Successful Management of Metastatic Transmissible Venereal Tumour to Skin of Mammary Region

Authors

  • EE Varughese,

    Corresponding author
    • Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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  • VK Singla,

    1. Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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  • U Ratnakaran,

    1. Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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  • VK Gandotra

    1. Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab, India
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Author's address (for correspondence): EE Varughese, Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab – 141004, India. E-mail: emy_12@hotmail.com

Contents

A Dalmatian female presented with a history of vaginal bleeding and was diagnosed as having transmissible venereal tumour (TVT) after cytological examination of the vaginal growth revealed typical TVT cells. A cytology of the aspirate from multiple nodules in the skin near the abdominal and inguinal pair of mammary glands revealed similar cells suggestive of metastasis to skin of mammary region. Chemotherapy was initiated with weekly injections of vincristine sulphate (0.025 mg/kg BW, IV, SID) and haematological examination was performed pre- and post-treatment to assess the prognosis of the patient and side effects of the drug. The major side effects observed during the course of the treatment were high body temperature, mild neutropaenia and significant decrease in packed cell volume, haemoglobin, total leucocyte and erythrocyte count. Four weekly injections of vincristine were administered, and 4 weeks from initiation of treatment, the tumour and nodules were gone, suggesting complete recovery.

Introduction

Canine transmissible venereal tumour (TVT) is a contagious round cell tumour of dogs. It is the only known naturally occurring tumour that can be transplanted as an allograft across major histocompatibility barriers within the same species, and even to other members of the canid family. Transmissible venereal tumour is most common in dogs 2–5 years old, and the disease is mostly seen in free-roaming, sexually active dogs in tropical and subtropical countries (Higgins 1966). In India, it is one of the most common tumours of dogs due to a large population of stray dogs.

The violent exertions associated with coitus in the dog render both sexes prone to genital injury and susceptible to transplantation of the tumour cells (Feldman 1929). The tumour may also be transferred when an affected dog licks its own genital area and then of another dog or when a normal healthy dog licks the genital area of an affected dog and then its own.

In the male dog, the tumour is usually located on the caudal part of the penis or the area of the glans penis, and occasionally on the prepuce. In the female dog, the tumour is usually found in the posterior part of the vagina, often at the vaginovestibular junction (Karlson and Mann 1952; Das and Das 2000). Tumours on the external genitalia of both sexes appear initially as small hyperaemic papules that later progress to nodular, papillary multi-lobulated, cauliflower-like or pedunculated proliferations. The tumour often oozes a serosanguinous or simple haemorrhagic fluid and eventually becomes ulcerated, with a necrotic appearance (Das and Das 2000). Metastasis is reported to occur in <5% of the cases involving skin, regional lymph nodes, tonsils, eyes, brain, pituitary, nose, tongue, lips, mammary region and thoracic and abdominal viscera (Karlson and Mann 1952; Das and Das 2000).

Diagnosis is based on history, clinical and cytological findings, and biopsy. A definitive diagnosis can be made by chromosome analysis and transmission studies (Karlson and Mann 1952). Vincristine is considered to be the most safe chemotherapeutic agent and effective resulting in cure, even in TVT patients with extra-genital metastasis (Calvert et al. 1982).

The efficacy of vincristine was evaluated on a case of TVT with metastasis to mammary region. Haematological and cytological examination was performed during chemotherapy to determine the outcome of the case.

Materials and Methods

A 28-kg Dalmatian female was presented with a history of vaginal bleeding for the last 45 days and swelling near the mammary region for 4 days. The last whelping was 4 months prior to presentation, and there was no history of a recent mating. There were no other presenting complaints, and the dog was currently on deworming and vaccinations. Per-vaginal examination, a complete blood count (CBC) and serum biochemistry profiling were performed prior to treatment. Cytological preparations from the vaginal tumour and aspirate from the nodules were made using sterile swabs and subsequently stained with Leishman stain. Four weekly injections of vincristine sulphate, SID, along with multivitamin supplementation were administered for 4 weeks.

