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.

A sub-hepatic nodule in a young female: Chase the case.

Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female. Sertoli-Leydig cell tumours (SLCTs) are rare, mixed sex-cord stromal tumours composed of varying proportions of both Sertoli and Leydig cells, which account for <0.5% of all ovarian tumours. The cytomorphologic features of SLCTs are not well described in literature. Herein, we describe the cytomorphologic features of an SLCT at an uncommon metastatic site in a young female.

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.

Collision Tumor of the Ovary Involving Sertoli-Leydig Cell Tumor and High-Grade Serous Carcinoma-Report of the First Case.

We report a collision tumor in the ovary of a 60-yr-old woman composed of high-grade serous carcinoma and Sertoli-Leydig cell tumor. Collision tumors in the ovary are rare and to the best of our knowledge, combination of ovarian high-grade serous carcinoma and Sertoli-Leydig cell tumor has not been described before.

DICER1 -Altered Extraovarian Moderately Differentiated Sertoli-Leydig Cell Tumor: Report of a Rare Case.

We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.

An Unusual Enteric Yolk Sac Tumor: First Report of an Ovarian Germ Cell Tumor Associated With a Germline Pathogenic Variant in DICER1.

A variety of unusual tumors are associated with both germline and somatic DICER1 pathogenic variants (PVs), including, in the female genital tract, embryonal rhabdomyosarcoma at various sites and ovarian Sertoli-Leydig cell tumor. There have been occasional reported cases of ovarian germ cell tumors [mainly yolk sac tumor (YST)] harboring DICER1 PVs but, as far as we are aware, none of these has been proven to have a germline provenance. We report an unusual enteric variant of ovarian YST in a 28-yr-old woman associated with a germline PV c.901C>T (p.Gln301Ter) in exon 7 of DICER1, accompanied by a somatic (YST-only) hotspot mutation: c.5437G>A, p.E1813K. To our knowledge, this is the first report of an ovarian germ cell tumor associated with a germline DICER1 PV. We review other reported cases of ovarian germ cell tumor with DICER1 PVs and discuss the differential diagnosis of this unusual variant of YST which was originally diagnosed as a mucinous adenocarcinoma.

Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli-Leydig cell tumour, microcystic stromal tumour and their mimics.

Within the last decade, molecular advances have provided insights into the genetics of several ovarian sex cord-stromal tumours that have otherwise been enigmatic. Chief among these advances are the identification of FOXL2, DICER1 and CTNNB1 mutations in adult granulosa cell tumours, Sertoli-Leydig cell tumours (SLCTs), and microcystic stromal tumours (MCSTs), respectively. As access to molecular diagnostic laboratories continues to become more widely available, the potential roles for tumour mutation testing in the pathological diagnosis of these tumours merit discussion. Furthermore, links to inherited cancer susceptibility syndromes may exist for some women with SLCT (DICER1 syndrome) and MCST [familial adenomatous polyposis (FAP)]. This review will address practical issues in deciding when and how to apply mutation testing in the diagnosis of these three sex cord-stromal tumours. The pathologist's role in recommending referral for formal risk assessment for DICER1 syndrome and FAP will also be discussed.

Ovarian Sertoli-Leydig cell tumors: an analysis of 13 cases.

