Intestinal Pathology Case Review Step 1 Practice Exam

Correct: B — Skip lesions with transmural inflammation and non-caseating granulomas
Crohn disease is characterized by transmural inflammation affecting all bowel layers, leading to complications like fistulas and abscesses. The pathognomonic findings are skip lesions (discontinuous areas of inflammation separated by normal mucosa) and non-caseating granulomas (seen in 30-50% of cases). The RLQ presentation with fistulas, creeping fat, and anemia are classic. CHRISTMAS (Cobblestone, Hemorrhage, R-skip, I-ileitis, S-structure, transmural, mucosa, A-aphthous, S-serosal) mnemonizes Crohn features. Terminal ileum is the most common site.

A— Continuous mucosal ulceration is UC, not Crohn.
C— Pseudopolyps are common in UC but not primary to Crohn.
D— Superficial inflammation is UC; Crohn is transmural.
E— Pseudomembranous pattern is C. difficile.

Correct: B — Continuous mucosal and submucosal inflammation with crypt abscesses, no transmural involvement
Ulcerative colitis (UC) is defined by continuous inflammation limited to the mucosa and submucosa, always involving the rectum and extending proximally in a contiguous pattern. Key pathologic features: crypt abscesses, crypt distortion, and absence of granulomas. The ULCCCERS mnemonic captures UC: Ulcers, Limited to colon, Continuous, Crypt abscesses, Colon cancer risk, Erythema nodosum/pyoderma gangrenosum, Rectum always involved, Superficial (no transmural). Bloody diarrhea and tenesmus are hallmark symptoms.

A— Transmural and skip lesions define Crohn, not UC.
C— Fissuring ulcers are more characteristic of Crohn.
D— Granulomas are rare in UC and favor Crohn.
E— Pseudomembranes indicate C. difficile.

Correct: B — Immune-mediated cross-reactivity between intestinal and extraintestinal antigens
Extraintestinal manifestations of IBD arise from immune-mediated mechanisms, not direct extension of disease. The combination of uveitis and erythema nodosum presented here are classic extraintestinal features that parallel disease activity and correlate with HLA-B27 and HLA-B8/DR3. Other extraintestinal manifestations include: ankylosing spondylitis, erythema nodosum, pyoderma gangrenosum, primary sclerosing cholangitis (PSC—UC association), and aphthous stomatitis. The uveitis and erythema nodosum tend to improve with control of intestinal inflammation.

A— Bacterial translocation may worsen inflammation but doesn't explain arthralgias or uveitis.
C— Direct extension does not account for systemic manifestations.
D— Granulomas are not found in extraintestinal lesions (no metastatic spread).
E— Immunoglobulin malabsorption is not the mechanism.

Correct: B — Toxin-mediated epithelial cell death and necrosis with fibrin and mucus exudate overlying denuded mucosa
Clostridium difficile produces two exotoxins: Toxin A (enterotoxin) and Toxin B (cytotoxin), which inactivate Rho family GTPases, leading to loss of tight junctions, epithelial cell death, and mucosal necrosis. The dead epithelial cells, fibrin, leukocytes, and mucus form the characteristic yellow-white pseudomembranes. Risk factors include prolonged antibiotic use (clindamycin, fluoroquinolones), advanced age, and immunosuppression. Diagnosis: PCR (most sensitive), GDH + toxin assay (high specificity), or NAAT. Treatment: oral vancomycin or fidaxomicin; FMT for recurrent disease.

A— Not invasive colonization; toxin-mediated injury is the mechanism.
C— Goblet cell hyperplasia does not produce pseudomembranes.
D— Inflammatory polyps (pseudopolyps) are a feature of chronic IBD.
E— Immune complex deposition is not the primary mechanism.

