Sex Cord-stromal Tumors Research Articles

Relevance of Molecular Pathology for the Diagnosis of Sex Cord-Stromal Tumors of the Ovary: A Narrative Review.

Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz-Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli-Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.

Molecular features for timely cancer diagnosis and treatment - tumors of the ovary, fallopian tube and endometrium.

Gynecologic pathology has moved, within only a few years, from being a diagnostic area devoid of molecular testing into a diagnostic discipline in which such analyses are becoming routine. The direct relevance of molecular characterization to the choice of treatment of patients with carcinomas originating in both the uterus and adnexae makes it likely that such testing will only expand along with our understanding of the molecular make-up of these tumors. As a consequence, gynecologic pathologists have become an integral part of patient management, rather than lab personnel providing external services.In parallel, molecular testing is expanding as a tool for diagnosing rare tumors affecting these organs, including soft tissue tumors, sex cord-stromal tumors and germ cell tumors, as well as other rare entities. Increased knowledge in this area bears directly on the ability to diagnose these tumors in a reproducible manner, as well as recognize and consult on genetic diseases. Hopefully, despite the inherent difficulty in studying rare cancers, it will also translate into new therapeutic options for the malignant ones among these rare cancers.

Histopathological spectrum of ovarian neoplasms - A 3 year hospital based study

: Ovarian neoplasms are the fifth leading cause of cancer mortality among females worldwide. It is associated with poor survival due to late clinical presentation with most cases presenting at stage III or stage IV.: The present study was undertaken to assess the histopathological spectrum of ovarian neoplasms according to the World Health Organization classification (2020) and to determine the frequency and age distribution of these neoplasms in a tertiary care hospital. : This observational study was conducted over a period of 3 years (August 2016 to July 2019) in the Department of Pathology, Gandhi Medical College, Telangana, India. All ovarian neoplasm specimens were routinely processed and histopathological examination was done for each specimen.: A total of 115 cases were included in the study out of which 97 (84.34%) cases were benign, 6 (5.22%) cases were borderline and 12 (10.44%) cases were malignant. Surface epithelial tumours were the most common, followed by germ cell tumours and sex cord-stromal tumours. The age group of 31-40 years showed the largest percentage of ovarian neoplasms.: Ovaries are a common site for tumours. Most patients present at late stages due to non-specific symptoms. Ovarian neoplasms are associated with a variety of clinical and morphological features and hence a correct histopathological diagnosis is required to institute appropriate therapy.

Diagnostic accuracy and replicability of Frozen section diagnosis in Ovarian Masses- A Tertiary health care institutional experience

Introduction: Ovarian neoplasms are a composite group of tumors including surface epithelial, germ cell and sex cord stromal tumors. A subgroup of neoplasms, borderline tumors are also present. The surgical management of each group of neoplasm is varied. Since preoperative diagnosis is arbitrary, the role of the intraoperative frozen section has become beneficial.
 Purpose: In our study, we aimed to evaluate the diagnostic accuracy of the frozen section by comparing it with the definitive histopathological report.
 Methods: This was a 5 years retrospective study (June 2018 to June 2023). Data of the patients have been retrieved from archives of Histopathology from the Department of Pathology. The specimens received, after gross examination few blocks have been prepared on the frozen section and finally processed for routine paraffin sections for the final histopathological report. Then the results of the frozen section and H&E sections were compared and categorized as benign, borderline and malignant to get the accuracy of frozen section.
 Results: Out of 75 frozen section diagnoses included in our study, benign contributed 58.7%, borderline- 13.3% and malignant- 28%. The final paraffin sections revealed benign tumors- 57.3%, borderline- 10.7% and malignant- 32%. There were 7 discordant cases among which 2 were overdiagnosed and 5 were underdiagnosed.
 Conclusion: The overall accuracy rate of our study was 93.7% which is within the limit of the accuracy range reported in the literature. Hence, the intraoperative frozen section is an important diagnostic tool for surgeons in determining the treatment of ovarian masses with certain limitations.

