Large Cell Neuroendocrine Carcinoma of the Stomach: A Case Series

Abstract

Gastric large-cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive malignancy, accounting for less than 1.5% of all gastric cancers. It is associated with a poor prognosis and may arise through distinct oncogenic pathways, including neuroendocrine cell lineage origin or trans differentiation from gastric epithelial cells. This case series describes three patients diagnosed with gastric LCNEC. Case 1 involved an 88-year-old man who presented with weakness, lethargy, anorexia, and lower-extremity edema. Imaging revealed gastric wall thickening with suspected liver metastases. Histopathological examination confirmed poorly differentiated LCNEC. The patient received palliative radiotherapy followed by carboplatin and etoposide but developed severe pancytopenia after the first chemotherapy cycle and died four months after diagnosis. Case 2 was a 67-yearold man who presented with epigastric and flank pain. Immunohistochemical analysis demonstrated positivity for chromogranin and synaptophysin, with a Ki-67 index of 55–60%, confirming a high-grade neuroendocrine carcinoma. Despite multimodal treatment, including chemotherapy and chemoradiotherapy, he developed brain metastasis and died shortly after craniotomy. Case 3 involved a 70-year-old man with diabetes who presented with progressive dysphagia and marked weight loss. Endoscopy revealed an esophageal neuroendocrine carcinoma and a large gastric cardia mass. Immunohistochemistry showed positivity for cytokeratin, chromogranin, TTF-1, and a Ki-67 index of 70–80%. The patient received platinum-based chemotherapy followed by concurrent chemoradiotherapy. These cases highlight the highly aggressive clinical behavior of gastric LCNEC, its propensity for early metastatic dissemination, and the poor prognosis despite multimodal treatment. Early recognition and accurate histopathological diagnosis are essential for appropriate management of this uncommon malignancy.