Characteristics and outcomes analysis of ovarian Sertoli-Leydig cell tumors (SLCTs): analysis of 15 patients.

INTRODUCTION: Because of limited information of Sertoli-Leydig cell tumors (SLCTs), the objective aimed to describe clinical parameters, management and treatment results of SLCTs. MATERIAL AND METHODS: We retrospectively reviewed 15 cases with SLCTs, who were treated in the Affiliated Hospital of Qingdao University between 2009 and 2020. Data of clinical parameters and treatment was studied. RESULTS: The age ranged 25-69 years. Elevated testosterone was observed in 4 patients. FIGO-stage: 14 were at Ia(10 moderately differentiated, 3 poorly differentiated, 5 retiform pattern).1 was at Ic. Patients with retiform pattern were more likely to exhibit endocrine function (p = 0.019, w = 0.61) and tumor diameter was significantly bigger in no endocrine function (p = 0.012, d = 1.52). All patients received surgical treatment. 8 received postoperative chemotherapy. The median follow-up was 66 months (20-112 months). 1 patient relapsed within 36 months and received cytoreductive surgery. She survived without disease after recurrence treatment. Of 5 patients who performed fertility sparing surgeries with the desire of childbirth, 3 had full-term pregnancy and 1 experienced a miscarriage. Another one has not tried to conceive. CONCLUSION: The prognosis of SLCTs is good. Our data showed patients with retiform pattern were more likely to exhibit endocrine function. The diameter of tumor was significantly bigger in no endocrine function. Conservative surgery is the preferred option for patients with the desire of fertility at stage Ia. Postoperative chemotherapy is advised to cases with high-risk factors, but the most effective chemotherapy regimen is still uncertain.

[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.

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.

DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects.

Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component.

Sertoli-Leydig cell tumors: hormonal profile after dynamic test with GnRH analogue: triptorelin represents a useful tool to evaluate tumoral hyperandrogenism.

We report the case of a 15-year-old woman with signs of hyperandrogenism affected by a Sertoli-Leydig cell tumor (SLCT). In our patient, blood analysis showed a high testosterone (T) level (T: 8.53 nmol/L; nv < 1.87 nmol/L) while the GnRH-analogue test demonstrated an exaggerated secretion of 17-hydroxyprogesterone (OHP), T, and androstenedione (A) by the ovary after stimulation. We compared the GnRH-analogue test of our patient with that obtained in a group of normal and healthy women (no. 8 subjects, 16-26 years old), men (no. 4 subjects, 18-28 years old), and in a group of PCOS patients with age and body weight compared. We found in our patient a value of OHP, 17-beta estradiol (E2) and T, from 2 to 18 times higher than healthy women. When we compared our patient with healthy men, we differently observed a comparable response of T. The response of our patient was also comparable with that observed in the PCOS group for E2. During the post-surgical follow up, the GnRH-analogue test of our patient showed a response of OHP, T, and E2 comparable with that of the PCOS group. The GnRH-analogue test is a useful tool to characterize steroidogenesis in SLCT.

Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review.

Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

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.

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.

Sertoli-Leydig cell tumor presenting hyperestrogenism in a postmenopausal woman: a case report and review of the literature.

OBJECTIVE: Sertoli-Leydig cell tumor (SLCT) accounts for <0.5% of all ovarian tumors, which is unusual in postmenopausal women. Postmenopausal women with SLCT usually become virilized. We report a postmenopausal woman with SLCT presenting with hyperestrogenism. CASE REPORT: We report a rare case of SLCT in a postmenopausal woman aged 61 years, who presented with postmenopausal bleeding, endometrial hyperplasia and mucous polyp, elevated estradiol, and decreased follicle-stimulating hormone (FSH) and luteinizing hormone (LH) values, all suggesting hyperestrogenism. Transvaginal ultrasound revealed several small cyst locules, detected inside the right ovary, with a maximum diameter of 7 mm. The diagnosis was delayed because of the atypical clinical manifestation and negative serum tumor markers. The frozen section investigation revealed SLCT intraoperatively, which was confirmed by histopathological and immunocytochemical examination. The tumor was positive for inhibin-alpha, pancytokeratin, and p53 and in isolated tumor cells, positive for Ki-67. CONCLUSION: This case of SLCT suggests the existence of a new specific type of endocrine complex disease.

Efficacy of selective venous sampling to localize a small ovarian androgen-producing tumor.

