The Canine Transmissible Venereal Tumor is a type of cancer that affects dogs. It's a rare and unusual disease that's been around for thousands of years.
This tumor is unique because it can be transmitted from one dog to another through direct contact during mating. It's a sexually transmitted infection, essentially.
The tumor typically appears as a mass on the dog's genital area, and it can cause a range of symptoms including discharge, bleeding, and swelling. In some cases, it can even lead to secondary infections.
The tumor is caused by a virus that's been identified as a member of the papovaviridae family. It's a distinct type of cancer that's different from other forms of the disease.
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Pathology and Diagnosis
Canine transmissible venereal tumors are histiocytic tumors that can be transmitted among dogs through direct contact with affected areas.
These tumors can be diagnosed through cytology, which involves examining cell samples under a microscope. Cell samples can be collected using a cotton-tipped swab or fine needle aspiration.
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The cells are then examined by a veterinary pathologist to determine if they are characteristic of a CTVT. In some cases, a biopsy may be necessary to confirm the diagnosis.
Histopathological examination reveals highly mitotic activity, polychromasia, and abundant cytoplasm in pleomorphic neoplastic cells. The cells are arranged in cell islands via thin fibrous tissue, which is a typical feature of CTVTs.
Cytological examination typically shows round cells with distinct cytoplasmic borders, oval or round nuclei, and delicate chromatin. Mitoses are frequent, and apoptotic bodies are observed, especially in the regression phase.
The tumor can be classified into progression and regression phases based on developmental stages. The progression phase is characterized by round cells arranged diffusely, while the regression phase involves the collapse of neoplastic tissue and the presence of apoptotic bodies.
Histopathology Characteristics
Histopathological examination is performed by removing a fragment of the mass, typically under local anesthesia, and processing it according to routine technique for optical microscopy.
The tumor cells are highly mitotic, with abundant cytoplasm and pleomorphic neoplastic cells that are separated into cell islands via thin fibrous tissue.
Histologically, TVTs are made up of a homogenous tissue with a compact mass of cells that are mesenchymal in origin and the borders of which cannot easily be differentiated.
A high nucleus: cytoplasm ratio is characteristic of the tumor cells, with a round nucleus and chromatin ranging from delicate to coarse and prominent nucleoli.
The tumor can be classified into progression and initial and final regression phases according to developmental stages, with the progression phase presenting as round cells arranged diffusely.
In the initial phase of regression, TILs appear and are widely distributed or associated with the conjunctival stroma.
The final regression phase involves collapse of the neoplastic tissue and the frequent presence of apoptotic bodies.
The tumor cells are usually arranged radially around blood and lymphatic vessels.
Cytological examination reveals the typical round to slightly polyhedral cells, with rather eosinophilic vacuolated thin cytoplasm and a round hyperchromatic nucleus with a nucleolus and a moderate number of mitotic figures.
The nucleus to cytoplasmic ratio is large, and the cells have a high number of mitotic figures.
Histologically, TVTs should be differentiated from mastocytomas, histiocytomas or malignant lymphomas.
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Mode of Transmission
TVT is a histiocytic tumor that can be transmitted among dogs and other canines through coitus, licking, biting, and sniffing tumor-affected areas.
The transmission of TVT can occur through the implantation of viable tumor cells in mucous membranes, especially if there are abrasions or loss of integrity on the surface.
TVT can only be experimentally induced by transplanting living tumor cells, not by killed cells or cell filtrates.
The tumor's karyotype is aneuploid but has characteristic marker chromosomes in all tumors collected in different geographic regions.
A LINE insertion near c-myc has been found in all tumors examined so far and can be used as a diagnostic marker to confirm that a tumor is CTVT.
TVT is usually transmitted to genital organs during sexual intercourse but can also affect the skin via direct implantation of tumor cells during contact between skin and tumor masses.
Tumor cells can be transferred between healthy animals that share the same MHC or into immunocompromised recipients, as the tumor cells induce an immune response in healthy recipients.
Cells can be derived from mutations induced by viruses, chemicals, or radiation of lymphohistiocytic cells and can then be disseminated by allogeneic transplantation.
