Outcome of Metastatic and Recurrent Ovarian Dysgerminoma Using Radiation Therapy and Chemotherapy in a Dog.

An 8 yr old female spayed poodle/terrier mixed-breed dog was referred for evaluation of a recurrent and metastatic ovarian dysgerminoma. A total dose of 20Gy was administered to both the mediastinal metastatic lesion and retroperitoneal recurrent dysgerminoma in five daily fractions of 4Gy. Acute side effects were mild and self-limiting. This was followed by several courses of chemotherapy using a variety of agents. Despite extensive disease, this patient was still alive at the time of publication, 524 days after presentation and 501 days following completion of radiation. This case report demonstrates tolerability and efficacy of palliative radiation and chemotherapy for this rare tumor type.

Anti-Muellerian hormone concentration in bitches with histopathologically diagnosed ovarian tumours and cysts.

Increased concentrations of Anti-Muellerian hormone (AMH) can indicate a granulosa cell tumour as shown in women, mares and cows. To investigate AMH to differentiate canine granulosa cell tumour from other ovarian pathologies, we evaluated the ovaries of 63 bitches. Blood serum samples were collected before surgery for AMH analysis. Ovaries were submitted for histopathological examination. Fourteen bitches showed normal ovaries. These bitches had AMH values between 0.12 and 0.99 ng/ml. In 20 bitches ovarian cysts i.e., follicular cysts (n = 8), corpora lutea cysts (n = 7), subsurface cysts (n = 5) were diagnosed. These dogs had AMH values of 0.11-2.09 ng/ml. Bitches with small luteinized follicular cysts had slightly higher AMH values than those without ovarian alteration. In 29 cases ovarian neoplasms i.e., granulosa cell tumour (n = 9), epithelial tumours (n = 16), dysgerminomas (n = 3) and one sarcoma were identified. Anti-Muellerian hormone values of bitches with an ovarian neoplasm except granulosa cell tumour ranged from 0.18 to 1.18 ng/ml. The AMH values of bitches with granulosa cell tumour ranged from 1.12 to ≤23 ng/ml and were significantly higher (p < .05) than in all of the other bitches. The cut-off of 0.99 ng/ml gave a sensitivity of 100% and a specificity of 94.44% to diagnose granulosa cell tumour. In conclusion, markedly elevated AMH concentrations in bitches are indicative for a granulosa cell tumour. However, negative testing does not rule out the existence of small one. Differentiation of GCT from luteinized follicular cysts may especially be difficult.

PRESUMPTIVE DYSGERMINOMA IN AN ORANGE-SPOT FRESHWATER STINGRAY (POTAMOTRYGON MOTORO).

A captive-born, 13-yr-old female orange-spot freshwater stingray, (Potamotrygon motoro), presented with an acute caudodorsal swelling. Ultrasonography revealed an intracoelomic mass of mixed echogenicity containing fluid pockets. The ray was euthanatized and gross postmortem examination confirmed the presence of a fluid-filled coelomic mass in the region of the reproductive tract. The mass was identified histologically as a malignant round cell tumor of the ovary. Although immunohistochemistry for protein gene product 9.5 (PGP9.5), octamer-3/4 (OCT-3/4), and inhibin was attempted, antibodies that had been validated in mammalian species did not cross-react with stingray control tissues and did not label neoplastic cells. The final diagnosis was a presumptive dysgerminoma.

Clinical and ultrasonographic findings of ovarian tumours in bitches: A retrospective study.

