Dual TP53 mutations in ovarian high-grade serous carcinoma combined with squamous cell carcinoma: a case report and systematic literature review

Objective This study reports a rare case of mixed ovarian carcinoma composed of squamous cell carcinoma (SCC) and high-grade serous carcinoma (HGSC) arising from endometriosis, and provides a systematic review of the relevant literature. Case presentation A 59-year-old female presented with bilateral ovarian cystic lesions (4.6 cm on the left, 9.6 cm on the right) and a mural nodule in the right ovarian cyst. Serum tumor markers were CA125 57.50 U/mL and CA19-9 6.74 U/mL. The patient underwent total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and appendectomy. Histopathological examination revealed a mixed carcinoma of the right ovary composed of SCC and HGSC, with adjacent serous borderline tumor and endometriotic cyst. The left ovary showed a serous borderline tumor with endometriosis. Next-generation sequencing (NGS) identified two distinct TP53 mutations: a missense mutation in the HGSC component and a splice-site mutation in the SCC component. The patient received six cycles of paclitaxel and carboplatin chemotherapy. Within two months after completing the treatment, tumor markers had normalized and no recurrence was detected.

We describe a 59-year-old woman diagnosed with stage IA mixed ovarian carcinoma (SCC and HGSC), in which two distinct TP53 gene mutations were identified. A systematic literature review was conducted using PubMed, Embase, and Web of Science databases.

A total of eight published cases of ovarian mixed carcinoma containing a squamous component were identified. Of these, five originated from endometriosis and one from a mature cystic teratoma. Histologically, five cases were endometrioid adenocarcinoma with squamous differentiation, while others included clear cell carcinoma, mucoepidermoid carcinoma, and HGSC (the present case), each admixed with SCC components.

This is the first reported case of ovarian HGSC coexisting with SCC. Given its extreme rarity, standardized treatment strategies have not yet been established. Similar content being viewed by others Data availability All datasets generated for this study are included in the article.

