Liver metastasis of ovarian granulosa cell tumors: A case report and literature review

Liver metastasis of ovarian granulosa cell tumors: A case report and literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Liver metastasis of ovarian granulosa cell tumors: A case report and literature review Longjun Zhao, Tingting Jiao, Lili zheng, Xiaoping Ma, Aihua Li, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7033602/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Jan, 2026 Read the published version in BMC Women's Health → Version 1 posted 11 You are reading this latest preprint version Abstract Background：Granulosa cell tumors (GCT) are a distinct type of sex cord-stromal tumor with low-grade malignancy. It frequently recurs due to pelvic dissemination or direct spread, whereas liver metastasis rarely occurs. Here, we report a rare case of a GCT in which recurrence with liver metastasis occurred 14 years later. We also discuss the imaging findings, histological features, and therapeutic approaches, and conducted a review of similar reported cases. Case presentation： A 61-year-old female presented with a 14-year history of ovarian tumor resection for GCT. She was admitted to our hospital due to complaints of epigastric distension and acid regurgitation. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a hepatic mass measuring approximately 8 cm in diameter. Following surgical resection, histopathological examination of the sample revealed tumor cells with "coffee-bean-like" nuclei, a characteristic feature of GCT. Additionally, eosinophilicunstructured Call-Exner bodies were observed. Immunohistochemical analysis confirmed positive immunoreactivity for the inhibin α, CD99 and CD56 markers. On the basis of these findings, the tumor was diagnosed as a hepatic metastasis of an ovarian GCT. The patient remained recurrence-free for 7 years following hepatic resection. Conclusions：Herein, we report a rare case of hepatic metastasis derived from a GCT that was diagnosed 14 years after initial oophorectomy. This case highlights the potential for late recurrence of ovarian GCT, even in the decades following primary treatment. Close long-term follow-up is essential to detect recurrence early and optimize patient outcomes. Sex cord stromal tumors Granulosa cell tumor Liver metastasis Late recurrence Figures Figure 1 Figure 2 Introduction Ovarian granulosa cell tumors (GCTs) originate from ovarian granulosa cells and represent 70% of ovarian sex cord-stromal tumors and 2%~5% of ovarian malignancies[ 1 ]. Owing to its unique hormone-producing activity, GCT often presents with endocrine-related symptoms that facilitate early detection. Reproductive-aged patients typically present with menstrual irregularities, such as menorrhagia, intermenstrual bleeding, and secondary amenorrhea, whereas postmenopausal patients commonly present with abnormal vaginal bleeding. GCT typically follows an indolent natural course. Currently, surgical resection serves as the cornerstone of GCT management, generally resulting in favorable short-term prognoses. Early-stage patients have a 5-year survival rate exceeding 90%. However, GCT has a remarkable tendency to recur, firmly establishing itself as a prototypical long-term recurrent malignancy within the domain of gynecological oncology. The recurrence rate of ovarian GCT ranges from 25–30%. Most recurrent cases present as local pelvic and abdominal dissemination[ 2 ]. Hepatic metastases from GCTs are infrequent, accounting for approximately 5–6% of all recurrent events [ 3 ]. Herein, we report a unique case of an ovarian GCT. Fourteen years after the initial oophorectomy, the patient experienced recurrence in the form of liver metastasis. The patient was successfully treated with partial hepatectomy. Case Presentation A 61-year-old female patient was admitted to the Hepatobiliary Surgery Department of Liaocheng People’s Hospital on April 4, 2018, with the chief complaint of " upper abdomen distension and regurgitation for over one year". She experienced acid regurgitation and belching on an empty stomach, without associated symptoms such as nausea, vomiting, diarrhea or melena. During an outpatient visit, abdominal computed tomography (CT) at our hospital revealed low-density lesions in the left lobe of the liver, which led to her hospitalization with the diagnosis of "liver space- occupying lesion". The patient had a 15-year history of hypertension and was on oral telmisartan for treatment. Nine years ago, she underwent resection of a left renal cyst. Fourteen years prior, owing to "torsion of the ovarian granulosa cell tumor pedicle", she had undergone hysterectomy and bilateral salpingo-oophorectomy. On physical examination, the abdomen was flat and soft, without tenderness or rebound tenderness. The liver and spleen were not palpable below the costal margins, and there was no hepatic percussion pain. Tumor markers, such as alpha-fetoprotein (AFP), carbohydrate antigen 19 − 9 (CA19-9), cancer antigen 125 (CA 125), and carcinoembryonic antigen (CEA), were all within the normal reference range. Abdominal contrast-enhanced dynamic CT findings: In the posterior lower segment of the right lobe of the liver, there is a cystic-solid-mixed-density focus measuring 8.1 × 5.9 cm. The CT values of the solid part in the the arterial, portal venous, and delayed phases are approximately 55 HU, 83 HU, and 70 HU, respectively. The boundary of the lesion is distinct, and it protrudes toward the surface of the liver and into the abdominal cavity (Fig. 1 a, 1 b). Enhanced magnetic resonance imaging (MRI) revealed an irregular space-occupying lesion in the S5 segment of the liver. The lesion exhibited long T1 and isointense T2 abnormal signals (Fig. 2 a, 2 b). The signal intensity within the lesion was heterogeneous, and its boundary was distinct. On diffusion-weighted imaging (DWI), the lesion showed a heterogeneous high signal. During the enhanced scan, nodular enhancement was observed at the periphery of the lesion in the arterial phase. In the portal venous phase, the enhanced area of the lesion expanded. However, in the delayed phase, the lesion still presented heterogeneous enhancement. The size of the lesion was approximately 8.6 × 6.3 × 9.8 cm. Multiple round lesions with long T2 signals of varying sizes were detected in the liver. No obvious enhancement was found in these lesions during the enhanced scan. The largest one had a diameter of approximately 0.8 cm. Moreover, there was no evidence of obvious dilation of the intrahepatic bile ducts. During the liver tumor resection performed under general anesthesia in April 2018, the tumor was found to be located in the fifth and sixth segments of the liver, measuring approximately 8 × 7 × 7 cm. It protruded into the abdominal cavity and adhered to the hepatic flexure of the colon, duodenal bulb, and anterior surface of the right kidney. Upon dissection of the adhesions, the tumor was noted to have a complete capsule, without