Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST.

OBJECTIVE: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes. METHODS: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features. RESULTS: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation. CONCLUSION: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.

Component Patterns and Survival Outcomes in Patients with Mixed Malignant Ovarian Germ Cell Tumors: A Retrospective Cohort Study.

AIMS: To evaluate the component patterns and risk stratification in patients with mixed malignant ovarian germ cell tumors (mMOGCT). METHODS: A retrospective study of 70 mMOGCT patients treated in our hospital between 2000 and 2022 was conducted. The recurrence-free survival (RFS), disease-specific survival (DSS), and risk stratification systems based on scoring the identified prognostic factors were assessed. RESULTS: Yolk sac tumor component was the most common type (80%), followed by dysgerminoma (50%), immature teratoma (40%), embryonic carcinoma (27.1%), and chorionic carcinoma (15.7%). The 5-year RFS and DSS rates were 77.9% and 87.9%, respectively. International federation of gynecology and obstetrics (FIGO) stage III-IV (RR 3.253, P = 0.029) and normalization of tumor marker (TM) ≤ 3 cycles of chemotherapy (RR 6.249, P = 0.017) were risk factors for RFS and DSS, respectively. Significant DSS (RR 8.268, P = 0.006) was also noted between patients who had normalized TM ≤ 4 and ≥5 cycles of chemotherapy. FIGO stages I-II and stages III-IV were scored as 0 and 2, respectively. AFP normalization ≤3, 4, and ≥5 cycles of chemotherapy were scored as 0, 1, and 4, respectively. A total score of 0, 1-2, and ≥3 stratified patients into low-risk (43 patients), intermediate-risk (13 patients), and high-risk groups (14 patients), respectively. Patients in three risk stratifications manifested significant differences in DSS (P = 0.010) but not in RFS (P > 0.05). CONCLUSION: Distinct different component patterns existed among mMOGCT patients, and predicting survival outcomes in a universal model was challenging.

Laparoscopic retroperitoneal lymphadenectomy for ovarian mixed germ cell tumor in a patient with situs inversus totalis; reporting the first case worldwide with literature review and in silico analysis.

BACKGROUND: Situs inversus totalis (SIT) is a rare autosomal recessive inheritance at which the abdomino-thoracic organs are mirror-image transposed. Germ cell tumors originate from the primitive germ cell of the ovary and testis. CASE REPORT PRESENTATION: A rare association between malignant ovarian mixed germ cell tumor and SIT was presented in a 32-years-old Egyptian female, successfully treated with laparoscopic total abdominal hysterectomy, right salpingo-oophorectomy, and retroperitoneal lymphadenectomy (laparoscopic retroperitoneal lymphadenectomy) of both sides. This case is considered the first of its kind worldwide. CONCLUSION: SIT may be associated with malignant ovarian germ cell tumors. Surgical intervention could be done laparoscopically.

A Comprehensive Review of Current Trends in the Diagnosis and Treatment of Ovarian Germ Cell Tumors.

Ovarian germ cell tumors constitute a rare and intricate spectrum of neoplasms characterized by diverse histological subtypes. This comprehensive review elucidates the classification, diagnosis, treatment, prognosis, and unique challenges associated with these tumors. The classification is rooted in histological attributes, with principal subtypes encompassing dysgerminoma, immature teratoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, and mixed germ cell tumors. Each subtype bears distinct characteristics and clinical implications, necessitating precise diagnosis and tailored therapeutic strategies. Diagnosis hinges upon recognizing the broad clinical presentation, employing imaging techniques (such as ultrasound and MRI), evaluating tumor markers (alpha-fetoprotein and beta-human chorionic gonadotropin), and conducting histopathological examinations where necessary. Staging, primarily utilizing the International Federation of Gynecology and Obstetrics (FIGO) system, is pivotal in determining the extent of disease, guiding treatment choices, and facilitating prognostic assessment. Treatment modalities encompass surgery, chemotherapy (including standard regimens and emerging therapies), radiation therapy, targeted therapies, and immunotherapy. Prognosis is influenced by histological subtype, tumor stage, patient age, surgical success, response to chemotherapy, and tumor markers, while predictive biomarkers are continually emerging. Despite advances in treatment, ovarian germ cell tumors pose distinct challenges, including late diagnosis, treatment-related side effects, and the enigma of chemoresistance. An integral aspect of comprehensive care is supportive strategies to manage symptoms and offer psychological and emotional support. This review accentuates the vital role of early diagnosis and multidisciplinary care in optimizing outcomes. Future research directions and evolving clinical practices are explored in these intricate and distinctive malignancies, highlighting the dynamic landscape of ovarian germ cell tumors.

