Sex Cord-stromal Tumors Research Articles

SATB2 Cytoplasmic Expression is Characteristic of a Subset of Ovarian Stromal Cells and Sex Cord Stromal Tumors.

Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear transcription factor that shows consistent nuclear staining in colorectal adenocarcinoma and osteosarcoma. Following the observation of cytoplasmic staining with this marker in luteinized ovarian stromal cells, we studied the expression of SATB2 in ovarian stromal cells, various types of follicular cysts, and sex cord-stromal tumors. Eighty-five cases were stained for SATB2. Ovarian hilar Leydig cells (n = 12), luteinized stromal cells (n = 10), corpora lutea (n = 4), luteinized follicular cysts (n = 4), and stromal hyperthecosis (n = 6) exhibited consistent, usually diffuse, granular cytoplasmic staining. In addition, Leydig cell tumors (n = 1) and steroid cell tumors (n = 4) showed diffuse cytoplasmic staining. SATB2 also exhibited cytoplasmic staining in most Sertoli-Leydig cell tumors (n = 16) and gynandroblastomas (n = 3) confined to the Leydig cell component. Adult granulosa cell tumors (n = 14), juvenile granulosa cell tumors (n = 3), sex cord tumors with annular tubules (n = 3), cellular fibromas (n = 3), sclerosing stromal tumors (n = 1), and thecomas (n = 1) were negative apart from cytoplasmic staining in associated luteinized stromal cells. SATB2 cytoplasmic staining has not been previously described in these lesions but is characteristic of a variety of ovarian stromal cells and sex cord-stromal tumors, in particular, those exhibiting luteinization or a Leydig or steroid cell component. SATB2 staining may be of value in identifying luteinized or Leydig cells when these are morphologically inconspicuous.

Histomorphological Study of Different Ovarian Lessons in a Tertiary Care Hospital

Objective: The present study is to ascertain the relative frequency, histologic types, and age distribution of both neoplastic and non–neoplastic ovarian lesions in the Rajshahi medical college hospitals and compare the results with similar studies in other regions of this country and abroad.
 Methods & Materials: This cross-sectional study was conducted in the Department of Pathology, Rajshahi Medical College, over one year from January 2021 to December 2021. A total of 144 cases of ovarian lesions were included in this study. Inflammatory conditions and developmental anomalies were excluded.
 Result: Out of 144 cases of ovarian masses studied, 104 (72%) were neoplastic. The common types were Surface epithelial tumors (70%), germ cell tumors (23%), and sex-cord stromal tumors (7%). The age range of ovarian tumors was 5 to 70 yrs, and the highest incidence was between 21-50 yrs. Most of the ovarian tumors were bilateral (85%).
 Conclusion: Varying types of both non-neoplastic and neoplastic ovarian lesions were seen. Benign tumors were more common than malignant tumors in all age groups. Surface epithelial cell tumors, followed by germ cell tumors, were the most common tumor. Serous cystadenoma was the most common tumor. Tumour types varied in different age groups.
 TAJ 2022; 36: No-1: 17-22

Obstetric Results after Fertility-Sparing Management of Non-Epithelial Ovarian Cancer.

To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. The study included 146 patients with germ cell (GCT, n = 84) and sex cord-stromal tumors (SCST, n = 62), who underwent fertility-sparing surgery. Adjuvant chemotherapy was administered to 86 (58.9%) patients. Most cases (133 out of 146) were staged FIGO I. The 5- and 10-year disease-free survival rates were 91% and 83%, respectively. The recurrence risk was not associated with tumor histology, stage or age. Twenty-four months after the treatment, the rate of recurrence was higher than the rate of childbearing. The childbearing rates kept rising after the treatment and exceeded the rate of recurrence after 2 years. The cumulative incidence rates of birth 36, 60 and 120 months after treatment were 13.24%, 20.75%, and 42.37%, respectively. Chemotherapy was not related to childbearing. The patients' age was related to the chance of childbearing. The prognoses of GCT and SCST are similar. Close follow-ups along with contraception should be offered to women during the first two years after treatment due to the increased risk of recurrence. After this period, relapses are rare and women can safely become pregnant.

