Transmission of canine transmissible venereal tumour between two dogs in the UK.

Canine transmissible venereal tumour (CTVT) is a contagious cancer spread by transfer of living cancer cells. Occasional cases are observed in the UK in dogs imported from endemic regions. Here, we report a case of imported canine transmissible venereal tumour that was transmitted to a second dog within the UK. Transmission of genital canine transmissible venereal tumour occurred despite neutered status of the second dog. The aggressive course of disease in both cases, which included metastasis, resistance to therapeutic interventions and ultimate euthanasia of both dogs, is described. The diagnosis of canine transmissible venereal tumour was made using a combination of cytology, histology, immunohistochemistry and PCR to detect the LINE-MYC rearrangement. Practitioners unfamiliar with canine transmissible venereal tumour are reminded of this disease of concern, particularly when imported dogs are placed in multi-dog households, irrespective of neuter status.

Sex disparity in oronasal presentations of canine transmissible venereal tumour.

BACKGROUND: The canine transmissible venereal tumour (CTVT) is a contagious cancer spread by the direct transfer of living cancer cells. CTVT usually spreads during mating, manifesting as genital tumours. However, oronasal CTVT is also occasionally observed, and presumably arises through oronasal contact with genital CTVT tumours during sniffing and licking. METHODS: Given that sniffing and licking transmission behaviours may differ between sexes, we investigated whether oronasal CTVT shows sex disparity. RESULTS: Twenty-seven of 32 (84%) primary oronasal tumours in a CTVT tumour database occurred in males. In addition, 53 of 65 (82%) primary oronasal CTVT tumours reported in the published literature involved male hosts. These findings suggest that male dogs are at four to five times greater risk of developing primary oronasal CTVT than females. This disparity may be due to sex differences in licking and sniffing activity, perhaps also influenced by sex differences in CTVT accessibility for these behaviours. CONCLUSION: Although oronasal CTVT is rare, it should be considered as a possible diagnosis for oronasal tumours, particularly in male dogs.

Relationship between plasma cell-free DNA changes and lysyl oxidase during the treatment and prognosis of canine transmissible venereal tumors.

BACKGROUND: Transmissible venereal tumors (TVT) are a wide range of canine tumors for which there are no effective markers to monitor the therapeutic response in real-time. Circulating biomarkers can be valuable in early cancer diagnosis and prognosis. Accordingly, this study aimed to investigate the significance of the cell-free DNA (cfDNA) and cfDNA integrity index to monitor the response of TVTs to vincristine and compare them with lysyl oxidase activity. Plasma and sera were collected from fifteen male dogs within four weeks before drug administration. The analytical method was mainly based on the quantitative polymerase chain reaction (qPCR) technique for short and long cfDNAs and lysyl oxidase activity was measured in serum. RESULTS: The results of the cfDNA integrity index showed a significant (p < 0.05) difference in the baseline concentration compared to the second and third weeks (with cut-off values of 1.118 and 93.33% specificity). The cfDNA integrity index increased over time due to the reduction of short cfDNAs in the first week after treatment. Lysyl oxidase activity increased during the fourth week (p < 0.001), but there were no significant differences in the other weeks compared to the baseline. The ROC analysis of lysyl oxidase revealed high sensitivity (100%) and specificity (90%) on the second and third weeks compared to the baseline. Multivariate analysis between cfDNA integrity index and lysyl oxidase showed significant correlation (p < 0.05) only in baseline results. CONCLUSIONS: Overall, short cfDNA, the cfDNA integrity index, and lysyl oxidase activity can be proposed as diagnostic biomarkers and putative prognostic candidates in TVT patients. These biomarkers can be combined with cytology to quickly diagnose TVT.

Rhinoscopic Appearance and Clinical Features of a Nasal Transmissible Venereal Tumor in a Dog.

