Ovarian Neuroendocrine Neoplasms: Challenges and Future Perspectives

<b>Background</b>: Ovarian neuroendocrine neoplasms (O-NENs) are extremely rare, representing less than 1% of all ovarian neoplasms and under 5% of all neuroendocrine tumors (NETs). They encompass two primary histological subtypes: well-differentiated carcinoids and poorly differentiated neuroendocrine carcinomas, which display distinct biological behaviors and prognoses. The ovary can also be a site of metastasis from extra-ovarian NETs. Owing to their rarity, clinical management lacks standardization, and diagnosis is often incidental following surgery for presumed epithelial ovarian neoplasms. <b>Objectives</b>: This review aims to provide an updated synthesis of current evidence on the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment strategies, and prognosis of O-NENs, highlighting unmet clinical needs. <b>Methods</b>: A literature search was performed on PubMed for the years 2014-2024 using the keywords: "ovarian neuroendocrine tumor", "ovarian neuroendocrine neoplasm", "ovarian neuroendocrine carcinoma", and "ovarian carcinoid". Only articles published in English were considered. Given the rarity of the disease, in addition to meta-analyses and systematic reviews, relevant case reports and case series were also included to provide a comprehensive clinical picture, yielding 32 eligible articles. <b>Results</b>: Evidence indicates that O-NENs remain understudied, with most data derived from case reports and small series. Clinical presentations vary from asymptomatic masses to hormone-related syndromes, often mimicking other ovarian pathologies. Diagnostic work-up typically follows the same protocol as epithelial ovarian cancer, with the neuroendocrine nature only recognized postoperatively. Treatment strategies are empirical and largely extrapolated from extra-ovarian NETs due to the absence of specific guidelines. Prognosis varies widely depending on histotype, stage, and secretory activity. <b>Conclusions</b>: O-NENs pose significant diagnostic and therapeutic challenges due to their rarity and heterogeneity. Greater clinical awareness, multidisciplinary management, and multicenter research are essential to establish evidence-based protocols and improve patient outcomes.