Sex Cord Research Articles

Identifying SOX17 as a Sensitive and Specific Marker for Ovarian and Endometrial Carcinomas

Similar to PAX8, SOX17 was recently identified as a master transcription factor of ovarian cancer based on RNA sequencing data. We explored SOX17 utility in diagnosing ovarian tumors and other gynecologic tumors. We systematically evaluated SOX17 expression on tissue microarrays of 398 ovarian tumors of various types, 93 endometrial carcinomas, 80 cervical carcinomas, and 1371 nongynecologic carcinomas, such as those of kidney, thyroid, breast, colon, bladder, liver, bile duct, adrenal gland, pancreas, brain, and lung and malignant melanoma. In addition, we evaluated SOX17 expression in whole tissue sections from 60 gynecologic carcinomas and 10 angiosarcomas. The results demonstrated that SOX17 was highly expressed in most ovarian and endometrial tumors with strong intensity. However, unlike PAX8, it was predominately negative in other tested tumor types, including kidney and thyroid tumors. In particular, SOX17 was highly expressed in the following pathologic subtypes of ovarian tumors: serous carcinoma, clear cell carcinoma, endometrioid carcinoma, and germ cell tumors. SOX17 was mostly negative in mucinous carcinoma and sex cord stromal tumors. In addition, SOX17 was expressed in vascular endothelial cells and was positive in all tested angiosarcomas. In summary, our results demonstrate that SOX17 is a sensitive and specific marker for ovarian nonmucinous carcinomas and endometrial carcinomas. For ovarian germ cell tumors and angiosarcomas, SOX17 demonstrates higher specificity than PAX8, with comparable sensitivity. Furthermore, SOX17 positivity in endothelial cells serves as an internal positive control, making it an excellent marker.

Role of Frozen Sections in Diagnosing Female Genital Tract Lesions: A Tertiary Centre Study in Chennai, India

Introduction: Female Genital Tract (FGT) malignancies are common with ovarian cancers having high incidence and mortality. The asymptomatic character, difficult location and lack of effective screening methods make Intraoperative Frozen Section (IFS) an effective diagnostic test to guide the surgical decisions. Aim: To assess the performance of IFS, describe the associated demographic, clinicopathological factors and identify the errors leading to discordance when compared with Permanent Section (PS). Materials and Methods: A retrospective study of all the consecutive IFS consultations related to FGT lesions received in the Pathology Department between January 2013 to June 2022 was conducted between July 2022 to September 2022 at ESIC Medical College and Hospital, Chennai, Tamil Nadu, India. Cases with IFS deferred until PS section were excluded. The FS and PS reports, demographic, clinicopathological data, Risk of Malignancy Index (RMI), imaging and biochemical records were retrieved. In-depth descriptive analysis of clinicopathological parameters as frequency and percentage, frequency distribution of PS diagnosis, concordant and discordant categorisation, reasons for the discordance were described and the diagnostic accuracy of Frozen Section (FS) tool was calculated. Mean, Frequency (n) and percentage (%) analysis was done for the complete collected data. Results: Out of the total 35 FGT related IFS consultations received, 32 (91.43%) was for Ovarian Tumours (OT), which included 26 surface epithelial tumours, three sex cord stromal tumours, two germ cell tumours, one Krukenberg tumour. Two cases were deferred due to extensive haemorrhage and infarction. Confirmation of the diagnosis was the most common indication. The mean size of the OT (n=32) was 13 cm and ranged from 2 to 31 cm. RMI was low (<25) in 14 (44%, n=32), intermediate (25-250) in 10 (31%, n=32) and high (>250) in 8 (25%, n=32) of OT. The diagnostic accuracy of FS of all the FGT cases (n=35) was 85.71% (n=35 FGT cases) with an error rate of 14.29% was observed. Five OT cases had discordant FS diagnosis, 3 cases due to sampling error and mis-interpretation error in the remaining 2 cases. Artefacts like poor morphology due to tissue freezing, nucleomegaly, poor sectioning and section folding were observed in the discordant cases. Conclusions: Correct use of IFS along with careful preoperative work-up will help the surgeon intraoperatively. A good rapport among clinicians, pathologists and laboratory personnel will aid to improve the diagnostic accuracy. Periodic assessment of IFS tool is necessary as a quality check.

