Mixed Neuroendocrine and Non-neuroendocrine Tumor of Pancreato-Biliary Origin Treated Successfully with Peptide...

Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) are rare neoplasms composed of morphologically distinguishable neuroendocrine (NE) and non-neuroendocrine components, each representing at least 30% of the tumor volume. The NE component must be substantiated by immunohistochemistry. MiNENs generally have a poor prognosis, with a more aggressive component dictating overall survival and prognosis. Owing to its rarity, there are no specific validated treatment guidelines available for these tumors, and they are generally treated with surgery if possible. However, surgically unresectable or advanced tumors are generally treated with chemotherapy.

We report a case of an elderly woman who was referred to the neuroendocrine tumor (NET) unit following incidental findings of liver lesions found on cardiac magnetic resonance imaging (MRI) performed for an asymptomatic heart murmur. Histology from the liver biopsy revealed MiNEN with up to 60% grade 2 (Ki67: 19%) well-differentiated NET and up to 30% well-differentiated to moderately differentiated adenocarcinoma of possible pancreato-biliary origin; intrahepatic ductal primary could not be excluded. Her 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) revealed no FDG-avid lesions, and a ⁶⁸Gallium 1,4,7,10-tetraazacyclododecane-tetraacetic acid Tyr3-octreotate (⁶⁸ Ga-DOTATATE)-PET scan revealed multiple areas of intensely DOTATATE-avid liver lesions. Due to the absence of any primary imaging findings, the patient was diagnosed with MiNEN of possible pancreato-biliary origin.

She was started on lanreotide 120 mg every 28 days for 6 months, with no response to the treatment. Subsequently, the patient was treated with four cycles of ¹⁷⁷Lutetium-DOTATATE (Lutathera®) peptide receptor radionuclide therapy (PRRT). She tolerated the treatment well, with no significant side effects. MRI at the end of treatment revealed a partial response to treatment.

PRRT is currently not used in treatment protocols for the management of MiNENs; however, it could be considered a treatment option in patients with MiNENs, where there is a predominant component of well-differentiated NETs with ⁶⁸ Ga-DOTATATE avid lesions.