A retrospective study was carried out to investigate incidence, clinical signs and ultrasonographic findings of ovarian tumours in a population of dogs referred to the Veterinary Teaching Hospital of the University of Perugia (Italy) and Anicura Tyrus Veterinary Clinic (Terni, Italy). The period of study ranged from January 2005 to December 2021. A total of 1910 dogs were affected by neoplasia but only 35 of them (1.8%), of different breeds and ages, were found to have ovarian tumours. Ultrasound of the ovaries was performed based on clinical signs; the diagnosis was achieved after ultrasound findings prompted ovariohysterectomy and ovarian pathologic evaluation In our study, the age of bitches affected by ovarian neoplasia ranged from 3 to 20 years (mean 9.6 ± 3.8). The histopathological findings of ovarian masses identified 16 granulosa cell tumours (GCT) (46%), 7 adenomas (20%), 5 adenocarcinomas (14%), 2 teratomas (6%), 1 leiomyoma (3%), 1 luteoma (3%), 1 tecoma (3%), 1 dysgerminoma (3%), and 1 haemangiosarcoma (3%). In particular, with respect to clinical signs, 69% of bitches showed abnormalities of estrus cycle (short interestral interval, persistent estrus, prolonged interestral interval). The other main clinical signs included abdominal distention, palpable abdominal mass, vulvovaginal discharge, polyuria/polydipsia, mammary masses. When present, the laboratory abnormalities were slight anemia and leucocytosis with neutrophilia. The tumours were ultrasonographically classified as mainly solid: 12/35 (34%) (1 adenoma, 4 adenocarcinomas, 1 dysgerminoma, 1 haemangiosarcoma, 1 leyomioma, 1 luteoma, 1 GCT, 1 tecoma, 1 teratoma); solid with cystic component 13/35 (37%) (9 GCT, 2 Adenomas, 1 adenocarcinoma, 1 teratoma); and mainly cystic 10/35 (29%) (6 GCTs, 4 adenomas). In our study, the ultrasound examination allowed us to suspect ovarian neoplasia in asymptomatic subjects referred for breeding management or for preventive health check. On the basis of our data, we proposed to perform a complete periodic examination of the reproductive system once a year from 6 years. Nevertheless, the presence of ovarian neoplasms found in young subjects, during breeding management, suggest including routine ultrasound examination of the reproductive tract.

Dysgerminoma in an eastern rosella (Platycercus eximius eximius).

This report describes a case of dysgerminoma in a 21-year-old eastern rosella (Platycercus eximius eximius) that presented with dyspnea and a severely distended coelom. The bird was euthanatized, and a large, left-sided coelomic mass was identified. Microscopically, the mass was composed of sheets and nests of round to polygonal neoplastic cells with lacy cytoplasm. The neoplastic cells were weakly positive for vimentin and c-kit but negative for pancytokeratin, AE1, and inhibin. On the basis of the histomorphology and immunoreactivity, the neoplasm was determined to be a dysgerminoma. The variability of histologic appearance and immunohistochemical staining of dysgerminomas in humans compared with veterinary species is discussed.

A retrospective analysis on the outcome of 18 dogs with malignant ovarian tumours.

Little evidence is available regarding the prognosis of dogs with malignant ovarian tumours. The objective of this retrospective study was to describe the outcomes and determine the prognostic factors for dogs with malignant ovarian tumours following treatment, including surgery with or without adjuvant therapy. Eighteen dogs were studied, their median age was 12 years (range: 7-15 years), and their median body weight was 6.9 kg (range: 2.3-17.8 kg). Following histopathologic diagnoses revealed that granulosa cell tumour was the most common type (n = 9), followed by dysgerminoma (n = 5), and adenocarcinoma (n = 4). Eleven dogs had surgery alone. Seven dogs had surgery with adjuvant therapy, including chemotherapy and/or radiotherapy. The median survival time (ST) was 1009 days when only deaths owing to the ovarian tumours were considered, and predictors of median ST were T-category (≥ T3, 443 days vs ≤ T2, 1474 days; P = .002), presence of metastatic disease (present, 391 days vs absent, 1474 days; P < .001) and lymphovascular space invasion (present, 428 days vs absent, 1474 days; P = .003) in a univariate analysis. Median ST in dogs with granulosa cell tumour seemed longer than in dogs with dysgerminoma and adenocarcinoma, although the difference was statistically insignificant (1474 days vs 458 days, respectively; P = .10). Considering the good prognosis, aggressive treatment can be recommended for dogs with malignant ovarian tumours, especially early-stage cases. Despite metastasis being present at diagnosis, half of the dogs with metastasis survived for more than 1 year.

