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.

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.

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.

Reclassification of two germline DICER1 splicing variants leads to DICER1 syndrome diagnosis.

DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls.

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.

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.

Sertoli-Leydig cell ovarian tumour: a rare cause of virilisation and androgenic alopecia.

Sertoli-Leydig cell tumours (SLCTs) represent a rare cause of hyperandrogenic state. SLCTs are sex cord ovarian neoplasms, accounting for <0.2% of all ovarian tumours. Most of the sex cord-stromal tumours have a benign clinical course, with 10%-20% of them at risk of aggressive course. We report a case of a woman in her 30s who presented with androgenic alopecia, virilisation and secondary amenorrhoea. The evaluation revealed an extremely high testosterone level. Imaging for the localisation of source of excess testosterone with contrast-enhanced CT of the abdomen revealed a right ovarian mass. Hence, a diagnosis of testosterone-secreting ovarian tumour was considered. The patient underwent right salphingo-oophorectomy, and histopathology was reported as Sertoli cell tumour. Postoperatively, there was normalisation of serum testosterone levels with decrease in virilisation and resumption of spontaneous menstrual cycles. The patient conceived spontaneously after 2 months of surgery.

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.

Moderately differentiated Sertoli-Leydig cell tumor of ovary with associated mucinous carcinoma and carcinoid-A case report and review of literature.

Sertoli-Leydig Cell Tumors (SLCT) are very rare neoplasms of the ovary (0.2%) and they belong to the group of sex cord-stromal tumors. Of these, 20% of the cases show heterologous elements. We report a case of a 22-year-old woman who presented with complaints of lower abdominal pain and secondary amenorrhea for 10 months. Physical examination revealed right lower abdominal tenderness and fullness. Imaging showed a right ovarian mass. She underwent right salpingo-oophorectomy with bilateral pelvic lymphadenectomy and omentectomy. Microscopic examination revealed a neoplasm with varied histomorphological patterns. The predominant pattern was an atypical proliferative mucinous tumor with foci of microinvasion. The other component was that of moderately differentiated Sertoli-Leydig Cell Tumor. Focal areas resembling carcinoid were also noted. Immunohistochemistry was performed and the Sertoli-Leydig Cells were positive for CD56, calretinin, inhibin, vimentin, and ER. The glandular component was positive for CK20, EMA, CEA, and CDX2. Synaptophysin and chromogranin were positive within nests resembling carcinoid. With the given histomorphological features and immunohistochemistry findings, a diagnosis of moderately differentiated Sertoli-Leydig Cell Tumor of the ovary with associated mucinous carcinoma and carcinoid was rendered. The presence of heterologous elements in SLCTs has been reported to be associated with poor prognosis.

Sertoli-Leydig cell tumor, thyroid follicular carcinoma and rhabdomyosarcoma of the uterine cervix in a prepubertal girl with pathogenic germline variant in DICER1 gene.

BACKGROUND: DICER1 syndrome is a hereditary cancer predisposition syndrome which is related DICER1 gene and may present a variety of manifestations. CASE: A prepubertal girl with ovarian Sertoli-Leydig cell tumor, thyroid follicular carcinoma, embryonal rhabdomyosarcoma of the cervix and lung cyst is presented. Genetic analysis demonstrated mutation (c.3377delC, c.71delC) in 14q32.13 loci and confirmed the diagnosis of DICER1 syndrome. CONCLUSION: The case is presented to emphasize the importance of early diagnosis of alterations in DICER1 gene and close follow-up for the development of DICER1 syndrome related pathologies, and necessity for genetic evaluation of the family.

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.

Sertoli Leydig Cell Tumour Initially Misdiagnosed as Polycystic Ovarian Syndrome and Congenital Adrenal Hyperplasia: A Case Report.

Sertoli-Leydig cell tumor of the ovary is an unusual neoplasm that belongs to a group of sex cord-stromal tumors of the ovary and accounts for less than 0.5% of all primary ovarian neoplasms. They are often characterized by the presence of mass with androgen production and signs of virilization. Due to the substantially low incidence of Sertoli-Leydig cell tumors, information on clinical behavior, prognostic factors, and optimal management arelimited. Here in, we report a case of aprimary ovarian Sertoli-Leydig cell tumor in a 21-year-old student, previously diagnosed to have polycystic ovarian syndrome and subsequently congenital adrenal hyperplasia, who presented with a large abdominal mass and features of virilization along with elevated serum testosterone levels. Fertility sparing unilateral salpingo-oophorectomy was done and adjuvant chemotherapy was given after histopathology showed moderate to poorly differentiated Sertoli-Leydig cell tumor. Following surgery, her features of hyperandrogenism resolved and serum testosterone levels returned to normal.

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.

Sertoli-Leydig cell tumour in a patient with non-classic congenital adrenal hyperplasia: an uncommon duo.

Polycystic ovary syndrome is the most common cause of hyperandrogenism in young females. Other causes are congenital adrenal hyperplasia (CAH), androgen-producing tumours and drugs. The severity and tempo of virilisation help in distinguishing the tumoural from non-tumoural causes. We report a rare case of non-classic CAH and androgen-producing ovarian tumour in the same patient, causing hyperandrogenism. A 15-year-old female patient presented with secondary amenorrhea, excessive facial hair growth and clitoromegaly for 6 months. Due to severe virilisation, tumoural aetiology was considered. Investigations showed marked elevation of testosterone and mild elevation of 17 hydroxy progesterone (17OHP). Imaging confirmed right ovarian tumour. Adrenocorticotropic hormone stimulated 17OHP, was elevated confirming the diagnosis of underlying non-classic CAH. Surgical removal of the tumour was followed by improvement in hyperandrogenism, but persistent elevation of 17OHP confirmed the underlying presence of non-classic CAH.

Mesenteric extraovarian Sertoli-Leydig cell tumor without DICER1 hotspot mutation: a case report.

BACKGROUND: Ovarian Sertoli-Leydig cell tumors (SLCTs) with androgenic manifestations harbor DICER1 mutations in 30-60% of cases. Ovarian SLCTs without DICER1 hotspot mutations have been reported to exhibit elderly onset and no androgenic manifestations. We present the first case of a primary mesenteric SLCT without DICER1 hotspot mutation. CASE PRESENTATION: An 84-year-old woman presented with a 75-mm mesenteric solid tumor. She presented no androgenic or estrogenic manifestations. She underwent ileocecal resection. Histologically, her mesenteric tumor showed histopathological features that resembled moderately differentiated SLCT. Moreover, DICER1 hotspot mutation was not detected. CONCLUSIONS: We described the first case of heterotopic primary mesenteric SLCT without DICER1 hotspot mutation.