First Case of Mixed Poorly Differentiated Mucinous Adenocarcinoma and High-Grade Neuroendocrine Neoplasm With Amphicrine Differentiation

Abstract

Amphicrine carcinoma is a rare gastrointestinal carcinoma characterized by dual exocrine and neuroendocrine differentiation within individual tumor cells. Its rarity, overlapping morphological features with those of conventional adenocarcinoma, and evolving classification present diagnostic and therapeutic challenges. We report the rare case of a middle-aged man who presented with dysphagia and weight loss. Imaging revealed a distal esophageal mass, and biopsy confirmed adenocarcinoma. Following neoadjuvant chemoradiation, persistent disease led to esophagogastrectomy. Microscopic examination demonstrated extracellular mucin pools and glandular/cribriform structures, with co-expression of neuroendocrine markers (INSM1, synaptophysin, and chromogranin) and mucin within the same tumor cells. Electron microscopy confirmed the presence of dense-core neurosecretory granules, mucin droplets, and microvilli in the same tumor cells, supporting the diagnosis of amphicrine carcinoma. Amphicrine carcinoma is distinct from conventional adenocarcinoma and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs), with prognosis determined by histologic grade. Molecular profiling has revealed recurrent copy-number gains on chromosome 20q13.12-q13.2, involving MYT1, NTSR1, and ZBTB46, suggesting a distinct biological profile. Recognition of amphicrine carcinoma is critical for accurate diagnosis, prognostic assessment, and appropriate treatment. Diagnosis relies on careful evaluation of morphologic features and immunohistochemical findings, while histologic grade appears to predict prognosis. Awareness of this rare entity is essential for appropriate clinical management, and further studies are needed to better define its molecular characteristics and guide the development of targeted therapies.