Sex Cord-stromal Tumors Research Articles

Molecular tumor profiling and therapy selection in advanced gynecological cancers: A retrospective cohort analysis from the Australian Molecular Screening and Therapeutics (MoST) Program.

5526 Background: Gynecological (gyne) cancers are highly diverse with distinct sites of origin and histological subtypes that can limit development of evidence-based therapies. Comprehensive genomic profiling (CGP) has an increasing role in characterizing clinically relevant molecular subsets and in identifying actionable biomarkers with potential to guide therapy selection. Methods: MoST (ACTRN12616000908437) is an Australia-wide precision oncology program for adult patients (pts) with advanced cancers and limited treatment options. Tumor specimens are analysed by CGP and genomic results tiered by the level of evidence supporting matched therapies (https://topograph.info). Pts are followed for subsequent treatment and survival. Here, we present data for the MoST gyne cancer cohort. Results: Between Sept 2016 and Oct 2022, 533 gyne tumors were sequenced, with included pts having a minimum 4 months (mo) follow-up. Key histotypes included: ovarian serous (n=162) and non-serous (n=46) epithelial tumors; uterine carcinomas (n=99) and sarcomas (n=108); cervical carcinomas (n=51); germ cell and sex-cord stromal tumors (n=18); carcinosarcomas (n=33); and vulva/vaginal tumors (n=16). The median number of reported variants was 3 (IQR 2-5) and tumor mutational burden 3.1 mut/Mb (IQR 1.3—5.5, Range 0—284); 9 (2%) tumors were microsatellite unstable; and 22 (4%) had high level loss-of-heterozygosity (confirmed on validated genome-wide assays). The most common pathways involved in this pan-gyne cohort were: p53 (n=287, 54%), PI3K/AKT (n=227, 43%), cell cycle (n=182, 34%), and mitogen-activated protein kinase (n=91, 17%). Pathogenic mutations in BRCA1/2 were identified in 29 tumors (5%; 18 in ovarian serous cancers), whereas 81 tumors (15%) had alterations in other homologous recombination genes, most commonly uterine sarcomas (n=32, 30%). Actionable genomic biomarkers matched to a clinically active treatment (TOPOGRAPH tier 1-3) were identified in 207 (39%) tumors. In 19 pts (3.5%) who received Tier 1-3 matched therapy after CGP, a trend towards longer survival was observed (median OS 22.3 mo, 95% CI 17.3 to not reached) compared to those receiving unmatched therapy (n=65, median OS 14.9 mo, 10.2 to 22.1, p=0.052) following CGP. No OS difference was seen in pts who received matched investigational therapy (Tier 3B/4, n=31, median OS 17.0 mo, 8.1 to NR) versus only unmatched therapy (n=118, median OS 14.0 mo, 11.3 to 22.5; HR 0.97, 0.57 to 1.64; p=0.91). Conclusions: CGP identified actionable genomic results in nearly half of advanced gyne cancers, with enrichment in particular histotypes that supports testing above current standard of care. Trends in prolonged OS with subsequent matched therapies may be better realized with earlier testing and improved drug/clinical trial access.

PD-L1 expression, morphology, and molecular characteristic of a subset of aggressive uterine tumor resembling ovarian sex cord tumor and a literature review

BackgroundUterine tumors resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm of unknown etiology and has undetermined malignant potential. The emergence of recurrent UTROSCT case reports has led to its initial identification as a tumor of low malignancy potential. Owing to its low incidence, we currently lack any in-depth studies regarding the subset of UTROSCTs that may be aggressive in nature. Here, we sought to identify unique characteristics in aggressive UTROSCT.Methods19 cases of UTROSCT were collected. Their histologic and tumor immune microenvironment were evaluated by three gynecologic pathologists. The gene alteration was also detected by RNA sequencing. For later analyses regarding differences between benign and malignant tumors, we supplemented our 19 included cases with additional reports from the literature.ResultsInterestingly, we found PD-L1 expression in stromal tumor-infiltrating immune cells (stromal PD-L1) was markedly higher in aggressive UTROSCT. Patients with high stromal PD-L1 (≥ 22.5 cells/mm2) had worse prognosis. When our cases were added with previous cases identified in the literature, we discovered that aggressive UTROSCT was more likely to have significant mitotic activity and NCOA2 gene alterations than benign UTROSCT. Consistence with those results, patients with significant mitotic activity and gene alteration of NCOA2 had worse prognoses.ConclusionsCollectively, high expression of stromal PD-L1, significant mitotic activity, and gene alteration of NCOA2 may be useful markers to predict aggressive UTROSCT.

