• View in gallery

    Photograph of an 8-year-old sexually intact Maltese dog with a 3-cm-diameter, semi-firm, bright-red, ulcerated mass affecting almost the entire left side of the vulva.

  • View in gallery

    Photomicrographs of a fine-needle aspirate from the mass (A) and histologic sections of the mass (B–D). A—The fine-needle aspirate consisted of large numbers of round neoplastic cells with an eccentric nucleus, coarsely stippled chromatin, a conspicuous nucleolus, and discrete intracytoplasmic vacuoles. Anisokaryosis was mild to moderate, and binucleated cells were occasionally seen (arrowhead). A few scant, degenerated RBCs and inflammatory cells were also present. Romanowski stain; bar = 5 µm. B—On histologic examination, round neoplastic cells were arranged in sheets and supported by a delicate fibrovascular stroma. Neoplastic cells had dense chromatin, a single nucleolus, and a moderate amount of eosinophilic, slightly granular cytoplasm. A few lymphocytes and neutrophils had infiltrated the neoplasm. H&E stain; bar = 20 µm. Neoplastic cells had strong cytoplasmic immunoreactivity to lysozyme (C) and CD45 (D). H&E stain; bar = 10 µm.

  • 1.

    Cohen D. The canine transmissible venereal tumor: a unique result of tumor progression. Adv Cancer Res. 1985;43:75112.

  • 2.

    Flórez LMM, Ballestero HF, Duzanski AP, et al. Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor. Pesqui Vet Bras. 2016;36:844850.

    • Search Google Scholar
    • Export Citation
  • 3.

    Abeka YT. Review on canine transmissible venereal tumor (CTVT). Cancer Ther Oncol Int J. 2019;14:19.

  • 4.

    Pye RJ, Woods GM, Kreiss A. Devil facial tumor disease. Vet Pathol. 2016;53:726736.

    • Crossref
    • Export Citation
  • 5.

    Hill DL, Yang TJ, Wachtel A. Canine transmissible venereal sarcoma: tumor cell and infiltrating leukocyte ultrastructure at different growth stages. Vet Pathol. 1984;21:3945.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Rogers KS. Transmissible venereal tumor. Compend Contin Educ Pract Vet. 1997;19:10361045.

  • 7.

    Stubbs EL, Furth J. Experimental Studies on venereal sarcoma of the dog. Am J Pathol. 1934;10:275286.

  • 8.

    Ballestero Fêo H, Montoya Flórez L, Yamatogi RS, et al. Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs? Vet Comp Oncol. 2018;16:370378.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Santos Do Amaral A, Bassani-Silva S, Ferreira I, et al. Cytomorphological characterization of transmissible canine venereal tumor. Rev Port Ciênc Vet. 2007;102:253260.

    • Search Google Scholar
    • Export Citation
  • 10.

    Meinkoth JH, Cowell RL. Recognition of basic cell types and criteria of malignancy. Vet Clin North Am Small Anim Pract. 2002;32:12091235.

    • Search Google Scholar
    • Export Citation
  • 11.

    Lima CRO, Rabelo RE, Vulcani VAS, et al. Morphological patterns and malignancy criteria of transmissible venereal tumor in cytopathological and histopathological exams. Braz J Vet Res Anim Sci. 2013;50:238246.

    • Search Google Scholar
    • Export Citation
  • 12.

    Park MS, Kim Y, Kang MS, et al. Disseminated transmissible venereal tumor in a dog. J Vet Diagn Invest. 2006;18:130133.

  • 13.

    Ferreira AJ, Jaggy A, Varejäo AP, et al. Brain and ocular metastases from a transmissible venereal tumour in a dog. J Small Anim Pract. 2000;41:165168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ganguly B, Das U, Das AK. Canine transmissible venereal tumour: a review. Vet Comp Oncol. 2016;14:112.

  • 15.

    Strakova A, Murchison EP. The changing global distribution and prevalence of canine transmissible venereal tumour. BMC Vet Res. 2014;10:168.