invasion of the surrounding tissues. The mass was adjacent to the gallbladder, and multiple liver cysts were also observed. Gross examination of the tumor revealed a texture resembling that of putrid fish, with areas containing old, dark red blood. The tumor was cystic and solid, and the solid portion consisted of grayish-yellow to grayish-red, fleshy, necrotic tissue (Fig. 2 a). The cut surface was fine, and the cyst wall was 0.2 cm thick. The closest margin from the tumor to the resection edge was 0.4 cm. The cut surface of the remaining liver tissue appeared grayish-red, without any obvious abnormalities. Intraoperative frozen-section pathology indicated a malignant liver tumor, with sarcoma being considered a possible diagnosis (Fig. 2 b). Postoperative paraffin pathology analysis revealed a cystic-solid tumor in the liver. This tumor was predominantly composed of short spindle cells, among which round epithelioid cells were sporadically distributed. The cells presented with mild pleomorphism, exhibiting occasional nuclear fissures. Additionally, some cells had nuclear grooves and a pseudochrysanthemum-like structure (Fig. 2 c, 2 d). On the basis of these observations, metastasis from an adult ovarian granulosa cell tumor was suspected. Notably, there was no typical intravascular tumor thrombus or nerve invasion. The liver capsule remained intact, and the surgical resection margin was free of tumor cells. The immunohistochemical results were as follows: CD99 (+), CEA (-), hepatocyte (-), glypican-3 (-), CK19 (-), CK7 (-), CK (AE1/AE3) (-), vimentin (+), EMA (-), Ki-67 (1% +), β- catenin (partial+), CD56 (spindle cell partial+), inhibin-α (a small number of epithelioid cells +), calletinin (CR) (a small number of epithelioid cells +), and Syn (-). Considering the immunohistochemical findings, the morphological characteristics observed via HE staining, and the patient’s medical history, the diagnosis was consistent with metastasis of the ovarian granulosa cell tumor. Table 1 Literature review: clinical characteristics of patients with liver metastasis from GCTs Authors Year of publication No of cases Age at presentation for liver metastasis (years) Symptoms at presentation Time from primarydiagnosis to hepatectomy(years) Time from liver metastasis to hepatectomy(years) Other organs metastasis [ 4 ]Rodriguez Garcia et al. 1996 1 62 Abdominal mass 6 5 No [ 5 ]Ali, SZ. 1998 1 65 Right upper quadrant and weight loss 18 6 yes [ 6 ]Crew et al. 2005 1 58 dyspnea 12 10 yes [ 7 ]Lordan et al. 2007 1 64 Recurrent chest infection, abdominal pain 15 6 yes [ 8 ]Madhuri et al. 2010 3 N/A Dyspnea abdominal pain(2 patients) 17/9/6 2.7/1/0 Yes [ 9 ]Chua et al. 2011 2 46/31 N/A 12/6 0/14.3 Yes [ 10 ]Andreou et al. 2012 5 N/A N/A N/A N/A N/A [ 4 ]Fujita et al. 2015 1 43 Abdominal distention and ascites 25 0 Yes [ 11 ]Yu et al. 2015 1 62 Abdominal pain 27 0 Yes [ 12 ]Antony et al. 2017 1 35 Abdominal pain and ascites 5 4 Yes [ 13 ]Koganezawa et al 2020 1 76 Incidental 22 8 No [ 14 ]Ammar Aleter et al. 2021 1 56 Abdominal pain 9 0 Yes [ 15 ]Yang He et al 2021 1 51 Incidental 13 3 Present case 2022 1 61 Abdominal distention and regurgitation 14 4.5 No Discussion Among sex cord stromal tumors, ovarian granulosa cell tumors are relatively rare low-grade malignant neoplasms and represent the most prevalent type. On the basis of ovarian cancer survey data from 2018, from 2010–2014, the global incidence rate of sex cord stromal tumors was approximately 3/100000, with an annual growth rate of 2.3% [ 16 ]. A body mass index exceeding 30 kg/m 2 , along with a family history of breast cancer or ovarian cancer, are commonly identified as contributing factors. Granulosa cell tumors can be classified into adult and juvenile types, which exhibit distinct differences in their molecular pathological characteristics and prognoses. Adult granulosa cell tumors constitute approximately 95% of all granulosa cell tumors and predominantly affect women aged 50–55 years, whereas juvenile granulosa cell tumors are borderline tumors that occur almost exclusively in adolescents and young women under the age of 30. Granular cells possess hormonal activity and are able to synthesize estradiol along with transforming growth factors, notably inhibin and anti-Mullerian hormone (AMH). Multiple studies have firmly demonstrated that in female patients with GCT, the levels of AMH and inhibin increase[ 17 ]. Moreover, there was a positive correlation between the levels of these two factors and the diameter of the tumor. The serum levels of AMH and inhibin have high sensitivity (92% vs 93%, respectively) and specificity (81% vs 83% respectively). As a result, the detection of these two markers plays a crucial role in differentiating granulosa cell tumors from epithelial ovarian tumors and predicting the recurrence of these tumors in clinical practice. Recent research revealed that a missense point mutation in the FOXL2 gene ( FOXL2 C134W ) serves as a potential initiator in the pathogenesis of GCT[ 18 ]. This mutation has been detected in 97% of granulosa cell tumor patients. The co-occurrence of FOXL2 C134W and SMAD4 can contribute to carcinogenesis. A TERT-124C > T promoter mutation, which is associated with high tumor invasiveness and a poor overall survival (OS) outcome, was identified in 42% of patients with GCTs[ 19 , 20 ]. These molecular markers may help predict GCT development and guide therapeutic strategies. Here, we present a case of a GCT with liver metastasis that was detected 14 years after an ovariectomy. The patient underwent successful resection of the liver tumor. Since no tumor biopsy was performed before the operation, an exact diagnosis could not be established at that time. The postoperative pathological findings indicated the presence of a GCT. Hematoxylin and eosin-stained specimens revealed that the tumor cells had "coffee bean-like" nuclear grooves, which are characteristic features of GCTs. Notably, the occurrence of a GCT originating from the liver has not been previously reported. On the basis of our case and relevant observations, we concluded that a GCT in the liver is a metastatic lesion resulting from the resection of an ovarian tumor. It is widely acknowledged that the late recurrence rate of GCTs is 25–30%. Liver metastases from GCTs are relatively uncommon, accounting for 5–6% of all GCT recurrences. Since Garcia et al. first described GCT liver metastasis in 1996, only 21 cases(including our case)of GCT treated with hepatectomy have been reported [ 4 , 15 ]. The interval from initial GCT diagnosis to hepatectomy is typically prolonged, as observed in our case. It is well known that GCTs are prone to late recurrence[ 12 ]. In our patient, liver metastasis occurred fourteen years after ovariectomy. Koganezawa I et al. reported the longest recurrence-free survival for GCTs, with a 30-year interval from primary tumor onset to pelvic recurrence[ 13 ]. Yu et al. reported a 27-year recurrence-free interval until liver