Profile of HER2/neu Expression in Surface Epithelial Ovarian Tumours: A Clinicomorphological Study

Introduction: Surface Epithelial Ovarian Tumours (SEOT) are most prevalent tumours and account for about two third of all ovarian cancers. Survival of ovarian carcinoma is poor despite optimal surgical and chemotherapeutic management. Evaluation of new diagnostic and prognostic Immunohistochemical (IHC) markers will be essential in this aspect. Aim: To evaluate quantitatively the profile of Human Epidermal growth factor Receptor 2 (HER2)/neu IHC expression with standard scoring system in SEOTs and their association with various clinicpathologic variables (age, laterality, CA 125 levels, histological subtype and FIGO staging). Materials and Methods: The present ambispective study was done in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India, from August 2020 to August 2022 with a sample size of 166 cases. All the histopathological samples of SEOT during the study period from August 2020 to August 2022 (prospective) and all borderline, malignant and few benign cases from June 2016 to August 2020 (retrospective) were also included in the study. Cases for which slides and blocks were not available and patient treated with neo adjuvant chemotherapy or radiotherapy were excluded in the study. For prospective cases after getting clinical history and Cancer Antigen 125 (CA 125) level, specimens were fixed, processed and Haematoxylin and Eosin (H&E), IHC staining was done as per standard lab protocol, for retrospective cases clinical history, CA 125 levels, pathological diagnosis and tissue blocks were retrieved, IHC performed and finally both prospective and retrospective cases HER2/neu IHC expression association was studied related to clinicopathological parameters. Results: Out of total sample, SEOT was the most common (n=184, 76.98%) tumour cases, followed by germ cell tumours (n=42, 17.57%) cases and least common was sex cord stromal tumour (n=13, 5.43%). HER2/neu had higher IHC expression in malignant tumours and showed statistically significant positive association with age (p-value=0.001), CA 125 level (p-value0.001), and histological diagnosis (p-value <0.001), but there is no significant association with size of tumour (p-value=0.786), parity (p-value=0.717), laterality (p-value=0.514) and the International Federation of Gynecology and Obstetrics (FIGO) grading (p-value=0.274). Conclusion: Malignant tumours had high HER2/neu IHC expression, thus emphasising its carcinogenic role and helps in the diagnostic differentiation of benign and borderline tumours with malignant potential from actual malignant tumours and can be a therapeutic target in future.

Germ Cell Tumors of the Ovary: A Review.

Ovarian germ cell tumors are a diverse group of benign and malignant neoplasms that occur in a wide age range, but with a predilection for younger age group. The majority are represented by the frequently encountered mature cystic teratomas. Malignant germ cell tumors are uncommon, and in some cases have a characteristic clinical presentation. However, from a histologic standpoint these tumors can sometimes be challenging to diagnose due to overlapping morphology with epithelial, and in some cases sex cord tumors. In these cases, a panel of immunohistochemical stains often facilitates the correct diagnosis. This review article discusses the clinicopathologic findings and pertinent ancillary studies of both common and uncommon germ cell tumors of the ovary.

