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Flashcards in Gastrointestinal - Pathology (1) Deck (38):
1

Salivary gland tumors

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

  • 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.

2

Achalasia

  • Definition
  • Barium swallow
  • Associations

  • 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.

3

Esophageal pathologies

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

  • 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.

4

Esophageal pathologies

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

  • 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.

5

Barrett esophagus (350)

  • Definition
  • Due to...
  • Associated with...

  • 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.

6

Esophageal cancer

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

  • 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

7

Acute gastritis (erosive)

  • Definition
  • Can be caused by...

  • 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.

8

Chronic gastritis (nonerosive)

  • Type A
  • Type B
  • A vs. B

  • 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).

9

Ménétrier disease

  • 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.

10

Stomach cancer

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

  • 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.

11

Peptic ulcer disease:
Gastric vs. duodenal ulcer

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

  • Pain
    • Gastric: Can be Greater with meals --> weight loss
    • DuodenalDecreases 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

12

Ulcer complications

  • Hemorrhage
  • Perforation

  • 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.

13

Malabsorption syndromes

  • Can cause...
  • Syndromes

  • 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

14

Tropical sprue

  • 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.

15

Whipple disease

  • 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.

16

Celiac sprue

  • Definition
  • Findings
  • Diagnosis
  • Treatment

  • 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.

17

Disaccharidase deficiency

  • Definition
  • Findings
  • Lactose tolerance test

  • 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

18

Abetalipoproteinemia

  • Definition
  • Presentation

  • 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.

19

Pancreatic insufficiency

  • Definition
  • Findings
  • D-xylose absorption test

  • 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.

20

Inflammatory bowel diseases:
Crohn disease

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

  • 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).

21

Inflammatory bowel diseases:
Ulcerative colitis

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

  • 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

22

Irritable bowel syndrome

  • Definition
  • Findings
  • Treatment

  • 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.

23

Appendicitis

  • Definition
  • Symptoms
  • Differential
  • Treatment

  • 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.

24

Diverticulum

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

  • 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.

25

Diverticulosis

  • Definition
  • Caused by...
  • Symptoms
  • Complications

  • 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.

26

Diverticulitis

  • Definition
  • Symptoms
  • Treatment

  • 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.

27

Zenker diverticulum

  • Definition
  • Symptoms

  • 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).

28

Meckel diverticulum

  • Definition
  • Symptoms
  • Diagnosis
  • Mnemonic

  • 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).

29

Intussusception

  • Definition
  • Age

  • 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.

30

Volvulus

  • Definition
  • Location

  • 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.

31

Hirschsprung disease

  • Definition
  • Cause
  • Presentation
  • Diagnosis
  • Treatment

  • 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.

32

Other intestinal disorders

  • Adhesion
  • Angiodysplasia
  • Duodenal atresia

  • 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.

33

Other intestinal disorders

  • Ileus
  • Ischemic colitis
  • Meconium ileus
  • Necrotizing enterocolitis

  • 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).

34

Colonic polyps

  • Definition
  • Adenomatous
    • Malignancy
    • Symptoms

  • 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).

35

Colonic polyps

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

  • 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.

36

Colorectal cancer

  • Epidemiology
  • Risk factors
  • Presentation
  • Diagnosis

  • 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.

37

Colorectal cancer

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

  • 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.

38

Molecular pathogenesis of CRC

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

  • 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

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