metastasis developed [ 11 ]. Table 1 summarizes the epidemiological and clinical characteristics of ovarian GCTs with liver metastasis treated by hepatectomy. Notably, most liver metastases are diagnosed several years after the primary tumor, which is consistent with our patient’s course[ 14 ]. This finding aligns with current literature recommendations. Given that ovarian GCT is typically a low-grade malignancy, long-term follow-up is essential for most patients, who should be counseled on the disease’s indolent natural history. Currently, there are no established standardized recommendations or clinical practice guidelines specifically for managing recurrent GCTs. Clinically, however, various therapeutic approaches, including surgical resection, chemotherapy and radiotherapy, are employed to treat recurrent GCTs[ 21 – 23 ]. Previous reports have shown that surgical resection to eliminate residual lesions can improve the postoperative quality of life of patients and facilitate recurrence-free survival [ 12 ]. In our patient, liver metastasis was identified as the sole site of GCT recurrence, with no evidence of additional metastatic foci. Consequently, we performed liver tumor resection. Surgical resection is believed to achieve a disease-free state, offering the potential for long-term survival. Surgery remains the cornerstone of treatment for GCTs, with surgical staging performed in accordance with the FIGO ovarian cancer staging system. Staged surgery is a critical determinant of prognosis and guides postoperative management strategies. For women who have completed childbearing, total hysterectomy combined with pelvic and retroperitoneal lymphadenectomy is recommended. In contrast, younger patients may opt for fertility-sparing staged surgery to preserve reproductive function. For those with advanced or recurrent granular cell tumors, tumor cytoreductive surgery represents the most effective therapeutic approach. Postoperative adjuvant chemotherapy for GCT remains controversial. The MITO-9 study demonstrated that adjuvant chemotherapy fails to reduce recurrence rates in phase IC of granulosa cell tumors and does not alter outcomes for patients with recurrence. Current recommendations advocate for repeat surgery when feasible, with chemotherapy avoided in the absence of residual tumor[ 24 ]. In our case, the patient underwent liver tumor resection for isolated hepatic metastasis, the sole site of GCT recurrence. No additional adjuvant therapy was administered following this recurrence treatment. With a follow-up period exceeding 7 years after hepatectomy, no evidence of recurrent liver metastasis was observed. Declarations Ethics approval and consent to participate: This study was approved by the Ethics Committee of Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University, according to the 1975 Declaration of Helsinki and its later ethical standards. Consent for publication: Written informed consent was obtained from the participants included in this study. Availability of data and materials: Not applicable. Competing interests: The authors declare that they have no conflicts of interest, financial or otherwise. Funding: This study was supported by the Natural Science Foundation of Shandong Province (ZR2016CB12). Author contributions: LJZ, TTJ, LLZ, XZ and YZ contributed to the con­ception and data collection. LJZ, TTJ, XPM, AHL and YZ drafted the manuscript and critically revised it. Acknowledgements: We would like to express our gratitude to Jinqiang Yan for the work on H&E examination. References Colombo N, Parma G, Zanagnolo V, Insinga A. Management of ovarian stromal cell tumors. J Clin Oncol. 2007;25(20):2944–51. Hasiakos D, Papakonstantinou K, Karvouni E, Fotiou S. Recurrence of granulosa cell tumor 25 years after initial diagnosis. Report of a case and review of the literature. Eur J Gynaecol Oncol. 2008;29(1):86–8. Fujita F, Eguchi S, Takatsuki M, Kobayashi K, Kanetaka K, Ito M, et al. A recurrent granulosa cell tumor of the ovary 25 years after the initial diagnosis: A case report. Int J Surg Case Rep. 2015;12:7–10. Rodriguez Garcia JI, Gonzalez Gonzalez JJ, Garcia Florez LJ, Floriano Rodriguez P, Martinez Rodriguez E. Hepatic metastases of granulosa cells tumour of the ovary. HPB Surg. 1996;10(1):55–7. Ali SZ. Metastatic granulosa-cell tumor in the liver: cytopathologic findings and staining with inhibin. Diagn Cytopathol. 1998;19(4):293–7. Crew KD, Cohen MH, Smith DH, Tiersten AD, Feirt NM, Hershman DL. Long natural history of recurrent granulosa cell tumor of the ovary 23 years after initial diagnosis: a case report and review of the literature. Gynecol Oncol. 2005;96(1):235–40. Lordan JT, Jones RL, Karanjia ND, Butler-Manuel S. Debulking hepatectomy for an unusual case of a grade 1 stage 1 granulosa cell tumour of the ovary with late metastases. Oncology. 2007;72(1–2):143–4. Madhuri TK, Butler-Manuel S, Karanjia N, Tailor A. Liver resection for metastases arising from recurrent granulosa cell tumour of the ovary–a case series. Eur J Gynaecol Oncol. 2010;31(3):342–4. Chua TC, Iyer NG, Soo KC. Prolonged survival following maximal cytoreductive effort for peritoneal metastases from recurrent granulosa cell tumor of the ovary. J Gynecol Oncol. 2011;22(3):214–7. Andreou A, Brouquet A, Bharathy KG, Perrier ND, Abdalla EK, Curley SA, et al. Liver resection for liver metastases from nondigestive endocrine cancer: extrahepatic disease burden defines outcome. Surgery. 2012;151(6):851–9. Yu S, Zhou X, Hou B, Tang B, Hu J, He S. Metastasis of the liver with a granulosa cell tumor of the ovary: A case report. Oncol Lett. 2015;9(2):816–8. Antony MA, Pavithran K, Vijaykumar DK, Sudheer OV. Long-term survival following repeat liver resections in metastatic ovarian granulosa cell tumor: Case report with review of the literature. South Asian J Cancer. 2017;6(2):87–8. Koganezawa I, Tomita K, Nakagawa M, Ozawa Y, Kobayashi T, Sano T, et al. Right trisectionectomy for liver metastasis of granulosa cell tumor: a case report and literature review. Surg Case Rep. 2020;6(1):125. Aleter A, Mahajan PS, Petkar MA, Abdulmajeed HA, Khalaf H, Elmoghazy W, et al. Late Cystic Metastasis of an Ovarian Granulosa Cell Tumor to the Liver. Cureus. 2021;13(9):e18051. He Y, Yang Y, Wang T, Wang W. Hepatic metastasis of the ovarian granulosa cell tumor after 11 years of surgical resection and systemic chemotherapy of primary tumors: A case report. Asian J Surg. 2021;44(4):687–8. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68(4):284–96. Farkkila A, Koskela S, Bryk S, Alfthan H, Butzow R, Leminen A, et al. The clinical utility of serum anti-Mullerian hormone in the follow-up of ovarian adult-type granulosa cell tumors–A comparative study with inhibin B. Int J Cancer. 2015;137(7):1661–71. Weis-Banke SE, Lerdrup M, Kleine-Kohlbrecher D, Mohammad F, Sidoli S, Jensen ON, et al. Mutant FOXL2(C134W) Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors. Cancer Res. 2020;80(17):3466–79. Alexiadis M, Rowley SM, Chu S, Leung DTH, Stewart CJR, Amarasinghe KC, et al. Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing. Mol Cancer Res. 2019;17(1):177–85. Karstensen S, Kaiser K, Poulsen TS, Jochumsen K, Hogdall C, Marcussen N, et al. Ovarian Adult Granulosa Cell Tumors: A Scoping Review of DNA Alterations and Their Known Significance. Anticancer Res. 2025;45(1):1–10. Brown J, Brady WE, Schink J, Van Le L, Leitao M, Yamada SD, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer. 2014;120(3):344–51. Wagenaar HC, Pecorelli S, Vergote I, Curran D, Wagener DJ, Kobierska A, et al. Phase II study of a combination of cyclophosphamide, adriamycin and cisplatin in advanced fallopian tube carcinoma. An EORTC gynecological cancer group study. European Organization for Research and Treatment of Cancer. Eur J Gynaecol Oncol. 2001;22(3):187–93. Dubuc-Lissoir J, Berthiaume MJ, Boubez G, Van Nguyen T, Allaire G. Bone metastasis from a granulosa cell tumor of the ovary. Gynecol Oncol. 2001;83(2):400–4. Bergamini A, Ferrandina G, Candotti G, Taccagni G, Scarfone G, Bocciolone L, et al. Stage I juvenile granulosa cell tumors of the ovary: A multicentre analysis from the MITO-9 study. Eur J Surg Oncol. 2021;47(7):1705–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 12 Jan, 2026 Read the published version in BMC Women's Health → Version 1 posted Editorial decision: Revision requested 15 Sep, 2025 Reviews received at journal 11 Sep, 2025 Reviewers agreed at journal 28 Aug, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviews received at journal 21 Aug, 2025 Reviewers agreed at journal 02 Aug, 2025 Reviewers invited by journal 02 Aug, 2025 Editor assigned by journal 29 Jul, 2025 Editor invited by journal 07 Jul, 2025 Submission checks completed at journal 07 Jul, 2025 First submitted to journal 07 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7033602","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":494754011,"identity":"70fef27a-47ac-4907-91ad-9fcbe9bf66ac","order_by":0,"name":"Longjun Zhao","email":"","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Longjun","middleName":"","lastName":"Zhao","suffix":""},{"id":494754013,"identity":"23ef7ac7-401f-419b-896c-d30bc7e6e279","order_by":1,"name":"Tingting Jiao","email":"","orcid":"","institution":"Chinese PLA General Hospital, the Seventh Medical Center of PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tingting","middleName":"","lastName":"Jiao","suffix":""},{"id":494754015,"identity":"c9dad501-1056-4b05-ae2a-de3f5a255092","order_by":2,"name":"Lili zheng","email":"","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"zheng","suffix":""},{"id":494754017,"identity":"fdb44ddc-268b-4ffe-9ba1-69b5708996a5","order_by":3,"name":"Xiaoping Ma","email":"","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoping","middleName":"","lastName":"Ma","suffix":""},{"id":494754018,"identity":"d1053b12-12b0-4af2-b13b-d8f4e4593042","order_by":4,"name":"Aihua Li","email":"","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Aihua","middleName":"","lastName":"Li","suffix":""},{"id":494754019,"identity":"8a1dcbd1-3ac2-4463-a1ea-d08fc1b7eb1e","order_by":5,"name":"Xian Zhang","email":"","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xian","middleName":"","lastName":"Zhang","suffix":""},{"id":494754020,"identity":"66da97e3-ad63-4768-9e39-3f65cde24d05","order_by":6,"name":"Yan Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYDACCSjNL3+w8UHiPxsefvYGIrVIzmA+bPCBLU1GsucAkVoMbrClSc5gO2xjcMMBvw752c3PHn5ts8uTnN1jJs3Dc56H4QYD44ePObi1MM45Zm4s25ZczC9zxtiaR+I2D+PsBmbJmdtwa2GWSDCTlmxjTpzZkGN4m8fgNg+zzAE2Zl48Wtgk0r8BtdQnbjiQYyDNk3COh00iAb8WHokcM8mPbYcTN9xIS5KcceAADw8hLRISOWXSDOeOJ87sOXzY4GNDMo8Ez8FmvH6Rn5G+TfJHWXViP3sjMCob7Oztjzcf/PARjxZwEPCyofAZG/CrByn58YegmlEwCkbBKBjJAADVoVNXjb7/hAAAAABJRU5ErkJggg==","orcid":"","institution":"Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-07-03 03:08:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7033602/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7033602/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12905-026-04260-1","type":"published","date":"2026-01-12T16:31:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88755220,"identity":"4bfc330c-2334-46f3-ac2e-db004f0f2e1c","added_by":"auto","created_at":"2025-08-11 07:10:28","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":228023,"visible":true,"origin":"","legend":"\u003cp\u003eComputed tomography images and magnetic resonance imaging illustrated the irregular space-occupying lesion in liver. \u003cstrong\u003ea, b\u003c/strong\u003e Contrast-enhanced dynamic computed tomography image of a tumor 8 cm in diameter in the S5 segment of the liver. \u003cstrong\u003ec, d\u003c/strong\u003eEnhanced magnetic resonance imaging revealed an irregular occupation in the liver.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7033602/v1/5f8b850f83f66741dfa0132f.jpeg"},{"id":88755218,"identity":"2b17965d-b837-4c59-9714-4ca1452adbd2","added_by":"auto","created_at":"2025-08-11 07:10:28","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":353782,"visible":true,"origin":"","legend":"\u003cp\u003eThe surgical specimen exhibited a cystic-solid tumor. \u003cstrong\u003ea\u003c/strong\u003e In the surgical specimen, the solid component presented as grayish-yellow to grayish-red, necrotic, fleshy-like tissue. \u003cstrong\u003eb\u003c/strong\u003e Intraoperative frozen pathological section during the operation (×400). \u003cstrong\u003ec, d\u003c/strong\u003e H\u0026amp;E images revealed distinct features. A pseudochrysanthemum-like structure (Call-Exner body) and a “coffee bean-like” nuclear groove were observable for \u003cstrong\u003ec\u003c/strong\u003e (×100), and \u003cstrong\u003ed\u003c/strong\u003e (×400).\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7033602/v1/c3aed1b88e2af315fef2171d.jpeg"},{"id":100614655,"identity":"f6a064f8-f65d-48de-a634-6111c8f9663f","added_by":"auto","created_at":"2026-01-19 17:22:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1126135,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7033602/v1/2e7acb95-53f7-4e78-a300-83ed44f24ec8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Liver metastasis of ovarian granulosa cell tumors: A case report and literature review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOvarian granulosa cell tumors (GCTs) originate from ovarian granulosa cells and represent 70% of ovarian sex cord-stromal tumors and 2%~5% of ovarian malignancies[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Owing to its unique hormone-producing activity, GCT often presents with endocrine-related symptoms that facilitate early detection. Reproductive-aged patients typically present with menstrual irregularities, such as menorrhagia, intermenstrual bleeding, and secondary amenorrhea, whereas postmenopausal patients commonly present with abnormal vaginal bleeding. GCT typically follows an indolent natural course. Currently, surgical resection serves as the cornerstone of GCT management, generally resulting in favorable short-term prognoses. Early-stage patients have a 5-year survival rate exceeding 90%. However, GCT has a remarkable tendency to recur, firmly establishing itself as a prototypical long-term recurrent malignancy within the domain of gynecological oncology. The recurrence rate of ovarian GCT ranges from 25\u0026ndash;30%. Most recurrent cases present as local pelvic and abdominal dissemination[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Hepatic metastases from GCTs are infrequent, accounting for approximately 5\u0026ndash;6% of all recurrent events [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Herein, we report a unique case of an ovarian GCT. Fourteen years after the initial oophorectomy, the patient experienced recurrence in the form of liver metastasis. The patient was successfully treated with partial hepatectomy.