Cutaneous transmissible venereal tumor without genital involvement in a prepubertal female dog

An 11-month-old prepubertal crossbreed female dog was presented with multiple nodular lesions disseminated over the cervical, back, flank, and abdominal regions. The lesions were ulcerated and cauliflowerlike, or nodular and subcutaneous, measuring up to 13 cm in diameter. Cytologic preparations of one of the lesions revealed a uniform population of round to oval cells, with lightly basophilic cytoplasm that contained multiple distinct vacuoles. Frequent mitotic figures and occasional lymphocytes were also observed. The cytologic diagnosis was cutaneous transmissible venereal tumor (TVT) in a progressing growth phase. This was confirmed by histologic and immunohistochemical findings. Vaginal TVT was diagnosed later in the dog's mother. TVT is a contagious neoplasm of sexually mature dogs that usually is transmitted by coitus and affects the genital mucosa. To our knowledge, this is the first report of naturally occurring multicentric TVT in a prepubertal female dog and also is unique in its exclusively cutaneous (no mucosal) involvement. We speculate that transmission of neoplastic cells occurred during cohabitation and social/mothering behavior between the dogs. Despite the atypical clinical presentation, response to chemotherapy with vincristine was excellent, leading to complete regression of the neoplasm without relapse after 6 months.     

Ocular involvement of transmissible venereal tumor in a dog

A case of metastatic transmissible venereal tumor (TVT), with lesions on the penis, conjunctiva, buccal mucosa and skin (lips and trunk), is presented in this case report. The clinical picture is described along with the cytological and histopathological features of the tumor leading to definitive diagnosis of TVT. Possible reasons for the unusual metastatic behavior of TVT and full recovery of the dog after chemotherapy are discussed.     

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.     

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.     

Extragenital transmissible venereal tumour associated with circulating neoplastic cells in an immunologically compromised dog

An adult male intact boxer was presented because of diffuse cutaneous nodules. Fine‐needle aspirate revealed transmissible venereal tumour (TVT) cells. Neoplastic cells were also observed in the peripheral blood. Associated simultaneous diseases included leishmaniosis, demodicosis, papillomatosis and coccidiosis. Immunosuppression may have aggravated disease and triggered widespread metastases. The dog was hospitalized and administered oral amoxicillin/clavulanate, subcutaneous meglumine antimonite to treat leishmaniosis and oral chlortetracycline to treat coccidiosis. Intravenous injection of vincristine at weekly interval was used to treat TVT. A rapid regression of cutaneous nodules was noted; however, intractable diarrhoea developed, eventually leading to death after 18 days. This is the first report describing an unusual case of extragenital TVT associated with circulating neoplastic cells in an immunosuppressed dog presenting with multiple cutaneous nodules.     

ORTHOVOLTAGE RADIOTHERAPY OF CANINE TRANSMISSIBLE VENEREAL TUMORS

Eighteen dogs with transmissible venereal tumors were treated with orthovoltage radiotherapy. Total radiation doses ranged from 10 to 30 Gy, given during periods of one to 34 days. Tumor cure, defined as lack of recurrence within one year after completion of radiotherapy, was observed in all 18 dogs. In seven of eight dogs, tumors were cured with a single dose of 10 Gy. The tumor that recurred after the single 10 Gy dose had been treated with chemotherapy prior to radiotherapy and was subsequently cured with additional radiotherapy. Data presented indicate that transmissible venereal tumors are radiocurable and that a single dose of 10 Gy is sufficient for cure in most dogs.     

