Gastrointestinal - Pathology (1)

Question 1

Salivary gland tumors

• Generally…
• Pleomorphic adenoma (benign mixed tumor)
• ƒƒWarthin tumor (papillary cystadenoma lymphomatosum)
• Mucoepidermoid carcinoma

Answer 1

• Generally benign and occur in parotid gland
• Pleomorphic adenoma (benign mixed tumor)
  
  • The most common salivary gland tumor.
  • Presents as a painless, mobile mass.
  • Composed of chondromyxoid stroma and epithelium
  • Recurs if incompletely excised or ruptured intraoperatively.
• ƒƒWarthin tumor (papillary cystadenoma lymphomatosum)
  
  • A benign cystic tumor with germinal centers.
• Mucoepidermoid carcinoma
  
  • The most common malignant tumor
  • Has mucinous and squamous components.
  • Typically presents as a painless, slow-growing mass.

Question 2

Achalasia

• Definition
• Barium swallow
• Associations

Answer 2

• Definition
  
  • Failure of relaxation of LES due to loss of myenteric (Auerbach) plexus.
    
    • A-chalasia = absence of relaxation.
  • High LES opening pressure and uncoordinated peristalsis –>Ž progressive dysphagia to solids and liquids (vs. obstruction—solids only).
• Barium swallow
  
  • Shows dilated esophagus with an area of distal stenosis.
  • “Bird’s beak” [A].
• Associations
  
  • Associated with an increased risk of esophageal squamous cell carcinoma.
  • 2° achalasia may arise from Chagas disease.

Question 3

Esophageal pathologies

• Boerhaave syndrome
• Eosinophilic esophagitis
• Esophageal strictures
• Esophageal varices
• Esophagitis

Answer 3

• Boerhaave syndrome
  
  • Transmural, usually distal esophageal rupture due to violent retching
  • Surgical emergency.
• Eosinophilic esophagitis
  
  • Infiltration of eosinophils in the esophagus in atopic patients.
  • Food allergens –>Ž dysphagia, heartburn, strictures.
  • Unresponsive to GERD therapy.
• Esophageal strictures
  
  • Associated with lye ingestion and acid reflux.
• Esophageal varices
  
  • Painless bleeding of dilated submucosal veins in lower 1 ⁄3 of esophagus 2° to portal hypertension.
• Esophagitis
  
  • Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers), or chemical ingestion.

Question 4

Esophageal pathologies

• Gastroesophageal reflux disease
• Mallory-Weiss syndrome
• Plummer-Vinson syndrome
• Sclerodermal esophageal dysmotility

Answer 4

• Gastroesophageal reflux disease
  
  • Commonly presents as heartburn and regurgitation upon lying down.
  • May also present with nocturnal cough and dyspnea, adult-onset asthma.
  • Decrease in LES tone.
• Mallory-Weiss syndrome
  
  • Mucosal lacerations at the gastroesophageal junction due to severe vomiting.
  • Leads to hematemesis.
  • Usually found in alcoholics and bulimics.
• Plummer-Vinson syndrome
  
  • Triad of Dysphagia (due to esophageal webs), Iron deficiency anemia, and Glossitis (“Plumbers” DIG).
• Sclerodermal esophageal dysmotility
  
  • Esophageal smooth muscle atrophy Ž–> decreased LES pressure and dysmotility –>Ž acid reflux and dysphagiaŽ –> stricture, Barrett esophagus, and aspiration.
  • Part of CREST syndrome.

Question 5

Barrett esophagus (350)

• Definition
• Due to…
• Associated with…

Answer 5

• Definition
  
  • Glandular metaplasia
  • Replacement of nonkeratinized (stratified) squamous epithelium with intestinal epithelium (nonciliated columnar with goblets cells) in the distal esophagus [A].
• Due to…
  
  • Chronic acid reflux (GERD).
• Associated with…
  
  • Esophagitis, esophageal ulcers, and increased risk of esophageal adenocarcinoma.