Bilateral Gonadoblastoma in a 13-Year-Old Female with Turner Syndrome and Y Chromosome: A Case Report

Abstract Introduction/Objective Gonadoblastoma is a relatively rare type of ovarian tumor that has a high risk for patients with 45X/46XY. It is derived from the Y chromosome at its long arm GBY region, which contains the most likely candidate gene called testis-specific protein Y-encoded (TSPY). Methods/Case Report In this case report, we present a case of a 13-year-old girl with Turner syndrome whose cytogenetic test showed 45X with monosomy X and a siodicentric Yq chromosome. As she carried a high risk for the development of gonadoblastoma due to the presence of the Y chromosome and clinically had premature ovarian failure, she received further imaging studies, which did not reveal obvious ovarian masses. She underwent resections of bilateral fallopian tubes and ovaries. Bilateral fallopian tubes were unremarkable. However, within the bilateral ovarian tissue, foci of gonadoblastoma were found (0.5 to 0.6 cm), composed of large round germ cells (confirmed by positive OCT 3/4 and SALL4 stains) intermingled with oval-shaped sex cord-stromal cells forming tubular/cribriform structures (confirmed by positive staining for inhibin, calretinin, and FOXL2). The stromal cells of gonadoblastoma, but not germ cells, were positive for androgen receptor staining, while both components were negative for estrogen receptor staining. No invasive germ cell tumor or sex cord tumor was present. Results (if a Case Study enter NA) N/A Conclusion The positive androgen receptor staining in stromal cells of the gonadoblastoma supports the view that the Y chromosome-driven androgen system may play a role in the development of gonadoblastoma in a bi-cellular pattern.

Clinicopathological features and molecular genetic changes in 17 cases of uterine tumor resembling ovarian sex cord tumor

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that was recently reported to exhibit recurrent NCOA1-3rearrangement with the most frequent partners ESR1 and GREB1. In this study, the clinicopathological characteristics of 17 UTROSCT cases were summarized; among them, the fusion genes of 12 cases were retrospectively analyzed by targeted RNA sequencing. The mean age of our cohort was 47 years (19–67 y). Although the majority of UTROSCTs had clear boundaries on gross examination, microscopic infiltration into the myometrium was observed in 82.4 % of cases. The tumor cells showed diffuse, trabecular, nested, reticular, pseudopapillary, hollow and solid tubular patterns, expressing sex cord, epithelial, and myogenic markers. Six fusion genes, including ESR1::NCOA3 (n = 4), ESR1::NCOA2 (n = 2), ESR1::CITED2 (n = 2), GREB1::NCOA2 (n = 2), GREB1::NCOA1 (n = 1), and GREB1::NCOA3 (n = 1), were identified. The fusion genes of the three cases with recurrence and metastasis were GREB1::NCOA2, ESR1::NCOA3, and ESR1::CITED2. All 3 cases of recurrent tumors showed infiltrative growth, with moderate to severe dysplasia of tumor cells and different degrees of rhabdomyoid differentiation. This is the first report of the ESR1::CITED2 fusion genes in UTROSCT, and one of the two patients had recurrence and metastasis. Compared with UTROSCT withESR1 rearrangement, UTROSCT with GREB1 rearrangement was more common in elderly patientsand was more likely to present with intramural masses, less sex cord differentiation, poor prognosis, and relapse and metastasis.

Uterine Tumours Resembling Ovarian Sex-Cord Tumors: A Case Report and Review of the Literature.

Uterine tumors resembling ovarian sex-cord tumors (UTROSCT) are thought to develop from pluripotent uterine mesenchymal cells or endometrial stromal cells with secondary sex-cord differentiation. The patient was a 73-year-old postmenopausal woman who had abnormal vaginal bleeding, and she underwent a laparoscopic hysterectomy with bilateral salpingo-oophorectomy. The diagnosis was a case of UTROSCT. A scoping review of the UTROSCT case report present in the literature has been conducted, and 63 articles were found, of which 45 were considered for the 66 clinical cases examined. At the time of diagnosis, six metastatic localizations were found in 59 patients undergoing demolitive surgery (10.2%). Recurrences were diagnosed in 13/59 (22%) patients with multiple locations. A molecular study was performed in 18/66 cases (27.3%) and genetic alterations were found in 10/18 (55.6%) patients. UTROSCTs are considered rare uterine tumors, typically with a favorable prognosis, and are generally considered to have a good prognosis. But, from the review done, they may already manifest themselves at advanced stages, with the possibility of recurrences even at a distance. It would, therefore, be important to be able to define the most aggressive forms and, perhaps, molecular investigation with sequencing could help identify patients most at risk.

