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Objective: To summarize the imaging and clinical features of ovarian Sertoli–Leydig cell tumors (SLCT) to improve our understanding of the disease. Methods: The clinical and imaging data of 15 patients with SLCT confirmed by surgery and pathology were analyzed retrospectively. All patients underwent contrast-enhanced MRI, and five patients underwent contrast-enhanced CT. The expression levels of tumor markers and endocrine hormones were detected in 15 and 10 patients, respectively. Results: All 15 cases of SLCT were unilateral: 8 tumors in the left accessory and 7 tumors in the right accessory, and 4 solid tumors and 11 cystic solid tumors. MRI findings showed that solid components in masses were mainly indicated by intermediate intensity on T1WI and slight hyperintensity on T2WI, while cystic components were indicated by hypo-signal on T1WI and hyper-signal on T2WI. Solid components showed hyper-signals on DWI and hypo-signals on the ADC map. Four cases of solid tumors showed marked enhancement; all the solid components in five cases of cystic solid tumors showed marked enhancement, presenting as nodular, irregular septa, or cystic wall; and the other six cases of cystic solids showed mixed enhancement after administration of contrast medium. Among the six cases of mixed enhancement, five were moderately to poorly differentiated, and one was moderately differentiated. CT findings revealed that the solid components had soft tissue density, whereas cystic components had watery density. Three cases of solid tumors showed marked enhancement, while two cases of cystic solid tumors showed marked enhancement of the solid components or mixed enhancement. Nine patients had increased testosterone levels . Three patients had elevated AFP levels, two had elevated CA125 levels, and one had raised CA199 levels. Ten patients presented with androgen stimulation-related symptoms, two with estrogen stimulation-related symptoms, two with the co-action of estrogen and androgen and one without symptoms. Histopathological results showed that two cases were highly differentiated, seven were moderately differentiated, five were moderately to poorly differentiated, and one was poorly differentiated. Conclusion: SLCT presents as a solid or cystic solid mass, and solid components show either marked or mixed enhancement. Patients with moderate-to-poor and poor differentiation may present with mixed enhancement. SLCT often presents with symptoms related to stimulation of hormones, most commonly androgen.

An ovarian Sertoli–Leydig cell tumor is a rare type of sex cord–stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli–Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli–Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB–IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli–Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided. [ABSTRACT FROM AUTHOR]

Introduction: Ovarian sex cord stromal tumors present with ovarian masses and symptoms resulted from increased hormone secretion. Gynandroblastoma is a rare tumor consisting of two components: granulosa cell tumor and Sertoli or Sertoli-Leydig cell tumor. In this study, a rare case of recurrent gynandroblastoma consisting of Juvenile Granulosa cell tumor and Sertoli cell tumor is reported. Case Presentation: A 29-year-old woman referred to a medical center in Turkmenistan with irregular menstruation and spotting for one year and progressive abdominal pain for the past four months. A mass in the left ovary was reported on CT scan. The patient underwent left salpingo-oophorectomy surgery, and one pathologist diagnosed Granulosa cell tumor, while another diagnosed Androblastoma. 18 months later, the patient underwent laparotomy due to abdominal pain and an intra-peritoneal mass based on MRI. The pathologic diagnosis was Androblastoma. The patient came to Iran to continue treatment and after reviewing the pathology slides of both surgeries, a neoplastic lesion composed of Juvenile Granulosa cell tumor (70%) and well differentiated Sertoli cell tumor (30%) was found, establishing the recurrent Gynandroblastoma. Conclusion: Inadequate sampling of the tumor specimen and lack of sufficient accuracy in microscopic examination easily lead to the misdiagnosis of Gynandroblastoma. All patients with this tumor should be periodically followed up for several years in terms of recurrence. Furthermore, genetic screening for DICER1 mutation is important. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. • Most (92%, 175/191) ovarian Sertoli-Leydig cell tumors (SLCTs) present as FIGO stage I disease with a favorable prognosis. • FIGO stage I tumors with mesenchymal heterologous elements are at higher risk for recurrence when not receiving chemotherapy. • Somatic (tumor) DICER1 RNase IIIb hotspot variants were found in 97% of intermediately and poorly differentiated SLCTs. • More than half (58%, 91/156) of individuals were found to have a germline DICER1 pathogenic/likely pathogenic variant. • DICER1 surveillance recommendations facilitated detection of asymptomatic ovarian SLCT with nearly all resected as stage IA. [ABSTRACT FROM AUTHOR]