Question 6

Esophageal cancer

• Possible carcinomas
  
  • Worldwide
  • in the United States
• Presentation
• Risk factors

Answer 6

• Can be squamous cell carcinoma or adenocarcinoma.
  
  • Worldwide, squamous cell is more common.
    
    • Squamous cell—upper 2 ⁄3.
  • In the United States, adenocarcinoma is more common.
    
    • Adenocarcinoma—lower 1 ⁄3.
• Presentation
  
  • Typically presents with progressive dysphagia (first solids, then liquids) and weight loss
  • Poor prognosis.
• Risk factors include: (AABCDEFFGH)
  
  • Achalasia
  • Alcohol—squamous
  • Barrett esophagus—adeno
  • ƒƒCigarettes—both
  • ƒƒDiverticula (e.g., Zenker)—squamous
  • Esophageal web—squamous
  • Familial
  • Fat (obesity)—adeno
  • ƒƒGERD—adeno
  • ƒƒHot liquids—squamous

Question 7

Acute gastritis (erosive)

• Definition
• Can be caused by…

Answer 7

• Definition
  
  • Disruption of mucosal barrier –>Ž inflammation.
  • Especially common among alcoholics and patients taking daily NSAIDs (e.g., patients with rheumatoid arthritis).
• Can be caused by…
  
  • Stress
  • NSAIDs
    
    • Decreased PGE2 –> decreased gastric mucosa protection
  • Alcohol
  • Uremia
  • Burns
    
    • Curling ulcer—decreased plasma volume –> sloughing of gastric mucosa
    • Burned by the Curling iron.
  • Brain injury
    
    • Cushing ulcer—increased vagal stimulation –>Ž increased ACh –>Ž increased H+ production
    • Always Cushion the brain.

Question 8

Chronic gastritis (nonerosive)

• Type A
• Type B
• A vs. B

Answer 8

• Type A (fundus/body)
  
  • Autoimmune disorder characterized by Autoantibodies to parietal cells, pernicious Anemia, and Achlorhydria.
  • Associated with other autoimmune disorders.
• Type B (antrum)
  
  • Most common type.
  • Caused by H. pylori infection. 
  • Increased risk of MALT lymphoma and gastric adenocarcinoma.
• A comes before B:
  
  • Type A
    
    • Autoimmune
    • First part of the stomach (fundus/body).
  • Type B
    
    • H. pylori Bacteria
    • Second part of the stomach (antrum).

Question 9

Ménétrier disease

Answer 9

• Gastric hypertrophy with protein loss, parietal cell atrophy, and increased mucous cells.
• Precancerous.
• Rugae of stomach are so hypertrophied that they look like brain gyri.

Question 10

Stomach cancer

• Definition
• Intestinal
• Diffuse
• Virchow node
• Krukenberg tumor
• Sister Mary Joseph nodule

Answer 10

• Definition
  
  • Almost always adenocarcinoma.
  • Early aggressive local spread and node/liver metastases.
  • Often presents with acanthosis nigricans.
• Intestinal
  
  • Associated with H. pylori infection, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis.
  • Commonly on lesser curvature
  • Looks like ulcer with raised margins.
• Diffuse
  
  • Not associated with H. pylori
  • Signet ring cells [A]
  • Stomach wall grossly thickened and leathery (linitis plastica).
• Virchow node
  
  • Involvement of left supraclavicular node by metastasis from stomach.
• Krukenberg tumor
  
  • Bilateral metastases to ovaries.
  • Abundant mucus, signet ring cells.
• Sister Mary Joseph nodule
  
  • Subcutaneous periumbilical metastasis.