TFE3 nuclear expression as a novel biomarker of ovarian sclerosing stromal tumors and associated with its histological morphology

Sclerosing stromal tumors of the ovary are benign and tend to occur in youthful women with lobular structures at low frequencies. Three types of cells, including luteinized cells, short spindle myoid cells, and intermediate cells, are found in the lobules which abundant in the blood vessels. Currently, immunohistochemistry is used to detect normal follicles, sclerosing stromal tumors, granulosa cell tumors, and fibromas/thecomas. Our research results showed that transcription factor enhancer 3 (TFE3) was moderate to strong positive in the theca interna layer of normal follicles. TFE3 was expressed in seven out of eight sclerosing stromal tumors, mainly in luteinized cells. It did not express in 20 granulosa cell tumors. Of the nine fibromas/thecomas, TFE3 was weakly staining in 2 cases and negative in the remaining 7 cases. The expression of TFE3 was also weak in only one microcystic stromal tumor. 8 cases of sclerosing stromal tumors were analyzed by FISH using a TFE3 separation probe, and the results were negative. In short, as a nuclear transcription protein, TFE3 specifically expressed in sclerosing stromal tumors and could serve as a new marker for the diagnosis and differential diagnosis of sclerosing stromal tumors. Moreover, we speculate that TFE3 will promotes the formation of the vascular plexus after entry into the nucleus, which can further explain why sclerosing stromal tumors are different from other ovary sex-cord stromal tumors.

Prognostic factors and clinic-pathologic characteristics of ovarian tumor with different histologic subtypes-a SEER database population study of 41,376 cases.

Ovarian cancer is considered the leading cause of cancer-related deaths among all gynecological malignancies and a significant reason for mortality in women. This cohort study aimed to explore the survival trends of malignant ovarian tumors (MOT), cancer antigen 125 (CA125) level, and clinicopathological prognostic factors of MOT by histological subtype. Using the Surveillance, Epidemiology, and End Results (SEER) database, a total of 41,411 MOT cases diagnosed between January 2005 and December 2014 were extracted. According to the histological classification of MOT, four categories were included: epithelial ovarian carcinoma (EOC), malignant ovarian germ cell tumors (MOGCTs), malignant ovarian sex cord-stromal tumors (MOSCSTs) and ovarian neuroendocrine tumors (ONTs). We analyzed disease-specific survival (DS) and overall survival (OS) among the four categories, and their histological subtypes. Kaplan-Meier method was used to estimate survival curves, and log-rank test was used to evaluate differences between curves. Univariate and multivariate Cox proportional hazards models were applied to evaluate the prognostic impact of MOT. Significant predictors related to improved OS were younger age, low grade, early FIGO stage and localized SEER stage, while positive/elevated CA125 level was a risk factor. For MOGCT and MOSCST, 3-, 5- and 10-year DS rate estimates were all >80%, followed by ONT around 70%. Malignant epithelial cancer showed low DS rate at 3-year (70.7%), 5-year (58.7%), and 10-year (47.3%). EOC patients had the worst outcome, whereas MOGCT cases had the most favorable survival. Positive/elevated CA125 level led to poor prognosis. Furthermore, younger age, low grade, early FIGO stage and localized SEER stage were significant predictors for improved OS.

ESR1 Rearrangement as a Diagnostic and Predictive Biomarker in Uterine Tumor Resembling Ovarian Sex Cord Tumor: A Report of Four Cases.

UTROSCT are a rare entity that can sometimes present as metastatic disease. Hormonal therapy may address this issue.

Imaging findings of sex cord tumor with annular tubules: a case description.

Imaging findings of sex cord tumor with annular tubules: a case description.

Register-based and genetic studies of Prader-Willi syndrome show a high frequency of gonadal tumors and a possible mechanism for tumorigenesis through imprinting relaxation.

