Multiple Sex Cord-stromal Tumors in a Standardbred Stallion Testis.

A 12-year-old Standardbred stallion presented with a 5-month history of a growing mass in the left testis as well as an overall decrease in left testicular size. Palpation and ultrasonography of the left testis revealed a firm, hypoechoic, clearly delineated soft tissue mass in the craniolateral portion of the testis that measured 2.5 × 2.3 × 1.9 cm. Two smaller, hypoechoic regions also were visible ultrasonographically in the left testis, suggesting the presence of multifocal/multicentric neoplasia. The affected testis was very small (testicular volume of 40.3 cm3). The right testis was significantly larger (144.3 cm3), and the parenchyma was ultrasonographically normal. Due to the concern that these findings could indicate the presence of a more aggressive tumor type, unilateral orchiectomy was performed. Multiple soft tissue masses were identified grossly, and histopathologic evaluation identified the larger mass as a Sertoli cell tumor and the two smaller masses as mixed sex cord-stromal tumors with Sertoli cell and Leydig cell differentiation. To our knowledge, this the first report of concurrent Sertoli cell and mixed sex cord-stromal tumors in a single descended equine testis.

Immunohistochemical and Morphological Features of Bovine Granulosa Cell Tumours in Relation to Growth Pattern and Folliculogenesis.

Granulosa cell tumours (GCTs) are the most common type of bovine ovarian neoplasm. We describe the morphological and immunohistochemical features of GCTs (n = 26) and a thecoma (n = 1) using antibodies to cytokeratin AE1/AE3, vimentin, desmin, nectin-4, anti-Müllerian hormone (AMH), inhibin α, c-erbB-2 oncoprotein and proliferating cell nuclear antigen. The results indicate that, based on the expression similarity of AE1/AE3 and inhibin α, the macrofollicular growth pattern of GCTs derives from highly differentiated granulosa cells (GCs), the Graafian follicle or early atretic follicle. The trabecular growth pattern of GCTs is inferred to be derived from GCs of the atretic follicle in mature animals. AMH is a useful marker for diagnosing bovine sex cord-stromal tumours because it was expressed in all GCT cases and in the single case of thecoma.

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

BACKGROUND: Gonadoblastoma (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 PRESENTATION: A 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. CONCLUSION: Based 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.

Endocrinological characterization of an ovarian sex cord-stromal tumor with a Sertoli cell pattern in a Japanese Black cow.

A Japanese Black cow was evaluated for prolonged post-partum anestrus and enlargement of the right ovary. Transrectal ultrasonography revealed that the right ovary was markedly enlarged and had a solid appearance, while the left ovary was small and inactive. The presumptive diagnosis was directed towards granulosa-theca cell tumour (GTCT) which was supported by markedly elevated plasma anti-Müllerian hormone (AMH; 332.0 ng/ml), oestradiol (E2 ; 103.3 pg/ml) and immunoreactive inhibin (ir-INH; 2.1 ng/ml) in comparison with the diagnostic cut-off points for bovine GTCTs. Since the cow had been infertile and had swelling of the udder, slaughter was chosen. Histopathological examination revealed that the tumour was an ovarian sex cord-stromal tumour (SCST) with a Sertoli cell pattern. These findings suggest that plasma AMH, ir-INH and E2 could be possible biomarkers for bovine ovarian SCST with a Sertoli cell pattern, whereas this case could not be distinguished from GTCTs based on endocrinological profile.

Uterine Tumors Resembling Ovarian Sex Cord Tumors in Four Baboons ( Papio spp.).

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) are rare uterine neoplasms that exhibit prominent sex cord-like differentiation. The authors describe 4 cases of UTROSCTs that were identified as incidental lesions in female baboons. All baboons were in good body condition. One animal had a 2-mm-diameter yellow-tan mass in the uterine body along the attachment of the left broad ligament; the other 3 did not have any gross lesions in the uterus. Histologically, the myometrium contained multifocal well-demarcated neoplasms composed of cuboidal to columnar cells arranged in variable arrangements of sheets, nests, cords, trabecular, and retiform patterns that occasionally formed Call-Exner-like bodies. In all cases, the neoplastic cells were diffusely positive for WT-1 and negative for calretinin, CD99, and desmin. One case was positive for inhibin and CD10. To the best of the authors' knowledge, this is the first report of UTROSCTs in nonhuman primates and in the veterinary literature.

Fatal haemorrhage and neoplastic thrombosis in a captive African lion (Panthera leo) with metastatic testicular sex cord-stromal tumour.

