Histone H3 trimethylation on lysine 27 immunostaining pattern in DICER1-associated tumors.

Background: DICER1-associated tumors are heterogeneous and affect several organs. DICER1-associated primary intracranial sarcoma is associated with histone H3 trimethylation on lysine 27 (H3K27me3) loss in nucleus by immunohistochemistry. Methods: We explored the H3K27me3 immunostaining pattern in other DICER1-associated tumors. Twelve tumors from eleven patients with confirmed DICER1 mutations (sporadic and germline) data from a pancancer next-generation sequencing panel, and four tumors of pleuropulmonary blastoma (PPB) were retrieved from our database and stained with anti-H3K27me3 antibody. Results: The H3K27me3 expression in the nucleus showed heterogeneous mosaic loss in neoplastic Sertoli cell components in three of the five cases of moderately to poorly differentiated Sertoli-Leydig cell tumors. Among two tumors of DICER1-associated primary intracranial sarcoma, one showed complete loss of H3K27me3 in all neoplastic cells, whereas the other showed mosaic loss in the sarcomatous spindle cells. One DICER1-associated tumor with epithelial and mesenchymal differentiation, including pulmonary blastoma and PPB, showed mosaic loss of glandular epithelial and mesenchymal components. Four cases of type II PPB and a single case of type III PPB showed a similar mosaic loss of H3K27me3 staining restricted to large spindle cell components. All other components in all tumors-including Leydig cells; the areas of epithelial, cartilaginous, and rhabdomyomatous differentiation; and all cells of the remaining three cases (one papillary thyroid carcinoma and two cases of PPB type I)-demonstrated retained H3K27me3 staining. Conclusions: H3K27me3 expression is not universally lost in DICER1-associated tumors and thus is not predictive of DICER1 mutation status. The mosaic regional loss of H3K27me3 immunostaining is consistent in PPB type II and III, which can be a helpful diagnostic marker for these tumors and suggests a similarity to DICER1-associated intracranial sarcoma.

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.

Ultrasound-Histopathological Presentation of Thyroid and Ovary Lesions in Adolescent Patients with DICER1 Syndrome: Case Reports and Literature Overview.

BACKGROUND: DICER1, a cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she had developed pronounced androgenic symptoms, including a deepened male voice; facial, back, and neckline acne; hirsutism; and menstrual irregularities leading to secondary amenorrhea. A thyroid ultrasound identified a multinodular goiter (MNG) with cystic-solid lesions containing calcifications. An abdominal ultrasound identified a 5.7 × 6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to a total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease (TFND) was diagnosed bilaterally. DNA analysis using NGS, confirmed via the Sanger method, revealed a pathogenic heterozygotic variant c.2953C>T [p.Gln985*] in exon 18 of the DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 mL goiter. A month prior to his admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed MNG. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928*] in exon 17 of the DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed TFND bilaterally. CONCLUSIONS: Recent advances in genetic evaluation and in histological approaches indicate that MNG/TFND, although rare in the pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgenization, may warrant assessment also of the DICER1 gene within CPS molecular panel screening.

The Hidden Source of Testosterone Hypersecretion in a Female-A 30-Year Journey.

A Sertoli-Leydig cell tumor (SLCT) is a rare ovarian tumor that often excessively secretes testosterone and its precursor, leading to virilization in females. We present a case of a female patient with persistent, severe hyperandrogenism. Our patient had a history of left oophorectomy due to an ectopic pregnancy and initially presented with amenorrhea at the age of 30. Biochemical evaluations suggested ovarian hyperandrogenism. Despite the absence of an ovarian mass, she underwent a right oophorectomy and remained hyperandrogenic postoperatively. When she established care with our endocrinology clinic at the age of 58, she had more virilizing features and total testosterone levels ranging from 10.1 to 12.0 nmol/L (292-346 ng/dL; normal reference range for women: 0.07-1.56 nmol/L; 2-45 ng/dL). While biochemical evaluations were consistent with tumorous ovarian hyperandrogenism, ultrasound and computed tomography again failed to identify the source. Finally, an 18F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed a mass in the left adnexa, and she underwent removal of the mass. The final pathology confirmed SLCT. The case highlights that SLCT may be small and slow-growing and not readily visible on conventional imaging modalities.

