A rare case of Sertoli cell tumor in an adult male with testicular preservation.

Sertoli cell tumors are a rare subtype of testicular tumors. This report describes a 55-year-old male who presented with scrotal pain and a palpable mass. Diagnostic imaging revealed a hypoechoic mass in the left epididymis and a hyperechoic mass in the right testis. A right testis-sparing surgical procedure was performed, and subsequent histopathological analysis confirmed the presence of a benign Sertoli cell tumor. The patient experienced an uncomplicated postoperative course and was discharged on the same day. This case underscores the viability of testis-sparing surgery in the management of rare testicular tumors, emphasizing its potential for preserving testicular function.

Fluorescence in-situ hybridization assessment of spindle cell-rich testicular sex cord stromal tumors demonstrates multiple chromosomal gains across histologic subtypes.

Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) comprise a group that includes mostly (but not exclusively): myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST. These entities demonstrate histopathologic overlap, and prior genomic studies have failed to identify specific oncogenic drivers. Results of DNA sequencing suggest that different types of spindle cell-rich TSCSTs harbor a recurrent pattern of chromosomal gains. However, these results have not been validated by alternative methods and the extent of these changes within individual tumors remains unknown. We used a combination of commercially available fluorescence in-situ hybridization (FISH) probes (3q11.2, 6p24.3, 6q11.1, 6q23, 7q11.21-q11.22, 9p21.3, 11q13.3, 17p11.2) to enumerate a subset of chromosomes identified as altered (gained) in prior studies. We analyzed 10 cases (3 MGST, 4 unclassified TSCST, 3 AGCT), including 7 that had been previously sequenced. FISH demonstrated gains of chromosomes 3, 6, 7, 9, and 11 above the pre-established threshold (25%) in 50%, 80%, 70%, 20%, and 40% of cases, respectively, with gains of chromosome 17 being present in only 1 unclassified TSCST. The proportion of cells with chromosomal gains ranged from 26% to 60%. Tumors with available copy number data from prior genomic analyses showed a partial discordance between FISH and sequencing results. This study demonstrates that spindle-cell rich TSCSTs harbor a recurrent pattern of chromosomal gains, which are present in variable subsets of neoplastic cells. Further studies are needed to determine if these chromosomal changes represent a mechanism relevant for oncogenesis or a secondary event.

Results of a randomized phase II trial of paclitaxel and carboplatin versus bleomycin, etoposide and cisplatin for newly diagnosed and recurrent Chemonaive stromal ovarian tumors: An NRG oncology/gynecologic oncology group study14.

OBJECTIVES: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST). METHODS: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522. RESULTS: At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%). CONCLUSIONS: The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST.

A Rare Ovarian Mixed Sex Cord Stromal Tumor in a Patient with Ollier Disease: A Case Report.

This is a case report of a 10-year-old with Ollier disease and an ovarian mass. Ollier disease, a rare disorder characterized by multiple enchondromas resulting in bone deformities, has been occasionally associated with ovarian juvenile granulosa cell tumor. This patient developed signs of precocious puberty and was found to have an ovarian tumor; however, pathology revealed a mixed sex-cord stromal tumor with components of juvenile granulosa and Sertoli-Leydig cell tumor. Tumor genomic testing revealed an IDH1 mutation. Mixed sex-cord stromal tumors of this type, also called "gynandroblastomas," have been associated with DICER1 mutations and DICER1 tumor predisposition syndrome but never with Ollier disease. Our findings expand the known spectrum of syndromic associations with this tumor type, with implications for tumor screening.

Ovarian Sex Cord Stromal Tumor in a Free-Ranging Brown Bear (Ursus arctos).

Reports on neoplasms in bears are scarce, especially concerning ovarian tumors. A large primary ovarian neoplasm with multiple metastasis was found during the necropsy of a 14-year-old free-ranging Eurasian brown bear (Ursus arctos) from Northwestern Spain. Histopathology and immunohistochemistry allowed for the diagnosis of a sex cord stromal tumor. This is a complex group of neoplasms which differ in the predominant cell morphology and immunohistochemical features. The microscopic examination revealed two types of cells, one with eosinophilic cytoplasm, intermingled with larger vacuolated cells rich in lipids. The evaluation of the immunoreactivity to different markers, frequently used in the characterization of gonadal tumors (INHA, inhibin-alpha; PLAP, placental alkaline phosphatase; Ki-67; α-SMA, actin alpha-smooth muscle) and inflammation patterns (IBA1, ionized calcium-binding adapter molecule for macrophages; CD3 for T lymphocytes; CD20 for B lymphocytes), displayed significant INHA positive immunostaining of neoplastic cells, as well as inflammatory cell infiltration, mainly composed of macrophages and B lymphocytes. These findings were consistent with a malignant ovarian steroid cell tumor, not otherwise specified. The present study characterizes an unusual type of neoplasm, and also represents the first report of an ovarian sex cord stromal tumor in Ursidae.

