The Miscellaneous Mystery of Esophageal Cancer: New pathogenetic and clinical insights

Esophageal cancer is the 8th most common type of malignancy and the 6th most common cause of cancer mortality in the world. Worldwide more than 400,000 patients are newly diagnosed with esophageal cancer each year. The majority of patients (>90%) is diagnosed with the two most common histological subtypes: squamous cell carcinoma or adenocarcinoma of the esophagus. Esophageal squamous cell carcinoma arises from dysplastic squamous epithelium, usually as a result of chronic irritation. Substantial alcohol intake, especially in combination with smoking, greatly increases the risk of squamous cell carcinoma and accounts for more than 90 percent of all cases of squamous cell carcinoma of the esophagus in the developed world. Patients with recurring symptoms of reflux have an eightfold increase in the risk of developing esophageal adenocarcinoma. Ongoing gastroesophageal reflux results in the replacement of normal squamous epithelium by a columnar-lined esophagus, which is characterized by the presence of intestinal metaplasia. This so-called Barrett’s esophagus is the precursor lesion of esophageal adenocarcinoma, that develops through a metaplasia – dysplasia – carcinoma sequence.

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