Mixed Germ Cell-sex Cord-stromal Tumor 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.

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.

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.

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.

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.

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.

Immunohistochemical Study of Mixed Germ Cell Sex Cord Stromal Tumours in 13 Canine Testes

Mixed germ cell sex cord stromal tumours (MGSCTs) are composed of seminiferous tubules, filled with admixed neoplastic Sertoli cells (SCs) and germ cells (GCs). The aim of the present study was to describe 13 canine testicular MGSCTs and to investigate the histochemical features and the immunophenotype of the neoplastic GCs and SCs. Neoplastic SCs were always diffusely labelled for vimentin (VIM), neuron specific enolase (NSE), inhibin (INH)-α and anti-Müllerian hormone (AMH). Cytokeratins AE1/AE3 (CK) and desmin (DES) were expressed in 6/13 and 8/13 cases, respectively. Neoplastic GCs were labelled for placental alkaline phosphatase (PLAP) in 7/13 cases and for CD117 (KIT) in 8/13 cases, while 10 cases were stained uniformly by periodic acid-Schiff (PAS). Immature canine SCs are known to express CK, DES, INH-α and AMH, while immature GCs are stained by PAS and express PLAP and KIT. This GC phenotype also distinguishes between classical and spermatocytic seminoma, with the latter being negative for these markers. The results of the present study show that both neoplastic SCs and GCs in MGSCTs have a de-differentiated phenotype.

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.

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.

Precocious puberty in a 7-year-old boy: A novel case

A 7-year-old boy was referred for evaluation of precocious puberty, evidenced by penile enlargement and pubic hair formation. His testicular size was prepubertal bilaterally. A comprehensive hormonal evaluation showed an elevated serum testosterone value (4.0 nmol/L) and a prepubertal gonadotropin value. A 0.9-cm heterogenous left testicular mass was detected on scrotal ultrasonography. Inguinal exploration was performed with ultrasound-guided open testicular biopsy and orchiectomy. Pathologic evaluation of the orchiectomy specimen showed the unclassified type of a mixed germ cell sex cord stromal tumor (MGCSCST), composed of neoplastic Sertoli cells and seminoma-like germ cells. Isolated previous reports of unclassified MGCSCSTs of the testis are now thought to be reports of sex cord stromal tumors with entrapped non-neoplastic germ cells. In our patient, the germ cells appeared to be neoplastic with aberrant expression of c-kit and placental alkaline phosphatase, a high proliferative rate, and DNA aneuploidy. Postoperatively, the patient's serum testosterone concentrations returned to prepubertal values (<0.2 nmol/L) and puberty was halted. This case represents a novel cause of precocious puberty.

Immunohistochemical Evaluation of GATA-4 in Canine Testicular Tumors

GATA-4 is a transcription factor expressed in Sertoli cells and less commonly in Leydig (interstitial) cells but not germ cells in adult human beings, cattle, pigs, and mice. We examined GATA-4 in 76 formalin-fixed, paraffin-embedded canine testicular tumors, including 21 Sertoli cell tumors (SCT), 28 Leydig (interstitial) cell tumors (LCT), 24 seminomas (GCT), and 3 mixed germ cell sex cord-stromal tumors (MGSCT). Our hypothesis was that immunohistochemistry for GATA-4 could discriminate between germ cell and sex cord-stromal tumors of the canine testis. SCTs (21/21) had strong diffuse nuclear and weak and inconsistent cytoplasmic staining. LCTs (27/28) also had strong diffuse nuclear staining and much weaker and granular cytoplasmic staining. GCTs were negative for this marker. Sex cord-stromal cells of MGSCT were also positive. These results indicate that GATA-4 is mainly expressed in sex cord-stromal tumors and not in germ cell tumors of the canine testis.

Bilateral Testicular Germ Cell–Sex Cord–Stromal Tumor in a Pekin Duck (Anas platyrhynchos domesticus)

An intact male white pekin duck (Anas platyrhynchos domesticus) was presented for examination because of respiratory distress and 2- to 3-month history of lameness and lethargy. Results of radiography, ultrasonography, and cytologic examination revealed a large neoplastic mass in the coelom. The duck was euthanatized, and results of necropsy revealed 2 large, lobulated masses in the coelom and a small nodule on the liver. Histopathologic examination of the large masses revealed a collision pattern testicular tumor consisting of Sertoli, seminoma, and interstitial cell components. The hepatic nodule was a metastatic lesion consistent with a Sertoli cell testicular tumor. This is the first reported case of a mixed germ cell-sex cord-stromal tumor in a duck.

