Leydig Cell Tumor Research Articles

Cytokeratin-positive interstitial reticulum cell (CIRC) tumor in the lymph node: a case report of the transformation from the epithelioid cell type to the spindle cell type

BackgroundCytokeratin-positive interstitial reticulum cells (CIRCs), which are a subgroup of fibroblastic reticular cells (FRCs), are known to be present in the lymph nodes. There have been only a few cases of tumors derived from CIRCs.Case presentationWe have reported a new case involving a CIRC tumor in a 75-year-old man and reviewed the literature. The resected mediastinal lymph nodes showed epithelial-like proliferation of large atypical round and polygonal epithelioid cells. The tumor cells expressed CK8, CK18, CAM5.2, AE1/AE3, epithelial membrane antigen, vimentin, fascin, and some FRC markers, which is consistent with the diagnosis of a CIRC tumor. Following chemotherapy, the CIRC tumor was observed to have responded very well and became difficult to confirm on imaging, but a small cell lung carcinoma developed 12 months later. Chemoradiotherapy was performed, but the patient passed away 29 months after the initial diagnosis. The autopsy revealed the recurrence of the CIRC tumor, residual small cell lung carcinoma, and a very small latent carcinoma of the prostate. The relapsed CIRC tumor cells had a spindle shape; they were highly pleomorphic and had invaded the superior vena cava.ConclusionWe first reported autopsy findings of CIRC tumors and demonstrated the transformation of the tumor from the epithelioid cell type to the spindle cell type.

The Leydig cell tumour Scaled Score (LeSS): a method to distinguish benign from malignant cases, with additional correlation with MDM2 and CDK4 amplification.

To investigate the morphological and molecular characteristics of Leydig cell tumours (LCTs) of the testis for the identification of cases that may metastasise. Six parameters for a predictive model of the metastatic risk were evaluated in 37 benign and 14 malignant LCTs of the testis [LCT Scaled Score (LeSS)]. The tumour size (benign LCTs, mean 13.3mm; malignant LCTs, mean 44mm) (P<0.001) and five other parameters (infiltrative margins, necrosis, vascular invasion, mitotic count, and nuclear atypia) showed significant differences (Wilcoxon's test, P<0.001). Eight metastatic LCTs and one benign LCT had infiltrative margins. Foci of coagulative necrosis occurred in 10 metastatic LCTs, whereas vascular invasion was identified in nine of 14 metastatic LCTs and none of 37 benign LCTs. Benign LCTs showed <2 mitoses/10 high-power fields (HPFs), whereas a high mitotic count (range, 3-50 mitoses/10 HPFs) was a feature of malignant LCTs. These parameters were selected by use of an inferential analysis based on univariate logistic regression models to develop a score. A LeSS of <4 correctly identified all histologically and clinically benign LCTs. A LeSS of ≥4 correctly identified all malignant LCTs. MDM2 and CDK4 immunostains were applied in all 51 cases: benign LCTs were negative; three of 11 malignant LCTs (27%) showed strong and diffuse immunopositivity and high levels of MDM2 and CDK4 amplification as determined with fluorescence in-situ hybridisation analysis and next-generation sequencing. We provide a new tool, the LeSS, for the prediction of malignant behaviour in LCTs.

Risk of gonadal neoplasia in patients with disorders/differences of sex development

BackgroundPatients with disorders/differences of sex development (DSD), especially those possessing the Y chromosome, have a higher risk of gonadal germ-cell tumours (GCTs). We aimed to examine the incidence of different types of gonadal neoplasia and associated risk factors. MethodsA total of 1040 DSD patients aged ≥16 years participated in a cross-sectional multicentre European study (dsd-LIFE). Data on medical history were gathered from the patients’ archival medical documents. A web-based questionnaire was filled out individually by the participants. A physical examination was performed in all, while ultrasonography of gonads was carried out in 214 and semen analysis was performed for 53 patients. ResultsGerm-cell neoplasia was present in 12 % of patients with DSD and in 14 % of those with XY DSD. The highest risk (36 %) was observed in 46,XY patients with gonadal dysgenesis (GD): complete GD (33 %) and partial GD (23 %), but also in mixed GD (8 %) and complete androgen insensitivity syndrome (AIS) (6%). It was not reported in partial AIS, XX male, 46,XX DSD and congenital adrenal hyperplasia, Turner and Klinefelter syndromes, or in androgen biosynthesis defects. Benign sex cord-stromal tumours (Sertoli- and Leydig-cell tumours) were noted only in patients with complete AIS (3.1 %) and Klinefelter syndrome (14.3 %). A relationship between risk factors for GCT and gonadal neoplasia appearance, other than the Y chromosome, was not found. ConclusionAdult patients with GD and the Y chromosome have the highest risk of GCT and should be kept under thorough medical control and receive special medical follow-up to prevent the development of gonadal tumours.