Two cases of androgen-producing tumors, including a Sertoli-Leydig cell tumor in a woman of reproductive age and a Leydig cell tumor in a postmenopausal woman, are reported herein. In both cases, only selective venous sampling was able to detect the presence of the androgen-producing ovarian tumors.

Cervical sarcoma botryoides and ovarian Sertoli-Leydig cell tumor.

The case of a woman who developed a cervical sarcoma botryoides tumor at age 14 years and a right ovarian Sertoli-Leydig cell tumor with alpha-fetoprotein production at 27 years is presented. The sarcoma botryoides was a stage 1b, 4-cm, polypoid ectocervical tumor treated by radical hysterectomy and bilateral pelvic lymphadenectomy. The Sertoli-Leydig cell tumor was a stage 1a, 145-g mass removed piecemeal by right oophorectomy. Histologically, it was an intermediate Sertoli-Leydig cell tumor with a heterologous element composed of an endometrioid-like yolk sac tumor which was producing alpha-fetoprotein. There was no histological similarity between the two tumors. The patient is alive without evidence of disease, 16 years after diagnosis of her sarcoma botryoides and 3 years after her Sertoli-Leydig cell tumor. This is, to our knowledge, the third known association between these two rare gynecological tumors. The basis of the association remains unknown.

Sertoli Leydig cell tumor with malignant heterologous elements and raised alpha-fetoprotein: a case report.

A case of a Sertoli Leydig cell tumor in a young female with virilizing symptoms and an androgenic endocrine profile with raised serum alpha-fetoprotein is presented. The tumor consisted predominantly of malignant epithelial and mesenchymal heterologous elements. Such a combination in the same tumor has to the best of our knowledge not been previously reported in English literature. The Leydig cells were immunohistochemically positive for alpha-fetoprotein. Sertoli Leydig cell tumors should be included in the differential diagnosis of tumors with raised alpha-fetoprotein. Chemotherapy in addition to surgery has been recommended for these tumors.

[Two case of androgen-secreting ovary tumor].

Two cases of androgen-secreting ovary tumor were reported. patients' chief complaints were menoxemia and hirsutism; clitorism was found by physical examination. Their serum testosterone (T) were high (10.2-6.7nmol/L) and could not be suppressed to normal range by middle-dose dexamethasone inhibiting test. ACTH stimulating test could not stimulate the high serum T to raise futher, but HCG stimulating test could increase serum T to higher level. Pelvic examination, type B ultrasonic and CT scan confirmed a mass on one of the ovaries. Sertoli-Leydig cell tumor and gynandroblastoma were proved respectively by pathology. After removing the tumor, their serum T were returned to normal level.

Immunohistochemical and biochemical analysis of a human Sertoli-Leydig cell tumor: autonomous steroid production characteristic of ovarian theca cells.

OBJECTIVE: To ascertain the steroidogenic profile and location of steroidogenic enzymes in a steroid-secreting Sertoli-Leydig cell tumor of the ovary. METHODS: Steroid levels from peripheral, left ovarian (tumor), and right ovarian venous blood were measured. Tumor tissue was examined for the steroidogenic enzymes 17 alpha-hydroxylase (P450c17) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) by immunohistochemistry. Tumor cells were isolated and incubated in serum-free media. Thereafter, media were analyzed for steroid production, steroidogenic response to effectors, and metabolism of radiolabeled pregnenolone and androstenedione. RESULTS: Levels of C19 steroids and 17-hydroxyprogesterone (17OHP) were elevated in peripheral blood. The majority (80%) of steroids in serum from the left ovarian vein (tumor) were C19 steroids (dehydroepiandrosterone [DHEA], 45%; androstenedione, 27%, testosterone, 7%, with 13% 17OHP, 7% progesterone, and less than 1% estradiol (E2). Immunoreactivity for both P450c17 and 3 beta HSD was identified in clusters of large cells surrounded by nonimmunoreactive cells composing cord-like structures. Of the steroids that accumulated in the incubation medium of unstimulated, freshly isolated tumor cells, 84% were C19 steroids (DHEA, 44%; androstenedione, 36%; testosterone 2%, with 16% 17OHP and less than 1% progesterone and E2. Basal steroid production was not stimulated by LH or FSH. However, treatment with forskolin (10 mumol/L), dibutyryl cAMP (1 mmol/L), or steroid precursors (22-hydroxycholesterol, 1 mumol/L; pregnenolone, 1 mumol/L) increased the production of all steroids measured. Forskolin treatment increased androstenedione (fivefold), DHEA (tenfold), and 17OHP (40-fold) compared with basal levels. Incubation of freshly isolated cells with [3H]pregnenolone demonstrated the ability of these cells to metabolize this C21 steroid precursor to androstenedione, DHEA, and 17OHP. However, [3H]androstenedione was not readily metabolized by these cells to either estrone or testosterone. CONCLUSIONS: The steroidogenic properties of a steroid hormone-producing tumor were described. Cells isolated from this tumor produced steroids similar to those secreted by ovarian theca cells. These properties suggest that certain ovarian steroidogenic tumor cells may be an appropriate model for ovarian theca cells and could be used to develop steroid-secreting cell lines.