Rare occurrence of ovarian choriocarcinoma: ultrasound evaluation.

Choriocarcinoma of the ovary is a rare, highly malignant tumor showing malignant trophoblastic cells and produces human chorionic gonadotropins. It can be classified as gestational and non-gestational choriocarcinoma. Non-gestational choriocarcinoma is extremely rare. Treatment is Methotrexate-based chemotherapy for the gestational type. This case study is a rare case of ovarian choriocarcinoma managed by surgical resection, followed by methotrexate-based chemotherapy, and aimed to evaluate the ultrasound characteristics of ovarian choriocarcinoma and how to arrive at the diagnosis. In cases with an elevated serum beta-human chorionic gonadotropin (beta hCG), the finding of a highly vascularized adnexal mass on ultrasound evaluation should be underlined as a clue for suspecting choriocarcinoma, particularly if the female was young with no marriage history or history of sexual intercourse and also to be highly considered in married females with history of repeated abortions, molar pregnancy or uterine choriocarcinoma.

Reproductive outcomes after conservative treatment in early and advanced stage MOGCTs.

BACKGROUND: Malignant ovarian germ cell tumors usually occur in young women. The standard of care is fertility sparing surgery and comprehensive surgical staging followed by adjuvant chemotherapy with BEP (bleomycin, etoposide, cisplatin) if needed. The aim of this study was to analyze the reproductive outcomes after conservative treatment in patients diagnosed, treated and followed up in MITO (Multicenter Italian Trials in Ovarian Cancer) centers. METHODS: A questionnaire concerning gynecological symptoms, reproductive outcomes and fertility treatment was administered to 164 MOGCTs survivors. Data regarding patients deceased were collected from MITO-9 database. There were 114 patients diagnosed at reproductive age between 1983 and 2019 included. RESULTS: 109 patients answered the questionnaire and 5 patients decesased were included (median age 24.9 years). 78.1% were stage I,4.4% stage II, 14.9% stage III and 2.6% stage IV. 57.9% received chemotherapy, the mean number of cycles was 4.1. Median time to menstrual recovery after BEP was of 5.6 months range, only 1 case of premature ovarian failure was reported. Among the 114 patients 38 (33.3%) attempted to become pregnant, 29/38 (76.3%) got pregnant with a total of 44 conceptions. 40.9% received chemotherapy and 22.9% did not (p 0.048). Pregnancy desire was the only predictive factor associated with live births among women who attempted pregnancy after treatment. CONCLUSIONS: As MOGCTs affect women of child-bearing age, fertility preservation represents a major treatment issue. Our results are consistent with the available evidence, confirming that adjuvant chemotherapy for MOGCT does not impact the reproductive function and fertility.

Clinicopathological Features and Survival Trends of Non-Epithelial Ovarian Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

INTRODUCTION: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. MATERIALS AND METHODS: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. RESULTS: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. CONCLUSION: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs.

Depression and anxiety in women with malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST): an analysis of the AGO-CORSETT database.

INTRODUCTION: The intention of this study was to evaluate the level of anxiety and depression of malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) survivors and to identify possible alterable cofactors. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO Studygroup. Women who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Hospital Anxiety and Depression Scale (HADS) to evaluate distress. Predictors of distress (type of surgery, chemotherapy, time since diagnosis, recurrence, second tumor, pain) were investigated using multivariate linear regression analysis. RESULTS: 150 MOGCT and SCST patients with confirmed histological diagnosis completed the questionnaire median seven years after diagnosis. They had a HADS total score ≥ 13 indicating severe mental distress in 34% of cases. Patients after fertility-conserving surgery had lower probability of severe mental distress than those without fertility-conserving treatment (ß = - 3.1, p = 0.04). Pain was associated with the level of distress in uni- and multivariate analysis (coef 0.1, p < 0.01, coef. Beta 0.5). DISCUSSION: Severe mental distress was frequent in patients with MOGCT and SCST and the level of pain was associated with the level of distress. Fertility conserving therapy, however, was associated with less mental distress. Screening and treatment of pain and depression is required to improve mental well-being in survivors of MOGCT and SCST.