Testicular adrenal rest tumor (TART) in congenital adrenal hyperplasia misdiagnosed as Leydig cell tumor

Testicular adrenal rest tumor (TART) in congenital adrenal hyperplasia misdiagnosed as Leydig cell tumor

Leydig cell tumor of the ovary: a rare cause of postmenopausal virilization

Leydig cell tumor of the ovary: a rare cause of postmenopausal virilization

Hyperandrogenism caused by a leydig cell tumor of the ovary: A case report

Hyperandrogenism caused by a leydig cell tumor of the ovary: A case report

Glucagon-like peptide-1 receptor is expressed in human and rodent testis.

The incretin hormone glucagon-like peptide-l (GLP-1) is an important regulator of post-prandial insulin secretion, acting through a G protein-coupled cell surface receptor (GLP-1R). In addition to its expression in pancreatic β-cells, several studies suggested that GLP-1R is located in extra-pancreatic tissues. In this study, we examined for the first time the testicular distribution of the GLP-1R, both in normal human and neoplastic testicular tissues as well as in rodent testis and rodent testicular cell lines. The GLP-1R distribution in testicular section has been evaluated by immunohistochemistry, the specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA by RISH technology. While GLP-1R expression in terms of protein was detected by western blot analysis, Moreover, mRNA levels were determined in human testis, in rodent Leydig, and Sertoli cell lines. Using immunohistochemistrya specific staining for GLP-1R was detected in Leydig cells. The specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA only in these cell types. Species differences in the GLP-1R expression between humans and rodents were observed. Interestingly, a decreased expression of the receptor in rodent tumor Leydig cell line and an absence in human Leydig tumor samples was detected. It may be hypothesized that GLP-1R acts like an oncosuppressor in Leydig tumors. A role in regulation of hormone secretion by GLP-1 has been shown in other endocrine cells, therefore we hypothesized that GLP-1R is able to modulate somehow the Leydig cell function. In our findings, a careful evaluation of human testicular tissues and rodent testis revealed Leydig cells as a potential target for GLP-1. Collectively, an effect of GLP-1R in Leydig cell function may be presumed although future studies are needed to ascertain the GLP-1R's role both in normal and tumor Leydig cells.

Ovarian Gynandroblastoma with a Juvenile Granulosa Cell Tumor Component in a Postmenopausal Woman.

Ovarian gynandroblastoma (GAB) is an extremely rare sex cord-stromal tumor showing morphological evidence of both female (granulosa cell tumor) and male (Sertoli–Leydig cell tumor (SLCT)) components. Almost all GAB cases have been reported in children, adolescents, or women of reproductive age, and most of them typically have adult granulosa cell tumors as the female component. In contrast, GAB with a juvenile granulosa cell tumor (JGCT) component is a very rare condition; to the best of our knowledge, only one case of GAB with JGCT in a postmenopausal woman has been reported. In this report, we present an extremely rare case of ovarian GAB with JGCT in an elderly patient. A 65-year-old woman presented with an abdominal mass. Abdominopelvic magnetic resonance imaging revealed a large multiseptated cystic mass measuring 20 cm. No peritoneal seeding, lymph node enlargement, or hematogenous metastasis was identified. Laboratory test showed a slight elevation of serum CA 125 level (37.1 U/mL). Based on the preoperative clinical impression of ovarian cancer, she underwent a total hysterectomy with bilateral salpingo-oophorectomy. Grossly, the ovarian mass had a smooth and glistening surface without excrescences. The cut sections showed yellow-to-tan solid areas with foci of necrosis, myxoid degeneration, and hemorrhage, as well as multilocular cystic cavities filled with serosanguinous fluid. Histologically, the female component was characterized by JGCT displaying nodular growth patterns with follicle-like structures of various shapes and sizes. Most of the microcysts contained eosinophilic or basophilic secretions. The JGCT cells had indistinct cell borders, an abundant eosinophilic cytoplasm, and round-to-oval hyperchromatic nuclei with many mitotic figures. The SLCT component consisted predominantly of intermediately differentiated Sertoli cells forming lobulated solid nodules. They were arranged in cords, solid tubules, or nests, and possessed oval-to-spindle-shaped darkly stained nuclei and scant cytoplasm. In several foci, well-formed Sertoli cell tubules were loosely aggregated within areas of moderately differentiated SLCT. In summary, we described GAB in a postmenopausal woman with JGCT and SLCT as the female and male components, respectively. This is the second case of GAB with JGCT occurring in an elderly patient. Our findings can help pathologists and clinicians make accurate histological diagnoses of GAB with a JGCT component and plan an adequate treatment strategy for this rare tumor.