Mitotically Active Cellular Fibroma of the Ovary: A Case Report

Ovarian fibromas are benign sex cord stromal tumors composed of fibroblastic cells within a collagenous stroma. Fibromas are composed of spindled, ovoid to round cells and collagenous stroma. There are three types of benign fibromas: Fibroma with minor sex cord elements, cellular fibroma and mitotically active cellular fibroma. Fibromas are most common ovarian stromal tumors and encompasses approximately 4% of all ovarian tumors. Cellular fibromas represent approximately 10% of all ovarian fibromas. According to published studies median age of patients with ovarian fibroma is 48 years and are uncommon before 30. The potential of mitotically active cellular fibromas for reccurence and malignant transformation is low (approximately 1%) but possible. So, diagnosis od MACF is important in order to avoid misdiagnosis with ovarian fibrosarcomas and to avoid unnecessary overtreatment. Also, because of low but possible malignant potential in case of MACF, long term follow-up should be recommended. We report a case of mitotically active cellular fibroma in a 68 year old woman with previous vaginal hysterectomy without adnexectomy who applied to our clinic with mild pelvic pain and discomfort. Our intention is to point out its rarity among ovarian tumors and need for long term follow-up, because of its low but possible potential for reccurence and malignant transformation.

Ovarian Sertoli cell tumor: A rare case of sex cord stromal tumor in a three-year female

Sertoli–Leydig cell tumors (SLCTs), also known as androblastoma, are rare, accounting for less than 1% of ovarian neoplasms. The clinical manifestations of SLCT range from asymptomatic to severe virilization. The majority of Sertoli cell tumors are highly differentiated, with homogeneous nuclei and few mitotic signs among the neoplastic cells. This study is a case report of a 3-year-old girl who was admitted to Kashani hospital with abdominal pain and a protruding stomach. On the right side of the abdomen, there was a large, lump palpable. Inhibin, calretinin, actine, and WT1 were all detected as positive by immunohistochemistry (IHC) testing. However, CD30, NSE, synaptophysin, vimentin, chromogranin, S100, and AFP were all detected to be negative. Additional information about ovarian sex cord tumors is provided in this case. Sertoli cell tumor should be considered a differential diagnosis in a young girl who has hirsutism, irregular bleeding, and breast atrophy with a pelvic mass.

Testicular Neoplasms With Sex Cord and Stromal Components Harbor a Recurrent Pattern of Chromosomal Gains

A small subset of testicular sex cord-stromal tumors, designated as Sertoli-stromal cell tumors (SSCTs), comprises a mixture of Sertoli, spindle, and/or Leydig cells. The clinicopathologic features of these tumors have not been studied in any detail, and their molecular features are unknown. We, therefore, assessed the morphologic and genomic features of 14 SSCTs, including 1 tumor with features similar to the ovarian Sertoli-Leydig cell tumor (SLCT) with retiform tubules. The median age of the patients was 24 years (range, 10-55 years), and the median tumor size was 2.3 cm (range, 0.7-4.7 cm). All tumors showed Sertoli-like sex cord cells arranged in variably developed tubular structures, typically also forming nests and cords. These imperceptibly blended with a neoplastic spindle cell stroma or, in the SLCT, vacuolated to eosinophilic Leydig cells. Genomic analysis demonstrated the presence of a hotspot loss-of-function DICER1 mutation in the SLCT (patient 1) and hotspot gain-of-function CTNNB1 mutations in the tumors of patients 2 and 3, with both CTNNB1 variants being interpreted as possible subclonal events. The mutations were the only relevant findings in the tumors of patients 1 and 2, whereas the tumor of patient 3 harbored concurrent chromosomal arm-level and chromosome-level copy number gains. Among the remaining 11 tumors, all of those that had interpretable copy number data (9 tumors) harbored multiple recurrent chromosomal arm-level and chromosome-level copy number gains suggestive of a shift in ploidy without concurrent pathogenic mutations. The results of the present study suggest that CTNNB1 mutations (likely subclonal) are only rarely present in SSCTs; instead, most of them harbor genomic alterations similar to those seen in testicular sex cord-stromal tumors with pure or predominant spindle cell components. A notable exception was a testicular SLCT with morphologic features identical to the ovarian counterpart, which harbored a DICER1 mutation.

