Review on Sertoli-Leydig Cell Tumours of the Ovary.

Sertoli-Leydig cell tumours (SLCTs) represent a subset of mixed sex cord-stromal tumours (SCSTs), a rare form of non-epithelial ovarian tumours comprising less than 7% of malignant cases. Among other types of SCSTs, SLCTs are one of the more prevalent types observed in young adults. SLCTs are classified into 5 histologic categories based on differentiation levels and histological variants. Diverse chromosomal and genetic mutations have been identified in SLCTs, with the most well-studied being the genetic mutations observed in the Dicer 1, Ribonuclease III (DICER1) and the Forkhead Box L2 (FOXL2) genes. These mutations have important clinical implications and their mechanisms are discussed. Particularly, this review emphasizes the correlation between tumour differentiation, mutation status and virilization. Current common methods and difficulties in the clinical diagnosis of SLCTs are also considered, and the usefulness of immunohistochemistry is highlighted. Patient stratification for treatment is done according to the patient's age, stage of disease and prognostic factors. The gold standard of treatment is surgical resection and adjuvant chemotherapy is administered based on the risk of recurrence. The management of recurrence remains a major challenge. Apart from recurrence, there is also a risk of the development of a metachronous tumour, especially in patients with DICER1 syndrome. Hence, the diagnosis of a SLCT has important implications for genetic testing and patient surveillance even if the management of the tumour is successful. This scoping review serves to consolidate current knowledge on SLCTs and advocates for future research advancements to refine diagnosis, management, and prognosis.

Sertoli-Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort.

INTRODUCTION: Sertoli-Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli-Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants. METHODS: In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli-Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan-Meier analysis followed by a log rank test for differences between variables RESULTS: 41 women with Sertoli-Leydig cell tumors were identified. Median age was 41 years (range 6-79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I-II) and 0% in advanced tumor stages (stages III-IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli-Leydig cell tumor. CONCLUSION: The prognosis for women with Sertoli-Leydig cell tumors with localized disease is excellent. Women with advanced stages (III-IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli-Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.

Pediatric ovarian Sertoli-Leydig cell tumors with heterologous rhabdomyosarcoma elements: Clinical case series and review of the literature.

Sertoli-Leydig cell tumors (SLCTs) are rare ovarian neoplasms in pediatric patients. More exceedingly rare are SLCTs that also contain heterologous rhabdomyosarcoma (RMS) elements. For these patients, there is no standardized treatment. We report four cases of pediatric SLCT with heterologous RMS elements that were successfully treated with surgical resection and adjuvant chemotherapy. All four patients are alive and remain in remission.

Sertoli-Leydig cell tumor in two siblings with DICER1 syndrome: A case report and literature review.

RATIONALE: DICER1 syndrome is an autosomal-dominant tumor predisposition syndrome associated with numerous cancerous and noncancerous conditions. The most common sex cord-stromal tumor associated with DICER1 syndrome is Sertoli-Leydig cell tumor of the ovary (SLCT), which is extremely unusual and accounts for < 0.5% of all ovarian neoplasms. SLCT predominantly affects adolescents and young female adults. To date, there are only a few case reports of ovarian SLCT with underlying germline DICER1 mutations. The diagnosis and treatment of this rare malignancy remains challenging in the clinic mainly due to its rarity and varied presentation. PATIENT CONCERNS: A 21-year-old Chinese girl (proband) was admitted in hospital for experiencing a lower abdominal pain and irregular vaginal bleeding for half a year. She was initially diagnosed with abdominal cavity mass prior to surgical operation. The other 20-year-old patient is the younger sister of the proband, who was diagnosed with ovarian cysts and had irregular menstruation and amenorrhea for 4 months. The elder sister underwent an uncomplicated bilateral ovarian tumor resection. Given a high degree of malignancy, comprehensive staged fertility-preserving surgery, including left adnexectomy, omentectomy, pelvic, and para-aortic lymphadenectomy, was performed. Since the other patient requested to maintain her fertility, tumor resection was only conducted in the right ovary. DIAGNOSES: The elder sister was diagnosed as poorly differentiated SLCT accompanied with heterologous stage IC rhabdomyosarcoma (RMS) based on its typical pathology features and molecular characteristics from immunohistochemistry (IHC) staining. The younger sister was diagnosed as poorly differentiated SLCT. Targeted next-generation sequencing (NGS) detected DICER1 mutation in the plasma samples and postoperative tumor tissues of both patients. INTERVENTIONS: Both patients underwent surgical tumor resection, followed by combination chemotherapy with bleomycin, etoposide, and cisplatin for 4 cycles. OUTCOMES: Patients received the above clinical interventions but eventually died from disease recurrence. The elder sister died from disease relapse after one and a half years postsurgery. The younger sister had a relapse of the disease 1 year later, but she refused the comprehensive staged surgery and died from disease relapse quickly. LESSONS: Ovarian SLCT patients with DICER1 mutations and a family history have a high degree of malignancy and are associated with a poor prognosis. With ongoing research efforts on DICER1 mutations, genetic screening and counselling on a regular basis is recommended for predicting potential future cancer risk of individuals with DICER1 syndrome family history.

