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M. Devouassoux-Shisheboran, M. Vacher-Lavenu (2014)[The observatory of rare malignant gynecologic tumors].
Annales de pathologie, 34 1
V. Kottarathil, M. Antony, Indu Nair, K. Pavithran (2013)Recent Advances in Granulosa Cell Tumor Ovary: A Review
Indian Journal of Surgical Oncology, 4
Adam Gittleman, A. Price, C. Coren, Mudnia Akhtar, V. Donovan, D. Katz (2003)Radiology–Pathology Conference: Juvenile granulosa cell tumor
Clinical Imaging, 27
J. Park, K. Jin, Daeyeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Kyu-rae Kim, Young-Tak Kim, J. Nam (2012)Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary.
Gynecologic oncology, 125 1
N. Abu-Rustum, A. Restivo, J. Ivy, R. Soslow, P. Sabbatini, Y. Sonoda, R. Barakat, D. Chi (2006)Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the ovary.
Gynecologic oncology, 103 1
S. Ala-Fossi, J. Mäenpää, R. Aine, P. Koivisto, A. Koivisto, R. Punnonen (1997)Prognostic significance of p53 expression in ovarian granulosa cell tumors.
Gynecologic oncology, 66 3
E. Novak, J. Brawner (1934)Granulosa cell tumors of the ovary
American Journal of Obstetrics and Gynecology, 28
Shuiping Yu, Xue-ling Zhou, Binzong Hou, B. Tang, Jie Hu, Songqing He (2014)Metastasis of the liver with a granulosa cell tumor of the ovary: A case report
Oncology Letters, 9
X. Tao, A. Sood, M. Deavers, K. Schmeler, A. Nick, R. Coleman, L. Milojević, D. Gershenson, Jubilee Brown (2009)Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa cell tumors.
Gynecologic oncology, 114 3
S. Sekkate, Mouna Kairouani, B. Serji, H. M’rabti, I. ghissassi, H. Errihani (2014)[Granulosa cell tumors of the ovary].
Bulletin du cancer, 101 1
S. Ellouze, S. Krichen-Makni, K. Trabelsi, L. Ayadi, A. Sellami, A. Khabir, S. Hammami, H. Mnif, T. Sellami-Boudawara (2006)Tumeur de la granulosa de l'ovaire : À propos de 16 cas
Journal De Gynecologie Obstetrique Et Biologie De La Reproduction, 35
R. Ranganath, V. Sridevi, S. Shirley, V. Shantha (2007)Clinical and pathologic prognostic factors in adult granulosa cell tumors of the ovary
International Journal of Gynecologic Cancer, 18
L. Wu, W. Zhang, L. Li (2000)[Prognostic factors in granulosa cell tumor of the ovary].
Zhonghua fu chan ke za zhi, 35 11
N. Thomakos, I. Biliatis, I. Koutroumpa, M. Sotiropoulou, A. Bamias, M. Liontos, G. Vlachos, A. Rodolakis (2016)Prognostic factors for recurrence in early stage adult granulosa cell tumor of the ovary
Archives of Gynecology and Obstetrics, 294
J. Korach, T. Perri, M. Beiner, Tima Davidzon, E. Fridman, G. Ben-Baruch (2009)Promising Effect of Aromatase Inhibitors on Recurrent Granulosa Cell Tumors
International Journal of Gynecologic Cancer, 19
G. Koukourakis, V. Kouloulias, M. Koukourakis, G. Zacharias, C. Papadimitriou, K. Mystakidou, K. Pistevou-Gompaki, J. Kouvaris, A. Gouliamos (2008)Granulosa Cell Tumor of the Ovary: Tumor Review
Integrative Cancer Therapies, 7
A. Ayhan, M. Salman, M. Velipaşaoğlu, M. Sakinci, K. Yuce (2009)Prognostic factors in adult granulosa cell tumors of the ovary: a retrospective analysis of 80 cases.
Journal of gynecologic oncology, 20 3
Cheng-Fa Chou, Wen-Chih Huang (2016)Granulosa cell tumor of the ovary
Tzu-Chi Medical Journal, 28
S. Ellouze, S. Krichen-Makni, K. Trabelsi, L. Ayadi, A. Sellami, Abdelmajid Khabir, S. Hammami, H. Mnif, T. Sellami-Boudawara (2006)[Granulosa-cell tumor of the ovary: report of 16 cases].