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 61-year-old female patient was admitted to the Hepatobiliary Surgery Department of Liaocheng People\u0026rsquo;s Hospital on April 4, 2018, with the chief complaint of \" upper abdomen distension and regurgitation for over one year\". She experienced acid regurgitation and belching on an empty stomach, without associated symptoms such as nausea, vomiting, diarrhea or melena. During an outpatient visit, abdominal computed tomography (CT) at our hospital revealed low-density lesions in the left lobe of the liver, which led to her hospitalization with the diagnosis of \"liver space- occupying lesion\". The patient had a 15-year history of hypertension and was on oral telmisartan for treatment. Nine years ago, she underwent resection of a left renal cyst. Fourteen years prior, owing to \"torsion of the ovarian granulosa cell tumor pedicle\", she had undergone hysterectomy and bilateral salpingo-oophorectomy. On physical examination, the abdomen was flat and soft, without tenderness or rebound tenderness. The liver and spleen were not palpable below the costal margins, and there was no hepatic percussion pain. Tumor markers, such as alpha-fetoprotein (AFP), carbohydrate antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (CA19-9), cancer antigen 125 (CA 125), and carcinoembryonic antigen (CEA), were all within the normal reference range.\u003c/p\u003e\u003cp\u003eAbdominal contrast-enhanced dynamic CT findings: In the posterior lower segment of the right lobe of the liver, there is a cystic-solid-mixed-density focus measuring 8.1 \u0026times; 5.9 cm. The CT values of the solid part in the the arterial, portal venous, and delayed phases are approximately 55 HU, 83 HU, and 70 HU, respectively. The boundary of the lesion is distinct, and it protrudes toward the surface of the liver and into the abdominal cavity (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003eEnhanced magnetic resonance imaging (MRI) revealed an irregular space-occupying lesion in the S5 segment of the liver. The lesion exhibited long T1 and isointense T2 abnormal signals (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb). The signal intensity within the lesion was heterogeneous, and its boundary was distinct. On diffusion-weighted imaging (DWI), the lesion showed a heterogeneous high signal. During the enhanced scan, nodular enhancement was observed at the periphery of the lesion in the arterial phase. In the portal venous phase, the enhanced area of the lesion expanded. However, in the delayed phase, the lesion still presented heterogeneous enhancement. The size of the lesion was approximately 8.6 \u0026times; 6.3 \u0026times; 9.8 cm. Multiple round lesions with long T2 signals of varying sizes were detected in the liver. No obvious enhancement was found in these lesions during the enhanced scan. The largest one had a diameter of approximately 0.8 cm. Moreover, there was no evidence of obvious dilation of the intrahepatic bile ducts.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eDuring the liver tumor resection performed under general anesthesia in April 2018, the tumor was found to be located in the fifth and sixth segments of the liver, measuring approximately 8 \u0026times; 7 \u0026times; 7 cm. It protruded into the abdominal cavity and adhered to the hepatic flexure of the colon, duodenal bulb, and anterior surface of the right kidney. Upon dissection of the adhesions, the tumor was noted to have a complete capsule, without invasion of the surrounding tissues. The mass was adjacent to the gallbladder, and multiple liver cysts were also observed. Gross examination of the tumor revealed a texture resembling that of putrid fish, with areas containing old, dark red blood. The tumor was cystic and solid, and the solid portion consisted of grayish-yellow to grayish-red, fleshy, necrotic tissue (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). The cut surface was fine, and the cyst wall was 0.2 cm thick. The closest margin from the tumor to the resection edge was 0.4 cm. The cut surface of the remaining liver tissue appeared grayish-red, without any obvious abnormalities. Intraoperative frozen-section pathology indicated a malignant liver tumor, with sarcoma being considered a possible diagnosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003ePostoperative paraffin pathology analysis revealed a cystic-solid tumor in the liver. This tumor was predominantly composed of short spindle cells, among which round epithelioid cells were sporadically distributed. The cells presented with mild pleomorphism, exhibiting occasional nuclear fissures. Additionally, some cells had nuclear grooves and a pseudochrysanthemum-like structure (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed). On the basis of these observations, metastasis from an adult ovarian granulosa cell tumor was suspected. Notably, there was no typical intravascular tumor thrombus or nerve invasion. The liver capsule remained intact, and the surgical resection margin was free of tumor cells. The immunohistochemical results were as follows: CD99 (+), CEA (-), hepatocyte (-), glypican-3 (-), CK19 (-), CK7 (-), CK (AE1/AE3) (-), vimentin (+), EMA (-), Ki-67 (1% +), β- catenin (partial+), CD56 (spindle cell partial+), inhibin-α (a small number of epithelioid cells +), calletinin (CR) (a small number of epithelioid cells +), and Syn (-). Considering the immunohistochemical findings, the morphological characteristics observed via HE staining, and the patient\u0026rsquo;s medical history, the diagnosis was consistent with metastasis of the ovarian granulosa cell tumor.