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Objective: We presented a rare case of drug-induced thrombotic microangiopathy (DI-TMA) following chemotherapy with the regimen of bleomycin, etoposide, and cisplatin (BEP) in a patient with malignant ovarian germ cell tumor (MOGCT). The objective is to highlight the difficulty in diagnosing and treating DI-TMA associated with BEP chemotherapy., Case Report: A 21-year-old woman presented with a pelvic mass. Fertility-sparing staging surgery was performed, and a diagnosis of endodermal sinus tumor was confirmed. The patient received the first course of adjuvant chemotherapy with BEP regimen, but she developed symptoms of anemia, thrombocytopenia, and acute kidney injury. DI-TMA was diagnosed after thorough examinations, and she improved gradually by three courses of plasma exchange. Adjuvant chemotherapy was discontinued due to DI-TMA, and she kept disease-free for 17 months after the operation., Conclusion: DI-TMA, a rare lethal complication in MOGCT patients receiving the BEP regimen, requires prompt diagnosis and appropriate treatments., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To compare surgery and survival outcomes between neoadjuvant chemotherapy and primary debulking surgery in patients with advanced ovarian yolk sac tumor., Methods: In this retrospective cohort analysis, patients with stage III to IV ovarian yolk sac tumor or mixed germ cell tumors containing yolk sac tumor elements, and who underwent surgery at Peking Union Medical College Hospital between January 2011 and December 2021, were identified. Patient characteristics, treatment, and survival data were analyzed between the two groups., Results: A total of 40 patients were enrolled: 19 patients received neoadjuvant chemotherapy followed by interval surgery, and 21 patients were treated with primary debulking surgery. After neoadjuvant chemotherapy, the surgical conditions of patients were improved. All patients achieved cytoreduction to R0 or R1 at interval surgery. No statistical difference was found in 3-year disease-free survival and overall survival between the neoadjuvant chemotherapy group and the primary debulking surgery group (log rank p=0.4 and 0.94). Patients had less blood loss (328.4 vs 1285.7 mL, p=0.029), lower transfusion volume (1044.4 vs 3066.7 mL, p=0.011), and fewer peri-operative complications (15.8% vs 47.6%, p=0.032) at the interval debulking surgery after neoadjuvant chemotherapy compared with patients who underwent primary debulking surgery., Conclusion: For patients with advanced-stage ovarian yolk sac tumor, neoadjuvant chemotherapy followed by interval surgery is an alternative option, especially for those who cannot tolerate the primary debulking surgery because of high tumor burden and vulnerable status., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian immature teratoma is a rare subtype of germ cell tumour that can be pure or associated with non-teratomatous germ cell tumour elements and is graded based on extent of the immature neuroectodermal component. Immature teratoma (IT) can also be associated with somatic differentiation in the form of sarcoma, carcinoma, or extensive immature neuroectodermal elements and may produce low levels of serum alpha-fetoprotein. Variable interpretation of these issues underlies diagnostic and management dilemmas, resulting in substantial practice differences between paediatric and adult women with IT. The Malignant Germ Cell International Consortium (MaGIC) convened oncologists, surgeons, and pathologists to address the following crucial clinicopathologic issues related to IT: (1) grading of IT, (2) definition and significance of 'microscopic' yolk sac tumour, (3) transformation to a somatic malignancy, and (4) interpretation of serum tumour biomarkers. This review highlights the discussion, conclusions, and suggested next steps from this clinicopathologic conference., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The lack of appropriate preclinical models of ovarian yolk sac tumor (OYST) is currently hindering the pursuit of new methods of treatment and investigation of the pathogenesis of the disease. We developed and characterized an OYST patient-derived xenograft (PDX) model in this study., Methods: Tumor fragments from a patient with an OYST were implanted subcutaneously into BALB/c Nude mice. Engrafted xenografts were compared with the original tumor according to histology, immunohistochemistry, humanized identified, and drug efficacy testing with in vivo treatment programs., Results: There was a high degree of histologic and immunohistochemical (IHC) resemblance between the established PDX model and its corresponding human tumors. Bleomycin, etoposide, and cisplatin (JEB) chemotherapy regimens were effective in clinical patients and were effective in the OYST PDX model; therefore, the effect of PDX intervention was consistent with clinical outcomes of OYSTs., Conclusion: We have successfully established an OYST PDX model. This OYST model preserves the basic molecular features of the primary human tumor, thereby providing a valuable method to preclinically evaluate new treatments and explore disease pathogenesis.

Background: Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients., Patients and Methods: Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients., Results: We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P < .001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P = .62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival., Conclusion: Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adult guidelines recommend BEP (bleomycin, etoposide, cisplatin) for all ovarian germ cell tumours, causing debilitating toxicities in young patients who will survive long term. Paediatricians successfully reduce toxicities by using lower bleomycin doses and substituting carboplatin for cisplatin, while testicular and paediatric immature teratomas (ITs) are safely managed with surgery alone., Aim: The aim was to determine whether reduced-toxicity treatment could rationally be extended to patients older than 18 years., Methods: Multicentre cohort study was carried out in four large UK cancer centres over 12 years., Results: One hundred thirty-eight patients were enrolled. Overall survival was 93%, and event-free survival (EFS) was 72%. Neoadjuvant/adjuvant chemotherapy (82% BEP) caused 27 potentially chronic toxicities, and one patient subsequently died from acute lymphoblastic leukaemia. There was no difference in histology, stage or grade in patients ≤/>18 years, and EFS was not different in these age groups (≤18:28% and >18:28%; log-rank P = 0.96). Histological subtype powerfully predicted EFS (log-rank P = 4.9 × 10 -7 ). Neoadjuvant/adjuvant chemotherapy reduced future relapse/progression in dysgerminoma (n = 37, chemo:0% vs. no chemo:20%), yolk sac tumour (n = 23, 26.3% vs.75%) and mixed germ cell tumour (n = 32, 40%vs.70%) but not in IT (n = 42, 33% vs.15%). Additionally, we observed no radiological responses to chemotherapy in ITs, pathological IT grade did not predict EFS (univariate hazard ratio 0.82, 95% confidence interval: 0.57-1.19, P = 0.94) and there were no deaths in this subtype., Conclusion: Survival was excellent but chemotherapy toxicities were severe, implying significant overtreatment. Our data support the extension of reduced-toxicity, paediatric regimens to adults. Our practice-changing findings that IT was chemotherapy resistant and pathological grade uninformative strongly endorse exclusive surgical management of ovarian ITs at all ages., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs)., Methods: Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) ≥2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed., Results: One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception., Conclusions: One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.

