Extraovarian Dysgerminoma Involving the Uterine Cervix: A Rare Case Report With Literature Review.

Primary extraovarian dysgerminoma (EOD) is a very rare disease. There is no literature about primary EOD involving the uterine cervix. We herein present details of a unique case of primary EOD involving the uterine cervix. A 46-year-old woman with uterine cervical tumor was referred to our institution with atypical genital bleeding. A polypoid tumor localized to the uterine cervix was found. Cervical biopsy detected malignant components of likely nonepithelial cell origin. Preoperative imaging examinations showed a uterine cervical tumor measuring ~5 cm, suggestive of malignancy without distant or lymph node metastases. The patient underwent abdominal radical hysterectomy with pelvic lymph node dissection according to the standard treatment for stage IB3 cervical cancers. The pathological diagnosis was dysgerminoma involving the uterine cervix and the right fallopian tube. Immunohistochemical results were as follows: SALL4 (+), octamer-binding transcription factor 4 (+), D2-40 (+), and c-Kit (+). She received 3 cycles of adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. The disease did not recur up to 14 months after surgery. This is the first-ever published case of primary EOD involving the uterine cervix among previously reported EOD cases. Reported cases of EOD in female genital tract are also reviewed. Our case provides more extensive insights for pathologists to consider the differential diagnosis of cervical lesions. In our case, combination therapy involving a surgical approach-according to cervical cancers and adjuvant chemotherapy as used for ovarian dysgerminomas-was effective. Future verification is needed regarding the best approach for treating uterine cervical dysgerminomas.

Undetectable anti-Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis.

OBJECTIVE: Individuals with 45,X/46,XY or 46,XY gonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti-Müllerian hormone (AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise. DESIGN, PATIENTS AND MEASUREMENTS: Individuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999-2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used. RESULTS: Thirteen males and 16 females were included, 20 with 46,XY and 9 with 45,X/46,XY DSD. Three females had dysgerminoma alongside gonadoblastoma; two gonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre-GCNIS and/or pre-gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non-(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells. CONCLUSIONS: Undetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XY or 46,XY gonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function.

Ovarian dysgerminoma: clues to the radiological diagnosis.

Ovarian dysgerminoma (OD) is a rare germ cell tumor accounting for 1%-2% of all malignant ovarian tumors and is generally associated with a good prognosis. The condition is more frequent in young women and can arise in dysgenetic gonads that contain gonadoblastomas. While the definitive diagnosis of OD is only possible histologically, certain radiological features can provide facilitating clues. A large, unilateral, solid, lobulated ovarian tumor with markedly enhancing septa should raise the suspicion of OD in young women. Serum lactate dehydrogenase is characteristically elevated in this tumor type and can complement its diagnosis and postoperative follow-up; however, it is a nonspecific marker. Moreover, knowing the mimickers of OD is essential to optimizing the radiological image interpretation and allowing for adequate management and timely treatment. Therefore, in this article, the radiological and clinical-pathologic features of ODs were reviewed to allow radiologists to become familiarized with them and narrow the diagnostic possibilities when facing this type of tumor.

Late Diagnosis of Swyer Syndrome in a Patient with Bilateral Germ Cell Tumor Treated with a Contraceptive Due to Primary Amenorrhea.

Swyer syndrome is a special form of DSD (disorders of sex development), so-called pure gonadal dysgenesis with a karyotype 46, XY and a female phenotype. One of the most important problems in patients with DSD is the risk of gonadal tumors. We present a case of a 26-year-old patient with Swyer syndrome. The patient had primary amenorrhea and no puberty characteristics. In ultrasound imaging in the vicinity of the uterus, there were two homogeneous structures. A genetic diagnosis was also performed, which showed karyotype 46, XY. The patient underwent a bilateral gonadectomy. Histopathological examination revealed the presence of dysgerminoma in both dysgenetic gonads. The follow-up of five years now did not show any changes suspected of invasion. We concluded that the primary amenorrhea, along with the absence of development of sexual characteristics, should prompt an expanded diagnosis for disorders of sex development. Gonadal dysgerminoma should be suspected even in the absence of tumor features on ultrasound and blood laboratory tests. Early prophylactic gonadectomy could protect patients from developing tumors in dysgenetic gonads.

Yolk sac tumor and dysgerminoma in the left gonad following gonadoblastoma in the right gonad in a 46,XY DSD with a novel SRY missense mutation: a case report.

