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Current Oncology
Special Issues
High-Grade Neuroendocrine Neoplasms
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High-Grade Neuroendocrine Neoplasms

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

Deadline for manuscript submissions: closed (31 July 2025) | Viewed by 3915

Special Issue Editor

Dr. Thorvardur Halfdanarson

E-Mail Website
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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Current Oncology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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 (3 papers)

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18 pages, 430 KB  
Article
Germline Mutations in DNA Repair Genes in Patients with Pancreatic Neuroendocrine Neoplasms: Diagnostic and Therapeutic Implications
by Beata Jurecka-Lubieniecka, Małgorzata Ros-Mazurczyk, Aleksandra Sygula, Alexander J. Cortez, Marcela Krzempek, Anna B. Tuleja, Agnieszka Kotecka-Blicharz, Marta Cieslicka, Malgorzata Oczko-Wojciechowska and Daria Handkiewicz-Junak
Curr. Oncol. 2025, 32(11), 631; https://doi.org/10.3390/curroncol32110631 - 10 Nov 2025
Viewed by 514
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess [...] Read more.
Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations. Full article
(This article belongs to the Special Issue High-Grade Neuroendocrine Neoplasms)
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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 2016
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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Other

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10 pages, 3956 KB  
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
Viewed by 541
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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