Chapter 17 part 2--GI tract--Esophagus part 2

Question 1

Barrret esophagus

Answer 1

• complication of chronic GERD
• intestinal metaplasia within the esophageal squamous mucosa
• 10% of individuals with chronic GERD have it

Question 2

Typical Barret esophagus patient

Answer 2

• white male between age 40-60
• increased risk of esophageal adenocarcinoma!!
• preinvasive dysplasia detected in 0.2% to 2% of patients with Barrett esophagus anually

Question 3

Gross morphology of Barrett Esophagsus

Answer 3

-Patches of red, velvety mucosa above GE junction

Question 4

Microscopic morphology of Barrett Esophagus–features used to diagnose

Answer 4

• Intestinal type columnar epithelium, particularly mucin secreting goblet cells is usually required for diagnosis!
• gastric cardia-type epithelium present above GE junction may also be acceptable for diagnosis
• when present, dysplasia is classified as low or high grade

Question 5

Barrett esophagus–Intramucosal carcinoma is characterized by?

Answer 5

-neplastic cell invasion into lamina propria

Question 6

Clinical features of Barrett Esophagus–how to diagnose

Answer 6

• Dx requires both gross (endoscopic) and biopsy confirmation
• once identified periodic surveillance endoscopy performed to look for dysplasia or frank malignancy

Question 7

How to treat multifocal high grade dysplasia (with high risk for progression) or carcinoma

Answer 7

• requires esophagectomy!

- Newer modalities (laser ablation, photodynamic therapy) also used

Question 8

Esophageal tumors

Answer 8

• Adenocarcinoma

- Squamous cell carcinoma

Question 9

Esophageal Adenocarcinoma

Answer 9

• largely evolve from dysplastic changes in Barret mucosa
• most common in white males (7:1 male to female)
• accounts for half of all U.S. esophageal cancers

Question 10

Pathogenesis of esophageal adenocarcinoma

Answer 10

• stepwise accumulation of genetic and epigenetic alterations from Barret esophagus to adenocarcinoma:
• 1) Early: chromosomal and p53 abnormalities
• 2)more changes: amplification of c-ERB-B2 and cyclin D1 and E genes and mutations in Rb and the p16/INK4a CDK inhibitor

Question 11

Gross morphology of esophageal adenocarcinoma

Answer 11

-range from exophytic nodules to excavated and deeply infiltrative masses, mostly in distal 3rd of esophagus

Question 12

Microscopic morphology of esophageal adenocarcinoma

Answer 12

• typically produce mucin and form glands, often with intestinal type morphology
• diffusely infiltrative signet-ring tumors are less common
• rarely, see adenosquamous or small, poorly differentiated cells

Question 13

Clinical features of esophageal adenocarcinoma

Answer 13

• occasionally found during evaluation for GERD or surveillance for Barrett esophagus
• typically present with dysphagia, weight loss, hematemesis, chest pain or vomiting
• most found at advanced stages so 5yr survival is less than 25%!!

Question 14

Squamous cell carcinoma

Answer 14

• typically in adults older than 45
• men 4x more than women
• blacks 6x more than whites

Question 15

Risk factors for squamous cell carcinoma

Answer 15

• alcohol and tobacco use
• caustic esophageal injury
• previous mediastinal radiation
• achalasia
• Plummer Vinson syndrome
• frequent consumption of hot beverages

Question 16

Geographic variability of esophageal squamous cell carcninoma

Answer 16

-highest incidence in Iran, central china, Hong Kong, Brazil and South Africa

Question 17

Pathogenesis of esophageal squamous cell carcinoma

Answer 17

• Multifactorial
• environment and diet–synergistic effect modified by genetic factors
• Alcohol and tobacco syndergize to increase risk and contribute to majority of cancers in US
• Nutritional deficiencies and polycyclic hydrocarbons, nitrosamines, other mutagenic compounds (from fungal contaminants) and HPV all contribute to geographic variation

Question 18

Recurrent genetic abnormalities associated with Squamous cell carcinoma of esophagus

Answer 18

• amplification of SOX2 TF gene
• overexpression of cyclin D1
• LoF mutations in TP53, E-cadherin and NOTCH1

Question 19

Half of esophageal squamous cell cancers occur where?

Answer 19

-in middle third of esophagus

Question 20

Morphology of SCC of esophagus

Answer 20

• begin as in situ gray-white plaqulike mucosal thickenings
• can subsequently expand as exophytic lesions, ulcerate or become diffusely infiltrative with wall thickening and luminal stenosis
• A rich submucosal lymphatic network promotes circumferential and longitudinal spread; tumors can invade deeply into adjacent mediastinal structures
• Most tumors are moderately to well differentiated; less common variants are verrucous, spindle and basaxoid squamous cell carcinomas

Question 21

Clinical features of esophageal squamous cell carcinomas

Answer 21

• insiduous onset; symptom onset is late
• dysphagia, obstruction, weight loss, hemorrhage, iron deficiency anemia, sepsis secondary to ulceration or respiratory fistulas with aspiration
• Superficial carcinomas have a 5 year survival rate of 75% but overall 5 yr survival rate is = 20%