Prader-Willi syndrome (PWS) is a rare disease caused by a lack of expression of inherited imprinted genes in the paternally derived Prader-Willi critical region on chromosome 15q11.2-q13. It is characterized by poor feeding and hypotonia in infancy, intellectual disability, behavioral abnormalities, dysmorphic features, short stature, obesity, and hypogonadism. PWS is not a known cancer predisposition syndrome, but previous investigations regarding the prevalence of cancer in these patients suggest an increased risk of developing specific cancer types such as myeloid leukemia and testicular cancer. We present the results from a Swedish national population-based cohort study of 360 individuals with PWS and 18,000 matched comparisons. The overall frequency of cancer was not increased in our PWS cohort, but we found a high frequency of pediatric cancers. We also performed whole-genome sequencing of blood- and tumor-derived DNAs from a unilateral dysgerminoma in a 13-year-old girl with PWS who also developed bilateral ovarian sex cord tumors with annular tubules. In germline analysis, there were no additional findings apart from the 15q11.2-q13 deletion of the paternal allele, while a pathogenic activating KIT mutation was identified in the tumor. Additionally, methylation-specific multiplex ligation-dependent probe amplification revealed reduced methylation at the PWS locus in the dysgerminoma but not in the blood. In conclusion, our register-based study suggests an increased risk of cancer at a young age, especially testicular and ovarian tumors. We found no evidence of a general increase in cancer risk in patients with PWS. However, given our limited observational time, further studies with longer follow-up times are needed to clarify the lifetime cancer risk in PWS. We have also described the second case of locus-specific loss-of-imprinting in a germ cell tumor in PWS, suggesting a possible mechanism of carcinogenesis.

Magnetic Resonance Imaging in the Diagnosis of Female Adnexal Masses: Comparison With Histopathological Examination.

Introduction Adnexal masses present a special diagnostic challenge because it is difficult to differentiate between benign and malignant lesions clinically. The diagnosis of malignancy is vital, and imaging is the most important part of the evaluation of adnexal masses. This study was conducted with the goal of comparing the accuracy of magnetic resonance imaging (MRI) in diagnosing female adnexal masses in comparison with histopathology examination (HPE). A total of 70 female patients with suspected adnexal lesions were selected for the study. After obtaining informed consent from the patients, an MRI was performed with a subsequent histopathological examination of the lesion. Results The study revealed that MRI demonstrated 27% non-neoplastic, 47% benign, and 26% malignant lesions. HPE, the gold standard for identifying and classifying pathological masses, positively identified the lesions and classified them as non-neoplastic, surface epithelial-stromal, germ cell, and sex cord-stromal tumors. The present study of 70 cases with adnexal masses showed a strong positive correlation between MRI and HPE findings. Conclusion MRI provides the added advantage of visualization of the tumor matrix with differential identification of the fatty and cystic tissue through heterogeneous signals and enhancement indicating aggressiveness and local spread. MRI has greater diagnostic accuracy when compared to ultrasonography (USG), with HPE as the gold standard for discriminating between benign and malignant adnexal masses.

Histopathological Types of Ovarian Cancer in Different Age Group of Patients; A Single Institution Experience

Objective: To see the relationship between age and histological types among patients presenting with ovarian cancer at tertiary care hospital, of Karachi Pakistan. Study Design: Cross-sectional study. Place and Duration of study: Department of medical oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan from Mar 2019 to May 2020. Methodology: Three fifty women presenting with confirmed diagnosis of ovarian carcinoma were included irrespective of their age. The information regarding socio-demographics and family history were noted on pre-designed proforma. Pathology reports were obtained from all the patients and information regarding age, stage and histological type were noted. World Health Organization classification was used to classify the histological type of tumours. All data was entered and analyzed using SPSS version 23. Results: The mean age of the study sample was estimated as 44.27±12.7 years ranging from 14-92 years. According to histological type, most of the females had surface epithelial tumors 307(87.71%), followed by sex cord-stromal tumors 20(5.7%) and germ cell tumors tumors 19(5.43%) respectively. The statistically significant difference was observed between age and histological types and subtypes of ovarian cancer (p<0.05). Conclusion: It is concluded that age is an important factor in determining risk of developing different types of ovarian cancers. Serous type of epithelial ovarian cancer is the most common type and commonly present in 4th to 5th decade of life. Germ cell ovarian tumor is second most common type and present in 2nd decade of life.

Ovarian preservation in gynecologic oncology: current indications and techniques.