ClinicoPathological Overview of Ovarian Tumors and Diagnostic Utility of Imprint Cytology

Introduction: For intra-operative diagnosis of ovarian tumors, imprint cytology is the method which gives result within 20 min. It does not affect the quality and utility of the specimen for histopathology. Despite advances in genetics and imaging, histopathological analysis remains the mainstay of ovarian tumor diagnosis. Aim: To describe incidence, age distribution, histological characteristics and whenever feasible, correlate the histopathological diagnosis of ovarian tumors with the imprint cytology technique. Materials and Methods: A total of 200 patients with ovarian tumors were included in this ambispective study from January 2017 to April 2022 at the Dr. D. Y. Patil Medical College, Hospital and Research Center, Pimpri. Results: One hundred and forty-eight (74%) of the 200 cases were benign, while 52 (26%) were malignant. The peak age incidence of benign tumors was in the second to fourth decades and malignant ovarian tumors was in fourth to sixth decades. Ovarian tumors involved the left ovary (n = 104, 52%) more than the right ovary (n = 90, 45%). Out of 200 cases, 130 cases (65%) were surface epithelial ovarian tumors, followed by 50 cases (25%) were germ cell tumors, followed by 14 cases (7%) were sex cord stromal tumors followed by 3 cases (3%) were secondary/metastatic tumors of ovary. Imprint cytology technique done on 148 cases (74%) showed 100% correlation with the histopathological diagnosis. Conclusion: Imprint cytology diagnosis correlated with the histopathological diagnosis of ovarian tumors.

Clinicopathological features of Adult Granulosa Cell Tumour of OvaryA Case Series of 14 Cases

Adult Granulosa Cell Tumour (AGCT) is the most common sex cord stromal tumour of ovaries. These tumours in comparison with epithelial tumours are of low-grade malignant potential and have low recurrence rate after surgical procedure. In this case series, a retrospective search for ovarian AGCT cases from January 2016 till January 2021 was done. A total of 14 cases were included. Parameters studied in this case series were age, laterality, gross, architectural pattern, call Exner bodies, nuclear grooves, necrosis, mitotic count and tumour staging. After studying all the cases, it was reported that mean age of presentation was 44 years (range 21-64 years), unilateral with right-sided dominance (71.4%), grossly 78.5% of the cases were solid cystic with haemorrhagic area, with mean tumour size of 9 cm, 57.1% cases had call Exner bodies, and all the cases showed nuclear groves. Most of the cases, 85.7% presented with low mitotic count of <4/10 High Power Field (HPF). Rare presentation of endometroid carcinomaendometrium World Health Organisation (WHO) Female Genital Tract (FGT) fifth edition), and mature teratoma of contralateral ovary presented in one case each. This case series outlines characteristic histomorphological feature, frequent presentation at lower stage, and low mitotic count, these characteristic features act as prognostic marker for recurrence prediction.

Case Report - Fibrosarcoma of Ovary

Fibrosarcoma of ovary, a tumour arising do novo or secondary to malignant transformation of benign fibromatous tumours, is an extremely rare malignant sex cord stromal tumour of ovary. As on today, the total number of reported cases throughout the world is not more than hundred, There is no clearcut diagnostic criteria, prognostic factor and treatment modalities. Usually it presents as unilateral solid tumour. It can occur at any age though postmenopausal diagnosis is more frequent. Majority of the patients present with vague abdominal pain and a lump in lower abdomen arising from ovary. Ultrasonographic findings usually reveals unilateral solid homogenous tumour in ovary with uneven echo enhancement and increased vascularity. Serum tumor markers and sex hormones such as CA-125 usually found within normal levels. Peroperative frozen section study often concludes into wrong diagnosis, postoperative histopathological diagnosis usually reveals spindle cells with high mitotic activity with Background of fibrous tissue. Depending on mitotic activity, cellular atypia associated with haemorhage and necrosis, it is differentiated from benign fibroma with mitotic activity. Immunohistochemistry findings may be positive for vimentin, á-inhibin, SMA, estrogen receptor, progesterone receptor. Ki-67 positive rate is associated with degree of severity of malignancy i.e, grading and prognosis. Our case was having the above features and was confirmed postoperatively by histological and later by histochemistry with positive Vimentin and Ki-67. As there were not enough cases to conclude a final treatment protocol, so far treated cases revealed total cytoreductive surgery followed by postoperative chemotherapy has the better prognosis. A round, solid unilateral heterogenous ovarian tumor should be taken in differential diagnosis of ovarian fibrosarcoma. As this is an extremely rare tumour of the ovary, there is usually no rise of specific tumuor marker, no conclusive diagnostive criteria available at present, clinical studies involving multicentered approach associated with studies at molecular level is a prime requirement for the gynaecologist to diagnose and treat in a better way in future. J Bangladesh Coll Phys Surg 2023; 41: 89-92