BACKGROUND: The study of neoplasia in wildlife species contributes to the understanding of cancer biology, management practices, and comparative pathology. Higher frequencies of neoplasms among captive non-domestic felids have been reported most commonly in aging individuals. However, testicular tumours have rarely been reported. This report describes a metastatic testicular sex cord-stromal tumour leading to fatal haemorrhage and thrombosis in a captive African lion (Panthera leo). CASE PRESENTATION: During necropsy of a 16-year-old male African lion, the left testicle and spermatic cord were found to be intra-abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow masses. Encapsulated haemorrhage was present in the retroperitoneum around the kidneys. Neoplastic thrombosis was found at the renal veins opening into the caudal vena cava. Metastases were observed in the lungs and mediastinal lymph nodes. Histology revealed a poorly differentiated pleomorphic neoplasm comprised of round to polygonal cells and scattered spindle cells with eosinophilic cytoplasm. An immunohistochemistry panel of inhibin-α, Ki-67, human placental alkaline phosphatase, cytokeratin AE1/AE3, cKit, vimentin and S100 was conducted. Positive cytoplasmic immunolabeling was obtained for vimentin and S100. CONCLUSIONS: The gross, microscopic and immunohistochemical findings of the neoplasm were compatible with a poorly differentiated pleomorphic sex cord-stromal tumour. Cause of death was hypovolemic shock from extensive retroperitoneal haemorrhage and neoplastic thrombosis may have contributed to the fatal outcome. To our knowledge, this is the first report of sex cord-stromal tumour in non-domestic felids.

Co-occurrence of a metastatic mammary liposarcoma and an ovarian sex-cord stromal tumor in a dog.

Sarcoma arising in the mammary gland is a rare tumor in dogs, and primary liposarcoma with metastatic behavior has never been previously reported among canine mammary tumors. A 14-year old female poodle had a mammary mass diagnosed as pleomorphic liposarcoma. Two years following surgical removal, the tumor recurred in the mammary gland with lymph node metastases. In addition, a sex-cord stromal tumor was identified in the ovary. Immunohistochemistry was performed on both tumors that were positive for oestrogen and progesterone receptors. Moreover, the ovarian tumor was positive for calretinin. This is the first report to the authors' knowledge, of the co-occurrence of a pleomorphic liposarcoma of the mammary gland and an ovarian sex-cord stromal (gonadostromal) tumor in the dog.

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.

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.

Mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor in a ferret.

A 5-year-old male ferret presented with an enlarged canalicular testis in the left inguinal region. Microscopically, the enlarged testis consisted of a diffuse intimately admixed proliferation of c-kit-positive germ cell-like and Wilms tumor-1 protein-positive Sertoli cell-like components, but no Call-Exner body was detected. In addition, the compact proliferation of steroidogenic acute regulatory protein-intense positive interstitial cells was identified in a separate peripheral area of the mass. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as a mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor.

Immunohistochemical characterization of nonhuman primate ovarian sex cord-stromal tumors.

This study evaluates the immunoreactivity of 12 sex cord-stromal tumors of nonhuman primates (11 granulosa cell tumors and 1 luteoma). The markers selected are used in the characterization of gonadal tumors in dogs and other species, including cytokeratins AE1/AE3, GATA-4, inhibin-α, neuron-specific enolase, protein gene product 9.5, and vimentin. A normal nonhuman primate ovary was used as a control and to optimize immunolabeling. Staining was graded as follows: 0 (nonstaining), 1+ (< 10% positive cells), 2+ (10%-50% positive cells), and 3+ (> 50% positive cells). Calretinin, GATA-4, neuron-specific enolase, and vimentin were the most consistently expressed markers (12 of 12). Cytokeratins AE1/AE3 were also consistently expressed (11 of 12). Inhibin-α and protein gene product 9.5 were expressed in 8 and 10 sex cord-stromal tumors, respectively. Results indicate that immunoreactivity of nonhuman primate sex cord-stromal tumors is similar to that observed in other species and that calretinin, GATA-4, and neuron-specific enolase are the most consistently expressed markers in nonhuman primate sex cord-stromal tumors.

A case report of an uncommon sex-cord stromal tumor consisted of luteal and sertoli cells in a spayed bitch.