BACKGROUND: Approximately 10-15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY DSD caused by a novel missense mutation in the HMG region of SRY rapidly progressing to germ cell tumors (GCTs). CASE PRESENTATION: An adolescent female (15 years old) exhibiting primary amenorrhea was later diagnosed as a 46,XY female with bilateral gonadal dysplasia on the basis of peripheral lymphocyte karyotype 46,XY and a novel missense mutation in SRY (c.281 T > G, p.L94R). The novel missense mutation (c.281 T > G, p.L94R) and its adjacent region were conserved. Protein structure analysis showed that the mutant site was located in the middle of the HMG domain, and the mutant protein had a diminished ability to bind to DNA. Imaging examination revealed an adolescent female with a naive uterus. Laparoscopy and initial pathological examination revealed left gonadal dysplasia and right gonadal dysplasia with gonadoblastoma (GB). Right gonadectomy by laparoscopy was performed upon consent from the patient's parents. Less than 1 year postoperatively, the left gonadal gland deteriorated as observed by the findings of a mass in the left adnexal region by pelvic MRI and serum AFP > 1000 ng/ml by serological tests, and then total hysterectomy and adnexal and left gonadectomy by laparoscopy were performed. The GCT stage was classified as stage Ic according to FIGO. At this time, pathologic examination showed that the left gonad had progressed to yolk sac tumor and dysgerminoma. The patient underwent chemotherapy post-operatively but developed type III myelosuppression and tumor recurrence several months later. CONCLUSIONS: The patient initially presented with right gonadoblastoma but chose only right gonadectomy by laparoscopy to preserve the female sex characteristics, which resulted in rapid deterioration of the left gonad and poor treatment outcomes. This case demonstrates the importance of early genetic diagnosis and treatment of 46,XY female DSD.

Paediatric Ovarian Dysgerminoma: A Case Report.

Dysgerminoma is the most common malignant germ cell tumour of the ovary. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. This is usually detected in youth, before the age of 20 years. Ovarian or adnexal tumours are very rare in patients below the age of 18 years, most of them being functional cysts, only 10% being malignant. Here is a rare case of an 8 years old girl with dysgerminoma who underwent right-sided salpingo-oophorectomy for unilateral involvement with conservation of fertility and now the patient is on chemotherapy as the tumour metastasized to the pre-aortic lymph node. Keywords: case reports; dysgerminoma; metastasis; paediatrics.

Disgerminoma ovariano na gestação: relato de caso / Ovarian dysgerminoma in pregnancy: a case report

Os disgerminomas são tumores malignos de células germinativas ovarianas, são raros, geralmente acometem mulheres em idade fértil e têm bom prognóstico e sobrevida elevada. Paciente de 20 anos, primigesta com 26 semanas de gestação, foi admitida no centro obstétrico da Fundação Hospitalar Santo Antônio em Blumenau- SC com quadro de dor abdominal intensa refratária à analgesia e desconforto respiratório. Ressonância magnética demonstrou derrame pleural, moderada ascite e volumosa lesão expansiva de aspecto sólido-cístico em anexo direito. Foram realizadas salpingo-oforectomia à direita e omentectomia parcial e coletado lavado peritoneal. Anatomopatológico evidenciou disgerminoma. A paciente seguiu acompanhamento gestacional nos serviços de pré-natal de alto risco e oncologia. Devido à imaturidade fetal, manteve-se conduta expectante e, após o parto normal com 37 semanas, foi realizado estadiamento e iniciada quimioterapia adjuvante. Devido à baixa incidência e à raridade de tumores de células malignas ovarianas, relatos de casos como este são importantes para discutir as melhores estratégias de manejo clínico.(AU)

Dysgerminomas are rare malignant ovarian germ cell tumors that generally affect adolescence and early adulthood, have a good prognosis and high survival. Patient 20 years old, gestation 1, at 26 weeks of gestation, was hospitalized at the obstetric center of Fundação Hospitalar Santo Antônio in Blumenau-SC, with severe abdominal pain refractory to analgesia and respiratory discomfort. Magnetic resonance showed pleural effusion, moderate ascites and a massive expansive lesion with a solid cystic aspect in the right ovary. Right salpingoophorectomy, partial omentectomy and peritoneal lavage were collected. Anatomopathological evidence showed dysgerminoma. Patient followed gestational follow-up at high-risk prenatal and oncology services. Due to fetal immaturity, expectant management was maintained and after vaginal delivery at 37 weeks, staging was performed and adjuvant chemotherapy was started. Due to the low incidence and rarity of ovarian malignant cell tumors, case reports such as this one are important to discuss the best clinical management strategies.(AU)

Long-Term Outcomes and Factors Related to the Prognosis of Pure Ovarian Dysgerminoma: A Retrospective Study of 107 Cases.

