Single-cell mRNA sequencing of giant panda (Ailuropoda melanoleuca) seminoma reveals the cellular and molecular characteristics of tumour cells.

Testicular tumours are zoonoses that can occur in not only human, but other animals, include giant pandas. A middle-aged male giant panda named Fufu was diagnosed with a testicular tumour and underwent surgery to remove the entire left testis. The testis was mainly composed of three substantive parts: normal tissue on the outside, tumour tissue in the middle, and necrosis in the centre. HE stains revealed that the tumour was a seminoma. Single-cell mRNA sequence was applied to characterise cellular states and molecular circuitries of giant panda testicular seminoma. Only germ cell markers expressed in nearly all tumour cells, and the tumour cells appeared to be the same subtype of seminoma cells. We identified four clusters with unique genes expression. They were early apoptosis cells (EAC), inactive cells (IC), active cells subcluster 1 (AC-1) and active cells subcluster 2 (AC-2). We utilised monocle tools and found that IC cells was in the initiation stage, and EAC was one type of terminal stage, suggesting that tumour cells may undergo apoptosis in the future. AC-2 was another type of terminal stage, representing a group of progressive cells. Our study represents the first report to utilise scRNA-seq to characterise the cellular states and molecular circuitries of a giant panda testicular tumour. This investigation proposes CD117 and CD30 as dependable markers for future pathologic diagnosis. Our findings also suggest that CTSV and other genes with unique expression patterns in active and progressive giant panda seminoma cells may act as early prognostic biomarkers.

MicroRNA as epigenetic regulators of canine cryptorchidism.

Cryptorchidism, the failed descent of one or both testes into the scrotum, is a common developmental disorder in male dogs. Cryptorchidism may affect canine fertility, reducing the quality of the semen, and may promote spermatic cord torsion and onset of neoplasia. MicroRNAs (miRNAs) are epigenetic regulators of gene expression and their dysregulation is associated with disorders of spermatogenesis and testis neoplasia. The present study aimed at investigating the expression of miRNAs in formalin-fixed, paraffin-embedded (FFPE) canine retained testes and testes affected by seminoma, and at integrating miRNAs to their target genes. Forty testicular FFPE specimens from 30 dogs were included - 10 scrotal and 10 contralateral retained from 10 unilateral cryptorchid dogs; 10 tumoral testes affected by seminoma from non-cryptorchid dogs; 10 scrotal normal testes from non-cryptorchid dogs included as the control. The expression level of three miRNAs, namely miR-302c-3p, miR-302a-3p, and miR-371-3p, associated with testicular disorders, were quantified using RT-qPCR. The comparative analysis demonstrated that the level of miR-302a-3p and miR-371a-3p were quantifiable exclusively in control testes. The expression level of miR-302c-3p was higher in the control than in the other groups; its expression decreased in retained testes compared to scrotal testes and testes with seminoma. Gene Ontology analysis pointed out that these miRNAs may be involved in the modulation of estrogen and thyroid hormone signaling pathways. In conclusion, this study demonstrated that miRNAs are dysregulated in canine cryptorchid and seminoma-affected testes compared to control tissues, confirming the pivotal role of miRNAs in cryptorchidism.

Diagnosis of Seminoma With Metastasis to the Brain and Kidneys in a Moluccan Eclectus (Eclectus roratus) Using Advanced Contrast Based Imaging.