Journal de gynecologie, obstetrique et biologie de la reproduction, 35 8 Pt 1
Hindawi International Journal of Surgical Oncology Volume 2018, Article ID 4547892, 4 pages https://doi.org/10.1155/2018/4547892 Research Article Granulosa Cell Tumor of the Ovary: A Retrospective Study of 31 Cases and a Review of the Literature Manel Dridi , Nesrine Chraiet, Rim Batti, Mouna Ayadi, Amina Mokrani, Khedija Meddeb, Yosra Yahiaoui, Henda Raies, and Amel Mezlini Department of Medical Oncology, Salah Aza¨ız Institute, Faculty of Medicine of Tunis, Tunis El Manar University, Tunis, Tunisia Correspondence should be addressed to Manel Dridi; email@example.com Received 9 February 2017; Revised 18 June 2017; Accepted 13 September 2017; Published 29 March 2018 Academic Editor: Anil D’cruz Copyright © 2018 Manel Dridi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Adult granulosa cell tumors (AGCTs) are the most common sex cord-stromal tumors. Unlike epithelial ovarian tumors, they occur in young women and are usually detected at an early stage. eTh aim of this study was to report the clinical and pathological characteristics of AGCT patients and to identify the prognostic factors. Methods. All cases of AGCTs, treated at Salah Aza¨ız Institute between 1995 and 2010, were retrospectively included. Kaplan-Meier’s statistical method was used to assess the relapse-free survival and the overall survival. Results. The final cohort included 31 patients with AGCT. The mean age was 53 years (35–73 years). Patients mainly presented with abdominal mass and/or pain (61%,𝑛=19 ).Meantumorsizewas20cm.Themajorityofpatientshadastage I disease (61%,𝑛=19 ). Two among 3 patients with stage IV disease had liver metastasis. Mitotic index was low in 45% of cases (𝑛=14 ). Surgical treatment was optimal in almost all cases (90%,𝑛=28 ). The median follow-up time was 14 years (1–184 months). Ten patients relapsed (32%) with a median RFS of 8.4 years (6.8–9.9 years). Mean overall survival was 13 years (11–15 years). Stage I disease and low-to-intermediate mitotic index were associated with a better prognosis in univariate analysis (resp.,𝑝=0.05 and 𝑝=0.02) but were not independent prognostic factors. Conclusion. GCTs have a long natural history with common late relapses. Hence, long active follow-up is recommended. In Tunisian patients, hepatic metastases were more frequent than occidental series. eTh prognosis remains good and initial staging at diagnosis is an important prognostic factor. 1. Introduction Tunisian population and then identify relapse and overall survival prognostic factors. Granulosa cell tumors (GCTs) represent only 5% of all ovar- ian cancers. However, they are the most common subtype of 2. Methods ovarian sex-cord tumors (70%) . They rfi st were reported by Rokitanski in 1855 . We conducted a retrospective single-center cohort study of Although there is no consensus on the pathogenesis of these all patients with AGCT diagnosed and treated in the Medical tumors, most investigators believe they originate from early Oncology Department at Salah Aza¨ız Institute for cancer ovarian mesenchyma as they are composed of granulosa cells, from 1995 to 2010. Quantitative variables were expressed as theca cells, and fibroblasts in different degrees . mean and median values. Qualitative variables are expressed Hyperoestrogenism reported in patients with GCT is as absolute and relative frequencies. Statistical analyses were related to tumor production of oestrogens, anti-Mul ¨ lerian performed using SPSS 20.0 software. Kaplan-Meier’s statis- hormone, and inhibin B . According to histological nd- fi tical method was used to assess the recurrence-free survival ings, two different subtypes of GCT were identified: adult and overall survival (95% confidence interval). (AGCT) and juvenile (JGCT). AGCTs are more frequent . Surgery is the mainstay of treatment. Chemotherapy and/or 3. Results radiotherapy are considered in patients with advanced stage or with unresectable recurrent disease . In this study, we A total of 31 women with a mean age of 53 years (35–73 aimed to describe epidemiologic characteristics of AGCT in years) were included in the study. 