Background: Whereas among pediatric oncologists, ovarian yolk sac tumor (O-YST) is considered a chemosensitive tumor, it is often cited as an adverse prognostic factor in adult women with ovarian germ cell tumors., Methods: The Malignant Germ Cell International Consortium data set included 6 pediatric clinical trials (United States, United Kingdom, and France) and 2 adult gynecology clinical trials (United States). Any patient with an O-YST that was International Federation of Gynecology and Obstetrics stage IC or higher and treated with a platinum-based chemotherapy was eligible. Age was modeled as a continuous and a categorical variable (children, 0-10 years; adolescents, 11-17 years; and adults, ≥18 years). In addition, analyses to establish the optimal cut point for age were conducted. Tumors were coded as pure YST (YST +/- teratoma), mixed YST (YST + other malignant germ cell component), or putative YST ("mixed" germ cell tumor + alpha-fetoprotein >1000 ng/mL). Histology, stage (II/III vs IV), preoperative alpha-fetoprotein levels (<1000; 1000-10,000, or >10,000 ng/mL), and chemotherapeutic regimen (carboplatin vs cisplatin) were analyzed as covariates., Results: Two hundred fifty-one patients (median age, 13 years; range, 0-38 years) were identified (78 children, 139 adolescents, and 34 adults). Histology was pure, mixed, and putative in 129, 56, and 66 cases, respectively. Twenty-six patients had stage IV disease, similarly distributed in the 3 age groups. Median follow-up was 5.8 years. The overall 5-year event-free survival and overall survival was 91% (95% confidence interval, 87%-94%) and 96% (92%-98%), respectively. Age did not affect risk of event or death, modeled either as a categorical or continuous variable. Analysis failed to identify an age cut point that affected risk. None of the other covariates investigated had a prognostic impact on event-free survival or overall survival., Conclusions: Ovarian yolk sac tumors have an excellent outcome across all age-groups. Age has no apparent impact on the probability of event or death, allowing pediatric and gynecologic oncologists to enroll patients onto joint pediatric and adult trials.

Yolk sac tumours are rare ovarian malignancies accounting for less than 1% of malignant ovarian germ cell tumours. They are mostly seen in adolescents and young women and are usually unilateral making fertility preservation imperative. Raised alpha-feto protein level is the hallmark of this tumour. We describe stage III yolk sac tumour in a girl child.

Background: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact., Methods: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively., Results: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS., Conclusions: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs., Conflict of Interest Statement: No conflict of interest., (Copyright © 2016. Published by Elsevier Inc.)

Purpose of Investigation: Little is known regarding ovarian yolk sac tumor (YST) in postmenopausal females. The authors aimed to investigate the clinical features and prognosis of postmenopausal patients with ovarian YST., Materials and Methods: Five cases of ovarian YST in postmenopausal females were retrospectively reviewed. A MEDLINE search was performed to identify postmenopausal patients with ovarian YST., Results: Four patients had Stage I or II disease (Stage IC, IIC, and IIB in one, two, and one patient, respectively), and one patient demonstrated an unclear stage. All five patients received surgery and postoperative chemotherapy. Four of the patients received chemotherapy with a regimen of bleomycin, etoposide, and cisplatin, and one patient received cisplatin as first-line chemotherapy. Of the four patients who had no residual tumors at the initial surgery, three patients recurred at 3.0, 8.5, and 9.0 months after diagnosis, respectively. The three patients who had recurrence lived for an additional time of 21.8, 10.0, and 11.5 months after relapse. Four patients died of the disease at 30.8, 18.5, 14.5, and 8.5 months after diagnosis; one patient survived without tumor at 40.0 months. The three-year survival was 20.0%. Of the 12 cases identified from the literature, the three-year survival was 34.0%., Conclusion: The clinical features of ovarian YST in postmenopausal females, such as stage distribution, were similar compared to young patients. Postmenopausal patients with ovarian YST may have a worse prognosis compared to young patients.

