In some cases associated with MENIN loss were also found mutation affecting VHL tumor suppressor gene that determined a constitutive hypoxia transcription factors (HIF) activation and uncontrolled angiogenesis (16, 17), suggesting that MENIN loss or mutation is a key initiator in PNET tumorigenesis (15, 18–21). The gene discussed is MEN1; the disease is primitive neuroectodermal tumor.