Comparison of immunohistochemical profiles of ovarian germ cells in dysgerminomas of a captive maned wolf and domestic dogs.

We characterized the immunohistochemical expression profiles of dysgerminomas from a 16-y-old maned wolf and 13 domestic dogs using the following biomarkers: Sal-like protein 4 (SALL4), octamer-binding transcription factor 3/4 (OCT3/4), placental alkaline phosphatase (PLAP), c-kit, and vimentin. The maned wolf had nonspecific and long-standing clinical signs of lethargy, anorexia, and weight loss, and was euthanized because of poor prognosis. At autopsy, the left ovary was effaced by a 12 × 8 × 6 cm mass, comprised of anaplastic cells with a mitotic count of 20 mitoses in 10 high power fields. Dysgerminomas from 7 of 13 domestic dogs had nuclear expression of SALL4. Dysgerminomas from the maned wolf and 2 domestic dogs had both nuclear and cytoplasmic expression of SALL4. Cytoplasmic expression of PLAP and OCT3/4 was present in dysgerminomas from the maned wolf and 3 (PLAP) or 4 (OCT3/4) domestic dogs. All dysgerminomas expressed vimentin. Membranous c-kit expression was rare in the dysgerminoma from the maned wolf, and variable in dysgerminomas from 4 domestic dogs. A dysgerminoma from a domestic dog had cytoplasmic expression of c-kit. SALL4 is a useful marker to confirm germ cell origin of dysgerminoma in canids.

Immunohistochemistry diagnosis of an ovarian dysgerminoma in one bitch.

An ovarian enlargement (diameter, 8 cm) was identified and surgically excised from a 5-year-old female dog. Microscopic examination of the multinodular neoplasm revealed sheets of polygonal neoplastic cells with large nuclei, frequent mitosis, necrosis and haemorrhage. Immunohistochemically, the neoplastic cells were positive for vimentin and alkaline phosphatase but were negative for CD3, CD79a, cytokeratin, alpha-fetoprotein, inhibin-alpha and S-100. The histopathological diagnosis of the mass was unilateral ovarian dysgerminoma.

Surgical resection of a dysgerminoma in a mare.

A mare was referred for further evaluation of a mass found in the left caudal abdomen during a routine postpartum reproductive palpation. The mare was clinically normal with no history of health problems. Ultrasonographic examination of the mass confirmed its presence, but the origin of the mass could not be accurately determined. Routine haematology and serum biochemistry results were within normal limits. The mare was initially treated conservatively with antibiotics, but the mass continued to increase in size, so it was surgically excised. The mass involved the left ovary. The mare showed transient abdominal pain after surgery, but developed no other complications and was in foal 7 months later. On histology, the mass was diagnosed as a dysgerminoma, a rare ovarian tumour of germ cell origin.

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.

Ovarian dysgerminomas in two mountain chicken frogs (Leptodactylus fallax).

This report describes the gross, histologic, and immunohistochemical features of ovarian dysgerminomas in two adult female mountain chicken frogs (Leptodactylusfallax) from the same zoological institution. One frog was found dead, and the other frog had been ill for several days with a bloated abdomen and lethargy. On necropsy, large, pale multilobulated masses replaced the left ovary in both frogs, and one frog also had numerous smaller nodules scattered throughout the coelomic viscera. Histologically, these masses were composed of sheets and cords of polyhedral discrete germ cells consistent with the diagnosis of dysgerminoma. Neoplastic cells stained positive with immunohistochemistry for Oct4, which has been reported to detect stem cells including germ cells in a variety of species, including humans. Ovarian tumors are uncommonly encountered in both reptiles and amphibians, and this report is the first report of dysgerminoma in any amphibian species.

Excess of seminomas observed in Vietnam service U.S. military working dogs.

