Germ Cell Sex Cord-stromal Tumors Research Articles

Canine testicular tumors: An 11-year retrospective study of 358 cases in Moscow Region, Russia.

Background and Aim:Canine testicular tumors are among the most common reproductive tract tumors in male dogs and have been studied in many countries. However, to the best of our knowledge, studies with a large sample size have not been conducted in Russia. This study aimed to provide the latest information on the prevalence of canine testicular tumors in the Veterinary Oncology Scientific Center for Small Animals “Biocontrol” in Moscow, Russia, in 2010-2020 and the characteristics of the affected canine population.Materials and Methods:A retrospective review of patients and histological reports was collected and analyzed from 358 dogs with 447 testicular tumors within 11 years.Results:The mean age of the affected dogs was 10.4 years, whereas that of dogs with Sertoli cell tumors was 9.4 years p=0.009. This study includes mixed-breed dogs (18.4%), Yorkshire Terriers (8.8%), Labrador Retrievers (7.9%), Golden Retrievers (5.0%), and Fox Terriers (3.4%). The most common tumors were interstitial cell tumors (n=227, 50.8%). In contrast, 107 (23.9%) seminomas, 80 (17.9%) Sertoli cell tumors, 19 (7.4%) mixed germ cell-sex cord-stromal tumors, and 26 (7.6%) testicular tumors developed from cryptorchid testes, which included 16 (61.5%) Sertoli cell tumors, 10 (38.5%) seminomas, and no interstitial cell tumors.Conclusion:This study provides baseline information on the prevalence of canine testicular tumors in the described population, including the median age of each tumor type and overrepresented dog breeds. We further found that the most common scrotal testicular tumor was interstitial cell tumor, whereas Sertoli cell tumor was the most common in cryptorchid testicles.

A five-year cohort study on testicular tumors from a population-based canine cancer registry in central Italy (Umbria)

Canine testicular tumors account for about 90 % of tumors affecting the male genitalia. Seminomas (SEM), Sertoli cell tumors (SCT), and interstitial cell tumors (ICT) are the most common histological diagnoses, but their incidence shows high variability among studies. Our aim is to report the results on the analysis of testicular tumors recorded by the population-based Umbria Canine Cancer Registry (CCR) for a 5-year time period and to assess the value of tumor major diameter, measured during trimming, in discriminating neoplastic from non-neoplastic lesions.The study was conducted on 388 testicular tumors (on 1969 total male tumors) diagnosed in 355 dogs from 2014 to 2018. The median incidence was 35 cases/100,000 dogs, with a proportion equal to 19,7 % of all tumors. The incidence on neutered male dogs was 352/100,000. Most tumors were ICTs (50 %), with fewer SEMs and SCTs (29 % and 17 %, respectively). Only 3 % of tumors were mixed germ cell-sex cord-stromal tumors (MGC-SCST). Ten percent of cases had multiple tumors in the same testicle, with SEM-ICT being prevalent (69.2 %). Tumors in cryptorchid testes were 5.9 % of the total, mostly SCT (60.9 %). Mean age at diagnosis was 10.7 ± 2.7, with similar values for different tumor types. Significant incidence ratios (IRR) were found in Golden retriever (IRR 7.18, CI95 % 4.72–10.92) and in English cocker spaniel (IRR 2.30, CI95 % 1.28–4.13) when compared with mixed breed dogs. A value of 0.3 cm (major diameter) of lesions at the moment of trimming was helpful in discriminating a final tumor histological diagnosis from a non-tumor lesion. Since the number of tumors included in this evaluation was limited, further studies to confirm the diagnostic value of this measure are recommended.Our results provided information on the incidence of canine testicular tumors in Umbria region that can be compared with future results and incidence from other geographical areas if provided with reliable data on the total population, can offer solid information on the incidence and proportion of different tumor types in specific territories, contributing also to the supervision of its inhabitants’ health. Moreover, pathological data such as the major diameter of tumors can be obtained and contribute to diagnostic routine and standardization.

Histological and immunohistochemical characterization of 17 gonadal tumours in koi carp (Cyprinus carpio koi).

