1. Esophagus cancer Dr Sanei Associated professor of pathology GI and Liver patholoogist

2. Pathogenesis food or water rich in nitrates and nitrosamines food or water rich in nitrates and nitrosamines tobacco smoke, alcohol, and various vitamin deficiencies tobacco smoke, alcohol, and various vitamin deficiencies achalasia achalasia Plummer-Vinson syndrome Plummer-Vinson syndrome strictures resulting from acid or lye ingestion strictures resulting from acid or lye ingestion HPV types 16 and 18. 0% to 66% HPV types 16 and 18. 0% to 66%

3. Molecular Features cyclin D1 and cyclin E cyclin D1 and cyclin E p53, Rb, and p16 in up to 80% p53, Rb, and p16 in up to 80% epidermal growth factor receptor (EGFR), seen in from 29% to 92% epidermal growth factor receptor (EGFR), seen in from 29% to 92%

4. SQUAMOUS DYSPLASIA low grade and high grade low grade and high grade 60% to 90% 60% to 90% erythematous, friable, and irregular in more than 80% erythematous, friable, and irregular in more than 80% Erosions, plaques, and nodules Erosions, plaques, and nodules normal endoscopically normal endoscopically reactive epithelial changes indefinite for dysplasia reactive epithelial changes indefinite for dysplasia chemotherapy or radiotherapy chemotherapy or radiotherapy esophagitis secondary to reflux, or other causes such as drug effect esophagitis secondary to reflux, or other causes such as drug effect

5. INVASIVE SQUAMOUS CELL CARCINOMA early (superficial) and late (advanced) early (superficial) and late (advanced) middle third of the esophagus in 50% to 60% of cases middle third of the esophagus in 50% to 60% of cases Superficially invasive tumors are more commonly multicentric up to 20% 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% 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. In patients treated with preoperative radiation or chemotherapy, the tumor may be invisible or perhaps replaced with a shallow surface erosion.

6. cytokeratins 13, 14, 18, and 19.[65], [66] CK7 reactivity is present in up to 29% of cases 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 majority of cases are negative for both cytokeratins 7 and 20 most tumors express the nuclear antigen p63 most tumors express the nuclear antigen p63 Focal positivity for neuroendocrine markers such as chromogranin and synaptophysin Focal positivity for neuroendocrine markers such as chromogranin and synaptophysin Mucin stains may show focal positivity Mucin stains may show focal positivity

15. Differential Diagnosis lung squamous cell carcinomas thyroid transcription factor F1 (TTF-1), lung squamous cell carcinomas thyroid transcription factor F1 (TTF-1), pseudoepitheliomatous hyperplasia pseudoepitheliomatous hyperplasia melanoma melanoma lymphoma lymphoma pseudodiverticulosis pseudodiverticulosis

16. VARIANTS OF SQUAMOUS CELL CARCINOMA

17. Basaloid Squamous Cell Carcinoma

19. Carcinosarcoma

21. Verrucous Squamous Cell Carcinoma

23. Lymphoepithelioma-Like Carcinoma

24. ADENOCARCINOMA More than 95% of esophageal adenocarcinomas develop in association with Barrett's esophagus More than 95% of esophageal adenocarcinomas develop in association with Barrett's esophagus Non–Barrett's-Associated Adenocarcinoma Non–Barrett's-Associated Adenocarcinoma extremely rare and arise either from foci of gastric heterotopia extremely rare and arise either from foci of gastric heterotopia submucosal gland/duct system submucosal gland/duct system Adenoid Cystic Carcinoma Adenoid Cystic Carcinoma

25. CARCINOMA WITH MIXED SQUAMOUS AND GLANDULAR ELEMENTS adenoacanthoma adenoacanthoma adenosquamous carcinoma adenosquamous carcinoma mucoepidermoid carcinoma mucoepidermoid carcinoma

28. METASTASES lung, breast, and stomach lung, breast, and stomach renal cell carcinoma renal cell carcinoma