Current concepts in the diagnosis and management of neuroendocrine neoplasms of unknown primary origin

Abstract

Neuroendocrine neoplasms (NENs) of unknown primary origin (UPO-NENs) are advanced neoplasms constituting 11-22% of all NENs that by definition their primary tissue of origin has not been identified with standard diagnostic work-up. Delineating the primary site of origin of UPO-NENs has important implications for selecting the appropriate treatment and overall prognosis. The small bowel, followed by the lung and pancreas are the most prevalent primary sites of origin of UPO-NENs that are uncovered during an extensive and prolonged diagnostic work-up; however, a number of UPO-NENs may still remain occult even after prolonged follow-up. A number of diagnostic algorithms that incorporate histopathological, molecular, imaging (either morphological or functional imaging), and serum biomarkers can help to identify the primary tumor origin. It is expected that advances in these fields will help reduce significantly the number of UPO-NENs.