Disorders of the Esophagus Adriana Acurio M.D. Department of Pathology Mt. Sinai Hospital

Anatomy/Histology of the Esophagus The esophagus is lined by non-keratinized stratified squamous epithelium It can withstand abrasion from foods but is sensitive to acid The lower esophageal sphincter protect the lower esophagus from gastric acid

Tracheoesophageal Fistulas Most common congenital esophageal anomaly, communication between trachea and esophagus Often associated with atresia (incomplete esophageal development)

Tracheoesophageal Fistulas Most common presentation is regurgitation during feeding Aspiration, suffocation, pneumonia, and severe fluid and electrolyte imbalances can occur Esophageal atresia is associated with congenital heart defects, genitourinary malformations, and neurologic disease

Esophageal Diverticula Outpouchings of the wall that contain all layers of the esophagus Zenker Diverticulum (pharyngoesophageal diverticulum) is located immediately above the upper esophageal sphincter Traction Diverticula occurs in the mid esophagus Epiphrenic diverticula are located immediately above the diaphragm

Esophageal Diverticula Diverticula occur in areas of weakened esophageal wall Zenker diverticula can accumulate large amounts of food causing regurgitation and aspiration pneumonia Epiphrenic diverticula are often seen in association with reflux esophagitis

Motor Disorders of the Esophagus Dysphagia: difficulty swallowing Odynophagia: pain on swallowing Achalasia: absence of peristalsis in the body of the esophagus and failure of the LES to relax in response to swallowing Primary/Idiopathic: failure of distal esophageal inhibitory neurons Secondary: Chagas disease, Trypanosoma cruzi infection destroys myenteric plexus causing aperistalsis and esophageal dilatation. Also caused by infiltrative disorders such as malignancy, amyloidosis, sarcoidosis

Inflammatory Disorders of the Esophagus Chemical Esophagitis Infectious Esphagitis Candida Herpes Cytomegalovirus Reflux Esophagitis (GERD) Reflux and Barrett’s esophagus

Chemical Esophagitis Corrosive acids or alkalis, alcohol, and heavy smoking are common irritants Medications can cause esophageal injury when pills get stuck in the esophagus instead of dissolving in the stomach (pill esophagitis) Chemotherapy and radiation therapy are important causes of iatrogenic esophagitis Chemical injury causes self-limited pain and dysphagia but in more severe cases hemorrhage or perforation may occur

Infectious Esophagitis Mostly affect immunocompromised Candida esophagitis: Candidiasis presents as small white plaques with hyperemic borders, in severe cases grayish pseudomembranes are seen Histologically, the candidal psuedomembrane contains fungal hyphae, necroinflammatory debris and fibrin

Infectious Esophagitis Herpes Esophagitis: Early lesions show plaques that may resemble candidiasis. Asl lesions evolve, large punched-out ulcers develop Histologically, epithelium shows nuclear viral inclusions within a rim of degenerating epithelial cells at the margin of the ulcer CMV Esophagitis: Grossly similar to Herpes infeciton Microscopically, shallower ulcers show characteristic nuclear and cytoplasmic inclusions in endothelial and stromal

Viral Esophagitis Herpes CMV

Reflux Esophagitis Most common type of esophagitis The lower esophageal spinchter (LES) is the most important barrier against reflux In the absence of proper LES tone the gastric contents (which are under positive pressure) enter and damage the epithelium of lower esophagus In addition, bile from the duodenum may exacerbate injury Lower LES tone and higher abdominal pressure may be see in : alcohol and tobacco use, obesity, central nervous system depressants, pregnancy, hiatal hernia, delayed gastric emptying LES From A.D.A.M.com

Reflux Esophagitis If reflux persists, the squamous epithelium becomes thickened, hyperemic and ulcerated Microscopically, the epithelial basal layer is hyperplastic and intaepithelial eosinophils and neutrophils are seen

Reflux Esophagitis Clinically, reflux esophagitis is called gastroesophageal reflux disease (GERD) Most common in adults >40 ys symptoms include dysphagia and heartburn Regurgitation or even severe chest pain in severe cases Treatment with proton pump inhibitors or H2 histamine receptor antagonists are usually effective Complications are related to duration of symptoms and include ulceration, bleeding and Barrett esophagus

ESOPHAGEAL ADENOCARCINOAM Barrett Esophagus GERD Barrett Esophagus DYSPLASIA =PREMALIGNANT ESOPHAGEAL ADENOCARCINOAM Replacement of the squamous esophageal epithelium by columnar epithelium (intestinal metaplasia) as a reaction to GERD injury Affects the lower esophagus, may extend higher Most common in men (40-60 yo), Caucasian Dysplasia is detected in about 2% of Barrett’s cases/year and it is associated with persistent GERD

Barrett Esophagus Morphology Endoscopically, it appears as “tongues” of red, velvety mucosa above the GE junction Histologically, intestinal metaplasia is composed of goblet cells wit cytoplasmic mucus vacuoles The diagnosis of Barrett esophagus requires both: Abnormal endoscopic findings and histology of intestinal metaplasia Normal gastroesophageal junction Barrett esophagus

Barrett and Dysplasia Dysplasia is identified by increased N/C ratio, atypical mitoses, hyperchromasia , cellular crowding (stratification) and abnormal architecture Based on the degree of cytologic and architectural atypia, dysplasia is categorized as low or high grade Invasion of neoplastic cells into the lamina propria results intramucosal carcinoma

Esophageal Carcinoma Esophageal Adenocarcinoma Squamous Cell Carcinoma

Esophageal Adenocarcinoma Arises from preexisting Barret esophagus and involves the lower 1/3 Risk is increased by smoking, obesity, and prior radiation Most common in men (M:F=7:1), Caucasians Most common type in US

Squamous Cell Carcinoma Usually arises in the upper or middle 1/3 esophagus Major risk factors include Alcohol and tobacco Consumption of hot beverages Achalasia Esophageal web (Plummer Vinson Syndrome) Chemical injury (lye ingestion) Most common in men (M:F=4:1), African-Americans Most common type of esophageal carcinoma worldwide

Esophageal Carcinoma Patients usually present late, predicting a poor prognosis Symptoms include: Progressive dysphagia (solids liquids) Weight loss Hematemisis Hoarseness (recurrent laryngeal nerve involvement) and cough (tracheal involvement) are seen in SqCC Lymph node involvement: Upper 1/3= cervical Middle 1/3= mediastinal/ tracheal Lower 1/3= celiac/gastric Overall 5-year survival is low; <20% in Adeno and <10% SqCC