Genetics and Immunology
Canine transmissible venereal tumor (CTVT) cells have a unique genetic makeup. They have fewer chromosomes than normal dog cells, typically ranging from 57 to 64 chromosomes, which are very different in appearance from normal dog chromosomes.
CTVT cells also have a distinct genetic code that is often unrelated to the DNA of their host. This is evident in the c-myc insertion found in all tumor cells of this type of cancer.
The genetic code of CTVT cells is so similar across all tumor cells that it's as if they're all sharing the same genetic blueprint. This uniformity is a hallmark of this type of cancer.
In terms of immunology, CTVT is antigenic in dogs, meaning it can trigger an immune response. This response can be both cell-mediated and humoral, involving the activation of various immune cells and the production of antibodies.
CTVT cells can evade the host's immune system by suppressing the expression of certain immune molecules, such as MHC-one and two. They can also secrete immune-suppressive cytokines that limit the infiltration of immune cells into the tumor tissue.
Genetics
CTVT cells have a unique genetic makeup, with fewer chromosomes than normal dog cells. They typically contain 57-64 chromosomes, which is a significant reduction from the normal 78 chromosomes found in healthy dog cells.
One notable characteristic of CTVT cells is that many of their chromosomes are metacentric or submetacentric, meaning their centromere is located closer to the middle of the chromosome. This is in contrast to normal dog chromosomes, which are mostly acrocentric with a centromere near the end.
The genetic code of CTVT cells is often extremely similar, regardless of the host dog's DNA. This suggests that the cancer cells have developed a distinct genetic profile that is not influenced by the host's genetic material.
Immunology
TVT, a type of round cell tumor, has a tumor immunohistochemical staining profile of histiocytic cells. Histiocytes are a subset of leu-kocytes that arise from bone marrow-derived stem cell precursors.
These cells can differentiate into two lineages: monocyte/macrophage and dendrite cells. Dendrite cells are critical regulators of adaptive immune responses and key cells in tumor antigen presentation.
TVT is antigenic in dogs and provokes both cell-mediated and humeral immune responses. The biological behavior of rapid growth and subsequent regression can be explained by the initial ability of the tumor cells to regulate the host's immune response.
This is achieved through various pathophysiological mechanisms, including the lack of low-level expression of MHC-one and two on tumor cells and the secretion of a B-cell cytotoxic agent(s).
TVT also downregulates monocyte-derived dendrite cell differentiation, reduces dendrite cell survival and function, and limits the infiltration of inflammatory cells into tumor tissue.
Treatment and Prevention
Surgery may be difficult due to the location of these tumors, and even if successful, it often leads to recurrence.
Chemotherapy is very effective for TVTs, with a prognosis for complete remission being excellent. The most common chemotherapy agents used are vincristine, vinblastine, and doxorubicin.
The use of autohaemotherapy in treatment of TVTs has shown promising results in many cases, making it a viable option for some pet owners.
Radiotherapy may be required if chemotherapy does not work, and it's essential to consult with a veterinarian to determine the best course of treatment.
Prevention is key, and controlling stray or free-ranging dogs is crucial in reducing the transmission of CTVT. This can be achieved through dog licensing laws, spay and neuter encouragement campaigns, and managing the number of free-roaming dogs.
Stray dogs serve as a reservoir for the disease, making it difficult to control. However, measures such as strict spay, neuter practices, and effective treatment of clinical cases are helping to control the transmission.
Dog owners and breeders can take steps to prevent the disease by carefully examining all males and females before mating and preventing mingling of valued dogs with strays.
Preventing physical contact between infected dogs and non-infected dogs is essential, and owners should wash their hands after handling dogs and disinfect anything that may be contaminated with living cells from dogs.
The tumor cannot be transmitted from dogs to other animal species or to people, so owners don't need to worry about passing it on to their family members or other pets.
Here are some key prevention measures:
- Manage the number of free-roaming dogs
- Maintain strict spay, neuter practices
- Effectively treat clinical cases
- Prevent mingling of valued dogs with strays
- Wash hands after handling dogs
- Disinfect contaminated surfaces
Carcinogenesis and Biological Behavior
Canine transmissible venereal tumor is a type of cancer that can be quite persistent. In most cases, it remains local, affecting only the area where it first developed. This means it can become increasingly bothersome if left untreated.