Correct: B — Toxic megacolon with perforation risk; contact surgical team for urgent colectomy evaluation
Fulminant C. difficile colitis presents with severe systemic toxicity, shock, marked colonic dilatation (>5-6 cm), and elevated lactate. This constellation indicates toxic megacolon, which carries imminent risk of perforation and sepsis. Management includes aggressive fluid resuscitation, electrolyte correction, high-dose vancomycin or fidaxomicin, and **surgical consultation for potential total colectomy**—the only definitive treatment for fulminant disease with toxic megacolon. Metronidazole is inadequate for severe disease. Do NOT delay surgical evaluation.

A— SBP is not the primary complication of C. difficile colitis.
C— Hepatic encephalopathy is not a feature of C. difficile.
D— C. difficile is gram-positive, but vancomycin monotherapy is insufficient for fulminant disease without surgery.
E— Strictures are a late complication, not the acute risk.

Correct: B — Right colon; erosion of a vasa recta running at the apex of the diverticulum
Painless hematochezia from diverticulosis typically arises from the right colon and results from erosion of a vasa recta at the apex of the diverticulum. Diverticula are pseudo-diverticula (herniation of mucosa through the muscularis propria) that form where blood vessels pierce the colonic wall. The sigmoid colon is the most common site of *diverticulitis* (painful), but the right colon is the more common bleeding source. Bleeding is typically self-limited; transfusion rarely needed. Sigmoidcolon diverticulosis predominates in Western populations due to low-fiber diet.

A— Perforation causes diverticulitis, not isolated painless bleeding.
C— Transmural inflammation (diverticulitis) would cause pain.
D— Hemorrhagic polyps are not a feature of diverticulosis.
E— Hemorrhoids would present differently.

Correct: C — NPO, IV fluids, broad-spectrum antibiotics, close monitoring; percutaneous drainage if abscess enlarges or clinical deterioration occurs
Acute uncomplicated diverticulitis with small abscess is managed conservatively with NPO status, IV hydration, and broad-spectrum antibiotics covering gram-negative and anaerobic bacteria (e.g., ceftriaxone + metronidazole, or ampicillin-sulbactam). Percutaneous drainage is reserved for abscesses >4 cm or clinical deterioration (sepsis, peritonitis). Most cases resolve within 48–72 hours. Elective sigmoid colectomy is recommended after recovery from the initial episode to prevent recurrence. Urgent surgery is indicated for perforation, peritonitis, or failed conservative management.

A— Urgent surgery is not indicated for uncomplicated diverticulitis with small abscess.
B— Clear liquid diet is too permissive; NPO is appropriate.
D— C. difficile coverage is not indicated here.
E— Monotherapy is inadequate.

Correct: B — Colovesical fistula; erosion of infected diverticulum through the colonic wall into the adjacent bladder dome
Colovesical fistula is a complication of recurrent diverticulitis caused by erosion of an inflamed diverticulum through the colonic wall into the bladder. The bladder dome (peritoneal portion) is the most common site of entry. Classic presentation: pneumaturia (gas in urine) and fecaluria, often preceded by recurrent UTIs or lower abdominal pain. Diagnosis confirmed by CT cystography showing intraluminal air. Treatment is surgical resection of the involved colon segment with primary anastomosis and bladder repair. Elective colectomy after the first episode of uncomplicated diverticulitis reduces risk of fistula formation and recurrence.

A— Colocutaneous fistula (though rare) would present with drainage from the abdomen.
C— Enterocutaneous is less common with diverticulitis.
D— Rectovesical fistula is not a typical diverticulitis complication.
E— Vesicolithiasis is unrelated to fistula formation.

Correct: B — Villous architecture and high-grade dysplasia; complete endoscopic resection with negative margins
Villous adenomas carry higher cancer risk than tubulovillous or tubular types due to their architecture exposing more epithelium to malignant transformation. High-grade dysplasia (HGD) further increases risk. Management depends on: (1) **morphology** (sessile vs. pedunculated), (2) **degree of dysplasia**, and (3) **ability to achieve complete endoscopic resection**. For this villous adenoma with HGD, **complete endoscopic resection** with margin confirmation is appropriate if technically feasible. If resection is incomplete or invasive carcinoma is present, surgical consultation is warranted. Follow-up colonoscopy at 2-6 months, then per guidelines.