A 20-year-old male Moluccan eclectus (Eclectus roratus) was presented with a history of falling off the perch, ataxia, unilateral blindness, hyporexia, and progressive lethargy. The eclectus was found to have a leukocytosis (52 × 103 cells/µL), characterized by an absolute and relative heterophilia (42.6 × 103 cells/µL and 82%, respectively), relative lymphopenia (18%), elevated bile acids (88 µmol/L), and elevated triglycerides (236 mg/dL). Radiographic images revealed a mass effect within the caudal coelom. After 13 days of outpatient supportive care, the patient was rechecked and had normalized bile acids (<35 µmol/L), static triglycerides (232 mg/ dL), and hyperuricemia (18.6 mg/dL). Computed tomography was performed antemortem with and without iodinated contrast agent, 4 mL/kg IV over 2 minutes, and a mass was found associated with the left kidney. Due to worsening neurologic signs and involvement with surrounding structures, the owner elected euthanasia. Before the postmortem examination, a postmortem intravascular contrast agent was used to provide a more thorough visualization of internal anatomical structures, including left renal vasculature disruption, mass vasculature, caudal coelomic organ displacement, and increased irregular optic chiasm radiodensity. Postmortem, a 4 × 4.1 × 5.1-cm white to tan mass was identified. Histopathology confirmed a seminoma with metastasis to the kidneys and optic chiasm. Seminomas have been described in avian species; however, seminoma metastasis in an eclectus parrot confirmed by histopathology has not been reported, and optic chiasm metastasis of a seminoma has not been described in any avian species. This report describes postmortem computed tomographic angiography of metastatic seminoma in a Moluccan eclectus with metastasis to the optic chiasm.

Widespread metastasis of a spermatocytic seminoma with concomitant hepatic peliosis in a Southern African hedgehog (Atelerix frontalis).

ABSTRACT: A six-year-old intact male Southern African hedgehog (Atelerix frontalis) presented with a history of chronic mild to moderate weight loss, and sub-acute hind limb ataxia that progressed to complete paralysis, at which point the hedgehog was euthanised. At autopsy, a large multinodular pale mass had completely replaced the left testicle and transcoelomically metastasised to the diaphragm and the peri-renal area, from where it then invaded the vertebral column and spinal cord. Multifocal, irregular to round, well-demarcated, blood-filled, proliferative lesions were also present in the hepatic parenchyma. Histological analysis of both the testis and metastatic lesions revealed diffuse sheets of neoplastic cells with moderate pale cytoplasm, large irregular to round nuclei and mostly one prominent magenta nucleolus, consistent with metastatic seminoma. The neoplastic cells were negative for periodic acid-Schiff (PAS) stain and positive for CD117 by immunohistochemistry (IHC). Taken together with the morphology of the neoplastic cells and the advanced age of the animal, this is suggestive of a spermatocytic seminoma. Histological analysis of the liver revealed multifocal lesions consisting of large anastomosing blood-filled spaces bordered by compressed hepatocytes, consistent with hepatic peliosis. This is the first report of a neoplasm in the Southern African hedgehog (Atelerix frontalis), the first report of a metastatic seminoma in a hedgehog, together with diagnosis of spermatocytic subtype, and the first report of a hedgehog with concomitant hepatic peliosis.

Atypical cytomorphologic description of a seminoma in a rabbit.

Seminoma is reported as a rare disease associated with specific micro-morphologic findings. In the present report, we describe the case of a testicular seminoma in a 7-year-old Holland Lop rabbit, in which the cytology presented an atypical pattern. Upon presentation, the left testicle was severely enlarged, and the patient also had a history of radiation therapy for a previously diagnosed thymoma. Following excision and histopathology of the abnormal organ, results showed a mixed intratubular-diffuse pattern with evidence of torsion. Moreover, cytology revealed a cohesive pattern with multiple malignancy criteria. To our knowledge, this is the first published report of a seminoma with these cytologic features.

A case of neoplastic synchronism in a dog.

INTRODUCTION: Synchronous primary tumors are considered severe, comorbid conditions in people representing neoplasm that develop independently and concomitantly. A diagnosis of synchronous tumors was made in a dog, underlying the difficulties to reach it without the aid of multiple diagnostic techniques aimed to demonstrate the simultaneous coexistence of different tumor types. MATERIALS AND METHODS: A 7-year-old male Boxer dog presented several tumors located on the skin of the left hind limb and the scrotal region. Moreover, additional tumors in the testicles, after palpation and ultrasound examination, were detected. Following diagnostic results, the cutaneous tumor, scrotum, and testes were surgically removed. RESULTS: Pathological investigations revealed the presence of five different tumors: a cutaneous mast cell tumor; a scrotal melanocytoma; three testicular neoplasms (Sertoli Sustentacular cell tumor, seminoma, and interstitial Leydig cell tumor). CONCLUSIONS: The present report describes a neoplastic synchronism due to the presence of five different primary tumors in a dog and, for the first time the presence of a collision testicular tumor together with other non-testicular primary tumors. The occasional finding underlines the importance of the knowledge of such conditions in the process of decision-making and in carrying out all the proper diagnostic procedures for a correct diagnosis and clinical staging.

