Sex Cord-stromal Tumors Research Articles

Follicle-Stimulating Hormone Receptor Expression and Its Potential Application for Theranostics in Subtypes of Ovarian Tumors: A Systematic Review.

Ovarian cancer mortality rates have not decreased significantly in the past years. As most women are still diagnosed in an advanced stage, there is a need for new treatment strategies for recurrent disease. A potentially new developing targeted approach, theranostics, combines diagnostics and treatment using radiopharmaceuticals. Through target receptors, imaging and treatment of malignant tissue can be achieved. For ovarian malignancy, the follicle-stimulating hormone (FSH) receptor may serve as a possible target since expression appears to be limited to ovarian cells. In this systematic review, we aim to gather all available literature on the expression of the FSH receptor in ovarian tumors. Pubmed, Embase and the Cochrane databases were searched until December 2023 for eligible studies. The search yielded 41 studies, mostly regarding serous carcinomas, sex cord-stromal tumors (SCSTs) and cell lines of serous and SCSTs. Various techniques were used to analyze the expression of the FSH receptor. For serous carcinomas, conflicting results on the expression of the FSH receptor were found. Studies on SCSTs, mainly studying the subtype of granulosa cell tumors, all showed positive expression of the FSH receptor. In the cell lines studies, the KGN cell line derived from a granulosa cell tumor shows positive expression in all studies. Available studies show that SCSTs express the FSH receptor. A theranostic approach targeting the FSH receptor may, therefore, provide a useful new approach for this malignancy with limited therapeutic options in recurrent disease.

A clinicopathological study about the epidemiology of granulosa cell tumors in Lebanon

BackgroundGranulosa Cell Tumors (GCT) are considered the most frequent type of sex-cord stromal tumors. These tumors constitute 3-6% of neoplasms of the ovaries. GCTs are divided into 2 types: Juvenile GCT (JGCT) and Adult GCT (AGCT). Most patients are diagnosed early in the course of the disease and tend to have a favorable prognosis. In the surgical treatment of GCT, two main factors play role in the determination of feasibility of the surgery: age and tumor stage.MethodsA retrospective study was conducted on 65 consecutive female patients diagnosed with ovarian GCT at different hospitals across Lebanon who were referred to the National Institute of Pathology, Beirut-Lebanon, between January 2000 and January 2020. Then, they were divided according to types: adult versus juvenile type. Statistical analysis was carried out using Stata, version 16.ResultsThe incidence of GCT in a Lebanese population was 16.2 per million per year. The mean age of the studied population was 55.6 years. AGCT was the most common with a prevalence of 91% versus 19% for JGCT. Also, inhibine (the most important immunomarker) was found in 77.2% of adult cases. High mitotic index and high tumor size which are predictors for poor prognosis were respectively 20% and 36.9%. Concerning the histopathological features, Grooved nuclei and Exner bodies were less frequently observed in juvenile type (16.7% for both) compared to adult type (36.9%). Most patients with GCT were diagnosed in the early course of disease mainly due to the manifestation of the symptoms as abdominal pain, postmenopausal bleeding or intermenstrual bleeding, and the good diagnosis and screening practices in Lebanon. Regarding the recurrent cases, a significant correlation with high mitotic index (76.9%), high tumor size (92.3%) and advanced stage (46% for stage 3 and 46% for stage 4) was found with a p < 0.05.ConclusionsThe incidence of GCT in the Lebanese population is 16.2 per million per year. The majority of patients with GCT in Lebanon are of Adult type representing around 90% of cases. Older age, high mitotic index and big tumor size are predictors for poor outcomes.

New insights on testicular cancer prevalence with novel diagnostic biomarkers and therapeutic approaches.

Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.

Sex Cord-Stromal Tumors of the Ovary: An Update and Review. Part II - Pure Sex Cord and Sex Cord-Stromal Tumors.

We review the time honored but still frequently challenging features of ovarian sex cord-stromal tumors and also emphasize new developments, including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part to the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr. Robert E. Scully. In part I, we reviewed the pure ovarian stromal tumors. Now, in part II, we present the major clinical, pathologic, and genomic features of pure sex cord and sex cord-stromal tumors.

