Polyps and Neoplasms

GI Polyps Overview - Polyp Parade Primer

Polyp: Abnormal tissue growth protruding from mucous membrane into lumen. Classification:

• Histology (Malignant Potential):
  • Non-neoplastic: Low/no malignant risk (hyperplastic, inflammatory, hamartomatous).
  • Neoplastic: Premalignant/malignant (adenoma, carcinoma).
• Gross Appearance (Shape):
  • Sessile: Broad-based, flat.
  • Pedunculated: Stalked.

⭐ Adenomatous polyps are common neoplastic polyps, precursors to colorectal cancer.

Non-Neoplastic Polyps - Benign Bumps

• Hyperplastic: Most common; colonic; serrated/sawtooth crypts on histology; usually no malignant potential.
• Inflammatory (Pseudopolyps): Result from mucosal damage/repair (e.g., IBD); inflamed granulation tissue; no malignant potential.
• Hamartomatous: Disorganized, mature tissue.
  • Peutz-Jeghers Polyps: Arborizing smooth muscle core. Syndrome (AD): mucocutaneous pigmentation, ↑ risk of GI & non-GI cancers (pancreas, breast, lung, ovary, testis). 📌 PJS: Pigmentation, Jejunum, Sex-cord tumors.

    ⭐ Peutz-Jeghers syndrome carries a notable lifetime risk for various cancers, including pancreatic and breast.

  • Juvenile Polyposis: Cystically dilated glands, inflamed stroma. Syndrome (AD): ↑ colorectal cancer risk if multiple polyps (> extbf{5}).

Adenomatous Polyps - The Risky Raisins

• Neoplastic polyps; precursors to colorectal cancer (CRC).
• Types:
  • Tubular: Most common (~75%), pedunculated, lowest risk.
  • Villous: Sessile, frond-like; highest malignant risk. 📌 Villainous Villous!
  • Tubulovillous: Mix, intermediate risk.
• All show epithelial dysplasia (low/high grade).
• Malignancy Risk Factors: Size (> 2cm), villous architecture, high-grade dysplasia.
• Adenoma-Carcinoma Sequence:

![Histology of Villous Adenoma](https://ylbwdadhbcjolwylidja.supabase.co/storage/v1/object/public/notes/L1/Pathology_Gastrointestinal_Pathology_Polyps_and_Neoplasms/7daeaf2c-ea84-46c2-894f-437645ea9442.jpg)

⭐ Villous adenomas, though less common than tubular, carry the highest risk of progressing to carcinoma.

Colorectal Carcinoma - The Colon Culprit

• Epidemiology: Common; Risks: age, diet (↓fiber, ↑red meat), IBD (UC > Crohn's), family Hx (FAP, Lynch).
• Molecular Pathways:
  • APC/β-catenin (CIN, ~80%): Chromosomal instability.
  • MSI (~15%): Defective DNA mismatch repair (dMMR).

• Staging (TNM): T (invasion depth), N (nodes), M (mets: liver, lung).
• Screening: Colonoscopy (age 45-50), FOBT.

⭐ Right-sided colon cancers often present with iron-deficiency anemia; left-sided with altered bowel habits/obstruction.

Other Key GI Neoplasms - Gut's Varied Villains

• Esophageal Ca:
  • SCC: Upper 2/3; Risks: Smoking, alcohol.
  • Adeno: Lower 1/3; From Barrett's esophagus.
• Stomach Ca (Adeno): Lauren classification.
  • Intestinal: Glandular; H. pylori, nitrosamines.
  • Diffuse: Signet ring cells; Linitis plastica.
• GISTs: CD117 (c-KIT)+; Interstitial cells of Cajal origin.
• Carcinoids: Neuroendocrine (NETs); Appendix/ileum common; Serotonin.
• MALT Lymphoma: Stomach; Strong H. pylori association.

⭐ Diffuse type gastric cancer (signet ring cells, linitis plastica) often presents at an advanced stage and has a poorer prognosis than intestinal type.

Hereditary GI Cancer Syndromes - Family Fault Lines

• FAP: APC (AD). 100s+ adenomas; CRC ~100% by age 40.
• Gardner: FAP variant (APC). Polyps, osteomas, desmoid tumors.
• Turcot: APC/MMR genes (AD). Polyps + CNS tumors (medulloblastoma/glioblastoma).
• Lynch (HNPCC): MSH2, MLH1 (AD). Early CRC (often proximal), endometrial Ca. 📌 Amsterdam II/Bethesda criteria.
• Peutz-Jeghers: STK11 (AD). Hamartomatous polyps, mucocutaneous pigmentation. ↑GI, breast, pancreas Ca risk.
• Juvenile Polyposis: SMAD4, BMPR1A (AD). Hamartomatous polyps. ↑CRC, gastric Ca risk.

⭐ Lynch syndrome (HNPCC) is the most common cause of inherited colorectal cancer, accounting for 2-4% of all CRCs.

High‑Yield Points - ⚡ Biggest Takeaways

• FAP: APC gene mutation, numerous adenomas, 100% CRC risk untreated; colectomy vital.
• Lynch Syndrome (HNPCC): MMR gene defects; ↑ CRC (right-sided) & endometrial cancer.
• Peutz-Jeghers: STK11/LKB1; hamartomas, pigmentation; ↑ multi-cancer risk.
• Adenoma-carcinoma sequence: APC → KRAS → p53 mutations drive most CRCs.
• Serrated polyps (SSA/P): Malignant potential, linked to BRAF mutations, CIMP pathway.
• Juvenile polyps: Common in children; syndrome form (JPS) has ↑ CRC risk.