Early menopause represents a relevant clinical issue for women. Nevertheless, this issue should be balanced with the risks of ovarian metastasis, ovarian recurrence, and the risk of recurrence in hormone-sensitive gynecological cancers. The purpose of this review was to provide an overview on current indications and techniques of ovarian preservation in patients with gynecological cancers. The potential discussion about ovarian conservation could be proposed to patients with FIGO-stage IA grade 1-2 endometrioid endometrial cancer aged 40 years or less, FIGO-stage IB1-IB2 node-negative cervical cancer with squamous cell carcinoma and HPV-associated adenocarcinoma, FIGO-stage IA-IC grade 1-2 serous, endometrioid, mucinous expansile pattern ovarian cancer, any stage germ cell ovarian tumors, and FIGO-stage IA sex cord-stromal tumors. Technique to perform ovarian transposition in cervix cancer is also reported. Ovarian conservation is a surgical approach that involves preserving one or both ovaries during the treatment of gynecologic cancers. This approach has gained popularity in recent years, as it offers several benefits to the patient, including the preservation of hormonal function and fertility. The decision to perform ovarian conservation depends on several factors, such as the stage and type of cancer, the patient's age, fertility desire, and should be carefully discussed with patients.

Role of scrape cytology smear preparation in the diagnosis of ovarian masses-utility and pitfalls.

Scrape cytology technique is useful for rapid intraoperative diagnosis of ovarian mass lesions that acts as an adjunct to frozen section examination. Though ovaries can be accessed by laparoscopy and USG guided FNAC, there are controversial reports regarding the safety of these procedures. The present study has been designed to evaluate the role of scrape cytology in a variety of ovarian mass lesions. To study the cyto-morphology of ovarian mass lesions and to evaluate the role of scrape cytology technique in correctly diagnosing the ovarian lesions taking histopathological diagnosis as gold standard. This is a prospective observational study done on 61 ovarian mass lesions as received from the Obstetrics and Gynecology department of our Institution. Out of 61 cases, 58 (95.08%) cases were correctly diagnosed with respect to categorization and typing. The age ranged from 14 to 65 years with the mean age being 38.1 years. On histopathology, out of 61 cases, 39 (63.93%) were epithelial along with sub categorization of benign, borderline, and malignant, 13 (22.9%) were germ cell tumors, 5(8.19%) were sex cord stromal tumors, 3 (4.91%) were hemorrhagic cysts and the remaining 1 (1.63%) was massive ovarian edema. Thus, on comparing with histopathology, the sensitivity and specificity of scrape cytology technique were 93.55% and 96.67%, and the diagnostic accuracy was 95.08%. Scrape cytology of ovarian lesions can give quick and reliable results. Also, proper training of cytopathologists chiefly regarding the sampling technique, gross presentation of ovarian lesions and interpretation of scrape cytology smears is needed. Further studies to provide standard guidelines and reporting criteria will prove to be helpful.

Mixed sex cord-stromal tumor (gynandroblastoma) with malignant morphology involving both ovaries: a case report.

Mixed sex cord-stromal tumors, which consist of poorly differentiated Sertoli cells and Leydig cells and juvenile granulosa cell tumor tissue, are extremely rare. Most of these tumors are unilateral and stage I at the time of diagnosis; nonetheless, according to the available relevant English-language literature, these tumors maintain a malignant potential. We herein report a case involving a 15-year-old girl diagnosed with a mixed sex cord-stromal tumor (gynandroblastoma with juvenile granulosa cell tumor component). Left salpingo-oophorectomy was initially performed, and the diagnosis of a juvenile granulosa cell tumor was established. Right salpingo-oophorectomy was performed 1 year later, at which time the specimen showed a different growth pattern involving epithelioid cells and tubules, resembling a Sertoli-Leydig cell tumor. Immunohistochemical staining was performed and the specimen was compared with that obtained 1 year earlier. We concluded that the tumors were linked and most likely constituted a gynandroblastoma (mixed form of sex cord-stromal tumor). Although this is an extremely uncommon ovarian tumor, it should be considered when diverse tumor morphology is identified. Bilateral metachronous involvement of the ovaries is possible. The grade of the Sertoli-Leydig cell component may influence the prognosis of such a tumor.

Ovarian Masses in Children and Adolescents: A Review of the Literature with Emphasis on the Diagnostic Approach.