61% of cases presented 2 International Journal of Surgical Oncology with abdominal mass and/or abdominal pain in (𝑛=19 ). Table 1: Characteristics of patients with recurrent disease. Postmenopausal bleeding was reported in 32% of cases (𝑛= 𝑁=10 100% 10). Ultrasound imaging was performed in all cases and Age showed mainly cystic unilateral mass (80%𝑛=25 ). Median Mean (years) 52 — tumor size was 20 cm (4–33 cm). Abnormally elevated levels Range 35–64 — of serum tumor marker CA-125 were reported in 42% of patients (𝑛=13 ). Inhibin B was not studied in any of our Stage patients. Stage I 6 60% Histological features identified were micro/macrofollicles Stages II–IV 4 40% with cores “coeff e bean” (74%), Call-Exner bodies (55%), Tumor size and necrosis (22%). Mitotic index measured in only 22 Mean (cm) 20 — patients was mainly low (64%). The staging breakdown Mitotic index was as follows: stage I represents 61% (stage IC: 58% of Low 4 40% stageI),stageII10%,stageIII19%,andstage IV 10%. Intermediate 1 10% Metastases locations were mainly liver (67%) and pleura High 1 10% (33%). The primary treatment was surgery in all cases. Missing 1 40% 28 patients (90%) underwent hysterectomy with bilateral Type of resection salpingo-oophorectomy. Nonoptimal surgery was reported in 3 cases (10%). Intraoperative tumor rupture occurred Optimal 7 70% in 5 patients (16%). Adjuvant treatment was chemotherapy Nonoptimal 3 30% followed by hormonal therapy in one woman (3%) and Tumor rupture chemotherapy alone in 18 women (58%). No patient received Yes 1 10% adjuvant radiotherapy. No 9 90% Adjuvant chemotherapy was a platinum-based regi- Adjuvant chemotherapy men: cyclophosphamide-cisplatin in 13 patients (72%) and Yes 5 50% bleomycin-etoposide-cisplatin in 6 patients (28%). No 5 50% Mean overall survival was 13 years (11–15 years). Overall Time to relapse survival at 10 years was 90%. Mean (years) 3 — The median follow-up time was 14 years (1–184 months). Median RFS was 8.4 years (6.8–9.9 years). Relapses were Site of relapse reported in 10 patients (32%); among them, 6 had local Pelvic 6 60% recurrence (60%). Characteristics of these patients are shown Liver 1 10% in Table 1. All these women underwent surgery followed Abdominal nodes 3 30% by platinum-based chemotherapy. Following univariate Cox regression modeling, only stage I disease and low-to- intermediate mitotic index were signicfi antly associated with improved survival. In this stage, the 5-year OS was 98% versus GCTpresentsatearly stagein81%ofcases(stageI,71%;stage 65% (𝑝=0.04) and the median OS was 46.3 months versus II, 10%) and at late stage in 19% of cases (stage III, 11%; stage 42 months (𝑝 = 0.01), respectively (Table 2). High mitotic IV, 8%) . In our study, the largest tumor size was 33 cm index was associated with poor survival (42 months versus with stage III (19%) and large tumors were common in our 46.3 months,𝑝 = 0.01). No independent prognostic factor study. StageIVdisease wascomparabletoliterature(10%). was identified in the multivariate analysis. Metastatic sites of GCTs pulmonary and skeletal metastases are uncommon; 15% of relapses occurred in retroperitoneum nodes . Hepatic metastases are rare with an incidence 4. Discussion of 5-6% of all GCT recurrences but authors think that AGCT is averyraretumor with aknowngood prognosis. In these metastases are misdiagnosed as end-stage primary liver fact,only31patientswereincludedinour studyfrom1995 cancer . We found higher rate of hepatic pleural metastasis to 2010, and this is the rst fi published study conducted in a and nodes compared to literature (67%, 33%, and 30%, resp.) Tunisian population. because almost all cases were histologically confirmed. Since it is a rare disease, limited data are available . eTh mainstay of treatment is a complete surgery (hys- Clinical findings of our population are comparable to the terectomywithbilateral salpingo-oophorectomy)withstag- literature findings. AGCTs usually occur in menopausal or ing for early stage and debulking surgery for advanced stage postmenopausal women (average age: 50–54 years) . or recurrent disease . The most reported signs in the literature are abdominal Fertility-preserving surgery with unilateral salpingo- pain and/or abdominal distension (30% to 50%) and hor- oophorectomy is an option in young patients with stage IA monal event such as postmenopausal bleeding, amenorrhea, GCT. Available data showed that there is not much difference and intermenstrual bleeding . eTh size usually reported in survival with a conservative approach when compared to in the literature is >10 cm (73.5%) but it can vary from the radical surgery (97% versus 98%, resp.). The 5-year and a small nonpalpable lesion to large masses (3–24 cm) . 