Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
Ovarian Neuroendocrine Neoplasms: Challenges and Future Perspectives / Di Vito, V., Veroi, G., Rizza, L., Rota, F., Baiocchini, A., Macciomei, M.C., Lubrano, C., La Salvia, A., Lania, A., Grillo, L.R., Migliaccio, S., Rindi, G., Baldelli, R., Di Vito, V., Veroi, G., Rizza, L., Rota, F., Baiocchini, A., Macciomei, M.C., Lubrano, C., et al.. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 14:24(2025). [10.3390/jcm14248833]
Ovarian Neuroendocrine Neoplasms: Challenges and Future Perspectives
Veroi G.;Migliaccio S.;Baldelli R.;Veroi G.;Baldelli R.
2025
Abstract
Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