A 2-year-old male neutered mixed breed dog was referred for evaluation of left-sided unilateral epistaxis and mucoid discharge following adoption from Mexico 2 months prior to presentation. Computed tomography (CT) showed soft tissue that filled the entirety of the left nasal passage with mild turbinate loss. Subsequent rhinoscopy revealed multifocal patches of discrete, white, wispy, vascularized abnormal tissue in the left nasal cavity. Cytology and histopathology procured with rhinoscopic-guidance were suspicious for transmissible venereal tumor (TVT). Confirmation of a TVT diagnosis was made with polymerase chain reaction for the long interspersed element inserted upstream of the c-myc gene. The dog was treated with 4 cycles of vincristine (0.5 mg/m2, IV, once every 7 days) with complete and sustained resolution of clinical signs shortly after the third cycle. Nasal TVT in dogs is an uncommon presentation of a neoplasm that primarily results in genital or oral lesions. There is a void in the veterinary literature regarding the rhinoscopic appearance, as well as limited clinical descriptions of nasal TVT. Therefore, the objectives of this report were to provide a detailed description of the rhinoscopic appearance of a canine nasal TVT, in addition to clinical features, diagnostic findings, CT imaging, and successful therapeutic management.

Nasal transmissible venereal tumours in 12 dogs - a retrospective study.

OBJECTIVE: The aim of this study was a retrospective analysis of clinical manifestation and treatment outcome of the nasal form of transmissible venereal tumours (TVT). MATERIAL AND METHODS: Twelve dogs suffering from nasal TVT were included in this study. Patients with primary genital lesions were excluded from the study. Signalment, physical examination and laboratory findings, results of further diagnostics, and treatment results were recorded in all patients. RESULTS: The study population comprised 9 male and 4 female dogs with an (estimated) age ranging from 3 to 7 years. With one exception all dogs originated from Ukraine. Symptoms of nasal TVT included sneezing, nasal bleeding (all cases), skull infiltration (9 cases), oronasal fistulas (9 cases) and cutaneous fistulas (5 cases). Animals received vincristine sulfate at 0.7 mg/m2 i. v. weekly. The treatment course consisted of 4-9 cycles (median 5 cycles). Complete remission was achieved in all cases. All dogs were disease-free during the follow-up period (median 23.5 months, range 12-56 months). All patients tolerated the treatment very well. CLINICAL SIGNIFICANCE: In conclusion, our data suggest that nasal TVT can have a good response to vincristine treatment. TVT should be considered as a differential diagnosis in sneezing dogs with nasal discharge or bleeding especially in young dogs and in dogs with suspected nasal tumours, even in countries without a stray animal population.

Diagnosis and Management of an Oronasal Fistula Secondary to Nasal Transmissible Venereal Tumor in a Dog.

Canine transmissible venereal tumor (CTVT) is a contagious tumor commonly seen in populations of sexually intact dogs that have close contact with each other. CTVT is one of only 3 known naturally transmissible, contagious tumors in which the mutated tumor cell is thought to have originated in an individual canid about 11000 years ago. Clinical history, signalment, cytological and histologic evaluation are typically sufficient for reaching a diagnosis, although immunohistochemistry(IHC) may be necessary for unique presentations of this neoplasm. This case report describes the diagnosis of an oronasal CTVT using histopathology and IHC, followed by treatment of the tumor with chemotherapy and surgical correction of a defect caused by the tumor.

Canine transmissible venereal tumor: First report of three clinical cases from Tripoli, Libya.

Canine transmissible venereal tumour (CTVT) is frequently reported in dogs and is responsible for high morbidity rates and economic losses. Three clinical cases were presented at the clinic of the Faculty of Veterinary Medicine, University of Tripoli. One male and two female German shepherds were diagnosed with CTVT based on case history and tumor shape. The diagnosis was confirmed by histopathological examination. The dogs were treated with vincristine intravenously at a dose of 0.025 mg/kg and recovered fully within 4 weeks. All three dogs remained alive with no evidence of recurrence. These first cases of CTVT reported from Libya show the importance of combining case history, clinical examination and laboratory confirmation to arrive at a definitive diagnosis and implement effective therapy.

