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Esophagus cancer Dr Sanei Associated professor of pathology GI and Liver patholoogist Pathogenesis food or water rich in nitrates and nitrosamines tobacco smoke, alcohol, and various vitamin deficiencies achalasia Plummer-Vinson syndrome strictures resulting from acid or lye ingestion HPV types 16 and 18. 0% to 66% Molecular Features cyclin D1 and cyclin E p53, Rb, and p16 in up to 80% epidermal growth factor receptor (EGFR), seen in from 29% to 92% SQUAMOUS DYSPLASIA low grade and high grade 60% to 90% erythematous, friable, and irregular in more than 80% Erosions, plaques, and nodules normal endoscopically reactive epithelial changes indefinite for dysplasia chemotherapy or radiotherapy esophagitis secondary to reflux, or other causes such as drug effect INVASIVE SQUAMOUS CELL CARCINOMA early (superficial) and late (advanced) middle third of the esophagus in 50% to 60% of cases Superficially invasive tumors are more commonly multicentric up to 20% of cases fungating (60% of cases), ulcerating (25% of cases), or infiltrative (15% In patients treated with preoperative radiation or chemotherapy, the tumor may be invisible or perhaps replaced with a shallow surface erosion. cytokeratins 13, 14, 18, and 19.[65], [66] CK7 reactivity is present in up to 29% of cases majority of cases are negative for both cytokeratins 7 and 20 most tumors express the nuclear antigen p63 Focal positivity for neuroendocrine markers such as chromogranin and synaptophysin Mucin stains may show focal positivity Differential Diagnosis lung squamous cell carcinomas thyroid transcription factor F1 (TTF-1), pseudoepitheliomatous hyperplasia melanoma lymphoma pseudodiverticulosis VARIANTS OF SQUAMOUS CELL CARCINOMA Basaloid Squamous Cell Carcinoma Carcinosarcoma Verrucous Squamous Cell Carcinoma Lymphoepithelioma-Like Carcinoma ADENOCARCINOMA More than 95% of esophageal adenocarcinomas develop in association with Barrett's esophagus Non–Barrett's-Associated Adenocarcinoma extremely rare and arise either from foci of gastric heterotopia submucosal gland/duct system Adenoid Cystic Carcinoma CARCINOMA WITH MIXED SQUAMOUS AND GLANDULAR ELEMENTS adenoacanthoma adenosquamous carcinoma mucoepidermoid carcinoma METASTASES lung, breast, and stomach renal cell carcinoma