Whole Exon Sequencing of Primary Lesion and Liver Metastatic Lesion in Pancreatic Neuroendocrine Tumor：A Case Report and Review of the Literature

Abstract Background: Pancreatic neuroendocrine neoplasms(p-NENs) are classified into neuroendocrine tumors (NET) G1, G2, G3, and neuroendocrine carcinoma (NEC) according to WHO classification. NET and NEC are different pathogenesis. The two kinds of tumors that occurred in the same part have not been reported. We found 4 foci of NEN G3 in a primary pancreatic NET G2. The cell atypia was obvious with Ki67 index of 50-70%, focal necrosis, there were 12 hepatic metastatic nodules with similar morphology to NEN G3, which is difficult to identify NEC and NET G3.Case presentation: A patient with pancreatic NET was selected to perform whole exome sequencing on primary pancreatic NET G2 and liver metastatic NEN G3 paraffin tissues.NET G2 had 13 somatic mutations, while NEN G3 had 72 somatic mutations and Copy number variation in 4 genes. P.S493N point mutation of TRIOBP gene was detected in NET G2 and NEN G3. 5-fold amplification of MDM4 is found in the metastatic liver lesion.Conclusion: NET G2 and NEN G3 are closely related to TRIOBP gene. Oncogene amplification (MDM4) in liver metastases may be associated with morphological malignant transformation.