Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

Moderately-differentiated Ovarian Sertoli-Leydig Cell Tumor With a Concurrent Serous Borderline Tumor in a 16-year-old Girl.

Sertoli-Leydig cell tumors (SLCT) are rare tumors of the ovary with a peak incidence in the second to third decade of life. Serous borderline tumors (SBT) are epithelial ovarian neoplasms which occur at a median age of 50 years. A co-occurrence of SLCT and SBT has not yet been reported. Here, we describe a case of a 16-year-old girl who presented with irregular menses, virilization, and an abdominopelvic mass. The mass was surgically removed and an intraoperative consultation revealed an 18.5 cm solid and cystic ovarian mass with the presence of co-existing SLCT and SBT. The diagnosis was confirmed on permanent sections after extensive sampling and immunohistochemical stains. The SLCT showed positive staining for calretinin, inhibin, CD99, and androgen receptor. MART-1 immunostain highlighted the Leydig cells. The SBT showed classic features including hierarchically branching papillae lined by stratified serous epithelium. This pediatric case is the first reported case of a Sertoli-Leydig cell tumor arising in association with a serous borderline tumor.

An Ovarian Sertoli-Leydig Cell Tumor with Elevated Alpha-Fetoprotein in an Adolescent: A Rare Case Report and Literature Review.

An ovarian Sertoli-Leydig cell tumor is a rare type of sex cord-stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli-Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli-Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB-IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli-Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided.

Ovarian Sertoli-Leydig Cell Tumor With Heterologous Hepatocytes and a Hepatocellular Carcinomatous Element.

Sertoli-Leydig cell tumors are a group of tumors composed of variable proportions of Sertoli cells, Leydig cells, and sometimes heterologous elements. We describe the case of a 68-yr-old woman who presented with abdominal distention. A computed tomographic scan revealed a large right adnexal mass without evidence of intrahepatic tumors, and a complete cytoreductive surgery was performed. Pathologic examination revealed a moderately differentiated Sertoli-Leydig cell tumor with various heterologous elements, including gastrointestinal-type glands, insular carcinoid, and aggregations of hepatocytes without significant cytologic atypia. Moreover, adjacent to these hepatocytes, extensive overgrowth of highly atypical hepatocyte-like cells, providing a striking morphologic similarity to hepatocellular carcinoma of the liver, was identified. Both the heterologous hepatocytes and hepatocellular carcinomatous tumor cells were immunohistochemically positive for alpha-fetoprotein, hepatocyte paraffin 1, and arginase-1. Some Sertoli cells adjacent to the heterologous hepatocytes were also positive for alpha-fetoprotein and hepatocyte paraffin 1. The present case showed that a tumor morphologically and immunohistochemically analogous to hepatocellular carcinoma of the liver can arise in the ovary, in association with Sertoli-Leydig cell tumors.

The clinical features and reproductive prognosis of ovarian neoplasms with hyperandrogenemia: a retrospective analysis of 33 cases.

The aim of this study is to review the natural course, clinical features, and reproductive prognosis of ovarian tumors associated with hyperandrogenemia. We retrospect 33 patients of ovarian tumors with hyperandrogenemia. Thirty cases (91%) were sex cord-stromal tumors. Sertoli-Leydig cell tumors, Leydig cell tumors, and steroid cell tumors were the most common types. It is not possible, to predict the pathological subtypes based on androgen levels alone. Most of these tumors were solid masses, with an average diameter of 3.9 cm. These tumors are soft or fragile, no clear boundary with normal tissue, thus excision is superior to exfoliation. The average disease course of the top three tumors was 32.6, 35.4, and 67.7 months, respectively. Among 11 married women with a desire to get pregnant, nine cases resumed menstrual periods after surgery and became pregnant naturally. Hyperandrogenemia might predict a better prognosis. The asynchronism of hyperandrogenemia and undetectable tumor may cause irreversible change and emotional depress, the methods of early diagnosis need further study.

Accuracy of intra-operative frozen section and its role in the diagnostic evaluation of ovarian tumors.

UNLABELLED: Summary OBJECTIVE: This retrospective study was undertaken to evaluate the accuracy and role of intra-operative frozen section in the diagnosis of ovarian tumors. MATERIALS AND METHODS: Retrospective study of 804 ovarian frozen section results between June 2010 and June 2014 was examined to determine the accuracy of frozen section diagnosis. The intra-operative frozen section diagnosis was compared with the permanent (paraffin) section and the overall accuracy, sensitivity, specificity, and positive and negative predictive values of the frozen section were studied. RESULTS: The overall accuracy to determine the status of malignancy was 92.6%. There were 38 (7.4%) false negative and no false positive frozen section diagnoses.The sensitivity, specificity, and positive predictive and negative predictive values for benign ovarian tumors were 100.0%, 97.0%, 91.3%, and 100.0%, respectively; for borderline tumors they were 64.3%, 97.0%, 91.5%, and 94.0%, respectively, and for malignant tumors they were 90.0%, 100.0%, 100.0%, and 85.5%, respectively. CONCLUSION: This study concluded that frozen section appears to be an adequate technique for the histopathological diagnosis of ovarian tumors, with some limitations observed among borderline and mucinous tumors.