A— Surveillance alone is inadequate for HGD.
C— Colectomy is not routinely indicated for resectable adenomas without invasion.
D— Incineration without histology is inappropriate.
E— Prophylactic colectomy is not standard for adenomas.

Correct: B — BRAF mutation and CIMP activation leading to hypermethylation, gene silencing, and microsatellite instability (MSI-H)
Sessile serrated lesions (SSLs) are characterized by BRAF mutations (~80% of SSLs) and CpG island methylator phenotype (CIMP), which leads to epigenetic silencing of tumor suppressors (e.g., MLH1, VIM) and high microsatellite instability (MSI-H). This molecular pathway is distinct from the classical APC→KRAS→TP53 adenoma-carcinoma sequence and explains why SSLs are often "interval cancers" (occurring between screening colonoscopies) with aggressive behavior, especially when right-sided. Complete endoscopic resection of SSLs is recommended, with surveillance colonoscopy in 12 months (more frequent than for classic adenomas due to CIMP/MSI-H phenotype).

A— SSLs are often small and flat, not large or villous.
C— TP53 mutations occur late in classic adenoma-carcinoma sequence.
D— KRAS mutations are part of the classic pathway, not the SSL pathway.
E— Lynch syndrome is caused by MLH1/MSH2/MSH6/PMS2 *germline* mutations, not somatic BRAF.

Correct: B — Desmoid tumors and congenital hypertrophy of the retinal pigment epithelium (CHRPE); screen with abdominal imaging and ophthalmology
Familial adenomatous polyposis (FAP) is caused by germline APC mutations and presents with hundreds to thousands of adenomatous polyps by age 20–30, with 100% cancer risk by age 50 if untreated. Extracolonic manifestations include: desmoid tumors (benign fibromatous lesions arising from mesentery or abdominal wall, can be life-threatening), CHRPE (pigmented spots in the retina—benign but pathognomonic), osteomas, and dental abnormalities. Management: **total colectomy with ileal pouch–anal anastomosis (IPAA) or total proctocolectomy by age 20–30**. Surveillance for desmoids with imaging, ophthalmology evaluation for CHRPE.

A— Gastric polyps are less common and not the primary extracolonic manifestation.
C— Pancreatic cancer is not a major FAP complication.
D— Esophageal SCC is not FAP-associated.
E— Medullary thyroid carcinoma is part of MEN2, not FAP.

Correct: B — MLH1 or MSH2; colorectal cancer risk ~70% and endometrial cancer risk ~30% by age 70
Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) is caused by germline mutations in mismatch repair (MMR) genes: MLH1 (~30%), MSH2 (~40%), MSH6 (~10%), PMS2 (~5%). Classic presentation: early-onset colorectal cancer, endometrial cancer in women, and right-sided CRC (often within cecum/ascending colon). MSI-H and lack of MLH1/MSH2 protein on IHC are diagnostic. Lifetime colorectal cancer risk: ~70%; endometrial: ~30%. Management: **colonoscopy every 1–2 years starting age 20–25** (or 2 years before earliest cancer diagnosis in family). Aspirin and NSAIDs may reduce cancer incidence. Prophylactic hysterectomy is considered in women.

A— BRCA1 is associated with hereditary breast/ovarian, not Lynch syndrome.
C— TP53 (Li-Fraumeni) is different from Lynch.
D— PTEN (Cowden) predisposes to breast/thyroid.
E— STK11 (Peutz-Jeghers) causes hamartomas.

Correct: B — STK11 mutation; hamartomatous polyps with intussusception risk and increased GI and non-GI malignancy
Peutz-Jeghers syndrome (PJS) is caused by STK11 (LKB1) tumor suppressor mutations and features mucocutaneous pigmentation (dark brown macules on lips, buccal mucosa, and digits—present by age 5) and hamartomatous polyps throughout the GI tract, especially the small bowel. Polyps are **benign hamartomas but can cause obstruction by intussusception** (the primary acute risk in children/adolescents). Additional risks: cumulative GI cancer risk ~40% (colorectal, gastric, pancreatic, biliary) and non-GI cancers (breast, lung, ovary). Management: surveillance with capsule endoscopy or MR enterography; polypectomy if >1.5 cm or causing symptoms.

