SYP and neoplasm: The histopathological diagnosis of NENs relies on characteristic morphological features and on the demonstration of the neuroendocrine phenotype of tumor cells through the immunohistochemical detection of a panel of markers including at least synaptophysin and chromogranin A. Insulinoma-associated protein 1 (INSM1) has recently been proposed as a promising nuclear marker, since it is highly sensitive and specific for NENs, irrespective of origin and differentiation status (III, A).