Background: MiNEN are a rare histological subgroup defined by the association of at least two morphologically different neoplastic components, including one neuroendocrine. The diagnosis and therapeutic management of MiNEN is considered challenging resulting from the rarity and heterogeneity of this subgroup.
Case: We present the case of a 68-year-old Caucasian male who attended the emergency department with symptomatic hypoglycaemia on a background of poorly controlled type 2 diabetes, weight loss and constipation. ECOG performance status was 2. A CT scan revealed a pancreatic tail mass with extensive bilobar liver metastases, the largest of which was in segment 5 measuring 6x4 cm. A liver biopsy revealed a high grade mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN), consisting of acinar cell carcinoma and a focus of neuroendocrine carcinoma (NEC) of large cell type. The acinar cell carcinoma was suspected more predominant than the neuroendocrine component. Immunostaining was diffusely positive for CK7 and bcl10; chromogranin, synaptophysin and trypsin were moderately expressed. CEA, CD56, CA199 and p53 were negative; Ki67 was >70% in hot spots. 68Ga-DOTATATE PET/CT scan showed no sites of increased uptake. As per specialist NET multidisciplinary meeting and in the absence of specific guidelines, he was treated with gemcitabine (due to the predominant acinar component) and cisplatin (given the focal high grade NEC component). Dose modifications were required based on the borderline performance status and thrombocytopenia secondary to splenomegaly due to tumour related splenic vein compression. Following the first cycle of chemotherapy, he continued to deteriorate and was deemed unfit for further chemotherapy and was managed with best supportive care. He died only 3 months from initial diagnosis.
Conclusion: MiNEN is a rare entity which requires timely and accurate diagnosis. This case highlights the inadequacy of relevant clinical evidence, the difficulties associated with determining optimal therapeutic approaches and the poor prognosis associated with high grade MiNEN. The identification of genomic markers to define the molecular heterogeneity of MiNEN will be essential for the development of targeted treatments and prediction of patient outcomes.