Sertoli-Leydig Cell Tumor (SLCT) of the Ovary - A Case Report

Sertoli-Leydig Cell Tumor (SLCT) is an extremely rare and distinctive sex cord-stromal tumor. Ovarian sex cord-stromal tumors are infrequent tumors that differ from the more frequent epithelial neoplasm and have strong association with hormone-mediated syndromes, presentation in a wide age range, and the diagnosis is usually at early-stage disease with a good outcome. SLCT typically present with pelvic or abdominal pain and tenderness, mass, and or abnormal menstruation, and with hormonal activity reported predominantly after menarche. We report a case of 18-year-old unmarried female presented with severe pain and lump in the lower abdomen. She was a case of primary amenorrhea with normal secondary sex characters. She was a suspected case of twisted ovarian tumor on USG and underwent laparotomy followed by total excision of the lump and histopathology report revealed Sertoli-Leydig Cell Tumor. Though it is a rare tumor, the possibility of Sertoli-Leydig Cell Tumor in a young woman should be kept in mind. Key Words: Ovarian tumor, Sclerosing stromal tumor, sex cord-stromal tumor, Sertoli- Leydig Cell Tumor.&#x0D; Bangladesh J Obstet Gynaecol, 2017; Vol. 32(2) : 117-120

Testicular tumors in 190 dogs: clinical, macroscopic and histopathological aspects

ABSTRACT: This study aimed to characterize the prevalence and clinical, macroscopic and histopathological aspects of dogs affected by testicular tumors based on biopsy specimens from the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (LPV-UFSM) over 19 years. Parameters regarding the age, size, and breed of the affected dogs were also established. Of all dogs with some type of neoplasm submitted to histopathological analysis at the LPV over these 19 years (n=1,900), 213 (11.2%) had at least one testicular neoplasm. The tissues of 190 dogs (with 220 neoplasms) were available for histological reassessment. The dogs in this study had different types of testicular tumors with relatively similar frequencies. In descending order, the most frequent testicular neoplasms were seminomas (88/220), Leydig (interstitial) cell tumor (LCT; 64/220), Sertoli cell tumor (SCT; 61/220), and mixed germ cell-sex cord stromal tumor (MGSCT) (07/220). Among the dogs of defined breed (119 cases), large breeds had the largest number of cases (50/119), followed by small (47/119) and medium-sized (22/119) breeds. The ages of dogs affected by testicular tumors ranged from 10 months to 18 years. Increased testicular volume was the most common clinical manifestation. Eleven dogs presented information about clinical signs suggestive of hyperestrogenism syndrome (feminization). In seminomas, the diffuse pattern predominated over the intratubular pattern. Two sites (luminal and basal compartments) suggestive of the onset of neoplastic transformations in germ cells were observed in intratubular seminomas. They corroborate the hypothesis that canine seminomas possibly have pathogenesis similar to that observed in human spermatocytic seminomas. The SCTs and LCTs presented high cell morphology variation. SCTs had neoplastic cells organized in five different histological arrangements. As for LCT, solid-diffuse and cystic-vascular histological patterns were the most commonly observed. Through this study, it was possible to establish some of the leading clinical, macroscopic, and histopathological aspects of testicular neoplasms diagnosed over 19 years in the area covered by the LPV-UFSM.

