Sertoli Cell Tumor Research Articles

Ovarian sex cord-stromal cell tumors and the risk of sex hormone-sensitive cancers.

Sex cord-stromal cell tumors (SCST) are rare tumors of the ovary. Some of the SCSTs secrete hormone originating from the sex or stromal cell of the ovaries. Previous studies have indicated an increased risk of breast and endometrial cancers. However, these studies focused only on the SCST-subtype adult granulosa cell tumor, the estimates stem from selected cohorts and lack a well described cohort making it difficult to adjust for possible confounders. We examinined the incidence of other primary hormone sensitive cancers and comparing the risk to a matched cohort of women without SCST. This is a nested cohort study evaluating women diagnosed with sex cord-stromal cell tumors (SCSTs). We established the cohort of women diagnosed with SCSTs using Systematized Medical Nomenclature for Medicine (SNOMED) codes from the Danish Pathology Register. SCST diagnoses were considered valid if the primary diagnosis was established at a tertiary referral center or confirmed by at least two pathologists. A 1:10 matched control group, matched on birth year, was selected from national registries. Variables for follow up of cases and controls were drawn from national registries including assessment of rates of breast, ovarian and endometrial cancer, hormone use, Charlson Comorbidity Index and sociodemographics. Hazard ratios (HRs) for cancer rates were calculated using multivariate Cox proportional hazards models with SCST exposure estimated in early and delayed models to capture cancer rates over time. Standardized incidence ratios (SIRs) for very rare SCSTs were determined using log-linear Poisson models. Among the 1,516 tumors assigned SNOMED codes for SCSTs, 1,387 met the inclusion criteria after pathologic chart review. The majority had benign tumors, primarily thecoma/fibrothecoma (66%), while 26% had adult granulosa cell tumors (aGCTs). Increased rates for breast cancer were found in thecomas (HR: 1.2; 95% CI 1.0-1.4). In the analysis of all SCSTs combined, an increased rate of synchronous endometrial cancer was found (HR: 3.3; 95% CI 2.7-4.1). In sub-group analysis, malignant and benign SCSTs showed significantly higher HRs for synchronous endometrial cancer, notably in aGCTs (HR: 10.7; 95% CI 5.7-20.1). In the model assessing the rates of endometrial cancer two months after surgical removal of the SCST, no increased rates were found. Sertoli cell tumors were linked to an increased incidence of breast cancer (SIR: 18.9; 95% CI 2.7-134). Both Sertoli and Leydig cell tumors were associated with a higher incidence of synchronous endometrial cancer, with SIRs of 41.4 (95% CI 10.4-166) and 44.9 (95% CI 18.7-108), respectively. In conclusion, women with SCSTs have an increased rate of synchronous endometrial cancer and women with benign SCSTs have an increased rate of synchronous ovarian cancer. A marginally increased rate of breast cancer was found in women with thecomas. There is no increased rate of breast cancer among women with aGCT. It is recommended that women diagnosed with hormone-secreting SCSTs and additional risk factors for endometrial cancer (abnormal uterine bleeding and/or abnormal endometrial thickness) undergo an endometrial biopsy to assess for the presence of cancer.

Transferrin Receptor 2 in Canine Testicular Tumors: An Emerging Key Role in Seminomas.

Transferrin Receptor 2 (TfR2) is a homolog of Transferrin Receptor 1 (TfR1), involved in regulating intra and extracellular iron levels. Altered iron pathways have been associated with cancer onset and progression; however, their role in canine tumors remains poorly explored. This study investigated TfR2 immunohistochemical expression in non-neoplastic canine testis for the first time and in the most common types of canine testicular tumors: intratubular seminomas (ITSEMs), diffuse seminomas (DSEMs), Leydig cell tumors (LCTs), and Sertoli cell tumors (SCTs). Immunohistochemical analysis revealed a differential pattern of TfR2 expression according to tumor type, with high expression observed in ITSEMs and DSEMs, occasional expression in LCTs, and absence in SCTs. These results suggest that TfR2 may play a relevant role in canine seminoma development. Furthermore, the specific expression of TfR2 in seminomas highlights its potential as a therapeutic target, where its role in iron regulation and possible compensatory mechanisms warrant further investigation.