Question 11

Peptic ulcer disease:
Gastric vs. duodenal ulcer

• Pain with meals / weight
• H. pylori infection
• Mechanism
• Other causes
• Risk of carcinoma
• Other

Answer 11

• Pain
  
  • Gastric: Can be Greater with meals –> weight loss
  • Duodenal: Decreases with meals –> weight gain
• H. pylori infection
  
  • Gastric: In 70%
  • Duodenal: In almost 100%
• Mechanism 
  
  • Gastric: Decreased mucosal protection against gastric acid 
  • Duodenal: Decreased mucosal protection or increased gastric acid secretion
• Other causes
  
  • Gastric: NSAIDs
  • Duodenal: Zollinger-Ellison syndrome
• Risk of carcinoma 
  
  • Gastric: Increased
  • Duodenal: Generally benign
• Other
  
  • Gastric: Often occurs in older patients
  • Duodenal: Hypertrophy of Brunner glands

Question 12

Ulcer complications

• Hemorrhage
• Perforation

Answer 12

• Hemorrhage
  
  • Gastric, duodenal (posterior > anterior).
  • Ruptured gastric ulcer on the lesser curvature of the stomach –>Ž bleeding from left gastric artery.
  • An ulcer on the posterior wall of the duodenum –>Ž bleeding from gastroduodenal artery.
• Perforation
  
  • Duodenal (anterior > posterior).
  • May see free air under the diaphragm [A] with referred pain to the shoulder.

Question 13

Malabsorption syndromes

• Can cause…
• Syndromes

Answer 13

• Can cause…
  
  • Diarrhea, steatorrhea, weight loss, weakness, and vitamin and mineral deficiencies.
• These Will Cause Devastating Absorption Problems.
  
  • ​Tropical sprue
  • Whipple disease
  • Celiac sprue
  • Disaccharidase deficiency
  • Abetalipoproteinemia
  • Pancreatic insufficiency

Question 14

Tropical sprue

Answer 14

• Malabsorption syndrome
• Similar findings as celiac sprue (affects small bowel), but affects the entire small intestine and responds to antibiotics.
• Cause is unknown, but seen in residents of or recent visitors to tropics.

Question 15

Whipple disease

Answer 15

• Malabsorption syndrome
• Infection with Tropheryma whipplei (gram positive)
• PAS (+) foamy macrophages in intestinal lamina propria, mesenteric nodes.
• Cardiac symptoms, Arthralgias, and Neurologic symptoms are common.
• Most often occurs in older men.
• Foamy Whipped cream in a CAN.

Question 16

Celiac sprue

• Definition
• Findings
• Diagnosis
• Treatment

Answer 16

• Definition
  
  • Malabsorption syndrome
  • Autoimmune-mediated intolerance of gliadin (wheat) leading to malabsorption and steatorrhea.
  • Decreased mucosal absorption that primarily affects distal duodenum and/or proximal jejunum.
  • Associated with HLA-DQ2, HLA-DQ8, and northern European descent.
  • Associated with dermatitis herpetiformis.
• Findings
  
  • Anti-endomysial, anti-tissue transglutaminase, and anti-gliadin antibodies
  • Blunting of villi
  • Lymphocytes in the lamina propria [A]. 
  • Moderately increased risk of malignancy (e.g., T-cell lymphoma).
• Diagnosis
  
  • Serum levels of tissue transglutaminase antibodies are used for diagnosis.
• Treatment
  
  • Gluten-free diet.

Question 17

Disaccharidase deficiency

• Definition
• Findings
• Lactose tolerance test

Answer 17

• Definition
  
  • Malabsorption syndrome
  • Most common is lactase deficiency Ž–> milk intolerance.
  • Since lactase is located at tips of intestinal villi, self-limited lactase deficiency can occur following injury (e.g., viral diarrhea).
• Findings
  
  • Normal-appearing villi.
  • Osmotic diarrhea.
• Lactose tolerance test: (+) for lactase deficiency if…
  
  • Administration of lactose produces symptoms, and
  • ƒƒGlucose rises < 20 mg/dL

Question 18

Abetalipoproteinemia

• Definition
• Presentation

Answer 18

• Definition
  
  • Malabsorption syndrome
  • Decreased synthesis of apolipoprotein B
    
    • Ž–> inability to generate chylomicrons
    • –> decreased secretion of cholesterol, VLDL into bloodstream
    • –>Ž fat accumulation in enterocytes.
• Presents in early childhood with failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness.