Tumor de células de Leydig puro de ovario en mujer premenopáusica

Los tumores de células de Leydig del ovario son un tipo raro de tumores del estroma del cordón sexual, con menos de 0,1% de todos los tumores de ovario. Representan un desafío diagnóstico, no solo por su incidencia esporádica sino también por presentar imágenes aparentemente normales. Aunque son más comunes en las mujeres menopaúsicas, también se ha descrito casos en mujeres premenopáusicas. La característica clínica más común es la aparición de virilización rápida y progresiva; más de 75% de las pacientes muestra signos de virilización debido a la sobreproducción de testosterona. La concentración sérica de testosterona representa el marcador más útil en el diagnóstico del tumor ovárico secretor de andrógenos. El tumor de células de Leydig ovárico siempre debe ser considerado en mujer en edad reproductiva con síntomas de virilización. Se presenta un caso de tumor de células de Leydig puro de ovario en mujer premenopáusica.

Toxicological Effects of Cadmium on Mammalian Testis.

Cadmium is a heavy metal, and people are exposed to it through contaminated foods and smoking. In humans and other mammals, cadmium causes damage to male testis. In this review, we summarize the effects of cadmium on the development and function of the testis. Cadmium causes severe structural damage to the seminiferous tubules, Sertoli cells, and blood-testis barrier, thus leading to the loss of sperm. Cadmium hinders Leydig cell development, inhibits Leydig cell function, and induces Leydig cell tumors. Cadmium also disrupts the vascular system of the testis. Cadmium is a reactive oxygen species inducer and possibly induces DNA damage, thus epigenetically regulating somatic cell and germ cell function, leading to male subfertility/infertility.

Interstitial Leydig Cell Tumorigenesis—Leptin and Adiponectin Signaling in Relation to Aromatase Expression in the Human Testis

Although epidemiological studies from the last years report an increase in the incidences of Leydig cell tumors (previously thought to be a rare disease), the biochemical characteristics of that tumor important for understanding its etiology, diagnosis, and therapy still remains not completely characterized. Our prior studies reported G-protein coupled estrogen receptor signaling and estrogen level disturbances in Leydig cell tumors. In addition, we found that expressions of multi-level-acting lipid balance- and steroidogenesis–controlling proteins including peroxisome proliferator-activated receptor are altered in this tumor. In order to get deeper into the other molecular mechanisms that regulate lipid homeostasis in the Leydig cell tumor, here we investigate the presence and expression of newly-described hormones responsible for lipid homeostasis balancing (leptin and adiponectin), together with expression of estrogen synthase (aromatase). Samples of Leydig cell tumors (n = 20) were obtained from patients (31–45 years old) and used for light and transmission electron microscopic, western blotting, and immunohistochemical analyses. In addition, body mass index (BMI) was calculated. In tumor mass, abundant lipid accumulation in Leydig cells and various alterations of Leydig cell shape, as well as the presence of adipocyte-like cells, were observed. Marked lipid content and various lipid droplet size, especially in obese patients, may indicate alterations in lipid homeostasis, lipid processing, and steroidogenic organelle function in response to interstitial tissue pathological changes. We revealed significantly increased expression of leptin, adiponectin and their receptors, as well as aromatase in Leydig cell tumors in comparison to control. The majority of patients (n = 13) were overweight as indicated by their BMI. Moreover, a significant increase in expression of phospholipase C (PLC), and kinases Raf, ERK which are part of adipokine transductional pathways, was demonstrated. These data expand our previous findings suggesting that in human Leydig cell tumors, estrogen level and signaling, together with lipid status, are related to each other. Increased BMI may contribute to certain biochemical characteristics and function of the Leydig cell in infertile patients with a tumor. In addition, altered adipokine-estrogen microenvironment can have an effect on proliferation, growth, and metastasis of tumor cells. We report here various targets (receptors, enzymes, hormones) controlling lipid balance and estrogen action in Leydig cell tumors indicating their possible usefulness for diagnostics and therapy.