We report a rare case of benign sex cord-stromal tumor consisted largely of luteoma with minor portion of Sertoli cell tumor located at the position of the left ovary excision in an 11-year-old ovariectomized bitch. Granulosa cell component was lacking, and both luteal and Sertoli cell portions were entirely positive for inhibin alpha and neuron-specific enolase, whereas luteoma portion alone was positive for Wilms' tumor-1 (WT1), immunohistochemically. The results suggest that this tumor is a possible complication of incomplete ovarian excision at the time of ovariectomy and consisted of uncommon hybrid of luteal and Sertoli cells to be diagnosed as an unclassified sex cord-stromal tumor if applied in human cases. WT1-expression pattern suggested the signature of the difference in the phenotype of these cell types.

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.

Biphasic malignant testicular sex cord-stromal tumor in a cotton-top tamarin (Saguinus oedipus) with review of the literature.

A 20-year old male cotton-top tamarin (Saguinus oedipus) was presented with unilateral enlargement of an intrascrotal testicle. Fine-needle aspiration cytology demonstrated a neoplastic population with Call-Exner-like bodies and features of malignancy. The animal was castrated, and histologic examination revealed a biphasic sex cord-stromal tumor, with one region resembling Sertoli-cell tumor and one region resembling granulosa-cell tumor, with extensive microfollicular pattern and many Call-Exner bodies. Eight months after castration, the animal was euthanized on discovery of a caudal abdominal mass that displaced organs, was highly infiltrative, and extended into the paravertebral musculature with lysis of vertebral bone. Metastases to lymph node and lung were also present. Histologic examination of the abdominal tumor showed multifocal formation of Call-Exner bodies in an otherwise highly dedifferentiated population. Positive immunolabeling for alpha inhibin confirmed the sex cord-stromal origin of the abdominal and paravertebral tumor masses. This case has similarities to malignant testicular granulosa-cell tumor of humans.

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.

Malignant mixed sex cord-stromal tumour in a stallion.

A 30-year-old Standardbred stallion was examined for unilateral scrotal swelling. Physical and ultrasound examinations revealed a painless enlarged left testis with a non-homogeneous echogenicity, when compared with the controlateral testis. The stallion underwent left unilateral orchiectomy. Grossly, the excised testis was irregularly enlarged (12 x 9 x 9 cm; weight: 530 g) and firm. The sections showed that testicular parenchyma was replaced by a lobulated, greyish-white mass, which involved the epididymal head. At microscopy, a dual Leydig and Sertoli cell tumour component could be seen. Neoplastic Sertoli cells were prevalent and presented pleomorphic cells, mitotic figures and occasional vascular invasion. Tumour patterns showed tubular and solid areas, cord-like or diffuse in appearance, among which newly formed Leydig cell nests and low-density fibrillar bundles were interposed. Immunohistochemically, a weak to moderate immunostaining for vimentin, AE(1)/AE(3) cytokeratin, alpha-1-antitrypsin and CD99 antigens was found in the growing Sertoli cells, whose nuclear MIB-1 labelling index scored 13 +/- 2%. The Leydig tumour cells, on the other hand, displayed a moderate to strong positivity for alpha-inhibin, vimentin, AE(1)/AE(3) cytokeratin, neurone-specific enolase and CD99. On the basis of these findings, a diagnosis of malignant mixed sex cord-stromal tumour was made.

Ovarian steroid cell tumor resembling luteoma associated with hyperadrenocorticism (Cushing's disease) in a dog.

An ovarian steroid cell tumor was diagnosed in a 6.5-year-old female Rottweiler. The animal was polydipsic and polyuric, with an enlarged, pot-bellied abdomen. Radiographs and ultrasound examinations revealed an approximately 13-cm-diameter cystic mass below the right kidney. A low-dose dexamethasone suppression test was consistent with hyperadrenocorticism. Surgical exploration revealed an enlarged, lobulated left ovary approximately 10 cm in diameter, weighing 550 gs. Histologically, the ovarian tumor consisted of dense sheets and nests of round to polyhedral cells with abundant, finely vesiculated cytoplasm. The overall features were most consistent with ovarian steroid cells tumor resembling luteoma and associated with hyperadrenocorticism.

Ovarian sex cord-stromal tumours in cattle, with particular reference to the lamination of basal laminae.

Three cases of bovine sex cord-stromal tumours, including a sex cord tumour with annular tubules and two granulosa cell tumours, are described. These tumours had tubular structures and hyaline or eosinophilic bodies, composed of multilayered basal laminae. The present study suggests that bovine granulosa cell tumours of the ovary are able to show morphology similar to that of Sertoli cell tumours of the testis and that sex cord tumours with annular tubules arise from granulosa cells but indicate Sertoli cell differentiation.