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.

Seminoma in an adult striped dolphin Stenella coeruleoalba: tomographic, macroscopical, histological and immunohistochemical study.

Testicular neoplasms have been extensively described and characterized in domestic animals, but reports in wildlife species, including marine mammals, are scarce. This case report describes a testicular seminoma in an adult striped dolphin Stenella coeruleoalba stranded along the coasts of the Canary Islands. Post-mortem computerized tomography (CT) showed a prominent enlargement of the cranial pole of the right testicle, displacing the intestinal loops. Necropsy gross findings confirmed the presence of a testicular mass, bulging at the cut surface, with multiple well-delimitated whitish nodular lesions. Histologically, intratubular and diffuse neoplastic germinative cell proliferation was described. Complementary immunohistochemical assessments for vimentin and CD117 antibodies were negative. To the authors' knowledge, this is the first seminoma described in a S. coeruleoalba. We suggest that post-mortem (PM) pre-necropsy CT in dolphins is a useful tool for anatomic-guided pathology in such cases.

Testicular tumors in 190 dogs: clinical, macroscopic and histopathological aspects / Neoplasmas testiculares em 190 cães: aspectos clínicos, macroscópicos e histopatológicos

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.(AU)

Este estudo teve por objetivo caracterizar a prevalência, aspectos clínicos, macroscópicos e histopatológicos dos cães acometidos por neoplasmas testiculares, a partir dos espécimes de biópsias do Laboratório de Patologia Veterinária da Universidade Federal de Santa Maria (LPV-UFSM) em 19 anos. Parâmetros quanto à idade, porte, raça dos cães acometidos também foram estabelecidos. De todos os cães com algum tipo de neoplasma submetido à análise histopatológica no LPV nesses 19 anos (n=1.900), 213 (11,2%) tinham ao menos um neoplasma testicular. Os tecidos de 190 cães (com 220 neoplasmas) estavam disponíveis para reavaliação histológica. Os cães deste estudo apresentaram diferentes tipos de neoplasmas testiculares com frequências relativamente semelhantes. Em ordem decrescente, os neoplasmas testiculares mais frequentes foram: seminomas (88/220), leydigomas (64/220), sertoliomas (61/220) e o tumor misto de células germinativas e do estroma do cordão sexual (MGSCT; 07/220). Dentre os cães com raça definida (119 casos), as raças de grande porte tiveram o maior número de casos (50/119), seguido das raças de pequeno (47/119) e médio porte (22/119). As idades dos cães acometidos por neoplasmas testiculares variaram de 10 meses a 18 anos. Aumento de volume testicular foi a manifestação clínica mais comum. Onze cães tinham informações sobre sinais clínicos sugestivos da síndrome da feminilização. Nos seminomas, houve o predomínio do padrão difuso sobre o intratubular. Dois locais (compartimentos luminal e basal) sugestivos de início das transformações neoplásicas nas células germinativas foram observados nos seminomas intratubulares, corroborando com a hipótese de que os seminomas caninos possivelmente tem patogênese semelhante à observada nos seminomas espermatocíticos humanos. Sertoliomas e leydigomas foram neoplasmas com alta variação na morfologia celular. Os sertoliomas tinham células neoplásicas dispostas em cinco arranjos histológicos distintos. Quanto aos leydigomas, os padrões histológicos sólido-difuso e cístico-vascular foram os mais comumente observados. Através deste estudo foi possível estabelecer alguns dos principais aspectos clínicos, macroscópicos e histopatológicos dos neoplasmas testiculares diagnosticados em 19 anos na área de abrangência do LPV-UFSM.(AU)