Pregnant Women With Malignant Ovarian Tumors: A Case Series

Ovarian cancer management during pregnancy is a topic of limited research due to low occurrence rates of malignant adnexal tumors. To shed further light on this issue, we present a case series of 22 pregnant ovarian cancer patients referred to an academic hospital's gynecology oncology department over six years. Data on each patient's demographic and clinical background were collected using a registry software recording surgical tumor staging, disease-free survival (DFS), and overall survival (OS). According to the data analysis reports, subtype epithelial tumor and germ cell pathology were equally 45.4%. However, sex-cord tumors were observed in a smaller percentage of cases (9.1%). Serous adenocarcinoma was the most common subtype among those with epithelial tumors (60%). Meanwhile, 72.7% of these pregnant women had a palpable mass in physical examination. In addition, adnexal mass was detected in 95.4% of ultrasonography. Due to the young age of the patients, fertility-preserving surgery was performed on 63.6% of patients, and chemotherapy was prescripted on 59% of patients. Over a six-year follow-up period, there was a recurrence rate of 22.7%, while DFS and OS were reported as 56% and 82%, respectively. In conclusion, treatment of ovarian malignancies during pregnancy requires an experienced multidisciplinary approach. However, more extensive studies with larger samples are needed to gain more insight into the treatment of ovarian cancer during pregnancy.

Impact of surgery and chemotherapy in ovarian sex cord-stromal tumors from the multicentric Salomé study including 469 patients. A TMRG and GINECO group study

ObjectiveIdentifying prognostic factors and evaluating the impact of adjuvant chemotherapy in patients with sex cord stromal tumors (SCST) is crucial. In this study, we aimed to address these challenges. MethodsWe conducted a retrospective analysis of data from 13 centers of the French Rare malignant gynecological tumors (TMRG) network. We enrolled 469 adult patients with malignant SCST who received upfront surgery since 2011 to July 2015. Results75% were diagnosed with adult Granulosa cell tumors, and 23% had another subtype. With a median follow-up of 6.4 years, 154 patients (33%) developed a first recurrence, 82 (17%) two recurrences, and 49 (10%) three recurrences. Adjuvant chemotherapy was administered in 14.7% of patients at initial diagnosis. In relapse, perioperative chemotherapy was administered in 58.5%, 28.2%, and 23.8% of patients, respectively, in the first, second, and third relapse.In the first-line therapy, age under 70 years, FIGO stage, and complete surgery were associated with longer progression-free survival (PFS). Chemotherapy had no impact on PFS in early-stage disease (FIGO I-II). The PFS was similar using BEP or other chemotherapy regimens (HR 0.88 [0.43; 1.81]) in the first-line therapy. In case of recurrence, PFS was statistically prolonged by complete surgery, but perioperative chemotherapy use did not impact PFS. ConclusionChemotherapy use did not impact survival in the first-line or relapse setting in SCST. Only surgery and its quality demonstrated benefit for PFS in ovarian SCST in any lines of treatment.

Sclerosis in Sex Cord-Stromal Tumors Other Than the Sclerosing Stromal Tumor: A Report of 70 Cases.

