## Histopathological Distinction: Diffuse vs Intestinal Gastric Cancer ### Key Microscopic Features **Key Point:** The hallmark of diffuse-type (signet-ring cell) carcinoma is individual cell infiltration with mucin-filled signet-ring cells that lack cohesion and glandular differentiation, whereas intestinal-type shows organized glandular structures. ### Comparative Table | Feature | Diffuse-Type (Signet-Ring) | Intestinal-Type | | --- | --- | --- | | **Cell morphology** | Individual signet-ring cells with mucin vacuoles | Columnar cells forming glands | | **Growth pattern** | Infiltrative, non-cohesive | Glandular, cohesive masses | | **Background mucosa** | Normal or minimally altered | Intestinal metaplasia, chronic atrophic gastritis | | **Depth of invasion** | Often transmural at diagnosis | Variable, may be early | | **Prognosis** | Worse, advanced at presentation | Better if early-stage | | **Genetics** | CDH1 mutations (E-cadherin loss) | APC, TP53, KRAS mutations | ### Clinical Pearls **High-Yield:** Diffuse-type gastric cancer presents at a more advanced stage because the infiltrative pattern is not easily detected endoscopically and often involves the submucosa and muscularis propria before diagnosis. **Clinical Pearl:** Signet-ring cell carcinoma is associated with *linitis plastica* (leather-bottle stomach) — diffuse thickening of the gastric wall without a discrete mass — which carries a very poor prognosis (5-year survival <10% even after gastrectomy). **Mnemonic:** **SIGNET** = **S**ignet cells **I**nfiltrate **G**astric wall **N**on-cohesively, **E**ach cell separate, **T**ransmural spread. ### Why This Discriminates The **absence of glandular structures and presence of individual mucin-filled signet-ring cells** is the single most specific histological feature that separates diffuse-type from intestinal-type carcinoma. This morphology directly reflects loss of E-cadherin (CDH1 gene mutation), which is pathognomonic for diffuse-type disease. [cite:Robbins 10e Ch 17]
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