Intestinal Pathology Step 1 Practice Exam

Correct: B — Ectopic gastric mucosa in Meckel diverticulum
A positive Tc-99m pertechnetate scan (Meckel scan) localizes ectopic gastric mucosa within a Meckel diverticulum. This heterotopic tissue secretes hydrochloric acid, which can ulcerate the adjacent ileal mucosa, causing bleeding. Meckel's diverticulum is a remnant of the vitelline duct with Rule of 2's: 2% of population, 2 feet from ileocecal valve, 2 inches long, 2 types of ectopic tissue (gastric or pancreatic), 2x more common in males, presents before age 2 in most symptomatic cases.

A— Pancreatic heterotopia may cause obstruction but does not concentrate pertechnetate.
C— Diverticulitis alone would not concentrate the radionuclide.
D— Adenoma is not the classic bleeding source in Meckel.
E— Pseudo-diverticula are common in the colon but do not explain Meckel.

Correct: B — Incomplete neural crest cell migration causes aganglionosis
Hirschsprung disease (congenital aganglionic megacolon) results from failure of neural crest cells to migrate completely from the proximal intestine toward the rectum during weeks 5–12 of gestation. This leads to a segment lacking ganglion cells (aganglionosis), most commonly the distal rectum and sigmoid. Without enteric ganglia, peristalsis cannot propel stool, causing functional obstruction. The RET gene (receptor tyrosine kinase) is implicated in short-segment disease.

A— Mesodermal issues would affect muscularis, not ganglia specifically.
C— Endodermal differentiation produces the epithelium, not ganglia.
D— Mesoderm apoptosis would not explain selective absence of ganglia.
E— Hirschsprung is characterized by absence, not hyperplasia of nerves.

Correct: B — Venous congestion causes mucosal bleeding (currant jelly stool)
Intussusception is the telescoping of a proximal bowel segment (intussusceptum) into a distal segment (intussuscipiens), dragging the mesentery with it. This compression obstructs venous return, leading to venous congestion and mucosal edema. Continued pressure compromises capillary flow, causing bleeding into the bowel lumen. The mixture of blood and mucus produces the characteristic currant jelly stools. Peak incidence is 3 months to 3 years; most cases are idiopathic (viral prodrome → lymphoid hyperplasia as lead point in terminal ileum). Air or hydrostatic reduction is often successful if performed within 24–48 hours.

A— Gastric acid exposure is not the primary mechanism.
C— Early intussusception causes bleeding before translocation.
D— Hypermotility does not cause this specific blood-and-mucus pattern.
E— Methemoglobin conversion is not relevant to intussusception.

Correct: C — Transmural necrosis with perforation and sepsis
Acute mesenteric ischemia from SMA thromboembolism (often from AFib) is a surgical emergency. The small bowel supplied by the SMA is extremely vulnerable to ischemic necrosis because it has limited collateral circulation. Without prompt reperfusion (within hours), the bowel undergoes transmural infarction, leading to perforation, bacterial peritonitis, and sepsis. The classic presentation is severe pain with minimal exam findings ("pain out of proportion to exam"). Risk factors include AFib, hypercoagulable states, atherosclerosis, and low-flow states.

A— Overgrowth occurs in chronic ischemia, not acute necrosis.
B— Strictures develop after recovery from chronic ischemic colitis.
D— Carcinoid syndrome is not a complication of mesenteric ischemia.
E— Secondary lactase deficiency is seen in mucosal injury, not primary to acute ischemia.

Correct: B — Splenic flexure (Griffith's point) is a watershed zone
The splenic flexure (Griffith's point) and rectosigmoid junction (Sudeck's point) are watershed zones — areas of relatively tenuous vascular supply at the junction of major arterial territories (SMA and IMA). During systemic hypotension or low-flow states, these zones are the first to become ischemic because they depend on collateral flow. Ischemic colitis classically spares the rectum because it has dual blood supply from the IMA and hypogastric arteries. The sigmoid and descending colon are also vulnerable. Most cases of ischemic colitis are reversible if perfusion is restored quickly.

A— Cecum is supplied by the ileocolic artery (well-perfused).
C— Hepatic flexure is supplied by SMA branches (less vulnerable).
D— Rectum is dual-supplied; relatively spared.
E— Transverse colon proximal to flexure has better collaterals.