Detection of progressive and regressive phase and LINE-1 retrotransposon in transfected dogs with transmissible venereal tumor during chemotherapy.

Canine transmissible venereal tumor (CTVT) is a tumor that commonly occurs in genital and extragenital sites of both genders. Long interspersed nuclear elements (LINE-1) retrotransposon has a pivotal role in allogenic transfection among uncontrolled dog populations. This study aimed to perform pathomorphological, immunohistochemical, and in situ polymerase chain reaction (PCR) evaluation of CTVT (n = 18) in transfected dogs during chemotherapy. Immunohistochemically, tumor phases were investigated by using specific markers (CD3, CD4, CD8, CD79, and transforming growth factor beta [TGF-ß]), and investigated an amplified specific sequence of TVT LINE-1 retrotransposon by in situ PCR. Polyhedral-shaped neoplastic cells that had large, round, hypo/hyperchromatic nuclei and eosinophilic cytoplasm were detected. All marker results were positive, especially in the early weeks of recovery. CD4 and TGF-ß markers were conspicuously positive at the initial stage. In situ PCR LINE-1 sequence was initially positive in only four cases. It is believed that the CD and TGF-ß markers provide phase identification at tumor initiation and during chemotherapy. It is thought that presence of T and B lymphocytes, which have roles in cellular and humoral immunity, is needed so that regression of the tumor is possible.

Evaluation of a genetic assay for canine transmissible venereal tumour diagnosis in Brazil.

The canine transmissible venereal tumour (CTVT) is a transmissible cancer that is spread between dogs by the allogeneic transfer of living cancer cells. The infectious agents in CTVT are the living cancer cells themselves, which are transmitted between dogs during coitus. CTVT first arose several thousand years ago and the disease has a global distribution and is frequently observed in dogs from Brazil. We evaluated the utility of a LINE-MYC quantitative polymerase chain reaction for diagnosis of CTVT cases in Brazil. Our analysis indicated that the LINE-MYC rearrangement was detectable in all CTVT samples but not in their corresponding hosts. This genetic assay proves to be a useful tool for providing a definitive molecular diagnosis of CTVT, which presents with varying degrees of aggressiveness and invasiveness in different host dogs and can therefore be a diagnostic challenge in some specific cases.

Insertion of the LINE-1 element in the C-MYC gene and immunoreactivity of C-MYC, p53, p21 and p27 proteins in different morphological patterns of the canine TVT / Inserção do elemento LINE - 1 no gene C-MYC e imunorreatividade das proteinas C-MYC, p53, p21 e p27 nos diferentes padrões morfológicos do tumor TVT

The canine transmissible venereal tumor (TVT) affects the external genitalia of dogs by the natural transplant of viable tumor cells. Thus, this research aimed to diagnose and characterize TVT morphological patterns, identify the insertion of the LINE-1 element in C-MYC gene, by means of the polymerase chain reaction (PCR), and evaluate the immunohistochemical expression of C-MYC, p53, p21 and p27 proteins. The relationship between C-MYC and p53 proteins and their interference on the expression of p21 and p27 were also studied. For that, 20 samples of naturally occurring TVT were used, subjected to cytopathological, histopathological and immunohistochemical analysis, and to molecular diagnosis of neoplasia. The increased tissue expression and the correlation among C-MYC, p53, p21 and p27 proteins indicate reduction and/or loss of their functionality in the TVT microenvironment, with consequent apoptotic suppression, maintenance of cell growth and progression of neoplasia.(AU)