Ovarian Sertoli-Leydig Cell Tumors: Epidemiological, Clinical and Prognostic Factors.

OBJECTIVE: To describe a series of cases of ovarian Sertoli-Leydig cell tumors (SLCTs). METHODS: Retrospective review of 12 cases of SLCT treated at the Hospital do Câncer de Barretos, Barretos, state of São Paulo, Brazil, between October 2009 and August 2017. RESULTS: The median age of the patients was 31 years old (15-71 years old). A total of 9 patients (75.0%) presented symptoms: 8 (66.7%) presented with abdominal pain, 5 (41.7%) presented with abdominal enlargement, 2 (16.7%) presented with virilizing signs, 2 (16.7%) presented with abnormal uterine bleeding, 1 (8.3%) presented with dyspareunia, and 1 (8.3%) presented with weight loss. The median preoperative lactate dehydrogenase (LDH) was 504.5 U/L (138-569 U/L), alpha-fetoprotein (AFP) was 2.0 ng/ml (1.1-11.3 ng/ml), human chorionic gonadotropin (ß-hCG) was 0.6 mUI/ml (0.0-2.3 mUI/ml), carcinoembryonic antigen (CEA) was 0.9 ng/ml (0.7-3.4 ng/ml), and cancer antigen 125 (CA-125) was 26.0 U/ml (19.1-147.0 U/ml). All of the tumors were unilateral and surgically treated. Lymphadenectomy was performed in 3 (25.0%) patients, but none of the three patients submitted to lymphadenectomy presented lymph node involvement. In the anatomopathological exam, 1 (8.3%) tumor was well-differentiated, 8 (66.7%) were moderately differentiated, and 3 (25.0%) were poorly differentiated. A total of 5 (55.6%) tumors were solid-cystic, 2 (22.2%) were purely cystic, 1 (11.1%) was cystic with vegetations, and 1 (11.1%) was purely solid, but for 3 patients this information was not available. The median lesion size was 14.2 cm (3.2-23.5 cm). All of the tumors were at stage IA of the 2014 classification of the International Federation of Gynecology and Obstetrics (FIGO). A total of 2 (16.7%) patients received adjuvant treatment; 1 of them underwent 3 cycles of paclitaxel and carboplatin every 21 days, and the other underwent 4 cycles of ifosfamide, cisplatin and etoposide every 21 days. None of all of the patients had recurrence, and one death related to complications after surgical staging occurred. CONCLUSION: Abdominal pain was the most frequent presentation. There was no ultrasonographic pattern. All of the SLCTs were at stage IA, and most of them were moderately differentiated. Relapses did not occur, but one death related to the surgical staging occurred.

OBJETIVO: Descrever uma série de casos de tumores de células de Sertoli-Leydig (TCSLs) ovarianos. MéTODOS: Revisão retrospectiva de 12 casos de TCSL tratados no Hospital de Câncer de Barretos entre outubro de 2009 e agosto de 2017. RESULTADOS: A mediana de idade foi 31 anos (15­71 anos). Um total de 9 pacientes (75,0%) apresentaram sintomas: 8 (66,7%) apresentaram dor abdominal, 5 (41,7%) apresentaram aumento abdominal, 2 (16,7%) apresentaram virilização, 2 (16,7%) apresentaram sangramento uterino anormal, 1 (8,3%) apresentou dispareunia, e 1 (8,3%) apresentou emagrecimento. A mediana de desidrogenase láctica (DHL) foi 504,5 U/L (138­569 U/L), alfafetoproteína (AFP) foi 2,0 ng/ml (1,1­11,3 ng/ml), gonadotrofina coriônica humana (ß-hCG) foi 0,6 mUI/ml (0,0­2,3 mUI/ml), antígeno carcinoembrionário (CEA) foi 0,9 ng/ml (0,7­3,4) ng/ml, e antígeno cancerígeno 125 (CA-125) foi 26,0 U/ml (19,1­147,0 U/ml), todos pré-operatórios. Todos os tumores foram unilaterais e tratados cirurgicamente. Realizou-se linfadenectomia em 3 (25,0%) pacientes, porém, nenhuma das três apresentou acometimento linfonodal. No exame anatomopatológico, 1 tumor (8,3%) era bem diferenciado, 8 (66,7%) eram moderadamente diferenciados, e 3 (25,0%) eram pouco diferenciados. Um total de 5 (55,6%) tumores eram sólido-císticos, 2 (22,2%) eram puramente císticos, 1 (11,1%) era cístico com vegetações, e 1 (11,1%) era puramente sólido, mas para 3 pacientes estas informações não estavam disponíveis. A mediana da dimensão da lesão foi 14,2 cm (3,2­23,5 cm). Todos os tumores eram estádio IA de acordo com a classificação de 2014 da Federação Internacional de Ginecologia e Obstetrícia (FIGO, na sigla em inglês). Duas (16,7%) pacientes receberam adjuvância; uma realizou 3 ciclos de paclitaxel e carboplatina a cada 21 dias, e a outra 4 ciclos de ifosfamida, cisplatina e etoposide a cada 21 dias. Dentre todas as pacientes, nenhuma apresentou recidiva e houve um óbito relacionado a complicações após estadiamento cirúrgico. CONCLUSãO: Dor abdominal foi a apresentação mais frequente. Todos os TCSLs eram estádio IA e a maioria era moderadamente diferenciada. Não ocorreram recidivas, mas ocorreu um óbito relacionado ao estadiamento cirúrgico.

