GI Pathology Flashcards
Oral Herpes
Due to HSV-1; Dormant in ganglia of trigeminal nerve; Stress and sunlight can cause reactivation
Squamous Cell Carcinoma of Oral Mucosa
Tobacco and alcohol are risk factors; Floor of mouth; Oral leukoplakia and erythroplakia precursor lesions (cannot be scraped off)
Mumps
Bilaterally inflamed parotid glands; Orchitis, pancreatitis and aseptic meningitis; Elevated serum amylase; Risk of sterility
Pleomorphic Adenoma
Benign tumor composed of stromal and epithelial tissue; most common tumor in salivary gland; Mobile, painless circumscribed mass in angle of jaw; High recurrence; May transform into carcinoma with signs of facial nerve damage
Tracheoesophageal Fistula
Connection btw. esophagus and trachea; Most commply proximal esophageal atresia with distal esophagus arising from the trachea;
Presents with vomiting, polyhydramnios, abdominal distention and aspiration
Esophageal Web
Thin protrusion of esophageal mucosa; most often upper esophagus; dysphagia for poorly chewed food; Increased risk of esophageal squamous cell carcinoma
Plummer-Vinson Syndrome
Severe iron deficiency anemia, esophageal web and beefy red tongue due to atrophic glossitis
Zenker Diverticulum
Outpouching of the pharyngeal mucosa through acquired defect in muscular wall; False diverticulum; Arises above the upper esophageal sphincter at esophageal and pharynx junction;
Presents with dysphagia, obstruction and halitosis
Mallory-Weiss Syndrome
Longitudinal laceration of mucosa at the GE junction; caused by severe vomiting (eg. alcohol or bulimia);
Presents with painful hematemesis
Risk of Boerhaave syndrome - rupture of esophagus leading to air in the mediastinum and subcutaneous emphysema (air bubbles beneath the skin/crackling noises)
Esophageal Varices
Dilated submucosal veins in lower esophagus; Arise secondary to portal hypertension (L. gastric vein backs up into the esophageal vein –> varices)
Asymptomatic, but risk of rupture: painless hematemesis
Most common cause of death in cirrhosis
Achalasia
Disordered esophageal motility with inability to relax LES; Due to damaged ganglion cells in myenteric plexus (loss of NO)
Can be idiopathic or secondary to insult (eg. Trypanosoma Cruzi)
Presents with dysphagia for solids and liquids, Putrid breath, high LES pressure, Bird Beak sign on barium swallow, increased risk for esophageal squamous cell carcinoma
GERD
Reflux of acid from stomach due to reduced LES tone; Risk factors: alcohol, tobacco, obesity, fat-rich diet, caffeine, hiatal hernia
Clinical features: Heartburn, asthma and cough, damage to teeth enamel, ulceration of stricture with Barret esophagus is a late complication
Paraesophageal Hernia
Herniate next to esophagus; bowel sounds in lower lung field; lung hypoplasia
Barrett Esophagus
Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells (intestinal epithelium)
May progress to dysplasia and adenocarcinoma
Esophageal Carcinoma: Adenocarcinoma
Malignant proliferation of glands (most common type in West)
Arises from preexisting Barrett esophagus
Usually involves lower 1/3 of esophagus
Esophageal Carcinoma: Squamous
Malignant proliferation of squamous cells
Usually arises in the upper or middle 3rd of esophagus
Major risk factors: alcohol, tobacco, hot tea, achalasia, esophageal webs, esophageal injury (lye ingestion)
Presents with hoarse voice and cough (tracheal involvement)
Lymph Node Metastases in Esophageal Carcinoma
Depends on location in esophagus:
Upper 1/3 - cervical nodes
Middle 1/3 - mediastinal or tracheobronchial nodes
Lower 1/3 - celiac and gastric nodes
Esophageal Carcinoma Symptoms
Presents late; progressive dysphagia (solids –> liquids), weight loss, pain and hematemesis
Gastroschisis
Congenital malformation of the anterior abdominal wall leading to exposure of abdominal contents
Omphalocele
Persistent herniation of bowel into umbilical cord due to failure of herniated intestines to return to the body cavity during development
Contents are covered by peritoneum and amnion of umbilical cord
Pyloric Stenosis
Congenital hypertrophy of pyloric smooth muscle
More common in males
Presents two weeks after birth as projectile NON-bilious vomiting, visible peristalsis and olive like mass in the abdomen
Treatment is cutting muscle away (myotomy)
Acute Gastritis