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLiterature review: clinical characteristics of patients with liver metastasis from GCTs\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYear of publication\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo of cases\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAge at presentation for liver metastasis (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSymptoms at presentation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTime from primarydiagnosis to hepatectomy(years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eTime from liver metastasis to hepatectomy(years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eOther organs metastasis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]Rodriguez Garcia et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1996\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal mass\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]Ali, SZ.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1998\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRight upper quadrant and weight loss\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eyes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]Crew et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003edyspnea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eyes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]Lordan et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRecurrent chest infection, abdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eyes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]Madhuri et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDyspnea abdominal pain(2 patients)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17/9/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.7/1/0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]Chua et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46/31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12/6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0/14.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]Andreou et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eN/A\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]Fujita et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal distention and ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]Yu et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]Antony et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal pain and ascites\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]Koganezawa et al\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIncidental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]Ammar Aleter et al.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]Yang He et al\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2021\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eIncidental\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent case\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAbdominal distention and regurgitation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAmong sex cord stromal tumors, ovarian granulosa cell tumors are relatively rare low-grade malignant neoplasms and represent the most prevalent type. On the basis of ovarian cancer survey data from 2018, from 2010\u0026ndash;2014, the global incidence rate of sex cord stromal tumors was approximately 3/100000, with an annual growth rate of 2.3% [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A body mass index exceeding 30 kg/m\u003csup\u003e2\u003c/sup\u003e, along with a family history of breast cancer or ovarian cancer, are commonly identified as contributing factors.\u003c/p\u003e\u003cp\u003eGranulosa cell tumors can be classified into adult and juvenile types, which exhibit distinct differences in their molecular pathological characteristics and prognoses. Adult granulosa cell tumors constitute approximately 95% of all granulosa cell tumors and predominantly affect women aged 50\u0026ndash;55 years, whereas juvenile granulosa cell tumors are borderline tumors that occur almost exclusively in adolescents and young women under the age of 30.\u003c/p\u003e\u003cp\u003eGranular cells possess hormonal activity and are able to synthesize estradiol along with transforming growth factors, notably inhibin and anti-Mullerian hormone (AMH). Multiple studies have firmly demonstrated that in female patients with GCT, the levels of AMH and inhibin increase[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Moreover, there was a positive correlation between the levels of these two factors and the diameter of the tumor. The serum levels of AMH and inhibin have high sensitivity (92% vs 93%, respectively) and specificity (81% vs 83% respectively). As a result, the detection of these two markers plays a crucial role in differentiating granulosa cell tumors from epithelial ovarian tumors and predicting the recurrence of these tumors in clinical practice. Recent research revealed that a missense point mutation in the FOXL2 gene (\u003cem\u003eFOXL2\u003c/em\u003e\u003csup\u003e\u003cem\u003eC134W\u003c/em\u003e\u003c/sup\u003e) serves as a potential initiator in the pathogenesis of GCT[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This mutation has been detected in 97% of granulosa cell tumor patients. The co-occurrence of \u003cem\u003eFOXL2\u003c/em\u003e\u003csup\u003e\u003cem\u003eC134W\u003c/em\u003e\u003c/sup\u003e and \u003cem\u003eSMAD4\u003c/em\u003e can contribute to carcinogenesis. A TERT-124C\u0026thinsp;\u0026gt;\u0026thinsp;T promoter mutation, which is associated with high tumor invasiveness and a poor overall survival (OS) outcome, was identified in 42% of patients with GCTs[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These molecular markers may help predict GCT development and guide therapeutic strategies.\u003c/p\u003e\u003cp\u003eHere, we present a case of a GCT with liver metastasis that was detected 14 years after an ovariectomy. The patient underwent successful resection of the liver tumor. Since no tumor biopsy was performed before the operation, an exact diagnosis could not be established at that time. The postoperative pathological findings indicated the presence of a GCT. Hematoxylin and eosin-stained specimens revealed that the tumor cells had \"coffee bean-like\" nuclear grooves, which are characteristic features of GCTs. Notably, the occurrence of a GCT originating from the liver has not been previously reported. On the basis of our case and relevant observations, we concluded that a GCT in the liver is a metastatic lesion resulting from the resection of an ovarian tumor.