Clinicopathological Features and Survival Trends of Non-Epithelial Ovarian Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database

Introduction: Owing to their low incidence, no reliable statistics about prognostication derived from large sample sizes have been reported of malignant ovarian germ cell tumors (MOGCTs) and sex cord-stromal tumors (SCSTs). The present study aimed to investigate the clinicopathological prognostic factors and the survival trends of MOGCTs and SCSTs. Materials and Methods: Patients with MOGCTs and SCSTs were recorded in the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2000 and 2019. Clinical, demographic, and treatment characteristics were compared between groups of MOGCTs and SCSTs. Cox risk regression analysis and Kaplan-Meier survival curves were used to compare overall survival (OS) and cancer-specific survival (CSS) and to assess the prognostic factors. Results: Information about 2,506 patients with MOGCTs and 1,556 patients with SCSTs was extracted from the SEER database, respectively. Aged <40 years and single were more common in patients with MOGCTs than in those with SCSTs. The vast majority of patients with MOGCTs and SCSTs underwent surgery (98.1% vs. 94.5%; p < 0.001), and women with MOGCTs were more likely to receive chemotherapy than women with SCSTs (56.1% vs. 32.2%; p < 0.001). For both patients before and after propensity-score matching, the 5-year OS rates of patients with SCSTs were lower than those of patients with MOGCTs (p < 0.05). In multivariate Cox regression analysis, both age and surgery were independent predictors of OS in patients with MOGCTs and SCSTs. FIGO staging was an independent predictor of CSS in MOGCT patients. Tumor size and chemotherapy were also independent predictors of CSS in patients with SCSTs. Conclusion: Compared to patients with SCSTs, those with MOGCTs tended to be younger and had a higher OS and CSS. Adjuvant chemotherapy after surgery did not prolong OS and CSS in patients with SCSTs.

Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors.

Sertoli cell tumor is a type of testicular sex cord-stromal tumor (TSCST) typically driven by gain-of-function CTNNB1 variants. Recently, molecular studies have identified TSCSTs (including Sertoli cell tumors) with loss-of-function APC variants, raising the possibility that germline APC alterations may predispose to TSCSTs. In this study, we evaluated 4 TSCSTs from 4 individual patients, including 3 APC -mutant neoplasms identified in prior studies (1 in a patient with familial adenomatous polyposis [FAP] and 2 in patients with unknown syndromic status) and 1 tumor of unknown mutational status diagnosed in a patient with known FAP. Three neoplasms were typical Sertoli cell tumors, and 1 was a malignant unclassified TSCT. All neoplasms exhibited diffuse nuclear beta-catenin expression. Non-neoplastic tissue could be obtained for DNA sequencing in the 3 Sertoli cell tumors. Comparative assessment of non-neoplastic and lesional tissue in these cases suggested that germline APC variants with subsequent inactivation of the gene (loss of heterozygosity) were the likely oncogenic driver of these Sertoli cell tumors. In the malignant unclassified TSCSTs, APC inactivation was also interpreted as the most likely driver event, and the germline origin of the variant was inferred using a recently published method. The results of this study suggest that pathogenic germline APC alterations (eg, FAP and variants thereof) may predispose to TSCSTs.

Exploring the Role of DICER1 Mutations in Ovarian Sex Cord-Stromal Tumors: A Retrospective Analysis and Implications for Surveillance

Objective: Ovarian sex cord-stromal tumors (OSCSTs) are a rare and heterogeneous group, accounting for less than 1% of all malignancies and about 10% of ovarian tumors in childhood and adolescence. Some OSCSTs have been associated with germline pathogenic DICER1 variations. This study aims to determine the incidence of DICER1 pathogenic variations in a small cohort of OSCSTs and evaluate the clinicopathological features and patient outcomes. Material and Methods: We retrospectively reviewed the medical records of the patients diagnosed with OSCSTs between 2014-2021. Molecular genetic sequencing of the tumor samples to detect a RNase IIIb domain hot spot mutation in DICER1 was performed in five patients. Results: Molecular genetic sequencing of the tumor samples revealed a DICER1 gene mutation in exon 27 c.5437G&gt;C (p.E1813Q) in a patient with Sertoli-Leydig cell tumour. Conclusions: Although our study included a small number of patients, our findings highlight the importance of knowing the possible association between OSCSTs and pathogenic germline DICER1 variants since detecting this mutation may provide the opportunity for surveillance of related conditions that could improve long-term outcomes and survival, and also enable screening of family members.