Aim: The aim of this study was to investigate prognostic factors, including postoperative chemotherapy regimen, for the treatment of ovarian yolk sac tumour (YST), and resulting fertility outcome., Methods: A multi-institutional retrospective investigation was undertaken to identify patients with ovarian pure or mixed YST who were treated between 1980 and 2007. Postoperative chemotherapy regimen and other variables were assessed in univariate and multivariate analyses. Additionally, the reproductive safety of the BEP (bleomycin, etoposide and cisplatin) regimen was evaluated., Results: There were 211 patients enrolled from 43 institutions. The BEP regimen and a non-BEP regimen were administered to 112 and 99 patients as postoperative chemotherapy, respectively. In univariate and multivariate analyses, age⩾22, alpha-fetoprotein⩾33,000 ng/ml, residual tumours after surgery and non-BEP regimen were independently and significantly associated with poor overall survival (OS). BEP was significantly superior to non-BEP in 5-year OS (93.6% versus 74.6%, P=0.0004). Reduced-dose BEP (<75% standard-dose bleomycin and<50% etoposide dose) was significantly associated with poorer 5-year OS compared with standard-dose BEP (89.4% versus 100%, P=0.02 and 62.5% versus 96.9%, P=0.0002). All patients who underwent fertility-sparing surgery recovered their menstrual cycles. Sixteen of 23 patients receiving BEP (70.0%) and 13 of 17 patients receiving non-BEP (76.5%) who were nulliparous at fertility-sparing surgery and married at the time of investigation gave birth to 21 and 19 healthy children, respectively., Conclusions: The results of the present study suggest that standard-dose BEP should be administered for ovarian YST. BEP is as safe as non-BEP for preserving reproductive function., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: The aim of the study was to identify the role of neoadjuvant chemotherapy (NACT) in the treatment of the patients with advanced stage ovarian yolk sac tumor (OYST)., Methods: The comparative study was based on 53 cases with advanced stage OYST registered at Peking Union Medical College Hospital from 1995 to 2010. Twenty one cases were treated with NACT followed by interval debulking surgery (IDS). Thirty two cases were treated with primary debulking surgery (PDS). Data on patient characteristics, treatment and survival were analyzed and compared between two groups to assess the outcome of NACT., Results: After NACT, the overall status of the patients was improved significantly. Patients in NACT had better optimal cytoreduction rate and less peri-operative morbidities. Seven patients (13.2%) suffered from relapse. There was a significantly better PFS for patients with ovarian tumor size >20cm in the NACT than those underwent PDS. Residual disease >2cm was the independent risk factor of relapse., Conclusions: NACT is the better treatment option for some patients with advanced stage OYST, especially for those with unresectable tumors and poor general condition., (Copyright © 2014. Published by Elsevier Inc.)

Background: Malignant ovarian germ cell tumors are rare, and knowledge of their prognostic factors is limited, with little available randomized data. This study was conducted to evaluate the clinicopathologic characteristics of malignant ovarian germ cell tumors and to determine the association of their prognostic factors to primary treatment failure., Methods: The medical records of 57 patients with stages I to IV malignant ovarian germ cell tumor were retrospectively reviewed, and their clinicopathologic and treatment-related data were collected and analyzed., Results: The median age at the diagnosis was 23.3 years (range: 8-65 years), and the median follow-up period was 108 months (range: 48-205 months). The histological types of the tumors were immature teratoma (n = 24), dysgerminoma (n = 20), endodermal sinus tumor (n = 8), mixed germ cell tumor (n = 4), and choriocarcinoma (n = 1). 66.7% of the patients had stage I disease; 5.2%, stage II; 26.3%, stage III; and 1.8%, stage IV. After the initial surgery, 49 patients (86%) received cisplatin-based chemotherapy. The five-year survival rate was 96.5%. There were six primary treatment failures, with two of the patients dying of the disease, and the median time to the recurrence was 8 months. The histological diagnosis (P < 0.0001), tumor stage (P = 0.0052), elevation of beta-hCG (P = 0.0134), operation methods (P = 0.0006), and residual tumor after the salvage surgery (P < 0.0001) were significantly associated with the risk of primary treatment failure in the univariate analysis. In the multivariate analysis, the residual tumor after the salvage surgery was the only significant variable associated with primary treatment failure (P = 0.0011, Hazard ratio = 29.046, 95% Confidence interval 3.832-220.181)., Conclusion: Most malignant ovarian germ cell tumors have excellent prognoses with primary treatment, and good reproductive outcomes can be expected. Because primary treatment failure is associated with the residual disease after the salvage surgery, knowledge of the presence or absence of this risk factor may be helpful in risk stratification and individualization of adjuvant therapy in malignant ovarian germ cell tumors. Further large-scale prospective studies to confirm these results should be performed.

Background: Ovarian yolk sac tumour (OYST) is a very rare malignancy arising in young women. Our study aimed to evaluate long-term outcomes and to identify prognostic parameters likely to help make appropriate risk-based decisions about therapy in this disease., Methods: This retrospective study is based on prospectively recorded OYST cases at the Institut Gustave-Roussy. A univariate analysis using the logrank test evaluated possible associations between survival and patient or disease covariates. The multivariate analysis was performed using the Cox proportional hazard regression method., Results: Between 1976 and 2006, 84 patients were registered. Since 1991, most of the patients have undergone fertility-sparing surgery. With a median follow-up of 71 months, the overall 5-year and event-free survival rates are 84% and 79%, respectively. In the multivariate model only the absence of ascites and a favourable serum AFP decline rate were significantly associated with better overall survival., Conclusions: Patients with a poor prognosis factor such as an unfavourable serum AFP decline may be considered for aggressive treatment whereas those with good prognostic factors could be given less courses of chemotherapy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Cisplatin is used as a key drug for ovarian yolk sac tumor (YST), but relapse may occur. Details of the molecular mechanism responsible for cisplatin resistance remain unclear., Methods: We established cisplatin-resistant ovarian YST cells (NOY1-CR) from parent NOY1. To characterize these cells, we examined cross-resistance to other anticancer drugs. Then, cDNA microarray analysis was performed to quantify gene expression in NOY1 and NOY1-CR cells. The expression of several potential genes related to drug resistance was compared with parent cells by real-time PCR and Western blotting. Knockdown experiments using small interfering RNA (siRNA) were also performed to confirm the genetic association with drug resistance., Results: The IC(50) for cisplatin of NOY1-CR was 22.3-fold higher than that for parent cells. NOY1-CR cells showed cross-resistance to some drugs, but not to VP-16 and bleomycin. Microarray analysis identified 315 up-regulated and 412 down-regulated genes in NOY1-CR cells. Knockdown of GSTA1, which was up-regulated in resistant cells, by GSTA1 siRNA restored cisplatin sensitivity in NOY1-CR cells., Conclusions: Our data suggest the molecular mechanisms of cisplatin resistance and show the potential for GSTA1 to become a novel therapeutic target for cisplatin-resistant ovarian YST., (Copyright © 2010 S. Karger AG, Basel.)