A 12-Year-Old Girl with Juvenile Granulosa Cell Tumor of the Ovary, Presenting with Adolescent Hyperprolactinemia, Galactorrhea, and Amenorrhea.

BACKGROUND Juvenile-type granulosa cell tumors (JGCTs) are a rare subtype of sex cord stromal tumor with a characteristic histology that is commonly found in the first 3 decades of life. It most commonly presents with symptoms of hyperestrogenism, which may present as precocious pseudopuberty or as menstruation-related symptoms, allowing for early detection of the tumor. CASE REPORT We present the case of a 12-year-old girl who presented to her primary care provider (PCP) with secondary amenorrhea with intermittent abdominal pain, who underwent an ultrasound for further evaluation, which revealed a large incidental pelvic mass. She was admitted to the Emergency Department (ED) and had findings of galactorrhea and hyperprolactinemia on examination. Imaging studies demonstrated a large ovarian mass measuring 15.0×9.0×18.8 cm that was resected, and subsequent pathology results showed JGCT stage 1A. CONCLUSIONS Prognosis of granulosa cell tumors (GCT) largely depends on its initial size, stage at diagnosis, residual tumors after surgery, and the subtype of GCT. If the patient is of reproductive age, fertility-sparing surgical options must be considered and patients must be regularly monitored for recurrence. JGCTs can present with minimal to no symptoms of precocious puberty in young girls but may present with amenorrhea, which may be considered normal for their developmental age. Although JGCTs are rare, they are important to include in differential diagnoses of younger female patients with abdominal pain, especially if accompanied by hormonal irregularities.

True hermaphroditism with sex cord tumor with annular tubules (SCTAT): a rare case report and review of the literature

BackgroundTrue hermaphroditism is a rare condition. It is defined as the presence of both testicular and ovarian tissues in the same individual. Sex cord tumour with annular tubules (SCTAT) is a rare stromal tumour of the sex cord that occurs mostly in the ovaries.Case presentationA 16-year-old girl presented to the gynaecology department with primary amenorrhea. Gynaecological examination revealed an enlarged clitoris that looked like a small penis. The chromosome karyotype was chimaera. The postoperative pathology confirmed true hermaphroditism with SCTAT. The patient underwent hormonal replacement after an operation and had no evidence of recurrence for 6 months.ConclusionCases of true hermaphroditism with SCTAT are extremely rare conditions. Surgery and hormonal replacement are important for improving the prognosis of such patients.

Intraoperative endoscopy-assisted tumor debulking in pediatric peutz-jeghers syndrome with early onset massive polyp burden phenotype

Peutz-Jeghers Syndrome is an autosomal dominant disorder linked to abnormalities in STK11, and is associated with mucocutaneous pigmentation, sex cord tumors, and gastrointestinal polyps. While it is extremely rare in children under the age of 2, several cases of profound disease have been documented in this population. Here, we detail a case of Peutz-Jeghers Syndrome presenting initially as intussusception, where massive polyp burden nearly occluded the duodenum of a 15-month-old patient and required multimodal operative intervention. Further, we posit that race-based implicit bias may contribute to delays in care and the identification of patients at risk for rare diseases, particularly with atypical presentation, such as the child highlighted in this case. • Varying genetic anomalies may yield more aggressive expression of Peutz-Jeghers Syndrome. • Variance in phenotypic aggression may require alternative screening models. • Social determinants of health and disparities should be considered in screening guidelines.