  • 16.

    Gaspar LFJ, Ferreira I, Colodel MM, Brandão CVS, Rocha NS. Spontaneous canine transmissible venereal tumor: Cell morphology and influence on P-glycoprotein expression. Turk J Vet Anim Sci. 2011;34:447454.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Alzate JM, Montoya-Florez LM, Pérez JE, Rocha NS, Pedraza-Ordonez FJ. The role of the multi-drug resistance 1, p53, b cell lymphoma 2, and bcl 2-associated X genes in the biologic behavior and chemotherapeutic resistance of canine transmissible venereal tumors. Vet Clin Pathol. 2019;48:730739.

    • Search Google Scholar
    • Export Citation
  • 18.

    Mukaratirwa S, Gruys E. Canine transmissible venereal tumour: cytogenetic origin, immunophenotype, and immunobiology: a review. Vet Q. 2003;25:101111.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Yadav A, Kumar P, Panihar S, et al. Clinico-histopathological studies in canine transmissible venereal tumour. Int J Curr Microbiol Appl Sci. 2018;7:27142719.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Hsiao YW, Liao KW, Hung SW, Chu RM. Effect of tumor infiltrating lymphocytes on the expression of MHC molecules in canine transmissible venereal tumor cells. Vet Immunol Immunopathol. 2002;87:1927.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Yang TJ, Chandler JP, Dunne-Anway S. Growth stage dependent expression of MHC antigens on the canine transmissible venereal sarcoma. Br J Cancer. 1987;55:131134.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Frampton D, Schwenzer H, Marino G, et al. Molecular signatures of regression of the canine transmissible venereal tumor. Cancer Cell. 2018;33:620633.e6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Duncan JR, Prasse KW. Cytology of canine cutaneous round cell tumors. Vet Pathol. 1979;16:673679.

  • 24.

    Marchal T, Chabanne L, Kaplanski C, Rigal D, Magnol JP. Immunophenotype of the canine transmissible venereal tumour. Vet Immunol Immunopathol. 1997;57:111.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Murray M, Helen ZJ, Martin W. A study of the cytology and karyotype of the canine transmissible venereal tumour. Res Vet Sci. 1969;10:565568.

    • Search Google Scholar
    • Export Citation
  • 26.

    Setthawongsin C, Techangamsuwan S, Tangkawattana S, Rungsipipat A. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis. J Vet Med Sci. 2016;78:11671173.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Fonseca LS, Mota LSLS, Colodel MM, Ferreira I, Brandão CVS, Rocha NS, et al. Spontaneous canine transmissible venereal tumor: association between different phenotypes and the insertion LINE-1/c-myc. Rev Colomb Cienc Pecu. 2012;25:402408.

    • Search Google Scholar
    • Export Citation
  • 28.

    Kabuusu RM, Stroup DF, Fernandez C. Risk factors and characteristics of canine transmissible venereal tumours in Grenada, West Indies. Vet Comp Oncol. 2010;8:5055.

    • Search Google Scholar
    • Export Citation
  • 29.

    McGrotty Y, Knottenbelt C. Significance of plasma protein abnormalities in dogs and cats. In Pract. 2002;24:512517.

  • 30.

    Nemec A, Drobnic-Kosorok M, Butinar J. The effect of high anticoagulant K3-EDTA concentration on complete blood count and white blood cell differential counts in healthy beagle dogs. Slov Vet Res. 2005;42:6570.

    • Search Google Scholar
    • Export Citation
  • 31.

    Amber EI, Henderson RA, Adeyanju JB, Gyang EO. Single-drug chemotherapy of canine transmissible venereal tumor with cyclophosphamide, methotrexate, or vincristine. J Vet Intern Med. 1990;4:144147.

    • Search Google Scholar
    • Export Citation
  • 32.

    Ramadinha RR, Teixeira RS, Bomfim PC, et al. Canine transmissible venereal tumor response to chemotherapy with vincristine sulfate and vinblastine. Braz J Vet Med. 2016;38:6569.