Ovarian sertoli-leydig cell tumors: epidemiological, clinical and prognostic factors / Tumores de células de Sertoli-Leydig ovarianos: fatores epidemiológicos, clínicos e prognósticos

Abstract Objective To describe a series of cases of ovarian Sertoli-Leydig cell tumors (SLCTs). Methods Retrospective review of 12 cases of SLCT treated at the Hospital do Câncer de Barretos, Barretos, state of São Paulo, Brazil, between October 2009 and August 2017. Results The median age of the patients was 31 years old (15-71 years old). A total of 9 patients (75.0%) presented symptoms: 8 (66.7%) presented with abdominal pain, 5 (41.7%) presented with abdominal enlargement, 2 (16.7%) presentedwith virilizing signs, 2 (16.7%) presented with abnormal uterine bleeding, 1 (8.3%) presented with dyspareunia, and 1 (8.3%) presented with weight loss. The median preoperative lactate dehydrogenase (LDH) was 504.5 U/L (138-569 U/L), alpha-fetoprotein (AFP) was 2.0 ng/ml (1.1-11.3 ng/ml), human chorionic gonadotropin (β-hCG) was 0.6 mUI/ml (0.0-2.3 mUI/ml), carcinoembryonic antigen (CEA) was 0.9 ng/ml (0.7-3.4 ng/ml), and cancer antigen 125 (CA-125) was 26.0 U/ml (19.1-147.0 U/ml). All of the tumors were unilateral and surgically treated. Lymphadenectomy was performed in 3 (25.0%) patients, but none of the three patients submitted to lymphadenectomy presented lymph node involvement. In the anatomopathological exam, 1 (8.3%) tumor was well-differentiated, 8 (66.7%) were moderately differentiated, and 3 (25.0%) were poorly differentiated. A total of 5 (55.6%) tumors were solid-cystic, 2 (22.2%) were purely cystic, 1 (11.1%) was cystic with vegetations, and 1 (11.1%) was purely solid, but for 3 patients this information was not available. The median lesion size was 14.2 cm (3.2-23.5 cm). All of the tumors were at stage IA of the 2014 classification of the International Federation ofGynecology andObstetrics (FIGO). A total of 2 (16.7%) patients received adjuvant treatment; 1 of themunderwent 3 cycles of paclitaxel and carboplatin every 21days, and the other underwent 4 cycles of ifosfamide, cisplatin and etoposide every 21 days. None of all of the patients had recurrence, and one death related to complications after surgical staging occurred. Conclusion Abdominal pain was the most frequent presentation. There was no ultrasonographic pattern. All of the SLCTs were at stage IA, and most of them were moderately differentiated. Relapses did not occur, but one death related to the surgical staging occurred.