Results

Physical examination revealed pink mucous membranes, slightly enlarged popliteal lymph nodes and rectal temperature (RT) of 104°F. Multiple nodules were observed in the skin near the abdominal and inguinal pair of mammary glands (Fig. 1). Clinical examination revealed serosanguinous exudate oozing from the vulva, and a 1.5–2.0-cm-diameter cauliflower-like growth was palpated within the posterior vagina. The CBC revealed a relative neutrophilia with mild–moderate toxic changes of the neutrophils (Table 1). Cytologic examination of the vaginal growth revealed cells with a round, hyperchromatic nucleus, large unstained nucleoli, pale blue cytoplasm with clear, distinct vacuoles and fairly distinct cytoplasmic borders suggestive of typical TVT cells (Fig. 2). Aspirates from the nodules revealed similar cells, confirming metastasis to the skin of mammary region (Fig. 3). As the dog was hyperthermic, 2 ml of analgin (Novalgin; Aventis ® Pharma Ltd, Gujarat, India) was administered intramuscularly to reduce the fever. For treatment, vincristine sulphate (Cytocristin, Cipla®; Cipla Ltd., Mumbai, India) (0.025 mg/kg BW, IV, SID) and multi-vitamin syrup (Vitabest, Virbac®, Paris, France) at 5 ml BID, p.o. for 15 days were advised. One week after the first injection, there was reduction in size of the tumour and nodules, and RT was 103.6°F with a marked decrease in total leucocyte count to 8660 cells/mm3 (Table 1). Cytology of the vaginal mass revealed a considerable decrease in the number of typical TVT cells and an increase in macrophages and leucocytes, suggestive of an ongoing immune response to treatment (Fig. 4). The vincristine sulphate (0.025 mg/kg BW, IV, SID, Cytocristin, Cipla®) treatment was repeated. One week after the second treatment, there was minimal tumour mass with significant reduction in size of nodules (Fig. 5), and RT was 103.4°F. The vincristine sulphate (0.025 mg/kg BW, IV, SID, Cytocristin, Cipla®) treatment was repeated a third time. One week later, the tumour and nodules were gone (Fig. 6), RT was 103.6°F, and the last injection of vincristine sulphate was administered. Four weeks after the start of the treatment, the tumour and nodules were gone.

Table 1. Complete blood count and biochemistry parameters used for routine pre-and post-treatment assessment
Parameters (units) [Normal range]Day of presentation1st week post-treatment2nd week post-treatment3rd week post-treatment4th week post-treatment
Haemoglobin (g%) [12–19]1614.213.713.212.4
Total leucocyte count (cells/cu mm) [5–14 × 103]20 0008660839080907994
Total erythrocyte count (cells/cu mm) [5–7.9 × 106]7.32 × 1066.89 × 1066.75 × 1066.55 × 1066.43 × 106
Packed cell volume (%) [35–57]42.136.138.239.138.5
Platelet count [211–621 × 103]272 × 103325 × 103500 × 103550 × 103575 × 103
Neutrophils (%) [58–85]8656565757
Lymphocytes (%) [8–21]1444444343
Total bilirubin (mg/dl) [0–0.3]0.20.20.20.20.2
SGOT/AST (U/l) [13–15]3851525558
SGPT/ALT (U/l) [10–109]2316243035
Blood urea nitrogen (mg/dl) [8–28]1612899
Creatinine (mg/dl) [0.5–1.7]1.51.21.21.21.2
Figure 1.

Multiple nodules (black arrows) near the abdominal and inguinal pair of mammary glands

Figure 2.

Vaginal cytology reveals typical transmissible venereal tumour (TVT) cells with round hyperchromatic nucleus (white arrow), large unstained nucleoli (yellow arrow), pale blue cytoplasm with clear, distinct vacuoles (black arrow) and fairly distinct cytoplasmic border (red arrow)

Figure 3.