Most abdominal masses in the pediatric population derive from the ovaries. Ovarian masses can occur in all ages, although their incidence, clinical presentation and histological distribution vary among different age groups. Children and adolescents may develop non-neoplastic ovarian lesions, such as functional cysts, endometrioma, torsion, abscess and lymphangioma as well as neoplasms, which are divided into germ cell, epithelial, sex-cord stromal and miscellaneous tumors. Germ cell tumors account for the majority of ovarian neoplasms in the pediatric population, while adults most frequently present with epithelial tumors. Mature teratoma is the most common ovarian neoplasm in children and adolescents, whereas dysgerminoma constitutes the most frequent ovarian malignancy. Clinical manifestations generally include abdominal pain, palpable mass, nausea/vomiting and endocrine alterations, such as menstrual abnormalities, precocious puberty and virilization. During the investigation of pediatric ovarian masses, the most important objective is to evaluate the likelihood of malignancy since the management of benign and malignant lesions is fundamentally different. The presence of solid components, large size and heterogenous appearance on transabdominal ultrasonography, magnetic resonance imaging and computed tomography indicate an increased risk of malignancy. Useful tumor markers that raise concern for ovarian cancer in children and adolescents include alpha-fetoprotein, lactate dehydrogenase, beta subunit of human chorionic gonadotropin, cancer antigen 125 and inhibin. However, their serum levels can neither confirm nor exclude malignancy. Management of pediatric ovarian masses needs to be curative and, when feasible, function-preserving and minimally invasive. Children and adolescents with an ovarian mass should be treated in specialized centers to avoid unnecessary oophorectomies and ensure the best possible outcome.

The Impact of Surgery & Chemo in Treating Sex Cord-Stromal Tumors

The Impact of Surgery & Chemo in Treating Sex Cord-Stromal Tumors

Ovarian sclerosing stromal tumour: Report of a new entity with immunohistochemical study.

Sclerosing stromal tumour (SST) is a rare benign sex cord stromal tumour occurring in women in their second and third decades. Patients usually present with menstrual irregularity and pelvic pain. Microscopically, this tumour is characterized by epithelioid and spindle cells arranged in pseudolobules separated by areas with fibrous deposition of various amount. Presence of ‘staghorn like’ proliferating vasculature is the hallmark feature of this tumour. The main differential diagnoses are thecoma and fibroma. Immunohistochemistry can be used to differentiate these tumours. This relatively new entity should be kept in mind while reporting ovarian tumour in a young female. We have described SST in an 18 year old female in this case report. Bangladesh Journal of Medical Science Vol. 22 No. 03 July’23 Page : 712-717

A Case of Uterine Tumor Resembling Ovarian Sex Cord Tumor With Prominent Myxoid Features.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor with low malignant potential that commonly occurs in middle age. Although more than 100 cases have been reported to date, myxoid morphology is not well documented. Here, we present a 75-yr-old woman with abnormal vaginal bleeding, with an 8-cm mass in the uterine corpus detected by irregular, high-intensity signaling on T2-weighted imaging. The uterine mass had a glistening mucinous appearance on gross examination. Microscopically, most of the tumor cells were floating in the myxoid stroma. The tumor cells formed clusters or nests with abundant cytoplasm, while some exhibited trabecular or rhabdoid appearances. Immunohistochemically, tumor cells were positive for pancytokeratin (AE1/AE3), α-smooth muscle actin, CD10, progesterone receptor, and some sex cord markers such as calretinin, inhibin, CD56, steroidogenic factor-1. Electron microscopy demonstrated epithelial and sex cord differentiation. This tumor was negative for JAZF1-JJAZ1 fusion gene that is frequently found in low-grade endometrial stromal sarcoma. Fusion genes related to UTROSCT, including NCOA2/3, were not detected by reverse transcription polymerase chain reaction. The present case suggests that UTROSCT should be included in the differential diagnosis of myxoid uterine tumors.

Clinical Challenges in the Management of Malignant Ovarian Germ Cell Tumours.