Exploring the histogenesis of STK11 adnexal tumour using electron microscopy

STK11 adnexal tumour is a recently described female genital tract tumour, usually identified in a paratubal location, often associated with Peutz-Jeghers syndrome (PJS) and with STK11 gene alterations identified in most of the cases. Morphologically, this tumour is composed of cells arranged in a variety of patterns, including cords, trabeculae, tubules and cystic and acinar structures. The cells are only moderately pleomorphic and mitotic activity is variable. As tumour cells express epithelial, sex cord stromal and mesothelial markers, STK11 adnexal tumour may be of sex cord stromal, epithelial or mesothelial origin; a Wolffian origin has also been suggested. We report the ultrastructural features of two STK11 adnexal tumours and compare their ultrastructural features with those of other sex cord stromal tumours, a granulosa cell tumour cell line, as well as the known ultrastructural features of epithelial, mesothelial and Wolffian cells. On ultrastructural examination, two STK11 adnexal tumours showed an admixture of elongated cells with regular elongated nuclei and polygonal cells with nuclei showing markedly irregular outlines and prominent nucleoli. Extracellular collagen fibres were identified. These are common ultrastructural features of sex cord stromal tumours, principally sex cord tumour with annular tubules; no ultrastructural features of epithelial, mesothelial or Wolffian cells were found. These findings in conjunction with the shared clinical and genetic association with PJS and shared molecular changes in STK11 gene suggest that STK11 adnexal tumour represents a poorly differentiated sex cord tumour.

Sex Cord-Stromal Tumors of the Ovary: An Update and Review. Part I - Pure Ovarian Stromal Tumors.

In two separate reviews, we review the time-honored but still frequently challenging features of ovarian sex cord-stromal tumors, and also emphasize new developments including unusual morphologic appearances that, despite the relative rarity of many of the tumors, result in a disproportionate number of differential diagnostic problems, variant immunohistochemical profiles, and specific molecular and syndromic associations. These neoplasms are also of historical interest as current knowledge is still based in significant part on the contributions of 2 giants of gynecologic pathology, Dr Robert Meyer and Dr Robert E. Scully. In part I, we present the major clinical, pathologic, and genomic features of the pure ovarian stromal tumors including comments on differential diagnosis and briefly note significant historical contributions. In part II we will discuss pure sex cord and sex cord-stromal tumors.

Adult-type granulosa cell tumor associated with elevated luteinizing hormone: Two rare case reports.

Adult-type granulosa cell tumors (AGCTs), which account for 2% to 5% of all malignant ovarian tumors, are rare sex cord-stromal tumors that usually secrete excess estrogens, but they can also secrete androgens. We report 2 patients of childbearing age with AGCT who presented with the complaint of abnormal menstruation and elevated luteinizing hormone (LH), and mildly elevated testosterone. The ovarian tumors had hormonal activity. The 2 patients underwent laparoscopic left adnexectomy. The second patient underwent 4 cycles of chemotherapy with paclitaxel and carboplatin as adjuvant treatments. Their postoperative pathology confirmed AGCTs. Also, their menstrual cycle returned to normal, with normal serum LH and testosterone levels. There was no sign of recurrence. The cases suggest that elevated serum LH levels may be a sign of unknown tumors in cases of oligomenorrhea or secondary amenorrhea. It is useful to evaluate the serum levels of inhibin B and anti-Müllerian hormone to improve the early recognition of ovarian granulosa cell tumors.

Successful pregnancy outcome with a large ruptured juvenile granulosa cell tumor: A case report

Background: Juvenile granulosa cell tumors (JGCTs) are rare sex cord stromal tumors diagnosedmainly in premenarchal girls and women younger than 30 years. Case presentation: A 19-year-old primigravida at 36 weeks of gestation presented to the labor ward withcomplaints of generalized abdominal pain, headaches, and reduced fetal movements for two days.Ultrasound revealed a left-sided 15.7 by 15 cm large cyst and a solid mass of increased vascularity withmaternal ascites. The biophysical profile of the fetus was 4/8 (no movement or tone but the presence ofrespiration and amniotic fluid). An emergency exploratory laparotomy was performed, and intraoperativefindings revealed a massive torsed right ovary with a ruptured ovarian mass with grossly edematous and necrosed fallopian tubes. Following a safe cesarean section delivery of the fetus, a right salpingo-oophorectomy with cystectomy was performed. The histopathological results confirmed the diagnosis of JGCT FIGO stage IC2. Postoperatively, the patient was treated with six sessions of chemotherapy(cisplatin and paclitaxel). Post-chemotherapy magnetic resonance imaging showed normal abdominalviscera with minimal free fluid in the posterior cul de sac and a normal left ovary. Inhibin B levels droppedto 3.17, and the patient is on follow-up for the next 5 years with repeated tumor marker testing andcomputed tomography scans.Conclusion: JGCT is a very uncommon pregnancy tumor, and aggressive treatment is necessary foradvanced-stage tumors such as the one in this case to prevent recurrence or even death.