    • Search Google Scholar
    • Export Citation
  • 33.

    Decuadro A, Ruiz N, Menéndez C, et al. Lomustine therapy for vincristine-resistant canine transmissible venereal tumor: a case report. Rev Bras Med Vet. 2021;43:19.

    • Search Google Scholar
    • Export Citation

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Pathology in Practice

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  • 1 Department of Veterinary Clinic, Faculty of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu, Brazil
  • | 2 Department of Veterinary Surgery and Reproduction, Faculty of Veterinary Medicine and Animal Science, São Paulo State University, Botucatu, Brazil
  • | 3 Nucleus of Pathological Anatomy, Adolfo Lutz Institute, São Paulo, Brazil
  • | 4 Laboratory of Wildlife Comparative Pathology, Department of Pathology, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
  • | 5 Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC

Abstract

In collaboration with the American College of Veterinary Pathologists

History

An 8-year-old 3.6-kg sexually intact female Maltese dog was referred to the Veterinary Hospital of São Paulo State University with a 5-day history of a 3-cm-diameter, semi-firm, bright-red, ulcerated mass affecting almost the entire left side of the vulva (Figure 1). One month before the evaluation, the dog had had outdoor access. The dog had an up-to-date annual vaccination status, and no previous history of illness was reported. However, the dog had never received any anthelmintic treatments. A moderate number of ticks (Rhipicephalus sanguineus) was observed.

Figure 1
Figure 1

Photograph of an 8-year-old sexually intact Maltese dog with a 3-cm-diameter, semi-firm, bright-red, ulcerated mass affecting almost the entire left side of the vulva.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0253

Gross and Clinicopathologic Findings

A CBC revealed a slightly high mean corpuscular hemoglobin concentration (39.7%; reference interval, 32% to 36%). The results of a serum biochemistry profile were unremarkable except for a slightly high total protein concentration (10.2 g/dL; reference interval, 6.0 to 8.0 g/dL), mild hypoalbuminemia (2.0 g/dL; reference interval, 2.6 to 3.3 g/dL), and moderate hyperglobulinemia (8.20 g/dL; reference interval, 2.7 to 4.4 g/dL).

Formulate differential diagnoses, then continue reading.

Cytologic, Histopathologic, and Immunohistochemical Findings

Cytologic examination of a fine-needle aspirate of the vulvar mass revealed a mildly cellular sample infiltrated with large round cells containing a moderate amount of pale-blue cytoplasm with multiple coarse, clear vacuoles and an eccentric, hyperchromatic nucleus with a single prominent nucleolus (Figure 2). Anisokaryosis was mild to moderate, and binucleated cells were seen occasionally. The background had few neutrophils and lymphocytes.

Figure 2
Figure 2

Photomicrographs of a fine-needle aspirate from the mass (A) and histologic sections of the mass (B–D). A—The fine-needle aspirate consisted of large numbers of round neoplastic cells with an eccentric nucleus, coarsely stippled chromatin, a conspicuous nucleolus, and discrete intracytoplasmic vacuoles. Anisokaryosis was mild to moderate, and binucleated cells were occasionally seen (arrowhead). A few scant, degenerated RBCs and inflammatory cells were also present. Romanowski stain; bar = 5 µm. B—On histologic examination, round neoplastic cells were arranged in sheets and supported by a delicate fibrovascular stroma. Neoplastic cells had dense chromatin, a single nucleolus, and a moderate amount of eosinophilic, slightly granular cytoplasm. A few lymphocytes and neutrophils had infiltrated the neoplasm. H&E stain; bar = 20 µm. Neoplastic cells had strong cytoplasmic immunoreactivity to lysozyme (C) and CD45 (D). H&E stain; bar = 10 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.05.0253