THU643 Hyperandrogenism Caused By A Steroid Cell Tumor Of The Ovary In A Postmenopausal Woman

Abstract Disclosure: M.S. Myint: None. A. Pinero-Pilona: None. Introduction Steroid cell tumor-not otherwise specified (SCT-NOS) is a subtype of steroid cell tumors which, in turn, is a subtype of sex cord-stroma tumors of the ovary. SCTs are exceedingly rare, account for less than 0.1% of all ovarian tumors, can secrete androstenedione, α-hydroxyprogesterone, and testosterone, and cause hyperandrogenism. We present a case of SCT-NOS, which was revealed postoperatively and was associated with breast cancer. Clinical Case A 74-year-old postmenopausal woman presented approximately a year after the onset of hirsutism, frontal alopecia and an elevated serum total testosterone (TTST) 341 ng/dl (reference range 3 to 41 ng/dL) and free testosterone (FRTST) 10.5 pg/mL (reference range 0.0 to 4.2 pg/mL). She has no clitoromegaly, acne, striae, or changes in voice and no history of infertility or PCOS. Physical examination was significant for cushingoid appearance, frontal alopecia, and hirsutism on the face. Her estradiol level was 213 pg/mL (reference range 0 to 30 pg/mL), FSH and LH levels were in the postmenopausal range, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, and morning cortisol were normal. Pelvic ultrasonography and CT of the abdomen and pelvis did not reveal an adrenal or ovarian abnormality. We suspected an ovarian source and thus recommended bilateral oophorectomy due to the markedly elevated testosterone level and postmenopausal status. We also started spironolactone. Before setting up for surgery, she was diagnosed with invasive lobular left breast cancer and underwent surgery and radiotherapy. Then, she had bilateral salpingo-oophorectomy. After surgery, TTST dropped to 4 ng/dL and FRTST to 2 pg/mL. Her hyperandrogenic symptoms significantly subsided. Pathology revealed a 1.5 cm red-brown nodule within the left ovary. The nodule contains polygonal cells with vacuolated cytoplasm arranged in nests, cords, and sheets. Cells were positive in calretinin and inhibin and negative in Reinke crystal. A steroid cell tumor, NOS was confirmed. Pathologic features associated with aggressive clinical behavior were not present. Conclusion The incidence of SCT-NOS is highest in women of childbearing age but rare in postmenopausal women. There were only a few case reports of SCT-NOS, most of which are relatively larger and revealed on imaging. In our case, the imaging did not localize the tumor. Sex cord-stromal tumors are often not visualized on imaging. Failure to identify a tumor on imaging does not rule out the presence of a tumor. One should always rule out androgen-secreting tumors in cases of significantly high testosterone. When imaging fails to reveal a tumor, bilateral oophorectomy should be considered in postmenopausal women and an ovarian and adrenal venous sampling in women of childbearing age. It is worth doing so because hyperandrogenism is associated with an increased risk of endometrial and breast cancer. Presentation: Thursday, June 15, 2023

THU227 Isosexual Peudo-precocious Puberty Due To Leydig Cell Tumor In A Prepubertal Child