The First Sertoli Cell Tumor of the Adrenal Gland is Potentially Associated with Arterial Hypertension

Introduction: Sertoli cell tumors are rare sex cord-stromal tumors, accounting for less than 1% of primary testicular tumors. They typically arise in the testes and ovaries, with other localizations being uncommon. We present the case of a Sertoli cell tumor in the adrenal gland, which, to our knowledge, is the first reported in the literature. Case Presentation: A 44-year-old male patient was admitted to the clinic for endocrine surgery for laparoscopic surgery of a right adrenal gland incidentaloma measuring 57 × 47 × 59 mm, discovered during a routine abdominal ultrasonography. The patient had a history of hypertension but no other comorbidities. Biochemical and physical examinations revealed no signs of hypercortisolism. Urinary metanephrine and normetanephrine levels were within normal limits. A right laparoscopic adrenalectomy was performed, and a 5 cm tumor was identified without evidence of locoregional invasion. Pathological examination confirmed a Sertoli cell tumor of the adrenal gland. Immunohistochemical analysis revealed positive staining for vimentin, steroidogenic factor 1 (SF1), and beta-catenin, while chromogranin A, hCG, PSA, and TTF1 were negative. The Ki-67 index was 3%. The patient was subsequently referred to a urologist, where testicular ultrasonography showed no abnormalities. There were no signs of recurrence during a 15-month follow-up period. Additionally, the patient’s biannual antihypertensive treatment was discontinued by a cardiologist 1.5 months post-surgery. Conclusions: Sertoli cell tumors are an exceptionally rare entity. To our knowledge, this is the first reported case of a primary Sertoli cell tumor originating in the adrenal gland. Given their potential for malignancy, regular follow-up and additional diagnostic evaluations may be necessary. Laparoscopic adrenalectomy appears to be a suitable definitive treatment for this condition.

12405 A Severe Case Of Virilization Of Premenopausal Woman Secondary To A Rare Testosterone Producing Sertoli Cell Tumor

Abstract Disclosure: S. Waheed: None. N.J. Vernetti: None. S. Nakhle: None. Introduction: We present a case of a premenopausal woman with elevated testosterone who was diagnosed with an aggressive Sertoli cell tumor of the ovary. Case Description: A 49-year-old multiparous female presented to the clinic with hirsutism and markedly elevated testosterone levels. Her symptoms started a year before the presentation with diffuse alopecia, acne, and increased muscle mass. Last menstrual periods were 3 years, prior to the presentation.Denies any exposure to testosterone herself or indirectly through family. On physical exam, blood pressure 170/122 coarse features, oily skin, and muscular build. She had terminal hair loss and increased hair growth on face and arms. Laboratory data revealed testosterone levels of 9280 ng/dl (reference range premenopausal 18-55 ng/dl), free testosterone > 50 ng/dl (premenopausal0-4.2 ng/dl), LH <0.3 mIU/mL (2.4-12.6 mIU/mL), FSH <0.3 mIU/mL (3.6-12.5 mIU/mL), 17-OHP 2270 ng/dl (15-70 ng/dl), DHEA-S 71 ug/dl (<229 ug/dl), LDL 128 mg/dl, Creatinine 1.29 and hematocrit 56% (34-44.6%). CT abdomen/pelvis showed 10 cm ovarian mass. She underwent Total Abdominal Hysterectomy-Bilateral Salpingo Oophorectomy (TAH-BSO). After the surgery, her testosterone levels normalized and features of hyperandrogenism resolved. Pathology report revealed sex cord stromal tumor Not otherwise specified (NOS) with cellular atypia and possible aggressive behavior. Discussion: Androgen-producing tumors in women are rare neoplasms that can cause secondary virilizing characteristics. Of patients presenting with symptoms of hyperandrogenism, these tumors are found in ∼0.2% of cases. Androgen-producing tumors can arise from the ovary or the adrenal gland. Those arising from the ovary are rare, accounting for <5% of all ovarian tumors. Few cases of steroid cell tumors, not otherwise specified, have been reported in the literature.Testosterone elevation of more than 2 times upper normal limit increases the suspicion for cancer. In our patient, testosterone was 180 times above the normal range for women and 15 times above the normal range for men. With rapid virilization and significant elevation in testosterone, an androgen producing ovarian tumors should be considered. Presentation: 6/2/2024

Conservative management of gynecomastia in Peutz-Jeghers syndrome: Case series and review of the literature.