Reports on abdominal tumours in koi carp are scarce and most are from the gonads. Their histological diagnosis is challenging due to the occurrence of mixed populations of neoplastic cells and the few availability of cross-reactive antibodies in fish tissues. The present study aims to provide a histopathological characterization of seventeen gonadal tumours, enriched by a wide antibody panel (vimentin, CD117, placental alkaline phosphatase-PLAP, AE1/AE3 cytokeratin, E-cadherin, proliferating cell nuclear antigen-PCNA, müllerian-inhibiting substance-MIS, GATA4 and Inhibin-α) applied on whole and tissue microarray (TMA) sections. Abdominal enlargement was associated with tumours filling 30%-80% of the abdominal cavity; frequently, the gonads had been completely replaced by neoplastic tissue. Twelve cases were characterized as sex cord-stromal tumours (SCSTs), three as germ cell tumours (GCTs), one as mixed germ cell sex cord-stromal tumour (MGCSCST) and one as carcinoma. By immunohistochemistry, PLAP enabled confirmation of GCTs, ovarian carcinoma and the objective identification of a further cell component in 8 out of the 12 SCSTs that were reclassified as mixed tumours. The use of an immunohistochemical panel can help in refining the histological diagnosis, but the morphological diagnosis still represents the main tool for the characterization of these tumours in koi carp.

Gonadoblastoma versus ovarian mixed germ cell-sex cord stromal tumor in women or girls with no evidence of a disorder of sex development: A problem in differential diagnosis

Gonadoblastoma occurring in a normal girl or woman has been confused with ovarian mixed germ cell-sex cord stromal tumor (MGC-SCST) due to a lack of knowledge that the former occurs occasionally in a normal woman or girl. In this article, we develop histological criteria that facilitate the distinction of gonadoblastoma in an individual with a normal karyotype and no evidence of a disorder of sex development from ovarian MGC-SCST. We reviewed the histological findings of gonadoblastoma occurring in normal individuals and compared them to cases of ovarian MGC-SCST in our files. The histological findings of gonadoblastoma differ substantially from those of ovarian MGC-SCST. Importantly, gonadoblastoma contains two types of transformed germ cells, some histologically benign and others premalignant, whereas MGC-SCST contains only a single type, typically premalignant in the ovary and benign in the testis. Furthermore, degenerative changes of hyalinization and calcification are common in gonadoblastoma, whereas they are extremely rare in MGC-SCST. Although the great majority of cases of gonadoblastoma occur in an individual with a disorder of sex development and an abnormal karyotype, a substantial number arise in a normal woman or girl with no evidence of a disorder of sex development. In the latter circumstance, it is important to distinguish gonadoblastoma from ovarian MGC-SCST. It is very likely that those gonadoblastomas arising in a normal individual develop through a different molecular pathway than the ones that occur in the dysgenetic gonads of an individual with a disorder of sex development.

Testicular tumors in 190 dogs: clinical, macroscopic and histopathological aspects

ABSTRACT: This study aimed to characterize the prevalence and clinical, macroscopic and histopathological aspects of dogs affected by testicular tumors based on biopsy specimens from the Laboratório de Patologia Veterinária of the Universidade Federal de Santa Maria (LPV-UFSM) over 19 years. Parameters regarding the age, size, and breed of the affected dogs were also established. Of all dogs with some type of neoplasm submitted to histopathological analysis at the LPV over these 19 years (n=1,900), 213 (11.2%) had at least one testicular neoplasm. The tissues of 190 dogs (with 220 neoplasms) were available for histological reassessment. The dogs in this study had different types of testicular tumors with relatively similar frequencies. In descending order, the most frequent testicular neoplasms were seminomas (88/220), Leydig (interstitial) cell tumor (LCT; 64/220), Sertoli cell tumor (SCT; 61/220), and mixed germ cell-sex cord stromal tumor (MGSCT) (07/220). Among the dogs of defined breed (119 cases), large breeds had the largest number of cases (50/119), followed by small (47/119) and medium-sized (22/119) breeds. The ages of dogs affected by testicular tumors ranged from 10 months to 18 years. Increased testicular volume was the most common clinical manifestation. Eleven dogs presented information about clinical signs suggestive of hyperestrogenism syndrome (feminization). In seminomas, the diffuse pattern predominated over the intratubular pattern. Two sites (luminal and basal compartments) suggestive of the onset of neoplastic transformations in germ cells were observed in intratubular seminomas. They corroborate the hypothesis that canine seminomas possibly have pathogenesis similar to that observed in human spermatocytic seminomas. The SCTs and LCTs presented high cell morphology variation. SCTs had neoplastic cells organized in five different histological arrangements. As for LCT, solid-diffuse and cystic-vascular histological patterns were the most commonly observed. Through this study, it was possible to establish some of the leading clinical, macroscopic, and histopathological aspects of testicular neoplasms diagnosed over 19 years in the area covered by the LPV-UFSM.