Origin of unreactive hyaline bodies from erythrocytes in genital tumors.

Two genital tumors, one a lipid virilizing cell tumor of the ovary, the other an ovarian Sertoli-Leydig cell tumor with retiform pattern, were studied focusing attention on the numerous eosinophilic hyaline bodies that were present both in the extracellular spaces and within the cytoplasm of the proliferating cells. Histochemistry and immunohistochemistry revealed that they were PAS positive and alpha-1-fetoprotein negative. Under electronmicroscopy these hyaline bodies appeared to correspond to variably altered red blood cells: red blood cell ghosts, erythrocytes with Heinz bodies, phagocytosed erythrocytes. Our findings could explain the origin of at least a part of the hyaline bodies found in similar or in other unrelated pathologies.

Sertoli-Leydig cell tumour of the ovary--a rare cause of virilization after menopause.

A case of Sertoli-Leydig cell tumour of the ovary causing virilization in a postmenopausal woman is presented. The patient had increasing facial hair growth, deepening of the voice, a dull pain in the lower part of the abdomen and enlargement of the clitoris. Laboratory investigations showed an elevated level of plasma testosterone. Considering an ovarian tumour the most likely cause of the above-mentioned findings, hysterectomy with bilateral salpingo-oophorectomy was performed. Both ovaries were macroscopically normal at operation, but pathological examination revealed a small well-differentiated Sertoli-Leydig cell tumour in the left ovary. Follow-up 3 months later showed decreasing signs of virilization and normalization of the hormone levels.

Raised serum alpha-fetoprotein in Sertoli-Leydig cell tumor (androblastoma) of ovary: report of two cases.

Two cases of Sertoli-Leydig cell tumor (SLCT) of the ovary associated with elevated serum alpha-fetoprotein (AFP) levels are described. A 16-year-old girl (case 1) had a Sertoli-Leydig cell tumor containing heterologous elements in the form of mucinous epithelium; AFP was demonstrated within the Sertoli cells by immunohistochemical techniques. An 11-month-old girl (case 2) had a SLCT with a retiform pattern and heterologous elements in the form of cells resembling hepatocytes; AFP was localized in the hepatocytes by immunohistochemical techniques.

[Endocrine profile and electron microscopic study of ovarian androblastoma].

The endocrine profile of a 23-year-old woman with an androblastoma of the right ovary and the results of electron microscopic observation of the tumor are presented. The calculated ratio of testosterone in testosterone intraoperative peripheral vein blood, right ovarian vein blood, and right ovarian tumor fluid was 1:1.4:4.0. The peripheral levels of hormones before right salpingo-oophorectomy were testosterone, 6.26 ng/ml; dehydroepiandrosterone, 17.80 ng/ml; androstenedione, 1.61 ng/ml; and cortisol, 16.5 micrograms/ml, and the corresponding levels at 14 days after surgery were 0.50 ng/ml; 13.80 ng/ml; 1.27 ng/ml; and 15.2 micrograms/ml, respectively. The tumor was responsive to hCG, resulting in a marked increase in the serum concentrations of testosterone, androstenedione, and dehydroepiandrosterone (3.7 times, 5.3 times, and 2.4 times, respectively). Preoperatively, an elevated basal level of luteinizing hormone (LH) and a normal basal level of follicle-stimulating hormone (FSH) (high LH:FSH ratio, 6.6) were found. The electron microscopic findings for the tumor revealed Leydig cells, Sertoli cells, transitional cells with features of both Sertoli cells and Leydig cells, and dark cells. The dark cells had features similar to dark cells of normal ovarian stroma.