Ovarian Sertoli-Leydig Cell Tumor Research Articles

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.

Reclassification of two germline DICER1 splicing variants leads to DICER1 syndrome diagnosis

DICER1 syndrome is an inherited condition associated with an increased risk of developing hamartomatous and neoplastic lesions in diverse organs, mainly at early ages. Germline pathogenic variants in DICER1 cause this condition. Detecting a variant of uncertain significance in DICER1 or finding uncommon phenotypes complicate the diagnosis and can negatively impact patient care. We present two unrelated patients suspected to have DICER1 syndrome. Both females (aged 13 and 15 years) presented with multinodular goiter (thyroid follicular nodular disease) and ovarian tumours. One was diagnosed with an ovarian Sertoli-Leydig cell tumour (SLCT) and the other, with an ovarian juvenile granulosa cell tumour, later reclassified as a retiform variant of SLCT. Genetic screening showed no germline pathogenic variants in DICER1. However, two potentially splicing variants were found, DICER1 c.5365-4A>G and c.5527+3A>G. Also, typical somatic DICER1 RNase IIIb hotspot mutations were detected in the thyroid and ovarian tissues. In silico splicing algorithms predicted altered splicing for both germline variants and skipping of exon 25 was confirmed by RNA assays for both variants. The reclassification of the ovarian tumour, leading to recognition of the association with DICER1 syndrome and the characterization of the germline intronic variants were all applied to recently described DICER1 variant classification rules. This ultimately resulted in confirmation of DICER1 syndrome in the two teenage girls.

Progressive ovarian sertoli – leydig cell tumor: case report

Introduction: Ovarian Sertoli – Leydig Cell Tumor (SLCT) are one of sex cord tumor that has incidence rate less than 0,2% of all ovarian tumors. It occurs predominantly in second and third decades of lifetime. It has characteristics mostly low–grade malignant although poorly differentiated type may behave more aggressively. Clinical characterstic of ovarian SLCT usually hormonal changes, nevertheless in patients without hormonal changes, the manifestation of the disease consists of abdominal pain and abdominal enlargement, and palpable adnexal mass on physical diagnostic. Case: a 52 years woman that has been undergo right salpingooforectomy 5 months prior with PA result shows poorly differentiated sertoli – leydig cell tumor, and refusing to chemotherapy. She came with chief complaint of abdominal enlargement since 3 months accompanied with lower abdominal pain 2 weeks prior. Ultrasound examination shows cystic ovarian neoplasm with solid part size 9 x 9 x 9 cm from left adnexa. Tumor markers that arise are Alpha–Fetoprotein (AFP) 52 ng/mL and Lactate Dehydrogenase (LDH) = 432 U/mL which correspond to sex cord tumor. She has undergone Laparotomy Total Abdominal Hysterectomy Left Salpingooforectomy and chemotherapy afterward. Conclusion: Ovarian Sertoli – Leydig Cell Tumors (SLCT) are a rare sex cord ovarian tumor that may behave more aggressively as it poorly differentiated. It has manifestations of hormonal changes and also abdominal enlargement.

Pediatric primary extra-ovarian Sertoli Leydig cell tumor of the retroperitoneum.

Ovarian Sertoli Leydig cell tumors (SLCT) accounts for less than 0.5% of all ovarian malignancies. The incidence of primary extra-ovarian SLCT is extremely rare with reported cases occurring in young adult women till now. We report case of primary retroperitoneal extra-ovarian SLCT in a seven-year girl child without any hormonal manifestation. She presented with complaint of left side abdominal swelling associated with intermittent pain for a duration of six months. CT scan revealed a huge retroperitoneal space-occupying lesion abutting the dorsal vertebrae and present posterior to pancreas, spleen and left kidney. The tumor was diagnosed as extraovarian Sertoli Leydig cell tumor with intermediate differentiation on histopathology and immunohistochemistry.

