Origin
  • Intestinal-variant gastric carcinomas appear to derive from cells that have previously undergone metaplasia to an small intestine mucosa-like cell due to long-term presence of chronic gastritis. Diffuse-variant gastric carcinomas appear to derive from native cells of the gastric epithelium that has undergone neoplastic transformation.
Pathogenesis
  • The pathogenesis of gastric carcinoma is still poorly understood although the ingestion of nitrate-containing foods may be the root cause. Nitrates present in salted and dried foods may be converted to carcinogens by gastric bacteria, including possibly Helicobacter pylori, eventually inducing neoplastic conversion of gastric cells. In the case of the intestinal-variant, intestinal metaplasia associated with long-term chronic gastritis due to either H. pylori-mediated or autoimmune-mediated etiologies may represent the first hit along the sequence of neoplastic transformation. It should be noted that no association between the diffuse-variant and H. pylori has been found.
Morphology
  • Histology
    • The basic distinguishing feature between diffuse- and intestinal-variant gastric carcinomas is the cohesiveness of neoplastic cells. Intestinal-variant cells display good cohesion and thus grow in discrete masses and often glandular masses resembling Colonic Adenocarcinoma. In contrast, diffuse-variant cells do not attach to one another and thus diffusely infiltrate the wall of the stomach. In addition, in the diffuse-variant, cytosolic boluses of mucus eccentrically shift the nuclei, thus giving a "Signet Ring" like appearance to the neoplastic cells.
  • Grossly
    • Gastric Carcinomas tends to occur more frequently in the distal stomach at the antrum and pylorus muscle along the lesser curvature. Regardless of the variant there are four major gross growth patterns which gastric carcinomas display. Exophytic growth results in protrusion of the tumor protrudes into gastric lumen. Flat growth of the tumor often results in a grossly inobservable mass. Excavated growth is observed as an eroded area of mucosa which must be differentiated from Peptic Ulcer Disease which has a smooth base and punched out margins; in contrast, carcinomas display an irregular necrotic base and heaped-up margins. Linitis Plastica is only observed in the diffuse-variant in which entire stomach is infiltrated by neoplastic cells, rendering the stomach wall thick and rigid similar to a "leather-bottle".
Clinical Consequences
  • Sadly, gastric carcinomas are typically asymptomatic until fairly advanced resulting in a poor five year survival rate. Patients may present with anorexia or weight loss as well as nausea, vomiting, or abdominal discomfort. Metastatic spread can occur through any variety of routes although particular locations of metastasis possess historical eponyms. For example, Virchow's Node refers to metastasis to supraclavicular lymph node, Krukenberg Tumor refers to bilateral metastasis to ovaries, and Sister Mary Joseph Node refers to metastasis to the peri-umbilical lymph node.