Gastropathology Pathology

## Summary This comprehensive study guide details the pathology of various tumours affecting the gastrointestinal tract, covering the oesophagus, stomach, colon, and appendix. It provides an overview of oesophageal adenocarcinoma and squamous cell carcinoma, highlighting their distinct risk factors, locations, and demographics. Gastric tumours discussed include different types of polyps, adenocarcinoma (intestinal vs. diffuse), MALT lymphoma, carcinoid tumours, and GIST, with emphasis on their aetiology, morphology, and unique clinical features like linitis plastica and carcinoid syndrome. The colorectal section elaborates on non-neoplastic and neoplastic polyps, detailing two major genetic syndromes, Familial Adenomatous Polyposis (FAP) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC), contrasting their genetic basis and clinical presentation. Colorectal adenocarcinoma and its prognostic factors are also addressed. Finally, appendix tumours, specifically carcinoid and adenocarcinoma, are described, along with the severe complication of Pseudomyxoma Peritonei. The document concludes with quick-reference tables and high-yield facts to aid in understanding and recall of crucial information. ## Key Points - **Oesophageal Adenocarcinoma**: Arises in the distal 1/3, primarily in white males with Barrett oesophagus as a precursor. Associated with TP53 mutations. - **Oesophageal Squamous Cell Carcinoma (SCC)**: Found in the middle 1/3, strongly linked to alcohol and tobacco synergy, and HPV in high-risk regions. - **Gastric Adenocarcinoma (Intestinal Type)**: Typically bulky, discrete, gland-forming tumours. - **Gastric Adenocarcinoma (Diffuse Type)**: Characterized by signet ring cells, diffuse infiltration, and can lead to "Linitis Plastica" (leather bottle stomach). - **Gastric MALT Lymphoma**: Develops secondary to chronic *H. pylori* gastritis; early-stage disease may regress with *H. pylori* eradication. - **Carcinoid Tumours**: Neuroendocrine tumours, most common in GIT. Carcinoid syndrome occurs when liver metastases are present, allowing vasoactive substances to bypass hepatic metabolism. - **Gastrointestinal Stromal Tumour (GIST)**: Most common mesenchymal tumour of the abdomen, arising from Interstitial Cells of Cajal, driven by activating mutations in c-KIT or PDGFRA tyrosine kinases, treatable with Imatinib. - **Neoplastic Colorectal Polyps (Adenomas)**: Characterized by cytologic dysplasia, these are precursors to colonic adenocarcinoma. - **Familial Adenomatous Polyposis (FAP)**: Caused by APC gene mutation, leading to >100 adenomatous polyps and near-certain colorectal cancer by age 30 if untreated. - **Hereditary Non-Polyposis Colorectal Cancer (HNPCC)/Lynch Syndrome**: Due to DNA mismatch repair gene defects, resulting in microsatellite instability and colorectal cancer at an earlier age than sporadic cases, but with fewer polyps than FAP. - **Colorectal Adenocarcinoma Prognosis**: Determined by depth of invasion (T stage) and presence/absence of lymph node metastases (N stage). - **Appendix Carcinoid**: Most common appendix tumour, usually benign, often an incidental finding at the distal tip. - **Pseudomyxoma Peritonei**: A severe complication of mucin-producing appendiceal tumours, where the abdomen fills with tenacious mucin, often ultimately fatal. ## Detailed Notes ### Oesophagus ### Oesophageal Adenocarcinoma **Who**: White males; 7× more common in men; highest in developed Western countries; one of the fastest-rising cancers in incidence **Risk Factors**: Barrett oesophagus, chronic GERD, documented dysplasia, tobacco, obesity, radiation | Protective: fruits & vegetables **Pathogenesis** Each step = accumulation of genetic + epigenetic changes. Epithelial clones from non-dysplastic Barrett persist and accumulate mutations over time. **Morphology** * **Location**: Distal 1/3 of oesophagus; may invade gastric cardia * **Gross**: Early = flat/raised patches → Late = exophytic mass OR ulcerated OR diffusely infiltrating * **Microscopy**: Mucin-producing, gland-forming tumour; Barrett oesophagus present adjacent to tumour ### Oesophageal Squamous Cell Carcinoma (SCC) **Who**: Adults >45 yrs; males 4× more; 6× more in African Americans than whites (NOT fully explained by alcohol/tobacco); incidence varies >100-fold between countries **High-incidence countries**: Iran, central China, Hong Kong, Argentina, Brazil, South Africa **Risk Factors**: Alcohol + tobacco (synergistic), poverty, nutritional deficiencies, caustic oesophageal injury, achalasia, Plummer-Vinson syndrome, very hot beverages, mediastinal radiation, polycyclic hydrocarbons, nitrosamines, fungus-contaminated foods, HPV (high-risk regions only) **Pathogenesis** **Morphology** * **Location**: Middle 1/3 of oesophagus (contrast: adenocarcinoma = distal 1/3) * **Gross**: Early = small grey-white plaque-like thickenings → Later = polypoid/obstructing OR ulcerated OR diffusely infiltrative (wall thick