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The medium-low differentiation Sertoli-Leydig cell tumor (SLCT) has the tendency to become a malignant tumor. A case of SLCT in an 18 -year-old young woman was reported. Amenorrhea was the first symptom. Within then 10 months, she gradually developed defeminizing symptoms of breast atrophy, as well as signs of virilization such as protruding Adam′s apple, growth of lip beard, deep voice, and clitoral hypertrophy. She had a medical history of thyroid nodule surgery 6 years ago, and the function of thyroid was normal. A large cystic-solid tumor of the left ovary was found under the laparotomic exploration, approximately 10 cm in diameter. Operation was performed, including left adnexectomy, right ovary biopsy, bilateral para-colonic sulcus peritoneal biopsy and greater omentum biopsy. The postoperative pathological diagnosis indicated the medium -low differentiation of SLCT. The patient subsequently recovered well after 4 cycles of chemotherapy with paclitaxel liposome and carboplatin, and was successful childbirth. For women of childbearing age who exhibit de feminization or even masculinization, the possibility of ovarian SLCT should be considered. Fertility preserving surgery and radical surgery should be individualized according to the tumor grading. Patients with high risk of postoperative recurrence should receive timely chemotherapy to reduce the risk of secondary surgery and death. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

An ovarian Sertoli–Leydig cell tumor is a rare type of sex cord–stromal tumor of the ovary. Typically, it presents as abdominal pain or androgenic manifestations in women in the second to third decade of life. While cases of ovarian Sertoli–Leydig cell tumor associated with increased levels of alpha-fetoprotein are rare, they are reported to be the most common alpha-fetoprotein-producing ovarian non-germ cell tumor. We report the case of a 16-year-old patient, who presented with complaints of amenorrhea that had lasted for one year. Transabdominal ultrasound revealed the presence of a tumor in the right ovary, measuring 9.3 × 5.8 cm in size. The laboratory investigation showed an increased level of alpha-fetoprotein. The patient underwent laparoscopic right salpingo-oophorectomy. Histopathological examination confirmed the presence of a moderately differentiated (G2) Sertoli–Leydig cell tumor in the right ovary. For reproductive-age patients with disease confined to the ovary, fertility-sparing surgery is recommended. According to the current recommendations, the administration of adjuvant chemotherapy is indicated in cases of the presence of heterologous elements, poorly differentiated tumors, or FIGO stages IB–IV. As there were no high-risk factors and no residual disease in this case, there were no indications for further treatment with adjuvant chemotherapy. A recent follow-up visit showed that the patient is in complete remission. This report presents a detailed description of the findings, differential diagnosis, clinical course, chosen treatment, and prognosis. Also, a comprehensive literature review of ovarian Sertoli–Leydig cell tumors, focusing on their clinical presentation, laboratory findings, macroscopic and histopathological features, genetics, clinical management, prognostic factors and follow-up, is provided.

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.

Simple Summary: In the present review, we illustrate the interests of molecular pathology for establishing an integrated histomolecular diagnosis of ovarian sex cord–stromal tumors as well as its use for prognosis and treatment. We discuss the key morphological, immunohistochemical and molecular features of each entity, as well as their respective differential diagnoses. This review is organized from the predominant cell morphology to the molecular pathology, based on a practical point of view for the pathologist. Five groups are defined: (i) Group 1: predominance of fibromatous/thecomatous cells and/or stromal cells of unusual morphology; (ii) Group 2: predominance of steroid or luteinized cells; (iii) Group 3: predominance of follicular cells; (iv) Group 4: predominance of Sertoli cells; and (v) Group 5: predominance of sarcomatoid/unclassified/poorly differentiated cells. Diagnostic algorithms are proposed to differentiate each entity within the sex cord–stromal tumor category, and the contribution of molecular pathology for diagnostic purposes is discussed. 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. [ABSTRACT FROM AUTHOR]