Clinical outcome of lymphadenectomy in malignant ovarian germ cell tumors: a systematic review and meta-analysis.

Malignant ovarian germ cell tumors (MOGCTs) are predominately diagnosed in young patients and account for most preadolescent malignant ovarian tumors. Currently, due to the high sensitivity of MOGCTs to chemotherapy and the optimal survival rate after chemotherapy, some researchers have recommended opting for non-surgical treatment. However, the effect of lymphadenectomy (LND) on the survival of patients with MOGCT remains controversial. We conducted a systematic review and meta-analysis to compare the clinical outcomes of LND and non-LND in MOGCT surgeries in order to summarize the clinical experience. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to December 26, 2021. Data on the rates of survival, relapse, and adverse effects were evaluated using Review Manager software. Fourteen studies with 10,759 participants were included in this review. There were 5863 and 4896 patients in the LND- and LND+ groups, respectively. Pooled results showed that although disease-free survival (DFS) was significantly improved in the LND+ group compared to the LND- group (HR: 0.74; 95% CI: 0.56 to 0.97; 2091 participants), LND did not significantly affect overall survival (OS) (HR: 0.82; 95% CI: 0.51 to 1.31; 5298 participants). The operation time was significantly longer in the LND+ group than in the LND- group (P<0.001). Blood loss (P=0.004) and complication rate (P=0.003) were also significantly higher in the LND+ group than in the LND- group. There was no significant difference in mortality rate (P=0.500). LND was associated with an improvement in DFS. However, there was no significant difference in OS in MOGCTs. We recommend that LND should not be a routine surgery for children or young patients with MOGCTs; although it may be beneficial for older people, advanced stage tumors, specific pathological types, and non-chemotherapy patients.

Ovarian Germ Cell Tumors: Pictorial Essay.

Ovarian germ cell tumors of the ovary represent a histologically heterogenous group of tumors with a high incidence at reproductive age. Patients with this pathology are very often young women with amenorrhea. The aim of this article is to present a pictorial essay of this rare pathology and to promote a national tumor registry and protocol. The treatment is individualized according to age, and fertility-sparing surgery is the actual standard of surgical treatment for young patients in early stage of the disease.

Parity is associated with better prognosis in ovarian germ cell tumors, but not in other ovarian cancer subtypes.

Ovarian cancer is influenced by reproductive factors, with a reduced risk of epithelial ovarian cancer in parous women. Nonepithelial ovarian cancer frequently affects young women and often precedes or occurs during the childbearing years. However, the impact of reproductive factors on ovarian cancer survival remains unclear: in epithelial ovarian cancer, data are conflicting, and subtype-specific associations have not been examined, and in nonepithelial ovarian cancer, it has not been studied. Using Swedish registers, we evaluated associations between women's reproductive history and cancer-specific mortality by subtype of epithelial and nonepithelial ovarian cancer in 3791 women born 1953 and later, diagnosed from 1990 to 2018. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using Cox-proportional hazard models. Parity was associated with a 78% decreased risk of cause-specific mortality in 243 women with germ cell tumors (GCTs) (parous vs nulliparous, adjusted for age at diagnosis: HR: 0.22 [95% CI 0.07-0.62]), with a decreased risk with increasing number of births (per birth: HR: 0.60 [95% CI 0.38-0.95]). We found no evidence of associations between parity and cause-specific mortality among the 334 patients with sex-cord stromal tumors, nor among the 3214 patients with epithelial ovarian cancer; neither overall, nor by subtype. In conclusion, in our large, population-based study, parity was associated with a clearly better prognosis in GCTs but not in the other ovarian cancer subtypes. Future research on how hormone exposure impacts GCT development may lead to a better understanding of mechanisms affecting survival.

Incidence and outcomes of malignant ovarian germ cell tumors in Korea, 1999-2017.