A Case of Adolescent Ovarian Sertoli-Leydig Cell Tumor and Literature Review

A Case of Adolescent Ovarian Sertoli-Leydig Cell Tumor and Literature Review

Severe intrahepatic cholestasis of pregnancy due to a Sertoli-Leydig cell tumour in a woman with polycystic ovary syndrome: a case report

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a common gestational complication characterized by pruritus and elevated bile acids, usually occurring in the third trimester when the serum estrogen and progesterone levels are highest. Hyperandrogenism during pregnancy is a pathological state that is mostly induced by polycystic ovary syndrome (PCOS) but rarely by concomitant androgen-secreting ovarian tumours. To date, no correlation has been drawn between ICP and hyperandrogenism.Case presentationHere, we present a rare case of early-onset severe ICP in a PCOS patient conceived via in vitro fertilization-embryo transfer, with worsening hirsutism and acne due to high levels of testosterone and dehydroepiandrosterone sulphate, both of which were produced by a fast-growing ovarian Sertoli–Leydig cell tumour. Her serum estradiol was also very high, which was speculated to be converted from the circulating androgens by the placenta. She had preterm premature rupture of membranes and delivered at 30 weeks, followed by a rapid remission of ICP as her serum estradiol dropped. However, the excessive androgens did not retreat until the large ovarian tumour was surgically removed.ConclusionThis unusual case highlights the concurrence of original hyperandrogenism and subsequent hyperestrogenism during pregnancy and the resultant confounding manifestations. Obstetricians should be aware of the potential association between androgen excess and ICP via placental aromatization.

Embryonal Rhabdomyosarcoma of the Uterine Cervix: A Clinicopathologic Study of 94 Cases Emphasizing Issues in Differential Diagnosis Staging, and Prognostic Factors.

Embryonal rhabdomyosarcoma of the uterine cervix (cERMS) is rare and frequently associated with DICER1 mutations. We report 94 tumors that arose in patients aged 7 to 59 (median=23) years and presented with vaginal bleeding (52), protruding vaginal mass (17), cervical polyp (8), or expelled tumor fragments per vagina (5). Nine had DICER1 syndrome, 8 of whom had other syndromic manifestations including ovarian Sertoli-Leydig cell tumor (7), multinodular goiter (3), pleuropulmonary blastoma (2), pineoblastoma (1), and osteosarcoma (1). Syndromic patients were younger than nonsyndromic patients (16 vs. 24y). Tumor size ranged from 2 to 24 (median=4.5)cm. Ninety-two tumors were polypoid, most being grape-like (77 of 92). They were characterized by aggregates of primitive cells, almost always exhibiting a cambium layer, within a variably myxoedematous stroma and were hypocellular (63), moderately cellular (22), or hypercellular (9). Entrapped glands, typically scant, were present in 84 tumors. Primitive hyperchromatic ovoid to spindled cells with minimal cytoplasm predominated but differentiated rhabdomyoblasts with abundant eosinophilic cytoplasm (having cross-striations in 30) were seen in 83 tumors; they were often sparse but predominated in three. Nine tumors showed areas of intersecting fascicles and 4 zones with densely cellular (solid) growth. Cartilage was present in 38. Anaplasia was seen in 15 tumors, as was necrosis. Mitotic activity ranged from 1 to 58/10 high-power fields (median=8). The varied microscopic features resulted in a spectrum of differential diagnostic considerations, mainly typical and cellular forms of fibroepithelial polyps, Mullerian adenosarcoma, and other sarcomas. Follow-up was available for 79 patients ranging from 6 to 492 (median=90) months. Treatment information was available in 62 and included polypectomy in 6 patients (2 also received chemotherapy), limited resection in 26 (14 also received chemotherapy), hysterectomy in 29 (15 with adjuvant chemotherapy), and biopsies only in 1 (with chemotherapy). Staging was possible in 56 tumors; according to the "uterine sarcoma" system (tumor size and extent) they were: stage I (10/56; could not be further subclassified as size not available), IA (22/56), IB (18/56), IIA (2/56), IIB 3/56), IIIC (1/56). According to the "adenosarcoma" system (depth of invasion and extent) they were: stage IA (26/56), IB (14/56), IC (10/56), IIA (2/56), IIB (3/56), IIIC (1/56). Eight patients had local recurrence following incomplete excision (10%). Eleven of 79 patients had extrauterine recurrences (14%) and 9 died of disease (11%). Older age was associated with extrauterine recurrence (median 44 vs. 22; P =0.002) and decreased disease-specific survival (median 44 vs. 22; P =0.02). For patients with tumors initially confined to the cervix, the adenosarcoma staging system was superior to the uterine sarcoma staging system for predicting survival ( P =0.02). Three patients with DICER1 syndrome who underwent fertility-preserving surgery developed a second primary cERMS 7, 7, and 12 years after their primary tumor. All 9 patients with DICER1 syndrome had tumors confined to the cervix and none died of disease. This study highlights the intriguing clinical aspects of cERMS including its long-known tendency to occur in the young but also more recently appreciated association with DICER1 syndrome. Establishing the diagnosis may still be difficult because of the hazard of sampling a neoplasm which in areas may appear remarkably bland and also because of its potential confusion with other neoplasms. This study indicates that this tumor has a good prognosis at this site and in selected cases a conservative surgical approach is a realistic consideration.

