9.2 Inflammatory Bowel Disease & Colorectal Neoplasms
Key Takeaways
- Ulcerative colitis affects mucosal/submucosal layers continuously starting from the rectum, while Crohn disease presents with transmural, skip lesions anywhere from mouth to anus with non-caseating granulomas in 40-50% of cases.
- Patients with ulcerative colitis or Crohn colitis require surveillance colonoscopy every 1-2 years starting 8 years after disease onset.
- Colorectal cancer screening for average-risk individuals begins at age 45 and continues through age 75 (colonoscopy every 10 years, FIT annually, or sDNA-FIT every 3 years).
- Individuals with a first-degree relative with colorectal cancer diagnosed before age 60 must start screening at age 40 (or 10 years younger than the youngest affected relative) with colonoscopy every 5 years.
- Familial Adenomatous Polyposis (FAP) is caused by autosomal dominant APC gene mutations (chromosome 5q21), producing >100 adenomatous polyps and 100% risk of colorectal adenocarcinoma by age 40 if prophylactic total proctocolectomy is not performed.
Last updated: July 2026
9.2 Inflammatory Bowel Disease & Colorectal Neoplasms
High-Yield Overview: Lower gastrointestinal disorders require differentiating non-infectious inflammatory bowel disease (Crohn disease vs. Ulcerative Colitis) and recognizing precancerous polyps and hereditary cancer syndromes. Mastering screening intervals for average-risk and high-risk populations is among the most heavily tested topics on the USMLE Step 2 CK.
Crohn Disease vs. Ulcerative Colitis
Inflammatory bowel disease (IBD) consists of two major disorders resulting from dysregulated immune responses to intestinal microbiota.
| Feature | Crohn Disease | Ulcerative Colitis |
|---|---|---|
| Anatomical Distribution | Mouth to anus with "skip lesions"; terminal ileum involved in 80% | Rectum extending proximally in a continuous fashion; isolated to colon |
| Depth of Inflammation | Transmural (full-thickness, muscularis propria) | Mucosal and submucosal layers only |
| Rectal Involvement | Frequently spared | Always involved (100%) |
| Endoscopic Appearance | Cobblestone mucosa, linear aphthous ulcers, creeping fat | Erythematous, friable mucosa, pseudopolyps, loss of haustra ("lead pipe") |
| Histopathology | Non-caseating granulomas (40-50%), transmural lymphoid aggregates | Crypt abscesses with neutrophilic infiltrates, superficial ulcerations |
| Structural Complications | Strictures, internal/perianal fistulas, abscesses, bowel obstruction | Toxic megacolon, severe lower GI hemorrhage, perforation |
| Serological Markers | ASCA positive (Anti-Saccharomyces cerevisiae) | p-ANCA positive |
| Smoking Impact | Exacerbates disease; increases relapse risk | Protective; smoking cessation may trigger disease flares |
| Surgical Management | Non-curative; segmental resection reserved for complications | Curative via total proctocolectomy with IPAA |
Extraintestinal Manifestations of IBD
Extraintestinal features can correlate directly with bowel activity or run an independent course.
Cutaneous Manifestations
- Erythema Nodosum: Tender, erythematous nodules on anterior shins. Correlates directly with bowel inflammation activity (Crohn > UC).
- Pyoderma Gangrenosum: Painful, rapidly progressive necrotic ulcer with violaceous, undermined borders. Correlates poorly with bowel disease activity (UC > Crohn).
Ocular & Hepatobiliary Manifestations
- Episcleritis: Scleral injection and mild irritation; tracks with bowel disease activity.
- Anterior Uveitis: Ocular pain, photophobia, and ciliary flush; independent of bowel disease activity.
- Primary Sclerosing Cholangitis (PSC): Strongly associated with Ulcerative Colitis (80% of PSC cases have underlying UC). Features p-ANCA positivity and "beading" of intra- and extrahepatic bile ducts on MRCP. Elevates risk of cholangiocarcinoma.
Metabolic Complications Unique to Crohn Disease
- Calcium Oxalate Kidney Stones: Unabsorbed fat in the lumen of the inflamed terminal ileum binds luminal calcium. Unbound free oxalate is hyperabsorbed in the colon, precipitating in urine.
- Cholesterol Gallstones: Impaired bile acid reabsorption in the diseased terminal ileum depletes the bile acid pool, increasing bile lithogenicity.
Medical Management & IBD Complications
Pharmacotherapy
- Mild-to-Moderate UC: Topical (suppository/enema) or oral 5-ASA derivatives (mesalamine, sulfasalazine).
- Acute Flares: Systemic corticosteroids (prednisone, IV methylprednisolone) for short-term remission induction ONLY.
- Moderate-to-Severe IBD: Anti-TNF agents (infliximab, adalimumab), anti-integrin agents (vedolizumab), or IL-12/23 inhibitors (ustekinumab) combined with thiopurines (azathioprine).
Toxic Megacolon
- Diagnosis: Transverse colon diameter >6 cm on plain abdominal radiograph accompanied by systemic toxicity (fever, tachycardia >120/min, leukocytosis >10,500/mm^3, anemia).
- Management: Nasogastric decompression, IV fluid resuscitation, IV broad-spectrum antibiotics, and IV methylprednisolone. Emergency subtotal colectomy is required if medical improvement fails within 24–48 hours or if perforation occurs.