Acidic damage to stomach due to imbalance between mucosal defenses and acidic environment
Risk factors: severe burn (Curling Ulcer), NSAIDS, heavy alcohol consumption, chemotherapy, shock and increased intracranial pressure (Cushing Ulcer)
Acid damage results in superficial inflammation, erosion (loss of superficial epithelium) or ulcer (loss of mucosal layer)
Curling Ulcer
Hypovolemia –> decreased blood supply; Due to severe burn
Cushing Ulcer
Increased intracranial pressure –> increased stimulation of vagus nerve leading to increased acid production from parietal cells
Autoimmune Chronic Gastritis
Autoimmune destruction of gastric parietal cells in the stomach body and fundus; Associated with antibodies against parietal cells or IF; pathogenesis T cell mediated (type IV)
Clinical features:
1) Atrophy of mucosa with intestinal metaplasia,
2) Achlorhydria (low acid production) with increased gastrin levels and antral G-cell hyperplasia
3) Megaloblastic (pernicious) anemia due to lack of IF
Increased risk of gastric adenocarcinoma (intestinal type)
H. Pylori Chronic Gastritis
Produces ureases and proteases that weaken mucosal defenses; antrum is most common site
Presents with epigastric abdominal pain; Increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type) and MALT lymphoma
Triple therapy tx.
Duodenal Peptic Ulcer
Solitary mucosal tumor involving proximal duodenum; Almost always due to H. Pylori, but rarely ZE; Almost never malignant
Presents with epigastric pain that improves with meals
Ulcer with hypertrophy of Brunner glands (produce mucus in duodenum to neutralize H+)
Gastric Peptic Ulcer
Usu. due to H. Pylori, but can also be due to bile reflux and NSAIDs; presents with epigastric pain that worsens with meals (opposite duodenum); Usu located in the lesser curvature of the antrum; Rupture carries risk of bleeding from L. gastric artery;
May be gastric carcinoma - irregular with heaped up margins
Intestinal Type Gastric Carcinoma
Presents as large, irregular ulcer with heaped up margins Commonly involves lesser curvature of antrum
Risk factors: intestinal metaplasia (H. pylori or autoimmune), nitrosamines in smoked foods (Japan) and blood type A
Diffuse Type Gastric Carcinoma
Characterized by signet ring cells that diffusely infiltrate the gastric wall; Desmoplasia (reaction of stroma-fibrous tissue and blood vessels) results in thickening of stomach wall (linitis plastica)
Not associated with H. Pylori, intestinal metaplasia or nitrosamines
Gastric Carcinoma Presentation
Presents late with weight loss, abdominal pain, anemia and early satiety; Rarely presents with acanthosis nigricans (dark velvety skin patches) or Leser Trelat sign (lots of suborrhea keratoses); Spread to lymph nodes can involve the L. supraclavicular node (Virchow node)
Distant mets most commonly involve the liver, periumbilical region (sister Mary Joseph nodules seen in intestinal type); Bilateral ovaries (Krukenberg tumor seen in diffuse type)
Krukenberg Tumor
Bilateral mets of gastric carcinoma to ovaries; seen with diffuse type of cancer
Duodenal Atresia
Failure of duodenum to canalize; Associated with Down Syndrome;
Clinical features: polyhydramnios, distention of stomach and blind lop of duodenum; Double Bubble sign; bilious vomit
Meckel Diverticulum
Outpouching of all three layers of the bowel wall (true diverticulum); Arises due to failure of the vitelline duct to involute
Rule of 2s: seen in 2% of pop., 2 inches long and located in the small bowel within 2 feet of the ileocecal valve, can present during the first two years of life with bleeding, volvulus, intussusception or obstruction (mimics appendicitis)
Volvulus
Twisted bowel along its mesentery; results in obstruction and disruption of the blood supply with infarction; Most common locations are the sigmoid colon (elderly) and cecum (young adults)
Intussusception
Telescoping of the proximal segment of bowel forward into distal segment –> obstruction and disruption of blood supply –> infarction –> currant jelly stools
Associated with lymphoid hyperplasia (eg. due to rotavirus)
Usu. arises in the terminal ileum, leading to intussusception into the cecum
In adults most common cause is tumor
Small Bowel Infarction
Highly susceptible to ischemic injury; Transmural infarction occurs with thrombis/embolism of the SMA (eg. afib, vasculitis) or thrombosis of the mesenteric vein (eg. polycythemia vera, lupus); Mucosal infarction occurs with marked hypotension;