Resumo Objetivo Descrever uma série de casos de tumores de células de Sertoli-Leydig (TCSLs) ovarianos. Métodos Revisão retrospectiva de 12 casos de TCSL tratados no Hospital de Câncer de Barretos entre outubro de 2009 e agosto de 2017. Resultados A mediana de idade foi 31 anos (15-71 anos). Um total de 9 pacientes (75,0%) apresentaram sintomas: 8 (66,7%) apresentaram dor abdominal, 5 (41,7%) apresentaram aumento abdominal, 2 (16,7%) apresentaram virilização, 2 (16,7%) apresentaram sangramento uterino anormal, 1 (8,3%) apresentou dispareunia, e 1 (8,3%) apresentou emagrecimento. A mediana de desidrogenase láctica (DHL) foi 504,5 U/L (138-569 U/L), alfafetoproteína (AFP) foi 2,0 ng/ml (1,1-11,3 ng/ml), gonadotrofina coriônica humana (β-hCG) foi 0,6 mUI/ml (0,0-2,3 mUI/ml), antígeno carcinoembrionário (CEA) foi 0,9 ng/ml (0,7-3,4) ng/ml, e antígeno cancerígeno 125 (CA-125) foi 26,0 U/ml (19,1-147,0 U/ml), todos pré-operatórios. Todos os tumores foram unilaterais e tratados cirurgicamente. Realizou-se linfadenectomia em 3 (25,0%) pacientes, por em, nenhuma das tr^es apresentou acometimento linfonodal. No exame anatomopatológico, 1 tumor (8,3%) era bem diferenciado, 8 (66,7%) eram moderadamente diferenciados, e 3 (25,0%) eram pouco diferenciados. Um total de 5 (55,6%) tumores eram sólido-císticos, 2 (22,2%) eram puramente císticos, 1 (11,1%) era cístico com vegetações, e 1 (11,1%) era puramente sólido, mas para 3 pacientes estas informações não estavam disponíveis. A mediana da dimensão da lesão foi 14,2 cm (3,2-23,5 cm). Todos os tumores eram estádio IA de acordo com a classificação de 2014 da Federação Internacional de Ginecologia e Obstetrícia (FIGO, na sigla em inglês). Duas (16,7%) pacientes receberam adjuvância; uma realizou 3 ciclos de paclitaxel e carboplatina a cada 21 dias, e a outra 4 ciclos de ifosfamida, cisplatina e etoposide a cada 21 dias. Dentre todas as pacientes, nenhuma apresentou recidiva e houve um óbito relacionado a complicações após estadiamento cirúrgico. Conclusão Dor abdominal foi a apresentação mais frequente. Todos os TCSLs eram estádio IA e a maioria era moderadamente diferenciada. Não ocorreram recidivas, mas ocorreu um óbito relacionado ao estadiamento cirúrgico.

Sertoli-Leydig cell tumor of the ovary: Analysis of a single institution database and review of the literature.

AIM: To evaluate the clinical characteristics and outcome of ovarian Sertoli-Leydig cell tumors (SLCTs) managed at a single institution. METHODS: The hospital records of 17 patients with the diagnosis of ovarian SLCT between 1994 and 2018 were reviewed retrospectively. RESULTS: The median age of the patients was 30 years (range, 18-67 years). All the patients had unilateral tumors. All of the 17 were stage 1 tumors. Two (11.8%) patients were stage 1C1 and two (11.8%) patients were stage 1C2. Thirteen (76.5%) patients were stage 1A. Three (17.6%) of the tumors were well differentiated, 11 (64.7%) were intermediately differentiated, 1 (5.9%) was poorly differentiated, and the degree of the differentiation was not identified for 2 (11.8%) patients. One showed retiform pattern and one had heterologous elements at the histopathologic evaluation. Among the 17 patients, we identified structural/vascular renal and ureteral anomalies in 3 (17.6%) patients. Eight patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, seven underwent unilateral salpingo-oophorectomy or oophorectomy and two underwent cystectomy with or without additional surgical staging procedures. Four patients received adjuvant chemotherapy. All the 17 patients were alive and free of disease for 1-287 months after the diagnosis. Median follow-up time was 78 months. None of the patients recurred. CONCLUSION: Sertoli-Leydig cell tumors are rare ovarian malignancies with low recurrence rates and have a favorable outcome compared to malignant epithelial tumors of the ovary. Main treatment is surgical resection and it is appropriate to prefer fertility sparing conservative surgeries for young patients.

Results from a Monocentric Long-Term Analysis of 23 Patients with Ovarian Sertoli-Leydig Cell Tumors.