Microscopic sex cord-stromal proliferations in extraovarian heterotopic sites: Report of a rare case and review of the literature.

Microscopic heterotopic extraovarian sex cord-stromal proliferations were first reported in the literature in 2015 by McCluggege. Afterwards, few similar cases have been described. Herein, we report the fourteenth case of microscopic heterotopic sex cord-stromal proliferation and the third case sited in the pelvic peritoneum. The clinical history of these rare cases suggests their benign nature. Knowledge of this histological pattern is important for differential diagnoses such as malignant pathologies and metastatic diseases.

Postmenopausal Hyperandrogenism Associated With Synchronous Ovarian Brenner Tumor, Bilateral Leydig Cell Tumor, and Adrenal Mass.

Hyperandrogenism in postmenopausal females may arise from either ovarian or adrenal sources and can pose a challenging diagnostic dilemma. We present the case of a 66-year-old female with postmenopausal hyperandrogenism with virilization, adrenal incidentaloma, and concurrent finding of two extremely rare ovarian tumors, including bilateral Leydig cell tumor and Brenner tumor. Laboratory tests showed elevated testosterone and androstenedione and normal dehydroepiandrosterone sulfate (DHEAS). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone and incomplete suppression of androstenedione. Computed tomography (CT) scan showed a left adrenal nodule and an unremarkable appearance of the ovaries. The pelvic ultrasound did not show an ovarian tumor on the right ovary, and the left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Histopathology showed bilateral Leydig cell tumors and a left ovarian Brenner tumor. At one-year postoperative follow-up, alopecia improved, and testosterone level normalized. This case highlights the importance of diagnostic pathways and interdisciplinary collaboration in managing rare clinical scenarios of hyperandrogenism in postmenopausal females. As in our case, surgeons may be hesitant to remove normal-appearing ovaries. While the three presented tumor types in this case arise from distinct tissues and exhibit different histological characteristics, the presence of such a unique triad prompts consideration of potential unifying pathogenic mechanisms.

Outcomes in ovarian Sertoli-Leydig cell tumor: A report from the International Pleuropulmonary Blastoma/DICER1 and Ovarian and Testicular Stromal Tumor Registries.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, representing <0.5% of all ovarian tumors. We sought to describe prognostic factors, treatment and outcomes for individuals with ovarian SLCT. METHODS: Individuals with SLCT were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Medical records were systematically abstracted, and pathology was centrally reviewed when available. RESULTS: In total, 191 participants with ovarian SLCT enrolled, with most (92%, 175/191) presenting with FIGO stage I disease. Germline DICER1 results were available for 156 patients; of these 58% had a pathogenic or likely pathogenic germline variant. Somatic (tumor) DICER1 testing showed RNase IIIb hotspot variants in 97% (88/91) of intermediately and poorly differentiated tumors. Adjuvant chemotherapy was administered in 40% (77/191) of cases, and among these, nearly all patients received platinum-based regimens (95%, 73/77), and 30% (23/77) received regimens that included an alkylating agent. Three-year recurrence-free survival for patients with stage IA tumors was 93.6% (95% CI: 88.2-99.3%) compared to 67.1% (95% CI: 55.2-81.6%) for all stage IC and 60.6% (95% CI: 40.3-91.0%) for stage II-IV (p < .001) tumors. Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements treated with surgery alone were at higher risk for recurrence (HR: 74.18, 95% CI: 17.99-305.85). CONCLUSION: Most individuals with SLCT fare well, though specific risk factors such as mesenchymal heterologous elements are associated with poor prognosis. We also highlight the role of DICER1 surveillance in early detection of SLCT, facilitating stage IA resection.

A case of ovarian endometrioid carcinoma: Atypical MR imaging.