Question 19

Pancreatic insufficiency

• Definition
• Findings
• D-xylose absorption test

Answer 19

• Definition
  
  • Malabsorption syndrome
  • Due to cystic fibrosis, obstructing cancer, and chronic pancreatitis.
• Findings
  
  • Causes malabsorption of fat and fat-soluble vitamins (vitamins A, D, E, K).
  • Increased neutral fat in stool.
• D-xylose absorption test
  
  • Normal urinary excretion in pancreatic insufficiency
  • Decreased excretion with intestinal mucosa defects or bacterial overgrowth.

Question 20

Inflammatory bowel diseases:
Crohn disease

• Possible etiology
• Location
• Gross morphology
• Microscopic morphology
• Complications
• Intestinal manifestation
• Extraintestinal manifestations
• Treatment
• Mnemonic

Answer 20

• Possible etiology
  
  • Disordered response to intestinal bacteria.
• Location
  
  • Any portion of the GI tract, usually the terminal ileum and colon.
  • Skip lesions, rectal sparing.
• Gross morphology
  
  • Transmural inflammation Ž–> fistulas.
  • Cobblestone mucosa, creeping fat, bowel wall thickening (“string sign” on barium swallow x-ray [A]), linear ulcers, fissures.
• Microscopic morphology
  
  • Noncaseating granulomas and lymphoid aggregates (Th1 mediated).
• Complications
  
  • Strictures (leading to obstruction), fistulas, perianal disease, malabsorption, nutritional depletion, colorectal cancer, gallstones.
• Intestinal manifestation
  
  • Diarrhea that may or may not be bloody.
• Extraintestinal manifestations
  
  • Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, pyoderma gangrenosum, aphthous ulcers, uveitis, kidney stones.
• Treatment
  
  • Corticosteroids, azathioprine, methotrexate, infliximab, adalimumab.
• Mnemonic
  
  • For Crohn, think of a fat granny and an old crone skipping down a cobblestone road away from the wreck (rectal sparing).

Question 21

Inflammatory bowel diseases:
Ulcerative colitis

• Possible etiology
• Location
• Gross morphology
• Microscopic morphology
• Complications
• Intestinal manifestation
• Extraintestinal manifestations
• Treatment
• Mnemonic

Answer 21

• Possible etiology
  
  • Autoimmune.
• Location
  
  • Colitis = colon inflammation.
  • Continuous colonic lesions, always with rectal involvement.
• Gross morphology
  
  • Mucosal and submucosal inflammation only.
  • Friable mucosal pseudopolyps with freely hanging mesentery [B].
  • Loss of haustra Ž–> “lead pipe” appearance on imaging.
• Microscopic morphology
  
  • Crypt abscesses and ulcers, bleeding, no granulomas (Th2 mediated).
• Complications
  
  • Malnutrition, sclerosing cholangitis, toxic megacolon, colorectal carcinoma (worse with right-sided colitis or pancolitis).
• Intestinal manifestation
  
  • Bloody diarrhea.
• Extraintestinal manifestations
  
  • Pyoderma gangrenosum, erythema nodosum, 1° sclerosing cholangitis, ankylosing spondylitis, apthous ulcers, uveitis.
• Treatment
  
  • ASA preparations (sulfasalazine), 6-mercaptopurine, infliximab, colectomy.
• Mnemonic
  
  • Ulcerative colitis causes ULCCCERS:
  • Ulcers
  • Large intestine
  • Continuous, Colorectal carcinoma, Crypt abscesses
  • Extends proximally
  • Red diarrhea
  • Sclerosing cholangitis

Question 22

Irritable bowel syndrome

• Definition
• Findings
• Treatment

Answer 22

• Definition
  
  • Recurrent abdominal pain associated with ≥ 2 of the following:
    
    • Pain improves with defecation
    • Change in stool frequency
    • Change in appearance of stool
  • No structural abnormalities.
  • Most common in middle-aged women.
  • Pathophysiology is multifaceted.
• Findings
  
  • Chronic symptoms.
  • May present with diarrhea, constipation, or alternating symptoms.
• Treatment
  
  • Treat symptoms.

