Neuroendocrine neoplasms revisited—the challenges of reclassifying tumor

Excerpt

Neuroendocrine neoplasms (NEN) constitute a heterogenous group of malignancies that arise from the diffuse neuroendocrine cell system [1]. Given the wide distribution of these cells, NEN may develop in nearly any organ but are most commonly diagnosed in the gastroenteropancreatic (GEP) tract and the lung. In addition to immunohistochemical expression of the neuroendocrine markers chromogranin A and synaptophysin, classification, prognosis and treatment is defined by the tumor proliferation rate measured by Ki-67 expression. Until recently, patients with GEP-NEN were classified either as well-differentiated neuroendocrine tumors (NET) G1/2 (Ki-67 < 20%) or as aggressive neuroendocrine carcinomas (NEC) G3 (Ki-67 > 20%) [2]. However, following the observation that in the G3 cohort some patients present with maintained neuroendocrine morphology and a more indolent clinical behavior, the new group of NET G3 was added to the World Health Organization (WHO) classification [3]. Such reclassifications challenge not only diagnostic algorithms but also result in a variety of clinical questions, as in fact only scarce data on the management of NET G3 are yet available and there is currently no approved drug for NET G3. …