Sclerosis is well-known in sclerosing stromal tumors (SSTs), as its name indicates, but has not been evaluated in other ovarian sex cord-stromal tumors (SCSTs). Its presence in other SCSTs has sporadically caused diagnostic problems in cases we have seen, and this prompted us to review SCSTs with appreciable sclerosis; tumors containing at least 20% sclerosis were included. Seventy cases were identified: 20 thecomas, 20 juvenile granulosa cell tumors (JGCTs), 8 adult granulosa cell tumors (AGCTs), 5 sex cord tumors with annular tubules, 6 retiform Sertoli-Leydig cell tumors (SLCTs; all of the intermediate differentiation), 4 nonretiform SLCTs (3 well-differentiated, 1 of intermediate differentiation with heterologous elements), 4 Sertoli cell tumors, and 3 microcystic stromal tumors (MSTs). Paucicellular sclerotic zones comprised 20% to 95% of the tumors and when conspicuous often obscured diagnostic features. Thirty-one tumors (10 thecomas, 19 JGCTs, 1 AGCT, and 1 MST) showed sclerotic zones focally enveloping nodules of tumor cells, imparting a pseudolobular appearance, and sclerosis often occurred within lobules as well. Ten of these (5 thecomas and 5 JGCTs) also had prominent staghorn blood vessels, generating a low-power appearance focally similar to SST. In 17 tumors, the sclerosis resulted in "compression" of the tumor cells into cords and/or solid tubules. Correct diagnosis in these cases is dependent on careful examination of the cellular zones of the neoplasms, but awareness of the extent of sclerosis that may be seen in diverse SCSTs may be crucial in suggesting the correct diagnosis particularly when the material is limited as in the intraoperative setting. Our findings highlight for the first time the occurrence and character of sclerosis in sex cord tumors other than SSTs and fibromas. Sclerosis is seen in descending proportion of the tumor types as follows: retiform SLCTs, thecomas, MSTs, JGCTs, sex cord tumors with annular tubules, Sertoli cell tumors, AGCTs, and nonretiform SLCTs. Its character can vary somewhat, having particular features in the sex cord tumor with annular tubules (hyaline material within tubules often coalescing and extending beyond the nests to form confluent aggregates) and retiform SLCTs (common in papillary cores).

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that mainly harbors NCOA1-3 rearrangements with partner genes ESR1 or GREB1 . Here, we explored 23 UTROSCTs by targeted RNA sequencing. The association between molecular diversity and clinicopathologic features was investigated. The mean age of our cohort was 43 years (23-65y). Only 15 patients (65%) were originally diagnosed with UTROSCTs. Mitotic figures ranged from 1 to 7/10high power fields, of primary tumors and increased from 1 to 9/10high power fields in recurrent tumors. Five types of gene fusions were identified in these patients, including GREB1::NCOA2 (n=7), GREB1::NCOA1 (n=5), ESR1::NCOA2 (n=3), ESR1::NCOA3 (n=7), and GTF2A1::NCOA2 (n=1). To our knowledge, our group included the largest cohort of tumors with GREB1::NCOA2 fusions. Recurrences were most common in patients with GREB1::NCOA2 fusion (57%), followed by 40% ( GREB1::NCOA1 ), 33% ( ESR1::NCOA2 ), and 14% ( ESR1::NCOA3 ). The recurrent patient who harbored an ESR1::NCOA2 fusion was characterized by extensive rhabdoid features. Both of the recurrent patients who harbored GREB1::NCOA1 and ESR1::NCOA3 had the largest tumor sizes in their own gene alteration groups, and another recurrent GREB1::NCOA1 patient had extrauterine involvement. The GREB1 -rearranged patients were of older age, larger tumor size, and higher stage than non- GREB1 -rearranged patients ( P =0.004, 0.028, and 0.016, respectively). In addition, the GREB1 -rearranged tumors presented more commonly as intramural masses rather than non- GREB1 -rearranged tumors presenting as polypoid/submucosal masses ( P =0.021). Microscopically, nested and whorled patterns were frequently seen in GREB1- rearranged patients ( P =0.006). Of note, estrogen receptor expression was weaker than progesterone receptor in all 12 GREB1- rearranged tumors, whereas the similar staining intensity of estrogen receptor and progesterone receptor was observed in all 11 non- GREB1- rearranged tumors ( P <0.0001). This study demonstrated that UTROSCTs were present at a younger age in the Chinese population. The genetic heterogeneity of UTROSCTs was correlated with variable recurrence rate. Tumors with GREB1::NCOA2 fusions are more likely to recur compared with those with other genetic alterations.