Question 23

Appendicitis

• Definition
• Symptoms
• Differential
• Treatment

Answer 23

• Definition
  
  • Acute inflammation of the appendix due to obstruction by fecalith (in adults) or lymphoid hyperplasia (in children).
• Symptoms
  
  • Initial diffuse periumbilical pain migrates to McBurney point (1 ⁄3 the distance from anterior superior iliac spine to umbilicus).
  • Nausea, fever
  • May perforate –>Ž peritonitis
  • May see psoas, obturator, and Rovsing signs.
• Differential
  
  • Diverticulitis (elderly), ectopic pregnancy (use β-hCG to rule out).
• Treatment
  
  • Appendectomy.

Question 24

Diverticulum

• Definition
• “True” diverticulum
• “False” diverticulum or pseudodiverticulum

Answer 24

• Definition
  
  • Blind pouch [A] protruding from the alimentary tract that communicates with the lumen of the gut.
  • Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed “false” in that they lack or have an attenuated muscularis externa.
  • Most often in sigmoid colon.
• “True” diverticulum
  
  • All 3 gut wall layers outpouch (e.g., Meckel).
• “False” diverticulum or pseudodiverticulum
  
  • Only mucosa and submucosa outpouch.
  • Occur especially where vasa recta perforate muscularis externa.

Question 25

Diverticulosis

• Definition
• Caused by…
• Symptoms
• Complications

Answer 25

• Definition
  
  • Many false diverticula of the colon, commonly sigmoid.
  • Common (in ~50% of people > 60 years).
  • Associated with low-fiber diets.
• Caused by…
  
  • Increased intraluminal pressure and focal weakness in colonic wall.
• Symptoms
  
  • Often asymptomatic or associated with vague discomfort.
  • A common cause of hematochezia.
• Complications
  
  • Diverticulitis, fistulas.

Question 26

Diverticulitis

• Definition
• Symptoms
• Treatment

Answer 26

• Definition
  
  • Inflammation of diverticula classically causing LLQ pain, fever, leukocytosis [B].
  • Sometimes called “left-sided appendicitis” due to overlapping clinical presentation.
• Symptoms
  
  • May perforate –>Ž peritonitis, abscess formation, or bowel stenosis.
  • Stool occult blood is common +/– hematochezia.
  • May also cause colovesical fistula (fistula with bladder) –>Ž pneumaturia.
• Treatment
  
  • Give antibiotics.

Question 27

Zenker diverticulum

• Definition
• Symptoms

Answer 27

• Definition
  
  • Pharyngoesophageal false diverticulum [A].
  • Herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor.
  • Most common in elderly males.
• Presenting symptoms
  
  • Dysphagia, obstruction, foul breath from trapped food particles (halitosis).

Question 28

Meckel diverticulum

• Definition
• Symptoms
• Diagnosis
• Mnemonic

Answer 28

• Definition
  
  • True diverticulum.
  • Persistence of the vitelline duct.
  • May contain ectopic acid–secreting gastric mucosa and/or pancreatic tissue.
  • Most common congenital anomaly of the GI tract.
• Symptoms
  
  • Can cause melena, RLQ pain, intussusception, volvulus, or obstruction near the terminal ileum.
  • Contrast with omphalomesenteric cyst = cystic dilation of vitelline duct.
• Diagnosis
  
  • Pertechnetate study for uptake by ectopic gastric mucosa.
• The five 2’s:
  
  • 2 inches long.
  • 2 feet from the ileocecal valve.
  • 2% of population.
  • Commonly presents in first 2 years of life.
  • May have 2 types of epithelia (gastric / pancreatic).