Nasal and oral masses in a dog

A 5-year-old, intact male, stray dog was presented in poor body condition, with pallor, muzzle deformity, multiple oozing fistulas with grass awns, bilateral sanguinopurulent nasal discharge and a fleshy friable mass occupying part of the hard palate. A friable mass occupying both nasal cavities was found on rhinoscopy. The dog had moderate nonregenerative normochromic-microcytic anemia, thrombocytopenia, hyperglobulinemia, and hypoalbuminemia. Cytologic preparations of the nasal and oral masses contained a neoplastic population of round cells with intracytoplasmic and extracellular vacuoles. Leishmania amastigotes also were observed, in the cytoplasm of macrophages and, occasionally, within neoplastic cells. A diagnosis of transmissible venereal tumor and concurrent leishmaniosis was made. Treatment with vincristine and allopurinol resulted in complete resolution of clinical signs and disappearance of the masses. The presence of amastigotes in neoplastic TVT cells may suggest an alternative mode of transmission of canine leishmaniosis where these diseases co-exist.     

Comparative immunohistochemical characterization of canine seminomas and Sertoli cell tumors

Primary testicular tumors are the most common causes of cancer in male dogs. Overall, the majority of canine patients should be cured by testicular surgery. However, tumor markers are not well-known in veterinary medicine. We sought to determine using immunohistochemistry whether the combined human testicular tumor markers (placental alkaline phosphatase, OCT3/4, CD30, alpha-fetoprotein, inhibin-alpha, vimentin, c-KIT, and desmin) are expressed in canine seminomas and Sertoli cell tumors (SCTs). We examined 35 canine testicular tumors, 20 seminomas and 15 SCTs. c-KIT was expressed markedly in canine seminomas. Both inhibin-alpha and vimentin were expressed significantly in canine SCTs. The results of this study demonstrate differences and similarities between tumor marker expression of testicular tumors in dogs and humans. All the main markers in current routine use are discussed as well as potential useful markers for benign and malignant tumors, and tumor progression.     

Immunohistochemical study of autophagy associated molecules and cell adhesion molecules in canine intracranial granular cell tumors

Granular cell tumors (GCTs) are characterized by abundant eosinophilic cytoplasmic granules. Based on the hypothesis that canine intracranial GCT is a subtype of meningioma and its cytoplasmic granules are formed through autophagy processes, histopathological and immunohistochemical examination were performed on biopsy samples from 7 cases of canine intracranial GCTs and 15 cases of conventional meningiomas. Histopathologically, 7/7 cases of GCTs involved the meninges; foci of meningothelial-like cells were observed in 3/7 cases; brain invasion was observed in 2/7 cases. Immunohistochemically, neoplastic cells of GCTs were positive for E-cadherin and negative for S100, cytokeratin, CD204, and β-catenin in 7/7 cases. Neoplastic cells of 15/15 cases of meningiomas were positive for E-cadherin, and negative for S100 and CD204. Immunoreactivity of meningiomas for cytokeratin and β-catenin was observed in 6/15 cases and 8/15 cases, respectively. Cytoplasmic granules of GCTs were positive for ubiquitin (5/7), p62 (5/7), and LC3 (7/7). Compared to GCTs, the ratios of ubiquitin (6/15) and p62 (3/15) positive cases were lower in meningiomas, and 15/15 cases were negative for LC3. These findings indicate that the biological natures of GCTs including anatomical location, histopathological features and immunoreactivity for E-cadherin are almost in conformity with those of meningiomas. The immunoreactivity for autophagy associated molecules may suggest the possible involvement of autophagy in cytoplasmic granule formation of canine intracranial GCTs.     

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.     

Clinico-pathological studies on the effect of different anti-neoplastic chemotherapy regimens on transmissible venereal tumours in dogs

