A Perplexing Case of a Germ Cell Tumor: A Case Report.

Germ cell tumors (GCTs) are associated with pure gonadal dysgenesis or Swyer syndrome. Swyer syndrome usually presents with primary amenorrhea, streak ovaries, and mixed GCT. However, our patient presented with secondary amenorrhea, normal female external genitalia, and a mixed GCT. Constitutional karyotype was suggestive of 46,XY. Management comprised chemotherapy, followed by surgery. Histopathology was suggestive of dysgerminoma complicating a gonadoblastoma. The purpose of reporting this case is its rarity and the importance of diagnosing an XY karyotype, as the incidence of GCTs is higher in these patients.

Dysfunctional labor and hemoperitoneum secondary to an incidentally discovered dysgerminoma: a case report.

BACKGROUND: Ovarian dysgerminoma, a subtype of malignant germ cell tumor (GCT), is a rare ovarian neoplasm that is infrequently found in the gravid patient. When dysgerminomas do occur in pregnancy, the rapidly growing tumors can have a heterogeneous presentation and lead to peripartum complications and morbidity. Due to the rarity of this condition, diagnostic and therapeutic strategies are not well described in the literature. CASE PRESENTATION: A healthy multigravida with an uncomplicated antenatal history presented for elective induction of labor. She had a protracted labor course, persistently abnormal cervical examinations, and eventually developed a worsening Category II tracing that prompted cesarean birth. Intraoperatively, a 26 cm pelvic mass later identified as a Stage IA dysgerminoma was discovered along with a massive hemoperitoneum. The mass was successfully resected, and the patient remains without recurrence 6 months postoperatively. CONCLUSION: Although rare and generally indolent, dysgerminomas can grow rapidly and cause mechanical obstruction of labor and other complications in pregnancy. Pelvic masses, including malignant neoplasms, should be included in as part of a broad differential diagnosis when evaluating even routine intrapartum complications such as abnormal labor progression. Additionally, we demonstrate that adnexal masses can be a source of life-threatening intraabdominal hemorrhage.

Need for risk-adapted therapy for malignant ovarian germ cell tumors: A large multicenter analysis of germ cell tumors' patients from French TMRG network.

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.

Two Cases of Hypercalcemia in Pediatric Ovarian Dysgerminoma.

OBJECTIVE: To discuss the finding of hypercalcemia in pediatric ovarian dysgerminoma. METHODS: Two cases of pediatric ovarian dysgerminoma that presented with hypercalcemia are discussed. RESULTS: Hypercalcemia is a rare finding in ovarian dysgerminoma. CONCLUSION: Ovarian dysgerminoma should be considered in pediatric patients presenting with signs of hypercalcemia. Parathyroid hormone, parathyroid hormone related protein, and 1,25 dihydroxyvitamin D may elucidate the cause of hypercalcemia.

Outcome of Metastatic and Recurrent Ovarian Dysgerminoma Using Radiation Therapy and Chemotherapy in a Dog.

An 8 yr old female spayed poodle/terrier mixed-breed dog was referred for evaluation of a recurrent and metastatic ovarian dysgerminoma. A total dose of 20Gy was administered to both the mediastinal metastatic lesion and retroperitoneal recurrent dysgerminoma in five daily fractions of 4Gy. Acute side effects were mild and self-limiting. This was followed by several courses of chemotherapy using a variety of agents. Despite extensive disease, this patient was still alive at the time of publication, 524 days after presentation and 501 days following completion of radiation. This case report demonstrates tolerability and efficacy of palliative radiation and chemotherapy for this rare tumor type.

Conundrums in the management of malignant ovarian germ cell tumors: Toward lessening acute morbidity and late effects of treatment.

One of the most extraordinary stories in the chronicles of gynecologic cancers has been that of malignant ovarian germ cell tumors. Prior to the mid-1960s, most patients died of disease. Fifty years later, most survive. Precisely because high cure rates are achievable, the concentration over the past decade has been on minimizing toxicity and late effects. The present review focuses on five areas of interest related to the management of malignant ovarian germ cell tumors that highlight the different therapeutic strategies practiced by pediatric and gynecologic oncologists: 1) primary surgery, 2) surgery alone (surveillance) for patients with FIGO stage IA disease, 3) postoperative management of FIGO stage IC-III disease, 4) postoperative management of pure immature teratoma, and 5) postoperative management of metastatic pure dysgerminoma. All of these topics share a common overarching theme: Lessening acute morbidity and late effects of treatment.

Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays.

UNLABELLED: Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). MATERIALS AND METHODS: A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. RESULTS: The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. CONCLUSIONS: OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapy for OC in the future.

