135. Pathology Esophagus

Question 1

What does the normal esophagus look like: type of epithelium, submucosa, type of muscle, EG Junction

Answer 1

Stratified squamous epithelium
Submucosa: esophageal glands secrete mucin
Upper 1/3: striated/skeletal muscle
Middle 1/3: mixed
Lower 1/3: smooth muscle

EGJ: squamocolumnar junction, where esophageal epithelium meets stomach simple columnar epithelium (Z Line)

Question 2

GERD

• what is it, predisposing factors, sx
• Endoscopy findings
• 4 histo findings
• 4 complications

Answer 2

GERD: inflammatory process due to reflux of gastric/duodenal contents into esophagus 2/2 failure of anti-reflux mechanisms
RF: structural (hiatal hernia), delayed gastric emptying (DM, pyloric stenosis), high intragastric pressure (pregnancy, obesity, ascites), high gastric acid production
sx: heartburn, regurgitation, odynophagia (pain swallow), dysphagia

Endoscopy: hyperemia/erythema (RED), patches resembling leukoplakia (more keratinization/layers)

Histo: 1. basal cell hyperplasia (>15% thickness), 2. vascular congestion and extension of vascular papillae to top half of thickness, 3. Mixed inflammatory infiltrate (red cells, squiggly nuclei), 4. Ballooning of squamous cells (high water content)

Complications: 1. erosions (loss superficial epithelium above MM), 2. ulcerations (loss epithelium down to MM), 3. strictures (from fibrosis 2/2 ulceration), 4. Barrett’s Esophagus

Question 3

EoE

• what is it
• etiology
• sx
• endoscopy (4)
• histo (5)

Answer 3

Chronic, immune-mediated disease with esophagus dysfx, eosinophil-predominant inflammation
Etiology: assoc w/ allergy, involves prox and distal esophagus, more prevalent in children/teens, 50% have peripheral eosinophilia
Sx: heartburn, odynophagia, dysphagia, vomiting, food aversion (lead to malnutrition/FTT)

Endo: Furrows/trenches, Rings, Strictures, White patches/plaques (non-specific increase production of squamous epithelium)

Histo: 1. Prominent eosinophils (>15 in 2 HPF, >25 in 1 HPF) 2. Eosinophilic microabscess (cluster near surface), 3. high intraepithelial lymphocytes, 4. Basal cell hyperplasia >15% thickness, 5. Fibrosis in LP (into vascular papillae)

Question 4

Barrett’s Esophagus

• what is it
• Etiology
• Endoscopy
• Histo
• Pathogenesis
• Complications

Answer 4

Conversion of normal squamous epithelium to metaplastic columnar epithelium (stomach)
Etiology: 6-12% GERD pts get this (hiatal hernia, white race, less acid clearance, less LES pressure at rest)
Endo: salmon-pink gastric mucosa in squamous lined whiter esophagus proximal to EGJ
Histo: GOBLET CELLS (intestinal metaplasia) in background of gastric-type mucin cells, columnar metaplasia
Pathogenesis: GERD = inflammation and ulceration of esophageal squamous mucosa = columnar metaplasia +/- intestinal metaplasia (Goblet cells)
Complications: ADENOCARDINOMA (metaplasia = dysplasia = adenocarcinoma) - due to accumulation of multiple genetic/epigenetic alterations - NEED INCREASED SCREENING

Question 5

Dysplasia

- low grade vs. high grade dysplasia

Answer 5

Low grade: epithelial nuclei elongated, crowded, dark
dysplastic cells: mucin depleted, less Goblet cell differentiation

High Grade/Carcinoma in Situ: more crypt complexity (cribiforming = swiss cheese; variability in crypt size/shape; extensive branching),
epithelium: has nuclear stratification (nuclei at diff places in cell), loss of polarity, pleomorphism (diff shape/sizes), more nucleoli size, more atypical mitoses
more mucin depletion and absence of goblet cell differentiation

Question 6

Adenocarcinoma

• location
• histo
• gross
• etiology
• prognosis

Answer 6

Same features as carcinoma in situ (high grade dysplasia) but INVADES TISSUE
location: distal esophagus, may extend to stomach (complication of Barrett’s)
Histo: disrupted and expansive MM fibers, dysplasia, cribiforming of crypts, abnormal glands
Gross: malignant epithelial tumor w/ glandular differentiation (near EGJ)
Etiology: 15-25% pts have Her2 oncogene mutation (may benefit from anti-Her2 antibody drugs - need to screen)
Prognosis: better with tumor limited to submucosa than muscularis propria

Question 7

Squamous Cell Carcinoma

• epidemiology
• location + prevalence among men and women
• etiology
• pathogenesis
• spread
• tx

Answer 7

Epi: most common esophageal malignancy worldwide (not in US) - N China, Iran, Russia, Finland, France, Switzerland
Prevalence: Males = Middle/Lower 1/3; Females = Upper 1/3 (assoc with Plummer-Vinson Syndrome = severe Fe deficient anemia)
Etiology: multifactorial (tobacco/alcohol carcinogens; HPV NOT a cause); diet (smoked foods, food w/ nitrate preserves, SPOILED VEGGIES)
Pathogenesis: Normal = Esophagitis = Atrophy = Dysplasia = SCC
Spread: 60% mets to lymph node, vertical spread thru esophageal wall to trachea, aorta, pericardium
tx: Esophagectomy (improves survival)

Question 8

Squamous Cell Carcinoma

• Histo
• Gross
• Sign of Invasive SCC
• Prognostic Factor

Answer 8

Histo: nuclear hyperchromasia (darker), pleiomorphism (diff shapes/sizes), high N:C ratio, high mitotic rate
Invasive SCC: KERATIN FORMATION
Gross: stenosing, nodular, ulcerated, lobulated
Middle 1/3 > Lower 1/3 > Upper 1/3

Prognostic Factor: Tumor Stage (in situ vs invasive T1-T4, specify LN involvement and distant mets)