Novel insights into the mixed germ cell-sex cord stromal tumor of the testis: detection of chromosomal aneuploidy and further morphological evidence supporting the neoplastic nature of the germ cell component.

The existence of a true mixed germ cell-sex cord stromal tumor (MGSCT) of the testis remains controversial. Based on our experience with rare testicular tumors in this spectrum, we sought to perform a detailed clinicopathologic and molecular study of MGCSCT. Eight cases of testicular MGSCT were morphologically reviewed, screened for chromosomal aberrations (using array comparative genomic hybridization (aCGH) and low pass genomic sequencing), and analyzed by next generation sequencing (The Illumina TruSight Tumor 170). Immunohistochemistry for OCT3/4, Nanog, SALL4, DMRT1, and inhibin was performed on the cohort. Clinical data and follow-up were assessed by medical record review. All patients were karyotypically normal men aged 27-74years (median 41). All tumors had a similar biphasic morphology characterized by various proportions of the sex cord component resembling granulosa cell tumor of adult type and the germ cell component cytomorphologically akin to spermatocytic tumor. Germ cells were haphazardly scattered throughout the tumor or arranged in larger groups, without tubular formation. In 4 cases, atypical mitoses were found within the germ cells. Additionally, in 2 cases there was invasion into the spermatic cord, adjacent hilar soft tissue and into the tumor capsule, which contained both tumor components. Immunohistochemically, focal nuclear expression of DMRT1 was found in the germ cell component in 7/7 analyzable tumors, while SALL4 was positive in 6 cases and negative in one case. All tumors were negative with OCT3/4 and Nanog. The sex cord stromal component had immunoreactivity for inhibin in 7/7 analyzable cases. Four of 8 cases were cytogenetically analyzable: 4/8 by low pass genomic sequencing and 2/8 by aCGH. The results of both methods correlated well, revealing mostly multiple chromosomal losses and gains. One case revealed loss of chromosome 21; 1 case had loss of chromosomes 21 and 22 and partial gain of 22; 1 case had loss of chromosomes 22 and Y, partial loss of X, and gain of chromosomes 20, 5, 8, 9, 12, and 13; and the remaining one gain of chromosomes 20, 3, 6, 8, 2x(9), 11, 2x(12), 13, 14, 18, and 19. Three cases were analyzable by NGS; clinically significant activating mutations of either FGFR3 or HRAS were not detected in any case. Follow-up was available for 4 patients (12, 24, 84, and 288months) and was uneventful in all 4 cases. The identification of extratesticular invasion of both the germ cell and sex cord stromal components, the DMRT1 expression, and the presence of atypical mitoses in germ cells argue for the neoplastic nature of the germ cell component. The molecular genetic study revealing multiple chromosomal losses and gains in a subset of the cases provides the first evidence that molecular abnormalities occur in testicular MGSCT. Multiple chromosomal aneuploidies, namely, recurrent losses of chromosomes 21 and 22 and gains of 8, 9, 12, 13, and 20, indicate that the germ cell component might be related to the morphologically similar spermatocytic tumor, which is characterized by extensive aneuploidies including recurrent gains of chromosomes 9 and 20 and loss of chromosome 7. In summary, our data support that rare examples of true MGSCT of the testis do exist and they represent a distinct tumor entity with admixed adult-type granulosa cell tumor and spermatocytic tumor components.