Abstract Disclosure: M. Baby: None. A. Xu: None. N. Shacham: None. E. Shapiro: None. B.C. Shah: None. Background: Testicular tumors account for 2-4% of all childhood cancers. Leydig cell tumors are the most common form of sex cord stromal tumors and represent 1-3% of all testicular tumors. In the pediatric population, testicular Leydig cell tumors present with signs of precocious puberty. Workup reveals low gonadotropins with elevated testosterone and testicular mass on ultrasound. Treatment involves surgical enucleation (partial orchiectomy) in most cases. Clinical case: We present the case of a 4 year 10 month old male who presented to endocrine clinic for precocious puberty. He developed pubic hair three months prior with body odor. He did not have any CNS symptoms including headaches or visual changes. There was no use of exogenous androgens at home. He was born full term, small for gestational age with an uncomplicated postnatal course. There was no family history of precocious puberty. Height was at the 99th percentile (z-score 2.7), weight 98th percentile (z-score 2.07), and BMI 86th percentile (z-score 1.09). On exam, he was lean and appeared muscular. His testes were asymmetrical with the right testicle measuring 3 ml and the left testicle 2 ml. Scrotal hair was curly and sparse, Tanner III. Stretched penile length was 7 cm (90th percentile), width was 3.2 cm. Results: Bone age was advanced to 10 year 0 months with height age of 7 year 3 months. Serum gonadotropins were low, testosterone was pubertal at 115 ng/dl (Electrochemiluminescence Immunoassay). Serum 17-hydroxyprogesterone (221 ng/dl, ref range 0-90 ng/dl) androstenedione (163 ng/dl, ref range = &amp;lt; 51 ng/dl), and IGF-1 (368 ng/ml, ref range 108 – 293 ng/ml) were elevated. ACTH, cortisol, thyroid profile, and prolactin were normal. Beta-HCG and AFP were negative. ACTH stimulation test showed normal response. Testicular ultrasound with doppler was performed; right testicle measured 1.82 x 1.06 x 1.36 cm, volume of 1.4 ml, while left measured 1.27 x 0.72 x 0.87 cm, 0.4 ml. Within the right testicle, there was a mass that was hypoechoic, vascular (with a testicular artery feeding branch in the periphery), multinodular and measured 1.2 x 0.8 x 1.10 cm (0.53 ml). He was referred to urology and underwent enucleation of the right testicular mass through an inguinal approach. Grossly, the mass appeared tan and lobulated and surgical pathology confirmed a benign Leydig cell tumor. The patient recovered well and post-operative serum testosterone level at 2 weeks was &amp;lt;2.5 ng/dl. Conclusion: We present a case of a testicular Leydig cell tumor that presented as peripheral precocious puberty marked by low gonadotropins and elevated testosterone with ultrasound findings of a vascular mass with testicular artery feeding branch in the periphery. Early detection of a Leydig cell tumor is crucial as it can be treated by enucleation thus salvaging the testes. Presentation: Thursday, June 15, 2023

SAT367 A Rare Case of Ovarian Cellular Fibroma Producing Testosterone

Abstract Disclosure: H.K. Rai: None. P. Dandona: None. Background: Ovarian fibromas are hormonally inactive, benign sex cord-stromal tumors. However, the occurrence of ovarian fibromas in a woman presenting with post-menopausal bleeding, hirsutism, and elevated testosterone levels raises suspicion of such tumors being functionally active.Case: 62-year-old menopausal woman presented for evaluation of worsening facial hair for the past year. She reported vaginal spotting for the past two months and was following up with a gynecologist. She denied acne, male pattern baldness, or any other virilizing features. She was also recently diagnosed with polycythemia; hematological workup was remarkable for elevated testosterone. Her blood work was significant for elevated testosterone levels and hemoglobin, results as follows: total testosterone: 160ng/dl (2-45 ng/dL), free testosterone: 25.4pg/ml (0.1-6.4 pg/ml), sex hormone binding globulin (SHBG): 26 nmol/L (14-73 nmol/L), estradiol: &amp;lt;15 pg/ml (post-menopausal range: &amp;lt;/=31 pg/ml), FSH: 17.3mIU/ml (23.0-116.3mIU/ml), LH: 19.1mIU/L (10.0-54.7 mIU/mL), prolactin: 5.7 ng/mL (2.0-20.0 ng/mL), DHEAS: 78 mcg/dL (12-133 mcg/dL), 8 AM cortisol: 17 mcg/dL (10-20 mcg/dL), ACTH: 11pg/ml (6-50pg/ml), Hb: 16.6g/dl (11.7-15.5 g/dL) and hematocrit: 49.8% (35.0-45.0%). Ultrasound pelvis showed heterogeneous thickened endometrium, small left-sided intramural leiomyoma of the uterus and ovaries were not well identified. MRI pelvis with and without contrast showed a 2.4 cm left uterine fibroid. A simple cyst was noted in the right ovary and two para-ovarian cysts were noted on the left ovary. The overall appearance of both ovaries was similar to a CT scan done a year earlier. She underwent a total hysterectomy with bilateral salpingo-oophorectomy. Surgical pathology was remarkable for cellular fibroma of both ovaries. After surgery, the patient's facial hair significantly improved, and she was noted to have normal testosterone levels (total testosterone: 23, free testosterone: 2.6, SHBG: 50). Her hemoglobin normalized as well, reaching a value of 13 g/dL. Conclusion: Our patient presented with post-menopausal bleeding, hirsutism, polycythemia, and increased testosterone levels. After she underwent total hysterectomy with bilateral salpingo-oopherectomy, her symptoms resolved. Testosterone and hemoglobulin levels returned to normal. Surprisingly, ovarian cellular fibroma on both sides was identified by surgical pathology. Ovarian cellular fibromas are rarely linked to endocrine activity, but with this case, we want to emphasize that its hormonal activity needs further exploration in the future. Presentation Date: Saturday, June 17, 2023

