Chapter 17 part 2--GI tract--Esophagus part 2 Flashcards
Barrret esophagus
- complication of chronic GERD
- intestinal metaplasia within the esophageal squamous mucosa
- 10% of individuals with chronic GERD have it
Typical Barret esophagus patient
- 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
Gross morphology of Barrett Esophagsus
-Patches of red, velvety mucosa above GE junction
Microscopic morphology of Barrett Esophagus–features used to diagnose
- 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
Barrett esophagus–Intramucosal carcinoma is characterized by?
-neplastic cell invasion into lamina propria
Clinical features of Barrett Esophagus–how to diagnose
- Dx requires both gross (endoscopic) and biopsy confirmation
- once identified periodic surveillance endoscopy performed to look for dysplasia or frank malignancy
How to treat multifocal high grade dysplasia (with high risk for progression) or carcinoma
- requires esophagectomy!
- Newer modalities (laser ablation, photodynamic therapy) also used
Esophageal tumors
- Adenocarcinoma
- Squamous cell carcinoma
Esophageal Adenocarcinoma
- 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
Pathogenesis of esophageal adenocarcinoma
- 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
Gross morphology of esophageal adenocarcinoma
-range from exophytic nodules to excavated and deeply infiltrative masses, mostly in distal 3rd of esophagus
Microscopic morphology of esophageal adenocarcinoma
- 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
Clinical features of esophageal adenocarcinoma
- 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%!!
Squamous cell carcinoma
- typically in adults older than 45
- men 4x more than women
- blacks 6x more than whites
Risk factors for squamous cell carcinoma
- alcohol and tobacco use
- caustic esophageal injury
- previous mediastinal radiation
- achalasia
- Plummer Vinson syndrome
- frequent consumption of hot beverages
Geographic variability of esophageal squamous cell carcninoma
-highest incidence in Iran, central china, Hong Kong, Brazil and South Africa
Pathogenesis of esophageal squamous cell carcinoma
- 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
Recurrent genetic abnormalities associated with Squamous cell carcinoma of esophagus
- amplification of SOX2 TF gene
- overexpression of cyclin D1
- LoF mutations in TP53, E-cadherin and NOTCH1
Half of esophageal squamous cell cancers occur where?
-in middle third of esophagus
Morphology of SCC of esophagus
- 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
Clinical features of esophageal squamous cell carcinomas
- 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%