Pregnancy and Childbirth After Sertoli-Leydig Cell Tumor Resection: A Case Study and Literature Review

Objectives: To explore the clinical manifestations and pathological features in the biopsy of ovarian Sertoli-Leydig cell tumor, as well as to improve the clinical understanding of the disease. Methods: A case of pregnancy and childbirth after Sertoli-Leydig cell tumor resection was retrospectively analyzed. The patients’ clinical data were collected, including the clinical manifestations, postoperative biopsy results, auxiliary examination results, immunohistochemical results, treatment, and prognosis of the patient. Results: (1) SLCT occurred unilaterally; (2) according to the International Federation of Obstetrics and Gynecology (FIGO), the clinical staging was stage IA; according to the pathological classification of malignant tumors, it was grade ? (moderately differentiated); (3) a healthy female live baby was delivered. Conclusion: Such tumors are rare low-grade malignancies and are even rarer in pregnancy. An increase in preoperative testosterone levels with positive ultrasonography results can be used to assist diagnosis; however, postoperative biopsy pathology remains the “gold standard” for the diagnosis of SLCTs. The definite diagnosis of SLCTs is of great significance for surgical planning and prognostic evaluation.

Pure Sertoli cell tumor of the ovary: A case report

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.

Neuroectodermal elements are part of the morphological spectrum of DICER1-associated neoplasms

Many sarcomas with DICER1 pathogenic variants (PVs) exhibit a characteristic morphology, including a subepithelial layer of malignant mesenchymal cells, areas of rhabdomyoblastic differentiation and cartilaginous and/or osseous elements. We report 5 DICER1-associated neoplasms (1 moderately to poorly differentiated Sertoli Leydig cell tumour and 4 sarcomas) containing variable amounts of neuroectodermal elements. The neoplasms predominantly involved or were in close proximity to the female genital tract (ovary, uterine corpus, abdominal and pelvic cavity) and occurred in females aged 14 months to 54 years. The neuroectodermal elements were characterised by solid and tubular/rosette-like patterns and variable immunoreactivity with SALL4 and neuroendocrine markers. In some cases, the neuroectodermal component was focal while in others it was exclusive. In one case, the focal neuroectodermal component within an ovarian Sertoli Leydig cell tumour resulted in extraovarian metastasis. In reporting these cases, we suggest that neuroectodermal elements, including pure neuroectodermal tumours, are part of the morphological spectrum of DICER1-associated neoplasms. It is important that pathologists recognize that a neuroectodermal component (often admixed with other elements) may be a feature of such neoplasms. This will facilitate appropriate tumour and/or germline testing which could lead to the identification of germline DICER1 PVs (DICER1 syndrome). Three of the patients we report were subsequently shown to have a germline DICER1 PV.

An Unusual Enteric Yolk Sac Tumor: First Report of an Ovarian Germ Cell Tumor Associated With a Germline Pathogenic Variant in DICER1.

A variety of unusual tumors are associated with both germline and somatic DICER1 pathogenic variants (PVs), including, in the female genital tract, embryonal rhabdomyosarcoma at various sites and ovarian Sertoli-Leydig cell tumor. There have been occasional reported cases of ovarian germ cell tumors [mainly yolk sac tumor (YST)] harboring DICER1 PVs but, as far as we are aware, none of these has been proven to have a germline provenance. We report an unusual enteric variant of ovarian YST in a 28-yr-old woman associated with a germline PV c.901C>T (p.Gln301Ter) in exon 7 of DICER1, accompanied by a somatic (YST-only) hotspot mutation: c.5437G>A, p.E1813K. To our knowledge, this is the first report of an ovarian germ cell tumor associated with a germline DICER1 PV. We review other reported cases of ovarian germ cell tumor with DICER1 PVs and discuss the differential diagnosis of this unusual variant of YST which was originally diagnosed as a mucinous adenocarcinoma.

