Neuroendocrine carcinoma of the esophagus: clinicopathologic study of 10 cases and verification of the diagnostic utility of mASH1, NeuroD1, and PGP9.5

Background Neuroendocrine carcinoma (NEC) of the esophagus is a rare histologic type that is aggressive and grows rapidly. Immunohistochemistry with conventional antibodies, such as synaptophysin, chromogranin A, and CD56, is widely performed. Several novel neuroendocrine markers, such as mammalian achaete-scute homolog 1 (mASH1), NeuroD1, and PGP9.5, were recently proposed. Methods From 1115 consecutive cases with esophageal cancer, 10 NEC cases (0.9 %) were enrolled and the clinicopathologic parameters, including prognosis, were compared with those of 32 squamous cell carcinomas (SCC) and 30 basaloid squamous carcinomas (BSC). Immunohistochemistry for mASH1, NeuroD1, PGP9.5 and for conventional antibodies was performed. Both monoclonal and polyclonal antibodies for NeuroD1 and PGP9.5 were evaluated. Results Six NEC cases were diagnosed as T1b (submucosal invasion), four of which were endoscopically resected. The remaining four cases with T3 or T4 died of the disease within 37 months. Of the six patients with T1b, three are alive with no evidence of disease for more than 50 months, although the prognosis is worse for NEC than for SCC and BSC. The mASH1, NeuroD1-monoclonal, NeuroD1-polyclonal, PGP9.5-monoclonal, and PGP9.5-polyclonal immunohistochemical markers were positive in 8, 8, 1, 7, and 6 NEC cases, respectively. The number of mASH1-positive cases and synaptophysin-positive cases was the same. mASH1 had good concordance with chromogranin A and CD56, and was superior to other novel antibodies. mASH1 had excellent specificity and sensitivity for NEC. Conclusion Esophageal NEC has a worse prognosis than SCC and BSC, even in T1b patients. mASH1 is an excellent novel marker for diagnosing esophageal NEC.