Esophageal Tumors • • • • • • •
Malignant: Squamous cell carcinomamost common Adenocarcinoma Other less common malignancies undifferentiated carcinoma Carcinoid tumor Melanoma Lymphoma Sarcoma
• Benign tumors generally mesenchymal, leiomyomas most common • Fibromas, lipomas, hemangiomas, neurofibromas, and lymphangiomas also occur
Adenocarcinoma • Arise from Barrett esophagus • Additional risk factors tobacco use and exposure to radiation • Risk reduced by diets rich in fresh fruits and vegetables • Some serotypes of Helicobacter pylori causing gastric atrophy are associated with decreased risk
• More common in men • Barrett esophagus to adenocarcinoma occurs through stepwise acquisition of genetic and epigenetic changes
Pathogenesis
Morphology • Usually occurs in distal third of esophagus and may invade adjacent gastric cardia • Appears as flat or raised patches in intact mucosa • Size >/=5 cm in diameter • May infiltrate diffusely or ulcerate and invade deeply
Adenocarcinoma
Microscopic • Barrett esophagus may be present adjacent to tumor • Commonly produce mucin and form glands mostly with intestinal-type morphology • Less frequently composed of diffusely infiltrative signet-ring cells or small poorly differentiated cells
Intestinal-type adenocarcinoma
Signet-ring adenocarcinoma
Clinical Features • • • • •
Pain or difficulty in swallowing Progressive weight loss Hematemesis Chest pain Vomiting
Squamous Cell Carcinoma • Occurs in adults >45 years of age • Males: females = 4:1 • Risk factors – Alcohol and tobacco use – Poverty – Caustic esophageal injury
– Achalasia – Tylosis – Plummer-vinson syndrome – Diets, deficient in fruits or vegetables – Frequent consumption of very hot beverages – Previous radiation to mediastinum (5 to 10 or more years after exposure)
Pathogenesis Recurrent abnormalities include: • Amplification of transcription factor gene SOX2 (involved in cancer stem cell self-renewal and survival) • Overexpression of cell cycle regulator cyclin D1 • Loss-of-function mutations in tumor suppressors TP53,E-cadherin, and NOTCH1.
Morphology • Common in middle third • Begins as in situ lesion squamous dysplasia • Early lesions small, gray-white, plaque-like thickenings • Later grow into polypoid or exophytic masses protruding into and obstruct lumen
• May be ulcerated or diffusely infiltrative lesions spread within esophageal wall causing thickening, rigidity, and luminal narrowing • May invade surrounding structures respiratory tree, aorta or mediastinum and pericardium
Microscopic • Most are moderately to well differentiated
• Sites of lymph node metastases vary with tumor location: • Cancers in upper third favor cervical lymph nodes • Middle third favor mediastinal, paratracheal, and tracheobronchial nodes • Lower third spread to gastric and celiac nodes
Clinical Features • Commonly presents with dysphagia, odynophagia (pain on swallowing) or obstruction • Prominent weight loss • Hemorrhage and sepsis due to tumor ulceration • Symptoms of iron deficiency • Aspiration of food via tracheoesophageal fistula