Two punch biopsy specimens measuring approximately 0.5 cm in diameter were collected from the vulvar mass, fixed in neutral-buffered 10% formalin, and processed routinely for histologic examination. Histologically, the vulvar mass consisted of a round-cell neoplasm arranged in closely packed sheets supported by a delicate fibrovascular stroma. Neoplastic cells had distinct cell borders and moderate amounts of pale eosinophilic, finely granular to clear cytoplasm (Figure 2). The nuclei were round and large, with coarsely stippled chromatin and a single prominent nucleolus. Anisokaryosis and anisocytosis were mild to moderate. Ten mitotic figures were seen per 2.37 mm2. Neoplastic cells exhibited strong membranous immunoreactivity to lysozyme (polyclonal rabbit antihuman lysozyme, 1:1,000 dilution; Dako) and CD45 (clone CA12.10C12, 1:25 dilution; Dr. Peter Moore, University of California), and were negative for immunoreactivity to CD79α (clone HM47/A9, 1:50 dilution; Biocare Medical), MUM-1 (clone BC5, 1:50 dilution; Biocare Medical), and CD3 (polyclonal, 1:500 dilution; Dako).

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: vulvar transmissible venereal tumor (TVT) in a dog.

Comments

A diagnosis of TVT was made in this dog based on the typical cytologic and histopathologic features of the mass. TVT is a round-cell neoplasm that predominantly affects the external genital mucosa of male and female dogs.1 In natural conditions, TVT only occurs in dogs. However, infection is occasionally reported in other canine species, such as foxes (Vulpes vulpes), coyotes (Canis latrans), and jackals (Canis aureus).2,3 In addition, TVT has been used as a research tool to understand more about devil facial tumor disease, which affects Tasmanian devils (Sarcophilus harrisii). Both tumors have similar characteristics, are the only naturally occurring transmissible tumors known to exist in vertebrates, and share the same immune escape mechanism of major histocompatibility complex class I downregulation after becoming established in a host.4 Transmission of TVT among dogs happens regardless of gender and typically involves implantation of viable tumor cells in mucous membranes during coitus in sexually mature dogs or through biting, licking, scratching, or smelling a carrier animal.57

TVT usually has a benign biologic behavior, but characteristics of malignancy, including metastasis, moderate to marked anisocytosis and anisokaryosis, frequent binucleation, moderate macrokaryosis, numerous cytoplasmic vacuoles, and atypical mitotic figures, have also been reported.811 The metastatic sites are the skin, subcutis, regional lymph nodes, skeletal muscle, spleen, liver, eye, brain, kidney, peritoneum, tongue, and mucous membranes.1214 The prognosis for complete remission in dogs with TVT is good unless metastatic involvement of the CNS or eye develops.14

In developed countries, TVT has been nearly eradicated as a result of policies that hinder abandonment of dogs and free-roaming dogs.15 However, sporadic cases have been reported in the United States (Arizona and North Dakota) and Australia (Northern Territory and Western Australia), and occasional cases have been reported in dogs imported from northern and western Europe.15 The Veterinary Pathology Service of the Faculty of Veterinary Medicine and Animal Science of São Paulo State University has established a TVT classification scheme based on cell morphology that allows TVTs to be categorized into 3 cytomorphologic patterns: lymphocytoid, mixed, or plasmacytoid. The plasmacytoid pattern is seen most commonly, and is the most malignant pattern with the worst prognosis, representing nearly all metastatic cases.9 It is also less sensitive to treatment with vincristine, possibly because of high-permeability glycoprotein expression and a greater number of DNA breaks.16,17 The case described in this report was classified as plasmacytoid pattern.

TVT can be classified as being in a progressive or regressive phase by means of histologic examination of H&E-stained sections.18 The progressive phase of the tumor is characterized by intense cellularity, with cells with a large amount of clear cytoplasm immersed in a delicate stroma, whereas the regressive phase has evidence of moderate to abundant stromal tissue forming bands that dissect and replace the neoplastic cells.8,19 Given the histologic description, it is possible to classify the case in this report as being in the progressive phase. The progressive phase consists of suppression of major histocompatibility complex classes I and II expression by tumor cells, generating decreased natural killer cell activity and impairing the function of host T cells and dendritic cells, contributing to tumor escape.20,21 In the regressive phase, tumor-infiltrating lymphocytes secrete cytokines that increase the concentrations of major histocompatibility complex classes I and II, contributing to tumor regression.20 Furthermore, it is suggested that chemokines such as CCL5 and CCL28, produced during keratinocyte activation and tissue inflammation, together with demethylation of upregulated genes are also associated with tumor regression.22

