diffuse type

The Lauren classification divides gastric adenocarcinoma into intestinal and diffuse types based on histology and pathogenesis. Diffuse-type gastric cancer is composed of poorly differentiated, discohesive cells (often signet ring cells filled with mucin that pushes the nucleus to the periphery) that infiltrate the gastric wall individually or in small clusters rather than forming glandular structures. This infiltrative growth pattern can produce linitis plastica, where the stomach wall becomes diffusely thickened and rigid ('leather bottle stomach') visible on imaging or endoscopy.

Unlike intestinal-type gastric cancer, diffuse-type is not strongly associated with H. pylori-induced chronic gastritis, intestinal metaplasia, or dietary carcinogens (nitrosamines, smoked foods). Instead, it has a stronger genetic component, notably associated with loss-of-function mutations in the CDH1 gene (E-cadherin), which is responsible for cell-cell adhesion; germline CDH1 mutations cause hereditary diffuse gastric cancer syndrome, prompting consideration of prophylactic gastrectomy in mutation carriers. Diffuse-type cancer tends to affect younger patients, has no clear geographic or sex predilection (unlike intestinal type, which is more common in older males and in high-incidence regions like Japan), and can spread transperitoneally, causing Krukenberg tumors (bilateral ovarian metastases with signet ring cells) or peritoneal carcinomatosis.

Clinically, diffuse-type gastric cancer often presents at a more advanced stage with a poorer prognosis compared to intestinal type, partly due to its infiltrative nature making it harder to detect early and resect completely. Management involves surgical resection when feasible, though the diffuse growth pattern often necessitates more extensive gastrectomy, and outcomes remain guarded due to the aggressive biology and early metastatic potential.