The Oncogenic FOXL2 C134W Mutation Is a Key Driver of Granulosa Cell Tumors.

A newly generated mouse model carrying a FOXL2 mutation characteristic of adult-type granulosa cell tumors shows that FOXL2 C134W shifts the transcriptome towards a signature of granulosa cell cancer and drives tumorigenesis.

Review of Sclerosing stromal tumor: A relatively rare ovarian neoplasm

Abstract Introduction/Objective Sclerosing stromal tumor (SST) is sex cord stromal tumor which is rare primary ovarian neoplasm. Because its clinical presentation and imaging findings accurate preoperative clinical diagnosis can be difficult. We report three cases of a sclerosing stromal tumor of ovary and histopathological presentation. Methods/Case Report Our patients had an age ranged from 27-40 years with primary ovarian neoplasm and as incidental in 64-year-old patient. Radiologically lobulated and heterogeneously enhancing, partially calcified masses with nodular rind of avid enhancement about the periphery of the lesion with high risk malignancy were seen. Grossly the masses had firm tan-white, solid, lobulated cut surfaces with patchy calcifications Results (if a Case Study enter NA) Microscopically all the three tumors showed a hyalinized, well-circumscribed nodule with few scattered trabeculae of spindled to plump cells with pale grey cytoplasm within a sclerotic stroma with few staghorn- like blood vessels around the periphery. Scattered calcifications were identified. No mitoses are identified. The reticulin stain showed pericellular focal nested staining pattern. There was no necrosis, pleomorphism, or features of malignancy were identified. Findings were consistent with a sclerosing stromal tumor. Conclusion Ovarian sex cord-stromal tumors are relatively infrequent neoplasms of all primary ovarian tumors. Clinical and sonographic findings alone do not predict the presence of this tumor. SSTs should be considered in differentials in young females with unilateral masses with cystic and solid masses. These tumors carry a good prognosis. Histopathological features along with immunohistochemsitry establish the diagnosis.

Malignant testicular unclassified sex cord stromal tumor: a case report

BackgroundMost testicular tumors are germ cell tumors; sex cord stromal tumors are infrequent, accounting for only 3–5% of testicular tumors. Unclassified sex cord stromal tumors are extremely rare. Generally, 10% of sex cord stromal tumors are malignant. We report a case of malignant unclassified sex cord stromal tumor with retroperitoneal lymph node metastasis at first visit and a corresponding literature review.Case presentationA 72-year-old Japanese man visited our department primarily for indolent right scrotum enlargement in September 2020. Blood biochemistry examination, urinalysis, and tumor markers (alpha-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) showed no abnormal findings. Contrast-enhanced computed tomography showed enlarged para-aortic lymph node (18 × 16 and 10 × 102 mm); a 50 × 452 mm mass with uneven contents was found in the right testicle. The patient underwent inguinal orchiectomy in September 2020. As per immunohistochemistry, the tumor cells were diffusely positive for SF-1 and Ki-67, partially positive for inhibin, and negative for CAM5.2, CK7, CK20, C-KIT, CD30, LCA, GATA-3, TTF-1, and PAX8. Calretinin was expressed in approximately 5% of tumor cells; thus, sex cord/gonadal stroma components were considered to be involved. The final pathological diagnosis was unclassified malignant sex cord stromal tumor. The patient was diagnosed with pT1, N1, M0, S0, and tumor–node–metastasis stage IIA disease. The patient received postoperative chemotherapy with four courses of etoposide and cisplatin therapy from November 2020. Post-chemotherapeutic computed tomography showed new metastatic lesions including lung, liver, pancreas, and para-aortic lymphadenopathy, which increased in size. Disease progression was observed. Cancer genome research was performed using the OncoGuide National Cancer Center oncopanel system; however, no gene mutation for which the drug could be expected to be effective was found. The patient opted for best supportive care at a nearby hospital and died from cancer progression in January 2022.ConclusionWe encountered a case of malignant testicular unclassified sex cord stromal tumor pathologically diagnosed as testicular tumor with retroperitoneal lymph node metastasis in a patient who underwent inguinal orchiectomy. Future data collection is necessary to establish multimodality therapy for malignant testicular unclassified sex cord stromal tumor.