Colorectal Polyps & Hereditary Cancer Syndromes
Neoplastic vs. Non-Neoplastic Polyps
- Hyperplastic Polyps: Non-neoplastic, small (<5 mm), located primarily in the rectosigmoid. Low malignant potential.
- Adenomatous Polyps: Precancerous via the classic adenoma-carcinoma sequence (APC -> KRAS -> TP53).
- Histology Risk: Villous > Tubulovillous > Tubular ("Villous is Villainous").
- Advanced Features: Size >=1 cm, high-grade dysplasia, or >=3 adenomas.
- Serrated Polyps: Premalignant via the CpG island methylator phenotype (CIMP) and BRAF mutation pathway.
Hereditary Polyposis & Non-Polyposis Syndromes
Hereditary Colorectal Cancer Suspicions
|
+---------------------------+---------------------------+
| |
Polyp Count >100 Polyps Few or No Polyps
| |
Test for APC Gene Mutation Test for Mismatch Repair
| (MMR / MSI-H) Genes
+------+------+ |
| | Lynch Syndrome (HNPCC)
FAP Gardner / Turcot (Colorectal + Endometrial
(Prophylactic Syndromes & Ovarian Cancers)
Colectomy) (Osteomas / Brain)
- Familial Adenomatous Polyposis (FAP): Autosomal dominant mutation in the APC tumor suppressor gene (chromosome 5q21). Hundreds to thousands of adenomatous polyps form during adolescence. 100% risk of CRC by age 40. Screening starts at age 10–12 with annual flexible sigmoidoscopy. Treatment: Elective total proctocolectomy.
- Gardner Syndrome: FAP + osteomas of mandible/skull, epidermoid cysts, desmoid tumors, and dental abnormalities.
- Turcot Syndrome: FAP or Lynch syndrome + central nervous system tumors (medulloblastoma, glioblastoma).
- Lynch Syndrome (HNPCC): Autosomal dominant mutation in DNA mismatch repair (MMR) genes (MSH2, MLH1, MSH6, PMS2) leading to microsatellite instability (MSI-H).
- Cancer Risks: 70-80% lifetime risk of CRC (proximal/right-sided predominance); 40-60% lifetime risk of endometrial adenocarcinoma in females; increased risk of ovarian, gastric, and urinary tract cancers.
- Surveillance: Colonoscopy every 1–2 years starting at age 20–25.
- Peutz-Jeghers Syndrome: Autosomal dominant STK11 mutation. Multiple hamartomatous polyps throughout GI tract + hyperpigmented mucocutaneous macules on lips, oral mucosa, palms, and soles.
Colorectal Cancer Screening & Clinical Presentation
Screening Guidelines (USPSTF)
| Risk Category | Clinical Criteria | Recommended Screening Protocol |
|---|---|---|
| Average Risk | Asymptomatic, age >=45, no family history of CRC | Start at age 45 through 75:<br>• Colonoscopy every 10 years<br>• Annual FIT<br>• Stool DNA-FIT (Cologuard) every 3 years |
| First-Degree Relative <60 Years | FDR diagnosed with CRC or advanced adenoma at age <60 | Start at age 40 (or 10 years younger than youngest relative's age at diagnosis); Colonoscopy every 5 years |
| First-Degree Relative >=60 Years | FDR diagnosed with CRC at age >=60 | Start at age 40; Colonoscopy every 10 years |
| IBD (UC or Crohn Colitis) | Pancolitis or left-sided colitis | Surveillance colonoscopy with biopsies every 1–2 years starting 8 years after symptom onset |
Clinical Presentation of Colorectal Carcinoma
- Right-Sided (Ascending) Lesions: Exophytic mass, chronic occult blood loss, microcytic iron deficiency anemia, fatigue. Bowel obstruction is rare due to large luminal diameter and liquid stool content.
- Left-Sided (Descending/Sigmoid) Lesions: Infiltrating "apple-core" mass, hematochezia, changes in bowel habits (pencil-thin stools), colonic obstruction.
Test Your Knowledge
A 28-year-old female presents with recurrent bloody diarrhea, abdominal cramping, and tenesmus for 4 months. Colonoscopy reveals continuous mucosal inflammation with crypt abscesses extending from the rectum up to the splenic flexure, with sparing of the terminal ileum. Biopsy confirms ulcerative colitis. She is successfully treated into remission with mesalamine. Assuming her disease remains controlled, at what time point should routine surveillance colonoscopy for colorectal carcinoma be initiated for this patient?
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Test Your Knowledge
A 46-year-old asymptomatic male presents to the clinic for a routine health maintenance examination. His 52-year-old brother was diagnosed with colon adenocarcinoma last year at age 51. The patient has no personal history of GI symptoms, polyps, or chronic medical conditions. Which of the following is the most appropriate colorectal cancer screening strategy for this patient?
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B
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D
Test Your Knowledge
A 31-year-old woman with a family history of colon and endometrial cancer in her mother (diagnosed at age 42) and maternal aunt (diagnosed at age 45) presents for evaluation. Genetic testing reveals a germline mutation in the MSH2 gene, confirming Lynch syndrome (HNPCC). Which of the following neoplasms carries the highest extra-intestinal risk in female patients with this syndrome?
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D