Mixed neuroendocrine non-neuroendocrine tumors: The quest for evidence

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are rare mixed tumors containing both neuroendocrine and non-neuroendocrine components that occupy at least 30% of the whole tumor. Biologically, both components appear to derive from an identical cellular precursor undergoing early dual differentiation or late transdifferentiation. While our understanding of MiNENs has improved in recent years, many areas of uncertainty remain. In this context, setting diagnostic criteria capable of capturing the continuum of disease biology while providing clinically meaningful information in terms of prognosis and response to treatments appears vital to advance the field and improve patients' outcomes. Evidence is needed to generate robust classification schemes, and multi-institutional cooperation will likely play a crucial role in building adequately powered cohorts to address some of the most pressing questions discussed in this Editorial. What is the minimum representation for each component needed to define MiNENs? How can the epidemiology of MiNENs change according to different diagnostic definitions? How can we generate the clinical evidence needed to optimize the management of MiNENs?