Tumors of the small and large intestines

1. Polyp Terminology

• Polyps = mucosal epithelial lesions that protrude into the gut lumen.
• Shape: pedunculated (narrow stalk) or sessile (no stalk).
• Origin:
  • Abnormal maturation / inflammation → non-neoplastic polyps
  • Epithelial proliferation + dysplasia → adenomas (neoplastic, preneoplastic)
• Hyperplastic polyps = most common polyp of colon & rectum.

2. Small Intestine Tumors

A) Peutz-Jeghers polyps (non-neoplastic, hamartomatous)

• AD disorder: multiple GI hamartomatous polyps + mucocutaneous melanin macules (lips, buccal mucosa, palms).
• Complication: intussusception.
• ↑ risk of breast, lung, pancreas carcinoma.

B) Benign mesenchymal tumors

• Leiomyoma, lipoma, fibroma.

C) Adenocarcinoma

• Grows as napkin-ring encircling lesion or polypoid fungating mass.
• Most arise in the duodenum → obstructive jaundice / pancreatitis.
• RF: chronic inflammation (e.g., Crohn disease).
• Histology: glandular/acinar, medullary, undifferentiated.
• Sx (late): cramping pain, N/V, weight loss.
• Usually advanced at Dx (wall penetration, mesentery, regional LN, liver mets) — still ~70% 5-yr survival after excision.

D) Carcinoid / Neuroendocrine tumors

• Arise from gut neuroendocrine cells; all potentially malignant (aggressiveness depends on site of origin).
• Appendix = most common site of gut carcinoid.
• Massive serotonin secretion → carcinoid syndrome: diarrhea, flushing, bronchospasm, cyanosis, skin telangiectasias.
• May be named by predominant product (e.g., gastrinoma, insulinoma).

E) Gastrointestinal lymphoma (MALT)

• Most common intestinal lymphoma; B-cell, marginal zone = extranodal marginal zone lymphoma.
• No liver/spleen/BM involvement at Dx (regional LN may be involved).
• Gastric MALT: H. pylori → chronic gastritis → atrophy → B/T-cell activation → mutations → lymphoma.
• Indolent; H. pylori eradication → regression.
• Generally better prognosis than other primary GI tumors.

3. Large Intestine Tumors

A) Non-neoplastic polyps

• Formed by abnormal maturation, inflammation or architecture → no malignant potential (with one exception below).
• Hyperplastic polyps: most common; small, nipple-like, rectosigmoid; often multiple.
  • Exception — sessile serrated adenoma (SSA): right colon, may be precursor of CRC (MSI pathway).
• Juvenile polyps: hamartomatous, lamina propria; children <5 yr; cause rectal bleeding / painful infarction; no malignancy.

B) Adenomas (neoplastic, preneoplastic)

• Pedunculated (small) or sessile (large); peak >60 yr.
• All arise from epithelial proliferation + dysplasia: adenoma → dysplasia → adenocarcinoma.
• Subtypes:
  • Tubular — mostly tubular glands; most common
  • Villous — villous projections; bleed more / symptomatic
  • Tubulovillous — mixed
  • Sessile serrated — serrated crypts (MSI pathway)
• Malignant risk ↑ with size, villous architecture, severity of dysplasia.
• All adenomas are resected on discovery.

C) Familial adenomatous polyposis (FAP)

• AD inherited; APC mutation (5q21).
• Adolescence: <100 polyps → age 30: 500–2500 polyps carpeting mucosa.
• Colorectal cancer risk ≈ 100% by midlife → prophylactic colectomy required.

D) Colorectal carcinoma (CRC)

• Adenocarcinoma of colon/rectum — one of the most common carcinomas in developed countries; peak 60–70 yr.
• Risk factors:
  • Hereditary (rare): FAP
  • Adenomatous polyp, ulcerative colitis
  • Diet: ↓ vegetable fiber, ↑ refined carbohydrates, ↓ vitamin A/C/E

Carcinogenesis — two pathways

Feature	APC / β-catenin (adenoma-carcinoma)	DNA mismatch repair (MSI)
Sequence	epithelial proliferation → adenoma → dysplasia → carcinoma	normal → SSA → carcinoma
Key hits	Loss of APC → β-catenin↑ → K-Ras mutation → 18q21 LOH (SMAD2/4, TGF-β) → p53 loss	Loss of MMR genes (MLH1, MSH2, MSH6, PMS1/2) → microsatellite instability
Location	Usually left/distal colon	Right colon (SSA)
Prognosis	Worse	Better

Morphology

• Proximal (right) colon: polypoid / fungating masses along cecum & ascending colon.
• Distal (left) colon: annular “napkin-ring” constrictions, lumen narrowing.
• Both penetrate the bowel wall.

Clinical features

• Asymptomatic for years.
• Right-sided: slow occult bleeding → iron-deficiency anemia, fatigue, dyspnea.
• Left-sided: obstruction (constipation/diarrhea/bloating, abdominal pain); bright red blood per rectum (rectosigmoid).
• Spread: direct + lymphatic + hematogenous. Mets order: regional LN → liver → lungs → bones → peritoneum (peritoneal carcinomatosis).

Diagnosis

• Rectal exam, fecal occult blood, barium enema.
• Colonoscopy + biopsy = gold standard.
• CT / imaging for staging mets.

💡 High-yield: Hyperplastic polyp = most common (rectosigmoid, benign). SSA = right colon, MSI precursor of CRC. Adenoma→carcinoma sequence: APC → KRAS → 18q (SMAD/DCC) → p53. FAP (AD, APC, ~100% cancer risk) → prophylactic colectomy. CRC presentation: right = anemia (polypoid), left = obstruction (napkin-ring). Appendix = #1 site of gut carcinoid; carcinoid syndrome requires liver mets to bypass first-pass. Gastric MALT lymphoma regresses with H. pylori eradication.