Targeted Disruption of Lats1 and Lats2 in Mice Impairs Testis Development and Alters Somatic Cell Fate.

Hippo signaling plays an essential role in the development of numerous tissues. Although it was previously shown that the transcriptional effectors of Hippo signaling Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) can fine-tune the regulation of sex differentiation genes in the testes, the role of Hippo signaling in testis development remains largely unknown. To further explore the role of Hippo signaling in the testes, we conditionally deleted the key Hippo kinases large tumor suppressor homolog kinases 1 and -2 (Lats1 and Lats2, two kinases that antagonize YAP and TAZ transcriptional co-regulatory activity) in the somatic cells of the testes using an Nr5a1-cre strain (Lats1flox/flox;Lats2flox/flox;Nr5a1-cre). We report here that early stages of testis somatic cell differentiation were not affected in this model but progressive testis cord dysgenesis was observed starting at gestational day e14.5. Testis cord dysgenesis was further associated with the loss of polarity of the Sertoli cells and the loss of SOX9 expression but not WT1. In parallel with testis cord dysgenesis, a loss of steroidogenic gene expression associated with the appearance of myofibroblast-like cells in the interstitial space was also observed in mutant animals. Furthermore, the loss of YAP phosphorylation, the accumulation of nuclear TAZ (and YAP) in both the Sertoli and interstitial cell populations, and an increase in their transcriptional co-regulatory activity in the testes suggest that the observed phenotype could be attributed at least in part to YAP and TAZ. Taken together, our results suggest that Hippo signaling is required to maintain proper differentiation of testis somatic cells.

Gonadal Sex Differentiation and Ovarian Organogenesis along the Cortical-Medullary Axis in Mammals.

In most mammals, the sex of the gonads is based on the fate of the supporting cell lineages, which arises from the proliferation of coelomic epithelium (CE) that surfaces on the bipotential genital ridge in both XY and XX embryos. Recent genetic studies and single-cell transcriptome analyses in mice have revealed the cellular and molecular events in the two-wave proliferation of the CE that produce the supporting cells. This proliferation contributes to the formation of the primary sex cords in the medullary region of both the testis and the ovary at the early phase of gonadal sex differentiation, as well as to that of the secondary sex cords in the cortical region of the ovary at the perinatal stage. To support gametogenesis, the testis forms seminiferous tubules in the medullary region, whereas the ovary forms follicles mainly in the cortical region. The medullary region in the ovary exhibits morphological and functional diversity among mammalian species that ranges from ovary-like to testis-like characteristics. This review focuses on the mechanism of gonadal sex differentiation along the cortical-medullary axis and compares the features of the cortical and medullary regions of the ovary in mammalian species.

Pathological Features of Ovarian Tumors, Diagnosed at a Tertiary Care Hospital in Afghanistan: A Cross-sectional Study.

In Afghanistan, research work is still in its infancy and there is no national level tumor registry at the moment in the country that could elaborate the histopathological features of ovarian tumors in the country. The current study was conducted with the aim to describe pathological characteristics of ovarian tumors diagnosed at tertiary level in Afghanistan. A descriptive cross-sectional study was conducted, including 198 cases diagnosed with ovarian tumors, that were consecutively included in the study from July 2017 to August 2020. All the cases were diagnosed at the Department of Pathology, French Medical Institute for Mothers and Children, Kabul, Afghanistan, that receives biopsy samples from all of the tertiary care institutions in Kabul. In the current study, majority of the ovarian tumors were benign and presented with nonspecific symptoms. The mean age at diagnosis was 34.4 (SD ±13.4). Benign tumors comprised 81.8%, borderline 1.5% and malignant 16.7% of the cases. Majority of the diagnosed tumors were from surface epithelium in origin, followed by germ cell tumors, sex cord stromal tumors, and a single metastatic tumor. The most common benign neoplasm was mature cystic teratoma, followed by benign serous cystadenoma. Considering the malignant tumors, serous cystadenocarcinoma and adult granulosa cell tumors were predominant, followed by endometrioid adenocarcinoma and mucinous cystadenocarcinoma. More than half of the ovarian tumors occurred between 21 and 40 years of age. In the current study, the proportion of malignant ovarian neoplasms was significantly less than benign lesions. Although, many of the pathological features related to ovarian neoplasms were similar to the features demonstrated in other regions of the world, there were important findings that were exclusively noted in the cases diagnosed in Afghanistan.