Clinical features: abdominal pain, bloody diarrhea, decreased bowel sounds
Lactose Intolerance
Decreased function of lactase found in the brush border; that breaks down lactose into glucose and galactose
Celiac Disease
Immune mediated damage of small bowel villi due to gluten exposure (gliadin); Associated with HLA-DQ2 and DQ8; Once absorbed, is deamidated by tissue transglutaminase (tTG) and presented by APCs via MHC II to Th cells –> tissue damage;
Clinical Presentation:
Abdominal distention, diarrhea and failure to thrive; chronic diarrhea and bloating; small herpes-like vesicles (dermatitis herpetiformis) due to IgA depositions at the tips of dermal papillae;
Findings:
Increased incidence of IgA deficiency; IgA antibodies against endomysium, tTG or gliadin
Duodenal biopsy reveals flattening of villi, hyperplasia of crypts and increased intraepithelial lymphocytes; Damage most prominent in duodenum
Tropical Sprue
Damage to small bowel villi due to unknown organism; results in malabsorption; Similar to celiac except occurs in tropic regions (eg. Caribbean), arises after infectious diarrhea and responds to antibiotics; Damage is most prominent in jejunum and ileum (secondary B12 or folate deficiency may be present)
Whipple Disease
Systemic tissue damage characterized by macrophages loaded with Tropheryma whippelii; Classically involves the small bowel lamina propria; Macrophages compress lacteals –> chylomicrons cannot be transferred to lymphatics –> fat malabsorption and steatorrhea
Can also involve the synovium of joints (arthritis), cardiac valves, lymph nodes and CNS
Abetalipoproteinemia
AR deficiency in apolipoprotein B-48 and B-100;
Results in malabsorption due to defective chylomicron formation (requires B-48); Absent plasma VLDL and LDL (requires B-100)
Carcinoid Tumor
Malignant proliferation of neuroendocrine cells; low grade malignancy; Tumor cells contain neurosecretory granules that are chromogranin +; Can arise anywhere in gut, but small bowel is most common; Secretes serotonin that can bypass liver metabolism once there are mets in the liver - seratonin is released into hepatic vein and leaks into systemic circulation via hepato-systemic shunts, resulting in carcinoid syndrome and carcinoid heart disease (fibrosis of heart valves on the R side
Carcinoid Syndrome
Characterized by bronchospasm, diarrhea, flushing of skin; symptoms can be triggered by alcohol or emotional stress, which results in release of serotonin from the Carcinoid tumor
Carcinoid Heart Disease
Characterized by R-sided valvular fibrosis (increased collagen) leading to tricuspid regurg. and pulmonary valve stenosis; L sided valvular lesions are not seen due to presence of monoamine oxidase (metabolizes serotonin) in lungs
Acute Appendicitis
Acute inflammation of appendix due to obstruction of appendix by lymphoid hyperplasia (children) or fecalith (adults); most common cause of acute abdomen;
Clinical Features:
Periumbilical pain (T10), fever and nausea; pain eventually localizes to right lower quadrant (McBurney point)
Rupture result sin peritonitis that presents with guarding and rebound tenderness
Periappendiceal abscess is a common complication
Ulcerative Colitis
Mucosal and submucosal ulcers (friable mucosal); Begins in rectum and can extend proximally up to the cecum - continuous involvement without skip lesions; Only involves the colon; LLQ pain with bloody diarrhea; Crypt abscesses with neutrophils; Pseudopolyps, loss of haustra (lead pipe sign on imaging);
Associations: Primary sclerosing cholangitis, p-ANCA positivity, ankylosing spondylitis, aphthous ulcers, uveitis, erythema nodosum, pyoderma gangrenosum
Smoking is protective
Complications: Toxic megacolon, colorectal carcinoma
Tx: 5-aminosalicylic preps. (mesalamine), 6-mercaptopurine, infliximab
Crohn Disease
Full thickness inflammation with knife-like fissures and strictures; Can be anywhere from mouth to anus with skip lesions (terminal ileum most common); LRQ pain with non-bloody diarrhea; Lymphoid aggregates with granulomas; Cobblestone mucosa, creeping fat and strictures (“string sign” on images);
Complications: Malabsorption, calcium oxalate nephroliathiasis, fistulas, carcinoma
