High-Grade Neuroendocrine Neoplasms

A special issue of Current Oncology (ISSN 1718-7729).

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 2746

Special Issue Editor


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Guest Editor
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55902, USA
Interests: gastrointestinal malignancies; thoracic malignancies; hepatobiliary tumors; neuroendocrine tumors

Special Issue Information

Dear Colleagues,

High-grade neuroendocrine neoplasms (NENs) are an increasingly encountered entity among providers who care for patients with NENs in general. High-grade NENs can either be well-differentiated grade 3 neuroendocrine tumors (G3 NETs) or poorly differentiated neuroendocrine carcinomas (NECs). Until relatively recently, G3 NETs were not recognized as a separate entity.

The current classification of high-grade (grade 3, G3) NENs clearly separates G3 NETs from NECs, but the distinction can be challenging for pathologists. Their natural history, response to therapy, and prognosis are very different, and only a few prospective trials have specifically addressed each entity within the G3 NEN spectrum.

This Special Issue aims to provide up-to-date information on the increasingly complex management of patients with G3 NENs. The role of the pathologist and the increasing role of molecular analysis will be discussed, and these discussions will be followed by reviews concerning the management of G3 NENs. As the management of G3 NETs differs substantially from the management of NECs, it will be discussed in a separate section. The current status of systemic therapy for NECs and the expanding roles of molecular testing and targeted therapy will be covered in detail.

We encourage all contributors, ideally a diverse group of contributors from different regions of the world, to add their voice and perspectives to the current state of the biology and management of patients with high-grade NENs.

Dr. Thorvardur Halfdanarson
Guest Editor

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Keywords

  • neuroendocrine tumor
  • neuroendocrine carcinoma
  • small cell carcinoma
  • large cell carcinoma
  • chemotherapy
  • immunotherapy
  • peptide receptor radionuclide therapy
  • alpha particle therapy

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Published Papers (2 papers)

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23 pages, 3454 KB  
Article
Searching for New Biomarkers of Neuroendocrine Tumors: A Comparative Analysis of Chromogranin A and Inflammatory Cytokines in Patients with Neuroendocrine Tumors
by Marlena Budek, Jarosław Nuszkiewicz, Jolanta Czuczejko, Marta Maruszak-Parda, Joanna Wróblewska, Jakub Wojtasik, Iga Hołyńska-Iwan, Marta Pawłowska, Alina Woźniak and Karolina Szewczyk-Golec
Curr. Oncol. 2024, 31(10), 6110-6132; https://doi.org/10.3390/curroncol31100456 - 12 Oct 2024
Cited by 1 | Viewed by 1860
Abstract
Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of [...] Read more.
Neuroendocrine neoplasms (NENs) present a diagnostic challenge due to their heterogeneous nature and non-specific clinical manifestations. This study aimed to explore novel biomarkers for NENs. Serum chromogranin A (CgA) levels and a panel of 48 inflammatory cytokines were analyzed in a cohort of 84 NEN patients and 40 healthy controls using enzyme-linked immunosorbent assay (ELISA) and multiplex ELISA. Significant alterations in cytokine levels were observed in the NEN patients compared to the controls, including elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α), and reduced levels of angiogenic factors like platelet-derived growth factor-BB (PDGF-BB) and tumor necrosis factor beta (TNF-β). Notably, cytokines such as growth-regulated alpha protein (GRO-α) and TNF-β demonstrated strong potential as diagnostic markers, with receiver operating characteristic (ROC) curve analyses showing high sensitivity and specificity. Additionally, a positive correlation was found between CgA levels and several inflammatory cytokines, suggesting their synergistic role in tumor progression. These findings highlight the limited reliability of CgA alone as a diagnostic marker and underscore the importance of a multi-marker approach in diagnosing and monitoring NENs. Further research on a larger cohort is necessary to validate these biomarkers and their potential clinical applications. Full article
(This article belongs to the Special Issue High-Grade Neuroendocrine Neoplasms)
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Case Report
Integrative Genomic and Clinicopathologic Characterization of Pure Primary Ovarian Large Cell Neuroendocrine Carcinoma: A Case Report and Molecular Insight
by Hyonjee Yoon, Chaewon Kim, Yongseok Lee, Jimin Ahn and Minjin Jeong
Curr. Oncol. 2025, 32(10), 540; https://doi.org/10.3390/curroncol32100540 - 27 Sep 2025
Abstract
Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by [...] Read more.
Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors. Full article
(This article belongs to the Special Issue High-Grade Neuroendocrine Neoplasms)
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