Margioula-Siarkou C, Almperi EA, Almperis A, Margioula-Siarkou G, Titilas G, Dinas K, Petousis S. Squamous Cell Carcinoma of the Ovary: A Rare Case. Cureus. 2024;16(11):e74547. https://doi.org/10.7759/cureus.74547. Montebello A, Maniscalco N, Grech M, Cuschieri A, Brockdorff KMV. Squamous cell carcinoma of the ovary arising from a mature cystic teratoma associated with hypercalcaemia. Br J Hosp Med (London England: 2005). 2024;85(7):1–5. https://doi.org/10.12968/hmed.2024.0086. Cai Z, Yang GL, Li Q, Zeng L, Li LX, Song YP, Liu FR. Squamous cell carcinoma associated with endometriosis in the uterus and ovaries: A case report. World J Clin cases. 2023;11(26):6240–5. https://doi.org/10.12998/wjcc.v11.i26.6240. Lou Z, Mei L, Wan Z, Zhang W, Gao J. A report of twenty cases of ovarian Brenner tumor and literature review: a case series study. BMC Womens Health. 2024;24(1):471. https://doi.org/10.1186/s12905-024-03316-4. Zhang T, Yang J, Li S, Shi X, Yang J. Ovarian squamous cell carcinoma: clinicopathological features, prognosis and immunotherapy outcomes. J gynecologic Oncol. 2025;36(4):e54. https://doi.org/10.3802/jgo.2025.36.e54. Nie X, Xu T, Cheng W. Comparative prognosis analysis of ovarian squamous cell carcinoma versus serous carcinoma: Insights from the SEER database. Int J Gynaecol Obstet. 2025;168(2):559–71. https://doi.org/10.1002/ijgo.15899. Zhang C, Ma T. Poorer prognosis of ovarian squamous cell carcinoma than serous carcinoma: a propensity score matching analysis based on the SEER database. J ovarian Res. 2020;13(1):75. https://doi.org/10.1186/s13048-020-00675-y. Terada T. Adenosquamous carcinoma of the ovary arising from endometriosis: two case reports. Cases J. 2009;2:6661. https://doi.org/10.1186/1757-1626-0002-0000006661. Shoji T, Takatori E, Murakami K, Kaido Y, Takeuchi S, Kikuchi A, Sugiyama T. A case of ovarian adenosquamous carcinoma arising from endometrioid adenocarcinoma: a case report and systematic review. J ovarian Res. 2016;9(1):48. https://doi.org/10.1186/s13048-016-0255-6. Li A, Sun S, Song T, Li X, Cheng W, Yao R, Zhang D, Cai Z, Zhang J, Zhai D, et al. Targeted therapy and immunotherapy for platinum-refractory advanced ovarian adenosquamous carcinoma: a case report. OncoTargets therapy. 2018;11:3705–11. https://doi.org/10.2147/ott.S162985. Mills A, Saleh M, Erdem Kombak F, Flint M, Kolev V. Mixed squamous and clear cell ovarian adenocarcinoma arising from endometriosis in a 71 year old patient. Gynecologic Oncol Rep. 2023;48:101225. https://doi.org/10.1016/j.gore.2023.101225. Iwaoki Y, Katsube Y, Toyota N. Adenosquamous carcinoma arising in a mature cystic teratoma of the ovary: a case report and review of the literature. Asia-Oceania J Obstet Gynecol. 1994;20(3):237–43. https://doi.org/10.1111/j.1447-0756.1994.tb00463.x. Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. Int J Gynaecol Obstet. 2021;155(1):61–85. https://doi.org/10.1002/ijgo.13878. Armstrong Deborah K, Alvarez Ronald D, Backes Floor J, Bakkum-Gamez Jamie N, Lisa B, Kian B, Andrew B et al. Chen Lee-may, Chitiyo Viola C., Cristea Mihaela : NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022: Featured Updates to the NCCN Guidelines %J Journal of the National Comprehensive Cancer Network. 2022, 20(9):972–980;https://doi.org/10.6004/jnccn.2022.0047 Lee J, Yun. A rare case of primary adenosquamous carcinoma arising from ovary. 2010. Sun Y, Chen Y, Zhang X, Chen H, Zhou F. Primary ovarian serous carcinomas with extensive squamous differentiation: a case report and literature review. BMC Womens Health. 2021;21(1):193. https://doi.org/10.1186/s12905-021-01336-y. Kurman RJ, Shih Ie M. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34(3):433–43. https://doi.org/10.1097/PAS.0b013e3181cf3d79. Mardi K, Goyal K, Jagota A. Incidental Primary Ovarian Squamous Cell Carcinoma Arising in Endometriosis Presenting As Adenomyosis-Related Abnormal Uterine Bleeding. Cureus. 2025;17(8):e90715. https://doi.org/10.7759/cureus.90715. Lisio MA, Fu L, Goyeneche A, Gao ZH, Telleria C. High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints. Int J Mol Sci. 2019;20(4). https://doi.org/10.3390/ijms20040952. Novikov FV, Anufriev AG, Efremov GD. High-grade Serous Carcinoma Occurring in a Serous Cystadenoma on the Background of a Serous Tubal Intraepithelial Carcinoma (STIC)-like Lesion: A Case Report With Literature Review. Int J Gynecol pathology: official J Int Soc Gynecol Pathologists. 2024;43(6):626–30. https://doi.org/10.1097/pgp.0000000000001018. Caruso G, Weroha SJ, Cliby W. Ovarian Cancer: A Review. JAMA. 2025;334(14):1278–91. https://doi.org/10.1001/jama.2025.9495. Chui MH, Song Q, Zhu J, Jiao Y, Wang B, Wang Y, Wang TL, Vang R, Shih IM. Early Genetic Divergence of High-Grade Carcinomas Originating from Low-Grade Serous Ovarian Neoplasms. Mod pathology: official J United States Can Acad Pathol Inc. 2025;38(1):100629. https://doi.org/10.1016/j.modpat.2024.100629. Tang L, Bian C. Research progress in endometriosis-associated ovarian cancer. Front Oncol. 