Late pulmonary metastasis of uterine tumour resembling ovarian sex cord tumour (UTROSCT) following radical surgery

Late pulmonary metastasis of uterine tumour resembling ovarian sex cord tumour (UTROSCT) following radical surgery

Recurrent Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A case report and systematic review

Recurrent Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A case report and systematic review

Fundamentals in the pathology of testicular tumours

The most common group of testicular tumours comprises germ cell tumours. Other primary testicular tumours are rare, but it is important to be aware of the wide variety of other, much rarer testicular tumours for the differential diagnosis. These tumours include sex cord stromal tumours and testicular adnexal tumours, which must be distinguished from metastases or somatic-type malignancies in germ cell tumours. Immunohistochemical markers and molecular alterations can help to correctly diagnose these tumours.

Oncological and endocrinological outcomes for children and adolescents with testicular and ovarian sex cord-stromal tumors. Results of the TGM13 National Registry.

Sex cord-stromal tumors (SCST) are hormonally active and rare. The aim was to describe their endocrinological presentation and outcomes. Patients (<19 years) registered in the TGM13 registry between 2014 and 2021 for SCST were selected. Sixty-three ovarian SCST (juvenile granulosa tumor (JGT) n=34, Sertoli-Leydig cell tumor (SLCT) n=17, other SCST n=12) were included. Median age was 13.1 years (0.4-17.4). Germline DICER1 pathogenic variant was present in 9/17 SLCT. Sixty-one were FIGO stage I (IC n=14). Adjuvant chemotherapy was administered for 15. Seven had recurrence (FIGO IA n=3, IX n=2, III n=2), leading to one death. With a median follow-up of 42 months (2.5-92), the 3-year progression-free survival (PFS) was 89% (95% CI 76%-95%). Median age was 6.4 years (0.1-12.9) among the 15 testicular SCST (Leydig cell tumor n=6, JGT n=5, Sertoli cell tumor n=3, mixed SCST n=1). Tumor-nodes-metastases (TNM) stage was pSI in 14. Eight underwent a tumorectomy, 7 an orchiectomy. None experienced recurrence. Endocrinological data were reviewed for 41 patients (18 prepubescent). Endocrine symptoms were present at diagnosis in 29/34 females and 2/7 males (gynecomastia). After a median follow-up of 11 months, 15 patients had persistent endocrine abnormalities: gynecomastia/breast growth (2 males, 1 prepubescent female), precocious/advanced puberty (4 prepubescent females), and hirsutism/menstruation disorders/voice hoarseness/hot flashes (8 pubescent females). The mean height at the last follow-up was within normal ranges (+0.3 standard deviation). SCSTs have a favorable prognosis. Tumorectomy appears safe with testicular primary. Endocrinological disorders, common at diagnosis, may persist warranting endocrinological follow-up.

P-35 Luteinized Thecoma in a postmenopausal woman with Hirsutism

Abstract Introduction We present a 59-year-old postmenopausal woman with a history of obesity and hypertension who sought medical attention due to severe hirsutism. She had been taking various medications, including levotiroksin for thyroid hormone replacement, asetyl salicylic acid as an antiplatelet agent, Betahistin for vertigo, and amlodipine 10 mg for hypertension. Clinical Case The patient had been experiencing severe hirsutism for a year and her complaining had been deteriorating. Her past medical history was significant for obesity and hypertension. She had undergone menopause ten years ago. Her hirsutism, and obesity prompted further investigation into her hormonal profile and pelvic health. On physical examination, the patient's height was 153 cm, and her weight was 109.7 kg, with a BMI of 46.6. Notably, she exhibited severe hirsutism, with Feriman Gallway score of 15. The patient's laboratory results revealed TSH level was elevated at 4.98 mIU/L, indicating subclinical hypothyroidism. Further hormonal evaluation showed increased FSH levels (40 IU/L) and LH levels (12 IU/L), consistent with diminished ovarian function. DHEAS (dehydroepiandrosterone sulfate) level was 121 µg/dL, PRL (prolactin) was 7 ng/mL and both were between normal ranges. Total testosterone level (416,09 ng/dL) and estradiol level was 34.11 pg/mL (0 - 32,2 pg/mL for postmenopausal women) were increased. Free testesteron was increased (22 nmol/L) and 17-α hydroxyprogesterone was 0,61 ng/mL. Cortisol after 1mg-dexamethasone suppression test (1-mg DST) was 0.65 ug/dl. In March 2021, the patient underwent a pelvic ultrasound, which was inconclusive due to obesity. However, no masses were detected in the ovaries. An abdominal MR was also performed, revealing no significant findings in the ovaries. She was prescribed spironolactone 100 mg per day and orlistat for weight loss. In November 2021, the patient underwent surgery due to the discovery of a left-sided sex cord-stromal tumor during the pelvic examination. The histopathological examination confirmed the diagnosis of "Luteinized Thecoma" in the left ovary. The tumor was composed of luteinized cells capable of producing androgens, explaining the patient's hirsutism. Following the surgery, the patient experienced a reduction in hirsutism, possibly due to the removal of the hormonally active tumor. Moreover, she exhibited weight loss since the last prescription, with her weight reducing to 98.3 kg, resulting in a BMI of 41.4. Conclusion Hyperthecosis is mostly reported in postmenopausal women, affecting less than 1% of women of reproductive age. This case illustrates the diagnostic journey of a postmenopausal woman with hirsutism. The discovery of a Luteinized Thecoma, a rare sex cord-stromal tumor, explains the patient's hirsutism.