Histologic and Immunohistochemical Characterization of a Testicular Mixed Germ Cell Sex Cord-Stromal Tumor and a Leydig Cell Tumor in a Dog

Mixed germ cell sex cord-stromal tumors (MGSCTs) of the testis are rare in dogs. We describe the histopathology and immunohistochemical characteristics of an MGSCT associated with a Leydig cell tumor in a cryptorchid testis. Histologically, MGSCT consisted of two nodules of seminiferous tubules lined by germ cells and Sertoli cells in variable proportions. Germ cells had variable size and nuclear features, with frequent giant cells. Germ cells were evenly mixed with Sertoli cells or located in the center of tubules. Markers that labeled mainly germ cells and few or no Sertoli or Leydig cells were calretinin, KIT, and PGP 9.5. E-cadherin, GATA-4, inhibin-alpha (INH-alpha), and neuron-specific enolase (NSE) were predominantly detected in Sertoli cells, whereas melan A was particularly expressed in Leydig cells and vimentin in all three cell types. OCT3/4 was not detected in any cell type. Although more cases of canine MGSCT need to be examined, our results suggest that an immunohistochemical panel of E-cadherin, GATA-4, INH-alpha, KIT, NSE, PGP 9.5, and melan A will help distinguish the three main cell types in canine testicular germ cell and sex cord-stromal tumors.

Recent Advances in the Pathology and Classification of Gonadal Neoplasms Composed of Germ Cells and Sex Cord Derivatives

In recent years, our understanding of neoplasms composed of germ cells and sex cord derivatives has increased. In this review, advances in the classification and pathology of ovarian germ cell-sex cord-stromal tumors are discussed. Only 2 neoplasms, each with a distinctive pathogenesis and clinicopathologic features, are included in this category. Gonadoblastoma is a tumor that usually occurs in the dysgenetic gonads of intersex patients that have a Y chromosome, whereas mixed germ cell-sex cord-stromal tumor arises in normal gonads in patients without sex chromosomal abnormalities. Ovarian mixed germ cell-sex cord-stromal tumors differ from their testicular counterparts in their histological appearance, immunohistochemical staining reactions, and biological behavior probably because the latter show a greater degree of maturity of their germ cell component. The introduction of cisplatin-based chemotherapy and the application of tumor markers have dramatically improved the clinical outlook for those patients who develop secondary malignant germ cell neoplasms.

Gonadoblastoma progressing to dysgerminoma in a 55-year-old woman with normal karyotype

Sir,Gonadoblastomas are classified as mixed germ cell–sex cord–stromal tumours and are composed of two main cell types intimately admixed; germ cells similar to those present in dysgerminoma, and s...

Mixed germ cell sex cord–stromal tumors of the testis and ovary. Morphological, immunohistochemical, and molecular genetic study of seven cases

We present the morphological, immunohistochemical, and molecular genetic features of three cases of testicular and four cases of ovarian mixed germ cell sex cord-stromal tumors (MGSCT). The germ cells in the testicular MGSCTs morphologically differed from those in classical seminomas by lacking the typical "square off" quality of the nuclei. In contrast to the nuclei in classical seminomas, their size in testicular MGSCTs was smaller and nucleoli were inconspicuous and the cytoplasm was Periodic Acid-Schiff (PAS) negative. Quite on the contrary, the variability in the size of the nuclei of the germ cells in the testicular MGSCTs was more similar to that seen in the germ cells of spermatocytic seminomas. Immunohistochemically, the germ cells of MGSCTs in one case reacted positively with antibody to AE1-AE3 by paranuclear dot-like or rodlike positivity. All three testicular MGSCTs had a negative reaction with the rest of antibodies, including placental alkaline phosphatase (PLAP), OCT4, and c-kit protein. Ovarian MGSCT in our series differed from the testicular lesions in both the germ cell component and the sex cord component. The germ cells in all four ovarian cases had cytomorphological and immunohistochemical features identical to those in classical seminomas/dysgerminomas. They possessed the typical "square off" quality of the nuclei, which were much more blastic, with more mitoses compared with the testicular tumors in our series, and they were PLAP (4/4), OCT4 (4/4) and c-kit protein (3/4) positive immunohistochemically. The cytoplasm of the germ cells in ovarian neoplasms contained PAS positive glycogen. Germ cells in one ovarian MGSCTs showed amplification of 12p. All other germ cells were negative for amplification of 12p. All five successfully analyzed cases showed no mutation in all studied exons and exon-intron junctions in c-kit and PDFGRA genes.