Pregnancy complicated by endodermal sinus tumor of the ovary is a very rare event. We present a case report of a pregnant woman with a ruptured primary endodermal sinus tumor of the ovary that was diagnosed at 13 weeks of gestation. After right salpingo-oophorectomy had been performed the patient received four cycles of combination chemotherapy (bleomycin, etoposide, and cisplatin) starting at the 15th week of pregnancy. The patient did not have any evidence of tumor recurrence for 23 months. Her baby did not have any evidence of malformations and showed normal growth and development at 21 months of follow up.

Background: The management of ovarian cancer during pregnancy represents a major challenge and requires close multidisciplinary team approach., Case: A 35-year-old pregnant woman with a yolk sac tumor underwent left salpingo-oophorectomy at 25 weeks of gestation. Chemotherapy was deferred to the end of the pregnancy owing to concerns for potential fetal risks. Alpha-feto protein level was used to monitor the underlying disease activity. The patient underwent exploratory laparotomy with cesarean section followed by total hysterectomy, omentectomy, right salpingooophorectomy, pelvic, and para-aortic lymphadenectomies at 32 weeks of gestation. She received four postoperative courses of chemotherapy (cisplatin, etoposide, and peplomycin). Currently, mother and child are doing well 6 months after the last chemotherapy cycle., Conclusion: In a case of yolk sac tumor in the second trimester of pregnancy, radical surgery combined with elective caesarian section followed by chemotherapy could achieve remission and rescue of fetus. However, the treatment needs to be individualized as there is lack of evidence.

Objective: The aim of this study was to investigate the outcome and reproductive function of patients with ovarian endodermal sinus tumor (EST) after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP)., Methods: Between 1995 and 2006, 1034 patients with the diagnosis of ovarian cancer were treated at a single institution. Among these patients, 51 had a confirmed diagnosis of malignant ovarian germ cell tumor (MOGCT) including 20 cases of EST. We retrospectively reviewed those patients with EST, who received BEP as adjuvant chemotherapy. The doses were 15 mg/day of bleomycin on days 1 to 3, 100 mg/m(2)/day IV of etoposide on days 1 to 3 and 20 mg/m(2)/day of cisplatin on days 1 to 5. The median number of total cycles was six (range between three and nine)., Results: The median age of the patients with EST was 18 years (range 5 to 36). All except two were nulliparous. The overall survival rate was 90% at a median follow-up of 70 months. Two patients (10%) had disease recurrence in the pelvis. Of the 15 patients who were treated with fertility-sparing surgery, all had regular menstruation following the completion of adjuvant chemotherapy, and two of these patients had pregnancies with live birth deliveries and no complications., Conclusion: In patients with EST, the cumulative high-dose BEP regimen resulted in excellent overall survival and did not seem to impair ovarian function.

Background: Ovarian yolk sac tumor (YST) is a very rare malignancy arising in young women. Chemotherapy has dramatically improved the prognosis. Current treatment consists of surgery followed by bleomycin, etoposide, and cisplatin (BEP) chemotherapy. However, given the rarity of this tumor, ovarian YST-specific survival and outcome after such treatment are not precisely known., Patients and Methods: This report concerns prospectively recorded cases that were either treated at Institut Gustave Roussy (Villejuif, France) or referred there for advice about therapy. From 1990 to 2006, 52 patients underwent surgery followed by BEP chemotherapy. Data on patient characteristics, treatment, survival, and fertility outcome were analyzed to assess treatment efficacy and gonadal toxicity after achieving a complete remission., Results: Thirty-five patients had stage I/II tumors while 17 patients presented with stage III/IV disease. With a median follow-up of 68 months, the overall 5-year survival and disease-free survival rates were 94% and 90%, respectively. Forty-one women underwent fertility-sparing surgery. Pregnancy was achieved in 12 of 16 (75%) women who attempted conception. Overall, 19 pregnancies have been recorded., Conclusions: BEP chemotherapy following fertility-sparing surgery is a very effective treatment of ovarian YSTs. Most of the patients who attempt conception after complete remission will have children.

Pregnancy complicated by endodermal sinus tumor of the ovary is extremely rare. The authors present a case report of a pregnant woman with persistent left adnexal mass and subsequently found to have a primary endodermal sinus tumor of the ovary that was diagnosed at 19 weeks of gestation. After left salpingo-oophorectomy had been performed, the patient chose to terminate the pregnancy before the initiation of combination chemotherapy with bleomycin, etoposide, and cisplatin. The response to chemotherapy was not satisfactory. The patient expired after seven cycles of treatment had been completed because of pulmonary fibrosis and the drug toxicity of bleomycin.