18F-FDG PET/CT features of Meigs syndrome induced by ovarian sex cord stromal tumors: a retrospective clinical study

The objective of this study was retrospectively to analyze the clinical characteristics and 18F-FDG PET/CT findings in Meigs syndrome (MS) patients. A total of 21 patients with MS induced by ovarian stromal tumors and 69 patients with pseudo-MS caused by ovarian cancer (OC-PMS) were subjected to evaluation using 18F-FDG PET/CT. Visual and semi-quantitative methods were employed to analyze the PET/CT findings. Visual analysis included recording whether the density of the primary tumor was uniform, whether there were cystic changes and calcifications, and the location of serous fluid accumulation. Semi-quantitative analysis involved the measurement of the tumor size, SUVmax, and SUVmean. No significant difference was observed in the size and density of primary tumors between the MS group and the OC-PMS group. However, the SUVmax and SUVmean of tumors in the MS group were found to be significantly lower than those in the OC-PMS group. The amount of serous cavity effusion caused by ovarian sex cord stromal tumors was found to be unrelated to the size of the tumor, SUVmax, and SUVmean but was positively correlated with the level of Ca125. MS patients have both benign ovarian tumors and ascites and/or pleural effusion, which may be accompanied by elevated Ca125 levels. This should be considered as one of the differential diagnoses for ovarian cancer. Understanding the PET/CT features of MS can facilitate the attainment of an accurate diagnosis before surgery.

Ropy and Wiry-Fibroma-Thecoma Testis

Fibrothecoma of testis emerges as an exceptionally discerned, sex cord stromal tumour comprised of spindle shaped, ovoid or spherical cells intermingled with quantifiably variable collagen. Sertoli cell or granulosa cell components are absent although minimal aggregates of diverse sex cord cells may be discerned. Mitotic activity is minimal ≤ 5 mitoses per 10 high power fields although up to 10 mitoses per 10 high power fields may be encountered. Generally, focal haemorrhage and necrosis are absent. Cellular density and stromal collagen is variable. Additionally designated as the cofibroma, testicular fibroma or neoplasm of thecoma/fibroma group, testicular fibrothecoma commonly incriminates testis or paratestis.

Solid ovarian tumor: A diagnostic and management dilemma

Abstract Pure Sertoli cell tumors (SCTs) are an uncommon type of ovarian sex cord–stromal tumor. The variety of symptoms, solid in nature and different histopathological presentation make it difficult the proper diagnosis and optimal treatment regimens in such tumor. Due to nonspecific clinical appearance, diagnosis is mistaken by ultrasound as fibroid or uterine mass. Intraoperative surprises and suspicious for malignancy due to the solid nature of the tumor lead to surgical management dilemma. The diagnosis is confirmed by histopathological examination only. The prognosis is excellent as most are detected in the early stages and surgical management is often curative in most cases. In this case, a 22 year old unmarried female presented to us with irregular periods for 5 years. Her trans-abdominal ultrasound revealed a solid hypoechoic mass of 5 x 6 centimeter size, in close approximate to the uterus on the right side, with probable diagnosis of broad ligament fibroid. On operative laparoscopy, uterus and left ovary was normal, the mass was originated from the right ovary, which was removed and its histopathological and immunohistochemistry report shows elevated alpha inhibin and steroidogenic factor 1 (SF 1) (Sex cord stromal marker) which is suggestive pure Sertoli cell tumor. There was no family/personal history of malignancy. She was treated with surgical resection and remains clear of disease. Prognostic indicators for SCTs include degree and type of heterologous element differentiation. Thorough characterization of such elements is crucial for adequate diagnosis and treatment.