Peutz-Jeghers syndrome (PJS) is a childhood-onset cancer predisposition syndrome that is associated with oral freckling and gastrointestinal polyposis. Male patients with PJS are at risk for large-cell calcifying Sertoli cell tumors in childhood. These tumors are estrogen-producing and can cause symptoms of precocious puberty, gynecomastia, and growth acceleration. Here we discuss our experience with spontaneous resolution or stabilization of breast enlargement without medical intervention in three patients with PJS and gynecomastia. These cases indicate that a watchful waiting approach can be considered in the management of gynecomastia in male children with PJS.

Preliminary Evidence of the Possible Roles of the Ferritinophagy-Iron Uptake Axis in Canine Testicular Cancer.

Iron is a key element in spermatogenesis; its metabolic pathway in the testis is strictly regulated. Alterations in iron metabolism are linked to various diseases, including cancer, and changes in iron metabolism-related proteins have been observed in multiple human, mouse and canine tumors. There is limited knowledge about iron metabolism in canine non-neoplastic and neoplastic testes. This study aimed to explore the immunohistochemical expression of molecules involved in iron uptake and storage [Transferrin Receptor 1 (TfR1), ferritin (FTH1), nuclear receptor coactivator 4 (NCOA4)] and PCNA in canine non-neoplastic and neoplastic testicular samples. Non-neoplastic testes showed moderate TfR1 expression in developing germ cells and Sertoli cells, high NCOA4 cytoplasmic immunostaining in the Sertoli cells and occasional cytoplasmic immunopositivity for FTH1 in the spermatogonia and Sertoli cells. In contrast, Leydig cell tumors (LCTs) and Diffuse Type Seminoma (DSEM) exhibited increased expression of TfR1, along with higher PCNA expression, suggesting a higher iron need for proliferation. Intratubular Type Seminoma (ITSEM) showed a higher FTH1 expression, indicating greater iron storage, while the increased NCOA4 expression in the LCTs and DSEM suggested ferritinophagy to release iron for proliferation. Sertoli cell tumors (SCTs) showed only NCOA4 expression. These preliminary findings highlight potential molecular targets for developing new anti-neoplastic treatments in canine testicular tumors.

Histopathological changes in testicular lesions in cats.

The aim of this retrospective study was to describe the neoplastic and non-neoplastic lesions seen on histopathological examination of cat testes in Hong Kong between 2018 and 2024. A total of 26 single or dual testes samples were collected from 18 cats by veterinarians at 14 veterinary clinics and submitted for histopathological examination. Laboratory records, including signalment, lesion location, age, breed and histopathological findings, were reviewed for each cat. Neoplastic testicular lesions were seen in three older cats (median age 8.5 years; range 3-17) compared with 18 non-neoplastic lesions in 15 cats (median age 1 year; range 0.5-3). The most common non-neoplastic lesions included inflammation (in the testes, epididymis, tunics and ductus deferens), cryptorchidism, and one case each of polyorchidism and epididymal cyst formation. Two of the testes with inflammation were identified on immunohistochemical staining as feline coronavirus-infected and one pair of testes was associated with the presence of extracellular Gram-negative bacteria at the lesion site. Three different neoplastic lesions were identified, one each of Sertoli cell tumour, leiomyoma and fibrosarcoma. Non-neoplastic testicular lesions were most common, including inflammation, cryptorchidism, polyorchidism and epididymal cysts. To our knowledge, leiomyoma and fibrosarcoma have not been reported in cat testes before and represent important differential diagnoses for testicular lesions.