PURPOSE: To report the clinical, ultrasound and histopathological characteristics, clinical management, and prognosis of 13 patients with Sertoli-Leydig cell tumors (SLCTs) of ovary. METHODS: 13 patients with pathologically confirmed ovarian SLCTs at International Peace Maternity and Child Health Hospital from 2010 and 2019 were included in this study. The clinical, ultrasound and histopathological characteristics, clinical management, and prognosis of 13 patients were retrospectively analyzed. RESULTS: The age ranged 25-68 years. Of the 8 (62%) patients presenting endocrine symptoms, 4 had post-menopausal hemorrhage, 4 had menstrual irregularity, 2 had androgenic manifestations, 1 had hirsutism, and 1 showed acne with thyroid nodules. 1 patient had elevated cancer antigen 125 (CA125), and 2 had elevated testosterone (T). The other 5 patients showed no symptoms of whom masses were detected incidentally by physical examination. All tumors were at stage I and confined to unilateral ovary. 11 tumors were solid or mixed solid-cystic masses with clear boundaries on ultrasound, and 1 tumor was a cystic mass. 7 tumors were intermediately differentiated and 6 were poorly differentiated, among which 1 case had heterologous elements (poorly differentiated) and 8 had a retiform pattern. Grade 2 endometrial cancer occurred in 2 cases (1 intermediately differentiated and 1 poorly differentiated). One case had multinodular goiter (intermediately differentiated). The patients were classified into endocrine function group (8/13) and no endocrine function (5/13). The proportion of retiform pattern of the group with endocrine function was significantly higher than that of no endocrine function group (p < 0.05). However, the mean age, diameter of tumors, and the proportions of poor differentiation and rupture showed no significant difference. All patients were treated with surgical excision. Three cases underwent surgery twice after the pathological results came out. For the final surgery, 1 patient underwent cystectomy, 3 underwent unilateral salpingo-oophorectomy, and 9 underwent total hysterectomy and bilateral salpingo-oophorectomy. 7 had received postoperative chemotherapy. All of 13 patients exhibited disease-free survival (DFS) with the longest follow-up time being 9 years. CONCLUSION: The clinical characteristics and imaging findings may provide information for the diagnosis of SLCTs. Higher percentage of retiform pattern was found in endocrine function group. Concurrence of Grade 2 endometrial carcinoma with SCLTs was reported. The prognosis of SLCTs is good. Conservative surgery is acceptable for young patients wishing to preserve fertility.

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.

FOXL2 Mutation Analysis of Ovarian Sex Cord-Stromal Tumors: Genotype-Phenotype Correlation With Diagnostic Considerations.

Correlation of FOXL2 mutation status with morphologic features and reticulin staining patterns was performed in a comprehensive single-institutional cohort of ovarian sex cord-stromal tumors. Fifty-one cases were included, 35 of which were morphologically diagnosed as adult granulosa cell tumor, 4 as Sertoli-Leydig cell tumor, 11 as fibroma/fibrothecoma and 1 as a thecoma. Of the adult granulosa cell tumors, 31 (88.6%) harbored FOXL2 mutation. Abundant pale cytoplasm was seen in 51.6% (16/31) of FOXL2 mutated tumors, compared with 6.7% (1/15) among FOXL2 wild type tumors (P=0.003). Nearly half of FOXL2 negative tumors showed individual pericellular reticulin staining pattern, while none of the FOXL2 positive cases demonstrated this feature (P=0.0001). Nested reticulin pattern was observed in 67.7% of FOXL2 positive tumors, compared with 20% of FOXL2 negative cases (P=0.004). Indeterminate reticulin staining pattern was seen in nearly one third of cases in both groups. Nested reticulin pattern was 87.5% specific and 67.7% sensitive for FOXL2 mutation, while individual reticulin pattern was 100% specific for absence of FOXL2 mutation. No statistical significance was observed between the 2 groups in tumor size, mitotic activity, nuclear atypia, and nuclear grooves. Follow-up was available for 44 patients ranging from 0.3 to 259 months (mean: 67.5 mo). Two patients developed recurrence, both of them harbored FOXL2 mutation. In conclusion, the pathology diagnosis of sex cord-stromal tumors continues to be difficult, and reticulin staining remains a valuable tool as an initial step in the diagnostic work-up. Individual pericellular reticulin pattern essentially rules out adult granulosa cell tumor, while cases with indeterminate or nested patterns can be subjected to FOXL2 mutation testing to aid the diagnosis.

Case report: an identical twin with Sertoli-Leydig cell tumor.

Our report details the workup and management of a 43-year-old woman with an identical twin who presented with 2 years of virilization and secondary amenorrhea. Serum total testosterone was elevated. An MRI did not identify adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated unilateral testosterone elevation. The patient underwent laparoscopic unilateral oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT). Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial hyperplasia and malignancy. Our goals are to review the workup of androgen-secreting tumors and discuss the clinical importance of the DICER1 mutation in the context of SLCT. In this case, an identical twin underwent DICER1 testing which was one of the essential steps in her clinical management.

[Ovarian Sertoli-Leydig tumor: A tricky tumor]. / La tumeur de Sertoli-Leydig ovarienne : une tumeur qui peut être piégeuse.