HISTOPATHOLOGICAL SPECTRUM OF OVARIAN TUMORS: A DESCRIPTIVE STUDY

Surface epithelial ovarian tumors was the most common category of ovarian tumors followed by germ cell tumors, sex cord stromal tumors and metastatic tumors in decreasing order of frequency. Incidence of benign tumors was much higher than malignant tumors with benign serous cystadenoma being the most common benign tumor and serous cystadenocarcinoma being the most common malignant tumor. Reproductive age group showed higher incidence of ovarian tumors whereas there was increasing incidence of malignancy with increasing age group. Exception to this was the higher incidence of malignant germ cell tumors in adolescent age group. Although nulliparity and low parity showed higher risk of malignancy, early menarche did not reveal any signicant increase in malignancy. Pain in abdomen was the most common symptom whereas ascites was more commonly seen with malignant tumors. Menstrual complaints were observed more commonly with tumors with functional stroma with possible role of hormonal inuence. Benign tumors showed cystic morphology and there was signicant increase in incidence of malignancy in tumors with complex or solid morphology. Thus age more than 50 years, post menopausal age group, solid and complex tumor morphology, presence of ascites, nulliparity or low parity and bilaterality of tumors signicant increased incidence of malignancy and thus these parameters can be used to predict the risk of malignancy in ovarian tumors. This was a descriptive study and analysis of data was done using chi square test and logistic regression analysis

Abstract #1406879: Not Always PCOS: A Case of Virilizing Steroid Cell Ovarian Tumor

Ovarian steroid cell tumors (SCTs) are a rare type of sex-cord stromal tumors that account for 0.1% of all ovarian tumors. These tumors can occur at any age and typically secrete hormones such as androstenedione and testosterone. We report a young woman with known microprolactinoma who presented with secondary amenorrhea and virilization and was found to have a steroid secreting ovarian SCT. A 32-year-old nulligravid woman with history of infertility presented for evaluation for amenorrhea. Three years ago, she developed oligomenorrhea and was subsequently found to have hyperprolactinemia and an 8mm pituitary microadenoma. Thyroid function tests and IGF-1 at the time were normal, no other workup was obtained. She was started on cabergoline, though after developing full body hives was switched to bromocriptine. Despite prolactin normalization from 69.9 to 14.7 ng/mL and shrinkage of pituitary adenoma to 7mm after 1 year of therapy, she developed amenorrhea, acne, and new facial hair. Her testosterone was found elevated 212ng/dL and she states was then diagnosed with PCOS. In light of no clinical improvement and mental health issues, she self-discontinued her bromocriptine and was lost to follow up. Upon current presentation she reported last menstrual period 24 months ago, continued acne and facial hair, and now temporal hair loss and deepening voice. Ferriman-Gallwey score was 20/36. She did not have clinical signs of Cushing’s syndrome. Repeat prolactin was 195ng/mL, pituitary MRI showed 3mm microadenoma, and bromocriptine was resumed. Workup for her hyperandrogenism revealed testosterone of 137ng/dL (ref 8-60), androstenedione 972 ng/dL (41-262), DHEA-S 284 mcg/dL (84.8-378), 17-OH-progesterone 23ng/dL, and hCG <0.5mIU/mL. Late night salivary cortisol levels were elevated to 0.213, 0.429, and 0.552mcg/dL (<0.090) with ACTH 27.3pg/mL (9.72-63.3). CT scan showed normal adrenal glands. A pelvic ultrasound revealed a 2.2cm left ovarian vascular mass. She underwent left salpingo-oophorectomy and pathology confirmed a 2.4cm benign steroid cell tumor. Follow up after surgery is currently ongoing. Amenorrhea despite prolactin normalization and signs of severe hyperandrogenism such as testosterone >150ng/dL, male pattern baldness, and vocal deepening should prompt physicians to consider androgen-secreting tumors. Our patient was found to have a rare ovarian SCT—these tumors can lead to precocious puberty in adolescents, virilization in adults, Cushing’s syndrome, and infertility. Our patient reports significant clinical improvement postoperatively.