OBJECTIVE: Malignant ovarian germ cell tumor (MOGCT) is a rare ovarian malignancy accounting for less than 5% of all ovarian cancers. We aimed to evaluate the incidence, survival, and subsequent malignancies after the diagnosis of MOGCT. METHODS: Data from the Korea Central Cancer Registry were used to identify MOGCTs between 1999 and 2017. The age-standardized rates (ASRs), 5-year relative survival rates (RSR) and standardized incidence ratio (SIR) for subsequent cancer after diagnosis of MOGCT were estimated. RESULTS: Of 2125 cases of newly diagnosed MOGCTs, 596 (28.0%) were diagnosed with dysgerminoma and 1529 (72.0%) with non-dysgerminoma. The ASR per 100,000 women-years was 0.539; ASR slightly increased over the study period (annual percent change [APC] = 1.01%; p = 0.02). There was an increase and decrease in the incidence of MOGCTs in the age groups 0-19 years (APC = 1.96%; p < 0.01) and ≥ 50 years (APC = -6.51%; p < 0.01), respectively. Patients with dysgerminoma showed significantly higher RSR than patients with non-dysgerminoma (98.0% vs. 94.9%, p < 0.01). Patients aged ≥50 years showed worst 5-year RSR (68.7%) than patients aged 0-19 years (97.8%) and 20-34 years (96.4%) (p < 0.01). The overall SIR for a subsequent cancer occurrence was 2.07, with the most frequent site of subsequent primary cancer being the thyroid (SIR = 2.78). CONCLUSIONS: Our data demonstrated an excellent prognosis of MOGCTs among Korean women. There was a slight increase in MOGCT prevalence, which was more pronounced among those aged <19 years. After MOGCT diagnosis, the risk of developing a subsequent malignancy was doubled compared with the general population.

The effect of fertility-sparing surgery on sexuality and global quality of life in women with malignant ovarian germ cell and sex cord stromal tumors: an analysis of the CORSETT database of the AGO study group.

PURPOSE: Malignant ovarian germ cell (MOGCT) and sex cord stromal tumors (SCST) are ovarian neoplasms that affect disproportionally young women. Little is known about the impact of surgical and adjuvant management of these patient's sexual life. This study investigated the effect of fertility-sparing surgery on sexual activity and global quality of life (gQoL) in women with MOGCT and SCST. METHODS: CORSETT was an observational, multicenter, mixed retrospective/prospective cohort study of the AGO study group. Women of any age who had been diagnosed with MOGCTs and SCSTs between 2001 and 2011 were asked to complete the Sexual Activity Questionnaire (SAQ) and the EORTC QLQ-C30. RESULTS: In total, 355 patients were included. Of these, 152 patients with confirmed histological diagnosis had completed the questionnaires. A total of 106 patients were diagnosed with SCST and 46 with MOGCT. Totally, 83 women (55%) were sexually active. After fertility-sparing surgery, patients had a 2.6 fold higher probability for being sexually active than after non-fertility-conserving treatment (unadjusted odds ratio (OR) 2.6, p = 0.01). After adjustment for age, time since diagnosis, FIGO stage, histology and phase of disease, the OR dropped to 1.8 (p = 0.22). Of the sexually active patients, 35 (42%) reported high levels of discomfort during intercourse; 38% after fertility-sparing; and 58% after non-fertility-sparing surgery (adjusted OR 2.8, p = 0.18). Women with fertility-conserving treatment reported a significantly better global QoL (Fadj 2.1, 6.2 points difference, p = 0.03) but not more pleasure during intercourse than women without fertility-sparing surgery (Fadj 0.4, p = 0.52). CONCLUSION: Fertility preserving approaches should be offered to every patient, when oncologically acceptable.

Uncommon Metastasis of Ovarian Dysgerminoma: A Case Report and Review of the Literature.

Ovarian malignant germ cell tumors (OMGCT) represent less than 10% of all ovarian tumors. Dysgerminoma is the most common malignant primitive germ cell tumor in young women, known for its curability and low propensity to invade and metastasize when diagnosed early. Herein, we report an unusual type of ovarian dysgerminoma (OD) metastasis with a brief review of the literature, lacking similar reported cases. To our knowledge, although there are several case reports of dysgerminoma metastases with variable anatomic location and presentation, vaginal metastasis has not been previously described. The local or systemic relapse together with local and distant metastasis is considered as an independent predictor of poor survival in patients with OD. In light of the absence of mutations status, our patient successfully responded to therapy. Currently, the patient remains in clinical remission. A specific follow-up plan is ongoing knowing that ovarian dysgerminomas tend to recur most often in the first 2-3 years after treatment.

Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors†.

Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes with copy number alterations (deletion and duplication region), functional annotation was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region and duplication region. In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YSTs). Moreover, POU5F1 was the most significant mutated gene with mutation frequency >10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region and duplication region) was found in two YST and nuclear staining in two dysgerminomas tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I (DExD/H-box helicase 58)-like receptor, Toll-like receptor and nuclear factor (NF)-kappa. Keratin 4 (KRT4), ribosomal protein L14 (RPL14), proprotein convertase subtilisin/kexin type 6 (PCSK6), poly(A)-binding protein cytoplasmic 3 (PABPC3), and sterile alpha and TIR motif containing 1 (SARM1) mutations were detected in both peripheral blood and tumor samples. Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

Imaging Appearance of Nongerminoma Pediatric Ovarian Germ Cell Tumors Does Not Discriminate Benign from Malignant Histology.

STUDY OBJECTIVE: Pediatric ovarian neoplasms with imaging appearance suggestive of teratoma are often presumed to have low risk of malignancy. We assessed the pre-operative imaging appearance of pediatric malignant ovarian germ cell tumors (MOGCT) and the presence of associated teratoma in a series of MOGCT. DESIGN: Retrospective review of clinical and pathology data. SETTING: Multicenter trial for extracranial malignant germ cell tumors in young female individuals by the Children's Oncology Group (COG study AGCT0132) that included yolk sac tumor, embryonal carcinoma and choriocarcinoma. PARTICIPANTS: Female individuals 0-20 years of age at enrollment with ovarian primary nonseminomatous malignant germ cell tumors. INTERVENTIONS: Review of data forms, including prospectively collected surgical checklist documenting imaging characteristics of the tumor, and review of pathology reports. MAIN OUTCOME MEASURES: Description of imaging appearance and frequency of mixed histology with benign teratoma elements. RESULTS: A total of 138 female individuals (11 months to 20 years of age) had primary ovarian tumors. Imaging appearance and pathology information were available for 133 patients. Among the 133 patients, tumor appearance was solid (10.5%), solid with calcification (3.0%), mixed cystic and solid (58.7%), mixed cystic and solid with calcification (24.8%), and unknown (3.0%). In all, 54% had elements of teratoma in addition to malignant histology. CONCLUSION: Mixed cystic and solid appearance with or without calcification was seen in 83.5% of pediatric ovarian malignant germ cell tumors. Associated benign teratoma was common. The presence of a mixed cystic and solid appearance on preoperative imaging should not dissuade the surgeon from obtaining preoperative serum markers and undertaking complete surgical staging.

Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord-Stromal Tumors: A Contemporary Review.

Non-epithelial ovarian tumors are heterogeneous and account for approximately 10% of ovarian malignancies. The most common subtypes of non-epithelial ovarian tumors arise from germ cells or sex cord and stromal cells of the gonads. These tumors are usually detected at an early stage, and management includes surgical staging and debulking. When indicated for advanced disease, most respond to chemotherapy; however, options for patients with refractory disease are limited, and regimens can be associated with significant toxicities, including permanent organ dysfunction, secondary malignancies, and death. Targeted therapies that potentially decrease chemotherapy-related adverse effects and improve outcomes for patients with chemotherapy-refractory disease are needed. Here, we review the molecular landscape of non-epithelial ovarian tumors for the purpose of informing rational clinical trial design. Recent genomic discoveries have uncovered recurring somatic alterations and germline mutations in subtypes of non-epithelial ovarian tumors. Though there is a paucity of efficacy data on targeted therapies, such as kinase inhibitors, antibody-drug conjugates, immunotherapy, and hormonal therapy, exceptional responses to some compounds have been reported. The rarity and complexity of non-epithelial ovarian tumors warrant collaboration and efficient clinical trial design, including high-quality molecular characterization, to guide future efforts.

Fertility-sparing surgery for patients with malignant ovarian germ cell tumors: 10 years of clinical experience from a tertiary referral center.