Characterization of common marmoset dysgerminoma-like tumor induced by the lentiviral expression of reprogramming factors.

Recent generation of induced pluripotent stem (iPSCs) has made a significant impact on the field of human regenerative medicine. Prior to the clinical application of iPSCs, testing of their safety and usefulness must be carried out using reliable animal models of various diseases. In order to generate iPSCs from common marmoset (CM; Callithrix jacchus), one of the most useful experimental animals, we have lentivirally transduced reprogramming factors, including POU5F1 (also known as OCT3/4), SOX2, KLF4, and c-MYC into CM fibroblasts. The cells formed round colonies expressing embryonic stem cell markers, however, they showed an abnormal karyotype denoted as 46, X, del(4q), +mar, and formed human dysgerminoma-like tumors in SCID mice, indicating that the transduction of reprogramming factors caused unexpected tumorigenesis of CM cells. Moreover, CM dysgerminoma-like tumors were highly sensitive to DNA-damaging agents, irradiation, and fibroblast growth factor receptor inhibitor, and their growth was dependent on c-MYC expression. These results indicate that DNA-damaging agents, irradiation, fibroblast growth factor receptor inhibitor, and c-MYC-targeted therapies might represent effective treatment strategies for unexpected tumors in patients receiving iPSC-based therapy.

[Malignant ovarian germ cell tumors. Current status of diagnosis and treatment]. / Tumores malignos de células germinales del ovario. Estado actual de su diagnóstico y tratamiento.

Malignant ovarian germ cell tumors (MOGCT) are extremely aggressive and rapidly growing neoplasms, with a peak incidence occurring in adolescent girls and young women. Its incidence in Mexico is three times higher than the observed in Western countries and the United States. Dysgerminoma, immature teratoma, yolk salc tumor, and mixed germ cell tumors make up more than 90% of all MOGCT.

Pediatric ovarian dysgerminoma presenting with hypercalcemia and chronic constipation: a case report.

Malignancy-associated hypercalcemia is a common finding among adult malignancies. However, the incidence of malignancy-induced hypercalcemia associated with germ cell tumor among pediatric patients is very rare. We describe a 9-year-old girl with an ovarian dysgerminoma presenting with chronic constipation and hypercalcemia. We review some of the causes of malignancy-associated hypercalcemia described in literature and treatment strategies. We also recommend considering oncological processes in the presence of hypercalcemia.

Characteristics of diagnosis and therapy of adolescent malignant ovarian tumors.

BACKGROUND: To improve the early diagnosis rate of adolescent malignant ovarian tumors, avoid misdiagnosis, select proper therapy, avoid excessive therapy, and render therapy more tolerable. MATERIALS AND METHODS: A comprehensive review of adolescent malignant ovarian tumors, such as types, difficulties of early diagnosis, therapeutic principles, prognosis, fertility preserving through the authors' clinical experience, with reference to Chinese and international literatures. RESULTS AND CONCLUSION: The majority of adolescent malignant tumors are malignant germ cell, the malignancy is high and it is difficult to diagnose in the early stage, likely to be ignored. Their diagnosis is therefore fundamental, while selecting the most appropriate therapeutic approach that also considers fertility-sparing without compromising prognosis and avoiding over-treatment.

[Dysgerminoma of the ovary. Presentation of case report].

Germ-cell tumors account for about 20% of all ovarian tumors and the dysgerminoma is the most common in this group. The treatment is surgical, followed by chemotherapy and radiotherapy in greater stage than IA. The aim of this article is to present a case report of 18-years-old patient with a left ovary dysgerminoma who had undergone a surgery--left-side ovariectomy. One year later when the patient was pregnant in 6 m.l., retroperitoneal recurrence was diagnosed by ultrasound examination. The patient has completed her pregnancy and delivered by caesarean section. Retroperitoneal recurrence of the same tumor, inoperable at this stage was histologically confirmed during the operation. The treatment continued with two courses of neoadjuvant chemotherapy followed by radical surgery with removal of the whole left kidney and the tumor. After that 2 courses of adjuvant chemotherapy were conducted, followed by prophylactic external beam radiotherapy for retroperitoneal lymph nodes. No data for local recurrences and distant metastases were found during the regular examinations, performed 2 years later. The treatment of dysgerminoma is discussed. This treatment must be complex one and should include radical surgery, chemotherapy and radiotherapy.

Molecular genetic analysis of bilateral ovarian germ cell tumors.