Endometrioid carcinoma is the second most common ovarian tumor, classified as an epithelial-stromal ovarian tumor, and is usually characterized by a cystic tumor with partial solid components on magnetic resonance (MR) images. In this case report, we discuss an 81-year-old female who presented with atypical genital bleeding and distended abdomen, for which she underwent abdominal computed tomography and MR imaging. Solid endometrioid carcinoma of the ovary is very rare but was confirmed in our patient during the histological examination after surgery.

Ovarian steroid cell tumors: what do we know so far?

Steroid cell tumors (SCT) of the ovary are rare, which has limited advances in the understanding of this enigmatic neoplasm. In this review, we summarize currently known clinicopathologic information on SCT. SCT are frequently hormonally active, leading to elevated serum and/or urine levels of androgenic hormones or their metabolites, and associated symptomatology, including virilization. The reported age at diagnosis is broad and has ranged from as young as 1 year old to 93 years old, although most patients were between ages 20 and 40 years. Most tumors are stage I and unilateral. The tumors are usually well circumscribed with a solid or solid to cystic cut surface. The tumors in one series reportedly ranged in size from 1.2 to 45 cm (average 8.4 cm). MRI is a useful imaging modality, typically showing a well delineated mass with contrast enhancement and lipid content on T2 and T1 weighted images, respectively. Microscopically, SCT display polygonal to epithelioid cells with abundant eosinophilic to vacuolated/clear cytoplasm and display an immunoprofile that is consistent with sex cord-stromal differentiation. Most cases are benign, without any recurrences after primary resection, but a subset - probably less than 20% of cases -are clinically malignant. Pathologic criteria that can specifically predict patient outcomes remain elusive, although features that correlate with adverse outcomes have been proposed based on retrospective studies. The molecular characteristics of SCTs are similarly under characterized, although there is some evidence of an enrichment for hypoxia-signaling gene mutations in SCT. In malignant SCT, the tumors generally show greater global genomic instability, copy number gains in oncogenes, and occasional BAP1 mutation. Future studies involving multi-institutional cohort and unbiased molecular profiling using whole exome/transcriptome sequencing are needed to help advance our molecular understanding of SCTs.

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

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

Is adjuvant chemotherapy necessary for 2014 FIGO stage IC adult granulosa cell tumor?: Multicentric Turkish study.

AIM: The aim of our study is to examine the clinical, surgical, and pathological factors of stage 1C adult granulosa cell tumor (AGCT) patients and to investigate the effects of adjuvant therapy on recurrence and survival rates in this patient group. METHODS: Out of a total of 415 AGCT patients treated by 10 tertiary oncology centers participating in the study, 63 (15.2%) patients with 2014 FIGO stage IC constituted the study group. The FIGO 2014 system was used for staging. Patient group who received adjuvant chemotherapy was compared with patient group who did not receive adjuvant chemotherapy in terms of disease-free survival (DFS), and disease-specific survival. RESULTS: The 5-year DFS of the study cohort was 89%, and the 10-year DFS was 85%. Those who received adjuvant chemotherapy and those who did not were similar in terms of clinical, surgical and pathological factors, except for peritoneal cytology. In the univariate analysis, none of the clinical, surgical or pathological factors were significant for DFS. Adjuvant chemotherapy and type of treatment protocol had no impact on DFS. CONCLUSION: Adjuvant chemotherapy was not associated with improved DFS and overall survival in stage IC AGCT. Multicentric and randomized controlled studies are needed for early stage AGCT in order to confirm these results and reach accurate conclusions.

Efficacy of cyclin-dependent kinase 4/6 inhibitors in combination with hormonal therapy in patients with recurrent granulosa cell tumor of the ovary: A case series.

Cyclin-dependent kinase inhibitors are approved in combination with hormonal therapy for treatment of hormone receptor expressing breast cancers. Activity in hormone receptor expressing gynecologic cancers has been postulated. Granulosa cell tumor of the ovary is one such cancer, which is relatively resistant to traditional cytotoxic chemotherapy. We report a case series of 7 heavily pre-treated patients with recurrent granulosa cell tumor of the ovary with a cyclin-dependent kinase inhibitor in combination with hormonal therapy, with 3 patients demonstrating partial response and 2 with stable disease. As of the data cutoff, 3 patients remained on treatment and 5 were alive, with true medians for duration of treatment and overall survival not reached (medians at data cutoff of 64 weeks and 62 months respectively). The treatment was generally well tolerated, with 1 patient choosing to discontinue treatment due to grade 3 fatigue. This regimen represents a possible option in the treatment of granulosa cell tumor of the ovary, warranting further prospective study for this unmet need in this indolent disease which often requires many lines of treatment.