Yolk sac tumors of the ovary (YST) are rare and highly malignant tumors occurring in children and young adults. Because of its rarity, YST prognostic factors remain unclear. Our purpose was to evaluate the prognostic factors in YST. We performed a retrospective review of 36 patients with pure YST from 1986 to 2006. The 5-year overall survival and progression-free survival were 66.6% and 68.8%, respectively. Patients with stage I-II disease had a more favorable prognosis than those with stage III-IV (p < 0.05). Those with an ascites volume of less than 100 ml or a residual tumor measuring less than 1 cm had improved to a relatively good prognosis. Neither serum AFP level nor age had any significant correlation with the prognosis in this study. In conclusion, the FIGO (International Federation of Gynecology and Obstetrics) stage, ascites volume and residual tumor size tended to affect the prognosis of YST.

Endometrioid adenocarcinoma of the ovary coexists very rarely with yolk sac tumor (YST). This unusual mixed tumor is thought to be a rare variant of endometrioid ovarian carcinoma because of its aggressive behavior, lack of response to chemotherapy, and unfavorable prognosis. We report a case of ovarian endometrioid adenocarcinoma with a YST component in a postmenopausal woman. The patient was treated by surgery and a combination of bleomycin, etoposide, and cisplatin and taxol and carboplatin. She has been clinically free of tumor for 20 months. Immunohistochemically, the YST component reacted for alpha-fetoprotein. YST areas were negative for both CA125 and sex-hormone receptors. Cytokeratin7 and epithelial membrane antigen were negative in YST, but positive in endometrioid adenocarcinoma. The occurrence of this unusual case suggests that even somatic carcinomas may acquire an extraembryonal germ cell differentiation.

Objective: To study the clinicopathologic features and biologic behavior of pediatric immature teratoma., Methods: The clinical data, pathologic features, immunohistochemical findings (for cyclin D1, P27 and Ki-67) and follow-up information of 39 cases of pediatric immature teratoma were analyzed., Results: Amongst the 39 cases studied, 12 arose in the sacrococcygeal region, 12 in testis, 5 in retroperitoneum, 4 in ovary, 4 in abdomen and 2 in mediastinum. Histologically, 16 cases were of grade 1, 8 cases of grade 2 and 15 cases of grade 3. Seven of the cases contained foci of yolk sac tumor. Immature neuroepithelial features used in histologic grading included the presence of primitive neural tubules, immature rosettes, undifferentiated neuroblastoma cells and primitive neuroectodermal structures. Immunohistochemical study showed that cyclin D1 was positive in 3 cases of grade 1 tumors, 4 cases of grade 2 tumors and 9 cases of grade 3 tumors. The positivity rates for p27 were 8, 3 and 6 cases respectively, while those for Ki-67 were 3, 4 and 13 cases respectively. Follow-up data were available in 30 cases. Three of them, including 2 cases with histologic grade 3 (with or without yolk sac tumor component), recurred after operation., Conclusions: The expression of cyclin D1 and Ki-67 is a useful adjunct in histologic grading. On the other hand, p27 overexpression shows little correlation with tumor grade. The prognosis of immature teratoma in children is different from that in adults. Sacrococcygeal immature teratoma occurring in patients younger than 1 year old and with low histologic grade do not require postoperative chemotherapy if the tumor is completely excised. Similarly, for testicular immature teratoma occurring in patients below 1 year of age, regardless of tumor grading, need no adjunctive therapy. On the other hand, ovarian immature teratoma with high histologic grade requires postoperative chemotherapy, regardless of age of the patients. The presence of microscopic foci of yolk sac tumor is a useful predictor of recurrence in pediatric immature teratoma.

Background: Mixed yolk sac tumors of the ovary are biologically aggressive even in early stage disease., Case: A 41-year-old woman presented with a large pelvic mass and anterior vaginal wall tumor. At surgery vaginal biopsies were performed followed by an exploratory laparotomy with resection of the mass. Pathology of the ovary revealed a primary yolk sac tumor associated with poorly differentiated endometrioid and undifferentiated carcinoma with vaginal metastasis only. She was initiated on bleomycin, etoposide, and cisplatin, with three additional cycles of etoposide and cisplatin. Initially the patient experienced a complete response, however her disease recurred and she currently is dead of her disease., Conclusion: To our knowledge this is the first case of a mixed ovarian germ cell tumor with vaginal metastasis.

Germinal cell tumours represent only 2-5% of all cancers of the ovary. However, the characteristics of the tumour and the patients have some special qualities as high rates of healing goes together with a strong desire to keep fertility intact because this condition occurs in female children and adolescent girls. Neither the prognosis nor the treatment of these tumours is homogeneous; the low incidence is the reason it is hard to develop prospective studies for establishing prognostic factors and specific treatments. The introduction of adjuvant chemotherapy into initial surgery has improved the prognosis of these patients. The BEP scheme has proved to be equally efficient and less toxic than PVB, and for this reason it has become the standard scheme despite the fact that no randomised studies have been carried out. The surgical treatment demands the application of the same principles seen in cytoreduction surgery of epithelial cancers of the ovary (maximum possible cytoreduction), though in many cases hysterectomy and double adnexectomy may be obviated. In view of the rarity of these tumours, it is advisable to work within cooperative groups that may have subgroups for the treatment of rare tumours. This will probably be the only way to move forward in the prospective knowledge of prognostic factors for these tumours.