Unraveling of Diagnosis Odyssey in A Girl with Primary Amenorrhea: A case report

ABSTRACT Background:Primary amenorrhea may result from congenital abnormalities in the development of the gonads, genital tract, or external genitalia or from a disturbance within the hypothalamic-pituitary-ovarian axis. Gonadal dysgenesis is a disorder of sex development in which the diagnosis is based on the histology of gonads and is the main cause of primary amenorrhea. Optimal protocol of management for phenotypic female with 46, XY gonadal dysgenesis involves prophylactic gonadectomy at diagnosis.Case Presentation: The patient was referred to our hospital at the age of 15 years old for primary amenorrhea. She was obese with no secondary sex sign. Gynecologic examination revealed a normal vagina and clitoris. Rectal Toucher examination revealed no internal genitalia structure. The laboratory data: FSH levels was above normal range, LH and testosterone levels were within normal range. Pelvic Ultrasonography uterus and vaginal structure and testis were not visualized. Cytogenetic and ARgene analysis found a 46, XY karyotype and no pathogenic variants. On laparoscopy, Mullerian structure and Wolffian remnant structure were identified and biopsies were performed. Based on histopathological examination and immunohistochemical markers of the right and left gonad showed the impression of Malignant Mixed Germ Cell-Sex Cord Stromal Tumor. SRY gene examination was positive.Examination of other DSD gene analysis has not been done. Second laparoscopy for gonadectomy and removal of Mullerian and Wolfiian remnant structure were performed. Conclusion:Chromosomal analysis should become the first line testing in primary amenorrhea followed by advanced molecular test. Multidisciplinary managements recommended for DSD cases.

Canine ovarian gonadoblastoma with dysgerminoma overgrowth: a case study and literature review

BackgroundGonadoblastoma (GB) is a rare mixed germ cell-sex cord-stromal tumour, first described in humans, commonly found in dysgenetic gonads of intersex patients that have a Y chromosome. However, this entity in not recognized in the WHO classification of tumours of genital system of domestic animals. Herein, we describe a case of ovarian gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour components, in a phenotypically and cytogenetically normal bitch.Case presentationA 17-year-old cross-breed bitch had a firm, grey-white multinodular mass in the left ovary. The tumour was submitted to histopathological examination and Y chromosome detected through karyotype analysis and PCR studies. Microscopically, the ovary was almost replaced by an irregular neoplasm composed of three distinct, intermixed elements: dysgerminoma, mixed germ cell-sex cord-stromal tumour resembling human GB and a proliferative sex cord-stromal tumour component. The germ cells of gonadoblastoma and dysgerminoma components were immunoreactive for c-KIT. Sex cord-stromal cells of gonadoblastoma were immunoreactive for α-inhibin. The sex cord-stromal tumour was immunoreactive for AE1/AE3, occasionally for α-inhibin and negative for epithelial membrane antigen (EMA). The karyotype was 78, XX and PCR analysis confirmed the absence of the Y chromosome.ConclusionBased on these findings, a diagnosis of gonadoblastoma with proliferation of dysgerminoma and sex cord-stromal tumour was made. This is the first case of ovarian gonadoblastoma in a female dog.

Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis

In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix-loop-helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei of spermatogonia but not in those of more mature germ cells. By way of contrast, TCLF5 is expressed in the nuclei of some clusters of primary spermatocytes that have entered meiosis 1, in secondary spermatocytes, and in round (early) spermatids in the seminiferous tubules of adults during the reproductive years. OCT4 is expressed in primordial germ cells but not in the seminiferous tubules of the normal adult testis during the reproductive years. DMRT1 is expressed in the germ cells of both testicular MGC-SCST and spermatocytic tumor, whereas TCLF5 is not expressed in either neoplasm. These low-grade neoplasms, however, differ histologically in that all the germ cell nuclei of testicular MGC-SCST resemble spermatogonia, whereas in spermatocytic tumor, the nuclei of the medium-sized and large cells resemble those of primary spermatocytes. Both neoplasms lack expression of OCT4. By way of contrast, in seminoma, a fully malignant testicular germ cell tumor, the germ cell nuclei express OCT4 but do not express either DMRT1 or TCLF5.