The role of stathmin expression in the differential diagnosis, prognosis, and potential treatment of ovarian sex cord-stromal tumors

BackgroundStathmin, a cytosolic microtubule-destabilizing phosphoprotein involved in the regulation of mitosis, is widely expressed in various malignancies and acts as an adverse prognostic factor. Our research analyzed its immunohistochemical expression on a large cohort of ovarian sex cord-stromal tumors, evaluating its potential utility in differential diagnosis, prognosis, and therapeutic application.MethodsWe examined 390 cases of ovarian sex cord-stromal tumors including 281 adult granulosa cell tumors (AGCT), 5 juvenile granulosa cell tumors (JGCT), 33 Sertoli-Leydig cell tumors (SLCT), 50 fibromas/thecomas (F/T), 11 Leydig cell tumors/steroid cell tumors (LCT/SterCT), 5 sex-cord stromal tumors NOS (SCST-NOS), 3 Sertoli cell tumors (SCT), and 2 sclerosing stromal tumors (ScST). Immunohistochemical analysis was performed using TMAs.ResultsStrong expression (> 50%) was observed in all cases of AGCT, JGCT, SLCT, SCST-NOS, SCT and 1 ScST. The other case of ScST exhibited mild expression (5–10%). The negative cases included exclusively F/T and LCT/SterCT, with F/T showing 24% of negative cases and LCT/SterCT comprising 64% of negative cases.ConclusionThe results of our study indicate that stathmin is neither a prognostic marker nor suitable for the differential diagnosis of challenging cases of ovarian sex cord-stromal tumors. However, its predictive value may be theoretically significant, as a decrease in stathmin expression potentialy influences response to chemotherapy treatment.

STK11 (LKB1) immunohistochemistry is a sensitive and specific marker for STK11 adnexal tumours.

STK11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz-Jeghers syndrome. [Correction added on 3 October 2024, after first online publication: 'ST11' in preceding sentence has been corrected to 'STK11' in this version.] It predominantly originates from the para-adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non-specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics. IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli-Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra-ovarian sex cord-stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo-ovarian high-grade serous carcinomas, five ovarian mesonephric-like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss. STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context.

Hematological, histomorphological, and immunohistochemical diagnosis of bilateral testicular Sertoli cell tumor in a Mongrel dog: a case history

Hematological, histomorphological, and immunohistochemical diagnosis of bilateral testicular Sertoli cell tumor in a Mongrel dog: a case history

The demographics of Sertoli cell carcinoma: A National Cancer Database analysis.

e17012 Background: Sertoli cell tumors (SCTs) are an extremely rare and lethal diagnosis responsible for roughly 1% of all testicular and ovarian carcinomas. No uniform treatment regimen with sufficient results has been established. Current combination of retroperitoneal lymph node dissection, chemotherapy, and radiation therapy provides the best known outcome. Analyzing trends in diagnosis may provide valuable information about its epidemiology. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 159 patients were found with a histologically confirmed diagnosis of SCTs (ICD-8640-3). Race, gender, Hispanic origin, type of treatment facility, insurance coverage, and distance from patient residence to treatment facility were analyzed via descriptive statistics, and trends in incidence were interpreted using regression analysis. Results: The number of patients diagnosed with SCTs has remained relatively consistent since 2004 (R^2 = 0.07), with approximately 9 diagnoses per year. Of the 159 patients found, the average age of diagnosis was 44.6 years (SD = 19.1, range = 2 – 89 years). A majority of patients were male (67%), while the remaining third were female (33%). Most of the patients were White (73%). Patient Hispanic status could not be reliably determined due to limited data. More patients were in the top income quartile (31%) than the second (24%), third (18%), or fourth (14%) quartiles, with 13% having unknown income status. Most patients were privately insured (59%), followed by coverage under Medicare/Medicaid (28%). More patients lived in metropolitan counties with a population of 250,000 or more (76%) compared to less-populated urban or rural regions (24%). The majority received treatment at comprehensive community cancer programs or academic/research programs (43%). Patients traveled an average of 30.2 miles (SD = 64.0, range = 0.5 – 474.9) to reach the treatment facility. Conclusions: SCTs remains a rare diagnosis. This study pursues a significant gap in existing knowledge on patient characteristics that may present with SCTs. Most patients were White, privately insured, in the top income quartile, and lived in metropolitan areas. This novel study may contribute data towards understanding the relationship between patient socioeconomic status and access to diagnosis. Further research is required to uncover the role of socioeconomic status in SCTs.