Background: The administration of chemotherapeutic drugs during pregnancy is rare. We describe a case of malignant ovarian tumor complicating pregnancy., Case: After laparotomy at 18 weeks of gestation, the patient received three courses of cisplatin, vinblastine, and bleomycin. Elective cesarean delivery was performed at 31 weeks of gestation. A normal infant was delivered, and no evidence of tumor recurrence was observed. Metastasis to the liver was detected in the fifth month after delivery. However, this was treated successfully with three courses of cisplatin, etoposide, and bleomycin. There was no evidence of recurrence observed at 65 months after the initial treatment., Conclusion: Although the risk of chemotherapy to the fetus cannot be assessed based on a single case, this experience is encouraging.

Background: Pregnancy complicated by endodermal sinus tumor (EST) of the ovary has rarely been reported., Case: A huge ovarian EST causing bowel obstruction was found in a 22-year-old patient at 34 weeks of gestation. Abnormally high alpha-fetoprotein (AFP) levels suggested a malignant germ cell tumor of the ovary. The patient was submitted to cesarean section and fertility sparing surgery, and then received four courses of combination chemotherapy. There was no evidence of recurrence 19 months after initial treatment but transvaginal ultrasound (US) evaluation showed an intrauterine pregnancy of six weeks. We delivered a 3,200 g healthy male baby with Apgar scores of 8 and 9 by elective cesarean section at 39 weeks of gestation., Conclusions: Successful outcome of a second pregnancy is possible after treatment with fertility sparing surgery and combination chemotherapy for an endodermal sinus tumor associated with a first pregnancy. Moreover checking of weekly AFP levels and performing monthly abdominal US could be effective for surveillance of these pregnancies. However management of EST during pregnancy should be based on consideration of the patient's presenting condition, preferences, and gestational age.

A 17 year-old female with stage IIIc endodermal sinus tumor of the ovary developed transient cortical blindness and severe hypertension after 5 cycles of PVB regimen consisting of cisplatin, vinblastine and bleomycin. Clinical and radiological findings were compatible with Posterior LeukoEncephalopathy (PLE). Her visual acuity and blood pressure completely recovered within a few days after supportive treatment with antihypertensive drug. This condition is unpredictable but it can be reversible without long term sequelae. Most reports suggested that this rare toxicity was from cisplatin therapy. However, the exact pathophysiogenesis of this condition was not known precisely. Prompt reduction in blood pressure and withdrawal of immunosuppressive agents might lead to rapid reversal of this syndrome and prevent permanent brain damage.

Background: There is a therapeutic dilemma for the pregnant patient with malignancy requiring chemotherapy., Case: We had a case of a 30-year-old pregnant woman with a yolk sac tumor who underwent right salpingo-oophorectomy at 22 weeks gestation. Chemotherapy during pregnancy was postponed because of concern with the risks of the chemotherapy to the fetus. After the operation, L2 fraction of alpha-fetoprotein (AFP) depending on the affinity for Lens culinaris agglutinin (LCA) as an indicator for a maternal source of AFP had been detectable since 30 weeks gestation and elevated rapidly with advancing gestation. Tumor recurrence was confirmed clinically at 34 weeks gestation. She was induced, delivering a healthy baby, and received seven complete chemotherapy courses (cisplatin, etoposide, and peplomycin). Currently, the mother (39 months after last chemotherapy) and child are doing well., Conclusion: AFP-L2 may be a sensitive indicator for a yolk sac tumor derived AFP, leading to an earlier detection of tumor recurrence during pregnancy.

We present, for the first time, two yolk sac tumors (YST) in women 37 and 18 years of age, one with a typical parietovisceral pattern and the other with a glandular pattern, which were associated with extensive areas of mucinous carcinoid (MC). The tumor in the first case had numerous nodules of tubulopapillary YST that merged with well-differentiated MC. This patient responded well to chemotherapy. The tumor in the second case consisted of an AFP-positive glandular YST, with a glandulopapillary pattern closely resembling fetal lung type adenocarcinoma, coexisting with an AFP-negative, cytokeratin 20-positive, atypical MC; transitional areas between the two components were also seen. In the material from the recurrences and metastases; however, no YST was present, the atypical MC having become the predominant component including areas that had become carcinomatous. There was a poor response to various chemotherapeutic regimens. AFP levels became negative during the course of disease paralleling the disappearance of the YST component and the overgrowth of an increasingly anaplastic MC. The patient died 1 year after diagnosis. We think that, in these cases, MC represented an unusual form of endodermal differentiation of the YST. It is important to differentiate the yolk sac and carcinoid components due to their different responses to chemotherapy and to evaluate the possibility of mucinous carcinoid developing into a highly aggressive carcinoma.

Background: Yolk sac tumor is a rare neoplasm characterized by high malignancy given its premature metastasis, that is frequent in adolescence., Case Report: A 21-year-old woman came to our observation for an ovarian cyst (13 cm in diameter). Following salpingo-oophorectomy, it was revealed as a yolk sac tumor by histological diagnosis. The patient exhibited a highly elevated level of alpha1-fetoprotein (AFP) (1156 UI/ml). She is now undergoing chemotherapy treatment., Conclusion: This is an interesting case of yolk sac tumor in a young girl, at an age typical for germ cell tumor. AFP represents a valid marker resulting in a useful diagnostic tool.

Bleomycin plus etoposide and cisplatin seem to be a promising alternative for women with ovarian cancer. We are reporting two cases with favorable pregnancy outcome after exposure to these chemotherapeutic agents at the second and third trimesters of pregnancy. A pregnant woman with a stage Ic yolk-sac tumor underwent a right oophorectomy with omentectomy, and received five cycles of bleomycin, etoposide and cisplatin from the 22nd week of pregnancy until delivery. The second case was a pregnant woman with a stage Ia immature teratoma who underwent right salpingo-oophorectomy and received two cycles of bleomycin, etoposide and cisplatin starting at 30th week of pregnancy. The two patients did not have any evidence of recurrence of ovarian cancer for 6 and 2 years, respectively. Their babies did not have any evidence of minor or major malformations, and showed normal neurological development at 6 and 2 years of follow-up, respectively.

