## Histological Distinction Between Gastric Cancer Types ### Diffuse-Type (Signet-Ring Cell) Gastric Cancer **Key Point:** Signet-ring cell carcinoma is characterized by **loss of cell-to-cell adhesion** (due to E-cadherin mutations) and abundant intracellular mucin accumulation, creating the pathognomonic "signet-ring" appearance. **High-Yield:** The defining feature is the **lack of glandular differentiation and cohesion**, with individual cells infiltrating the gastric wall without forming distinct glandular structures. ### Intestinal-Type Gastric Cancer **Key Point:** Intestinal-type adenocarcinoma shows **glandular differentiation** resembling intestinal mucosa, often arising from intestinal metaplasia in the setting of chronic atrophic gastritis. ### Comparative Table | Feature | Diffuse-Type (Signet-Ring) | Intestinal-Type | |---------|---------------------------|------------------| | **Cell cohesion** | Loss of adhesion (E-cadherin ↓) | Preserved | | **Mucin** | Abundant intracellular | Variable | | **Glandular pattern** | Absent / poorly formed | Well-formed glands | | **Associated precursor** | Hereditary diffuse gastric cancer (CDH1 mutation) | Intestinal metaplasia, chronic atrophitis | | **Depth of invasion** | Early infiltration of submucosa | Often detected later | | **Prognosis** | Worse (T1 tumours already advanced) | Better (if caught early) | | **Signet-ring cells** | Pathognomonic | Absent | ### Why This Matters Clinically **Clinical Pearl:** Signet-ring cell cancers infiltrate diffusely through the gastric wall without forming a discrete mass, making them harder to detect endoscopically. Even T1 signet-ring cancers have worse outcomes than T1 intestinal-type cancers because of their infiltrative nature. **Warning:** Do not confuse the **presence of signet-ring cells** (a histological finding) with **stage** — signet-ring cell carcinoma is a histological type, not a stage. However, it is inherently more aggressive at any given stage. [cite:Robbins 10e Ch 17]
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