Aspirate from the swelling revealed typical transmissible venereal tumour (TVT) cells

Figure 4.

Reduction in typical transmissible venereal tumour (TVT) cells and increase in macrophages (black arrow) and leucocytes (red arrow) suggestive of an ongoing immune response to treatment

Figure 5.

Significant reduction in size of nodules (black arrow) 2 weeks post-treatment

Figure 6.

Absence of nodules near the abdominal and inguinal pair of mammary glands

Discussion

Despite its malignant nature and ease of spread among animals, TVT is unique as it responds to a variety of treatment strategies (Nak et al. 2005). Chemotherapy of TVT has been attempted using several chemotherapeutic agents used alone (vincristine, cyclophosphamide, methotrexate, cyclophosphamide and doxorubicin) or in combinations (vinblastine with cyclophosphamide or methotrexate) (Das and Das 2000). However, among the different chemotherapeutic agents, single-agent therapy with vincristine sulphate at 0.025 mg/kg body weight intravenously at weekly intervals for two to five treatments has been found to be most effective, safe and convenient (Calvert et al. 1982). The present case responded to four treatments of vincristine with complete regression of the tumour from genital and extra-genital sites within 4 weeks of treatment. Complete recovery was evident from the absence of growth in the vagina and resolution of nodules from the mammary region suggesting effective control of metastasis. Failure on the part of the host to produce sufficient amount of antibodies against the TVT may be the reason for metastasis (Adams and Slaughter 1970).

Intratumoural leucocyte populations provided evidence that cell-mediated immunity and inflammation accompanied chemotherapy in the resulting tumour regression (Gonzalez et al. 2000). A subjective assessment of the cytology of the vaginal growth prior to initiation of treatment (Fig. 2) revealed a limited number of leucocytes, whereas cytology of the vaginal growth 1 week after initiation of treatment (Fig. 4) revealed an increase in the number of leucocytes associated with the process of tumour regression.

The toxicities of greatest concern after vincristine treatment are gastrointestinal upset, myelosuppression and local tissue injury due to drug extravasation (Rogers 1997). The major side effects observed in the present case were high body temperature, mild neutropaenia and significant decreases in PCV, haemoglobin, total leucocyte and erythrocyte count. The bitch remained healthy despite these changes.

Cytological examination is an easy and safe method for diagnosis and assessment of prognosis of TVT cases. Different stains can be used for staining of cytological smears. We used Leishman stain (Sigma-Aldrich, St. Louis, MO, USA) as it is easily available and easy to perform. The success of treatment can be observed by a decrease in the number of typical tumour cells (round to ovoid cells with distinct cytoplasmic borders, round nuclei with one or two prominent nucleoli and faintly light violet cytoplasm with large vacuoles) (Nak et al. 2005) and associated increase in leucocytes suggestive of tumour regression.

Of the total number of tumours in canine patients, TVT constitutes approximately 28.6% (Gandotra et al. 1993), which indicates that effective treatment and control is essential to curtail its spread within the canine population. Effective control can be achieved by careful monitoring of breeding practices and segregation of stray dogs from pet dogs. In conclusion, our results suggest that vincristine is an effective chemotherapeutic agent in the treatment of TVT with metastasis to the mammary region.

Acknowledgements

The authors wish to acknowledge the faculty of the Department of Veterinary Gynaecology and Obstetrics, Guru Angad Dev Veterinary and Animal Sciences University (GADVASU) for their help and advice. We also wish to thank the staff of Clinical Diagnostic Laboratory, Teaching Veterinary Clinical Complex, GADVASU for their timely efforts in delivering the clinical reports.

Conflicts of interest

None of the authors have any conflicts of interest to declare or have received funding for carrying out this case.

Author contributions

VKS, VKG, EEV and UR: Involved in the diagnosis and treatment on various days till recovery, EEV: Documentation of clinical records, writing of article, VKG and EEV: Editing of article.

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