O tumor venéreo transmissível canino (TVT) afeta a genitália externa de cães pelo transplante natural de células tumorais viáveis. Assim, esta pesquisa teve como objetivo diagnosticar e caracterizar TVT em padrões morfológicos, identificar a inserção do elemento LINE-1 em gene C-MYC, por meio da reação em cadeia da polimerase (PCR), e avaliar a expressão imuno-histoquímica do C-MYC, p53, p21 e p27. A relação entre C-MYC e as proteínas p53 e a sua interferência na expressão de p21 e p27 foram também estudadas. Para isso, foram utilizadas 20 amostras de ocorrência natural de TVT, submetido a exame citopatológico, histopatológica e imuno-histoquímica e ao diagnóstico molecular de neoplasia. A expressão aumentada do tecido e a correlação entre a C-MYC e as proteínas p53, p21 e p27 indicam redução e/ou perda de funcionalidade na TVT em seu microambiente, com consequente supressão apoptótica, manutenção do crescimento celular e progressão da neoplasia.(AU)

Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis.

Canine transmissible venereal tumor (CTVT) is the only naturally contagious tumor that is transmitted during coitus or social behaviors. Based on the tumor's location, the diagnosis of genital TVT (GTVT) is comparably easier than those in the extragenital area (ETVT) that are more easily incorrectly diagnosed. Fortunately, CTVT cells contain a specific long interspersed nuclear elements (LINE), inserted upstream of the myc gene, allowing a diagnostic polymerase chain reaction (PCR) based detection assay. The objectives of this study were aimed to improve the diagnostic accuracy by applying the diagnostic LINE1-c-myc PCR assay and fine needle aspiration (FNA) collection in direct comparison with standard cytological and histopathological analyses. Seventy-four dogs, comprised of 41 and 31 dogs with tumor masses at their external genitalia and extragenital areas (e.g. skin and nasal cavity), respectively, were included in this study. The signalment of these 65 dogs and clinical history of 20 client-owned dogs were collected. Samples were taken by biopsy for both histopathological examination and FNA for cytological examination and diagnostic PCR. The PCR products from 10 apparently CTVT samples were purified and sequenced. Sixty-one CTVT cases were diagnosed by cytological and histological analyses, but 65 were positive by the PCR assay. Overall, the PCR assay improved the accuracy of diagnostic CTVT results, especially for the more difficult ETVT tumors. Moreover, this PCR-based approach can facilitate the decision as to discontinue chemotherapy by discrimination between residual tumor cell masses and fibrotic tissue.

Canine transmissible venereal tumour: a review.

Canine transmissible venereal tumour (CTVT) is a contagious venereal tumour of dogs, commonly observed in dogs that are in close contact with one another, or in stray and wild dogs that exhibit unrestrained sexual activity. CTVT represents a unique, naturally transmissible, contagious tumour, where the mutated tumour cell itself is the causative agent and perpetuates as a parasitic allograft in the host. Clinical history, signalment and cytological features are often obvious for establishing a diagnosis though biopsy and histological examination may be needed in atypical cases. Most cases are curable with three intravenous injections of vincristine sulphate at weekly intervals. The role of stray and wild dogs makes the disease difficult to control and necessitates sustained animal birth control in stray dogs along with prompt therapy of the affected dogs. This review captures the manifold developments in different areas embracing this fascinating tumour, including its biology, diagnosis and therapeutic alternatives.

Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor.

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.

Immunohistochemical study of genital and extragenital forms of canine transmissible venereal tumor in Brazil / Estudo imuno-histoquímico de formas genitais e extragenitais do tumor venéreo transmissível canino no Brasil

