Neuroendocrine carcinoma of the esophagus: Clinicopathological and immunohistochemical features of 14 cases

Akinori Egashira,Shohei Yamaguchi,Masanobu Ueda,Reiko Kumagai,Ken-Ichi Taguchi,Yasushi Toh,Yasuharu Ikeda,Kazuhito Minami,Masaru Morita,Manabu Yamamoto,Renato Franco

doi:10.1371/journal.pone.0173501

Abstract

BackgroundNeuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus.MethodsFourteen patients diagnosed with NEC of the esophagus from 1998 to 2013 were included in this study. Clinicopathologic features, therapeutic outcomes and immunohistochemical results were analyzed.ResultsEleven out of 14 cases showed protruding or localized type with or without ulceration. Only three patients were negative for both lymph node and organ metastasis and seven cases were positive for metastases to distant organs and/or distant lymph nodes. Of the six patients with limited disease (LD), three patients were treated by surgery. Three patients with LD and seven patients with extensive disease (ED) were initially treated with chemotherapy, except for one who underwent concurrent chemo-radiotherapy due to passage disturbance. The median survival of patients with LD was 8.5 months, whereas that of patients with LD was 17 months. Among the 14 cases, 12 cases (83.3%), 13 cases (91.7%) and 12 cases (83.3%) showed positive immunostaining for choromogranin A, synaptophysin and CD56, respectively. Nine of 14 cases (64.2%) presented positive staining for c-kit and most (8/9, 88%) simultaneously showed p53 protein abnormality. Two cases were negative for c-kit and p53, and positive for CK20.ConclusionConsistent with previous reports, the prognosis of NEC of esophagus is dismal. From the results of immunohistochemical study, NEC of esophagus might be divided into two categories due to the staining positivity of c-kit and p53. This study provides new insight into the biology of NEC of the esophagus.

Highlights

Neuroendocrine carcinoma (NEC) is a relatively rare disease with a reported incidence between 0.4% and 2% among all malignancies of the esophagus [1,2,3]
Of the six patients with limited disease (LD), three patients were treated by surgery
A Ki67 or mitotic index of 20% or more is necessary for diagnosing NEC, the tumors with less than 20% Ki 67 positivity are diagnose as neuroendocrine tumors [5]

Summary

Introduction

Neuroendocrine carcinoma (NEC) is a relatively rare disease with a reported incidence between 0.4% and 2% among all malignancies of the esophagus [1,2,3]. NEC is categorized into two morphological types: small cell type and large cell type. The former is more frequent (approximately 90% of total cases) and most cases formerly recognized as small cell carcinoma or oat cell carcinoma of the esophagus were included [4]. NEC of the gastrointestinal tract presents relatively prominent features including submucosal growth, usually covered by normal epithelium with or without ulcerous lesion in the center. Neuroendocrine carcinoma (NEC) of the esophagus is a rare and highly aggressive disease but the biological features are poorly understood. The objective of this study was to analyze the clinicopathological and immunohistochemical features of NEC of the esophagus

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Results

Conclusion