Correct: B — Deamidated gluten peptides bound to HLA-DQ2/DQ8
In celiac disease, the enzyme tissue transglutaminase (tTG) deamidates glutamine residues in gluten peptides to glutamic acid, making them highly immunogenic. The deamidated peptides then bind to HLA-DQ2 or HLA-DQ8, which are present in nearly 95% of celiac patients. This triggers a CD4+ T cell response and B cell production of IgA antibodies against both the deamidated gluten and tTG itself. The pathology shows villous atrophy, crypt hyperplasia, and increased IELs. Diagnosis requires serology (anti-tTG IgA) and biopsy; treatment is a gluten-free diet.

A— tTG modifies the gluten, but the target is deamidated peptide.
C— Intact unmodified gluten is not recognized as an antigen.
D— While anti-tTG is produced, the peptide itself is the primary target.
E— ZO-1 is not the antigen in classic celiac disease.

Correct: B — Villous atrophy and increased IELs (celiac-associated)
Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten-sensitive enteropathy (celiac disease). Nearly all DH patients have celiac-type small intestinal histology (villous atrophy, increased IELs) even if asymptomatic. The skin shows granular IgA deposits at dermal papilla tips on direct immunofluorescence — a pathognomonic finding. DH is associated with anti-endomysial antibodies and anti-tTG IgA. Treatment is a gluten-free diet, and the skin lesions improve within weeks to months as the intestine heals.

A— Crypt abscess is seen in ulcerative colitis, not DH-associated disease.
C— Transmural inflammation is characteristic of Crohn disease, not DH.
D— Strictures develop in chronic Crohn disease.
E— Colonic crypt loss is seen in UC, not associated with DH.

Correct: B — Enterocutaneous/perianal fistulas from transmural disease
Crohn disease is characterized by skip lesions (discontinuous inflamed segments) and transmural inflammation affecting all layers of the bowel. The transmural involvement can penetrate the bowel wall, creating fistulas — abnormal connections to adjacent bowel (internal fistula), skin (enterocutaneous), or perirectal tissue (perianal/anorectal). Biopsy shows noncaseating granulomas in ~30–50% of cases. The mesentery becomes thickened ("creeping fat"). Most common sites: terminal ileum and right colon.

A— Toxic megacolon is a complication of UC, not Crohn.
C— Fulminant colitis with universal involvement is UC, not Crohn.
D— Massive hemorrhage is more typical of UC.
E— C. difficile infection is not a defining complication of Crohn.

Correct: B — Continuous mucosal inflammation without skip lesions
Ulcerative colitis (UC) is distinguished by: (1) continuous inflammation without skip lesions; (2) limited to mucosa and submucosa (non-transmural); (3) always involves the rectum and extends proximally; (4) crypt abscesses and crypt distortion on histology. UC increases risk of colorectal cancer and is associated with primary sclerosing cholangitis (PSC). Complications include toxic megacolon, perforation, and systemic manifestations (uveitis, pyoderma gangrenosum, PSC).

A— Granulomas are seen in Crohn, not UC (though UC may have rare granulomas in UC; Crohn is more typical).
C— UC does not involve small bowel; Crohn commonly affects terminal ileum.
D— Fistulas are a hallmark of Crohn, not UC.
E— While total colectomy can cure UC, it is not the only distinguishing feature.

Correct: A — Avoid anticholinergics and opioids (risk of perforation)
Toxic megacolon is a serious complication of IBD (more common in UC) characterized by colonic dilation >6 cm with loss of haustra and signs of systemic toxicity (fever, tachycardia, dehydration, electrolyte abnormalities). It is triggered by severe inflammation and can progress to perforation with peritonitis and sepsis. Anticholinergic agents and opioid antidiarrheals are contraindicated because they reduce colonic propulsive activity, increasing intraluminal pressure and perforation risk. Management includes IV fluids, electrolyte repletion, broad-spectrum antibiotics, high-dose IV corticosteroids, and often urgent colectomy.

B— IV steroids are indicated to reduce inflammation.
C— TNF-α inhibitors can be used in some cases.
D— 5-ASA is standard maintenance therapy.
E— Iron supplementation is safe and may be needed for anemia.