Androgen Insensitivity Syndrome with Bilateral Gonadal Sertoli Cell Lesions, Sertoli-Leydig Cell Tumor, and Paratesticular Leiomyoma: A Case Report and First Systematic Literature Review.

Androgen insensitivity syndrome (AIS) is a rare Mendelian disorder caused by mutations of the androgen receptor (AR) gene on the long arm of the X chromosome. As a result of the mutation, the receptor becomes resistant to androgens, and hence, karyotypically male patients (46,XY) carry a female phenotype. Their cryptorchid gonads are prone to the development of several types of tumors (germ cell, sex cord stromal, and others). Here, we report a 15-year-old female-looking patient with primary amenorrhea who underwent laparoscopic gonadectomy. Histologically, the patient's gonads showed Sertoli cell hamartomas (SCHs) and adenomas (SCAs) with areas of Sertoli-Leydig cell tumors (SLCTs) and a left-sided paratesticular leiomyoma. Rudimentary Fallopian tubes were also present. The patient's karyotype was 46,XY without any evidence of aberrations. Molecular genetic analysis of the left gonad revealed two likely germline mutations-a pathogenic frameshift deletion in the AR gene (c.77delT) and a likely pathogenic missense variant in the RAC1 gene (p.A94V). Strikingly, no somatic mutations, fusions, or copy number variations were found. We also performed the first systematic literature review (PRISMA guidelines; screened databases: PubMed, Scopus, Web of Science; ended on 7 December 2023) of the reported cases of patients with AIS showing benign or malignant Sertoli cell lesions/tumors in their gonads (n = 225; age: 4-84, mean 32 years), including Sertoli cell hyperplasia (1%), Sertoli cell nodules (6%), SCHs (31%), SCAs (36%), Sertoli cell tumors (SCTs) (16%), and SLCTs (4%). The few cases (n = 14, 6%; six SCAs, four SCTs, two SLCTs, and two SCHs) with available follow-up (2-49, mean 17 months) showed no evidence of disease (13/14, 93%) or died of other causes (1/14, 7%) despite the histological diagnosis. Smooth muscle lesions/proliferations were identified in 19 (8%) cases (including clearly reported rudimentary uterine remnants, 3 cases; leiomyomas, 4 cases). Rudimentary Fallopian tube(s) were described in nine (4%) cases. Conclusion: AIS may be associated with sex cord/stromal tumors and, rarely, mesenchymal tumors such as leiomyomas. True malignant sex cord tumors can arise in these patients. Larger series with longer follow-ups are needed to estimate the exact prognostic relevance of tumor histology in AIS.

Sertoli-Leydig Cell Tumor as a Cause of Elevated 17-OH Progesterone.

Virilizing ovarian tumors are rare but a clinically important diagnosis in a patient presenting with hyperandrogenism. Workup of hyperandrogenism is challenging with a broad range of differentials, including adrenal and ovarian pathology, tumoral or nontumoral in nature. Baseline follicular-phase 17-hydroxyprogesterone (17OHP) measurement is part of the investigation algorithm, and elevated levels are often associated with nonclassic congenital adrenal hyperplasia (NCCAH), which can have its first presentation in adolescence or adulthood. This case describes a young adult woman of reproductive age presenting with menstrual irregularity, raised testosterone, and 17OHP. After extensive workup and serial follow-up, she was found to have a Sertoli-Leydig cell tumor of the left ovary and underwent successful laparoscopic salpingo-oophorectomy with normalization of her menstrual irregularity and biochemical resolution of her testosterone and 17OHP levels.

DICER1-related Sertoli-Leydig cell tumor and rhabdomyosarcoma: An evolving disease with a challenging clinical course and treatment: A case report.