PMON227 Rare ovarian luteinized fibrothecoma as cause of severe hyperandrogenism in a pre-menopausal woman.

Abstract Ovarian fibromas and fibrothecomas constitute up to 4.7% of ovarian sex cord stromal tumors (OSCSTs). Luteinized fibrothecomas (LFs) are a histological subvariant of OSCSTs. Typically benign and rare, LFs are mostly diagnosed in post-menopausal women with only 30% in women <30. Only 11% of LFs present with androgen excess (AE). We describe a case of severe hyperandrogenism from an ovarian LF in a young woman with primary amenorrhea and infertility.A 23-year-old woman presented for evaluation of hyperandrogenism. Iatrogenic menarche occurred at age 22, induced by letrozole and medroxyprogesterone (MP). BP was 133/86 mm Hg and BMI was 52 kg/m2. Exam revealed diffuse obesity, severe hirsutism (Ferriman Gallwey score 29), and severe acanthosis nigricans, but no scalp alopecia, deep voice, violaceous striae or bruising. Total testosterone (TT) was 108 ng/dl (2-45), free testosterone (FT) 24.7 pg/ml (0.1-6.4 dialysis), prolactin 13.2 ng/ml (<30), DHEAS 2308 ng/ml (240-4330), and TSH 1.29 µIU/mL (0.45-5.33). FSH, LH and estradiol could not be interpreted due to unclear timing in cycle. 17-hydroxyprogesterone after MP challenge was 73 ng/dl (<200). Pelvic ultrasound (US) gave normal endometrial stripe of 3.82 mm. Pelvic US and MRI showed polycystic ovarian morphology without masses. CT abdomen showed normal adrenal glands. Ovarian and adrenal vein sampling (OAVS) lateralized AE to the left ovary (LO). LO TT was 5743 ng/dl with associated IVC sample of 139 ng/dl, ratio of 41, and right ovarian TT was 381 ng/dl with associated IVC sample of 32 ng/dl, ratio of 1.18. Just prior to left oophorectomy, preoperative TT was 103 ng/dl, FT 27.8 pg/ml (0.1-6.4 dialysis), and androstenedione (A4) 212 ng/dl (mid-follicular 51-213). Two days post-operatively, TT dropped to 55 ng/dl, FT 11 pg/ml (0.2-5), and A4 105 ng/dl. Pathology revealed a 3.8 cm LF. Six weeks post-operatively, TT and FT normalized to 18 and 3.6 (0.2-5), respectively.Features atypical for PCOS, including presentation outside age 15-25, rapid progression, TT >2× upper limit of normal (ULN), and free androgen index >4× ULN should prompt thorough evaluation. Adherence to guidelines for TT threshold >150 in a pre-menopausal woman and focus on PCO morphology would have provided false reassurance. Maintaining a high degree of suspicion for an androgen-secreting tumor (AST) is paramount when clinical presentation is atypical. OAVS is usually performed when imaging fails to reveal an abnormality, as small ovarian tumors cannot be excluded. Our patient presented with symptoms atypical for PCOS including severe hirsutism and TT >2× ULN, raising concern for an AST. OAVS lateralized AE to her LO. Resection resulted in testosterone normalization and finding of a rare LF. Identifying the source of AE is especially important in women of reproductive age to restore normal reproductive function. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Uterine Tumors Resembling Ovarian Sex Cord Tumors: A Clinicopathologic Study of 75 Cases Emphasizing Features Predicting Adverse Outcome and Differential Diagnosis.