Correct: B — Obstruction/perforation of diverticulum with inflammation and abscess
Diverticulitis occurs when a pseudo-diverticulum (outpouching of mucosa and submucosa through weakened muscular points where blood vessels penetrate) becomes obstructed by fecal matter or inspissated debris. This leads to bacterial overgrowth within the diverticulum, mucosal ulceration, and perforation. Inflammation extends into the pericolic fat, causing fever and leukocytosis. Small contained perforations form paracolic or pericolic abscesses. Sigmoid colon is most commonly affected (especially in Western populations with low-fiber diet). Risk increases with age.

A— Strictures develop as a long-term sequela, not acutely.
C— Overgrowth alone causes diarrhea, not acute inflammation.
D— Mesenteric ischemia is not the primary mechanism.
E— Carcinoma may coexist but is not the cause of acute diverticulitis.

Correct: B — Herniation adjacent to penetrating blood vessels
Colonic pseudo-diverticula are formed by herniation of mucosa and submucosa through weakened areas of the colonic wall at sites where blood vessels penetrate the muscularis. The blood vessel runs through the wall of the diverticulum. Erosion of the diverticulum or mucosal ulceration can expose and erode this vessel, causing painless bleeding (often brisk and requiring transfusion). Right-sided diverticula bleed more frequently than left-sided. Most diverticular bleeding stops spontaneously, but severe hemorrhage may require angiographic intervention or surgical resection.

A— Ectopic gastric mucosa is found in Meckel diverticula, not colonic pseudo-diverticula.
C— Inflammation causes diverticulitis, not typical painless bleeding.
D— Volvulus is not a feature of colonic diverticulosis.
E— Malignancy does not cause diverticular bleeding.

Correct: C — Villous architecture exposes dysplastic epithelium to carcinogens
Adenomatous polyps are classified histologically as: (1) Tubular (lowest cancer risk ~5%); (2) Tubulovillous (intermediate ~10–20%); (3) Villous (highest cancer risk ~40%). Villous adenomas have finger-like surface projections that expose a larger area of dysplastic epithelium directly to the colonic lumen and carcinogenic fecal contents. The increased surface area and prolonged contact with carcinogens increase the risk of malignant transformation. All adenomas are presumed to arise via the adenoma-carcinoma sequence (APC mutation → K-RAS → p53 loss).

A— Mucus secretion is not the primary factor in cancer risk.
B— Bacterial colonization does not explain cancer risk differences.
D— Hyperplastic polyps are distinct from adenomas and have very low cancer risk.
E— There is no evidence of protective mucin in tubular adenomas.

Correct: B — Benign hamartomas with arborizing smooth muscle and normal epithelium
Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition caused by STK11 mutations. The syndrome features: (1) mucocutaneous pigmentation (dark macules on lips, buccal mucosa, genitals); (2) benign hamartomatous polyps throughout the GI tract (especially small bowel), characterized by arborizing (tree-like) smooth muscle bundles and normal mucosa (not dysplastic); (3) intussusception (polyps act as lead points). Despite the benign histology of individual polyps, PJS carries increased cancer risk (gastric, small bowel, colon, pancreatic, breast, lung) due to the underlying STK11 mutation.

A— Dysplasia is not a feature of hamartomas.
C— Inflammatory pseudopolyps are post-ulcerative, not congenital.
D— Hyperplastic polyps are a separate entity with very low malignant potential.
E— Sessile serrated polyps have MLH1 methylation, not STK11 mutations.

Correct: B — MLH1 methylation causes mismatch repair deficiency and MSI
Sessile serrated polyps (SSPs) are flat or slightly raised polyps with irregular serrated crypt architecture. They are characterized by MLH1 promoter methylation (epigenetic silencing), which inactivates the MLH1 mismatch repair protein. This leads to microsatellite instability (MSI-H) — defective repair of repetitive DNA sequences — accelerating progression to cancer. SSPs are part of the serrated pathway to colorectal cancer and account for ~20–30% of colorectal cancers. They often occur in the right colon and have been missed on older screening techniques.

A— APC inactivation is typical of traditional adenomas, not SSPs.
C— K-RAS activation occurs but is not the primary mechanism of SSP cancer risk.
D— p53 loss occurs late in progression but is not the distinguishing feature.
E— Germline Lynch mutations cause hereditary MSI, not sporadic SSP MLH1 methylation.