A retrospective study of reproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in malignant ovarian germ cell tumors and sex cord-stromal tumors

BackgroundTo retrospectively investigate reproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in malignant ovarian germ cell tumors (MOGCT) and sex cord-stromal tumors (SCST).MethodsData from 32 MOGCT (6 dysgerminomas, 6 yolk sac tumors, 17 immature teratomas, and 3 mixed germ cell tumors) and 9 SCST (4 granulosa cell tumors and 5 sertoli-leydig cell tumors) aged from 18 to 35, treated in the Obstetrics and Gynecology Hospital of Fudan University from October 2003 to October 2013 were collected and analyzed.ResultsAverage follow up was (86.3 ± 34.4) months. Average diagnosed age was (25.3 ± 3.5) years. Average chemotherapy course was (4.4 ± 1.3) times. Patients are all living. Thirty one patients (75.6%) reported normal menstrual cycles. Twelve patients (29.3%) wished to conceive, 10 (83.3%) naturally conceived and 8 (66.7%) had lived birth.ConclusionsReproductive outcomes after fertility-sparing surgery and postoperative adjuvant chemotherapy in MOGCT and SCST are favorable, meanwhile education and consultation is needed.

Perspectives on testicular sex cord–stromal tumors and those composed of both germ cells and sex cord–stromal derivatives with a comparison to corresponding ovarian neoplasms

Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2% to 5% of cases. Both genetic and epigenetic factors account for the differences in frequency and histologic composition between testicular and ovarian SCSTs. For example, large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia occur in the testis but have not been described in the ovary. In this article, we discuss recently described diagnostic entities as well as inconsistencies in nomenclature used in the recent World Health Organization classifications of SCSTs in the testis and ovary. We also thoroughly review the topic of neoplasms composed of both germ cells and sex cord derivatives with an emphasis on controversial aspects. These include "dissecting gonadoblastoma" and testicular mixed germ cell-sex cord stromal tumor (MGC-SCST). The former is a recently described variant of gonadoblastoma that sometimes is an immediate precursor of germinoma in the dysgenetic gonads of patients with a disorder of sex development. Although the relationship of dissecting gonadoblastoma to the previously described undifferentiated gonadal tissue is complex and not entirely resolved, we believe that it is preferable to continue to use the term undifferentiated gonadal tissue for those cases that are not neoplastic and are considered to be the precursor of classical gonadoblastoma. Although the existence of testicular MGC-SCST has been challenged, the most recent evidence supports its existence; however, testicular MGC-SCST differs significantly from ovarian examples due to both genetic and epigenetic factors.

On the histogenesis of mixed germ cell-sex cord stromal tumour of the gonads

AimsThe origin of testicular mixed germ cell-sex cord stromal tumour (MGC-SCST) is uncertain, and the nature of this neoplasm is controversial. It has not been established whether the germ cells...

Spermatogonial Nature of the Germ Cell Component of Canine Testicular Mixed Germ Cell–Sex Cord Stromal Tumours

The present study has characterized the germ cell component of canine testicular mixed germ cell-sex cord stromal tumours (MGSCTs) by examining the histological nature and histochemical and immunohistochemical features using gonocytic and spermatogonial cellular markers, c-Kit, placental alkaline phosphatase (PLAP), protein gene product 9.5 (PGP9.5), Sal-like protein 4 (SALL4), and the periodic acid-Schiff (PAS) reaction. Histologically, all 45 examples of MGSCTs were classified as spermatocytic seminomas (SSs) and Sertoli cell tumours in combination. The germ cell component of all MGSCTs was negative by PAS staining. Immunohistochemically, PLAP immunoreactivity was lacking in the germ cell component of all MGSCTs, which is not consistent with a gonocytic origin. The germ cell component was positive for PGP9.5 and SALL4 in all MGSCTs and positive for c-Kit in 53% of MGSCTs, which is consistent with the phenotype of spermatogonia. Furthermore, the germ cell component in 71% of MGSCTs had moderate immunoreactivity for SALL4, which is suggestive of a spermatogonial phenotype. Conversely, 29% of cases had a minor population of germ cells showing strong SALL4 immunoreactivity, suggesting a phenotype similar to prespermatogonia. The results suggest that the germ cell component of canine MGSCTs is morphologically classified as SS, with the majority of cases showing the spermatogonial phenotype and some cases containing a small population of prespermatogonia.

