Tumours of the Gastrointestinal Tract

## Oesophageal Tumours ### 1. Oesophageal Adenocarcinoma - **Demographics:** White males; 7× more common in men; highest in developed Western countries. - **Risk Factors:** Barrett oesophagus, chronic GERD, documented dysplasia, tobacco, obesity, radiation. - **Protective Factors:** Fruits and vegetables. - **Pathogenesis:** Accumulation of genetic and epigenetic changes (TP53, chromosomal abnormalities). - **Morphology:** - **Location:** Distal 1/3 of oesophagus; may invade gastric cardia. - **Gross:** Early flat/raised patches; late exophytic mass or ulcerated. - **Microscopy:** Mucin-producing, gland-forming tumour; Barrett oesophagus adjacent to tumour. ### 2. Oesophageal Squamous Cell Carcinoma (SCC) - **Demographics:** Adults >45 yrs; males 4× more; higher incidence in African Americans. - **Risk Factors:** Alcohol and tobacco (synergistic), poverty, nutritional deficiencies, caustic injury, achalasia, Plummer-Vinson syndrome, hot beverages, HPV (high-risk regions). - **Morphology:** - **Location:** Middle 1/3 of oesophagus. - **Gross:** Grey-white plaque-like thickenings; later polypoid/obstructing or ulcerated. - **Microscopy:** Moderately to well differentiated; variants include verrucous and spindle cell. - **Spread:** Rich submucosal lymphatics lead to circumferential and longitudinal spread (skip lesions). - **Lymph Node Metastases:** - Upper 1/3: Cervical nodes. - Middle 1/3: Mediastinal, paratracheal, tracheobronchial. - Lower 1/3: Gastric and coeliac nodes. ## Gastric Tumours ### 1. Gastric Polyps - **Inflammatory & Hyperplastic Polyps:** Associated with chronic gastritis; risk of dysplasia increases with size. - **Gastric Adenomas:** Arise in background of chronic gastritis with intestinal metaplasia; premalignant; require complete excision. ### 2. Gastric Adenocarcinoma - **Aetiology:** H. pylori (most common), chronic atrophic gastritis, EBV infection. - **Histologic Types:** - **Intestinal Type:** Bulky, discrete, gland-forming cells. - **Diffuse Type:** Signet ring cells; diffuse infiltration leading to Linitis Plastica ("leather bottle stomach"). ### 3. Gastric MALT Lymphoma - Derived from mucosa-associated lymphoid tissue (MALT) induced by chronic H. pylori gastritis. - H. pylori eradication can lead to tumour regression in early stages. ### 4. Gastrointestinal Stromal Tumour (GIST) - Most common mesenchymal tumour of the abdomen; arises from Interstitial Cells of Cajal. - **Mutations:** Activating mutations in c-KIT or PDGFRA tyrosine kinases. - **Treatment:** Tyrosine kinase inhibitors (e.g., Imatinib). ## Colorectal Tumours ### 1. Colorectal Polyps - **Non-Neoplastic:** Inflammatory, Hamartomatous (Peutz-Jeghers), and Hyperplastic (no malignant potential). - **Neoplastic (Adenomas):** Characterized by cytologic dysplasia; precursors to adenocarcinoma. - **Sessile Serrated Adenomas:** Lack cytologic dysplasia but carry malignant potential. ### 2. Genetic Syndromes - **Familial Adenomatous Polyposis (FAP):** APC mutation (Chr 5); >100 polyps; cancer risk 100% by age 30; Chromosomal Instability (CIN) pathway. - **Hereditary Non-Polyposis Colorectal Cancer (HNPCC/Lynch):** DNA mismatch repair gene mutations (MLH1, MSH2); Microsatellite Instability (MSI) pathway. ### 3. Colorectal Adenocarcinoma - **Prognostic Factors:** 1. Depth of invasion (T stage) 2. Lymph node metastases (N stage). ## Appendix Tumours - **Carcinoid:** Most common; usually incidental at distal tip; almost always benign. - **Adenocarcinoma:** Can lead to intraperitoneal seeding; mimics mucinous ovarian tumours in women. - **Pseudomyxoma Peritonei:** Advanced complication where the abdomen fills with mucin; managed by debulking but often fatal. ## Summary Table | Tumour | Location | Key Feature | |---|---|---| | Oesophageal Adenocarcinoma | Distal 1/3 | Barrett oesophagus; TP53 mutation | | Oesophageal SCC | Middle 1/3 | Alcohol/Tobacco; HPV (some regions) | | Gastric Adenocarcinoma | Stomach | H. pylori; Signet ring cells | | GIST | Stomach | c-KIT mutation; Cajal cells | | Carcinoid | Small Intestine | Most aggressive site for carcinoids | | FAP | Colon | APC mutation; >100 polyps | | HNPCC | Colon | Mismatch repair defect; MSI |