Background:DICER1 tumor predisposition syndrome is characterized by an increased risk for development of pleuropulmonary blastoma, pituitary blastoma, multinodular thyroid goiter, thyroid carcinoma, sex cord stromal tumor, cystic nephroma, embryonal rhabdomyosarcoma, and tumors of the CNS, amongst others. Of this list, only pituitary blastoma is recognized as pathognomonic for the syndrome. Case report: We describe a 15-year-old female with bilateral, asynchronous Sertoli-Leydig cell tumors (SLCT). Both tumors harbored an identical germline frameshift mutation as well as unique somatic DICER1 hot-spot point mutations. Discussion: A review of bilateral SLCTs demonstrates that all patients with available DICER1 mutation status carried a germline DICER1 mutation (100%, 9 of 9). In cases with known somatic DICER1 status on bilateral tumors, all harbored distinct somatic mutations (100%, 5 of 5). Our findings support the notion that bilateral ovarian SLCTs are indeed separate events and do not represent recurrent or metastatic disease. [ABSTRACT FROM AUTHOR]

DICER1 mutation has been linked to development of Sertoli-Leydig cell tumor and cystic nephroma, among other neoplasms. We present a unique case of recurrent ovarian Sertoli-Leydig cell tumor in a pediatric patient with a known DICER1 mutation and history of cystic nephroma. She underwent surgical staging and adjuvant chemotherapy, and her recurrences have been treated with chemotherapy, whole-abdomen radiation therapy, and further surgical debulking. This report adds to the small body of evidence about this rare but unexpectedly highly aggressive tumor, especially in the recurrent setting, and reminds the reader of the importance of cancer diagnosis in this population. [ABSTRACT FROM AUTHOR]

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.

Objective: To evaluate the NKX3.1 expression by immunohistochemistry in normal testicular parenchyma and in Sertoli cell tumours and Sertoli Leydig cell tumours of the testes and ovary. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan, from 20102021. Methodology: We used immunohistochemistry to evaluate the positivity and loss of nuclear expression of NKX3.1 in the Sertoli cell tumour (11 cases), Sertoli Leydig cell tumour (31 cases) and in normal testicular parenchyma (7 cases). Results: In our study, there were 49 cases. All the cases of benign testicular parenchyma expressed positivity with nuclear staining of NKX 3.1 in Sertoli cells. Two out of 11 Sertoli cell tumours expressed positivity with nuclear positivity of NKX 3.1 in Sertoli cell component (18.18%) and 9 of the cases showed loss of staining of NKX 3.1 (81.8%). All Sertoli Leydig cell tumours showed loss of staining of NKX 3.1. Conclusion: Nuclear expression of NKX 3.1 is seen in Sertoli cells of normal testicular parenchyma. This staining is lost in Sertoli cell tumours and Sertoli Leydig cell tumours. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the NKX3.1 expression by immunohistochemistry in normal testicular parenchyma and in Sertoli cell tumours and Sertoli Leydig cell tumours of the testes and ovary. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan, from 2010-2021. Methodology: We used immunohistochemistry to evaluate the positivity and loss of nuclear expression of NKX3.1 in the Sertoli cell tumour (11 cases), Sertoli Leydig cell tumour (31 cases) and in normal testicular parenchyma (7 cases). Results: In our study, there were 49 cases. All the cases of benign testicular parenchyma expressed positivity with nuclear staining of NKX 3.1 in Sertoli cells. Two out of 11 Sertoli cell tumours expressed positivity with nuclear positivity of NKX 3.1 in Sertoli cell component (18.18%) and 9 of the cases showed loss of staining of NKX 3.1 (81.8%). All Sertoli Leydig cell tumours showed loss of staining of NKX 3.1. Conclusion: Nuclear expression of NKX 3.1 is seen in Sertoli cells of normal testicular parenchyma. This staining is lost in Sertoli cell tumours and Sertoli Leydig cell tumours.