DICER1 syndrome is a rare genetic disorder predisposing young patients to multiple types of cancer. A 17-year-old woman with a history of mixed Sertoli-Leydig cell tumor and juvenile granulosa cell tumor of the left ovary at age 14 presented with a pelvic mass. She underwent fertility preservation cytoreductive surgery and the pathology showed high-grade sarcoma with rhabdomyosarcomatous differentiation. After the surgery, patient received one cycle of chemotherapy but her disease continued to progress. She therefore underwent total hysterectomy, right salpingo-oophorectomy and hyperthermic intraperitoneal chemotherapy followed by consolidation chemotherapy. Magnetic resonance imaging revealed no evidence of the disease before and after the completion of her chemotherapy. Genetic testing confirmed the DICER1 pathogenic variant. However, she presented again with a recurrence of the disease 6 months later and ultimately died of the disease 11 months after the surgery. Our case demonstrates the challenging management of this rare disease in a young patient and the need for new and effective treatments.

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.

Imaging in gynecological disease (27): clinical and ultrasound characteristics of recurrent ovarian stromal cell tumors.

OBJECTIVE: To describe the clinical and ultrasound characteristics of recurrent granulosa cell and Sertoli-Leydig cell tumors. METHODS: This was a retrospective observational study performed at Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico, IRCCS, Rome (Gemelli center), Italy. Patients with a histological diagnosis of recurrent granulosa cell tumor or Sertoli-Leydig cell tumor were identified from the database of the Department of Gynecological Oncology. Those who had undergone a preoperative ultrasound examination at the Gemelli center between 2012 and 2020 were included, and the data retrieved from the original ultrasound reports. In all of these reports, the recurrent tumors were described using International Ovarian Tumor Analysis (IOTA) terminology. If a patient had more than one episode of relapse, information from all episodes was collected. If there was more than one recurrent tumor at the same ultrasound examination, all tumors were included. One expert sonographer also reviewed all available ultrasound images to identify typical ultrasound patterns using pattern recognition. RESULTS: We identified 30 patients with a histological diagnosis of recurrent granulosa cell tumor (25 patients, 55 tumors) or Sertoli-Leydig cell tumor (five patients, seven tumors). All 30 had undergone at least one preoperative ultrasound examination at the Gemelli center and were included. These women had a total of 66 episodes of relapse, of which a preoperative ultrasound examination had been performed at the Gemelli center in 34, revealing 62 recurrent lesions: one in 22/34 (64.7%) episodes of relapse, two in 4/34 (11.8%) episodes and three or more in 8/34 (23.5%) episodes. Most recurrent granulosa cell tumors (38/55, 69.1%) and recurrent Sertoli-Leydig tumors (6/7, 85.7%) were classified as solid or multilocular-solid tumors, while 8/55 (14.5%) recurrent granulosa cell tumors and 1/7 (14.3%) recurrent Sertoli-Leydig cell tumors were unilocular cysts and 9/55 (16.4%) recurrent granulosa cell tumors were multilocular cysts. The nine unilocular cysts had contents that were anechoic (n = 2) or had low-level echogenicity (n = 7), had either smooth (n = 4) or irregular (n = 5) internal cyst walls, and ranged in largest diameter from 8 to 38 mm, with three being < 20 mm and five being 20-30 mm. On retrospective review of the images, two typical ultrasound patterns were described: small solid tumor measuring < 2 cm (15/62, 24.2%) and tumor with vascularized echogenic ground-glass-like content (12/62, 19.4%). CONCLUSIONS: Some granulosa cell and Sertoli-Leydig cell recurrences manifest one of two typical ultrasound patterns, while some appear as unilocular cysts. These are usually classified as benign, but in patients being followed up for a granulosa cell tumor or Sertoli-Leydig cell tumor, a unilocular cyst should be considered suspicious of recurrence. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Relevance of Molecular Pathology for the Diagnosis of Sex Cord-Stromal Tumors of the Ovary: A Narrative Review.

Ovarian sex cord-stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz-Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli-Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.

Sertoli-Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort.

INTRODUCTION: Sertoli-Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli-Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants. METHODS: In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli-Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan-Meier analysis followed by a log rank test for differences between variables RESULTS: 41 women with Sertoli-Leydig cell tumors were identified. Median age was 41 years (range 6-79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I-II) and 0% in advanced tumor stages (stages III-IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli-Leydig cell tumor. CONCLUSION: The prognosis for women with Sertoli-Leydig cell tumors with localized disease is excellent. Women with advanced stages (III-IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli-Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.

