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Ovarian Neuroendocrine Neoplasms: Challenges and Future Perspectives.

Valentina Di Vito¹, Gabriele Veroi^1,2, Laura Rizza¹

¹Department of Endocrinology, San Camillo-Forlanini Hospital, 00152 Rome, Italy.

Journal of Clinical Medicine

|December 30, 2025

Summary

Ovarian neuroendocrine neoplasms (O-NENs) are rare tumors with varied presentations and prognoses. Improved awareness and multicenter research are crucial for developing standardized diagnostic and treatment protocols for these challenging ovarian neoplasms.

Keywords:

carcinoid tumors neuroendocrine carcinomas ovarian neuroendocrine neoplasms

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Area of Science:

Gynecologic Oncology
Endocrinology
Pathology

Background:

Ovarian neuroendocrine neoplasms (O-NENs) are exceptionally rare, accounting for <1% of ovarian neoplasms and <5% of all neuroendocrine tumors (NETs).
They include well-differentiated carcinoids and poorly differentiated neuroendocrine carcinomas, with distinct behaviors and prognoses.
Ovary can also be a site for metastasis from extra-ovarian NETs, complicating diagnosis and management.

Purpose of the Study:

To synthesize current evidence on epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of O-NENs.
To highlight existing unmet clinical needs in the management of these rare ovarian tumors.
To provide an updated overview for clinicians managing ovarian neuroendocrine neoplasms.

Main Methods:

Comprehensive literature search on PubMed (2014-2024) using keywords: "ovarian neuroendocrine tumor", "ovarian neuroendocrine neoplasm", "ovarian neuroendocrine carcinoma", "ovarian carcinoid".
Inclusion of meta-analyses, systematic reviews, case reports, and case series published in English.
Analysis of 32 eligible articles to provide a comprehensive clinical picture of O-NENs.

Main Results:

O-NENs remain understudied, with limited data primarily from case reports and small series.
Clinical presentations are diverse, ranging from asymptomatic masses to hormone-related syndromes, often mimicking other ovarian pathologies.
Diagnosis is frequently incidental post-surgery; treatment is empirical, extrapolated from extra-ovarian NETs due to lack of specific guidelines; prognosis varies widely.

Conclusions:

O-NENs present significant diagnostic and therapeutic challenges due to rarity and heterogeneity.
Increased clinical awareness and multidisciplinary management are essential for improving patient outcomes.
Multicenter research is vital for establishing evidence-based protocols for ovarian neuroendocrine neoplasms.