The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.

Background: Pregnancy complicated by endodermal sinus tumor of the ovary has rarely been reported., Case: A 32-year-old pregnant woman was found to have an ovarian tumor. At 19 weeks of gestation, tumorectomy was performed and a diagnosis of primary endodermal sinus tumor of the ovary (stage Ic) was made. Pregnancy was continued without postoperative chemotherapy. At 36 weeks of gestation, she underwent cesarean section combined with second-look laparotomy. A normal infant was delivered and there were no signs of recurrence. Subsequently, three courses of combination chemotherapy with bleomycin, etoposide, and cisplatin were administered. There was no evidence of recurrence at 27 months after initial treatment., Conclusions: Successful management of endodermal sinus tumor of the ovary in a pregnant woman is reported.

An ovarian endodermal sinus tumor was found in a 29-years old patient with a 32-week intrauterine gestation. She received caesarean section, conservative surgery and three courses of combination chemotherapy. She died 6 months after the diagnosis.

An ovarian mixed germ cell tumor in a 34-year-old woman contained a predominant component of polyembryoma as well as foci of choriocarcinoma, yolk sac tumor, and immature teratoma. No previous cases of identical composition have been found in the literature.

Background: Yolk sac tumors of the ovary are generally very responsive to chemotherapy; however, they are difficult to manage in the setting of platinum resistance where treatment options are limited and outcomes are poorer., Case: We present a 39-year-old woman who had a platinum-resistant yolk sac ovarian tumor. She achieved complete remission on an innovative regimen of docetaxel, gemcitabine, and thalidomide., Conclusion: The combination of docetaxel, gemcitabine, and thalidomide might be an active regimen for platinum-resistant ovarian nondysgerminomas and further investigation of this combination is warranted., (Copyright 2001 Academic Press.)

Objective: Our purpose was to evaluate the prognostic factors in yolk sac tumors of the ovary., Study Design: We performed a retrospective review of 47 patients with yolk sac tumors of the ovary from 1979 to 1997., Results: Twenty-two patients had pure yolk sac tumors and 25 had germ cell tumors with yolk sac tissue as a component of the disease. The 5-year survival rate in stages I, II, III, and IV was 95%, 75%, 30%, and 25%, respectively. Patients with stage I disease had a more favorable prognosis than those with stage III and IV disease (P <.001). All patients who did not respond to chemotherapy died of this disease within 36 months of the first treatment. Chemotherapy regimens that included cisplatin gave better results than those without cisplatin (P <.05). The difference in prognosis was significant in cases in which the size of residual tumor was <2 cm in diameter (P <.01) and in cases in which ascites was either absent or <100 mL in volume (P <.05). Coexistence of other components of ovarian germ cell tumors in histologic specimens, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, dissection of intrapelvic nodes, and p53 status had no significant correlation with the prognosis in this study., Conclusions: Staging and tumor-reductive surgery strongly affected the prognosis of this disease. Tumor-reductive surgery is advisable when ascites is minimal. Cisplatin-based chemotherapy after surgery was superior to chemotherapy without cisplatin; however, p53 status seemed to have no impact on chemosensitivity in yolk sac tumors of the ovary.

To describe our experience with malignant ovarian germ cell tumors with special reference to reproductive performance after remission, medical records of 31 patients were reviewed. The mean age at diagnosis was 18.6 years. Tumor by stage was I in 16 cases, II in 5, III in 5, IV in 3, and recurrence in 2. Histology was dysgerminoma in 7 cases, yolk sac tumor in 10, immature teratoma in 7, choriocarcinoma in 1, and mixed-type tumor in 6. Conservative surgery for fertility preservation was performed in 21 cases. Postoperative chemotherapy was given to all cases except two with stage Ia dysgerminoma. Of 31 cases, 4 including one fertility-preserved case died of disease. The other 27 cases including 20 fertility-preserved cases were successfully treated. Twenty-five cases (92.6%) have been followed longer than 60 months and 13 cases (48.1%) longer than 120 months. By the last follow-up, 8 of the 20 fertility-preserved cases delivered a total of 9 normal babies. Of the remaining 12 nonpregnant cases, 3 married, 9 have had regular menses, and 3 have had menstrual problems. Two of the latter three cases have been in hypergonadotropic anovulatory cycles. One patient has been diagnosed with tubal infertility caused by peritubal adhesion. Thus, management of the disease with fertility preservation is safe and the majority of patients can attain or retain normal ovarian function and reproductive potential.