Associations: Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, pyoderma gangrenosum, aphthous ulcers, uveitis, kidney stones
Smoking increases risk
Hirschsprung Disease
Defective relaxation and peristalsis of rectum and distal sigmoid due to congenital failure of ganglion cells (neural crest) to descend into myenteric and submucosal plexus
Clinical features: failure to pass meconium, empty rectal vault on digital rectal exam, massive dilation (megacolon) of bowel proximal to obstruction with risk of rupture;
Rectal suction biopsy reveals lack of ganglion cells
Associated with Down syndrome
Colonic Diverticula
Outpouching of mucosa and submucosa through muscularis propria; Arises when the vasa recta traverse the muscularis propria –> weak point in colonic wall; Sigmoid colon is most common location - L side
Usu. asymptomatic, but complications can include rectal bleeding (hematochezia), diverticulitis (obstruction) with appendix-like LLQ pain, fistulas (air, stool or bacteria in urine)
Angiodysplasia
Acquired malformation of mucosal and submucosal capillary beds; Usu arises in cecum and R colon due to high wall tension; Rupture classically presents with hematochezia
Hereditary Hemorrhagic Telangiectasia
AD disorder resulting in thin-walled blood vessels, esp in mouth and GI tract; Rupture presents as bleeding; Little telangiectasias around mouth and lips
Ischemic Colitis
Ischemic injury usu. at the splenic flexure (watershed area of SMA); Atherosclerosis of SMA is most common cause; presents with posprandial pain and weight loss; blood diarrhea
Irritable Bowel Syndrome
Relapsing abdominal pain with bloating, flatulence with changes in bowel habits (diarrhea or constipation) that improves with defecation; Related to disturbed intestinal motility; no identifiable pathologic change
Hyperplastic Colonic Polyps
Due to hyperplasia of glands; show a serrated appearance on microscopy; Usu. arise in L colon; Benign with no malignant potential
Adenomatous Colonic Polyps
Due to neoplastic proliferation of glands; benign but premalignant and may progress to adenocarcinoma via the adenoma-carcinoma sequence
Adenoma-Carcinoma Sequence
Describes the molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma:
1) APC TS mutation (sporadic or germline) increases risk for formation of polyp
2) K-ras mutation leads to formation of polyp
3) p53, DCC mutation and increased expression of COX-2 allows for progression to carcinoma
Greater risk for progression for adenoma to carcinoma is related to size >2cm, sessile growth and villous histology
Familial Adenomatous Polyposis
AD disorder characterized by 100s to 1000s of adenomatous colonic polyps; Due to inherited APC mutation (chr. 5) –> increased propensity to develop adenomatous polyps throughout colon and rectum; Prophylactic removal of colon and rectum otherwise most patients develop cancer by age 40
Gardner Syndrome
FAP with fibromatosis and osteomas; Fibromatosis is non-neoplastic proliferation of fibroblasts that arises in the retroperitoneum (desmoid) and locally destroys tissue; Osteoma is a benign tumor of bone that usu arises in skull
Turcot Syndrome
FAP with CNS tumors (medulloblastoma and glial tumors)
Juvenile Polyp
Sporadic, hamartomatous polyp in children <5; Usu is solitary rectal polyp that prolapses and bleeds
Peutz-Jeghers Syndrome
Hamartomatous polyps throughout GI tract and mucocutaneous hyperpigmented (freckle-like spots) on lips, oral mucosa, and genital skin; AD disorder; Increased risk for colorectal, breast and gynecologic cancers
Hereditary Nonpolyposis Colorectal Carcinoma (Lynch)
Due to inherited mutation in DNA mismatch repair enzymes; Increased risk for colorectal cancer, ovarian and endometrial cancer; Colon cancer arises de novo (not from polyp) at relatively early stage (usu. R sided) - microsatellite instability pathway
Left Sided Colon Cancer
Usu grows as napkin ring lesions; presents with decreased stool caliber (due to obstruction), LLQ pain and blood streaked stool; follows the mutator pathway
Right Sided Colon Cancer
Usu grows as a raised lesion; presents with iron deficiency anemia (occult bleeding) an vague pain; follows microsatellite pathway
Strep bovis endocarditis
Associated with colonic carcinoma
CEA
A serum tumor marker that is useful for assessing treatment response and detecting recurrence of colon cancer, but not useful for screening purposes