The cancer may sometimes disappear on its own due to an immune system response, but this is extremely rare. TVTs usually continue to grow.
In rare cases, TVTs can metastasize, or spread to other areas of the body, often to the nearby lymph nodes.
Diagnosis and Detection
Diagnosis of canine transmissible venereal tumor (CTVT) is usually made through cytology, which involves examining cell samples under a microscope.
Cell samples can be collected by swabbing the area with a cotton-tipped swab or by fine needle aspiration (FNA).
In some cases, a biopsy may be necessary if the cytology results are unclear.
Clinical signs of CTVT vary depending on the location of the tumor, but dogs with genital localization often have a hemorrhagic discharge.
In males, lesions usually localize on the glans penis, preputial mucosa, or bulbus glandis, while in bitches, tumors can be localized in the vestibule and/or caudal vagina.
Definitive diagnosis is based on physical examination and cytological findings typical of CTVT in exfoliated cells obtained by swabs, fine needle aspirations, or imprints of the tumors.
TVTs can cause a variety of signs depending on their anatomical localization, such as sneezing, epistaxis, epiphora, halitosis, and tooth loss.
A considerable hemorrhagic vulvar discharge may occur in bitches and can cause anemia if it persists.
In cases with extragenital localization of the TVT, clinical diagnosis is usually more difficult due to the variety of signs caused by the tumor's location.
Immunotherapy for CTVT
Immunotherapy for CTVT has shown promise in treating the disease. Researchers have found that inflammation and epithelial cell proliferation characterize the early response to VCR treatment.
The expression of many groups of genes occurs at the same time in the S-phase, including those involved in inflammation. This is followed by the host T-, NK-, and B-cell infiltration.
Studies have shown that the infiltration and presence of B-cell is a signature of acute allograft rejection. B-cell-related genes are also progressively upregulated during the R-phase of CTVT growth.
Interferon (IFN) plays a special role in enhancing MHC molecule expression on antigen-presenting cells during the R-phase. This activation of the host immune response can inhibit tumor cell growth and induce tumor cell apoptosis.
Combining a low-dose chemotherapeutic drug with immunotherapy may be advantageous for CTVT patients. This combination protocol can shorten the treatment duration compared to using VCR alone.
The addition of interferon may enhance the innate and adaptive responses of mononuclear cells and affect CTVT viability and proliferation. The strong response induced by VCR can cause the release of damage-associated molecular patterns from stressed or apoptotic cells.
This release of damage-associated molecular patterns can induce direct cognition of foreign DLA molecules and ultimately lead to CTVT regression.
CTVT Prevention and Control
CTVT is a difficult disease to control due to stray dogs serving as a reservoir. Stray dogs and poor policy control are the predisposed causes of CTVT transmission.
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Preventing physical contact between infected and uninfected dogs is essential. Dog owners and breeders should carefully examine all males and females before mating and prevent mingling of valued dogs with strays.
Stray dogs are a significant problem in many areas, especially rural areas where veterinary services may be lacking. CTVT cases are found more often in rural areas than in urban areas because of a lack of adequate veterinary services.
Managing the number of free-roaming dogs is crucial in controlling the transmission of CTVT. Measures such as managing stray dogs, maintaining strict spay and neuter practices, and effective treatment of clinical cases are helping to control the transmission.
Dog owners and breeders should not breed from affected animals, and careful examination of animals in breeding kennels before mating is recommended. The incidence of the disease has fallen where these factors have been in operation, and the disease is rare.
Preventing physical contact between infected dogs and others is essential, and hand washing and disinfecting contaminated items are recommended. The tumor cannot be transmitted from dogs to other animal species or to people.
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Clinical Characteristics
The clinical diagnosis of canine transmissible venereal tumor can be more difficult in cases with extra genital localization, which can cause a variety of signs depending on the anatomical localization of the tumor.
Sneezing, epistaxis, epiphora, halitosis, and tooth loss can all be symptoms of this condition, along with exophthalmoses, skin bumps, facial or oral deformation, and regional lymph node enlargement.
Dogs with genital localization often have a hemorrhagic discharge, which can be confused with urethritis, cystitis, or prostatitis.
The tumors can protrude from the prepuce and cause phimosis, a complication that can be challenging to manage.