Question 29

Intussusception

• Definition
• Age

Answer 29

• Definition
  
  • “Telescoping” of 1 bowel segment into distal segment, commonly at ileocecal junction.
  • Compromised blood supply –>Ž intermittent abdominal pain often with “currant jelly” stools.
• Age
  
  • Unusual in adults (associated with intraluminal mass or tumor that acts as lead point that is pulled into the lumen).
  • Majority of cases occur in children (usually idiopathic; may be associated with recent enteric or respiratory viral infection).
  • Abdominal emergency in early childhood.

Question 30

Volvulus

• Definition
• Location

Answer 30

• Definition
  
  • Twisting of portion of bowel around its mesentery
  • Can lead to obstruction and infarction.
• Can occur throughout the GI tract.
  
  • Midgut volvulus more common in infants and children.
  • Sigmoid volvulus more common in elderly.

Question 31

Hirschsprung disease

• Definition
• Cause
• Presentation
• Diagnosis
• Treatment

Answer 31

• Definition
  
  • Congenital megacolon characterized by lack of ganglion cells/enteric nervous plexuses (Auerbach and Meissner plexuses) in segment on intestinal biopsy.
  • Think of Hirschsprung** as a giant spring that has sprung in the colon.**
• Cause
  
  • Due to failure of neural crest cell migration.
  • Associated with mutations in the RET gene.
  • Risk increases with Down syndrome.
• Presentation
  
  • Bilious emesis, abdominal distention, and failure to pass meconium in the first 48 hours of life, ultimately manifesting as chronic constipation.
  • Dilated portion of the colon proximal to the aganglionic segment, resulting in a “transition zone.”
  • Involves rectum.
• Diagnosis
  
  • Diagnosed by rectal suction biopsy.
• Treatment
  
  • Resection.

Question 32

Other intestinal disorders

• Adhesion
• Angiodysplasia
• Duodenal atresia

Answer 32

• Adhesion
  
  • Fibrous band of scar tissue
  • Commonly forms after surgery
  • Most common cause of small bowel obstruction.
  • Can have well-demarcated necrotic zones.
• Angiodysplasia
  
  • Tortuous dilation of vessels Ž–> hematochezia.
  • Most often found in cecum, terminal ileum, and ascending colon.
  • More common in older patients.
  • Confirmed by angiography.
• Duodenal atresia
  
  • Causes early bilious vomiting with proximal stomach distention (“double bubble” on X-ray) because of failure of small bowel recanalization.
  • Associated with Down syndrome.

Question 33

Other intestinal disorders

• Ileus
• Ischemic colitis
• Meconium ileus
• Necrotizing enterocolitis

Answer 33

• Ileus
  
  • Intestinal hypomotility without obstruction –>Ž constipation and decreased flatus
  • Distended/tympanic abdomen with decreased bowel sounds.
  • Associated with abdominal surgeries, opiates, hypokalemia, and sepsis.
• Ischemic colitis
  
  • Reduction in intestinal blood flow causes ischemia.
  • Pain after eating Ž–> weight loss.
  • Commonly occurs at splenic flexure and distal colon.
  • Typically affects elderly.
• Meconium ileus
  
  • In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.
• Necrotizing enterocolitis
  
  • Necrosis of intestinal mucosa and possible perforation.
  • Colon is usually involved, but can involve entire GI tract.
  • In neonates, more common in preemies (decreased immunity).

Question 34

Colonic polyps

• Definition
• Adenomatous
  
  • Malignancy
  • Symptoms

Answer 34

• Definition
  
  • Masses protruding into gut lumen –>Ž sawtooth appearance.
  • 90% are non-neoplastic.
  • Often rectosigmoid.
  • Can be tubular [A] or villous [B].
• Adenomatous
  
  • Malignancy
    
    • Adenomatous polyps are precancerous.
    • Malignant risk is associated with increased size, villous histology, increased epithelial dysplasia.
    • Precursor to colorectal cancer (CRC).
    • The more villous the polyp, the more likely it is to be malignant
      
      • Villous = villainous.
  • Polyp symptoms
    
    • Often asymptomatic, lower GI bleed, partial obstruction, secretory diarrhea (villous adenomas).