A novel oral microtubule inhibitor utidelone capsule (UTD2): A phase 1 clinical study to assess the tolerability, safety, and efficacy in advanced solid tumors.

e15014 Background: Utidelone is a potential best-in-class novel microtubule stabilizing agent that offers several advantages including improved efficacy and safety, broader anti-cancer spectrum, blood-brain barrier penetrance, and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for advanced breast cancer in China since 2021 (30 mg/m2/d-5day in combination with capecitabine; 35mg/m2/d-5day for monotherapy’s recommended dose). Utidelone is not susceptible to P-glycoprotein, leading to better oral bioavailability and successful development of an oral capsule. This is the first-in-human study of Utidelone Capsule (UTD2) in the United States. Methods: This is an ongoing phase I, open-label, dose escalation study (NCT05681000). Eligible patients are aged ≥18, and have an ECOG PS of 0-1, life expectancy ≥12weeks, adequate organ functions, pathologic confirmed advanced solid tumor refractory to prior standard therapies. Patients are treated with UTD2 monotherapy. The starting dose is 25 mg/m2/d-5day, with planned escalation to 50, 75, 100 mg/m2/d-5day, 70 mg/m2/d-7day and 85 mg/m2/d-7day in a 21-day cycle. The primary objective is to determine DLT and MTD. Secondary objectives include efficacy, pharmacokinetic profile and phase II dose recommendation. Results: As of 22nd January 2024, 10 advanced solid tumor patients were enrolled with median age of 62.5 years (range 52.0-81.0), 5 females and 5 males. All patients had received prior treatment in advanced settings. Dose escalation is ongoing, and 100mg/m2/d-5day cohort is under evaluation. The first 8 patients were evaluated for efficacy with an outcome of 1 CR (ovarian cancer), 5 SD (prostate adenocarcinoma, testicular Sertoli cell tumor, non-small cell lung cancer, pancreatic adenocarcinoma and appendiceal adenocarcinoma) and 2 PD (carcinoma of fallopian tube and adenocarcinoma of sigmoid colon), among whom 5 patients are still on the treatment with durations of 2 to 11 cycles. The ovarian patient with CR was enrolled to the lowest dose cohort, and is still on treatment. She is heavily pre-treated with multiple prior lines including chemotherapies. Regarding safety, most treatment-emergent adverse events (TEAEs) were Grade 1/2, manageable, and included diarrhoea, nausea, alopecia. There were two cases of Grade 3 diarrhea that recovered to Grade 1 through dose reduction or medical support. No grade 4 or 5 adverse events and no treatment discontinuations due to AE were reported. There have been no DLTs and the MTD is not yet reached. Conclusions: This study has demonstrated encouraging anti-tumor activity with good tolerance and manageable safety profile of UTD2 in patients with heavily pre-treated advanced solid tumors. This study is still actively ongoing, and further data will be provided at time of presentation. Clinical trial information: NCT05681000 .

Cryptorchidism and testicular cancer in the dog: unresolved questions and challenges in translating insights from human studies†.

Cryptorchidism, the failure of one or both testes to descend into the scrotum, and testicular cancer show a strong correlation in both dogs and humans. Yet, long-standing medical debates persist about whether the location of undescended testes directly causes testicular cancer in humans or if both conditions stem from a common origin. Although testicular cancer is a prevalent disease in dogs, even less is known about its cause and correlation with testicular descent in this species. This review investigates the relation between these two disorders in dogs, drawing insights from human studies, and examines key biomarkers identified thus far. In addition, it explores potential causal links, including the impact of temperature on maturing testicular cells and a potential shared genetic origin. Notably, this literature review reveals significant differences between men and dogs in reproductive development, histological and molecular features of testicular tumors, and the prevalence of specific tumor types, such as Sertoli cell tumors in cryptorchid dogs and germ cell tumors in humans. These disparities caution against using dogs as models for human testicular cancer research and underscore the limitations when drawing comparisons between species. The paper concludes by suggesting specific research initiatives to enhance our understanding of the complex interplay between cryptorchidism and testicular cancer in dogs.

Familial syndromes associated with testicular and paratesticular neoplasms: a comprehensive review.