2024;14:1381244. https://doi.org/10.3389/fonc.2024.1381244. Pejovic T, Cathcart AM, Alwaqfi R, Brooks MN, Kelsall R, Nezhat FR. Genetic Links between Endometriosis and Endometriosis-Associated Ovarian Cancer-A Narrative Review (Endometriosis-Associated Cancer). Life (Basel Switzerland). 2024;14(6). https://doi.org/10.3390/life14060704. McHale MT. New Insights in Endometriosis Subtypes and Ovarian Cancer Risk. JAMA. 2024;332(6):460–1. https://doi.org/10.1001/jama.2024.12357. Rodríguez González E, Gracia M, Yébenes L, Gutiérrez AH. Ovarian squamous cell carcinoma associated with endometriosis. Int J Gynecol cancer: official J Int Gynecol Cancer Soc. 2025;35(2):100055. https://doi.org/10.1016/j.ijgc.2024.100055. Barnard ME, Farland LV, Wang YB, Trabert J, Doherty B, Meeks JA, Madsen HD, Guinto M, Collin E. Endometriosis Typology and Ovarian Cancer Risk. JAMA. 2024;332(6):482–9. https://doi.org/10.1001/jama.2024.9210. Adilbayeva A, Kunz J. Pathogenesis of Endometriosis and Endometriosis-Associated Cancers. Int J Mol Sci. 2024;25(14). https://doi.org/10.3390/ijms25147624. Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, et al. ESHRE guideline: endometriosis. Hum Reprod open. 2022;2022(2):hoac009. https://doi.org/10.1093/hropen/hoac009. Kvaskoff M, Mahamat-Saleh Y, Farland LV, Shigesi N, Terry KL, Harris HR, Roman H, Becker CM, As-Sanie S, Zondervan KT, et al. Endometriosis and cancer: a systematic review and meta-analysis. Hum Reprod Update. 2021;27(2):393–420. https://doi.org/10.1093/humupd/dmaa045. Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ (Clinical Res ed). 2022;379:e070750. https://doi.org/10.1136/bmj-2022-070750. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15. https://doi.org/10.1038/nature10166. Mandilaras V, Garg S, Cabanero M, Tan Q, Pastrello C, Burnier J, Karakasis K, Wang L, Dhani NC, Butler MO, et al. TP53 mutations in high grade serous ovarian cancer and impact on clinical outcomes: a comparison of next generation sequencing and bioinformatics analyses. Int J Gynecol cancer: official J Int Gynecol Cancer Soc. 2019;29(2):346–52. https://doi.org/10.1136/ijgc-2018-000087. Chao A, Lai CH, Chao AS, Lin CY, Wang YC, Huang HJ, Wu RC. Molecular characterization of ovarian squamous cell carcinoma originating from mature teratoma. J Mol Med. 2025;103(1):101–11. https://doi.org/10.1007/s00109-024-02505-w. McGranahan N, Swanton C. Clonal Heterogeneity and Tumor Evolution: Past, Present, and the Future. Cell. 2017;168(4):613–28. https://doi.org/10.1016/j.cell.2017.01.018. Funding This study was supported by grants from the National Clinical Key Specialty Construction Project and the Guangxi Clinical Key Specialty Construction Project. The funding sources had no involvement in the study design, data analysis, interpretation of results, or manuscript writing. Author information Authors and Affiliations Contributions C. Li and J. Lu contributed to the study conceptualization, formal analysis, visualization, and drafting of the original manuscript. C. Li, J. Lu, Q. Lan, L. Li, and S. Lu participated in data curation and validation. C. Li, J. Lu, Z. Chen, Q. He, and P. Hou were responsible for investigation, as well as resource acquisition and software utilization. W. Dai and Y. Tan played major roles in funding acquisition, project administration, methodology development, and overall supervision of the study. Y. Tan were also instrumental in the editing of the manuscript. All authors contributed to manuscript review and approved the final version of the manuscript. Corresponding authors Ethics declarations Ethics approval and consent to participate Ethical approval for this study was obtained from the Medical Ethics Committee of the LiuZhou TanZhong People’s Hospital. The approval notice, with reference number LW20251201. The need for informed consent was waived by the Medical Ethics Committee of the LiuZhou TanZhong People’s Hospital, because of the retrospective nature of the study. Consent for publication Written informed consent was obtained from the patient for the publication of their personal and clinical details, including any potentially identifying images, in this study. Competing interests The authors declare no competing interests. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 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To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. About this article Cite this article Li, Cl., Lu, Jp., Lan, Qx. et al. Dual TP53 mutations in ovarian high-grade serous carcinoma combined with squamous cell carcinoma: a case report and systematic literature review. J Ovarian Res (2026). https://doi.org/10.1186/s13048-026-02088-9 Received: Accepted: Published: DOI: https://doi.org/10.1186/s13048-026-02088-9