Objective: To improve the diagnosis and treatment of ovarian Sertoli-Leydig cell tumor (SLCT). Methods： Thirteen cases of ovarian SLCT admitted between June 2014 and July 2021 were analyzed retrospectively, including their clinical characteristics, diagnosis, treatment and prognosis. Results： The median age of onset was 31 years (13-72 years) in 13 patients. Eight patients (61.5%) had the androgenic manifestations (due to the elevated levels of testosterone), 3 patients (23.1%) presented with abnormal uterine bleeding, and the other two patients (15.4% ) had no obvious clinical symptoms. Imaging mainly showed cystic -solid tumors or solid tumors. All 13 patients underwent surgery, and diagnosed with ovarian SLCT by histopathology and immunohistochemistry. Eleven patients were at stage ⅠA, and 2 patients at stage ⅠC. Four patients underwent the complementary surgery to resect the affected adnexa and perform the multi-point pelvic and abdominal biopsy after 1-2 months of the initial operation and histopathological diagnosis. Two patients with SLCT at stage ⅠC underwent postoperative chemotherapy with the bleomycin + etoposide + cisplatin (BEP) regimen. The median follow-up time after surgery was 33 months. None of the 13 patients had a recurrence. Conclusions： Ovarian SLCT should be considered when women had abnormal endocrine symptoms and ovarian cystic-solid or solid masses. Surgery is main treatment for SLCT patient, and operative and postoperative histopathology will confirm the diagnosis of ovarian SLCT. Postoperative chemotherapy can be accordingly considered, and the postoperative multidisciplinary follow-up has been suggested. [ABSTRACT FROM AUTHOR]

Yanglin Ni,1 Xuan Zhou,2 Ling Wu,3 Ping Wu,3 Ying Liu,3 Yinnan Li,3 Li Cai,3 Xueshu Fu,3 Chunhua Zhang3 1Department of Gynaecology, Huai’an Hospital of Traditional Chinese Medicine, Huai’an, Jiangsu Province, People’s Republic of China; 2MyGenostics Inc., Beijing, People’s Republic of China; 3Department of Gynaecology, Huai’an Maternal and Child Health Hospital, Huai’an, Jiangsu Province, People’s Republic of ChinaCorrespondence: Chunhua ZhangDepartment of Gynaecology, Huai’an Maternal and Child Health Hospital, Huai’an, Jiangsu Province, People’s Republic of ChinaTel +8613952326117Email hafyzch@yeah.netIntroduction: DICER1 syndrome is a rare tumor predisposition syndrome caused by germline DICER1 mutation, which is related to a variety of benign and malignant diseases. Our report is the first described case of these three disease phenotypes of DICER1 syndrome. The female patient with a novel germline DICER1 nonsense mutation (c.1088_1089delCTinsAA p.F363X) in exon 8 that was inherited from her mother. In addition to germline DICER1 mutation, two different hotspot somatic DICER1 mutations were detected in her ovarian tissue and goiter tissue. Our report will expand the report of DICER1 mutations in DICER1-syndrome-related diseases and provide case references for further research in the future.Conclusion: When the related disease phenotype appears in childhood, it should be considered whether it is DICER1 syndrome. Genetic testing can help diagnose DICER1 syndrome and develop related surveillance strategies. Awareness of the DICER1 syndrome may result in early recognition of these rare pediatric tumors and appropriate therapeutic management.Keywords: case report, DICER1, Sertoli-Leydig cell tumor, multinodular goiter, cystic nephroma

Sertoli-Leydig cells tumors are rare ovarian neoplasms that can be managed with conservative resection given their generally excellent prognosis. Here we report a case of Sertoli-Leydig cell tumor mistakenly diagnosed as an invasive mucinous adenocarcinoma at time of intraoperative consultation because of its blue-mucinous appearance in the frozen section material. The patient subsequently underwent an extensive staging procedure revealing unilateral, ovarian confined disease. The mucinous features seen on frozen section were lost on the slides prepared from formalin fixed tissues. Immunohistochemical work up confirmed the diagnosis of a pure Sertoli-Leydig cell tumor. No heterologous elements were identified in this tumor. This case illustrates a hitherto unrecognized frozen section pitfall in evaluation of ovarian neoplasms. To the best of our knowledge, this is the first well documented case of pure Sertoli-Leydig cells tumor which resembled a well differentiated mucinous adenocarcinoma during frozen section.

Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases. [ABSTRACT FROM AUTHOR]

Abstract Pure Sertoli cell tumors are an uncommon variant of rare ovarian Sertoli‐Leydig cell tumors. Due to nonspecific clinical and imaging features, diagnosis is often made after histopathological examination. The prognosis is excellent as most are detected in the early stages and surgical resection is often curative in most cases.

