Small cell carcinoma of the ovary, hypercalcemic type: a mini review
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian neoplasm, predominantly affecting young women, often in their second or third decade of life. Despite its distinctive clinical and pathological features, diagnosis is frequently delayed due to over...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1645361/full |
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| author | Marta Tripepi Ana G. da Costa Dennis S. Chi Dennis S. Chi Jorge Lima Jorge Lima João Casanova |
| author_facet | Marta Tripepi Ana G. da Costa Dennis S. Chi Dennis S. Chi Jorge Lima Jorge Lima João Casanova |
| author_sort | Marta Tripepi |
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| description | Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian neoplasm, predominantly affecting young women, often in their second or third decade of life. Despite its distinctive clinical and pathological features, diagnosis is frequently delayed due to overlapping characteristics with other small round blue cell tumors. A hallmark of SCCOHT is the biallelic inactivation of the SMARCA4 gene, which leads to loss of BRG1 protein expression and disrupts epigenetic regulation via the SWI/SNF chromatin-remodeling complex. Unlike many other malignancies, SCCOHT exhibits low mutational burden and diploid karyotype, suggesting that epigenetic dysregulation, rather than genomic instability, is the underlying oncogenic mechanism. Clinically, SCCOHT often presents with nonspecific abdominal or pelvic symptoms and is uniquely associated with paraneoplastic hypercalcemia in up to two-thirds of cases. Diagnosis requires a combination of imaging, laboratory evaluation, histopathology, and immunohistochemistry. Treatment is not standardized but typically involves a multimodal approach, including radical surgery and platinum-based chemotherapy, often with multi-agent regimens. The role of radiotherapy is less well defined but may be considered for local control or palliation. Prognosis remains poor, with high recurrence rates and limited response to salvage therapy. Emerging molecular insights have prompted investigations into targeted therapies and immunotherapy, though clinical data are limited. Given the frequent presence of germline SMARCA4 mutations, genetic counseling is strongly recommended, and ongoing research is essential to improve diagnostic accuracy, personalize treatment, and enhance outcomes for this devastating malignancy. |
| format | Article |
| id | doaj-art-e7c3647ebae64c7389d247d231539c19 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-e7c3647ebae64c7389d247d231539c192025-08-20T03:36:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-08-011510.3389/fonc.2025.16453611645361Small cell carcinoma of the ovary, hypercalcemic type: a mini reviewMarta Tripepi0Ana G. da Costa1Dennis S. Chi2Dennis S. Chi3Jorge Lima4Jorge Lima5João Casanova6Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, Padua, ItalyGynecologic Oncology Unit, Obstetrics and Gynecology Service, Department of Surgery, Hospital da Luz Lisboa, Lisbon, PortugalGynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United StatesDepartment of OB/GYN, Weill Cornell Medical College, New York, NY, United StatesObstetrics and Gynecology Service, Department of Surgery, Hospital da Luz Lisboa, Lisbon, PortugalComprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ciências Médicas, NOVA Medical School (NMS), Faculdade de Ciencias Medicas (FCM), Universidade Nova De Lisboa, Lisbon, PortugalGynecologic Oncology Unit, Obstetrics and Gynecology Service, Department of Surgery, Hospital da Luz Lisboa, Lisbon, PortugalSmall cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and highly aggressive ovarian neoplasm, predominantly affecting young women, often in their second or third decade of life. Despite its distinctive clinical and pathological features, diagnosis is frequently delayed due to overlapping characteristics with other small round blue cell tumors. A hallmark of SCCOHT is the biallelic inactivation of the SMARCA4 gene, which leads to loss of BRG1 protein expression and disrupts epigenetic regulation via the SWI/SNF chromatin-remodeling complex. Unlike many other malignancies, SCCOHT exhibits low mutational burden and diploid karyotype, suggesting that epigenetic dysregulation, rather than genomic instability, is the underlying oncogenic mechanism. Clinically, SCCOHT often presents with nonspecific abdominal or pelvic symptoms and is uniquely associated with paraneoplastic hypercalcemia in up to two-thirds of cases. Diagnosis requires a combination of imaging, laboratory evaluation, histopathology, and immunohistochemistry. Treatment is not standardized but typically involves a multimodal approach, including radical surgery and platinum-based chemotherapy, often with multi-agent regimens. The role of radiotherapy is less well defined but may be considered for local control or palliation. Prognosis remains poor, with high recurrence rates and limited response to salvage therapy. Emerging molecular insights have prompted investigations into targeted therapies and immunotherapy, though clinical data are limited. Given the frequent presence of germline SMARCA4 mutations, genetic counseling is strongly recommended, and ongoing research is essential to improve diagnostic accuracy, personalize treatment, and enhance outcomes for this devastating malignancy.https://www.frontiersin.org/articles/10.3389/fonc.2025.1645361/fullsmall cell ovarian cancerhypercalcemic typehypercalcemiaSMARCA4ovarian cancerpregnancy |
| spellingShingle | Marta Tripepi Ana G. da Costa Dennis S. Chi Dennis S. Chi Jorge Lima Jorge Lima João Casanova Small cell carcinoma of the ovary, hypercalcemic type: a mini review Frontiers in Oncology small cell ovarian cancer hypercalcemic type hypercalcemia SMARCA4 ovarian cancer pregnancy |
| title | Small cell carcinoma of the ovary, hypercalcemic type: a mini review |
| title_full | Small cell carcinoma of the ovary, hypercalcemic type: a mini review |
| title_fullStr | Small cell carcinoma of the ovary, hypercalcemic type: a mini review |
| title_full_unstemmed | Small cell carcinoma of the ovary, hypercalcemic type: a mini review |
| title_short | Small cell carcinoma of the ovary, hypercalcemic type: a mini review |
| title_sort | small cell carcinoma of the ovary hypercalcemic type a mini review |
| topic | small cell ovarian cancer hypercalcemic type hypercalcemia SMARCA4 ovarian cancer pregnancy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1645361/full |
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