A 38-year-old man presents with concerns after finding out that his father was recently diagnosed with colon cancer. Family history is only significant for his paternal grandfather who also had colon cancer. A screening colonoscopy is performed, and a polyp is found in the ascending (proximal) colon, which on biopsy shows adenocarcinoma. A mutation in a gene that is responsible for which of the following cellular functions is the most likely etiology of this patient’s cancer?

Inhibits progression from G1 to S phase

A 31-year-old woman comes to the emergency department because of a 4-day history of fever and diarrhea. She has abdominal cramps and frequent bowel movements of small quantities of stool with blood and mucus. She has had multiple similar episodes over the past 8 months. Her temperature is 38.1°C (100.6°F), pulse is 75/min, and blood pressure is 130/80 mm Hg. Bowel sounds are normal. The abdomen is soft. There is tenderness to palpation in the left lower quadrant with guarding and no rebound. She receives appropriate treatment and recovers. Two weeks later, colonoscopy shows polypoid growths flanked by linear ulcers. A colonic biopsy specimen shows mucosal edema with distorted crypts and inflammatory cells in the lamina propria. Which of the following is the most appropriate recommendation for this patient?

Start annual colonoscopy starting in 8 years

Obtain barium follow-through radiography in 1 year

Obtain glutamate dehydrogenase antigen immunoassay now

Start annual magnetic resonance cholangiopancreatography screening in 10 years

A 19-year-old woman presents to the physician for a routine health maintenance examination. She has a past medical history of gastroesophageal reflux disease. She recently moved to a new city to begin her undergraduate studies. Her father was diagnosed with colon cancer at age 46. Her father's brother died because of small bowel cancer. Her paternal grandfather died because of stomach cancer. She takes a vitamin supplement. Current medications include esomeprazole and a multivitamin. She smoked 1 pack of cigarettes daily for 3 years but quit 2 years ago. She drinks 1–2 alcoholic beverages on the weekends. She appears healthy. Vital signs are within normal limits. Physical examination shows no abnormalities. Colonoscopy is unremarkable. Germline testing via DNA sequencing in this patient shows mutations in DNA repair genes MLH1 and MSH2. Which of the following will this patient most likely require at some point in her life?

Annual colonoscopy beginning at 20–25 years of age

Surgical removal of a desmoid tumor

Prophylactic proctocolectomy with ileoanal anastomosis

Measurement of carcinoembryonic antigen and CA 19-9 yearly

A 42-year-old woman presents to the physician because of an abnormal breast biopsy report following suspicious findings on breast imaging. Other than being concerned about her report, she feels well. She has no history of any serious illnesses and takes no medications. She does not smoke. She consumes wine 1–2 times per week with dinner. There is no significant family history of breast or ovarian cancer. Vital signs are within normal limits. Physical examination shows no abnormal findings. The biopsy shows lobular carcinoma in situ (LCIS) in the left breast. Which of the following is the most appropriate next step in management?

Careful observation + routine mammography

Left mastectomy + axillary dissection + local irradiation

Lumpectomy + breast irradiation

Cancer risk and surveillance in IBD for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Pathophysiology - From Gut Fire to Cancer

Chronic Inflammation: The primary driver. Persistent inflammation with high levels of pro-inflammatory cytokines (TNF-α, IL-6) and reactive oxygen species (ROS) causes continuous mucosal injury and repair.
Genetic Instability: This leads to oxidative DNA damage, promoting an "inflammation-dysplasia-carcinoma" sequence.
- Key mutation: p53 inactivation is a critical, early event.

Histology of colitis-associated dysplasia in IBD

⭐ In contrast to sporadic CRC, IBD-associated cancer arises from flat, invisible dysplasia and p53 mutations occur early in the process.

Risk Factors - The Usual Suspects

Disease Duration & Extent: Risk ↑ significantly after 8-10 years of colitis. Pancolitis carries a much higher risk than left-sided colitis or proctitis.
Severity of Inflammation: Greater histologic and endoscopic inflammation correlates with ↑ cancer risk.
Primary Sclerosing Cholangitis (PSC): A strong, independent risk factor for both cholangiocarcinoma and colorectal cancer (CRC).
Family History: First-degree relative with CRC, especially if diagnosed at < 50 years old.
Anatomic Factors: Presence of strictures or previous finding of dysplasia.

⭐ Patients with IBD and concomitant PSC have a very high CRC risk; surveillance colonoscopy should begin at the time of PSC diagnosis, regardless of colitis duration.

UC patient cases: Pancolitis vs. Left-sided Colitis

Surveillance Strategy - The Watchful Scope

Chromoendoscopy for dysplasia in ulcerative colitis

Initiation: Begin surveillance colonoscopy 8-10 years after diagnosis of pancolitis, or 12-15 years for left-sided disease.
Frequency: Every 1-3 years, based on risk stratification (e.g., family history, severity, PSC).
Procedure: High-definition colonoscopy, ideally with chromoendoscopy (dye spray) to enhance visualization.
- Biopsy Protocol: Random 4-quadrant biopsies every 10 cm, plus targeted biopsies of any suspicious lesions.

⭐ For patients with co-existing Primary Sclerosing Cholangitis (PSC), start annual surveillance immediately upon PSC diagnosis due to markedly ↑ CRC risk.

Dysplasia Management Flow

Dysplasia Management - Nipping Trouble in the Bud

Management hinges on whether dysplasia is endoscopically visible and resectable.

Invisible Dysplasia (Flat/Non-polypoid):
- Difficult to completely remove endoscopically.
- High risk for synchronous or metachronous cancer.
- Action: Proctocolectomy is the standard of care.
**Visible Dysplasia (Polypoid):
- Endoscopically Resectable: Complete removal (polypectomy) is possible.
  - Follow-up with surveillance colonoscopy in 3-6 months.
- Non-resectable: Treat as invisible dysplasia → Colectomy.

⭐ Any dysplasia found in a patient with IBD implies a "field defect," indicating widespread genetic instability in the colonic mucosa, significantly ↑ risk for CRC elsewhere in the colon.

High‑Yield Points - ⚡ Biggest Takeaways

Chronic inflammation is the primary driver of dysplasia and colorectal cancer (CRC) in IBD.

Risk is highest in ulcerative colitis (UC) and Crohn's colitis, especially with pancolitis and disease duration >8-10 years.

Primary Sclerosing Cholangitis (PSC) is a major independent risk factor for CRC.

Surveillance colonoscopy with chromoendoscopy and random biopsies begins 8-10 years post-diagnosis.

The goal is to detect dysplasia, a precursor to cancer, which may be invisible.

High-grade dysplasia or multifocal low-grade dysplasia are strong indications for colectomy.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play