Neuroendocrine Tumors of the Esophagus

Neuroendocrine system is not well developed in the esophagus, and as a result esophageal neuroendocrine tumors (NETs) are extremely rare. Anatomically esophageal NETs are classified under foregut neuroendocrine neoplasm (NENs) category, and their grading and staging follows the general rule as for foregut NETs of elsewhere. Several genetic and epigenetic alterations and molecular pathway dysregulations have been proposed to be involved in the pathogenesis of esophageal NENs including mTOR pathway. The most common presenting symptom of esophageal NET is dysphagia. Cases of typical carcinoid syndrome in NET of esophagus are very rare, and as its lung counterpart, syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can be seen in association with esophageal NET in extremely rare occasions as well. The 2010 WHO classification system divides NENs of esophagus into low- to intermediate-grade (grade 1–2) neuroendocrine tumors (NETs) and high-grade (grade 3) neuroendocrine carcinomas (NECs, large or small cell type), according to their histopathologic characterization and proliferation rate. Esophagus is the most common site of small cell carcinoma in the gastrointestinal tract and histologically indistinguishable from its counterpart in the lung. However, small cell neuroendocrine carcinoma (SCNEC) of esophagus may have a much more aggressive clinical course and tends to metastasize early. Despite combination radio-chemotherapies, the overall survival is very poor.