We report the case of a 15 years old teenage girl presenting with a primary amenorrhea and hypervirilisation symptoms. The clinical assessement found a 16cm wide heterogenous ovarian mass testosteronemia and alpha-foeto protein levels were increased. On gross exam the tumor was solid and cystic, multilocular containing serous and mucinous liquids. Microscopically, there was a sertoli cells rich solid area in which the cells had a trabecular and nested organization with Leydig cells between them and there was also a cystic area made of glandular structures lined with an intestinal muco-secreting epithelium. Next to these area, there were Sertoli cells and an oedematous stroma. The immunostaining showed that the Sertoli cells expressed, among others, the inhibine and the glands expressed the cytokeratins 7 and 20. A Sertoli and Leydig cells tumor of intermediate differentiation with heterologous elements diagnostic was made. This is a rare tumor, representing less than 0.5% of ovary tumors. Well differentiated tumors are not frequent. In one third of the cases, there are hypervirilisation symptoms, the imaging exams will serve to narrow the diagnosis and to do a full work-up to establish an extension. There are several histologic sub types caracterised by the existence of retiforms structures or heterologous elements. There are no specific immunostainings, this will only help to narrow the diagnosis and rule out some hypothesis. There are no guidelines for the management of the patients, indeed each center has its own practices. Those tumors have quite a good prognosis thanks to their early diagnosis at a stade where they are still confined to the ovary.

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.

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.

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.

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.

14-3-3 sigma is a useful immunohistochemical marker for diagnosing ovarian granulosa cell tumors and steroid cell tumors.

The distinction of ovarian granulosa cell tumors (GCTs) from other sex-cord stromal tumors may be difficult histologically. Many immunohistochemical markers have been studied for this differential diagnosis, but the available markers are not entirely specific for ovarian GCT. 14-3-3 sigma has been shown to play an anti-apoptotic role in maintaining the viability of immortalized granulosa cells. However, the potential use of this molecule as an immunohistochemical marker for the diagnosis of ovarian GCT has not been investigated. A total of 103 ovarian sex-cord stromal neoplasms were immunostained with 14-3-3 sigma. These tumors included 44 adult granulosa cell, 7 juvenile granulosa cell tumors, 12 steroid cell tumors, 3 well-differentiated Sertoli-Leydig cell tumors, 5 Sertoli cell tumors, 10 thecomas, 18 fibromas, 2 primary ovarian endometrial stromal sarcomas, and 2 unclassified sex-cord stromal tumors. Ten ovaries with cystic follicles were also included as controls. Perinuclear or cytoplasmic stain was considered to be positive. Granulosa cells within the cystic follicles were positive for 14-3-3 sigma protein. All ovarian GCT (51/51) and all steroid cell tumors (12/12) were positive for 14-3-3 sigma, and all Sertoli cell tumors, fibromas, thecomas, ovarian endometrial stromal sarcomas, and sex-cord stromal tumors, unclassified, were negative for 14-3-3 sigma. The percentage of positive cell staining is statistically significant (P<0.0001) between the above 2 groups of sex-cord stromal tumors. These findings provide the initial evidence of the overexpression of 14-3-3 sigma in granulosa cells and steroid-hormone-secreting cells. They further indicate that immunohistochemical staining of 14-3-3 sigma may be a useful marker in facilitating the diagnosis of ovarian GCT and steroid cell tumors.

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.

Pediatric primary extra-ovarian Sertoli Leydig cell tumor of the retroperitoneum.

Ovarian Sertoli Leydig cell tumors (SLCT) accounts for less than 0.5% of all ovarian malignancies. The incidence of primary extra-ovarian SLCT is extremely rare with reported cases occurring in young adult women till now. We report case of primary retroperitoneal extra-ovarian SLCT in a seven-year girl child without any hormonal manifestation. She presented with complaint of left side abdominal swelling associated with intermittent pain for a duration of six months. CT scan revealed a huge retroperitoneal space-occupying lesion abutting the dorsal vertebrae and present posterior to pancreas, spleen and left kidney. The tumor was diagnosed as extraovarian Sertoli Leydig cell tumor with intermediate differentiation on histopathology and immunohistochemistry.