Objective: In both adult women and children the potential for malignant recurrence from ovarian immature teratoma has prompted the standard use of chemotherapy after complete resection of the primary tumor. The efficacy of postoperative chemotherapy in children and adolescents with ovarian immature teratoma, however, has not been established. A pediatric intergroup trial (INT 0106) was designed to determine the need for postoperative chemotherapy in patients with ovarian immature teratoma after management with surgical resection only., Study Design: Between 1990 and 1995, 44 patients with completely resected ovarian immature tumor and without postoperative chemotherapy, who were able to undergo assessment, were accrued. Tumor tissue was evaluated by central pathology review to confirm diagnosis and determine tumor grading of immature neural elements. Patients were followed carefully for recurrence of disease with appropriate diagnostic imaging and serum marker studies., Results: Thirty-one patients had pure ovarian immature teratoma with a tumor grade of 1 (n = 17), 2 (n = 12), or 3 (n = 2). Age at diagnosis ranged between 1.5 and 15 years (median, 10). Of the 29 patients studied, the serum alpha-fetoprotein level was elevated in 10 (34%); the median level was 25 ng/ml. Thirteen patients had ovarian immature teratoma plus microscopic foci of yolk sac tumor. Tumor grade was 1, 2, or 3 in 1, 6, and 6 patients, respectively. Age ranged between 6 and 20 years (median, 12). In the 12 patients evaluated for serum alpha-fetoprotein, 10 (83%) had elevated levels; the median level was 262 ng/ml. The 4-year event-free and overall survival for the ovarian immature teratoma group and for the ovarian immature teratoma plus yolk sac tumor group was 97.7% (95% confidence interval, 84.9%-99.7%) and 100%, respectively. The only yolk sac tumor relapse occurred in a child with ovarian immature teratoma and yolk sac tumor who was then treated with chemotherapy and is alive and free of disease 57 months after recurrence., Conclusion: The results of this study suggest that surgery alone is curative for most children and adolescents with resected ovarian immature teratoma of any grade, even when elevated levels of serum alpha-fetoprotein or microscopic foci of yolk sac tumor are present. This experience strongly supports avoiding the long-term effects of chemotherapy in most children with ovarian immature teratoma by reserving postoperative therapy for cases with relapse.

Background: Combination chemotherapy has dramatically improved the prognosis of patients with nondysgerminomatous ovarian germ cell tumors (NDOGCT). However, guidelines are needed for the identification of patients at risk of relapse., Methods: The authors performed a retrospective analysis of women with NDOGCT managed during the period 1970-1994 at the Royal Marsden Hospital and other hospitals of the London Gynaecological Oncology Group., Results: Sixty-nine women were included; their median follow-up was 5.7 years (minimum, 12 months). The median age was 21 years (range, 4-44 years), with a histology of immature teratoma (IT) for 17 patients, endodermal sinus tumor (EST) for 20 patients, and mixed tumors for 32 patients. Thirty-five patients (51%) had Stage I disease. Nine patients with Stage I tumors were observed without further therapy (six with IT and three with mixed tumors), and one relapsed. Seven patients received non-platinum-based chemotherapy, and four relapsed. A total of 52 patients were treated with platinum-based chemotherapy, with relapse free and overall survival rates of 87% (95% confidence interval [CI], 73-93%) and 84% (95% CI, 70-91%), respectively. Of these patients, relapse was seen in 0 of 9 IT patients, 1 of 25 patients with mixed tumors, and 6 of 18 EST patients. With alpha-fetoprotein (AFP) > 1000 kU/L, relapse was seen in 6 of 18 patients compared with 1 of 33 relapses with lower AFP levels. In multivariate analysis, including all patients who received chemotherapy, AFP >1000 kU/L (P = 0.001) and non-platinum-based chemotherapy (P = 0.005) were associated with relapse. When only patients given platinum-based treatment were considered, EST histology (P = 0.003) and AFP >1000 kU/L (P = 0.003) were associated with relapse in univariate analysis; however, these factors were linked. No malignant tumor was found at second-look surgery performed on 24 patients. Of 26 women assessable for fertility, 24 subsequently recommenced regular menstrual function, and 11 patients had pregnancies., Conclusions: Platinum-based chemotherapy has been confirmed to be effective in the management of patients with NDOGCT. Relapses were principally seen among patients with AFP >1000 kU/L or pure EST histology. Efforts to improve outcome need to focus on patients with EST, whereas less intensive management strategies may be appropriate for some patients with IT.

Objective: The use of chemotherapeutic drugs in pregnancy is a rare occurrence. Experience and results need to be shared., Method: At 23 weeks gestational age, a patient was diagnosed with an endodermal sinus tumor of the ovary. She received one course of postoperative bleomycin, cisplatin, and etoposide. One week later, the patient was investigated for increasing abdominal pain and the fetus was noted to have ventriculomegaly., Results: The baby was delivered, and the patient was surgically staged and completed chemotherapy. Although the patient is alive and well 16 months after delivery, the infant has developed significant ventriculomegaly with cerebral atrophy., Conclusion: The etiology of this infant's significant cerebral atrophy is not clear. Tumor-specific, perioperative, or drug-related events must be considered., (Copyright 1999 Academic Press.)

We present a case of a 30-year-old pregnant woman in whom an ovarian mass was identified by ultrasonography at 15 weeks' gestation. A markedly elevated maternal serum alphafetoprotein (MSAFP) suggested a diagnosis of endodermal sinus tumour of the ovary. A right salpingo-oophorectomy at 19 weeks' gestation enabled histological confirmation of the diagnosis and suggested a stage 1 tumour. Unfortunately tumour recurrence necessitated further laparotomy and delivery by caesarean section at 32 weeks' gestation. A total abdominal hysterectomy and left salpingo-oophorectomy was undertaken with resection of the splenic flexure and formation of a double-barrelled colostomy after which no gross intraperitoneal tumour remained. Three weeks later a new suprahepatic tumour mass was excised and the colostomy was closed. The patient then received four cycles of combination chemotherapy with cisplatin, etoposide, and bleomycin. Unfortunately she developed a faecal fistula at the site of the colostomy. Germ cell tumours are highly responsive to chemotherapy. Over-zealous surgery particularly involving bowel resection may cause unnecessary morbidity and compromise the outcome.