Histopathological spectrum of ovarian tumors in tertiary care centre of central India

Abstract Background: Ovarian tumors are common, ranking third in frequency after cervical and uterine cancer. According to the World Ovarian Cancer Coalition Atlas 2018, India has the second-highest incidence of ovarian carcinoma worldwide. In Chhattisgarh, ovarian malignancy accounts for 5.21% of all malignancies in females. Materials and Methods: The present descriptive observational cross-sectional study encompassed 108 cases of ovarian tumors. A histopathological examination was done, and data was compiled and analyzed. Observations and Results: Among the 108 ovarian tumors, 59.25% were noted in women aged 40–59 years. The primary presenting symptom was abdominal pain, reported by 57.40% of the cases. The majority of ovarian tumors were unilateral, the right side being more common. Primary ovarian tumors constituted 91.66%, while 8.33% were classified as secondary or metastatic ovarian tumors. Of 108 cases, 55.5% were malignant, 40.7% were benign, and 3.7% were borderline tumors. Surface epithelial tumors accounted for 73.14% of the cases; germ cell tumors constituted 9.25%, sex cord-stromal tumors were 7.4%, and mesenchymal tumors were 1.85%. Among surface epithelial tumors, serous cystadenocarcinoma was most common. Mature cystic teratoma was the most common germ cell tumor, and granulosa cell tumor was the most common sex cord-stromal tumor. Conclusion: Ovarian tumors were more commonly seen in the peri and postmenopausal age group. Primary malignant epithelial tumors were the most common type of ovarian tumor. The histopathological evaluation of ovarian tumors remains the gold standard for definitive diagnosis.

Severe hemoperitoneum from spontaneous rupture of uterine tumor resembling ovarian sex-cord tumor: A very rare case.

SynopsisA case of uterine tumor resembling ovarian sex‐cord tumor with an unfamiliar presentation. Management was performed based on the clinical findings and the literature recommendations.

Incidence of sex-cord stromal tumor of the ovary: Is there a racial disparity? (2114)

Incidence of sex-cord stromal tumor of the ovary: Is there a racial disparity? (2114)

Detection of FOXL2 C134W Mutation Status by a Novel BaseScope In Situ Hybridization Assay is Highly Sensitive and Specific for Adult Granulosa Cell Tumors

Adult granulosa cell tumors (AGCTs) are a molecularly distinct group of malignant ovarian sex cord-stromal tumors (SCSTs) characterized by a nearly ubiquitous c.402C>G/p.C134W mutation in FOXL2 (hereafter referred to as “C134W”). In some cases, AGCT exhibits marked morphologic overlap with other SCSTs and has an identical immunophenotype, and molecular testing may be necessary to help confirm the diagnosis. However, molecular testing is time consuming, relatively expensive, and unavailable in many pathology laboratories. We describe the development and validation of an in situ hybridization (ISH) custom BaseScope assay for the detection of the FOXL2 C134W mutation. We evaluated 106 ovarian SCSTs, including 78 AGCTs, 9 juvenile granulosa cell tumors, 18 fibromas (cellular and conventional), and 1 SCST, not otherwise specified, as well as 53 epithelial ovarian tumors (42 endometrioid carcinomas and 11 carcinosarcomas) and 1 STK11 adnexal tumor for the presence or absence of FOXL2 wild-type and FOXL2 C134W RNA expression via BaseScope-ISH. Fifty-one tumors had previously undergone DNA sequencing of the FOXL2 gene. Across the entire cohort, the FOXL2 C134W probe staining was positive in 77 of 78 (98.7%) AGCTs. Two of 81 (2.5%) non-AGCTs also showed positive staining, both of which were epithelial ovarian tumors. The assay worked in tissue from blocks >20 years old. There was 100% concordance between the FOXL2 sequencing and BaseScope-ISH results. Overall, assessment of FOXL2 mutation status by custom BaseScope-ISH demonstrated 98.7% sensitivity and 97.5% specificity for the diagnosis of AGCT. BaseScope-ISH for FOXL2 C134W represents a reasonable alternative to sequencing, is quicker and less expensive, and is more easily incorporated than molecular testing into many pathology laboratories. It also has the advantage of requiring less tissue, and the neoplastic cells can be directly visualized on stained sections.