Background: Gynecologic sex cord‐stromal tumors (SCSTs) arise from sex cords of the embryonic gonad and may display malignant behavior. We describe the cytomorphologic features of SCSTs in females, including adult and juvenile granulosa cell tumors (AGCTs and JGCTs), Sertoli‐Leydig cell tumors (SLCTs), and steroid cell tumors (SCTs). Methods: We retrieved available cytology slides from females with a histologic diagnosis of sex cord‐stromal tumor between 2009 and 2020 from institutional archives and reviewed their cytoarchitectural features. Results: There were 25, 2, 2, and 1 cytology specimens from 19, 2, 2, and 1 patients (aged 7‐90 years, median 57 years) with AGCT, JGCT, SLCT, and SCT, respectively. Features common to all SCSTs included 3‐dimensional groups, rosettes, rare papillary fragments, abundant single cells and naked nuclei. Rosettes and a streaming appearance of cell groups were only seen in AGCTs, which also rarely featured eosinophilic hyaline globules and metachromatic stroma. AGCTs exhibited high nuclear:cytoplasmic (N:C) ratios, with mild nuclear pleomorphism, uniform nuclei with finely granular chromatin, nuclear grooves and small nucleoli; in contrast, other SCSTs lacked rosettes and nuclear grooves and had generally lower N:C ratios, greater nuclear pleomorphism, coarse chromatin and more abundant cytoplasm. Mitotic figures, necrosis, and inflammation were rarely identified. Conclusions: AGCTs show cytomorphologic features that are distinct from those of other SCSTs. Careful evaluation of the cytological features and ancillary studies (eg, immunochemistry for FOXL2, inhibin and calretinin, or sequencing for FOXL2 mutations) can aid in the accurate diagnosis of these tumors. Adult granulosa cell tumors show cytomorphologic features that are distinct from those of other types of sex cord‐stromal tumor, including microfollicular structures, eosinophilic hyaline globules, and longitudinal nuclear grooves in tumor cells. Careful evaluation of the cytologic features and ancillary studies (eg, immunochemistry for FOXL2, inhibin, and calretinin, or sequencing for FOXL2 mutations) can aid in accurate diagnosis of these tumors. [ABSTRACT FROM AUTHOR]

Sertoli-Leydig cell ovarian tumors (SLCT) are rare ovarian tumors of the sex cord-stroma subset. Their incidence peaks in the second to third decade of life. Most SCLT are diagnosed at an early stage and have a good prognosis. Fertility-sparing surgery may thus be offered. Adjuvant chemotherapy may be indicated according to prognostic factors. However, outcome in relapsing SLCT is poor. There is no evidence supporting a best treatment option upon relapse, but most publications combine radical surgery, chemotherapy, and rarely radiotherapy. Two years after left adnexectomy for FIGO IA SLCT, a now 22-year-old patient presented with peritoneal recurrence without involvement of the remaining ovary and uterus. Since there is no evidence of a survival benefit in the literature of macroscopically healthy contralateral ovary ablation in relapse and hormonal replacement therapy is contraindicative, we consented to endocrine-sparing surgery with conservation of the contralateral ovary, followed by 3 cycles of BEP chemotherapy regimen. Our patient is disease-free 16 months after relapse diagnosis. Since recurrence of SLCT has a very poor prognosis and hormonal treatment is contraindicated, endocrine-sparing surgery for young patients with a normal contralateral ovary might be a legitimate option. This is one of the first reported cases of conservative surgery in SLCT recurrence, we therefore aimed to illustrate its management in a young patient with considerations of contraception, fertility- and then endocrine-sparing surgery, and quality of life.

Competing Interests: Competing interests: None declared.

A 51-year-old perimenopausal female patient presented with hirsutism and voice thickening which was started approximately one and a half years ago. Her initial hormone assay revealed elevated plasma testosterone, 5a-dihydrotestosterone, and dehydroepiandrosterone (DHEA) levels and therefore androgen-secreting tumor was first suspected. However, the lesion was inconspicuous on transvaginal sonography, abdominal-pelvic computed tomography (CT) scan, and pelvic magnetic resonance (MRI) imaging. Consequently, 18F-fluorodeoxyglucose (FDG) positron emission tomography-CT was performed, which localized the lesion as a focal FDG uptake within the right adnexa. Total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed, and although visible gross mass lesions were not observed intraoperatively, pure Leydig cell tumor was pathologically confirmed within the right ovary. Plasma testosterone, 5a-dihydrotestosterone, and DHEA levels were normalized postoperatively. Clinical signs of virilization were also significantly resolved after 3-months of follow-up.