Metástase de seminoma em região orbital em cão - relato de caso / Metastatic seminoma in the orbital region in a dog - case report

O seminoma é uma neoformação testicular originária de células germinativas de ocorrência comum em cães, com maior prevalência em animais senis. Em geral, o comportamento biológico do seminoma canino é benigno. Relata-se neste trabalho um caso de seminoma com metástase em região orbital em um cão com 14 anos de idade. O animal foi atendido com queixa de aumento de volume em órbita esquerda, com posterior detecção de nódulo testicular. A punção aspirativa por agulha fina da massa orbital sugeriu tratar-se de linfoma de alto grau, contudo o diagnóstico definitivo de seminoma difuso foi estabelecido pela avaliação histopatológica, a qual revelou tratar-se de neoplasia maligna pouco diferenciada, sendo o diagnóstico de seminoma difuso confirmado pelo exame imunoistoquímico. Relatos de seminomas metastáticos em cães são incomuns. Objetivou-se com este trabalho relatar um caso de seminoma anaplásico difuso em cão cujo foco principal de metástase ocorreu em região orbital, além de descrever e discutir as dificuldades diagnósticas encontradas.(AU)

Seminoma is a testicular neoformation originating from germ cells, commonly occurring in dogs. With higher prevalence in senile animals, the biological behavior of canine seminomas generally benign. This case reports seminoma with mestastasis in the orbital region in a 14-year-old dog. The animal was treated with a complaint of increased volume in the left orbit, and later a nodule in the testicle was discovered. Fine-needle aspiration of the orbit mass initially indicated a high-grade lymphoma. The definitive diagnosis of diffused seminoma was established by histopathological examination, resulting in poorly differentiated malignant neoplasia. Finally, the diagnosis was confirmed through immunohistochemistry, being the result compatible with diffused seminoma. Metastatic seminomas reported in dogs are quite uncommon. In this work we report a case of diffused anaplastic seminoma in dogs, where the main focus of metastasis was observed in the orbital region, and we also describe and discuss the difficulties encountered in the diagnostic.(AU)

Mixed germ cell tumor composed of a tridermic testicular teratoma and seminoma in a rooster.

A 5-y-old backyard Araucana-Americana rooster was presented to the regional diagnostic laboratory with a history of progressive lethargy and respiratory signs. Autopsy revealed a single large mass of testicular origin in the coelomic cavity, causing compression of other organs. Histologically, the mass was 1 neoplasm with mixed components of 2 different germ cell tumors, namely a teratoma composed of elements of all 3 primordial germ cell lines (ectoderm, mesoderm, and endoderm), and a seminoma consisting of round or polygonal cells arranged in sheets supported by a scant fibrovascular stroma. Teratomas and seminomas are both considered to be uncommon neoplasms in poultry medicine. A testicular teratoma is composed of mature embryonic tissue derived from at least 2 of the 3 germinal layers. Seminomas and teratomas both arise from the germinal epithelium of seminiferous tubules and are classified as germ cell tumors. This neoplastic mass thus is a rare case of a mixed germ cell tumor.

Bilateral Malignant Seminoma With Ventricular Metastasis in a Bald Eagle ( Haliaeetus leucocephalus).

A 30-year-old bald eagle ( Haliaeetus leucocephalus) was presented with a history of hyporexia and lethargy. Results of initial hematologic testing, biochemical analysis, and fecal examination were unremarkable, and clinical signs did not resolve with supportive care and management changes. Results of echocardiography, based on auscultation of a murmur, and coelomic endoscopy, based on the presence of a soft tissue opacity on radiographs, as well as an aspergillosis panel were largely unsuccessful in determining a definitive diagnosis. Euthanasia was performed after the eagle did not recover from anesthesia after endoscopy. Necropsy results demonstrated bilateral testicular seminomas with metastases to the ventriculus. This case demonstrates an abnormal metastasis of a common reproductive tumor in an avian species.