BACKGROUND: Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous with regard to their clinical and histologic appearance. The risk of tumor development is higher in children with aberrant sexual differentiation. Development of gonadoblastomas is seen in young women with 46,XY gonadal dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs, mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically inapparent patients for sex chromosomal aberrations. PATIENTS AND METHODS: We analyzed tumor samples of 15 patients with synchronous bilateral oGCTs enrolled onto the consecutive MAKEI trials for non-testicular GCTs. Paraffin embedded samples from the Kiel German Childhood Tumor Registry were evaluated for the presence of Y-chromosomal sequences. Molecular genetic techniques included comparative genomic hybridization, polymerase chain reaction, and fluorescence in situ hybridization. RESULTS: Among 15 patients with bilateral oGCTs, Y-chromosomal DNA sequences were detected in 6 tumors. Both mature teratomas were negative for Y-chromosomal DNA. Thus, 5 of 12 malignant oGCTs and 1 immature teratoma (with elevated AFP) showed Y-chromosomal material. A 45(X,0) karyotype could not be demonstrated. CONCLUSIONS: These investigations provide additional insight into the development of oGCTs: mature teratomas, which develop from postmeiotic germ cells, are not associated with gonadal dysgenesis. Bilateral immature teratomas, dysgerminomas and mixed malignant oGCTs may frequently show Y-chromosomal DNA, indicating underlying but clinically inapparent gonadal dysgenesis. Thus, the presence of aberrant Y-chromosomal sequences appears to be involved in tumor development in about half of these patients.

Bilateral dysgerminoma in a patient with a previous diagnosis of Swyer syndrome.

A 16-year-old girl was referred to our center by her general physician because of primary amenorrhea. Her family history revealed an older sister with Swyer syndrome and gonadectomy at another institution. After thorough evaluation she received the same diagnosis, but unlike her sister, she refused gonadectomy. Four years later she presented with abdominal discomfort and a complex pelvic mass. She underwent exploratory laparotomy and histological examination revealed bilateral dysgerminoma without capsular invasion. The tumor was classified as stage IB. After surgery she underwent adjuvant chemotherapy with three cycles of BEP (bleomycin + etoposide + cisplatin). The present case emphasizes the importance of familial screening with a karyotype study in pure gonadal dysgenesis to prevent gonadal malignancy.

Primary retroperitoneal dysgerminoma presenting as an adrenal tumor: a case report and literature review.

Primary extragonadal germ cell tumors are rare and mostly occur in young men with predominance of nonseminomatous histology. We report an undescribed case of primary retroperitoneal dysgerminoma presenting as an adrenal tumor in a 17-year-old girl. Surgery was performed on a 10 × 9.5 cm sized adrenal gland tumor and the resected tumor showed unequivocal histological features of dysgerminoma. The diagnosis was confirmed by the tumor's germ cell immunophenotype. Postoperative ultrasonography, CT and PET over a 6-month period revealed no evidence of ovarian lesion. The patient is stable, but with a suspicious residual tumor after adjuvant chemotherapy.

Swyer syndrome, 46,XY gonadal dysgenesis, a sex reversal disorder with dysgerminoma: a case report and literature review.

BACKGROUND: Swyer syndrome, 46,XY gonadal dysgenesis, is a sex reversal disorder with a female phenotype. Germ cell tumors, including dysgerminoma, may arise in streak gonads of patients with gonadal dysgenesis. CASE: A 22-year-old female patient with a 46,XY karyotype was admitted to hospital for primary amenorrhea and a pelvic mass. Laparotomy exploration revealed a hypoplastic uterus and a 80 x 70 x 60 mm mass in the right gonad with extension to the pelvic peritoneum. Histologic finding in frozen section was dysgerminoma. Debulking surgery with pelvic lymphadenectomy was subsequently performed and the patient was given four cycles of chemotherapy (bleomycin, etoposide, and cisplatin) post-operation. CONCLUSION: The presence of Y chromosome in patients with 46,XY gonadal dysgenesis may increase the risk of gonadal tumors. A prophylactic bilateral salpingo-gonadenectomy should be advised to those patients.

[Malignant ovarian germ cell tumors--clinical characteristics and analysis of outcomes]. / Zlosliwe guzy germinalne jajnika--charakterystyka grupy chorych i analiza wyników leczenia.