Progressive ovarian sertoli – leydig cell tumor: case report

Introduction: Ovarian Sertoli – Leydig Cell Tumor (SLCT) are one of sex cord tumor that has incidence rate less than 0,2% of all ovarian tumors. It occurs predominantly in second and third decades of lifetime. It has characteristics mostly low–grade malignant although poorly differentiated type may behave more aggressively. Clinical characterstic of ovarian SLCT usually hormonal changes, nevertheless in patients without hormonal changes, the manifestation of the disease consists of abdominal pain and abdominal enlargement, and palpable adnexal mass on physical diagnostic. Case: a 52 years woman that has been undergo right salpingooforectomy 5 months prior with PA result shows poorly differentiated sertoli – leydig cell tumor, and refusing to chemotherapy. She came with chief complaint of abdominal enlargement since 3 months accompanied with lower abdominal pain 2 weeks prior. Ultrasound examination shows cystic ovarian neoplasm with solid part size 9 x 9 x 9 cm from left adnexa. Tumor markers that arise are Alpha–Fetoprotein (AFP) 52 ng/mL and Lactate Dehydrogenase (LDH) = 432 U/mL which correspond to sex cord tumor. She has undergone Laparotomy Total Abdominal Hysterectomy Left Salpingooforectomy and chemotherapy afterward. Conclusion: Ovarian Sertoli – Leydig Cell Tumors (SLCT) are a rare sex cord ovarian tumor that may behave more aggressively as it poorly differentiated. It has manifestations of hormonal changes and also abdominal enlargement.

A Boy with 46,XX Karyotype (SRY double-positive) having a Leydig Cell Tumor.

Leydig cell tumors are the most common type of testicular sex cord stromal tumors. Presence of Y chromosome is associated with tumor risk in sex development disorder (DSD), however tumor development without Y chromosome are extremely rare. A 16-year-old boy diagnosed with Leydig cell tumor due to a mass in the right testis was referred after the right orchiectomy. In physical examination, left testis was 10 ml, and a labium residue in penoscrotal region with bilateral gynecomastia was present. Karyotype was 46,XX, and SRY was double-positive in FISH analysis. Ifosfamide, carboplatin and etoposide chemotherapy was initiated due to Leydig cell tumor. Here, we report the first pediatric case having 46,XX, SRY double-positive testicular DSD with Leydig cell tumor.

A Deep Learning–Based System Trained for Gastrointestinal Stromal Tumor Screening Can Identify Multiple Types of Soft Tissue Tumors

The accuracy and timeliness of the pathologic diagnosis of soft tissue tumors (STTs) critically affect treatment decision and patient prognosis. Thus, it is crucial to make a preliminary judgement on whether the tumor is benign or malignant with hematoxylin-and-eosin-stained images. Here, we present a deep learning-based system, STT-BOX, with only hematoxylin-and-eosin images for malignant STT identification from benign STTs with histopathologic similarity. STT-BOX assumed gastrointestinal stromal tumor as a baseline for malignant STT evaluation, and distinguished gastrointestinal stromal tumor from leiomyoma and schwannoma with 100% area under the curve in patients from three hospitals, which achieved higher accuracy than the interpretation of experienced pathologists. Particularly, this system performed well on six common types of malignant STTs from The Cancer Genome Atlas data set, accurately highlighting the malignant mass lesion. Moreover, without any fine-tuning, STT-BOX was capable of distinguishing ovarian malignant sex-cord stromal tumors. Our study includes mesenchymal tumors that originated from the digestive system, bone and soft tissues, and reproductive system, where the high accuracy of migration verification may reveal the morphologic similarity of the nine types of malignant tumors. Further evaluation in a pan-STT setting would be potential and prospective, obviating the overuse of immunohistochemistry and molecular tests, and providing a practical basis for clinical treatment selection in a timely manner.

FOXL2 Mutation Status in Sex Cord-stromal Tumors Cannot be Predicted by Morphology.

Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The histopathologic diagnosis of these tumors can be challenging. A recurrent somatic mutation of the forkhead box L2 (FOXL2) gene has been identified in adult GCT. In this retrospective single-center study of 44 SCST, a morphologic review together with analysis of FOXL2 C134W was evaluated in relation to tumor morphology. In addition, TERT promoter mutation testing was performed. Twelve of 36 cases got an altered diagnosis based on morphology alone. The overarching architectural growth pattern in 32/44 (72.7%) tumors was diffuse/solid with several tumors showing markedly heterogeneous architecture. In correlation to FOXL2 C134W mutation status, cytoplasmic color, and nuclear shape, differed between the FOXL2 C134W positive and FOXL2 C134 W negative groups, but these differences were not significant when comparing them separately. Nineteen of 44 cases underwent TERT promoter sequencing with a positive result in 3 cases; 2 adult GCTs and 1 cellular fibroma. Three patients developed a recurrence of which 2 were FOXL2 C134W positive adult GCTs and the third was an unclassified SCST. In conclusion, the morphologic and immunohistochemical diagnosis of different SCSTs is challenging and one cannot reliably identify FOXL2 mutation-positive tumors solely by morphologic features. Therefore, broad use of molecular analysis of the FOXL2 C134W mutation is suggested for SCSTs, and further studies are needed to evaluate the clinical outcome of these tumors as well as the diagnostic and prognostic implications of TERT promoter mutations.

Ovarian Fibrothecoma: A Case Report

Introduction: Fibrothecal group tumours are part of the gonadal stromal and sex cord tumours (GSST) and represent 1-4.7% of all organic ovarian tumours and are usually benign. We felt it important to report a case in order to share our experience in the management of fibrothecal tumours of the ovary. Observation: This was a 51-year-old postmenopausal patient who was referred to the hospital for abdominal pain in the context of an abdominal mass. A clinical examination and abdominal ultrasound concluded that the left ovarian tumour was benign. A left annecxectomy was performed and the histological examination concluded that the tumour was benign. No tumour marker was measured and no CT scan was performed. The postoperative course was simple and the patient was followed for 3 months.

Abstract 1617: TGFBR1 as a novel therapeutic target in adult granulosa cell tumors

Abstract Adult granulosa cell tumor (AGCT) is a subtype of sex-cord stromal tumors and accounts for ~5% of all ovarian neoplasms. Nearly 100% of AGCT cases are caused by an oncogenic point mutation in the Forkhead Box L2 (FOXL2) transcription factor. Weis-Banke et al. found this gain-of-function mutation (FOXL2C134W) allows FOXL2 to hijack the nuclear SMAD2/3/4 complex, the downstream effector of transforming growth factor- ß (TGF-ß), and redirect to novel transcription sites, inducing transcription of epithelial to mesenchymal transition (EMT) and other oncogenes. We hypothesized that FOXL2 mutant AGCT would be sensitive to TGF-ß inhibition. To test this hypothesis, we treated two GCT cell lines with TP-6379, an orally available, investigational small molecule kinase inhibitor of TGFBR1 that has been shown to block the phosphorylation and nuclear translocation of SMAD2 and SMAD3 in cells. TP-6379 was tested in the KGN cell line, derived from an AGCT patient and heterozygous for the FOXL2C134W mutation, and the COV434 cell line, derived from a juvenile GCT patient, which is FOXL2 wild type (WT). KGN cells (IC50 = 135 nM) were observed to be more than 70-fold more sensitive to TP-6379 treatment than COV434 (IC50 = &amp;gt;10,000 nM), after a 6- and 7- day treatment, respectively. KGN cells that were edited to remove the WT FOXL2 or both the WT and FOXL2C134W alleles were observed to be 1.6-fold more sensitive to TP-6379 and 22-fold less sensitive than the parental KGN cells. In vivo testing using KGN cells is ongoing. Viably cryopreserved dissociated tumor cells (DTCs) from two AGCT patients and one JGCT patient, which contain a mixture of tumor, immune, endothelial, and other stromal cells, were also tested in proliferation assays with TP-6379. All three ex vivo samples were positive for the FOXL2C134W mutation as detected by a qPCR genotyping assay and were sensitive to TP-6379 (IC50 = 555-1600 nM) after 6-day treatment. Xenograft models using these patient samples are currently under development. TGF-ß signaling is also a master regulator of the tumor microenvironment (TME) and immune evasion by modulating deposition of extracellular matrix and suppression of immune cells. We performed an immunophenotyping assay in tissue microarrays of thin-needle biopsy cores of multiple cancer types by looking at the distribution of CD8 T cells within tumor and stroma. AGCT showed the strongest excluded and desert phenotype among the tested cancer types, where CD8 T cells were confined to the stroma or absent entirely. TP-6379 treatment was observed to increase expression and reverse TGF-ß induced suppression of HLA class I in KGN cells. These data suggest that TGF-ß may play a significant role in the TME of AGCT. In conclusion, preclinical data shows inhibition of TGFß signaling with TP-6379 in FOXL2C134W mutant AGCT is active at blocking cell growth and may prove to be a potential therapy in this rare disease. Citation Format: Curtis A. Allred, Richard E. Heinz, Yuta Matsumura, Tetyana V. Forostyan, David Kircher, Salah Sommakia, Thomas Welte, Veena Vuttaradhi, Jason M. Foulks, Steven L. Warner, R Tyler Hillman. TGFBR1 as a novel therapeutic target in adult granulosa cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1617.