PURPOSE: To describe a case series of patients with malignant ovarian germ cell tumors (MOGCT) treated exclusively with fertility-sparing surgery (FSS) with or without adjuvant chemotherapy. METHODS: We retrospectively reviewed the records of 27 patients with MOGCT treated in the Department of Obstetrics and Gynecology, University Hospital Center Zagreb, Croatia, between January 2009 and July 2019. RESULTS: The median age at diagnosis was 22 years, and the main symptom was abdominal distension (57.0%). The most prevalent histological subtype was immature teratoma (n = 13, 48.1%). Twenty-three patients (85.2%) had laparotomy and 4 (14.8%) had laparoscopy, without conversions. Lymphadenectomy was performed in 16 (59.3%) patients, with 184 removed lymph nodes, and omentectomy was performed in 19 (70.4%) patients. The rate of chemotherapy administration was 81.5%. The follow-up length ranged between 6.30 and 115.1 months (median: 49.60 months). No patient experienced tumor recurrence. The rate of complete gross resection was 100%. At the time of analysis, all patients were alive and disease free. Fifty percent of patients who actively tried to conceive after FSS became pregnant, with 12 deliveries. CONCLUSION: This study suggests that FSS is a safe treatment option for MOGCT, regardless of tumor stage and histological type.

Outcomes and prognostic factors of patients with recurrent and persistent malignant ovarian germ cell tumors.

OBJECTIVE: Due to the rarity of recurrent and persistent malignant ovarian germ cell tumors (MOGCTs), there is no standardized protocol for salvage therapy. This study aimed to investigate the outcomes and prognostic factors of patients with recurrent and persistent MOGCTs. METHODS: Clinical data for 59 patients with recurrent and persistent MOGCTs admitted to Peking Union Medical College Hospital from January 1, 2000, to April 30, 2018, were retrospectively analyzed. RESULTS: Twenty-one cases (35.6%) were recurrent, and 38 (64.4%) were persistent. Patient age ranged from 1 to 39 years, and disease stage was as follows: 33 stage I, 4 stage II, 21 stage III, and 1 stage IV. There were 19 immature teratomas, 26 yolk sac tumors, 1 dysgerminoma, and 13 mixed germ cell tumors. Regarding the primary surgery, fertility was preserved in 49 patients and not preserved in 10 patients. Among the patients who underwent fertility-preserving primary surgery, 40 had fertility preserved in the second operation, and 9 did not. In the mean follow-up of 52.6 months (range 2-279 months) after recurrence, 19 patients (32.2%) experienced a second relapse, and 16 (27.1%) died. The 5-year survival and progression-free survival rates after relapse were 70.0% and 67.0%, respectively. The optimal salvage surgery and chemotherapy regimen after relapse were independent prognostic factors (P < 0.05). CONCLUSIONS: The prognosis of recurrent and persistent MOGCTs was good after salvage therapy. The optimal salvage surgery and adjuvant standardized chemotherapy significantly impact patient prognosis. For young nulliparous patients, secondary fertility-sparing salvage therapy can be considered.

The impact of lymphadenectomy on prognosis and survival of clinically apparent early-stage malignant ovarian germ cell tumors.

OBJECTIVE: To determine the impact of lymphadenectomy (LND) on survival of clinically apparent early-stage malignant ovarian germ cell tumors (MOGCTs). METHODS: We retrospectively analyzed the survival of patients who were diagnosed with the three most common histopathology types of malignant ovarian germ cell tumors (yolk sac tumor, dysgerminoma and immature teratoma) and with clinical stage I and II disease, and treated at Sun Yat-sen University Cancer Center between 1 January 1970 and 30 September 2018. RESULTS: There were 227 stage I, 28 stage II and one stage IIIA cases after surgery. One hundred and twenty-six patients underwent lymphadenectomy and 130 did not. Only one lymph node metastasis (0.8%) was found in the lymphadenectomy group. Two hundred and twenty-four out of 256 patients (87.5%) received postoperative chemotherapy. There were five relapses (4.0%) in the lymphadenectomy group and four (3.1%) in the non-lymphadenectomy group. Median follow-up was 68 months (range, 1-388). The 10-year disease-free survival rate in the lymphadenectomy group and non-lymphadenectomy group were 88.2 and 96.4%, respectively (P = 0.412); the 10-year overall survival rate in the two groups were 95.7 and 98.2%; respectively (P = 0.798). The results showed that lymphadenectomy did not improve patient survival. CONCLUSIONS: Lymphadenectomy may have little impact on survival in patients with clinically apparent early-stage malignant ovarian germ cell tumors and may be omitted in the surgical treatment.