Correct: B — Exophytic tumor with chronic iron-deficiency anemia
Right-sided colorectal carcinoma (cecum, ascending colon) typically presents with: (1) exophytic, fungating growth (projecting into the lumen); (2) chronic occult bleeding → iron-deficiency anemia (presenting symptom); (3) **fatigue, dyspnea, palpitations** from anemia. The right colon has a larger lumen, so masses may grow large before causing obstruction. In contrast, left-sided CRC (rectosigmoid) often presents with change in bowel habits, obstruction, and napkin-ring appearance. Right-sided tumors have slightly worse prognosis (often stage III–IV at presentation).

A— Napkin-ring appearance is characteristic of left-sided CRC.
C— Change in bowel habits is more typical of left-sided disease.
D— Obstruction/perforation are complications of left-sided disease.
E— Visible bleeding suggests distal (rectal) involvement.

Correct: B — Napkin-ring stenosis causes mechanical obstruction
Left-sided colorectal carcinoma (descending and sigmoid colon) commonly presents with: (1) circumferential "napkin-ring" or "apple-core" appearance — a constricting annular lesion that narrows the lumen; (2) change in bowel habits (constipation, straining, pencil-thin stools from narrowing); (3) **visible bright red bleeding** (distal location); (4) **obstruction** if advanced. The stricturing nature causes progressive narrowing and partial obstruction, leading to alternating constipation and diarrhea as stool bypasses the stenotic segment.

A— Exophytic growth is more typical of right-sided CRC.
C— Adenomas do not present as carcinomas in this setting.
D— Fistulization is not the primary mechanism of obstruction.
E— Mucinous differentiation is not the cause of obstruction.

Correct: B — Desmoid tumors, osteomas, and congenital hypertrophy of RPE
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome caused by APC (adenomatous polyposis coli) gene mutations. Features: (1) **hundreds to thousands of colonic adenomas** by age 10–20; (2) **virtual 100% risk of CRC** by age 50 if untreated (requires prophylactic total colectomy); (3) extraintestinal manifestations: desmoid tumors (invasive fibromatosis), osteomas (benign bone lesions), congenital hypertrophy of retinal pigment epithelium (CHRPE), and increased risk of gastric, duodenal, and pancreatic cancers.

A— Lynch syndrome is due to mismatch repair genes, not APC.
C— Endometrial cancer and ovarian cysts are associated with Lynch, not FAP.
D— Gastric intestinal metaplasia is seen in some FAP families but is not a major feature.
E— PSC is associated with ulcerative colitis and Lynch syndrome, not FAP.

Correct: B — Mismatch repair deficiency causes microsatellite instability
Lynch syndrome (hereditary nonpolyposis colorectal cancer, HNPCC) is caused by germline mutations in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2. These genes normally repair DNA replication errors. Deficiency leads to microsatellite instability (MSI-H) — accumulation of mutations in repetitive DNA sequences — dramatically accelerating cancer development. Cancers are often multiple and early-onset. Amsterdam Criteria identify Lynch syndrome families: ≥3 relatives with cancer, ≥2 generations, ≥1 before age 50, and FAP excluded. Associated cancers: CRC (most common), endometrial (second most common), ovarian, gastric, ureter/renal pelvis.

A— APC mutations cause FAP, not Lynch.
C— MLH1 methylation is somatic (not germline) and occurs in sporadic cancers.
D— MMR defects affect all genes, not selectively.
E— Lynch is hereditary, not purely environmental.

Correct: B — Severe immunosuppression impairs HPV clearance and allows persistence
Anal canal carcinoma is predominantly squamous cell carcinoma (unlike rectal/colonic CRC which is adenocarcinoma). It is strongly associated with human papillomavirus (HPV) infection (especially high-risk types 16 and 18). Risk factors include: (1) receptive anal intercourse; (2) HIV/AIDS (especially CD4+ <100); (3) history of anal intraepithelial neoplasia (AIN); (4) smoking. The severely immunosuppressed state (CD4+ <100) prevents normal immune clearance of HPV, allowing persistent infection and malignant transformation. Antiretroviral therapy and immune reconstitution significantly reduce anal cancer risk.

A— Smoking accelerates cancer risk but is not the primary mechanism without HPV.
C— Familial polyposis does not increase anal cancer risk.
D— Adenomatous polyps arise in the colon, not anal canal.
E— Diverticulitis is not associated with anal SCC.