Clinical outcome of patients diagnosed with testicular sex cord stromal tumors.

e17055 Background: Testicular Sex Cord Stromal Tumors (TSCST) are rare representing approximately 5% of testicular cancers. Leydig Cell Tumours (LCT) constitute 1-3% of testicular tumours, occur commonly in third to sixth decade and are up to 50mm in diameter. Sertoli Cell Tumours(SCT) constitute less than 1%, occur commonly in the fourth decade and have an average diameter of 35mm. High-risk histological features include; tumour size, increased mitotic activity, pleomorphic nuclei, necrosis, vascular invasion and rete testis invasion. Management is surgical with no standard chemotherapy or radiotherapy in adjuvant or metastatic setting. Methods: A retrospective review of epidemiology, radiological staging, histopathological features, relapse rate and treatment in 82 patients diagnosed with TSCST between 4/12/2001 -27/12/2018 at a tertiary referral centre. Results: 2,170 testicular cancer patients were diagnosed in this period of whom 82 patients (3.8%) had TSCST. 65 patients (2.9% ) had LCT,13 patients (0.59%) had SCT, 3 patients had Unclassified SCST and 1 patient had Mixed SCST. Median patient age for LCT was 43 years, SCT was 29 years, unclassified SCST was 46 years and for mixed SCST was 49 years (age range of TSCST was 18 - 82 years). Median size of LCT was 11mm (range 4 – 28 mm) in 43 patients and of SCT was 16mm (range 7 – 60mm) in 10 patients. 79 patients (3.6% ) presented with stage 1 disease. One patient with LCT and 4 high risk histological features on initial diagnosis had local retroperitoneal recurrence 4 years later and underwent surgical resection with 1year distant disease-free survival. On distant relapse, he was treated with mitotane. One patient presented with metastatic SCT with 4 histological high risk features. He was treated with carboplatin and etoposide. Median survival in the metastatic disease was 10.5 months. Conclusions: TSCST have an excellent prognosis with over 98% of patients are free of disease post-surgery. Our relapse rate is 1.2% which is lower than previously reported and is confined to patients with high risk features. Metastatic LCT and SCT are resistant to chemotherapy with poor survival.

Androgenic Granulosa Cell Tumor in an Adolescent Girl

Virilizing tumors may arise from adrenals or ovary. Androgen secreting ovarian tumors constitute less than 0.2% of cases of hyperandrogenism and less than 1% of all ovarian tumors. Hyperandrogenism is seen with Leydig cell tumors, Sertoli cell tumors, steroid cell tumors not otherwise specified and ovarian thecomas. Adult granulosa cell tumors (GCTs) are the most common type of ovarian sex cord tumors. These tumors usually produce estrogens and hence cause symptoms and signs of estrogen excess. GCTs mostly present in perimenopausal and postmenopausal women with complaints of abnormal uterine bleeding. Androgen secreting GCT is a rare clinical entity. Here we are reporting one such case in an adolescent girl with features of hyperandrogenism and ovarian mass.

Successful IVF Pregnancy in a Young Patient with Stromal Leydig Cell Tumour and Adenofibroma Simultaneously

Successful IVF Pregnancy in a Young Patient with Stromal Leydig Cell Tumour and Adenofibroma Simultaneously