HISTOMORPHOLOGY AND CLINICOPATHOLOGICAL STUDY OF OVARIAN NEOPLASM IN TERTIARY CARE HOSPITAL.

Background: Ovarian tumor is third leading cause of mortality in female. The spectrum of ovarian neoplasm has wild variety of lesions including benign and malignant tumors. Aims &amp; Objective: To study histomorphology of various ovarian neoplasms. Material and Method: This is a retrospective study of 105 cases of ovarian neoplasm done at tertiary care hospital between February 2022 to January 2023. Result:Total 105 cases were included in this study in which majority of cases was benign (80 cases) followed by malignant (22 cases) and borderline tumors (3 cases). Most common clinical presentation was pain in abdomen and age ranged between 21 to78 year. Consistency of benign tumor was cystic (84.7%) and solid in malignant tumors (90.5% ) in majority of cases. Among the cystic lesions most common retrieved uid was serous followed by mucinous and pulteceous. In histological variants, surface epithelial tumors seen in 81 cases, germ cell tumors seen in 20 cases, Sex-Cord stromal tumors seen in 3 cases and metastatic tumor seen in 01 case. Conclusion: Both neoplastic and non-neoplastic ovarian lesions generally present with similar clinical and radiological features. So, histopathological diagnosis is essential to differentiate various ovarian lesions and prediction of prognosis

SCLEROSING STROMAL TUMOR: A RARE SEX CORD STROMAL OVARIAN NEOPLASM

Sclerosing stromal tumor (SST) is an extremely rare, benign distinctive ovarian sex cord stromal tumor. The tumor occurs predominately in the second and third decades of life. Due to the presence of both solid and cystic components with rich vascularity,it can be mistaken for malignant ovarian tumors on ultrasonography and other radiological investigations. Distinctive histopathological features and immunohistochemistry(IHC) conrms the diagnosis. Proper diagnosis of SST is important, which prevents extensive surgical intervention done in cases of ovarian malignancy. Herein, we report clinical and histopathological features of SST in a 23year old female who presented with complaints of intermenstrual bleeding associated with abdominal pain and underwent laparoscopic cystectomy. It is imperative to consider sclerosing stromal tumor as one of the differential diagnosis in young females presenting with complex ovarian mass. Frozen section analysis could be done intraoperatively to rule out malignancy, so that conservative surgery can be performed

Histopathological spectrum of ovarian neoplasms at tertiary health care hospital

Background: The aim of the study was to identify histopathological pattern involving in ovarian neoplasm which where received for histopathological evaluation at tertiary health care centre over a period of 2 year in Pathology department at Guru Gobind Government Hospital, Shri M. P. Shah Government Medical College, Jamnagar.Materials and Methods: This Prospective and Retrospective study was conducted over a period of two year (January 2020 to December 2022) in the Department of Histopathology, shri M.P, Shah Government medical college, Jamnagar. The study included 100 cases of ovarian neoplasms . After proper fixation and thorough gross examination, sections were routinely processed and examined. The distribution of the various histomorphological spectrum of ovarian tumors was studied according to the WHO classification. Aims and Objectives 1) To study frequency of ovarian tumor.2) To study their histopathological features.3) To study age wise incidence of ovarian tumor.Results: In the present study, a total of 100 cases of Ovarian neoplasm were analyzed, out of which Surface epithelial tumors were the most prevalent, comprising 70 cases (70%). Serous cystadenomas were the most common benign neoplasm encountered in our study. Germ Cell Tumors 22 (22%), Mature teratoma were most common germ cell tumor. Sex cord Stromal Tumors 07 (07%). The majority of our patients were in the age group 31-40 years (45 patients, 45% of patients).Conclusion: The present study shows various histopathological features of ovarian neoplasm. Benign tumors are more common than malignant tumors. Among the benign tumors, serous tumors were most common of all. Thus, an accurate histological diagnosis is important to initiate a proper management plan.