Spectrum of DICER1 Germline Pathogenic Variants in Ovarian Sertoli-Leydig Cell Tumor.

Sertoli–Leydig Cell Tumors (SLCTs) are rare ovarian sex cord-stromal neoplasms, which predominantly affect adolescents and young female adults. The SLCTs clinical diagnosis and treatment remains challenging due to the rarity and the varied presentation. A large majority of SLCTs are unilateral, but also bilateral neoplasms have been reported, sometimes in the context of DICER1 syndrome. In fact, the most significant discovery regarding the molecular genetics basis of SLCTs was the finding of somatic and germline pathogenic variants in the DICER1 gene. The DICER1 protein is a key component of the micro-RNA processing pathway. Germline DICER1 pathogenic variants are typically inherited in an autosomal dominant pattern and are most often loss-of-function variants dispersed along the length of the gene. Contrarily, DICER1-related tumors harbor a characteristic missense “RNase IIIb hotspot” mutation occurring in trans, or, less frequently, loss of heterozygosity (LOH) event involving the wild-type allele. While DICER1 mutations have been identified in approximately 60% of SLCTs, especially in the moderately or poorly differentiated types, there are only a few case reports of ovarian SLCT with underlying germline DICER1 mutations. In this review, we focus on the molecular genetic features of SLCT, performing an extensive survey of all germline pathogenic variants modifying the whole sequence of the DICER1 gene. We point out that DICER1 genetic testing, coupled with an accurate variants classification and timely counseling, is of crucial importance in the clinical management of ovarian SLCT-affected patients.

Imaging, clinical, and pathologic findings of Sertoli-leydig cell tumors.

To explore the clinical features, imaging findings, and pathological manifestations of ovarian Sertoli-Leydig cell tumors (SLCTs). The clinical and pathological manifestations, tumor location, size, morphology, vascularity, computed tomography (CT) density, magnetic resonance imaging (MRI) signal intensity, and contrast enhancement patterns in five cases with SLCTs were retrospectively reviewed. SLCTs most commonly occurred in young women. Virilization was observed in three cases (60%). All five tumors were unilateral and oval or round, with a clear boundary. The solid part of the tumor was isoattenuated on the conventional CT scan, and showed isoattenuation or slight hypoattenuation relative to adjacent myometrium on T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI). On contrast-enhanced images, three tumors showed marked enhancement. DICER1 hotspot mutations were commonly seen in SLCTs. A highly vascularized mass with low signal intensity (SI) of the solid part on T2WI and androgen overproduction symptoms may suggest an SLCT.

28. Elevated 17-Hydroxyprogesterone (17-OHP) in Ovarian Sertoli-Leydig Cell Tumor

<h3>Background</h3> Ovarian Sertoli-Leydig cell tumors (SLCTs) are rare sex cord-stromal tumors, which account for less than 0.5% of all malignant ovarian neoplasms. Patients often present with signs of hyperandrogenism; examples include menstrual cycle irregularities, hirsutism and acne. SLCTs are typically associated with elevated levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S) and alpha fetal protein (AFP). Prior cases have reported an association of SLCTs with elevated 17-hydroxyprogesterone (17-OHP) which can create clinical confusion and the potential misdiagnosis of non-classic congenital adrenal hyperplasia (NCCAH). We present a case series of patients with SLCTs with concurrent 17-OHP elevation without the diagnosis of NCCAH. <h3>Case</h3> Case 1: A 15 year old presented for evaluation of secondary amenorrhea. Laboratory evaluation was remarkable for elevated total testosterone (692 ng/dL), DHEA-S (313 ug/dL), and 17-OHP (362 ng/dL). Computed Tomography (CT) scan of the abdomen and pelvis revealed a 5 cm right ovarian mass. She underwent diagnostic laparoscopy and right oophorectomy. Surgical pathology demonstrated stage 1A intermediate to poorly differentiated SLCT. Case 2: A 12 year old presented for evaluation of secondary amenorrhea. Laboratory evaluation was significant for elevated total testosterone (127 ng/dl), DHEA-S (242 ug/dl), and 17-OHP (461 ng/dl). Inhibin B and AFP were also elevated. Pelvic ultrasound revealed an enlarged solid appearing left ovary measuring 6 cm. She underwent exploratory laparotomy and left oophorectomy. Surgical pathology demonstrated stage 1A moderately to poorly differentiated SLCT. Case 3: A 14 year old presented for evaluation of irregular menses and deepening of voice. Laboratory evaluation was significant for elevated total testosterone (354 ng/dl) and 17-OHP (306 ng/dl). AFP was also elevated. CT scan of the abdomen and pelvis revealed a 31 cm complex mass likely arising from the right adnexa. She underwent exploratory laparotomy, right salpingo-oophorectomy. Surgical pathology demonstrated stage 1A moderately differentiated SLCT. <h3>Comments</h3> We present three cases of 17-OHP elevation in the setting of SLCT. One patient underwent evaluation for NCCAH with normal adrenocorticotropic hormone stimulation test. Recognition of the potential production of 17-OHP by SLCTs can prevent any unnecessary testing and delay in diagnosis and intervention. All tumors were remarkable for moderate to poorly differentiated histology. We theorize that the production of 17-OHP is secondary to underlying dysregulation of androgen production by the SLCTs and may predict a more poorly differentiated tumor. A larger case series would help to address this theory and further explore this rare association.

