A Comprehensive Review on Neuroendocrine Neoplasms: Presentation, Pathophysiology and Management

Abstract

This review focuses on neuroendocrine neoplasms (NENs), which represent a heterogeneous group of relatively uncommon tumors that arise from cells of the endocrine and nervous systems. Although diverse, these tumors share common features, such as an alike histological appearance, the presence of secretory granules and, often, the generation and release of hormones or biogenic amines. NENs have been categorized based on their clinical behavior, histology, anatomic location and proliferation rate—factors relevant to their treatment and prognosis. Previously, chiefly diagnosed by their clinical features, their presence incidental to widespread imaging techniques appears to be on the rise in the US and several other countries. In this light, this article summarizes their pathophysiology, staging and recent changes to clinical practice pertinent to their diagnosis and treatment. Neuroendocrine neoplasms (NENs) are a group of heterogeneous tumors with neuroendocrine differentiation that can arise from any organ. They account for 2% of all malignancies in the United States. A significant proportion of NEN patients experience endocrine imbalances consequent to increased amine or peptide hormone secretion, impacting their quality of life and prognosis. Over the last decade, pathologic categorization, diagnostic techniques and therapeutic choices for NENs—both well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs)—have appreciably evolved. Diagnosis of NEN mostly follows a suspicion from clinical features or incidental imaging findings. Hormonal or non-hormonal biomarkers (like serum serotonin, urine 5-HIAA, gastrin and VIP) and histology of a suspected NEN is, therefore, critical for both confirmation of the diagnosis and classification as an NET or NEC. Therapy for NENs has progressed recently based on a better molecular understanding, including the involvement of mTOR, VEGF and peptide receptor radionuclide therapy (PRRT), which add to the growing evidence supporting the possibility of treatment beyond complete resection. As the incidence of NENs is on the rise in the United States and several other countries, physicians are more likely to see these cases, and their better understanding may support earlier diagnosis and tailoring treatment to the patient. We have compiled clinically significant evidence for NENs, including relevant changes to clinical practice that have greatly updated our diagnostic and therapeutic approach for NEN patients.

Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives

“…High-grade NECs of the kidney, which include SCNECs and LCNECs according to the 2022 WHO classification, are extremely rare and aggressive malignancies [169]. As neuroendocrine cells have never been described so far in the renal parenchyma, it is possible that kidney NECs might arise from multipotent stem cells with a neuroendocrine differentiation [7].…”