Canine Transmissible Venereal Tumor (TVT)

Introduction
Canine Transmissible Venereal Tumor (TVT), also known as Sticker's sarcoma, is a unique and rare form of cancer in dogs. Unlike typical cancers, TVT is a transmissible neoplasm, meaning it spreads through the transfer of living cancer cells from one dog to another. This distinctive feature makes TVT an important subject of study in oncology and veterinary medicine.

Historical Background
TVT was first described in the late 19th century by Russian veterinarian M.A. Novinsky. The transmissible nature of TVT was demonstrated through experimental studies soon after its discovery. TVT remains one of the few naturally occurring transmissible cancers known to affect animals, providing a unique opportunity to study cancer biology and immunology.

Epidemiology
TVT is predominantly found in areas with high populations of stray or free-roaming dogs, particularly in tropical and subtropical regions. The disease is less common in well-controlled dog populations where pets are regularly monitored and spayed or neutered. In regions like India, studies have reported prevalence rates ranging from 23.5% to 28.3%, particularly in areas with poor control over animal reproduction and high stray dog populations.

Transmission
The primary mode of transmission for TVT is direct contact between dogs, especially during mating. However, the cancer can also spread through other forms of physical contact, such as licking or biting. The tumor cells are allogeneic, meaning they are genetically distinct from the host’s cells. Despite this, they manage to evade the host’s immune system, allowing the cancer to establish itself in new hosts.

Clinical Presentation
TVT most commonly manifests as a tumor on the external genitalia. In males, it typically affects the penis and prepuce, while in females, it is found on the vulva and vagina. The tumor often appears as a cauliflower-like growth that can be friable, ulcerated, and prone to bleeding. Although less common, TVT can also occur in the nasal cavity, oral cavity, and other mucous membrane surfaces. Metastasis to regional lymph nodes is possible but relatively rare.

Conclusion
Canine Transmissible Venereal Tumor is a unique and significant disease in the canine population. Its transmissible nature sets it apart from other cancers and poses challenges for control and treatment, particularly in regions with high populations of stray dogs. With effective treatment options available, particularly chemotherapy, the prognosis for TVT is generally positive. Continued research and public health efforts are essential to manage the disease and improve the health of affected dogs.

1. Department of veterinary gynecology & obstetrics TOPIC –  TRANSMISSIBLE VENERAL TUMOR SUBMITTED TO - DR. S.N SHUKLA SIR [HOD VGO DEPARTMENT] SUBMITTED BY- PRERANA BHOYAR [MVSC. 1st YEAR] COLLEGE OF  VETERINARY SCIENCE & A.H, JABALPUR. MP

2. SIGNALMENT Case No:  3310 Owner's Name: Mr.  Pravesh Species: Canine  Breed:  Mongrel Age: 4 yrs.   Sex: Female  Weight:  52 kg Color:   Brown and black Spayed: No

3. anamnesis Primary Complaint: Presence of a growth in the vagina. Duration: Growth noticed for the past 5 days. Progression: Rapid growth observed over the past few days. Symptoms: Blood spotting noticed wherever the dog sits and stands up. Behavioral Changes: Increased licking or scratching of the affected area. Estrus Cycle:  One month ago Breeding History: Bred twice. Last Mating: One month ago. Previous Infections:  No

4. General inspection Vaccination Status: Yes Current Medications:  None Diet and Appetite:  Reduced Appetite Behavior: Active & Alert Urine and Motion: Voided normally Abdominal Palpation: No abnormality detected

5. PHYSICAL examination General Appearance:  Normal Temperature:  102° F Lymph Nodes:  Enlargement of inguinal lymph node Mucous Membranes and Capillary Refill Time (CRT):  Normal

6. Diagnostic Tests Digital Vaginal Examination The vulvar lips were gently parted. A lubricated, gloved finger was inserted, assessing for masses, irregularities, texture, elasticity, and bleeding. Interpretation:          -Cherry red colored/cauliflower like        growth palpated.          - Presence of masses/nodules.          - Irregular/rough vaginal mucosa.

7. Cytology: Impression Smea r Sample collection involved gently parting the vulvar lips, using a sterile cotton swab to collect tumor cells, and pressing it onto a glass slide for an impression smear. Slides were air-dried, fixed with methanol if needed, and stained with Giemsa stain. Interpretation:   Positive findings included round cells with high nucleus-to-cytoplasm ratio, prominent nucleoli, distinct cytoplasmic vacuoles, and clustered cell arrangement indicating TVT.

8. Blood Tests: Complete Blood Count (CBC) and Biochemistry Profile Blood is collected via venipuncture, typically from a peripheral vein. Interpretation:  Decreased MCV, TLC, and neutrophils suggest anemia and immune compromise. Increased MCHC, lymphocytes, and SGOT indicate potential dehydration, immune response, and liver involvement in advanced TVT.

9. TREATMENT PLAN: CHEMOTHERAPY 04.06.24

10. CONTINUE... 8th day (After one  week) & 15th day ( After two week) Improvement in the blood parameters & tumor observed. 11.06.2024 18.06.2024

11. Case discussion: Transmissible venereal tumor

12. introduction Occurrence: TVT is a rare, sexually transmitted tumor in dogs, affecting the genital mucosa. Genetic Involvement: TVT cells exhibit clonality and unique genetic markers, distinct from host DNA. Histiocytic Origin: Derived from histiocytes, a type of immune cell, TVT demonstrates histiocytic characteristics. Research: Recent studies emphasize TVT's genetic stability and histiocytic lineage, contributing to its unique transmissible nature.

