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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.
Nevertheless, managing NENs is not only a challenge to pathologists but also requires treating physicians to have a profound understanding of the underlying tumor biology and for example hormonal syndromes caused by endocrine activity [4]. Assessment of somatostatin receptor expression is one key feature in this context and somatostatin analogues are part of standard therapy in somatostatin-receptor-positive patients. Interestingly, somatostatin analogues for functional NETs have been discovered nearly three decades ago and these drugs represent one of the earliest and best-established examples for personalized, targeted therapy in the era of modern medical oncology. Further approved compounds include Lu-177-based-PRRT, everolimus and sunitinib.
In the current issue of memo, a series of articles covering different topics in the field of NEN is presented. Despite increasing options for systemic therapy in advanced NEN, surgery is still the only curative approach for (localized) disease and we appreciate the article of Ulla Klaiber and Stefan Stättner [5] who provide a comprehensive overview on current standards in the surgical management of GEP-NETs. Furthermore, Iva Brcic and Hanna Henzinger present the pathologist’s view in diagnosing GEP-NENs [7] and highlight the molecular background. Finally, Markus Raderer shares the medical oncologist’s view of managing patients with NET G3 and “how to deal” with such a new entity [6].
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Kiesewetter B, Raderer M. How I treat neuroendocrine tumours. ESMO Open. 2020; https://doi.org/10.1136/esmoopen-2020-000811.
Klaiber U, Stättner S. Current standards in the surgical treatment of pancreatic and small intestinal neuroendocrine tumors. memo. 2022. https://doi.org/10.1007/s12254-022-00840-7.
Raderer M, Kiesewetter B. The NET G3 enigma: dealing with a “new” entity. memo. 2022. https://doi.org/10.1007/s12254-022-00848-z.
Henzinger H, Brcic I. From morphology to molecular targets—the pathologist’s view in diagnosing gastroenteropancreatic neuroendocrine neoplasms. memo. 2022. https://doi.org/10.1007/s12254-022-00850-5.
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B. Kiesewetter declares that she has no competing interests.
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Kiesewetter, B. Neuroendocrine neoplasms revisited—the challenges of reclassifying tumor. memo 15, 257–258 (2022). https://doi.org/10.1007/s12254-022-00852-3
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DOI: https://doi.org/10.1007/s12254-022-00852-3