\u003c/p\u003e\u003cp\u003eIt is widely acknowledged that the late recurrence rate of GCTs is 25\u0026ndash;30%. Liver metastases from GCTs are relatively uncommon, accounting for 5\u0026ndash;6% of all GCT recurrences. Since Garcia et al. first described GCT liver metastasis in 1996, only 21 cases(including our case)of GCT treated with hepatectomy have been reported [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The interval from initial GCT diagnosis to hepatectomy is typically prolonged, as observed in our case. It is well known that GCTs are prone to late recurrence[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our patient, liver metastasis occurred fourteen years after ovariectomy. Koganezawa I et al. reported the longest recurrence-free survival for GCTs, with a 30-year interval from primary tumor onset to pelvic recurrence[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Yu et al. reported a 27-year recurrence-free interval until liver metastasis developed [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the epidemiological and clinical characteristics of ovarian GCTs with liver metastasis treated by hepatectomy. Notably, most liver metastases are diagnosed several years after the primary tumor, which is consistent with our patient\u0026rsquo;s course[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This finding aligns with current literature recommendations. Given that ovarian GCT is typically a low-grade malignancy, long-term follow-up is essential for most patients, who should be counseled on the disease\u0026rsquo;s indolent natural history.\u003c/p\u003e\u003cp\u003eCurrently, there are no established standardized recommendations or clinical practice guidelines specifically for managing recurrent GCTs. Clinically, however, various therapeutic approaches, including surgical resection, chemotherapy and radiotherapy, are employed to treat recurrent GCTs[\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Previous reports have shown that surgical resection to eliminate residual lesions can improve the postoperative quality of life of patients and facilitate recurrence-free survival [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our patient, liver metastasis was identified as the sole site of GCT recurrence, with no evidence of additional metastatic foci. Consequently, we performed liver tumor resection. Surgical resection is believed to achieve a disease-free state, offering the potential for long-term survival.\u003c/p\u003e\u003cp\u003eSurgery remains the cornerstone of treatment for GCTs, with surgical staging performed in accordance with the FIGO ovarian cancer staging system. Staged surgery is a critical determinant of prognosis and guides postoperative management strategies. For women who have completed childbearing, total hysterectomy combined with pelvic and retroperitoneal lymphadenectomy is recommended. In contrast, younger patients may opt for fertility-sparing staged surgery to preserve reproductive function. For those with advanced or recurrent granular cell tumors, tumor cytoreductive surgery represents the most effective therapeutic approach.\u003c/p\u003e\u003cp\u003ePostoperative adjuvant chemotherapy for GCT remains controversial. The MITO-9 study demonstrated that adjuvant chemotherapy fails to reduce recurrence rates in phase IC of granulosa cell tumors and does not alter outcomes for patients with recurrence. Current recommendations advocate for repeat surgery when feasible, with chemotherapy avoided in the absence of residual tumor[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. In our case, the patient underwent liver tumor resection for isolated hepatic metastasis, the sole site of GCT recurrence. No additional adjuvant therapy was administered following this recurrence treatment. With a follow-up period exceeding 7 years after hepatectomy, no evidence of recurrent liver metastasis was observed.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was approved by the Ethics Committee of Liaocheng People’s Hospital and Liaocheng School of Clinical Medicine, Shandong First Medical University, according to the 1975 Declaration of Helsinki and its later ethical standards.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the participants included in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflicts of interest, financial or otherwise.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis study was supported by the Natural Science Foundation of Shandong Province (ZR2016CB12).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u0026nbsp;\u003c/strong\u003eLJZ, TTJ, LLZ, XZ and YZ contributed to the con­ception and data collection. LJZ, TTJ, XPM, AHL and YZ drafted the manuscript and critically revised it. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eWe would like to express our gratitude to Jinqiang Yan for the work on H\u0026amp;E examination.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eColombo N, Parma G, Zanagnolo V, Insinga A. Management of ovarian stromal cell tumors. J Clin Oncol. 2007;25(20):2944\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHasiakos D, Papakonstantinou K, Karvouni E, Fotiou S. Recurrence of granulosa cell tumor 25 years after initial diagnosis. Report of a case and review of the literature. Eur J Gynaecol Oncol. 2008;29(1):86\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFujita F, Eguchi S, Takatsuki M, Kobayashi K, Kanetaka K, Ito M, et al. A recurrent granulosa cell tumor of the ovary 25 years after the initial diagnosis: A case report. Int J Surg Case Rep. 2015;12:7\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRodriguez Garcia JI, Gonzalez Gonzalez JJ, Garcia Florez LJ, Floriano Rodriguez P, Martinez Rodriguez E. Hepatic metastases of granulosa cells tumour of the ovary. HPB Surg. 1996;10(1):55\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAli SZ. Metastatic granulosa-cell tumor in the liver: cytopathologic findings and staining with inhibin. Diagn Cytopathol. 1998;19(4):293\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrew KD, Cohen MH, Smith DH, Tiersten AD, Feirt NM, Hershman DL. Long natural history of recurrent granulosa cell tumor of the ovary 23 years after initial diagnosis: a case report and review of the literature. Gynecol Oncol. 2005;96(1):235\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLordan JT, Jones RL, Karanjia ND, Butler-Manuel S. Debulking hepatectomy for an unusual case of a grade 1 stage 1 granulosa cell tumour of the ovary with late metastases. Oncology. 2007;72(1\u0026ndash;2):143\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMadhuri TK, Butler-Manuel S, Karanjia N, Tailor A. Liver resection for metastases arising from recurrent granulosa cell tumour of the ovary\u0026ndash;a case series. Eur J Gynaecol Oncol. 2010;31(3):342\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChua TC, Iyer NG, Soo KC. Prolonged survival following maximal cytoreductive effort for peritoneal metastases from recurrent granulosa cell tumor of the ovary. J Gynecol Oncol. 2011;22(3):214\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAndreou A, Brouquet A, Bharathy KG, Perrier ND, Abdalla EK, Curley SA, et al. Liver resection for liver metastases from nondigestive endocrine cancer: extrahepatic disease burden defines outcome. Surgery. 2012;151(6):851\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYu S, Zhou X, Hou B, Tang B, Hu J, He S. Metastasis of the liver with a granulosa cell tumor of the ovary: A case report. Oncol Lett. 2015;9(2):816\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAntony MA, Pavithran K, Vijaykumar DK, Sudheer OV. Long-term survival following repeat liver resections in metastatic ovarian granulosa cell tumor: Case report with review of the literature. South Asian J Cancer. 