A syndromic association between a subset of testicular/paratesticular neoplasms is well established. Such examples include Carney complex and large cell calcifying Sertoli cell tumor, Peutz-Jeghers syndrome and intratubular large cell hyalinizing Sertoli cell neoplasia, and VHL syndrome and clear cell papillary cystadenoma of the epididymis.However, recent studies proposed potential novel links between some testicular and paratesticular neoplasms with certain tumor syndromes. While more studies are still needed to solidify these associations, recent research suggests that a subset of Leydig cell tumors may arise in patients with hereditary leiomyomatosis and renal cell carcinoma syndrome or that some seminomas may occur in Lynch syndrome patients. Additionally, an association between testicular sex cord stromal tumors and paratesticular sarcomas with Familial adenomatous polyposis syndrome and DICER1 syndrome, respectively, has been proposed as well. This review provides a comprehensive overview of the intricate relationship between familial syndromes and associated testicular and paratesticular tumors, shedding light on their clinicopathological and molecular characteristics.

β-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis.

Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of β-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of β-catenin alterations remain incompletely understood in this tumour type. In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using β-catenin immunohistochemistry and DNA sequencing. Immunohistochemistry revealed focal or multifocal nuclear β-catenin expression in 47% of the tumours. Diffuse nuclear β-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of β-catenin-positive and β-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional β-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. These results demonstrate that β-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of β-catenin in this tumour type.

Steroidogenic Acute Regulatory Protein Is a Useful Marker for Sex-Cord-Stroma Tumors and Normal and Neoplastic Adrenocortical Tissue.

Steroidogenic acute regulatory (StAR) protein is a mitochondrial transport protein with a critical regulatory role for steroid hormone production. The tissue distribution of StAR expression is limited to few human normal tissues. To assess the diagnostic and prognostic value of StAR immunohistochemistry analysis. A tissue microarray containing 19 202 samples from 152 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. StAR immunostaining occurred in 198 (1.2%) of the 17 135 analyzable tumors. StAR expression was observed in 27 of 152 tumor categories, 9 of which included at least 1 strongly positive case. The highest rate of StAR positivity occurred in Leydig cell tumors of the testis and the ovary (100%), steroid cell tumors of the ovary (100%), adrenocortical carcinomas (93%) and adenomas (87%), Sertoli-Leydig cell tumors (67%) and granulosa cell tumors of the ovary (56%), as well as seminomas (7%). Nineteen other tumor entities showed-a usually weak-StAR positivity in less than 6% of cases. A comparison with preexisting Melan-A (a melanocyte antigen) data revealed that StAR was more often positive in adrenocortical neoplasms and in Leydig cell tumors while StAR (but not Melan-A) was negative in Sertoli cell tumors. Our data provide a comprehensive overview on the patterns of StAR immunostaining in human tumors and suggest a diagnostic utility of StAR immunohistochemistry for supporting a diagnosis of Leydig cell tumors or of normal or neoplastic adrenocortical tissue.

Sertoli cell tumor in a 35-year-old woman – case report

Sertoli cell tumor in a 35-year-old woman – case report

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.

The Amalgamated Sophomore-Gonadoblastoma

Gonadoblastoma emerges as a benign gonadal neoplasm composed of germ cells and descendants of sex cord-stromal cells reminiscent of immature granulosa cells and Sertoli cells. Neoplasm is preponderantly associated with disorders of sexual development wherein majority (~80%) of neoplasms articulate phenotypic females. Tumefaction expounds primary amenorrhea and delayed sexual maturation with delayed development of genitalia and emergence of secondary sexual characters. Gonadoblastoma locus appears to be situated adjacent to Y centromere wherein TSPY gene is implicated in carcinogenesis. Commonly discerned distinct morphological configurations appear comprised of spherical or irregular clusters of immature Sertoli cells admixed with germ cells and circumscribing basement membrane. Intervening stroma exhibits enlarged, polygonal cells simulating Leydig cells admixed with focal calcification. Germ cells appear immune reactive to p53, placental alkaline phosphatase (PLAP), CD117/c-KIT and VASA protein or encoded testis specific Y protein. Testicular gonadoblastoma requires segregation from neoplasms such as Sertoli cell tumour. Genetic karyotyping is an essential investigation for distinguishing individuals with intersex disorders and potential occurrence of gonadoblastoma. Surgical extermination is a recommended mode of therapy for alleviating gonadoblastoma.

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.