A— APC causes adenomatous FAP, not Peutz-Jeghers.
C— SMAD4 causes juvenile polyposis, not Peutz-Jeghers.
D— MLH1 (Lynch) causes MSI-H adenocarcinoma.
E— BRCA2 (hereditary breast/pancreatic cancer) is not PJS.

Correct: B — SMAD4 or BMPR1A; hamartomatous polyps with colorectal cancer and extraintestinal features
Juvenile polyposis syndrome (JPS) is caused by mutations in SMAD4 (~65%) or BMPR1A (~30%), genes involved in TGF-β signaling. Features: multiple hamartomatous ("cherry-like") polyps throughout the GI tract, typically presenting in childhood with rectal bleeding or bleeding polyps. Polyps have characteristic histology of dilated glandular structures, stromal edema, and absence of dysplasia in the hamartoma itself. Colorectal cancer risk: ~10–20%. **SMAD4 mutations** are associated with **hereditary hemorrhagic telangiectasia (HHT)-like features** (vascular malformations, bleeding). Management: surveillance colonoscopy every 1–3 years; polypectomy if >1 cm or symptomatic.

A— STK11 is Peutz-Jeghers, which presents with pigmentation.
C— APC (FAP) causes adenomatous, not hamartomatous, polyps.
D— MLH1 (Lynch) causes MSI-H adenocarcinoma.
E— PTEN (Cowden) is distinct from JPS.

Correct: B — Presents with iron deficiency anemia from chronic occult bleeding; exophytic growth pattern
Right-sided (proximal) colorectal cancer (cecum, ascending colon, hepatic flexure) typically presents with iron deficiency anemia from chronic occult bleeding because the liquid stool does not cause mechanical obstruction—instead, the tumors grow exophytically into the lumen. In contrast, left-sided (distal) CRC presents with napkin-ring annular morphology, narrowing, and obstruction (change in bowel habits, visible bright red blood per rectum, tenesmus) because the colon is narrower and stool more solid. Right-sided CRC often presents late with anemia as the first sign, leading to worse prognosis. Surveillance and early detection are crucial.

A— Acute obstruction is more common with left-sided CRC.
C— Tenesmus and visible bleeding are left-sided features.
D— LLQ pain is more typical of left-sided tumors.
E— Napkin-ring stricture is classic for left-sided CRC.

Correct: B — Napkin-ring annular morphology with circumferential narrowing causing obstruction
Left-sided (distal) colorectal cancer typically exhibits a napkin-ring or annular growth pattern, where the tumor encircles the bowel, causing progressive narrowing (stricture). This explains the classic presentation of **pencil-thin stools** (narrow stool caliber due to luminal narrowing), tenesmus, and visible bright red bleeding. Change in bowel habits (constipation or diarrhea) is common. Because obstruction occurs, these tumors are usually detected earlier than right-sided cancers. The adenoma-carcinoma sequence in left-sided CRC typically follows: APC loss → KRAS mutation → TP53 inactivation.

A— Exophytic growth is right-sided; left-sided tumors are circumferential.
C— Fistulas are complications, not the primary growth pattern.
D— Superficial erosion would not cause obstruction.
E— Submucosal dissection is an endoscopic technique, not a tumor growth pattern.

Correct: B — APC loss → KRAS mutation → TP53 inactivation; typically 10–15 years
The adenoma-carcinoma sequence (Fearon-Vogelstein model) describes the stepwise molecular progression from normal epithelium to invasive carcinoma: (1) APC loss (initiating event, leads to early adenoma), (2) KRAS activation (intermediate adenoma, increased proliferation), (3) TP53 inactivation (late adenoma/high-grade dysplasia), and (4) loss of 18q (SMAD2/SMAD4) leading to invasive carcinoma. This progression typically takes **10–15 years**, providing a window for screening and polyp removal before malignancy. Tubular adenomas are lower risk than villous; LGD is lower risk than HGD. Endoscopic resection of adenomas at the LGD/HGD stage prevents progression to cancer in ~90% of cases.