Aiming to provide insight and discussing the problems related to the diagnosis and differential diagnosis of canine transmissible venereal tumor (CTVT), especially in its extragenital form, immunohistochemical evaluation was performed and a comparison was established by analysis of the microscopic appearance of 10 genital CTVTs and 13 exclusively extragenital CTVTs previously diagnosed by cytology and histopathology. CTVTs samples were incubated with biotinylated antibodies raised against specific membrane (anti-macrophage) and cytoplasmic antigens (anti-lysozyme, anti-S-100 protein, anti-vimentin and anti-CD18) and subsequently developed using streptavidin-biotin peroxidase and streptavidin-biotin-alkaline phosphatase methods. A strong reactivity with the anti-vimentin antibody was found in 100% of the tumors tested (22/22). No reactivity was found for the anti-lysozyme, anti-macrophage, anti-S-100 protein and anti-CD18. No histopathological or immunoreactivity differences between genital and extragenital CTVTs were found. These findings do not corroborate the hypothesis of histiocytic origin of CTVT (no reactivity to anti-lysozyme, anti-macrophage and anti-CD 18 antibodies). In addition, the antibody panel used is useful to narrow the differential diagnosis for lymphomas, histiocytic tumors, amelanotic melanomas, and poorly differentiated epithelial neoplasias, among others.

Com a finalidade de fornecer subsídios e discutir os problemas referentes ao diagnóstico e ao diagnóstico diferencial do tumor venéreo transmissível canino (TVTC), principalmente em sua forma extragenital, foi realizada a avaliação imuno-histoquímica e estabelecido termo de comparação com o aspecto microscópico em 10 TVTCs genitais e em 13 exclusivamente extragenitais previamente diagnosticados através de citologia e histopatologia. Os TVTCs foram testados para reagentes específicos de antígenos de membrana (anti-macrófago) e citoplasmáticos (anti-lisozima, anti-proteína S-100, anti-alfa-1-antitripsina, anti-vimentina e anti-CD18) com a utilização da técnica complexo avidina-biotina-peroxidase e estreptavidina-biotina-fosfatase Em 100% dos tumores testados (22/22) com anticorpo anti-vimentina houve forte imuno-reatividade. Não houve reatividade para os anticorpos anti-lisozima, anti-macrófago, anti-proteína S-100 e anti-CD18. Não houve diferença histopatológica e de imuno-reatividade entre os TVTCs genitais e extragenitais. Estes achados indicam que os TVTCs avaliados não são de origem histiocítica (ausência de reatividade dos anticorpos anti-lisozima, anti-macrófago e anti-CD18). O painel de anticorpos utilizado é útil para o diagnóstico diferencial deste tumor com linfomas, tumores histiocíticos, melanomas amelanóticos e neoplasias de origem epitelial pobremente diferenciadas, entre outros.

A case of ocular canine transmissible venereal tumor.

A 1-year-old, intact female mixed-breed dog was presented to St. George's University Small Animal Clinic in Grenada for a third eyelid mass. The dog was diagnosed with a rare ocular transmissible venereal tumor (TVT) and concurrent anaplasmosis, ehrlichiosis and dirofilariasis. Treatment with vincristine sulfate resulted in complete resolution of the TVT.

Cas de tumeur vénérienne canine oculaire transmissible. Une chienne de race croisée intacte âgée de 1 an a été présentée à la clinique pour petits animaux de l'Université St. George de la Grenade pour une masse de la troisième paupière. La chienne a été diagnostiquée avec une rare tumeur vénérienne oculaire transmissible (TVT) et l'anaplasmose, l'ehrlichiose et la dirofilariose concomitantes. Le traitement au sulfate de vincristine a produit une résolution complète de la TVT.(Traduit par Isabelle Vallières).

Progress in Fourier transform infrared spectroscopic imaging applied to venereal cancer diagnosis.

Fourier transform infrared imaging spectroscopy is a powerful technique that provides molecular and spatial information at the single-cell level. We report on the progress of this technology in the field of cancer research, focusing on human cervical cancer because of the inherent difficulty in grading this type of cancer and as a model for venereal cancers in dogs. Using a suite of multivariate imaging processing techniques, we demonstrate the potential of this technique to identify histologic features in the normal epithelium and cervical intraepithelial neoplasia stages I and III. We highlight the advantages and detail the barriers that need to be overcome before implementation of this technology in the clinical environment.