Sertoli leydig cell tumor of the ovary in a woman with cushing syndrome: A case report.

Sertoli-Leydig cell tumor (SLCT) is a rare tumor of the ovary.Cushing's syndrome (CS), on the other hand, is a clinical picture formed by the long-term high levels of glucocorticoids in the blood for any reason and the resulting symptoms. Exceptionally in some of cases, a tumor far from the adrenal region synthesizes adrenocortical hormones. Among such ectopic neoplasms, CS Tumors of the ovary that secrete cortisol as a cause of the disease is an exceptional case. In other words, in this case, we argue that the tumor in the ovary causes Cushing's syndrome by secreting cortisol and ACTH-like peptides. There are 5 cases reported in the literature. In this case report we present a case in which SCLT of the ovary was detected by histopathological examination in a patient who underwent laparoscopic surgery due to Cushing's syndrome and bilateral adnexal mass.

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.

Sertoli-Leydig cell tumor associated with a germline DICER1 pathogenic variant diagnosed during pregnancy: Considerations for treatment, surveillance, and prevention.

•This is the first report of a germline DICER1-associated Sertoli-Leydig cell tumor (SLCT) diagnosed in pregnancy.•SLCT is linked to DICER1 pathogenic variants, but little is known about management of DICER1-associated SLCT.•There is an extended risk for metachronous SLCT in patients with germline DICER1 pathogenic variants who retain an ovary.•Prophylactic contralateral salpingo-oophorectomy may be offered with shared decision making to patients with inherited SLCT.•Genetic testing for DICER1 should be offered to all patients with moderately or poorly differentiated SLCT.

Paraneoplastic Erythropoiesis in Patients With Ovarian Sertoli Leydig Cell Tumors: Retrospective Study From Tertiary Care Institute.

To study the clinical, paraneoplastic hematological presentation of Sertoli Leydig cell tumor patients. This retrospective study involved women with Sertoli Leydig cell tumors treated at JIPMER from 2018 to 2021. We reviewed the hospital registry for the Sertoli Leydig cell tumor among all the ovarian tumors being treated in the department of obstetrics and gynecology. We retrieved the datasheets of patients with Sertoli Leydig cell tumor and studied their clinical and hematological presentation, their management, complications, and follow-up. We had 5 patients of Sertoli Leydig cell tumor of 390 ovarian tumors operated during the study period. The mean age at presentation was 31.6 years. All 5 patients had hirsutism and menstrual irregularity. One patient presented with symptoms of polycythemia along with these complaints. Elevated serum testosterone was seen in all (mean being 688 ng/ml). Mean preoperative hemoglobin was 15.84%, and mean hematocrit was 50.14%. Fertility-sparing surgery was performed in 3 of them and the rest had complete surgery. All patients were in Stage IA. Histologically, one had Pure Leydig cell, three had steroid cell tumor not otherwise specified and one was mixed Sertoli Leydig cell tumor. After the operation, the hematocrit and testosterone levels came down to the normal range. The virilizing manifestations regressed over 4-6 months. With a follow-up period ranging from 1 to 4 years, all 5 patients are alive, one patient had a disease recurrence in the ovary after 1 year of primary surgery. She is disease-free following the second surgery. The rest of the patients had no disease recurrence and are disease-free following surgery. Virilizing ovarian tumors can have paraneoplastic polycythemia which needs to be looked into while evaluating these patients. Similarly, while evaluating polycythemia in young females, an androgen-secreting tumor has to be ruled out as it is reversible and completely treatable.

Novel pathogenic variant of DICER1 in an adolescent with multinodular goiter, ovarian Sertoli-Leydig cell tumor and pineal parenchymal tumor of intermediate differentiation.

OBJECTIVES: To present a case of a new pathogenic variant of DICER1. CASE PRESENTATION: 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli-Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. CONCLUSIONS: Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.

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.