During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs. To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology. We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction. Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam. Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease Control, further research is warranted if we are to clarify military service in Vietnam as a risk factor for testicular dysfunction. The testis should be made a priority site in the study of Vietnam experience-related cancers.

Intra-abdominal mass aspirate from an alopecic dog.

An 11-year-old female Yorkshire terrier was presented to the University of Minnesota Veterinary Medical Center for evaluation of a palpable intra-abdominal mass and alopecia. Abdominal ultrasonography revealed a large, complex, cavitary mass in the left caudal region of the abdomen. A fine needle aspirate of the mass was collected. A population of markedly pleomorphic, large, round to polygonal cells were found singly and in small noncohesive aggregates. The cells contained scant, clear to blue-gray cytoplasm, large, round to oval nuclei, and distinctly stippled to reticular chromatin. Cytologic findings were consistent with a tumor of ovarian origin, with a primary differential diagnosis of germ cell tumor. Hormonal analysis of serum revealed a marked increase in 14-OH-progesterone concentration (2.71 ng/mL, reference interval 0.05-0.69 ng/mL). Ovariohysterectomy was performed, and the mass was found to be in the area of the left ovary. Histologic evaluation of the reproductive tract confirmed a diagnosis of left ovarian dysgerminoma. Based on immunohistochemical stains, the tumor was negative for c-kit (CD117c) and single cells were positive for neuron-specific enolase. A right ovarian cyst and squamous metaplasia of the right uterine horn also were diagnosed. The cyst was presumed to be the source of 14-OH-progesterone, which likely resulted in the squamous metaplasia and dermatopathy. Three months after surgery, the progesterone concentration had returned to normal and the alopecia had nearly resolved. Dysgerminomas in dogs are reported rarely, but have a distinctive, recognizable, cytologic appearance and should be included in the differential diagnosis of an intra-abdominal mass in a reproductively intact female dog.

A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection.

Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10-9.15 and 2.61-17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per wk for 3 wk and in dogs using 50 times HTD per wk for 3 wk did not show any evidence of acute or chronic toxicity.

Germinomas and teratoid siphon anomalies in softshell clams, Mya arenaria, environmentally exposed to herbicides.

Seminomas and dysgerminomas are epizootic in softshell clams, Mya arenaria, from three Maine estuaries contaminated with herbicides. The first epizootic was discovered in 22% of clams collected as Searsport near Long Cove Brook and three culverts that conveyed heating oil and jet fuel spilled from a tank farm in 1971. Data from subsequent epizootiological studies and a series of long-term experimental exposures of softshell clams to no. 2 fuel oil, JP-4, and JP-5 jet fuel at the U.S. EPA, Environmental Research Laboratory in Narragansett, Rhode Island, and in the field did not support an etiology by these petroleum products. In the two recent epizootics reported here, the germinomas have been observed in 3% of the softshell clams collected from Roque Bluffs near Machiasport and from 35% of softshell clams collected from Dennysville. Mya collected at Dennysville had pericardial mesotheliomas and teratoid siphon anomalies in addition to gonadal neoplasms. Estuaries at Dennysville had been contaminated by herbicides in a 1979 accidental spray overdrift during aerial application of Tordon 101 to adjacent forests. Further investigation determined widespread use of the herbicides Tordon 101, 2,4-D,2,4,5-T, and other agrochemicals in an extensive forestry and blueberry industry in both the Roque Bluffs and the Dennysville areas. Herbicide applications at Searsport were confirmed for railroad property bordering Long Cove estuary and for Long Cove Brook adjacent to the estuary where a highway department reportedly cleans its spray equipment. Herbicide contamination is the only common denominator identified at all three sites where Mya have been found with gonadal neoplasms.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian neoplasia in ornamental hybrid carp (Nishikigoi) in Japan.