Recurrent Sertoli-Leydig cell tumor of ovary in 8-year-old girl.

Sertoli-Leydig cell tumors are rare sex cord-stromal neoplasms that account for <0.2% of ovarian tumors. These tumors with a retiform pattern pose difficult diagnostic problems, with the majority of being misinterpreted as serous papillary cystadenocarcinoma and endodermal sinus tumor. We report an 8-year-old female patient presented to our institution with a huge mass and pain in the lower abdomen and recurrence in the 10th months following the first operation. Only four cases of Sertoli-Leydig cell tumors have been reported under age of the eight years in the literature so far. It is difficult to define the stage and the morphology of Sertoli-Leydig cell tumors with retiform pattern in children and chemotherapy or radiotherapy administration is contraversial. However, fertility sparing surgeries should be considered as a first treatment choice on the time of the diagnosis and the recurrence.

Organ-sparing surgery for testicular tumours.

PURPOSE OF REVIEW: Testicular cancer represents the majority of testicular masses, and radical orchiectomy is still considered the standard-of-care. Testis-sparing surgery (TSS) can be an alternative to radical surgery in patients with small testicular tumours, bilateral or solitary testis masses. The aim of this manuscript is to review the current indications, oncological and functional outcomes of TSS. RECENT FINDINGS: Our review confirmed that literature lacks studies with a high level of evidence on comparing TSS with radical surgery. Indications for TSS are controversial, specifically for patients with normal contralateral testis. For nonpalpable testicular masses less than 2 cm, bilateral tumours and solitary testis mass, TSS seems to be a viable treatment option. Frozen-section examination is a critical tool for assessment at the time of TSS that allows for diagnosis of benign from malignant tumours and evaluation of margin. TSS has been shown to be associated with less fertility alterations, hormonal deficit and potential lower impact on sexual and psychosocial aspects. Intermediate to long-term follow-up results have not revealed any significant risk of local and/or distant recurrences after TSS. SUMMARY: TSS is well tolerated and feasible for selected patients with testicular mass without compromising oncological and functional outcomes. Further studies with a higher level of evidence are needed to confirm these findings.

Judicious DICER1 testing and surveillance imaging facilitates early diagnosis and cure of pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT) are both associated with germline mutations in DICER1. In this brief report, a maternal history of SLCT led to identification of a deleterious DICER1 mutation in the patient and her asymptomatic infant. Radiographic screening revealed a large Type I PPB, which was completely resected. Identification of DICER1 mutation carriers and imaging of children at risk for PPB may allow detection of PPB in its earliest and most curable form, leading to increased likelihood of surgical cure and decreased risks of treatment-related late effects.

Sertoli-Leydig cell tumor in a 12-year-old girl: a review article and case report.

BACKGROUND: The Sertoli and Leydig cell tumor is an unusual neoplasm that belongs to the sex cord-stromal tumors. Generally these tumors are associated with good prognosis. These tumors usually present virilizing symptoms such as oligomenorrhea or amenorrhea, hirsutism, voice raucity, laryngeal protuberance and clitoromegaly. CASE PRESENTATION: A 12 year old girl referred acute abdominal pain with no other clinical manifestations. An abdominal ultrasound showed a semisolid mass suggestive of ovarian tumor. The diagnosis was confirmed by a computed tomography. A unilateral salpingo oophorectomy was performed and the pathologist reported a Sertoli-Leydig tumor with intermediate differentiation. The outcome was excellent. CONCLUSIONS: These tumors represent a rare condition in children. However, they can occur at any age, therefore it is important to acknowledge the clinical manifestations, diagnostic approach and therapeutic options. In this case the patient presented unusual symptoms which makes it more interesting.

Does surgery to preserve fertility in Sertoli-Leydig cell tumours increase the likelihood of spontaneous conception?