The diagnosis of TVT is based on anamnesis and clinical, cytologic, and histologic findings; however, additional molecular and cytogenetic techniques can also be used.14 On cytologic examination, TVT cells have a distinct appearance. Neoplastic cells are round to oval with frequent mitotic figures, clumping chromatin, and 1 or 2 prominent nucleoli. The most striking cytologic finding is the presence of multiple, clear cytoplasmic vacuoles.14,23 TVT cells are distinctive when compared with the cells of other round-cell tumors, such as mast cell tumor, histiocytoma, and lymphosarcoma.23 Thus, cytologic examination is considered the first-choice diagnostic tool because it is a simple, minimally invasive, painless technique without cellular artifacts, compared with formalin-fixed biopsy samples.9 Histologically, the cellular morphology of TVTs may be challenging to distinguish from that of other round-cell tumors, especially when extragenital locations are involved.14

Immunohistochemical staining characteristics of TVTs and histiocytomas are identical (positive for vimentin, lysozyme, α1-antitrypsin, glial fibrillary acidic protein, CD45RA, and CD45; and negative for cytokeratins, S-100, and muscle markers).14,24 Therefore, the final diagnosis should be based on the clinical information in conjunction with cytologic and histopathologic findings. The immunohistochemical staining characteristics strongly suggest that TVTs have a histiocytic origin.14 In this reported case, the neoplastic cells were immunonegative for CD79α, MUM-1, and CD3, ruling out B-cell lymphoma, plasmacytoma, and T-cell lymphoma, respectively.

Cytogenetic studies support the theory of clonal transmission. In TVT cells isolated from animals from different geographic regions, the chromosome number varied from 57 to 59 (vs 78 chromosomes in clinically normal dogs), with 15 to 17 chromosomes being metacentric or submetacentric.25 These chromosomal changes may have resulted from balanced fusions and not from the gain or loss of genetic material.26 In addition, TVTs have a unique molecular characteristic based around a rearrangement of the protooncogene c-myc, which is absent in normal somatic cells and gametes, and other neoplasms. Rearrangement detected with an in situ PCR assay has been used as a diagnostic tool to make a definitive diagnosis of canine TVT.26,27

Dogs with TVT can have secondary lymphocytic infiltration to the lesion causing a mild degree of lymphopenia. Genital bleeding is present in some cases, causing anemia.28 In this dog, none of these hematologic changes was present. The serum biochemical abnormalities (ie, hypoalbuminemia, hyperglobulinemia, and hyperproteinemia) seen in this dog may have been secondary to dehydration or inflammation within the neoplasm.29 The high mean corpuscular hemoglobin concentration was probably an artifact resulting from plasma hypertonicity caused by an excess of EDTA in the collection tube.30

Treatment options for TVT include surgery, radiotherapy, and chemotherapy. Surgical treatment has low efficacy because of its high recurrence rate. Radiotherapy requires specialized equipment and has a high cost. Chemotherapy is preferred, and the drug of choice is vincristine.14,31 The therapeutic protocol involving vincristine does not cause behavioral or reproductive impacts.14 In cases of drug resistance or adverse effects, vinblastine or doxorubicin can be used as a single agent to treat TVTs.31,32 Cyclophosphamide and methotrexate are ineffective as single drugs and must be used in combination with vincristine to cause regression of TVTs.31 Lomustine (60 mg/m2, PO, q 3 weeks for 3 doses) had been reported to lead successfully to regression of vincristine-resistant TVTs.33 In this case, the dog underwent 5 chemotherapy sessions with vincristine (0.75 mg/m2, IV, once; then, 0.70 mg/m2, IV, q 1 week). A dose reduction between the first and subsequent vincristine doses occurred because adverse effects such as emesis, diarrhea, and hypoxia. Although the TVT in this case was classified as the plasmacytoid form, which is considered to be less sensitive to chemotherapy, there was complete tumor regression after treatment with vincristine.