Malignant metastatic steroid cell tumor NOS: A rare presentation of a subtype of sex cord stromal tumor

Steroid cell tumors – not otherwise specified (NOS) – are rare sex cord stromal tumors that lack characteristic histology, are benign, and usually present with androgenic manifestations. Metastatic malignant steroid cell tumors pose treatment challenges due to their chemoresistance nature. This is a case report of a metastatic steroid cell tumor – NOS with extensive peritoneal disease.

Treatment and survival of patients with malignant ovarian sex cord-stromal cell tumours: An analysis of the Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) study group CORSETT database.

Malignant sex cord-stromal cell tumours (SCST) account for only 7% of ovarian malignancies. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) study group has established a clinicopathological database to provide an overview of the current treatment strategies and survival of SCST patients and to identify research needs. Twenty centres provided mixed retro- and prospective data of patients with tumour specimens and second-opinion pathology review treated between 2000 and 2014. Descriptive analyses of treatment strategies, Kaplan-Meier curves and cox regression analyses were conducted. Two hundred and sixty-two SCST patients were included. One hundred and ninety-one Granulosa-cell tumour (GCT) and 17 Sertoli-Leydig cell tumour (SLCT) patients were stage I disease (>80%). Forty four GCT (18.7%) and two (8.3%) SLCT patients received adjuvant systemic treatment. After a median observation time of 78.2 months, 46% of all SCST patients experienced disease recurrence, treated predominantly with secondary debulking surgery (> 90%). Advanced FIGO stage, lymph node involvement and intra-operative capsule rupture were associated with disease recurrence on univariate analysis (all p < 0.05). Median OS time was not reached. In this analysis of SCST patients, adjuvant chemotherapy was unable to prevent disease recurrence. Despite high recurrence rates, overall survival rates were excellent.

Large cell calcifying Sertoli cell tumour: molecular and immunohistochemical assessment of a series comprising non-metastasising and metastasising neoplasms.

Large cell calcifying Sertoli cell tumour (LCCSCT) is a type of testicular sex cord-stromal tumour that may occur sporadically or in the context of Carney complex and other genetic syndromes. A subset is clinically malignant, and the molecular mechanisms that drive such aggressive behaviour remain unknown. METHODS AND RESULTS: We analysed 21 samples from 20 patients with LCCSCT (12 non-metastasising and eight metastasising) using PRKAR1A immunohistochemistry (IHC) and next-generation sequencing. Alltumours except two (cases 17 and 20, both metastasising) demonstrated loss of PRKAR1A expression. Among 11 cases with interpretable sequencing results, all harboured pathogenic single nucleotide variants of PRKAR1A. Evidence of loss of heterozygosity (LOH) of PRKAR1A was present in all tumours with interpretable zygosity data, but the mechanisms of LOH were different for non-metastasising and metastasising tumours. Non-metastasising tumours demonstrated only copy-neutral LOH, while metastasising tumours demonstrated a spectrum of mechanisms of LOH, including copy-loss LOH, two concurrent mutations or copy-neutral LOH. Relevant molecular findings in non-metastasising LCCSCT were limited to PRKAR1A variants. In contrast, all metastasising LCCSCTs with interpretable data harboured additional pathogenic variants, including (but not restricted to) BRCA2 mutations with evidence of LOH and bi-allelic CDKN2A/B deletions. Three patients harboured PRKAR1A variants of inferred germline origin, including one with Carney complex and two without known syndromic features. CONCLUSIONS: This study further confirms that PRKAR1A IHC is a useful diagnostic tool for both non-metastasising and metastasising tumours and suggests that molecular analyses can be helpful to identify non-metastasising tumours with malignant potential in selected patients. Importantly, these results highlight that germline assessment could be beneficial for all patients presenting with LCCSCT.