OBJECTIVES: Presentation of a group of patients with diagnosed malignant ovarian germ cell tumors (MOGCT), determination of prognostic factors and outcome analysis. MATERIAL AND METHODS: We selected patients with diagnosed malignant ovarian germ cell tumors from the patient registry of Cancer Center in Warsaw from 1990 to 2001. We analyzed clinical and pathological features of the study group, as well as methods and results of treatment. RESULTS: We collected documentation of 83 patients. Most were diagnosed with dysgerminoma and immature teratoma in the early stages of development. 73 patients received adjuvant chemotherapy after surgery At the end of the first line of treatment complete response was achieved in 63 patients (75.9%). Time to recurrence ranged from 25 to 518 days (mean 176 days). The most common site of recurrence was the true pelvis. The five-year overall survival was 62.7%. Significant favorable prognostic factor was early stage of disease and the histological diagnosis of dysgerminoma. From the 46 women after fertility-sparing surgery, 8 became pregnant. CONCLUSIONS: MOGCT are a group of potentially curable, yet very aggressive malignant ovarian tumors. The main condition for obtaining good results is quick diagnosis and appropriate treatment, usually surgery associated with multidrug chemotherapy The stage of the disease remains the most important prognostic factor. Patients diagnosed with dysgerminoma are a separate group with very good prognosis.

A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours.

Little evidence is available regarding the prognosis of dogs with malignant ovarian tumours. The objective of this retrospective study was to describe the outcomes and determine the prognostic factors for dogs with malignant ovarian tumours following treatment, including surgery with or without adjuvant therapy. Eighteen dogs were studied, their median age was 12 years (range: 7-15 years), and their median body weight was 6.9 kg (range: 2.3-17.8 kg). Following histopathologic diagnoses revealed that granulosa cell tumour was the most common type (n = 9), followed by dysgerminoma (n = 5), and adenocarcinoma (n = 4). Eleven dogs had surgery alone. Seven dogs had surgery with adjuvant therapy, including chemotherapy and/or radiotherapy. The median survival time (ST) was 1009 days when only deaths owing to the ovarian tumours were considered, and predictors of median ST were T-category (≥ T3, 443 days vs ≤ T2, 1474 days; P = .002), presence of metastatic disease (present, 391 days vs absent, 1474 days; P < .001) and lymphovascular space invasion (present, 428 days vs absent, 1474 days; P = .003) in a univariate analysis. Median ST in dogs with granulosa cell tumour seemed longer than in dogs with dysgerminoma and adenocarcinoma, although the difference was statistically insignificant (1474 days vs 458 days, respectively; P = .10). Considering the good prognosis, aggressive treatment can be recommended for dogs with malignant ovarian tumours, especially early-stage cases. Despite metastasis being present at diagnosis, half of the dogs with metastasis survived for more than 1 year.

Pure dysgerminoma of the ovary 35 years on: a single institutional experience.

OBJECTIVE: The aim of this study was to evaluate clinicopathologic characteristics, long-term outcome and reproductive function in women diagnosed with pure dysgerminoma of the ovary. METHODS: Sixty-five women with stage IA to IIIC pure ovarian dysgerminoma were identified and included in this retrospective study. Patients were treated at one institution between 1970 and 2005. RESULTS: Median age at diagnosis was 22.2 years (range 8.2-64.1 years). 72.3% of patients presented with stage I, 4.6% stage II and 21.5% stage III disease (1.5% stage unknown). Initial management was surgical for all patients: unilateral oophorectomy in 47 patients (72.2%), bilateral oophorectomy +/- hysterectomy in 14 (21.5%) and cystectomy alone in 3 (4.6%). Seventeen patients received chemotherapy (15 adjuvant, 2 for residual disease), 20 received adjuvant radiotherapy and one patient received both. Recurrence occurred in 6 (9.2%) patients (5 stage IA, 1 stage IIA). All recurrences occurred within 19 months of primary diagnosis. All patients were successfully salvaged with radiotherapy (2 patients), chemotherapy (1 patient) or a combination of surgery and chemotherapy (3 patients). Overall, median follow up from time of recurrence was 22.5 years (range 9.3-31.4 years). Median follow-up of all patients was 10.5 years (range 1.1-31.9 years). Fifteen patients reported an attempt to conceive posttreatment resulting in 12 pregnancies and 12 live births in 8 women. CONCLUSION: The long-term outcome of patients with pure ovarian dysgerminoma is excellent. Recurrences occur within 2 years of diagnosis and are treatable. Patients can be treated with fertility-sparing surgery and can expect good reproductive outcomes.

Successful pregnancy outcome after fertility-sparing surgery and chemotherapy for dysgerminoma.

Ovarian dysgerminoma is a rare malignancy of the ovary. This is a case report of a 30-year-old female, presenting with a huge ovarian mass along with multiple gallstones; she was treated by fertility-sparing excision of the mass and cholecystectomy, followed by chemotherapy. She later had an uneventful pregnancy and delivered a healthy baby.