BACKGROUND: Sertoli-Leydig cell tumors (SLCTs) represent less than 0.5% of ovarian tumors. Because of the rarity of this tumor and its peak in frequency at around 25 years of age, this study aimed to describe SLCT management strategies. OBJECTIVE: The objective of this study was to determine the management (i.e., conservative surgery and adjuvant chemotherapy) of ovarian SLCTs. RESULTS: This retrospective analysis included 23 patients treated for ovarian SLCTs. A centralized pathologic review of the tumors was conducted. Patients were referred to or treated in our institution for an ovarian SLCT between 1994 and 2015. The median age at diagnosis was 33 years (range, 4-82 years). According to the 2014 Federation of Gynecology and Obstetrics classification, tumors were classified as stage Ia (n = 15: well differentiated, n = 1; of intermediate differentiation, n = 8; undifferentiated, n = 4; and undefined, n = 2), stage Ib (n = 1), stage Ic1 (n = 5), stage IIb (n = 1), and stage IIIc (n = 1). Surgery was conservative in 13 patients (Ia, n = 7; Ib, n = 1; Ic1, n = 5) and radical in 10 patients (Ia, n = 8; IIb, n = 1; IIIc, n = 1). Seven patients received adjuvant chemotherapy with a cisplatin-based regimen (Ia, n = 2; Ic1, n = 3; IIb, n = 1) or docetaxel + gemcitabine (IIIc, n = 1). Median follow-up was 61 months (range, 15-252 months). Eight patients experienced a relapse (Ia, n = 2; Ib, n = 1; Ic1, n = 3; IIb, n = 1; IIIc, n = 1). Of these, six had at least one peritoneal carcinomatosis, and four died (Ic1, n = 2; IIb, n = 1; and Ia, n = 1). Two patients had a local relapse (one uterus and one ovary) and survived without disease after relapse treatment. The median time between the initial treatment and relapse was 28 months (range 9-70). CONCLUSION: Conservative surgery was safe for patients with stage Ia ovarian SLCTs. The place of conservative surgery for stage Ic1 remains to be defined. The best chemotherapy regimen remains to be defined. IMPLICATIONS FOR PRACTICE: For stage Ia disease, conservative surgery (in women of reproductive age) was safe and effective for treating ovarian Seroli-Leydig cell tumors. Adjuvant chemotherapy should be proposed for stage Ia when poor prognostic factors are present (poor differentiation, retiform pattern, or heterologous elements). For stage Ic1 and more severe stages, radical surgery and adjuvant chemotherapy should be considered. The combination of bleomycin, etoposide, and cisplatin was the most frequently used regimen, but the best chemotherapy regimen remains to be defined.

Sertoli-Leydig cell tumors of ovary: A case series.

INTRODUCTION: The purpose of this study was to report the clinical features, computed tomography (CT) and magnetic resonance imaging (MRI) findings, clinical management, and prognoses of 7 patients with Sertoli-Leydig cell tumors (SLCT) of ovary, and to review the literature of this rare condition. METHODS: Seven patients with pathologically confirmed ovarian SLCT were included. Their clinical, CT and MRI characteristics (CT images obtained from 6 patients and MR images from 4 patients), clinical management, and prognoses of 7 patients were retrospectively analyzed. RESULTS: Patients symptoms included irregular menstruation (n = 3), infertile (n = 1), vaginal bleeding after 7 years of menopause (n = 1), a palpable abdominal mass (n = 1), and abdominal pain (n = 1). Three patients had elevated alpha-fetoprotein (AFP), 1 had elevated cancer antigen 125 (CA125), and 2 had elevated Testosterone (T). The 7 tumors of 7 patients were solid or mixed solid-cystic mass with clear boundaries. The solid components of the tumors showed iso-dense on CT. On MRI, the solid components showed iso- or slightly low signal intensity (SI) on T1-weighted imaging (T1WI), high or slightly high SI on T2WI, and high on diffusion-weighted imaging (DWI) with low apparent diffusion coefficient (ADC) value. On contrast-enhanced CT and MRI, 1 tumor exhibited heterogeneous enhancement consisting of multiple nodules with relatively marked homogeneous enhancement, and other 6 tumors showed moderate or marked and constantly heterogeneous enhancements. All patients were treated with surgical excision. Only 3 had received postoperative chemotherapy. With the exception of 1 patient lost to follow-up, the other 6 patients exhibited tumor-free survival with a median follow-up time of 13.5 months, the longest follow-up time being 24 months. CONCLUSION: The patients of SLCT can present with hormonal magnification and manifest high AFP, CA125, and T levels. SLCT is characterized by a solid or mixed solid-cystic mass on CT/MR scans, and shows marked or moderated heterogeneous and constantly enhancement upon postcontrast study. The clinical characteristics and imaging findings are features and appropriated imaging should be performed whenever an SLCT is suspected.

An 88-year-old woman with flushing, alopecia and hirsutism and a Sertoli-Leydig cell tumour.

Sertoli-Leydig cell tumour (SLCT) is a rare, androgen-secreting sex cord-stromal tumour of the ovary that usually occurs in young premenopausal women. The major clinical manifestations are virilisation and defeminisation. The following case describes an 88-year-old G1P1 woman, 40 years after menopause, who presented with flushing, hirsutism, voice changes and alopecia along with significantly elevated levels of testosterone. Postoperative report revealed a well-differentiated SLCT in the left ovary. This case is unique in that SLCT is a very rare cancer and even more so in an 88-year-old woman. Taking this case into consideration, it becomes reasonable to check androgen and oestrogen levels in postmenopausal women, not only in patients with signs of virilisation, but also in those with non-classical presentations, such as flushing or heat spells.

Ovarian Sertoli-Leydig cell tumours: How typical is their typical presentation?