Nonepithelial ovarian cancers (NEOC) are a group of rare malignancies, including germ cell tumours (GCT) and sex cord-stromal tumours (SCST), along with small-cell carcinomas and sarcomas. GCTs represent 2-5% of ovarian cancers, with a yearly incidence of 4:100,000, and they usually affect young women and adolescents. Precursory germ cells of the ovary form the basis of GCT. They are histologically classified into primitive GCT, teratomas, and monodermal and somatic-type tumours associated with dermoid cysts. A primitive GCT can be either a yolk sac tumour (YST), dysgerminoma, or mixed germ cell neoplasm. Teratomas are either mature (benign) or immature (malignant). Given that malignant GCTs occur rarely compared to epithelial ovarian tumours (EOC), greater focus is required in their diagnosis and treatment. In this article, we review the epidemiology, clinical manifestations, diagnosis, and molecular biology, along with the management and therapeutic challenges.

Pathological discrimination between luteinized thecoma associated with sclerosing peritonitis and thecoma.

Similarities between luteinized thecoma associated with sclerosing peritonitis (LTSP) and thecoma, cause difficulty in clinical differential diagnoses. To improve the situation, we selected 10 specified molecular pathological markers that are frequently used in clinical pathology of ovarian sex cord-stromal tumors to determine whether they exert a discriminatory effect. Applying immunohistochemistry, we analyzed the expression of alpha-1,6-mannosylglycoprotein 6-beta-n-acetylglucosaminyltransferase B (MGAT5B), nuclear receptor coactivator 3 (NCOA3), proliferation marker protein Ki-67 (MKI67), estrogen receptor, progesterone receptor, Vimentin, receptor tyrosine-protein kinase erbB-2, Catenin beta-1 (β-Catenin), CD99 antigen (CD99) and Wilms tumor protein (WT1) in 102 cases of diseases containing 11 LTSP and 91 thecoma. Whole-exome sequencing and fluorescence in situ hybridization were used to examine the MGAT5B-NCOA3 fusion gene in LTSP. Statistical analysis was performed using t test, one-way analysis of variance test, and post hoc test. Six significant markers were verified for the discrimination between LTSP and thecoma, containing 4 upregulating indicators MGAT5B, NCOA3, MKI67, β-Catenin, and 2 downregulating markers CD99 and WT1 in luteinized cells. In addition, the MGAT5B-NCOA3 fusion gene was identified in LTSP for the first time with significantly rich expression compared to thecoma. We verified 6 significant molecular pathological markers containing MGAT5B, NCOA3, MKI67, β-Catenin, CD99, and WT1 and identified MGAT5B-NCOA3 fusion gene in LTSP; this work will help clinicians to discriminate between medical conditions and treat patients accurately.

Reproductive and oncologic outcomes in women with non-epithelial ovarian cancer: Single center experience over 25 years.

This study aimed to present our single-center clinical experience regarding tumor clinicopathologic features, treatment modalities, and reproductive and oncologic outcomes in patients with non-epithelial ovarian cancer (NEOC) over 25 years. A total of 100 patients with clinicopathological diagnosis of NEOC who were treated at our tertiary care center between 1996 and 2022 were included in this retrospective cohort analysis study. Data on demographic, clinical and obstetric characteristics of patients at the time of initial diagnosis as well as tumor clinicopathologic features, treatment modalities, and oncological and reproductive outcomes were recorded. NEOCs involved germ cell tumors (GCTs) in 46 (46%) patients and sex cordstromal tumors (SCSTs) in 54 (54%) patients. Thirty patients with GCTs and thirty-four patients with SCSTs possessed histological subtypes with malignant features. Most patients with GCTs (37%) and SCSTs (55.6%) had FIGO Stage 1 disease at the time of initial diagnosis. Overall, 76.6% of patients in the GCT group (n=23) underwent fertility-sparing surgery (FSS), while 76.5% of the patients in the SCST group (n=26) were treated with non-fertility-sparing surgical procedures. All patients who underwent FSS and had a recurrence in their follow-up (n=4) was stage 3 patients. Seven out of 10 patients (2 patients at stage 3 and 5 patients at stage 1) who desired pregnancy delivered between 38 and 40 gestational weeks without any congenital anomaly. The prognosis was excellent in both groups, with 5-year overall survival (OS) rates of 93.5% in GCTs and 96.3% in SCST groups. The 5-year disease-free survival was 89.1% in GCTs and 94.4% in SCSTs. FSS was not associated with worse oncologic outcomes. NEOCs usually have a good prognosis because they are detected at an early stage. FSS may be indicated for women of reproductive age with early-stage NEOCs.