10-year disease-specific survival was 97% and 94% . International Journal of Surgical Oncology 3 Table 2: Univariate analysis of overall survival. study too presents the same limitations as it is retrospective and included a small number despite its spread over 15 years. OS 𝑝 Patients whose tumors had a mitotic index< 4/10 HPF 5-year survival hadaDFSat80monthsof90%compared to 25%forpatients Stage with a higher mitotic index . These data were consistent Stage I 98% with our findings; high mitotic index was associated with 0.04 Stages II–IV 65% worse OS (42 months versus 46.3 months,𝑝=0.01). Tumor size (cm) Discording data were reported regarding the prognostic <10 85% value of age, tumor size, residual disease, and tumor rupture. 0.06 ≥10 78% In fact, Ayhan et al. found that patients aged below 60 years Mitotic index had better mean time of survival (154.6 versus 89.2 months, 𝑝 = 0.015) . Some studies showed that tumors larger Low 85% 0.01 than 10 cm had lower survival . Thomakos et al. showed Intermediate-high 60% that increased tumor size by one cm was associated with 13% Age (years) increase in recurrence risk. In our study, there was no impact ≤60 85% 0.9 of tumor size in recurrence (DFS at 5 years in tumor larger >60 86% than 10 cm was 50% versus 65% in tumors less than 10 cm, Nuclear atypia 𝑝=0.325). Yes 80% 0.3 In Ranganath et al.’s study, median survival of GCT no 87% patients who underwent optimal cytoreduction was 60 Residual disease months in contrast to 19 months for those who did not with RO 70% a decrease in survival from 82% to 22% . Tumor rupture 0.05 R1-2 57% was associated with a decrease in 25-year survival from 86% Tumor rupture in patients with stage IA disease to 60% in patients with stage Yes 68% IC . In our study, we did not find any impact on survival 0.22 No 76% of postoperative residual disease and tumor rupture. OS at 5 years in patients with residual disease was 57% versus 70% in patients with optimal cytoreduction (𝑝=0.05). In case of tumor rupture, OS at 5 years was 68% versus 76% in other Chemotherapy is recommended for patients with cases (𝑝=0.22). advanced stageand recurrentdisease.Inearly stageGCT, In the light of Ala-Fossi et al.’s study nd fi ings, P53 only high risk patients (large tumors, tumors with high mutation in GCT may be associated with poor prognosis . mitotic index, or ruptured tumors) should receive adjuvant GCTs have a tendency for late recurrence. The recurrence chemotherapy . rate in our study was 32%, whereas it was 44% in Wu et al.’s The most used chemotherapy regimen is a BVP study. In this letter, early relapses were signicfi antly related to advanced stage . The longes treportedtimetorecurrence (bleomycin, vinblastine, and cisplatin) or a BEP regimen, which substitutes etoposide for vinblastine . Hormonal was 40 years . In our study, median RFS was 8.4 years therapies such as megestrol and LHRH (luteinizing hormone- (6.8–9.9 years). Local pelvic recurrence was reported in 70% of cases; releasing hormone) agonists seem to be efficient in relapsing patients . In our study, only one patient was treated with only 9% of recurrences were abdominopelvic, 6% were hormonal therapy. retroperitoneal, 6% were pelvic and retroperitoneal, and 3% eTh majors factors suspected in a number of studies were were abdominopelvic and retroperitoneal . In our study, age, tumor size, rupture of tumor, mitotic activity, nuclear recurrences were mainly located in the pelvis (60%). atypia, aneuploidy (in 5–20% GCT), p53 overexpression, Multidisciplinary treatment approach usually consists of high Ki-67, and stage of the disease . We noted that the disease debulking followed by radiotherapy or chemotherapy disease stage was the most reported factor aeff cting survival andmay prolongtheDFS.Brownet al.usedbevacizumab in 8 patients with recurrent GCT. The response rate was 38% in GCT patients. However, these studies are limited by their retrospective analysis, the small number of patients included, and median progression-free survival was 7.2 months . and the heterogeneity of the different populations. Wu et al. reported,inalargeseriesof100 casesofGCT,survivalrates 5. Conclusion at 5 and 10 years of 98% and 96%, respectively, for stage I and 70% and 60%, respectively, for stage II . Similar data were Granulosa cell tumor is an uncommon ovary neoplasm. It found