Massive abdominal enlargements were observed in 21 adult carp 4--6 years old living in the breeding ponds of carp fisheries in northern Japan. The abdominal enlargement rapidly increased, and the affected fish died within a few months. At necropsy, single or multiple tumors, 1.5--25 cm (average, 10.6 cm) in diameter, were found in the abdominal cavity. Ovarian tissue was identified close to the tumors in 15 cases, and there was no evidence of anatomic continuity between the tumors and other viscera. It seems likely that all of these tumors arose in the ovaries. Histologically, the 21 tumors observed exhibited great variation, but they were composed mainly of various types of cells similar to those of human dysgerminoma, granulosatheca cell tumors, or embryonal carcinomas. Squamous cell nests were found with mesenchymal elements in one tumor. Thus, ovarian tumors in carp may have diverse histogenetic origins and probably arise both from germ cells and from ovarian mesenchyme. Areas of cellular pleomorphism, which suggested a malignant character, were seen in some of the tumors, but no evidence on metastasis was found. Tumor-bearing carp had generally been raised in ponds supplied by wells or underground springs in mountainous areas. Evidence of a possible environmental factors(s) is yet to be demonstrated.

Report of dysgerminoma in the ovaries of a snapping turtle (Chelydra serpentina) with discussion of ovarian neoplasms reported in reptilians and women.

A malnourished, captive, young adult (weight-11 kg, carapace length-25 cm), female snapping turtle (Chelydra serpentina) was presented for examination and treatment of malnutrition and multiple carapace necroses. Because treatment was unsuccessful, the animal was euthanatized and necropsied. The main necropsy observations showed the presence of a 9 cm greyish-white/yellow, soft, fleshy to fatlike mass involving the right ovary near the oviduct opening and multiple similar, pea-to-walnut sized masses involving both ovaries. Microscopic examination of formalin fixed, hematoxylin and eosin and silver stained tissue sections revealed the masses to be composed of primordial germ cells arranged in a pattern morphologically compatible with dysgerminoma as described in women and other mammals. Very rarely have ovarian neoplasms been reported in turtles or other reptiles. This is the first neoplasm described in the snapping turtle ovary and the first dysgerminoma reported in reptilians. A tabulation of previously documented ovarian neoplasia in reptiles and a comparison of this cancer to those occurring in women will be discussed.

Immunoreactivity of A103, an antibody to Melan A, in canine steroid-producing tissues and their tumors.

The monoclonal antibody A103 to the melanocytic differentiation antigen Melan A stains human steroid-producing cells and their tumors. A total of 200 formalin-fixed, paraffin-embedded canine normal tissues and hyperplastic and neoplastic lesions of the adrenal gland, testis, and ovary were immunohistochemically tested for Melan A with antibody A103. Leydig cell tumors (23/23, 100%), Sertoli cell tumors (14/15, 93%), and adrenocortical adenomas (12/13, 92%) were consistently positive. Adrenocortical carcinomas (23/35, 65%) and granulosa cell tumors (10/17, 59%) were less frequently positive. All pheochromocytomas, seminomas, and dysgerminomas were negative. The pattern of staining was cytoplasmic, but nuclear staining was also frequently seen in normal Leydig cells and their tumors. As in human tumors, immunohistochemistry for Melan A stains many canine steroid-producing tumors and can be used to distinguish these tumors from those of nonstereidogenic cells.

Spontaneous ovarian tumour in a medaka (Oryzias latipes).

Swelling of the abdomen was found in an adult female medaka (Oryzias latipes). Multiple tumour masses occupying most of the abdominal cavity were found at necropsy. Histologically, the tumour consisted of homogeneous round cells arranged in islands and occasional trabecular structures with thin capsules. Ova at various stages of maturation were seen in the periphery of the tumour mass. Metastasis was observed in the vicinity of the thyroid gland with accompanying infiltration by lymphocytic cells and also abdominal muscles. The tumour cells were characterized by a large ovoid nucleus with no aggregation of heterochromatin, occasional mitotic figures and prominent nucleoli. Examination by electron microscopy showed cells with scant cytoplasm but many ribosomes and a few other organelles. Annulate lamellae and dense cytoplasmic masses were also frequently observed. Based on the above features, the tumour was diagnosed as an ovarian dysgerminoma, the first reported case in a medaka.