OBJECTIVE: The aim of this study was to evaluate the long-term outcomes and the factors related to patient prognosis. MATERIALS AND METHODS: We retrospectively analyzed patients treated at the Department of Gynecology, Sun Yat-sen University Cancer Center, between January 1, 1968, and December 12, 2018. RESULTS: A total of 107 patients were identified. Of all patients, 79 (73.8%) presented with stage I disease, 14 (13.1%) stage II, 13 (12.2%) stage III, and 1 (0.9%) stage IV. All patients received surgery, with 70 (65.4%) undergoing fertility-sparing surgery (FS) and 37 (34.6%) nonfertility-sparing surgery (NFS). Ninety patients received postoperative chemotherapy. Nine of the 43 cases with a lymphadenectomy had metastasis (20.9%). The median follow-up time was 132 months (range, 1-536 months). The overall 5-year and 10-year survival was 95.1% and 91.7%, respectively. The 10-year survival rate for stage I and II-IV patients was 96.1% and 79.1%, respectively (p = 0.008). For the patients undergoing FS and NFS, the 10-year disease-free survival rate was 82.3% and 88.0%, respectively (p = 0.403). The 10-year disease-free survival rate for patients with or without lymphadenectomy was 95.1% and 78.4%, respectively (p = 0.040), and it was 92.5% and 76.0%, respectively (p = 0.041), for those with or without omentectomy. Fifteen patients relapsed, and 4 of them (26.7%) had recurrence in the lymph nodes. Eleven of the 15 relapsed patients (73.3%) had been successfully salvaged. LIMITATIONS: As a study of a rare disease, our analysis was limited by its small sample size and the deemed disadvantage of a retrospective study. CONCLUSION: Excellent treatment results can be achieved in dysgerminoma patients who received proper treatment. Lymphadenectomy may improve patient survival. Relapsed patients can also be successfully salvaged.

Ovarian dysgerminoma with pseudo-Meigs syndrome: A case report.

RATIONALE: Dysgerminoma is a rare malignant tumor of the ovary, more frequently occurring in young women. The main signs of pseudo-Meigs syndrome (PMS) are ascites and hydrothorax accompanying benign or malignant ovarian tumors (no fibroma or fibroma-like tumor). PATIENT CONCERNS: A 19-year-old woman with fever and chest tightness for 2 days. DIAGNOSES: Pectoral-abdominal computed tomography (CT) scan and contrast-enhanced magnetic resonance imaging revealed a large amount of right pleural effusion, a small amount of ascites, and a huge abdominopelvic mass measuring about 29.2cm × 11.8cm × 8.4 cm in the left ovary. The result of hydrothorax examination was consistent with the diagnosis of exudative pleural effusion. In addition, Rivalta-test showed a positive result and lactate dehydrogenase was elevated. The histopathological diagnosis was a giant germ cell tumor, which was consistent with dysgerminoma in terms of both morphology and immunophenotype. Based on these findings, a diagnosis of malignant ovarian neoplasm with PMS was made. INTERVENTIONS: Surgical resection of the tumor was performed. OUTCOMES: The patient recovered well after operation, and the pleural effusion and abdominal ascites vanished. No recurrence was observed during the 1-year follow-up period. LESSONS: Ovarian dysgerminoma with PMS is a rare malignant tumor of the ovary, which often occurs in young women. It should be considered in differential diagnosis of patients with a pelvic mass, ascites and pleural effusion. Early diagnosis and surgical treatment are beneficial to prolonged survival.

Swyer Syndrome: A Case of Dysgerminoma Solely within the Fallopian Tube.

BACKGROUND: 46XY pure gonadal dysgenesis (Swyer syndrome) is a rare disorder of sexual development. Patients have a 46XY karyotype, though phenotypically they appear female with normal external genitalia and vagina. Although patients exhibit normal Müllerian structures (uterus, fallopian tubes, and vagina), they possess a pair of bilateral undifferentiated gonad streaks. Delayed puberty and primary amenorrhea are the common presentations. There is an increased risk of developing tumors in the gonads and therefore a bilateral gonadectomy is recommended. CASE: A 16-year-old girl who presented with primary amenorrhea was diagnosed with Swyer syndrome. She underwent prophylactic bilateral gonadectomy and salpingectomies. She was discovered to have no gonadal malignancy, conversely dysgerminoma solely within the fallopian tube. SUMMARY AND CONCLUSION: Both bilateral salpingectomies and bilateral gonadectomies should be recommended as the operation of choice in patients with Swyer Syndrome.