Immunohistochemical Expression of Placental Alkaline Phosphatase in Five Cases of Seminoma in Rabbits.

Testicular seminoma is reported in the rabbit but data about the immunophenotype of these tumours are lacking. The classification of human testicular germ cell tumours includes spermatocytic tumour (ST) originating from the post-pubertal spermatogonia/spermatocytes, which metastasizes rarely, and seminoma (SE), originating from gonocytes, which is malignant and metastasizes frequently. Gonocytes express placental alkaline phosphatase (PLAP) and are stained with periodic acid-Schiff (PAS). We report five cases of seminoma in pet rabbits. Microscopically, all the cases were diffuse seminoma and in one case there was metastasis to a sublumbar lymph node. Immunohistochemical expression of PLAP was diffuse in this metastatic tumour, in two other cases it was multifocal, in another it was limited to rare cells and in the remaining case was negative. PAS-positive cells were detected only in the four cases that expressed PLAP. These four cases were therefore classified as SE and the tumour without PLAP labelling or PAS staining was defined as ST. Both forms of human germ cell tumour therefore occur in the rabbit. SE appears to be well represented and may show metastasis, paralleling the human counterpart. The results of this study provide a basis for further evaluations of the rabbit as a possible animal model for the study of human SE.

An Unusual Case of Metastatic Seminoma in a Dog.

An 8 yr old, reportedly castrated male Boston terrier presented with a history of generalized hyperesthesia and intermittent shifting leg lameness. Physical examination revealed a caudal abdominal mass and bilateral shoulder pain. A complete blood count, serum biochemistry panel, and urinalysis were unremarkable. Thoracic radiographs demonstrated bony proliferation and lysis of the third sternebra, an expansile lesion of the left tenth rib, and lucency in both proximal humeral metaphyses. Abdominal radiographs and ultrasound revealed a soft tissue mass within the caudoventral right abdomen. Ultrasonography also revealed an enlarged lymph node within the right retroperitoneal space. Exploratory laparotomy identified the mass as a retained testicle. A cryptorchidectomy, lymph node biopsy, and bilateral percutaneous core biopsies of the proximal humeri were performed. Histopathologic examination revealed malignant seminoma of the testicle with metastasis to lymph node and bone. Adjuvant chemotherapy was recommended, but it was declined by the owner. All follow-up was lost. This case highlights a unique case for causative hyperesthesia secondary to a novel site of metastasis from malignant seminoma. Metastasis to bone has not been reported in humans or dogs and represents a very unusual and aberrant variant of the normally relatively benign biological behavior of seminoma in the dog.

Bilateral Malignant Seminomas in Two Unrelated, Aged Trumpeter Hornbills (Bycanistes buccinator).

Seminomas occur infrequently in birds. Two cases of bilateral malignant seminomas in unrelated trumpeter hornbills (Bycanistes buccinator) are described. Case 1 was a 22-year-old trumpeter hornbill submitted for necropsy because of sudden death at a zoo in California. Postmortem examination revealed multiple masses within the body cavity, 2 of which replaced both testes. Case 2 was a 19-year-old trumpeter hornbill at a zoo in North Carolina that underwent exploratory surgery for a suspected gastrointestinal obstruction. Both testes were diffusely enlarged, compressing and replacing the adjacent kidneys. In both birds, the masses were composed of discrete, round to polyhedral cells, typical of seminomas. Examination of the ancestry of the hornbills showed they were unrelated to each other, suggesting a potential predisposition for these birds to develop seminomas.

Malignant seminoma in two unilaterally cryptorchid stallions.

Two unilateral cryptorchid stallions were referred to the clinic because of chronic debilitating condition with emaciation. Rectal examination, and ultrasound and gross examination revealed in both animals an abdominal mass, caudally of the kidney, and multiple nodules spread over the abdomen. Histologic analysis revealed an intra-abdominal malignant seminoma with intraperitoneal and renal metastasis. Interestingly, a seminoma was also present in the descended testis of the draught horse.