Thirty-two dogs affected with transmissible veneral tumour (TVT) were divided into three treatment groups. In group I vincristine sulphate at 0.025 mg/kg body weight, in group II vinblastine sulphate at 0.150 mg/kg body weight, and in group III vinblastine sulphate at 0.100 mg/kg body weight plus methotrexate at 0.35 mg/kg body weight were given intravenously at weekly intervals. Biopsies were performed on days 0, 3, 7 and 14. The tissues were preserved in 10% neutral buffered formalin and processed routinely for haematoxylin and eosin staining. Histopathologically, the untreated TVT was characterized by sheets or bundles of mostly rounded cells having a large, highly basophilic nucleus with a prominent, highly basophilic nucleolus. Both vincristine and vinblastine primarily affected the nuclei of neoplastic cells, causing condensation, karyorrhexis and karyolysis within 3 days of chemotherapy. The regressing tumour mass showed marked infiltration by lymphocytes, lymphoblasts and macrophages by day 7. There was nearly complete regression of the tumour by day 14, as shown by the almost complete loss of neoplastic cells, with fibrous tissue substitution. However, in group III, the changes occurred more slowly and more injections were needed for complete regression. In both groups I and II, 11/12 of the animals responded completely to the chemotherapy within 3 weeks, while in group III, 6/8 of the dogs responded to the treatment by 21–28 days.Abbreviations SD standard deviation - TVT transmissible venereal tumour     

Risk factors and characteristics of canine transmissible venereal tumours in Grenada, West Indies

We studied risk factors and characteristics of canine transmissible venereal tumours (TVTs) in Grenada. We abstracted data for 38 TVT cases and 114 TVT-free dogs submitted to a veterinary diagnostic laboratory between 2003 and 2006. Occurrence profiles, odds ratios (ORs), and logistic regression models for TVT were determined using a significance level of α = 0.05. TVT was found in 20 (52.6%) female and 18 (47.4%) male dogs. Of the TVT cases, 32 (84.2%) were between 1 and 7 years old, 20 (52.6%) were mixed breeds of dogs, 14 (36.8%) were Grenadian pothounds, while 4 (10.6%) were pure-bred dogs. Characteristic TVT lesions were genital growths [OR = 96.7; 95% CI (27,461), P < 0.001], genital bleeding [OR = 12.7; 95% CI (4.6, 39.2), P < 0.001] and secondary inflammation of TVT lesion [OR = 4.3; 95% CI (2, 10), P < 0.001]. Extragenital TVT lesions were observed in 23% (9/38) of dogs. An increased risk for TVT was associated with age as adult (1–7 years) dogs [OR = 12; 95% CI (1.6, 94), P < 0.001] and status as a Grenadian pothound [OR = 8.6; 95% CI (3, 25), P < 0.001]. Clinicians should educate dog owners about increased risk of TVT for Grenadian pothounds and consider TVT as a possibility for some extragenital tumours.     

Use of a murine xenograft model for canine transmissible venereal tumor

OBJECTIVE: To develop a murine model for canine transmissible venereal tumor (CTVT). ANIMALS: Thirty-three 6-week-old NOD/LtSz-scid (NOD/SCID) mice and seven 6-week-old C57BL/6J mice. PROCEDURE: Samples of CTVT were excised from a 3-year-old dog and inoculated SC into ten 6-week-old NOD/SCID mice to induce growth of xenograft transmissible venereal tumor (XTVT). To establish mouse-to-mouse transmission, samples of XTVT were removed and inoculated SC into 4 groups of 6-week-old NOD/SCID mice and into a control group. Samples of CTVT were also inoculated into immunocompetent C57BL/6J mice for a mouse antibody production (MAP) test. The canine and xenografted tumors were evaluated cytologically and histologically, and polymerase chain reaction was performed for detection of the rearranged LINE/c-MYC junction. RESULTS: 8 of 10 NOD/SCID mice that were inoculated with CTVT developed tumors 3 to 10 weeks after inoculation. In the second-generation xenograft, all mice developed tumors by postinoculation day 47; 1 X 10(6) of XTVT cells were enough to create a xenograft. Metastases developed in 4 of 20 mice. Xenografted and metastatic tumors retained cytologic, histologic, and molecular characteristics of CTVT. Results of the MAP test were negative for all pathogens. CONCLUSION: We established an NOD/SCID murine model for XTVT and metastasis of CTVT. This model should facilitate study of tumor transplantation, progression, and metastasis and should decrease or eliminate the need for maintaining allogenic transfer in dogs.     