2017;6(2):87\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoganezawa I, Tomita K, Nakagawa M, Ozawa Y, Kobayashi T, Sano T, et al. Right trisectionectomy for liver metastasis of granulosa cell tumor: a case report and literature review. Surg Case Rep. 2020;6(1):125.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAleter A, Mahajan PS, Petkar MA, Abdulmajeed HA, Khalaf H, Elmoghazy W, et al. Late Cystic Metastasis of an Ovarian Granulosa Cell Tumor to the Liver. Cureus. 2021;13(9):e18051.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHe Y, Yang Y, Wang T, Wang W. Hepatic metastasis of the ovarian granulosa cell tumor after 11 years of surgical resection and systemic chemotherapy of primary tumors: A case report. Asian J Surg. 2021;44(4):687\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTorre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018;68(4):284\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFarkkila A, Koskela S, Bryk S, Alfthan H, Butzow R, Leminen A, et al. The clinical utility of serum anti-Mullerian hormone in the follow-up of ovarian adult-type granulosa cell tumors\u0026ndash;A comparative study with inhibin B. Int J Cancer. 2015;137(7):1661\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeis-Banke SE, Lerdrup M, Kleine-Kohlbrecher D, Mohammad F, Sidoli S, Jensen ON, et al. Mutant FOXL2(C134W) Hijacks SMAD4 and SMAD2/3 to Drive Adult Granulosa Cell Tumors. Cancer Res. 2020;80(17):3466\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlexiadis M, Rowley SM, Chu S, Leung DTH, Stewart CJR, Amarasinghe KC, et al. Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing. Mol Cancer Res. 2019;17(1):177\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKarstensen S, Kaiser K, Poulsen TS, Jochumsen K, Hogdall C, Marcussen N, et al. Ovarian Adult Granulosa Cell Tumors: A Scoping Review of DNA Alterations and Their Known Significance. Anticancer Res. 2025;45(1):1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrown J, Brady WE, Schink J, Van Le L, Leitao M, Yamada SD, et al. Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: results of a phase 2 trial of the Gynecologic Oncology Group. Cancer. 2014;120(3):344\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWagenaar HC, Pecorelli S, Vergote I, Curran D, Wagener DJ, Kobierska A, et al. Phase II study of a combination of cyclophosphamide, adriamycin and cisplatin in advanced fallopian tube carcinoma. An EORTC gynecological cancer group study. European Organization for Research and Treatment of Cancer. Eur J Gynaecol Oncol. 2001;22(3):187\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDubuc-Lissoir J, Berthiaume MJ, Boubez G, Van Nguyen T, Allaire G. Bone metastasis from a granulosa cell tumor of the ovary. Gynecol Oncol. 2001;83(2):400\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBergamini A, Ferrandina G, Candotti G, Taccagni G, Scarfone G, Bocciolone L, et al. Stage I juvenile granulosa cell tumors of the ovary: A multicentre analysis from the MITO-9 study. Eur J Surg Oncol. 2021;47(7):1705\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Sex cord stromal tumors, Granulosa cell tumor, Liver metastasis, Late recurrence","lastPublishedDoi":"10.21203/rs.3.rs-7033602/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7033602/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground：Granulosa cell tumors (GCT) are a distinct type of sex cord-stromal tumor with low-grade malignancy. It frequently recurs due to pelvic dissemination or direct spread, whereas liver metastasis rarely occurs. Here, we report a rare case of a GCT in which recurrence with liver metastasis occurred 14 years later. We also discuss the imaging findings, histological features, and therapeutic approaches, and conducted a review of similar reported cases.\u003c/p\u003e\n\u003cp\u003eCase presentation：\u003c/p\u003e\n\u003cp\u003eA 61-year-old female presented with a 14-year history of ovarian tumor resection for GCT. She was admitted to our hospital due to complaints of epigastric distension and acid regurgitation. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a hepatic mass measuring approximately 8 cm in diameter. Following surgical resection, histopathological examination of the sample revealed tumor cells with \"coffee-bean-like\" nuclei, a characteristic feature of GCT. Additionally, eosinophilicunstructured Call-Exner bodies were observed. Immunohistochemical analysis confirmed positive immunoreactivity for the inhibin α, CD99 and CD56 markers. On the basis of these findings, the tumor was diagnosed as a hepatic metastasis of an ovarian GCT. The patient remained recurrence-free for 7 years following hepatic resection.\u003c/p\u003e\n\u003cp\u003eConclusions：Herein,\u003cstrong\u003e \u003c/strong\u003ewe report a rare case of hepatic metastasis derived from a GCT that was diagnosed 14 years after initial oophorectomy. This case highlights the potential for late recurrence of ovarian GCT, even in the decades following primary treatment. Close long-term follow-up is essential to detect recurrence early and optimize patient outcomes.\u003c/p\u003e","manuscriptTitle":"Liver metastasis of ovarian granulosa cell tumors: A case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-11 07:10:23","doi":"10.21203/rs.3.rs-7033602/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-15T12:54:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-11T06:24:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196544034727339087747500117360506295669","date":"2025-08-29T01:27:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"34902819441871429466077408151589410416","date":"2025-08-25T22:19:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-21T18:34:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"140995297573678731362905524345924784725","date":"2025-08-02T18:19:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-02T17:28:06+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-29T09:27:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-07T06:08:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-07T04:12:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-07-07T04:09:33+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15e93bb9-dcd8-4719-9016-e0430c706cf3","owner":[],"postedDate":"August 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T16:49:13+00:00","versionOfRecord":{"articleIdentity":"rs-7033602","link":"https://doi.org/10.1186/s12905-026-04260-1","journal":{"identity":"bmc-womens-health","isVorOnly":false,"title":"BMC Women's Health"},"publishedOn":"2026-01-12 16:31:01","publishedOnDateReadable":"January 12th, 2026"},"versionCreatedAt":"2025-08-11 07:10:23","video":"","vorDoi":"10.1186/s12905-026-04260-1","vorDoiUrl":"https://doi.org/10.1186/s12905-026-04260-1","workflowStages":[]},"version":"v1","identity":"rs-7033602","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7033602","identity":"rs-7033602","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}