Compilation and Embodiment-Leydig Cell Tumour Testis

Leydig cell tumour is a commonly discerned sex cord stromal tumour arising within testes. Previously designated as interstitial cell tumour, the cellular tumefaction recapitulates non neoplastic Leydig cells. Nearly &lt; 10% neoplasms appear overtly malignant. Neoplasm represents with diffuse or nodular pattern of tumour evolution. Constituent polygonal cells are pervaded with abundant, granular, eosinophilic cytoplasm, uniform spherical nuclei and prominent centric nucleoli. Intracytoplasmic Reinke’s crystals may be discerned.

Is there a role of cytoreductive surgery with HIPEC in recurrent ovarian granulosa cell tumors? An Indian cancer center experience with review of literature

Abstract Background: Granulosa cell tumors of the ovary represent the most common sex-cord stromal tumors. Though characterized by an indolent course and a good five-year survival rate, they tend to have late recurrences and subsequent poorer survival. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in women with recurrent granulosa cell tumors with peritoneal dissemination has not been well defined. Methods: All patients with adult or juvenile type granulosa cell tumors who underwent cytoreductive surgery with HIPEC with 70 mg/m2 of cisplatin for 60 minutes over a period of four years were retrospectively evaluated. We also performed a review of the literature on similar cases reported. Results: We identified eight patients with recurrent adult granulosa cell tumors (AGCT) who fulfilled our inclusion criteria. The mean operative duration was 340 minutes, inclusive of the duration of HIPEC. Fifty percent of patients suffered from postoperative morbidity. Grade 4 morbidity was observed in one patient. At a median follow-up of 35 months, four patients experienced disease recurrence. The median disease-free survival was 10 months (range: 6–31 months) and the median overall survival was 11.5 months (range: 7–40 months). Conclusion: Cytoreductive surgery (CRS) and HIPEC provides a unique opportunity for treating peritoneal dissemination in patients with recurrent ovarian AGCTs. This procedure is well tolerated with acceptable morbidity. Prospective studies are warranted to further elucidate the efficacy of this novel therapeutic approach in recurrent ovarian granulosa cell tumors.

Uterine tumor resembling ovarian sex-cord tumor - a rare gynecological neoplasm.

Uterine tumor resembling ovarian sex-cord tumor is a rare group of uterine neoplasms with unknown histogenesis and differentiation towards ovarian sex-cord elements. They are benign in nature with low malignancy potential. Diagnosis is based on immunohistochemistry and morphological features, and the distinction from other more malignant differentials is paramount to correctly individualizing treatment.

Unclassified Sex Cord/Gonadal Stromal Testis Tumour with a “Pure “Spindle Cell Component: Pathological Features And Review of The Literature

Background: About 2-5% of adult testicular tumors are classified as sex cord/stromal tumors, which are an uncommon group of tumors of the testis. Occasionally, a small percentage of Sex Cord/stromal Testis Tumors (SCST) that are primarily composed of spindle cells seem to be unclassifiable. There are about six cases reported where spindle cells predominate, four of which are consisting purely of spindle cells. At the morphologic level, a striking resemblance to a fibroma has raised the notion of a possible fibrothecoma, but this is not supported by the immunohistochemistry, and the features are consistent with an unclassified sex cord/stromal tumor with a “pure” spindle cell component. Description: A 45-year-old man with a firm mass in the lower pole of the left testis for 3 years. The patient had no comorbidities and no features of endocrinopathies. All blood tests were normal. The ultrasound showed a solitary hypoechoic mass with increased blood flow by Doppler scan. A well-circumscribed tumor measuring 30mmx 15mm with no discernible capsule was identified macroscopically. Microscopy showed a well-circumscribed spindle cell lesion with no necrosis, cytological atypia, or mitoses. The tumor cells appeared spindled with eosinophilic cytoplasm, vesicular nuclei, and occasional nucleoli. No nuclear grooves were noted in the tumour cells. No vascular invasion was present. Actin, calretinin, CD99, S100, and inhibin were positively immunoreactive. Conclusion: The findings were consistent with an Unclassified pure spindle SCST, a rare tumor with a benign course that must be distinguished from several spindle cell neoplasms. There are no biochemical markers for the diagnosis of this tumor, thus requiring meticulous clinical examination, especially if it is small in size. We report a case of “pure spindle cell sex cord stromal tumour of the testis in a 45 years old man in which the histomorphological as well as the immunohistochemical features are consistent with the diagnosis of unclassified sex cord/stromal testis tumor with “pure” spindle cell component.