Recurrent steroid cell tumor not otherwise specified with elevated testosterone and prolactin concentrations and impaired glucose metabolism: a case report.

Steroid cell tumor not otherwise specified (SCT-NOS) is a rare type of sex cord-stromal tumor with malignant potential. A 19-year-old woman underwent laparoscopic bilateral cystectomy, and postoperative pathology showed bilateral ovarian SCT-NOS. She had recurrence of the right tumor 8 years after the surgery, with shortened menstrual cycles, elevated testosterone and prolactin concentrations, and impaired glucose metabolism. We performed a laparoscopic right salpingo-oophorectomy. Testosterone and prolactin concentrations rapidly decreased and returned to the normal range after surgery. Subsequently, she had regular menstrual cycles and good glycemic control. The findings in our case suggest that there is a possibility of late recurrence in SCT-NOS. Therefore, we suggest that the postoperative follow-up period should be 10 years for this condition.

Recurrent Granulosa Cell Tumor in a Postmenopausal Woman: A Case Report and Literature Review.

Ovarian cancer is among the most common types of cancer suffered by the female population. As of United States Cancer Statistics (USCS) 2019, the National Cancer Institute reports the prevalence of ovarian cancer as 11.4 cases per every 100,000 each year. The highest prevalence is in the seventh decade of life. Of all the types, sex cord-stromal tumors (SCSTs) account for 5-8% of cases. They are a heterogeneous group of rare neoplasms originating from the ovarian matrix, and nearly 90% of the hormone-producing tumors are SCSTs. Hence, patients with SCSTs are known to present with excess estrogen and androgen signs and symptoms. Many SCSTs are known for their indolent course and tendency to affect the unilateral ovary. The prognosis of the malignancy depends on the subtype of SCST, the stage of the patient's disease, and age. Among all the types, 20-50% of the ovaries' granulosa cell tumors tend to recur decades after the initial presentation, and 70% of the recurrences end up with a very poor prognosis. This case will discuss a 68-year-old woman who presented with a recurrence of an adult granulosa cell tumor after 13 years in remission. The patient had been previously diagnosed with an adult granulosa cell tumor of the right ovary at age 55 and had undergone surgical resection along with chemotherapy.

Metastatic Testicular Sex Cord Tumor Harboring a EWSR1::ATF1 Gene Fusion-A Case Report of a Novel Neoplasm: "Inflammatory and Nested Testicular Sex Cord Tumor".

We present a case report of a 54-year-old male with a metastatic testicular sex cord tumor harboring a EWSR1::ATF1 gene fusion. The tumor displayed a solid and nested architecture with sclerotic stroma and variable inflammatory infiltrate, and was positive for SF-1, inhibin, EMA, CD30, and WT1 expression. Further genetic analysis identified a EWSR1::ATF1 gene fusion. Overall findings were consistent with an "inflammatory and nested testicular sex cord tumor," a recently described testicular neoplasm characterized by EWSR1::ATF1 gene fusion and aggressive clinical behavior. Due to the aggressive nature of this entity and the limited response to current treatment options available, identification of potential biomarkers for early diagnosis and targeted therapies are critical. This case report provides important insights into the genomic landscape of testicular sex cord-stromal tumors, especially within the CTNNB1-negative subset of patients with an aggressive clinical course, and further supports the distinction of "inflammatory and nested testicular sex cord tumor" as a separate entity from Sertoli cell tumors due to its characteristic morphological, immunohistochemical and molecular, features and clinical behavior.

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

PURPOSE: To assess the recurrence and birth rates among patients with non-epithelial ovarian cancer. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Update on Ovarian Sex Cord-Stromal Tumors.

This article focuses on the recent advances in ovarian sex cord-stromal tumors, predominantly in the setting of their molecular underpinnings. The integration of genetic information with morphologic and immunohistochemical findings in this rare subset of tumors is of clinical significance from refining the diagnostic and prognostic stratifications to genetic counseling.

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.

OBJECTIVE: Identifying 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. METHODS: We 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. RESULTS: 75% 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. CONCLUSION: Chemotherapy 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.