Collision tumor of ovary: imaging features and pathology

Objective To explore imaging findings and pathological features of ovarian collision tumors. Methods A retrospective analysis of preoperative imaging findings was performed in 8 female patients with surgical- pathological proven ovarian collision tumors. CT scans were performed in 5 cases, both CT and MRI were performed in 2 cases, and non-enhanced MR scans were performed in 1 pregnancy woman. Imaging results were compared with pathologic findings. Results Ovarian collision tumors in the eight patients consisted of 2 types tumors, originated from different ovarian tissues including surface epithelial cells, germ cell, or sex cord-stromal cell. Of the 8 ovarian collision tumors, 5 were located in the left ovary, and 3 in the right ovary. Ovarian collision tumors consisted of surface epithelial tumor and germ cell tumor (n=6) including mucinous cystadenoma and teratoma (n=4), mixed cystadenoma and teratoma (n= 1), and serous cystadenoma and struma- ovarii (n=1). Ovarian collision tumors in two cases consisted of surface epithelial tumor and sex cord-stromal tumor, and were mucinous cystadenoma and fibroma, respectively. Imaging findings included: all tumors in the 8 cases presented big or huge multiple complicated cystic mass with 9 to 26 cm in diameter. Germ cell tumor or sex cord-stromal tumor in collision tumor was smaller and located inside the tumor (n=3) and on the tumor wall (n=5). The boundary between two types of tumors in ovarian collision tumor was distinct and clear. Typical imaging features and densities (signals) of different tumors in ovarian collision tumors can be found on CT or MRI. Conclusions Ovarian collision tumors has some specific imaging and pathological characteristics. Imaging examination is helpful for most accurate diagnosis of ovarian collision tumors. Key words: Ovaries neoplasms; Magnetic resonance imaging; Tomography, X-ray computed; Pathology

Mixed germ cell–sex cord stromal tumor of the testis with an intratubular component: a problem in differential diagnosis

The origin of mixed germ cell-sex cord stromal tumor (MGC-SCST) of the testis is uncertain, and a controversy exists as to whether the germ cells in these tumors are neoplastic. Although intratubular components of the common and several uncommon forms of testicular germ cell tumors have been described, to our knowledge, intratubular MGC-SCST has not previously been reported in detail. In a study of 13 cases of testicular MGC-SCST, we observed entrapped seminiferous tubules in 7 cases and an intratubular component in 2, both of which were associated with extensive entrapped tubules. Intratubular MGC-SCST is distinguished from entrapped tubules by the occurrence of germ cells resembling spermatogonia in the adluminal compartment and the absence of tubular lumens. By way of contrast, the adluminal compartment of entrapped tubules is composed entirely of immature Sertoli cells, and lumen formation is observed in favorably oriented tubules. Although the germ cells in our cases of MGC-SCST do not show histologic features of malignancy, the observation of spermatogonia-like cells in the adluminal compartment of the tubule, sometimes with concomitant germ cell proliferation, and the infiltrative pattern of the germ cells in the extratubular component support their neoplastic nature. The intratubular component tends to be more centrally located than the adjacent entrapped seminiferous tubules suggesting that it originates from the latter. The tubules of intratubular MGC-SCST are not expanded except in the advanced stage and are approximately the same size as entrapped seminiferous tubules but are considerably smaller than those of the uninvolved testis that shows active spermatogenesis.

Expression of Transcription Factors and Nuclear Receptors in Mixed Germ Cell-Sex Cord Stromal Tumor and Related Tumors of the Gonads.