Ovarian Sertoli-Leydig cell tumours (OSLCT) are rare and typically present with androgenic manifestations in women of the 2nd-3rd decade. Out of 228 diagnoses of ovarian sex cord-stromal tumours recorded at an academic institution during a 14-year period, eight women were surgically treated for OSLCT. Patient mean age was 54.8 years (range 19-81), five women being in the postmenopausal stage (62.5%). Only one woman presented with androgenic manifestations (12.5%), four with abnormal/postmenopausal uterine bleeding (50%), and three with abdominal pain (37.5%). Fertility sparing or radical surgery was performed depending on patient age and stage of disease. The only patient with an advanced disease (FIGO stage IV) was referred to palliative care postoperatively. The other seven were at FIGO stage I. Five of them were free from disease at a mean follow-up of 67 months, while the remaining two were lost at follow-up. The youngest woman of the series, treated with fertility-preserving unilateral salpingo-oophorectomy at the age of 19, had two spontaneous pregnancies and deliveries of healthy babies during a 10-year follow-up period. In conclusion, our single institution 14-year experience demonstrates that the diagnosis of OSLCT is particularly challenging since many patients are older than expected and lack androgenic manifestations. Impact statement • What is already known on this subjectOvarian Sertoli-Leydig cell tumours (OSLCT) are rare and are thought to typically present with androgenic manifestations in women of the 2nd-3rd decade. • What the results of this study addOur single institution 14-year experience shows that a high proportion of women with ovarian Sertoli-Leydig cell tumours may not present with androgenic manifestations, and many of them also are in the postmenopausal stage. Most patients have a good prognosis and fertility-preserving surgery in younger women can lead to spontaneous pregnancies and deliveries of healthy children after treatment. • What are the implications of these findings for clinical practice and/or further researchThe diagnosis of OSLCT is particularly challenging and therefore not reached before surgery in most of the cases. However, while hysterectomy with bilateral salpingo-oophorectomy and surgical staging are recommended for women with higher stage or no fertility wish, fertility-sparing surgery should be considered in younger women with early disease. Therefore, further research should focus on non-invasive diagnosis possibly by means of laboratory or imaging techniques.

Ovarian Sertoli-Leydig cell tumors: a single institution experience and review of the literature.

Purpose ofinvestigation: Sertoli-Leydig cell tumors (SLCTs) of the ovary are rare, usually presenting as virilization in women in their second to third decade of life. Less than 10% of patients are older than age 50. The authors present a series of cases of SCLT managed at their institution. MATERIALS AND METHODS: A retrospective review was performed of all cases of ovarian SLCT diagnosed at a tertiary care institution between 1990-2014. Demographic data, clinical presentation, pathological findings, and treatment modalities were col- lected. RESULTS: Of the 16 patients diagnosed with SCLT over a 24-year period, nine patients (56%) were postmenopausal at the time of diagnosis, with a median age of 52.5 years (IQR = 39.7 years). These nine patients had a median interval of 14.7 years (IQR = 15) since the onset of menopause. Hyperandrogenism was a presenting feature in only five of 16 (31%) [median age of 49 (IQR= 26.5)] whereas postmenopausal bleeding was noted in two of 16 (12%). At diagnosis, tumor grade varied from well- to poorly-differentiated lesions, and eight patients (15%) received adjuvant chemotherapy. Disease-free survival over a median follow up of 31.5 months (IQR = 73.5 months) was 100% without recurrence. CONCLUSION: The present patient population was noticeably older than what has been described in literature, with the majority being postmenopausal. To the authors' knowledge, this is the largest series of postmenopausal patients with SLCT. Hyperandrogenism was evident in only a small sub-group. While the definitive management of SLCT remains controversial and varied, prognosis and risk of recurrence are reassuring.

[Sertoli-Leydig cell tumor of the ovary: case study of a 22-year old woman]. / Tumeur à cellules de Sertoli-Leydig de l'ovaire: à propos d'un cas chez une jeune fille de 22 ans.

Sertoli-Leydig cell tumors are rare secreting mesenchymal and sex cord-stromal tumors. However, they constitute one type of tumor most often responsible for virilization syndrome. A definite diagnosis is provided by histological examination following surgical excision of the tumor. It has no characterizing features on ultrasonography, in spite of the strong clinical presumption. Like many neoplasias, prognosis is related to the degree of cellular differentiation and to the presence of heterologous elements. The aim of our study was to report the case of a 22-year old woman suffering from a real virilization syndrome secondary to non-epithelial Sertoli-Leydig cell tumor of the ovary. Poorly differentiated Sertoli-Leydig tumors have high malignant potential. Treatment is surgical; taxane-platinum combination chemotherapy is an interesting adjuvant. Prognosis after surgical resection is related to the risk of relapses.

Ovarian Sertoli Leydig cell tumours in children and adolescents: an analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT).