The distribution of C-bands in canine transmissible venereal tumor cells

Colchicine-arrested metaphase preparations, derived from canine transmissible venereal tumor (TVT) cells grown in culture, were characterized based on the occurrence and distribution of constitutive heterochromatin. Analysis of the data with regard to the distribution of C-bands in the pericentric, interstitial and telomeric segments revealed a nonrandom distribution along the arms of many chromosomes with the bulk of the bands occurring in the centromeric region. The frequency of C-banded regions differed from those reported for normal dog cells and both primary and transplanted tumors. These results suggest that similar nondifferentially-stained TVT karyotypes do not necessarily exhibit identical distribution of constitutive heterochromatin.     

Immunohistochemical study of a granular cell tumor on the tongue of a dog

Abstract: A granular cell tumor (GCT; myoblastoma) was diagnosed on the tongue of a 12-year-old English Pointer with clinical signs of mild oral dysphagia. The diagnosis was confirmed by histopathologic examination and immunohistochemistry. The tumor was positive for S-100 protein, but also was positive for desmin, and was only weakly positive for PAS, which is unusual for GCTs. An epithelioid type of leiomyoma (leiomyo-blastoma) was considered less likely on the basis of negative staining for smooth muscle actin. Treatment consisted of surgical resection of the tumor. The animal was in excellent clinical condition 1 year after surgery. Although GCT of the tongue has been reported previously in the dog, determining the cell of origin is still problematic. Immunohistochemistry is helpful for histogenetic classification and necessary for differentiation from leiomyoblastoma.     

Immunohistochemical characterization of a malignant intraocular teratoid medulloepithelioma in a cockatiel

A 3-year-old cockatiel was presented for evaluation of a buphthalmic right eye (OD). The history included a traumatic event 5 months prior to presentation, and the referring veterinarian diagnosed cataract and secondary glaucoma. Computed tomography of the bird's orbital region revealed a large right orbital soft tissue mass that extended lateral to the orbital rim with obliteration of the globe without bone involvement. There was also no evidence of metastatic disease within the lungs or any abnormalities within the celomic cavity, therefore enucleation was recommended to achieve a histopathologic diagnosis and prognosis, and to palliate the clinical signs. Final diagnosis was malignant intraocular teratoid medulloepithelioma.     

Cytologic and immunohistochemical characterization of a primitive neuroectodermal tumor in the brain of a dog

A 6-year-old intact female Pointer dog was presented for evaluation of acute onset of ataxia, circling, and head tilt. Neurologic assessment revealed overall decreased postural reaction, left-sided hemiparesis with incoordination, rigidity of fore- and hindlimbs, strabismus of the right eye, and bilateral horizontal nystagmus. Using magnetic resonance imaging, a mass lesion was identified in the cerebrum adjacent to the left side of the cerebellum compressing the brain stem ventrally. The mass was incompletely resected, and during surgery fine-needle aspiration and biopsy of the mass were performed. Cytologically, smears were highly cellular and contained predominantly small to medium-sized discrete round cells with high nuclear to cytoplasmic ratios and round nuclei with rare deep clefts or indentation, smooth chromatin, and indistinct nucleoli. Numerous cytoplasmic fragments were noted in the background. The primary diagnosis was lymphoma; other differential diagnoses included neuroendocrine tumor and poorly differentiated tumor of neural origin. The histologic diagnosis was lymphoma, and the lesion was presumed to be metastatic. On immunohistochemical analysis, the cells expressed neither CD3 nor CD79a. Re-examination of the histologic section revealed disorganized sheets of cells with multifocal palisading and perivascular arrangements of rosette-like structures. An expanded panel of antibodies to vimentin, cytokeratin, glial fibrillary acid protein (GFAP), neuron-specific enolase (NSE), synaptophysin (SYN), S-100, and CD45 was applied to histologic sections. Neoplastic cells were immunoreactive for vimentin, NSE, and S-100. Based on the histologic appearance and immunophenotype of the tumor, a diagnosis of primitive neuroectodermal tumor (PNET) was made. PNET, although rare in dogs, should be considered as a differential diagnosis for round cell tumors in the brain.