Ovarian dysgerminoma in pregnancy: A case report.

RATIONALE: Although dysgerminomas are relatively uncommon among all ovarian neoplasms, representing for only about 2%, they account for 32.8 percent of malignant ovarian germ cell tumors. Their association with pregnancy is extremely rare; due to the low frequency of occurrence, there are few recommendations regarding pregnancy management; therefore, it is important to discuss and summarize the treatment strategy. PATIENT CONCERNS: We present the case of a 25 years patient, gestation 1, para 1, who was hospitalized in the clinic at 38/39 weeks of gestation at the beginning of labor. Following the ultrasound examination, a hypoechogenic lesion on the uterine fundus was found, suggestive of subterranean fibroid. After caesarean section, right adnexectomy was performed; the histopathological examination revealed, unexpectedly, the diagnosis of dysgerminoma. DIAGNOSES: Dysgerminoma as associated with pregnancy. INTERVENTIONS: Birth by Caesarean section and right adnexectomy. No other medical complications occurred. OUTCOMES: The histopathological and immunohistochemical examinations were consistent with the pure dysgerminoma. Oncology was staged AI, with the monitoring of markers and abdominal and pelvic magnetic resonance imaging at 3, 6, 9, and 12 months. LESSONS: Dysgerminoma is the most common ovarian malignancy associated with pregnancy with a good fetal maternal outcome. If these tumors are discovered accidentally during caesarean section, tumor markers and magnetic resonance imaging scanning should be done postoperatively to plan optimal treatment.

Ovarian Dysgerminoma: A Tertiary Center Experience.

Purpose: The aim of this study is to evaluate the oncologic outcome in patients with pure ovarian dysgerminomas treated and followed-up in our hospital. Methods: This study included 18 ovarian dysgerminoma patients with unilateral and/or bilateral salpingo-oophorectomy (BSO) ± hysterectomy+omentectomy+bilateral pelvic ± para-aortic lymphadenectomy+peritoneal cytologic sampling. Results: Four (22%) patients underwent definitive surgery, including type I hysterectomy and BSO. Only one of the remaining 14 patients underwent BSO because of bilateral streak gonad presence during intraoperative examination. Thirteen patients (72%) had conservative surgeries. In addition, staging surgeries were performed to all patients except for one patient with 16 weeks of pregnancy (patient #3) in the study group. Retroperitoneal lymphadenectomy was part of the staging procedure except for this pregnant patient. Lymph node metastasis was positive in four (22%) patients. Three (16%) patients recurred and none of them died because of disease during follow-up period. Two of the relapsed patients were treated with combination of surgery and chemotherapy, whereas the third patient received only chemotherapy for treatment. Conclusions: Fertility sparing surgery should be the choice of treatment in patients with pure ovarian dysgerminoma. In addition, staging surgery, including retroperitoneal lymph node dissection is obligatory for determining stage IA patients who are exempt from adjuvant chemotherapy. Close surveillance policy enables early detection of patients with recurrences in whom salvage therapy is highly curable.

Extraovarian dysgerminoma in a pregnant woman: an extremely rare finding.

Extraovarian germ cell tumors are very rare and their occurrence during pregnancy is exceptional. In this case report an abdominal mass was shown by ultrasonography, during a routine monitoring of a 26-year-old pregnant woman. The patient was left under radiological control in the following months in order to bring the pregnancy to term. A few months after the delivery, the patient underwent surgery and a diagnosis of extraovarian (abdominal) dysgerminoma was made. To the best of our knowledge, there are only 3 other case reports describing an extra-gonadal dysgerminoma occurring during pregnancy. The aim of this study was to report an extremely rare tumor, whose management can be challenging first because this neoplasm has some differences from its ovarian and testicular counterparts. Furthermore, the occurrence during pregnancy makes the multidisciplinary approach mandatory since 3 distinct but not independent entities are involved (tumor, mother and fetus).

Ovarian masses in children and adolescents: Analysis on 146 patients.