Comparison of the Prognostic Outcome between High-Grade Ovarian Sertoli-Leydig Cell Tumors (SLCTs) and Low-Grade SLCTs

The purpose of the current study was to compare prognostic outcomes between patients with high-grade ovarian Sertoli-Leydig cell tumors (SLCTs) and those with other low-grade SLCTs. We retrospectively reviewed medical records for 24 patients pathologically diagnosed with SLCTs between 2006 to 2019 at two institutions. The patients were grouped according to pathological grade: SLCT was classified as grade 1, well differentiated; grade 2, intermediated differentiated; or grade 3, poorly differentiated (Meyer's classification). Statistical analysis was performed to compare survival outcomes according to pathological grade. The median patient age was 42.5 years (range 16–75). Eighteen patients (75%) were International Federation of Gynecology and Obstetrics stage I, and none were diagnosed in stage IV. Nine patients (37.5%) were grade 3, and 15 patients (63.5%) were grades 1–2. When comparing clinical baseline characteristics of the grade 1–2 group with those of the grade 3 group, only serum CA125 level at diagnosis was significantly higher in the grade 3 group (38.34 vs. 382.29, p=0.002). Five patients experienced recurrence of grade 3 disease, while no recurrence was reported in grade 1–2 disease. Four of the five recurrent patients died. In result, grade 3 ovarian SLCT showed significantly poorer prognosis than grade 1–2 disease (overall survival, hazard ratio=14.25, 95% confidence interval=1.881–108.0; log-rank p=0.010). Our findings were consistent with the concept that patients with stage I/grade 1–2 tumors have a good prognosis without adjuvant chemotherapy. Since grade 3 ovarian SLCT appears to be relatively more fatal than grade 1 or 2, patients with grade 3 SLCT might require more aggressive surgical intervention and post-treatment surveillance.

A Case of Ovarian Sertoli-Leydig Cell Tumor With Rhabdomyosarcomatous Component Presented With Tumor Rupture

A Case of Ovarian Sertoli-Leydig Cell Tumor With Rhabdomyosarcomatous Component Presented With Tumor Rupture

Sertoli-Leydig Cell Tumors of the Ovary With Follicular Differentiation Often Resembling Juvenile Granulosa Cell Tumor: A Report of 38 Cases Including Comments on Sex Cord-Stromal Tumors of Mixed Forms (So-called Gynandroblastoma).