A nulligravida in her 30s presented with primary infertility and secondary amenorrhoea. General examination revealed virilisation; sonological examination detected a right ovarian solid mass. International Ovarian Tumour Analysis (IOTA) was suggestive of malignancy and serum testosterone was raised. A strong clinical suspicion and negative tumour markers pointed towards androgen producing sex cord stromal ovarian neoplasm. MRI excluded pelvic lymphadenopathy. Given the patient's desire for conception, fertility sparing staging laparotomy was done. Histopathology confirmed Sertoli-Leydig cell tumour (SLCT) International Federation of Gynaecology and Obstetrics stage IA. Serum testosterone fell drastically by day 10. Spontaneous menstruation resumed within 30 days. The significance of SLCTs as a differential diagnosis in young women with secondary amenorrhoea and virilising features underscores the role of fertility-preserving surgery in certain circumstances. Here we discuss the clinical features, diagnostic challenges and management strategies for SLCTs, emphasising the need for multidisciplinary collaboration and option of fertility preservation in early stages.

No metabolic impact of surgical normalization of hyperandrogenism in postmenopausal women with ovarian androgen-secreting tumours.

AIM: To examine the impact of surgical normalization of testosterone on body weight and on glucose and lipid metabolism and insulin sensitivity in a group of hyperandrogenic women with ovarian androgen-secreting tumours (OAST). METHODS: Five consecutive postmenopausal hyperandrogenic patients (aged 63 ± 5 years) with a diagnosis of OAST were prospectively evaluated. Clinical signs, symptoms and metabolic and hormonal parameters were collected at the time of the diagnosis and at follow-up, 12 months after surgical oophorectomy. A group of 15 age-matched and body mass index-matched postmenopausal control women served as a reference group. RESULTS: At baseline, patients with OAST had very high testosterone levels and inappropriately low gonadotrophin levels for their menopausal status. All the women were overweight or obese, and one had a history of polycystic ovary syndrome and Type 2 diabetes. Twelve months after surgical oophorectomy, testosterone and gonadotrophin levels returned to appropriate values for menopausal status in all patients; however, no change in body weight was found. Fasting glucose levels slightly increased (P < 0·05) without any significant change in other metabolic parameters. In the woman with diabetes, a moderate decrease in haemoglobin A1c occurred. Red blood cell count and haematocrit values were normalized (P < 0·05, respectively). CONCLUSION: Normalization of androgen levels achieved after surgical oophorectomy did not cause any significant change in body weight and insulin sensitivity. These findings may offer a different perspective on the impact of hyperandrogenaemia on metabolism.

Sertoli-Leydig cell tumors: current status of surgical management: literature review and proposal of treatment.

To identify the appropriate management we review the current literature on the diagnostic and different surgical procedures to which the patients affected by Sertoli-Leyding cell tumors (SLCTs) were submitted. Through the description of a case report we also propose an interdisciplinary diagnostic approach and a laparoscopic surgical staging, with a long-term follow-up. The analysis shows that pelvic ultrasound is primary diagnostic procedure, and only 36% of publications clearly describe to have performed more specific investigation. The hormone assessment is performed in the presence of specific endocrine symptoms. Laparoscopic approach is chosen by a few surgeon. Laparotomic surgery is preferred based in not recent recommendations for ovarian cancer treatment, although it is demonstrated the efficacy and safety of laparoscopy in the treatment of ovarian epithelial tumors. Different steps that are usually used for oncological ovarian cancer staging are not always performed. Conservative and fertility sparing surgery is commonly accepted, and even preferred due to the young age of patients. In the surgical treatment of SLCTs is necessary to adopt common guidelines, and evenly define the steps that the patient should be submitted. If are observed epithelial cancer oncological principles, laparoscopic surgery should be the approach of choice for these patients.

Ovarian Sertoli-Leydig cell tumor: a report of seven cases and a review of the literature.

The aim of this study was to investigate the clinicopathologic features, treatment and outcome of seven patients with an ovarian Sertoli-Leydig cell tumor (SLCT). Five patients presented with feminization, two with accompanying virilization. One presented with amenorrhea alone. Three of the five patients showing feminization symptoms had endocrine-related diseases. Histologically, five tumors were well differentiated, the other two were poorly differentiated. The latter two patients were misdiagnosed as having an ovarian epithelial carcinoma or granulosa cell tumor from frozen sections. Immunohistochemistry showed that the tumors were calretinin-positive in two patients and one was inhibin-positive. Four patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy(TAH/BSO) and two were treated by unilateral salpingo-oophorectomy. Among them, two patients received adjuvant chemotherapy. Six patients were free of disease in a follow-up of 2-34 years and one achieved a pregnancy. The remaining patient recurred 4 years later. Feminization as well as virilization might provide important clues for a preoperative diagnosis. Histological misdiagnosis is probable in poorly differentiated tumors. Conservative surgery including retention of fertility can be considered. However, the tendency for recurrence in poorly differentiated tumors should be considered.

Sertoli-Leydig cell tumor of the ovary: analysis of a single institution database.