OBJECTIVE: To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification. PATIENTS: Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n=23), French TGM protocols (n=10), Italian Rare Tumour Project (TREP) registry (n=6), and the Polish Pediatric Rare Tumour Study group (n=5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO). RESULTS: Median age was 13.9 (0.5-17.4) years. All patients underwent resection by tumour enucleation (n=8), ovariectomy (n=17), adenectomy isolated (n=18) or with hysterectomy (n=1). FIGO-stage: Ia 24pts., Ic 17pts., II/III 3pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic-III), eight relapsed, and five patients died. Eleven patients were initially treated with two to sixcycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70±0.07, relapse-free survival 0.81±0.06 and overall survival 0.87±0.05. CONCLUSIONS: Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated.

Clinicopathologic features of ovarian Sertoli-Leydig cell tumors.

BACKGROUND: Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. METHODS: A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. RESULTS: The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. CONCLUSIONS: Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.

Outcomes among patients with sex cord stromal tumour of ovary: experience from Pakistan.

BACKGROUND: Ovarian sex cord-stromal tumours (SCST) are relatively uncommon neoplasms that account for approximately 5-7% of all primary ovarian tumours. The aim was to report experience with sex cord stromal tumours (SCST) of ovary in a low and middle income country. METHODS: Clinical records of 56 patients with histopathologically-established SCST of ovary admitted to a tertiary care cancer hospital in Pakistan between April 1995 and December 2011 were reviewed. RESULTS: Median age at presentation was 41 years (Range 4-77). Forty one (73%) patients were premenopausal and 15 (26.8%) were postmenopausal. The most common presenting complaint was abdominal pain (28.1%). Thirty seven patients (66%) had stage-I, 2 had stage II and II each, and 15 (26.8%) had stage IV disease. Five years survival in patients with early stage (stages I & II) was 91% while in those in the late stage (II & IV) was 84% (p=0.79). Histopathologically, 49 patients (85.7%) had Granulosa cell tumour, and 7 (12.5%) had Sertoli Lyedig cell tumour. CA-125 was high only in 8 patients (14.3%). Adjuvant chemotherapy was give in 16 (28.6%). Thirty six (64%) were disease free at last follow up, 10 (18%) succumbed to disease and 10 (18%) were alive with disease. On univariate and multivariate analyses, late stage at presentation was the sole factor significantly associated with mortality. CONCLUSION: Ovarian sex cord-stromal tumours of ovary are relatively uncommon malignancies with good prognosis if diagnosed early and treated adequately. Survival in our study was comparable to those reported elsewhere. Among various factors, late stage of tumour at presentation was found to be the only factor significantly associated with mortality.

Sertoli-Leydig cell tumors of the ovary: a Taiwanese Gynecologic Oncology Group study.

OBJECTIVE: To report the natural history and prognosis of the uncommon Sertoli-Leydig cell tumor (SLCT) of the ovary. MATERIALS AND METHODS: A 20-year retrospective review was conducted by the Taiwanese Gynecologic Oncology Group (TGOG), including nine tertiary medical centers from different regions in Taiwan. The medical records for 40 cases of ovarian SLCT were collected. Pathology reviews were carried out by a panel of expert pathologists. RESULTS: After pathological review, 17 patients were subsequently excluded because the pathology slides were unavailable in five cases, and discrepant results from the initial diagnosis were found in 12 cases (34%). For the remaining 23 patients, the median age was 41 years. The most common symptom was irregular vaginal bleeding followed by an abdominal mass or amenorrhea. Most of the tumors were unilateral and confined to the right ovary, with an average size of 8.2 cm. Preoperative serum markers were available for 12 patients and were elevated for three patients. All patients underwent primary surgery. Six patients accepted adjuvant chemotherapy, and bleomycin, etoposide, and cisplatin were used in four of them. Clinical follow-up information was available in 21 patients with a median of 19 months. Eighty-two percent of patients were alive and free of disease up to the date of the last follow-up. Two patients died of the disease. CONCLUSION: This study demonstrates the extreme rarity of ovarian SLCT in Taiwan. Histological discordance between the diagnosis and central review proves the need for expertise review before treatment. For an improved understanding of the biological behavior and treatment strategy for this unique tumor, international collaboration is imperative.

A clinicopathological analysis of 40 cases of ovarian Sertoli-Leydig cell tumors.