Thirty-eight ovarian Sertoli-Leydig cell tumors that contained follicles are described; in 33 of them follicles imparted a microscopic appearance resembling that of the juvenile granulosa cell tumor. The average age of the patients (28 y), frequency of androgenic manifestations (40%), and dominant histopathologic features were all typical of Sertoli-Leydig cell tumor, mostly (80%) of intermediate differentiation. The remaining tumors were poorly differentiated; none were well differentiated. The follicles that mimicked juvenile granulosa cell tumor accounted for ∼5% to 40% of the tumor volume. They typically arose out of the characteristic lobules seen in Sertoli-Leydig cell tumors of intermediate differentiation. There appeared to be a gradual loosening of the stroma imparting a pale appearance to the lobules and on that background follicles emerged. The follicles were mostly relatively regular and round to oval with basophilic or eosinophilic secretion and when fully formed perfectly mimicked juvenile granulosa cell morphology. In 18 of these cases, and 5 others, follicles were present that had a nonspecific morphology and had a random, nonlobule-associated distribution. The presence of a juvenile granulosa-like appearance often raised consideration of the diagnosis of a sex cord-stromal tumor of mixed forms (so-called gynandroblastoma) but a multifocal origin within lobules of otherwise typical Sertoli-Leydig cell tumors, and overall tumor characteristics indicates aberrant differentiation within the latter tumor of a nature only sporadically noted in the prior literature. Such neoplasms should, in our opinion, not be placed in the grouping of a sex cord-stromal tumor of mixed forms but rather in the Sertoli-Leydig category.

Clinical Characteristics and Mutation Analyses of Ovarian Sertoli-Leydig Cell Tumors.

There are limited studies on Sertoli-Leydig cell tumors (SLCTs) and no data in the population of Chinese patients with SLCTs from the genetic level. In addition, previous studies on SLCTs have focused exclusively on mutations in the DICER1 gene and no data exists on the genetic landscape of SLCTs. Patients with moderately or poorly differentiated SLCTs who underwent surgical resection between January 2012 and October 2018 in our institution were recruited. Whole exome sequencing was performed on formalin-fixed, paraffin-embedded tumor tissue and peripheral blood or normal tissue samples. Seventeen patients were recruited with 19 tumor samples. The rate of tumor-associated germline mutations was 6 of 17 (35.3%), and that of DICER1 germline mutations was 4 of 17 (23.5%). Regarding clinical relapse, patients with germline tumor-associated mutations had significantly poorer prognosis than those without (p = .007), and those with germline DICER1 mutations were relatively more likely to exhibit clinical relapse, although not to a significant degree (p = .069). Regarding somatic mutations, firstly, the subclone evolution analysis demonstrated that the two tumors on the contralateral ovary were primary tumors, respectively. Secondly, somatic mutations were most commonly found in CDC27 (10/19, 52.6%), DICER1 (4/19, 21.1%), and MUC22 (4/19, 21.1%). And the analysis of cancer cell fractions showed that DICER1 mutations were correlated with tumorigenesis of SLCTs. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively). Our study indicates that genetic testing may have important clinical significance for patients with SLCTs, particularly for younger patients. Bilateral ovarian Sertoli-Leydig cell tumors were verified to be primary tumors from the genetic perspective. The rates of germline and somatic DICER1 mutations were 4 of 17 (23.5%) and 4 of 19 (21.1%), respectively. The rates of germline and somatic DICER1 mutations were higher in patients who were younger than 18 years than those in older patients (p = .022 and p = .001, respectively).

Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

Ovarian Sertoli-Leydig and granulosa cell tumor: comparison of epidemiology and survival outcomes.

To investigate the epidemiology, clinico-pathological characteristics and outcomes of patients diagnosed with malignant ovarian Sertoli-Leydig cell tumors (SLCTs) in comparison to granulosa cell tumors (GCTs). The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were accessed and patients diagnosed with a malignant SLCT and GCT between 1988 and 2013 were selected. Demographic and clinico-pathological characteristics were compared using the Mann-Whitney and chi-square tests. Overall (OS) and cancer-specific survival (CSS) rates were estimated with the Kaplan-Meier method and compared with the log-rank test. Cox hazard models were constructed to control for confounders. A total of 175 and 1361 patients diagnosed with SLCT and GCT, respectively, were identified. Compared to patients with GCT, those with SLCT were younger (median age 32 vs. 51years, p < 0.001) and more likely to present with larger tumors (median size 15 vs 9.5cm, p < 0.001) confined to the ovary (77.5% vs 69.2%, p = 0.031). Patients with SLCTs had worse CSS compared to those with GCTs, p < 0.001 (5-year rate was 76.2% vs 90.7%). After controlling for the presence of extra-ovarian disease and tumor size (≤ 10 vs > 10cm), SCLTs were associated with a worse cancer-specific mortality compared to GCTs. SLCTs are extremely rare, commonly arise in premenopausal patients. They are associated with a poorer prognosis compared to GCT.