PURPOSE: Ovarian masses in pediatric population are the most common genital neoplasms, and these masses are often benign. The purpose of this study is to evaluate the pediatric ovarian masses operated in our hospital. METHOD: The records of patients, under the age of 18 who were operated in our hospital due to ovarian mass between 2012 and 2018 were reviewed retrospectively. Clinical findings, operational procedures, histopathologies, tumor markers and radiological images were evaluated. FINDINGS: During the study, 146 patients (5 patients were bilateral) were evaluated. The average age of the study patients was 14.01 ± 4.02 years. 107 of the study patients were benign, 37 were malignant and 2 were borderline. The most common symptom in benign masses was tenderness in lower abdominal (75.7 %). 124 of the patients (86.1 %) were in post-menarche period. 34 of the patients had ovarian torsion. Open surgery was conducted on 79.5 % (116/146) of the patients, and laparoscopic surgery was conducted on 20.5 % (30/146). The rate of oophorectomy was 24.6 % (36/146) throughout the operations. The most frequently conducted surgical procedure was cyst excision in benign masses and oophorectomy in malignant masses. In neoplastic masses, the ratio of pelvic mass palpation; and in non-neoplastic masses, lower abdominal tenderness was more apparent. The rate of ovarian torsion was 23.6 % (25/107) in benign masses and 24.3 % (9/37) in malignant masses. OUTCOMES: Pediatric and adolescent ovarian masses are mostly benign and majority of these occur at post-menarche period. The most common symptom was pelvic tenderness in benign masses, and palpable pelvic masses in malignant masses. For future fertility and low incidence of malignancy in these patients, ovarian preserving surgery should be considered for the first operation.

Pregnancy with giant ovarian dysgerminoma: A case report and literature review.

RATIONALE: Dysgerminoma is an extraordinarily rare neoplasm arising from the malignant germ cells of the ovary. Early antenatal diagnosis and proper management of the neoplasm to improve maternal-neonatal results are the considerable challenges facing the gyne-oncologist. We summarize the clinical features and discuss treatment strategies of the ovary dysgerminoma (OD). Besides, we also review the literature on OD in PubMed, Web of Science Core Collection, Library of Congress, and LISTA from 1939 to 2019 to evaluate its clinical characteristics, feto-maternal compromise, management, and fertility outcome. PATIENT CONCERNS: A 25-year-old pregnant woman reported lower abdominal pain and vomiting. DIAGNOSIS: The patient was diagnosed as right OD. INTERVENTIONS: She received a cesarean section due to severe abdominal pain, delivered a healthy girl at 38 C 4 weeks of gestation, and accepted fertility-preserving surgery. However, the patient refused chemotherapy postoperatively. OUTCOMES: The patient was followed up 42 days, 3 months, and 6 months after surgery, and no tumor recurrence was observed. LESSONS: OD has non-specificity characteristics, including age, symptoms, image date, and tumor marks. However, these abnormal indicators may provide some evidence for accurate antenatal diagnosis. The management strategies should be considered comprehensively on an individual basis, and fertility-preserving surgery should be carried out in the second trimester if further pregnancy is desired. Adjuvant chemotherapy needs to be applied to the treatment of OD patients with The International Federation of Gynecology and Obstetrics (FIGO) stages II, III, and IV and timely chemotherapy is suggested if there are several weeks before the expected date of delivery. The overall prognosis of OD patients is excellent.

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.

46, XY complete gonadal dysgenesis with pubertal virilisation due to dysgerminoma/gonadoblastoma.

Complete gonadal dysgenesis (CGD) or Swyer syndrome is characterised by sexual infantilism in a phenotypic female with 46, XY karyotype. Patients with gonadal dysgenesis and Y-chromosome material are at a high risk of developing gonadoblastoma and dysgerminoma. A 16-year-old girl presented with progressive virilisation, poor breast development and primary amenorrhea. On evaluation, she was found to have male-range serum testosterone, large abdominopelvic mass lesion, elevated germ cell tumour markers and 46, XY karyotype. She underwent surgical excision of left gonadal mass and right streak gonad, histopathology of which revealed dysgerminoma and gonadoblastoma, respectively. A diagnosis of virilising germ cell tumour arising in the setting of 46, XY CGD was, therefore, made. This case highlights a rare presentation of 46, XY CGD and the need to consider early prophylactic gonadectomy in patients affected with this rare condition. The presence of dysgerminoma/gonadoblastoma should be suspected if a hitherto phenotypic female with CGD undergoes virilisation.