by Park et al. as the 5-year and 10-year OS rates in early isknownforrelapsingevenyears aeft r acurativetreatment. stage (stage I and II) disease were 99% and 90%, respectively, Hence, an active lifelong follow-up is recommended with whileinadvancedstage(stagesIII andIV) they were80%and clinical examination and tumor markers such as inhibin B 67%, respectively . . Disease stage seems to be the only reliable prognostic The same survival rates were found in our study with a factor. Knowing more about molecular pathogenesis of GCT significant prognostic value of stage as OS at 5 years was 98% may lead to identifying the place of targeted therapies in the in early stage and 65% in advanced stage (𝑝 = 0.04). Our disease management. 4 International Journal of Surgical Oncology Ethical Approval  R. Ranganath, V. Sridevi, S. S. Shirley, and V. Shantha, “Clinical and pathologic prognostic factors in adult granulosa cell tumors This study was approved by the institutional review boards of the ovary,” International Journal of Gynecological Cancer,vol. and the ethics committee of Salah Aza¨ız Institute of Oncol- 18, no. 5, pp. 929–933, 2008. ogy.  S.-L. Ala-Fossi, J. Maen ¨ pa¨a, ¨ R. Aine, P. Koivisto, A.-M. Koivisto, and R. Punnonen, “Prognostic significance of p53 expression in ovarian granulosa cell tumors,” Gynecologic Oncology,vol.66, Consent no.3,pp. 475–479, 1997.  N. R. Abu-Rustum, A. Restivo, J. Ivy et al., “Retroperitoneal As the treatment of each patient was decided in the multidis- nodal metastasis in primary and recurrent granulosa cell ciplinary meeting of the institute, oral consent was obtained tumors of the ovary,” Gynecologic Oncology,vol.103,no.1,pp. from the subjects. 31–34, 2006.  X. Tao, A. K. Sood, M. T. Deavers et al., “Anti-angiogenesis Conflicts of Interest therapy with bevacizumab for patients with ovarian granulosa cell tumors,” Gynecologic Oncology,vol.114,no.3, pp.431–436, eTh authors declare that they have no conflicts of interest.  “Observatoire des tumeurs malignes rares gynec ´ ologiques,” http:// www.ovaire-rare.org/TMRG/medecin/accueil medecin.aspx. References  D. Pectasides, E. Pectasides, and A. Psyrri, “Granulosa cell tumor of the ovary,” Cancer Treatment Reviews,vol.34, no.1, pp. 1–12, 2008.  A.M.Gittleman,A.P.Price,C.Coren,M.Akhtar, V.Donovan, and D. S. Katz, “Radiology-Pathology Conference: Juvenile granulosa cell tumor,” Clinical Imaging,vol.27,no.4,pp. 221– 224, 2003.  N.Thomakos,I.Biliatis,I.Koutroumpaetal., “Prognostic factors for recurrence in early stage adult granulosa cell tumor of the ovary,” Archives of Gynecology and Obstetrics,vol.294,no. 5, pp. 1031–1036, 2016.  J.-Y. Park, K. L. Jin, D.-Y. Kim et al., “Surgical staging and adjuvant chemotherapy in the management of patients with adult granulosa cell tumors of the ovary,” Gynecologic Oncology, vol. 125, no.1,pp. 80–86, 2012.  V.D.Kottarathil,M.A.Antony, I.R.Nair,and K.Pavithran, “Recent advances in granulosa cell tumor ovary: a review,” IndianJournalofSurgicalOncology,vol.4,no. 1, pp.37–47,2013.  S. Sekkat, M. Kairouani, B. Serji, H. M’Rabti, I. E. Ghissassi, and H. Errihani, “Granulosa cell tumors of the ovary,” Bulletin du Cancer,vol.101,no.1,pp.93–101,2014.  G.V.Koukourakis,V.E.Kouloulias, M. J. Koukourakisetal., “Granulosa cell tumor of the ovary: Tumor review,” Integrative Cancer eTh rapies ,vol.7,no.3, pp.204–215,2008.  S.Yu,X.Zhou,B.Hou,B.Tang, J.Hu,andS.He,“Metastasis of the liver with a granulosa cell tumor of the ovary: A case report,” Oncology Letters,vol.9,no. 2, pp.816–818,2015.  S. Ellouze, S. Krichen-Makni, K. Trabelsi, L. Ayadi, A. Sellami, A. Khabir et al., “Granulosa-cell tumor of the ovary: report of 16 cases,” Journal De Gynecologie, Obstetrique Et Biologie De La Reproduction,vol.35, 8Pt1,pp.767–772, 2006.  J.Korach,T.Perri,M.Beiner,T.Davidzon,E.Fridman,andG.B. Baruch, “Promising effect of aromatase inhibitors on recurrent granulosa cell tumors,” International Journal of Gynecological Cancer,vol.19,no.5,pp. 830–833, 2009.  L. Wu, W. Zhang, and L. Li, “Prognostic factors in granulosa cell tumor of the ovary,” Zhonghua Fu Chan Ke Za Zhi,vol.35,no. 11, pp. 673–676, 2000.  A. Ayhan, M. C. Salman, M. Velipasaoglu, M. Sakinci, and K. Yuce, “Prognostic factors in adult granulosa cell tumors of theovary:Aretrospectiveanalysisof80cases,” Journal of Gynecologic Oncology,vol.20,no.3,pp.158–163, 2009. 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