SUN-005 Hirsutism Due to Bilateral Leydig Cell Tumors

Severe hyperandrogenism in post-menopausal women is rare. It may be caused by either benign or malignant neoplasms of the adrenal or ovary. We report a rare case of a post-menopausal woman with hirsutism associated with virilization due to Leydig cell tumors (LCT) of both ovaries. Case report 61 yo female presented for evaluation of hirsutism. She had also been experiencing increased facial hair growth, deepening of voice, clitoromegaly, alopecia, and acne. Physical examination: normal vital signs. Patient had signs of virilization, including coarse hair along her upper lip, chin, lower abdomen and inner thigh with Ferriman-Gallwey score of 8, acne, and clitoromegaly. She had no signs of acanthosis nigricans or Cushing syndrome. Base line labs: Hemoglobin 16.2 gm/dL (ref 12.0 to 15.5), total testosterone 803 ng/dL (ref 3–41), free testosterone 20.2 pg/mL (ref 0.0–4.2), estradiol 77 pg/mL (<6.0−54.7), estrone 148 pg/mL (ref 7–40), FSH 11.5 mIU/mL (ref 25.8 - 134.8), LH 6.90 mIU/mL (ref 7.7 - 58.5), androstenedione 28 ng/dL (ref 17–99), DHEAS 99.9 mcg/dL (ref 19–205), dehydroepiandrosterone 512 ng/dL (ref 31–701), inhibin A 2.3 pg/mL (ref <5), inhibin B <7.0 pg/mL (ref 00-16.9), 17-alpha hydroxyprogesterone 187 ng/dl (ref <51). Her other serum markers such as anti -Mullerian hormone, alpha-fetoprotein, and hCG were normal. A CT scan of adrenals: normal. Similarly a transvaginal US did not show any ovarian pathology, however MRI of the pelvis showed homogeneous ovarian enhancement bilaterally and based on this information a diagnosis of ovarian hyperthecosis was considered and patient underwent laparoscopic bilateral oophorectomy. Pathology confirmed: LCT in both ovaries. Laboratory values performed 3 months later showed the following values: hemoglobin 14.2 gm/dL, total testosterone 13 ng/dL, free testosterone 1.4 pg/mL, LH 124 mIU/mL, FSH 99mIU/mL, estradiol <5.0 pg/mL. In 6 months she had significant improvement in hirsutism and virilization. Discussion Hyperandrogenism, especially serum testosterone in the male range with rapidly progressive hirsutism or virilization signs in a female indicates tumor etiology. Androgen-secreting ovarian tumors are usually small and often embedded in the ovary. Transvaginal US is useful in the diagnosis of ovarian tumors. However, in our case, transvaginal US failed while MRI scan showed bilaterally enlarged ovaries and with this information patient underwent bilateral oophorectomy. Although 5 cases of bilateral LCT are reported in the literature, LCT is unilateral 95% of the time, the pathogenesis of Leydig cell proliferation and LCT is unclear. In conclusion, androgen secreting tumors should be considered in women (especially in post-menopausal state) with hyperandrogenism and hirsutism. In fact, diffuse stromal Leydig cell hyperplasia and small Leydig cell tumors may be missed on imaging and in some cases only pathology can confirm the result.

SUN-011 Beyond PCOS - Ovarian Neoplasms Presenting with Hirsutism and Virilization

BACKGROUND: PCOS is the most common cause of hirsutism in women of reproductive age. The presence of virilization in addition to hirsutism should alert to the possibility of less common causes of hyper-androgenization (HA) in this population including otherwise uncommon functional ovarian neoplasms (FON). We present 3 cases of women initially thought to have PCOS in whom virilization was the prime clue to the correct diagnosis of FON. Clinical Case series: Case 1 is a 40yr old woman with obesity and dysmetabolic syndrome referred for hirsutism presumed due to PCOS. She had noted symptoms over 2–3 yrs with amenorrhea and associated infertility. Examination revealed marked hirsutism and virilization with Ferriman-Galleway score (FGS) of 20. Lab tests confirmed marked male range HA. Multiple imaging tests revealed no adrenal or ovarian mass lesions. FDG-PET scan finally revealed a left ovarian focus for which she has left oophorectomy that revealed a 1cm Leydig cell tumor, Her HA resolved post-op and spontaneous periods resumed. Case 2 is a 45yr old woman referred with possible PCOS who had 5 mth history of progressive hirsutism and generalized hypertrichosis, dull lower abdominal pain and amenorrhea. Examination revealed marked hirsutism with generalized hypertrichosis and virilization. FGS was 25 and clitoral index was 935mm2. Lab tests confirmed marked male range HA and abdominopelvic imaging show no adrenal lesions but a 5.2cm left ovarian mass. Left salpingo-oophorectomy revealed a steroid cell tumor and postoperatively her androgen levels normalized. Case 3 is 37 yr old woman with SLE and obesity with prior gastric bypass referred with presumed PCOS but presenting with 1 yr history of progressive hirsutism. She was initially thought to have non classical CAH and treated with oral glucocorticoids with no symptom improvement. Examination revealed marked hirsutism, virilization with elevated FGS and clitoromegaly. Lab tests showed marked male range HA but multiple imaging studies revealed no apparent adrenal or ovarian lesions. Patient had no fertility interests and so had elective total hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed a 2.5cm left ovarian Leydig cell tumor not apparent at surgery and post op her androgen levels normalized. Conclusion: The distinction between PCOS which is ubiquitous and FON which is rare hinges on careful history and examination. Rapid onset hirsutism with virilization should prompt suspicion of FON. Marked male range HA (total serum testosterone >250ng/dl) is another “red flag” finding. Persistent radiologic search for such lesions should continue as they may not be immediately apparent on routine abdominopelvic imaging.

