Abstract
Metastatic neuroendocrine neoplasms (NENs) with an unknown primary (UP) represent a specific subset that can concern both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). An appropriate diagnostic work-up is necessary to conclude for UP NEN, including complete pathological report and morphological and functional imaging. Therapeutical approach to UP NEN is controversial and nonevidence based, as only few clinical trials include UP NEN as a specific entity. While in UP NETs the identification of the primary site can have relevant therapeutic implications, it is not the case for UP NECs, where the high grade of the neoplasm usually indicates starting chemotherapy soon. In patients with a metastatic UP NENs, ENETS guidelines suggest to base treatment decisions on grading, functionality, somatostatin receptor status, tumor extent, and hepatic tumor burden.
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