A— KRAS first is incorrect; APC is the initiating event. Timeframe too short.
C— TP53 is typically later, not first. Mismatch repair genes are not part of this sequence.
D— SMAD4/BMPR1A are involved in hamartomatous syndromes, not classic adenoma-carcinoma.
E— BRAF/CIMP is the serrated pathway, not the classic sequence.

Correct: B — Colonoscopy every 2 years because disease duration >7 years and extensive colonic involvement
CRC surveillance in IBD is recommended based on several factors: disease duration (>7 years), extent (pancolonic involvement), presence of primary sclerosing cholangitis (PSC), and prior dysplasia history. For this patient with 15-year UC history involving the entire colon, colonoscopy every 2 years with targeted biopsies of suspicious areas (not random sampling) is indicated. Use of 5-ASA and sulfasalazine reduces CRC risk by ~40%. In cases of **indefinite dysplasia or high-grade dysplasia**, consider colectomy. In UC, **TP53 mutations** occur earlier than in sporadic CRC, and p53 testing may improve dysplasia detection. PSC-UC patients need particularly close surveillance (annual colonoscopy).

A— Annual colonoscopy is too frequent for patients without dysplasia.
C— Surveillance is essential given disease duration and extent.
D— Waiting 10 years is too long for this patient's risk profile.
E— Prophylactic colectomy is not routine without dysplasia.

Correct: B — Primary sclerosing cholangitis (PSC); screen with serology (alkaline phosphatase, ALT, bilirubin) and MRCP at diagnosis and periodically, annual colonoscopy for CRC screening
Primary sclerosing cholangitis (PSC) is a well-recognized extraintestinal complication of ulcerative colitis (not Crohn disease), affecting ~10% of UC patients. Features: progressive intrahepatic and/or extrahepatic bile duct strictures with beaded appearance on MRCP, elevated alkaline phosphatase and bilirubin, and increased cholangiocarcinoma risk (~10–20% lifetime). Screening: baseline serum alkaline phosphatase/ALT/bilirubin; MRCP if abnormalities present or at 10-year disease mark. PSC-UC patients have **higher CRC risk**—annual colonoscopy is recommended. Ursodeoxycholic acid may slow disease progression. No effective medical therapy; liver transplantation is reserved for advanced disease or cholangiocarcinoma.

A— Hepatitis B is not associated with UC.
C— Autoimmune hepatitis is distinct from PSC.
D— Budd-Chiari is a thrombotic complication, not a typical IBD complication.
E— Fulminant hepatic failure is not the typical presentation of PSC.

Correct: B — Mucosal ulceration and transmural inflammation impairing myenteric plexus function and peristalsis; NPO, IV fluids, high-dose IV corticosteroids, antibiotics, and urgent surgical consultation if no improvement in 48 hours
Toxic megacolon in severe UC (or Crohn disease) results from extensive mucosal ulceration and transmural inflammation that damages the myenteric (Auerbach) plexus, impairing coordinated peristalsis and allowing luminal gas accumulation. Clinical findings: colon diameter >5.5–6 cm (>5 cm is diagnostic), fever, toxemia, leukocytosis, elevated lactate, and peritoneal signs. Management: NPO, IV fluids, electrolyte correction, high-dose IV methylprednisolone, broad-spectrum antibiotics, and **urgent surgical consultation**—if no improvement within 48 hours, **urgent total colectomy** is indicated (only definitive treatment). Avoid antiperistaltic agents and laxatives. Mortality is high (5–40%) without timely surgical intervention.

A— Antibiotics alone are insufficient.
C— C. difficile is not the primary cause; high-dose corticosteroids are needed.
D— Laxative overuse is not the mechanism in IBD.
E— Neostigmine is used in pseudo-obstruction, not toxic megacolon.