OBJECTIVE: To evaluate the clinicopathological features of ovarian Sertoli-Leydig cell tumors (SLCTs) and to explore the reasonable therapy. METHODS: A total of 40 cases of SLCTs were retrospectively reviewed. RESULTS: The incidence of SLCTs was 0.41%, with a median age of 28 years. All tumors were confined to one ovary. Four tumors were well differentiated, 14 were intermediately differentiated, 20 were poorly differentiated, and 2 were undefined; 2 cases had heterologous elements, and 3 had a retiform pattern. The patients were classified into 3 groups: androgen excess (25/40), estrogen excess (6/40), and no endocrine changes (9/40). The percentages of tumors >10 cm in diameter were 8.0%, 16.7% and 40.0%, respectively; the percentages of poor differentiation were 40.0%, 50.0% and 77.8%, respectively; and the percentages of tumor rupture were 20.0%, 16.7% and 66.7%, respectively. One patient underwent cystectomy, 27 underwent unilateral salpingo-oophorectomy, and 12 underwent total hysterectomy and bilateral salpingo-oophorectomy. A total of 23 patients received postoperative chemotherapy. One patient died of diabetic nephropathy, and 3 were lost to follow up. The remaining 36 were followed up from 12 to 377 (average 70.4) months. Two patients with stage Ic tumors of poor differentiation had a recurrence within 13 and 21 months, and both obtained complete remission after the second surgery and chemotherapy. CONCLUSIONS: The prognosis of SLCTs is good, although poorly differentiated tumors may recur. Conservative surgery is acceptable for young patients wishing to preserve fertility, and postoperative adjuvant chemotherapy and long-term follow up are recommended to those with high-risk factors.

Ovarian Sertoli-Leydig cell tumors. a retrospective MITO study.

OBJECTIVE: To evaluate clinicopathologic features and to investigate the outcome of patients with ovarian Sertoli-Leydig cell tumors (SLCTs). METHODS: Data concerning 21 patients treated in 11 MITO centers were retrospectively reviewed. RESULTS: Median age was 37 (range 16-76). FIGO stage was: 17 (81%) IA, 1 (4.8%) IC, 1 (4.8%) IIB and 2 (9.5%) IIIC. Five patients (23.8%) had G1 tumor, ten (47.6%) had G2, and six (28.6%) had G3. Fertility-sparing operation was performed in 11 patients, while hysterectomy with bilateral salpingo-oophorectomy was executed in 10 patients; five patients received adjuvant chemotherapy (G2-3). Seven patients (33.3%) relapsed with a median time to recurrence of 14 months. Six recurrent patients had G2-3 disease, while one had G1. Four patients had stage IA disease, one IC and 2 stage IIIC. Patients with stage IA disease did not receive adjuvant chemotherapy. Two patients had pelvic recurrence, 4 abdominal (one with lymph nodal involvement), one on the contralateral ovary and the trocar access. Five patients underwent salvage surgery plus chemotherapy, while one received only salvage chemotherapy and one palliation. Five patients died of disease, four had received first treatment not in a MITO center. 5 year overall survival was 100% for patients with G1 disease and 77.8% for G2-3. 5 year overall survival was 92.3% for stage I and 33.3% for stage>I. CONCLUSIONS: The prognosis of patients with grade 1 SLCT is excellent without adjuvant chemotherapy. Patients with advanced stage or grade 2-3 tumors appear to benefit from postoperative chemotherapy.

Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations.

Embryonal rhabdomyosarcoma of the uterine cervix is an uncommon presentation of the most common soft-tissue sarcoma in the first decades of life. Unlike embryonal rhabdomyosarcoma in other anatomic sites, in which 70-80% of cases present before 9 years of age, the average age in our series of 14 cervical cases was 12.4 years (median, 13 years), with an age range of 9 months to 32 years at diagnosis. Of the 14 cases, 12 presented as a polyp at the cervical os; two patients had an infiltrative mass in the cervix without a botryoid polyp. The polyps measured 1.5-5 cm and all had the histopathological pattern of the sarcoma botryoides variant of embryonal rhabdomyosarcoma, with condensations of primitive and differentiated rhabdomyoblasts beneath the surface epithelium and around endocervical glands. Nodules of benign-appearing cartilage were present in the stroma of six cases (43%). One of the embyronal rhabdomyosarcomas from the youngest patient, 9 months old, also had a distinctive microscopic focus of immature tubular profiles in a primitive stroma; these tubules expressed epithelial and neuroendocrine markers. Two patients had a pleuropulmonary blastoma, one diagnosed 9 years before the embryonal rhabdomyosarcoma of the cervix and the other recognized synchronously. This latter 9-year old had a DICER1 germline mutation. One patient presented with hirsutism and had a Sertoli-Leydig cell tumor, an incidentally detected cervical embryonal rhabdomyosarcoma, and nodular hyperplasia of the thyroid. Although a pleuropulmonary blastoma was not documented in the latter patient, ovarian sex-cord stromal tumors and nodular hyperplasia of the thyroid are manifestations of the pleuropulmonary blastoma family tumor and dysplasia syndrome (OMIM 601200). Embryonal rhabdomyosarcoma of the cervix must be distinguished from other rare entities, including adenosarcoma, malignant mixed Mullerian tumor and low-grade stromal sarcoma, as the former has a better prognosis; 12 of our 14 patients remain disease-free following conservative surgery and chemotherapy. Our study suggests that cervical embryonal rhabdomyosarcoma may be another pathological manifestation in the spectrum of extrapulmonary pathology in the setting of pleuropulmonary blastoma.