AIM: To evaluate the clinicopathological features, management, survival and prognostic factors of patients with Sertoli-Leydig cell tumors of the ovary (SLCT) managed at a single institution. MATERIAL AND METHODS: The clinical records of patients with Sertoli-Leydig cell tumors of the ovary managed at the KK Women's and Children's Hospital, Singapore, between October 1998 and December 2008 were reviewed. Data of pathological features, treatment given and progress on follow-up was studied. RESULTS: Sertoli-Leydig cell tumor of the ovary accounted for 1.3% of malignant ovarian neoplasms. The median age of the patient was 30 years. The most common mode of presentation was with hormonal-related symptoms (80%) in the form of secondary amenorrhea, irregular menses and features of virilization. Thirteen of the 15 patients underwent surgical staging and all were found to have stage-I disease at the time of diagnosis. Ten patients with intermediate and poorly differentiated tumors received adjuvant bleomycin, etoposide and cisplatin (BEP) chemotherapy. Recurrent disease was detected in two patients (13.3%) during a median follow-up of 63 months, both of whom had poorly differentiated type of tumor. Both these patients underwent optimal debulking surgery followed by postoperative chemotherapy (BEP regimen). There were no disease -elated deaths and all patients were under complete remission at the last follow-up. CONCLUSION: As most Sertoli-Leydig cell tumors of the ovary are seen in young women and detected while still in the early stages, a favorable outcome can be achieved by conservative surgery. Patients with moderate and poorly differentiated types of tumors benefit from adjuvant chemotherapy. Recurrences tend to occur early and are commonly seen in patients with poorly differentiated tumors.

Bilateral poorly differentiated Sertoli-Leydig ovarian tumor associated with dysgerminoma: case report.

Sertoli-Leydig cell tumors are rare stromal tumors of the ovary. They account for less than 0.5% of ovarian neoplasms. From a histological point of view, they show large diversity, making their clinical symptoms diverse as well. They are mostly unilateral, with average diameter 13.5 cm at the moment of diagnosis. Histologically, poorly-differentiated Sertoli-Leydig tumors pose a diagnostic problem, often being clinically asymptomatic which makes their detection relatively late, preventing efficient treatment, and resulting in worse prognosis. This article presents a rare case of bilateral poorly-differentiated Sertoli-Leydig ovarian tumor, characterized by heterologous histological structure, without hormonal unbalance, and without signs of defeminization and/or virilization, its diagnostics, and treatment.

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.

Malignant ovarian Sertoli-Leydig cell tumor localized with selective ovarian vein sampling.

Sertoli-Leydig cell tumors (SLCT) are rare, comprising less than 0.5% of ovarian neoplasms. They are most often diagnosed in premenopausal women and may produce androgens, resulting in hirsuitism, voice deepening, frontal balding, terminal hair growth, and clitoromegaly. SLCT are malignant in 15%-20% of cases. We discuss a 25-year-old patient with persistent hyperandrogenemia. Noninvasive imaging cannot conclusively differentiate between SCLT and other diagnoses such as polycystic ovary syndrome, ovarian hyperthecosis, idiopathic hyperandrogenism, idiopathic hirsuitism, and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Selective ovarian vein sampling revealed a 15-fold greater testosterone production from the right ovary compared with the left, which guided appropriate surgical management.

Bilateral androblastoma (Sertoli-stromal cell tumor) of the ovary: a rare cause of virilization in a teenager.

A case of a 17-year-old patient diagnosed with bilateral androblastoma of the ovary is presented. The patient was admitted because of secondary amenorrhea, hirsutism and acne. After clinical, ultrasonographic and hormonal examinations an androgen-producing ovarian tumor was suspected and consequently laparotomy with right ovarian tumor excision and left ovary exploration was carried out. During surgery the right ovarian tumor was excised and exploration of the left ovary revealed an ovarian tumor with a diameter of 10 mm, which was then also excised. The pathologic diagnosis was a bilateral androblastoma of the ovary measuring 40 mm x 30 mm x 20 mm in the right ovary and 10 mm in diameter in the left ovary. We concluded that androblastomas, in spite of their low incidence, are a possibility that should always be considered in women of all ages presenting with signs of virilization.

Ovarian Sertoli-Leydig cell tumor in a 9-month-old infant with special histologic pattern.

A 9-month-old infant with left ovarian Sertoli Leydig cell tumors (SLCTs) was reported and the special histological pattern was that the main components of the tumor were leydig cells. She was the youngest reported case of the tumor. The patient had increased serum estradiol and A-Fetoprofein (AFP) and a left oophorectomy was performed. After surgery, the patient has not received any treatment. So far, the patient has been well and survived without recurrence for 40 months.