Question 35

Colonic polyps

• Hyperplastic
• Juvenile
  
  • Definition
  • Juvenile polyposis syndrome
• Hamartomatous
  
  • Peutz-Jeghers syndrome
  • Associations

Answer 35

• Hyperplastic
  
  • Most common non-neoplastic polyp in colon (> 50% found in rectosigmoid colon).
• Juvenile
  
  • Definition
    
    • Mostly sporadic lesions in children < 5 years old.
    • 80% in rectum.
    • If single, no malignant potential.
  • Juvenile polyposis syndrome
    
    • Multiple juvenile polyps in GI tract
    • Increased risk of adenocarcinoma.
• Hamartomatous
  
  • Peutz-Jeghers syndrome
    
    • Autosomal dominant syndrome featuring multiple nonmalignant
      hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia.
  • Associations
    
    • Associated with increased risk of CRC and other visceral malignancies.

Question 36

Colorectal cancer

• Epidemiology
• Risk factors
• Presentation
• Diagnosis

Answer 36

• Epidemiology
  
  • Most patients are > 50 years old.
  • ~ 25% have a family history.
• Risk factors
  
  • IBD, tobacco use, large villous adenomas, juvenile polyposis syndrome, Peutz-Jeghers syndrome.
• Presentation
  
  • Rectosigmoid > ascending > descending.
    
    • Ascending—exophytic mass, iron deficiency anemia, weight loss.
    • Descending—infiltrating mass, partial obstruction, colicky pain, hematochezia.
  • Rarely presents as Streptococcus bovis bacteremia.
  • Right side bleeds; left side obstructs.
• Diagnosis
  
  • Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion.
  • Screen patients > 50 years old with colonoscopy or stool occult blood test.
  • “Apple core” lesion seen on barium enema x-ray [A].
  • CEA tumor marker: good for monitoring recurrence, not useful for screening.

Question 37

Colorectal cancer

• Familial adenomatous polyposis (FAP)
• Gardner syndrome
• Turcot syndrome
• Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome)

Answer 37

• Familial adenomatous polyposis (FAP)
  
  • Autosomal dominant mutation of APC gene on chromosome 5q.
  • 2-hit hypothesis.
  • 100% progress to CRC unless colon is resected.
  • Thousands of polyps arise starting at a young age
  • Pancolonic
  • Always involves rectum.
• Gardner syndrome
  
  • FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium.
• Turcot syndrome
  
  • FAP + malignant CNS tumor.
  • Turcot = Turban.
• Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome)
  
  • Autosomal dominant mutation of DNA mismatch repair genes.
  • ~ 80% progress to CRC.
  • Proximal colon is always involved.

Question 38

Molecular pathogenesis of CRC

• There are 2 molecular pathways that lead to CRC:
• Order of gene events

Answer 38

• There are 2 molecular pathways that lead to CRC:
  
  • ƒƒMicrosatellite instability pathway (~15%):
    
    • DNA mismatch repair gene mutations –>Ž sporadic and HNPCC syndrome.
    • Mutations accumulate, but no defined morphologic correlates.
  • APC/β-catenin (chromosomal instability) pathway (∼85%)
    
    • –>Ž sporadic cancer.
• Order of gene events—AK-53.
  
  • Normal colon
  • –> Loss of APC gene
    
    • Decreased intercellular adhesion and increased proliferation
  • Colon at risk
  • –> K-RAS mutation
    
    • Unregulated intracellular signal transduction
  • Adenoma
  • –> Loss of tumor suppressor gene(s) (p53, DCC)
    
    • Increased tumorigenesis
  • Carcinoma