Acknowledgments

The authors declare that there were no conflicts of interest.

Mr. Dinau and Ms. Ghedin were 3rd-year veterinary students and Ms. de Moura was a 4th-year veterinary student at the Faculty of Veterinary Medicine and Animal Science of São Paulo State University in Brazil when the manuscript was written.

References

  • 1.

    Cohen D. The canine transmissible venereal tumor: a unique result of tumor progression. Adv Cancer Res. 1985;43:75112.

  • 2.

    Flórez LMM, Ballestero HF, Duzanski AP, et al. Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor. Pesqui Vet Bras. 2016;36:844850.

    • Search Google Scholar
    • Export Citation
  • 3.

    Abeka YT. Review on canine transmissible venereal tumor (CTVT). Cancer Ther Oncol Int J. 2019;14:19.

  • 4.

    Pye RJ, Woods GM, Kreiss A. Devil facial tumor disease. Vet Pathol. 2016;53:726736.

    • Crossref
    • PubMed
    • Export Citation
  • 5.

    Hill DL, Yang TJ, Wachtel A. Canine transmissible venereal sarcoma: tumor cell and infiltrating leukocyte ultrastructure at different growth stages. Vet Pathol. 1984;21:3945.

    • Search Google Scholar
    • Export Citation
  • 6.

    Rogers KS. Transmissible venereal tumor. Compend Contin Educ Pract Vet. 1997;19:10361045.

  • 7.

    Stubbs EL, Furth J. Experimental Studies on venereal sarcoma of the dog. Am J Pathol. 1934;10:275286.

  • 8.

    Ballestero Fêo H, Montoya Flórez L, Yamatogi RS, et al. Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs? Vet Comp Oncol. 2018;16:370378.

    • Search Google Scholar
    • Export Citation
  • 9.

    Santos Do Amaral A, Bassani-Silva S, Ferreira I, et al. Cytomorphological characterization of transmissible canine venereal tumor. Rev Port Ciênc Vet. 2007;102:253260.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Meinkoth JH, Cowell RL. Recognition of basic cell types and criteria of malignancy. Vet Clin North Am Small Anim Pract. 2002;32:12091235.

    • Search Google Scholar
    • Export Citation
  • 11.

    Lima CRO, Rabelo RE, Vulcani VAS, et al. Morphological patterns and malignancy criteria of transmissible venereal tumor in cytopathological and histopathological exams. Braz J Vet Res Anim Sci. 2013;50:238246.

    • Search Google Scholar
    • Export Citation
  • 12.

    Park MS, Kim Y, Kang MS, et al. Disseminated transmissible venereal tumor in a dog. J Vet Diagn Invest. 2006;18:130133.

  • 13.

    Ferreira AJ, Jaggy A, Varejäo AP, et al. Brain and ocular metastases from a transmissible venereal tumour in a dog. J Small Anim Pract. 2000;41:165168.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Ganguly B, Das U, Das AK. Canine transmissible venereal tumour: a review. Vet Comp Oncol. 2016;14:112.

  • 15.

    Strakova A, Murchison EP. The changing global distribution and prevalence of canine transmissible venereal tumour. BMC Vet Res. 2014;10:168.

    • Search Google Scholar
    • Export Citation
  • 16.

    Gaspar LFJ, Ferreira I, Colodel MM, Brandão CVS, Rocha NS. Spontaneous canine transmissible venereal tumor: Cell morphology and influence on P-glycoprotein expression. Turk J Vet Anim Sci. 2011;34:447454.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Alzate JM, Montoya-Florez LM, Pérez JE, Rocha NS, Pedraza-Ordonez FJ. The role of the multi-drug resistance 1, p53, b cell lymphoma 2, and bcl 2-associated X genes in the biologic behavior and chemotherapeutic resistance of canine transmissible venereal tumors. Vet Clin Pathol. 2019;48:730739.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Mukaratirwa S, Gruys E. Canine transmissible venereal tumour: cytogenetic origin, immunophenotype, and immunobiology: a review. Vet Q. 2003;25:101111.

