S3656 Mixed Neuroendocrine-Non-Neuroendocrine Neoplasm (MiNEN) of the Pancreas: A Rare Diagnostic and Therapeutic Challenge

Introduction: Pancreatic mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) are rare, aggressive malignancies characterized by the presence of both a neuroendocrine component, typically a poorly differentiated neuroendocrine carcinoma (PDNEC), and a non-neuroendocrine component, usually adenocarcinoma, each comprising ≥30% of the tumor. They are associated with poor prognosis. Their rarity, histologic heterogeneity, and limited clinical data can present diagnostic and therapeutic challenges. Case Description/Methods: A 75-year-old man with a history of coronary artery disease, stroke, and dementia presented with severe abdominal pain and decreased appetite for 2 weeks. Computed tomography of the abdomen and pelvis revealed a 4 cm mass in the pancreatic tail. A 2.2 cm nodule in the right lung and 2 small hepatic lesions were also noted. Endoscopic ultrasound demonstrated a hypoechoic mass with irregular borders. Pathology showed poorly differentiated carcinoma with mixed acinar and neuroendocrine features. Surgical oncology evaluated the patient and deemed him a high risk surgical candidate. The family opted against surgical resection. He was discharged with follow-up with medical oncology. He underwent computed tomography-guided biopsy of the right lower lobe (RLL) lesion, which was non-diagnostic due to insufficient tissue sample. He is currently planned for PET-computed tomography imaging for staging. Discussion: Pancreatic MiNENs account for approximately 0.5% of pancreatic adenocarcinomas and 5% of pancreatic neuroendocrine neoplasms. Acinar-type carcinomas with neuroendocrine components are exceedingly rare. Diagnosis requires immunohistochemical confirmation of both neuroendocrine (chromogranin, synaptophysin) and acinar (BCL-10) markers. Due to limited clinical data, management remains ill-defined. Surgical resection is the mainstay for non-metastatic disease. If adjuvant therapy is indicated or the tumor is unresectable, treatment typically targets the more aggressive component. In most cases, regimens follow protocols for gastroenteropancreatic neuroendocrine carcinomas (GEP NECs). When the neuroendocrine component is NEC, platinum-based chemotherapy is often used. Alternatively, gastrointestinal adenocarcinoma regimens such as FOLFOX or FOLFIRINOX may be considered, though supporting data remain limited. This case report underscores the need for further research to establish standardized treatment protocols for this rare and aggressive group of tumors.