13. synonyms Sticker's Sarcoma Infectious Sarcoma Venereal Granuloma Transmissible Genital Tumor Canine Transmissible Venereal Sarcoma (CTVS)

14. PREVALENCE  Free-Roaming Dogs: Common due to unrestricted mating, contributing to transmission. Young, Sexually Mature Animals: Typically affects dogs in their reproductive prime at age 2-5 years. Chromosome Abnormalities: TVT cells exhibit 57-64 chromosomes (average 59), contrasting with the normal canine count of 78. Geographical Distribution: Found predominantly in sub-tropical to tropical urban areas. Female Predominance: More frequently observed in female dogs due to anatomical susceptibility. Incidence:  In India, studies by Gandotra et al. (1993) and Singh (1993) reported that Transmissible Venereal Tumor (TVT) accounts for 23-43% of all tumors in the canine population nationwide. In Punjab, specifically, the prevalence ranges from 23.5% to 28.3%.

15. Etiology and transmission Origin of cell is unknown but assumed to be an undifferentiated round cell neoplasm of reticulo -endothelial origin. (Mozos et al., 1996) .  First tumor to be transmitted experimentally by Nowinsky in 1876. (Yang et al.., 1991) . Growth of tumor appears 15 to 60 days after implantation (Moulton et al, 1978). Exfoliation and transplantation of neoplastic cells due to physical contact during mating or licking of affected area is responsible for spread onto genital, oral or nasal mucosa. (Johnston 1991). Horizontal Transmission: Can spread through genital contact between dogs, including males and females.

16. Metastasis CTVT Progressive Phase Tumor Cell (Purple Cells) : Primary tumor-forming cells. Stromal Cell (Blue Elongated Cells) : Supportive surrounding cells. Tumor-Infiltrating Lymphocyte (Blue Rounded Cells) : Immune cells infiltrating the tumor. Antigen-Presenting Cell (APC) (Star-shaped Cells) : Cells presenting antigens, marked with MHC class I and II. MHC class I and II : Molecules for antigen presentation to T cells. Cytokines : TGFβ1 : Promotes tumor progression. IFNγ : Involved in immune response. IL6 : Involved in inflammation and immune response.

17. Clinical findings Small pink to red, 1 mm to 3 mm diameter nodules can be observed 2 or 3 weeks after transplantation.  Initial lesions - superficial dermo epidermal or pedunculated.  Multiple nodules fuse - larger, red, hemorrhagic, cauliflower like, friable mass (5cm-7cm)  Progress deeper in to the mucosa - multilobular s/c lesion (10-15 cm)  Tumors bleed easily, become larger, normally ulcerate and contaminate (Hoque, 2002)

18. diagnosis History   • Complaint of serosanguineous & hemorrhagic genital discharge.  • Licking of external genitalia or protrusion of mass.  • Sneezing or epistaxis Physical examination Male : caudal part of the glans penis from the crura to the bulbus glandis occasionally on the prepuce. phimosis mass protrude from the penis. (Das et al, 2000)  Female: junction between vestibule and caudal vagina rarely interfere with micturition hemorrhagic vulvar discharge if in vagina protrudes from vulva. Signs depending on anatomical location of the tumor – Epiphora, Halitosis and tooth loss , Exophthalmos Skin bumps, Facial, oral deformation along with regional lymph node ( Roggers 1997)

19. Continue... Exfoliative vaginal cytology: Round to oval cells with large nuclei containing prominent nucleoli  Eosinophilic vacuolated thin cytoplasm  Nucleus to cytoplasm ratio is higher Abnormal no. of Chromosome.   Haemato-biological examination: Polycythemia  PCR: Insertion of LINE at 5' end of TVT cell c- myc gene.

20. Stains used  Harris Hematoxylin and Eosin  Wright-Giemsa (WG) May-Grunwald-Giemsa  Leishman-Giemsa  PAP stain  New methylene blue

21. DIFFERENTIAL DIAGNOSIS: physical examination

22. Differential diagnosis: CELL CYTOLOGY 

23. Treatment  Chemotherapy:  Most effective and practical therapy  Vincristine: most frequently used drug  Least recurrence (Nak et al, 2005)  Good response Least side effects  Initial stages of progression (<1 yr.) : Cure rate approaches 100% (Bosco's and Ververidis , 2004)

24. Continue...

25. Radiotherapy: 

26. cryotherapy

27. BIOTHERAPY

28. SURGICAL MANAGEMENT

29. RECENT ADVANCEMENT A study concludes that the combination of Vincristine and Ivermectin exhibits a faster therapeutic response and fewer side effects in treating Canine Transmissible Venereal Tumor (CTVT) compared to Vincristine alone, which, although effective, shows delayed results and more side effects. This finding aligns with the research of Andrade et al. and Lapa et al. (2022)

30. SUPPORTIVE MANAGEMENT

31. THANK YOU!!