In this study, we compare the expression of OCT4, SALL4, and TSPYL1 in mixed germ cell-sex cord stromal tumor (MGC-SCST) of either gonad to that of normal adult testis, classic and spermatocytic seminoma, intratubular germ cell neoplasia, unclassified, gonadoblastoma, and dysgerminoma to determine the entity or entities that most closely resemble MGC-SCST by immunohistochemistry of germ cells. The most useful transcription factor was OCT4. In addition, to its already described value in distinguishing germinoma and embryonal carcinoma from yolk sac tumor and in differentiating classic from spermatocytic seminoma, we found that OCT4 is useful in confirming or ruling out potential malignancy in MGC-SCST of either gonad. Expression of OCT4 in most ovarian MGC-SCSTs resembles that of dysgerminoma, whereas most testicular examples resemble that of spermatocytic seminoma and normal adult testis. Thus, most MGC-SCSTs of the ovary are potentially malignant, and corresponding tumors of the testis are mostly benign; however, exceptions likely can be detected by the use of OCT4, potentially leading to more appropriate clinical management in some cases. SALL4 is an underutilized transcription factor that is useful in distinguishing testicular MGC-SCST from sex cord stromal tumor, unclassified in those neoplasms where the germ cells are sparse or unevenly distributed. Compared with other transcription factors studied, TSPY and its congener TSPYL1 have little value in the assessment of germ cell tumors because of their relatively wide range of expression in normal adult testis and in germ cell tumors.

Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report.

IntroductionOvarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary.Case presentationA four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX). Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up.ConclusionAlthough a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

FOXL2 and SOX9 Distinguish the Lineage of the Sex Cord–Stromal Cells in Gonadoblastomas

Gonadoblastomas are mixed germ cell sex cord-stromal tumors that arise in dysgenetic gonads and are composed of immature germ cells and sex cord-stromal cells of indeterminate differentiation. FOXL2 is one of the first genes expressed in female gonad development, and it is required for proper granulosa cell differentiation during folliculogenesis. SOX9 , a downstream target of SRY , the gene in the Y chromosomal sex-determining region, is required for testicular development and for the formation and maintenance of (pre-)Sertoli cells. This study characterized the sex cord-stromal cells of gonadoblastoma by evaluating the expression of these counteracting transcription factors. Archival paraffin-embedded material of 7 gonadoblastomas, 5 of which were overgrown by dysgerminoma, was examined by immunohistochemistry for expression and localization of FOXL2 and SOX9. The sex cord-stromal cells revealed strong nuclear staining for FOXL2 and were negative for SOX9 expression. Germ cells in the gonadoblastoma and dysgerminoma components showed no FOXL2 and SOX9 expression. Areas of transition between gonadoblastoma and dysgerminoma revealed nests with a gradual reduction of FOXL2 expression. Our results support the hypothesis that the sex cord-stromal cell component of gonadoblastomas is of granulosa cell origin. In addition, FOXL2 appears to be a useful marker for the evaluation of overgrowth by dysgerminomas and for the identification of the transition zone of "dysgerminoma in situ." As FOXL2 and SOX9 are differentially expressed, they also should be useful for distinguishing gonadoblastomas from intratubular germ cell neoplasias and can help to differentiate those with a Sertoli cell component from gonadoblastoma with a granulosa cell component.

Ovarian Mixed Germ Cell-sex Cord Stromal Tumour in a Dog

Ovarian Mixed Germ Cell-sex Cord Stromal Tumour in a Dog

Bilateral Testicular Mixed Germ Cell‐sex Cord‐stromal Tumours in a Stallion

An 18-year-old Friesian stallion was examined approximately one week after reportedly presenting scrotal swelling due to torsion of the spermatic cords. Upon presentation no scrotal swelling was noted, the testes were normally oriented, and no abnormalities of the spermatic cords were noted. However, both testes were smaller than expected for a mature stallion and deep palpation revealed that the consistency of the testes was nodular. Ultrasonographic evaluation of the testes revealed diffuse heterogeneous parenchyma with multiple hypoechoic nodular areas. Grossly, the testicular parenchyma was effaced by multiple gray-tan nodules of varying consistency interspersed with gray-white bands of tissue. Microscopic analysis revealed multiple pleomorphic neoplastic foci disseminated throughout both testes. Histological and immunohistochemical features were atypical and consistent with the diagnosis of bilateral testicular mixed germ cell-sex cord stromal tumours. Bilateral testicular tumours and testicular mixed cell tumours are extremely rare in stallions and this is the first report of bilateral testicular mixed germ cell-sex cord-stromal tumours in a stallion. Our findings indicate that certain ultrasonographic characteristics are suggestive of testicular tumour and that immunohistochemistry markers can be used to better characterize testicular neoplasms in stallions.