    • Search Google Scholar
    • Export Citation
  • 19.

    Yadav A, Kumar P, Panihar S, et al. Clinico-histopathological studies in canine transmissible venereal tumour. Int J Curr Microbiol Appl Sci. 2018;7:27142719.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Hsiao YW, Liao KW, Hung SW, Chu RM. Effect of tumor infiltrating lymphocytes on the expression of MHC molecules in canine transmissible venereal tumor cells. Vet Immunol Immunopathol. 2002;87:1927.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Yang TJ, Chandler JP, Dunne-Anway S. Growth stage dependent expression of MHC antigens on the canine transmissible venereal sarcoma. Br J Cancer. 1987;55:131134.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Frampton D, Schwenzer H, Marino G, et al. Molecular signatures of regression of the canine transmissible venereal tumor. Cancer Cell. 2018;33:620633.e6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Duncan JR, Prasse KW. Cytology of canine cutaneous round cell tumors. Vet Pathol. 1979;16:673679.

  • 24.

    Marchal T, Chabanne L, Kaplanski C, Rigal D, Magnol JP. Immunophenotype of the canine transmissible venereal tumour. Vet Immunol Immunopathol. 1997;57:111.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Murray M, Helen ZJ, Martin W. A study of the cytology and karyotype of the canine transmissible venereal tumour. Res Vet Sci. 1969;10:565568.

  • 26.

    Setthawongsin C, Techangamsuwan S, Tangkawattana S, Rungsipipat A. Cell-based polymerase chain reaction for canine transmissible venereal tumor (CTVT) diagnosis. J Vet Med Sci. 2016;78:11671173.

    • Search Google Scholar
    • Export Citation
  • 27.

    Fonseca LS, Mota LSLS, Colodel MM, Ferreira I, Brandão CVS, Rocha NS, et al. Spontaneous canine transmissible venereal tumor: association between different phenotypes and the insertion LINE-1/c-myc. Rev Colomb Cienc Pecu. 2012;25:402408.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Kabuusu RM, Stroup DF, Fernandez C. Risk factors and characteristics of canine transmissible venereal tumours in Grenada, West Indies. Vet Comp Oncol. 2010;8:5055.

    • Search Google Scholar
    • Export Citation
  • 29.

    McGrotty Y, Knottenbelt C. Significance of plasma protein abnormalities in dogs and cats. In Pract. 2002;24:512517.

  • 30.

    Nemec A, Drobnic-Kosorok M, Butinar J. The effect of high anticoagulant K3-EDTA concentration on complete blood count and white blood cell differential counts in healthy beagle dogs. Slov Vet Res. 2005;42:6570.

    • Search Google Scholar
    • Export Citation
  • 31.

    Amber EI, Henderson RA, Adeyanju JB, Gyang EO. Single-drug chemotherapy of canine transmissible venereal tumor with cyclophosphamide, methotrexate, or vincristine. J Vet Intern Med. 1990;4:144147.

    • Search Google Scholar
    • Export Citation
  • 32.

    Ramadinha RR, Teixeira RS, Bomfim PC, et al. Canine transmissible venereal tumor response to chemotherapy with vincristine sulfate and vinblastine. Braz J Vet Med. 2016;38:6569.

    • Search Google Scholar
    • Export Citation
  • 33.

    Decuadro A, Ruiz N, Menéndez C, et al. Lomustine therapy for vincristine-resistant canine transmissible venereal tumor: a case report. Rev Bras Med Vet. 2021;43:19.

    • PubMed
    • Search Google Scholar
    • Export Citation

Contributor Notes

Corresponding author: Dr. Negrão Watanabe (tnegrao@ncsu.edu)