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs), first characterized by Drs Clement and Scully in 1976, are rare neoplasms showing clinical, morphologic, and immunohistochemical overlap with a number of other uterine tumors, most being mesenchymal. Criteria for aggressive behavior are not clearly established. We report 75 tumors from patients ranging from 21 to 84 (mean=52.4) years. Seventy-one patients were treated by hysterectomy and 4 by conservative total excision. Thirty-eight tumors were intramyometrial, 34 submucosal, and 3 cervical; they ranged from 0.6 to 20 (mean=4.9)cm and were typically tan-yellow. Sixty-eight neoplasms were well-circumscribed and 7 had infiltrative borders (4 only minimally). In 56 tumors, a smooth muscle component was intimately admixed with the neoplastic cells ("pseudoinfiltration"; extensive in 29). Architectural patterns included cords (n=53), diffuse (n=51), hollow tubules (n=48), nests (n=38), trabeculae (n=37), retiform (n=23), solid tubules (n=21), pseudoangiomatoid (n=11), pseudopapillary (n=4), and whorled (n=2); typically, more than 1 pattern was seen. Tumor cells were epithelioid (n=62), epithelioid and spindled (n=12), or spindled (n=1) and/or rhabdoid (n=20; extensive in 2). Cytologic atypia was absent to mild in 57, moderate in 16, and moderate to severe in 2 tumors. Fifty-seven UTROSCTs had ≤2mitoses/10 high power fields (HPF), 12 had 3 to 5/10 HPF, and 6 >5/10 HPF. Necrosis was present in 3 and lymphovascular invasion in 1. Tumor cells showed a polyphenotypic immunohistochemical profile (with positivity for sex cord, smooth muscle, and epithelial markers), most commonly inhibin (17/33+) and calretinin (22/31+) positive. Five of 58 patients with follow-up (22 to 192; mean=73.2mo) had recurrences/metastases from 30 to 144 months, and 2 died of disease. Malignant tumors showed >3 of the following 5 features compared with benign tumors: size >5cm, at least moderate cytologic atypia, ≥3 mitoses/10 HPF, infiltrative borders, and necrosis. One of the 5 malignant tumors showed an extensive rhabdoid morphology. UTROSCTs are uncommon, show a wide morphologic spectrum, often pose problems in differential diagnosis, and typically have a benign outcome. Rare tumors are associated with late recurrences and a combination of more than 3 of the 5 features listed above predicted aggressive behavior in this series.

SCLEROSING STROMAL TUMOR: AN INCIDENTAL FINDING IN PATIENT OF INFERTILLITY

Ovarian sex cord stromal tumors are infrequent and represents only 7% of all ovarian neoplasm. Cells of origin of these tumors are primitive sex cords or stromal cells. The stromal cells comprise of theca cells, fibroblasts and Leydig cells whereas the gonadal primitive sex cords include granulosa cells and Sertoli cells. According to recent WHO classification sex cord stromal tumors are further subdivided into pure stromal tumors, pure sex cord tumors and mixed sex cord stromal tumors. Here we are going to discuss a rare case of pure stromal tumors i.e., Sclerosing stromal tumor.

Inhibin Alpha Expression in Human Tumors: A Tissue Microarray Study on 12,212 Tumors.

As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in <33% of cases of 46 additional tumor entities. In summary, these data support the use of INHA antibodies for detecting sex cord stromal tumors, granular cell tumors, and adrenocortical neoplasms. Since INHA can also be found in other tumor entities, INHA immunohistochemistry should only be considered as a part of any panel for the distinction of tumor entities.