MON-024 Steroid Cell Tumor, Not Otherwise Specified; A Rare Case of Hyperandrogenism

BACKGROUND:Steroid cell tumor is a rare sex cord stromal tumor. There are 3 types including steroid cell tumor not otherwise specified (NOS), stromal luteoma and leydig cell tumors.Steroid cell tumor (NOS) is the most common of all the subtypes. About 75% of the steroid cell tumor (NOS) are secretory. They can secrete androgens and estrogens. In a few cases, cortisol and renin secretion have been reported. The patient’s clinical features depend on the hormone secreted.CASE PRESENTATIONHere, we report a case of a 22-year-old woman who was seen at an outpatient clinic for hirsutism, irregular menstrual bleeding, and progressive weight gain. Examination revealed androgenic facial hair growth, clitoromegaly and obesity.Initial differentials on presentation were PCOS, ovarian or adrenal pathology. Initial LH, FSH values were normal. Lab investigation showed elevated testosterone, DHEAS and 17-OH progesterone levels. Baseline labs showed Androstenedione of 3345 ng/dl (41-262 ng/dl), DHEAS of 595.5 ug/dl (110- 431.7 ug/dl), 17-OH progesterone was 2394 ng/dl (follicular: 15-70 ng/dl, Luteal: 35-290 ng/dl), total and free testosterone was 558 ng/dl (premenopausal; 10-55ng/dl) and 33.0 pg/ml, (0.8-1.4pg/ml), respectively. Patient subsequently had an ACTH stimulation test which showed an increase in 17-OH progesterone from 384 ng/dl to 657 ng/dl and a repeat showed an elevation from 204 to 322 ng/dl, ruling out a late onset CAH. She was then sent for pelvic sonogram which showed the presence of a left ovarian mass 4.9x 4.8x 4.8 cm and a pelvic CT scan confirmed a left ovarian mass measuring 6.8x5.5x 5.5 cm and an unremarkable right ovary. She underwent a laparoscopic unilateral salpino-oophorectomy and histology confirmed the diagnosis of an ovarian steroid cell tumor (NOS). Post-surgery, the androgen levels returned to normal. The patient is now being followed for recurrence.CONCLUSIONWomen who present with virilism should be evaluated adequately with comprehensive history taking and physical examination along with appropriate biochemical tests and imaging studies to confirm tumor location and plan for surgery.

SUN-719 The Impact of FOXA3 on Testicular Steroidogenesis

The Forkhead box(Fox) transcription factors are evolutionarily conserved in organisms and regulate diverse biological processes during development as well as adult life. Among the Fox family, FoxA subfamily members Foxa1-3 have been termed `pioneer’ transcription factors as they bind both nucleosome-bound and nucleosome-free DNA targets with the same recognition site. Foxa3 is the only member of FoxA subfamily that is expressed in both male and female gonads. In the testis, Foxa3 is expressed in spermatids and interstitial Leydig cells. We focused our study to elucidate the role of FOXA3 in Leydig cells and its impact on testicular steroidogenesis. Expression of FOXA3 dramatically decreased in mouse Leydig cells during testicular development. In addition, the time-dependent expression of FOXA3 showed an opposite pattern to that of steroidogenic genes in cAMP-induced primary Leydig cells. Meanwhile, Nur77 is among the prime regulators of steroidogenesis in the testicular Leydig cells. Overexpression of FOXA3 in MA-10 cells (mouse Leydig tumor cell line) repressed the cAMP-induced Nur77 promoter activity, which further resulted in the reduced activity of Nur77-target steroidogenic gene promoters (StAR, CYP17A1and 3β-HSD). Similar to above results, the expression of Nur77 and its target genes,StAR, 3β-HSD and CYP11A1, were repressed by adenovirus-mediated overexpression of FOXA3 in mouse primary Leydig cells, although the expression of CYP17A1, another steroidogenic gene, was differentially affected. These results suggest that FOXA3 locally regulates the expression of steroidogenic genes through Nur77 during testicular development.