Gross and Microscopic Characteristics
Small pink to red nodules, about 1-3 mm in diameter, can be observed 2-3 weeks after transplantation.
These initial lesions are usually superficial dermoepidermal or pedunculated, and they can easily bleed.
Multiple nodules can fuse together, forming larger, red, hemorrhagic, cauliflower-like, friable masses that can be up to 5-7 cm in diameter.
As the tumors grow, they can progress deeper into the mucosa, forming multilobular subcutaneous lesions that can exceed 10-15 cm in diameter.
Cytologically, TVT cells are typically round to slightly polyhedral, with eosinophilic, vacuolated, thin cytoplasm and a round, hyperchromatic nucleus with a nucleolus.
A moderate number of mitotic figures can be observed, and the nucleus to cytoplasmic ratio is large.
Histologically, TVTs are made up of a compact mass of mesenchymal cells, and the borders of the tumor can be difficult to distinguish.
Lymphocytes, plasma cells, and macrophages can infiltrate the tumor tissue.
Clinical Characteristics
Clinical characteristics of this type of tumor can be quite varied and challenging to diagnose, especially when the tumor is located in an unusual area.
The location of the tumor plays a significant role in determining the symptoms your dog will exhibit. If the tumor is located on the penis, prepuce, or vulva, you may notice irregular thickening of the tissue.
Discomfort and intermittent bleeding can also occur in these areas. Some dogs may excessively lick the affected area, which can be a sign of discomfort or pain.
If the tumor is located within the mouth or on the tongue, you may observe cauliflower-like nodules that grow and continue to grow in these areas. They may eventually ulcerate and bleed.
In addition to these symptoms, you may also notice a hemorrhagic discharge, which can be mistaken for urethritis, cystitis, or prostatitis. This discharge can be a sign of a tumor located in the genital area.
In some cases, the tumor can cause a deformation of the perineal region, especially if it's located in the vulva. A considerable hemorrhagic vulvar discharge may occur, which can attract males and be mistaken for estrus by owners.
The tumors themselves often have a fragile consistency and a cauliflower or papillary appearance.
Figures
Histopathologic features of CTVT tissue are a crucial aspect of understanding the disease.
Histopathologic features of CTVT tissue at week 0 or before treatment with vincristine (4A) show the initial condition of the tumor.
Two weeks after treatment with vincristine, the histopathologic features of CTVT tissue (4B) reveal significant changes.
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Figure 1
Figures are a crucial part of visual communication, and Figure 1 is a great example of their importance. Figure 1 is a diagram that illustrates the concept of a figure in a very straightforward way.
A figure can be a simple shape or a complex image, but it always conveys a message or represents an idea. Figures can be used to clarify complex information, making it easier for people to understand.
In the context of Figure 1, we see a simple shape that represents a figure. This shape is a rectangle, which is a common figure used in many different contexts.
Figure 2
Figure 2 is a key visual in the article, and it's worth taking a closer look at what it's showing us. The image is a microscopic view of CTVT cells, highlighting two distinct cell types: lymphocytic (indicated by an arrow) and plasmacytic (starred).
This image is a representation of the cytomorphology of CTVT cells, which is the study of the shape and structure of cells. The different cell types and their characteristics are crucial in understanding the behavior and development of CTVT.
The image is taken using a 40X magnification, which allows for a detailed examination of the cells' morphology. This level of magnification is essential in identifying the specific cell types and their features.
CTVT cells have been immunocharacterized using several tumor markers, including CD3, CD79, PAX-5, and c-kit. However, the cell origin of CTVT is still unclear.
Figure 4
Figure 4 is a key part of understanding the histopathologic features of CTVT tissue. Histopathologic features of CTVT tissue are examined in this figure.
The figure shows two images, 4A and 4B, which represent CTVT tissue before and after treatment with vincristine. CTVT tissue is examined at week 0 or before treatment.
Image 4A shows the histopathologic features of CTVT tissue before treatment with vincristine. Two weeks after treatment with vincristine, the tissue is examined again in image 4B.
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Frequently Asked Questions
Is TVT in dogs contagious to humans?
No, TVT in dogs is not contagious to humans. However, it's still recommended to wear gloves when handling the tumor to prevent potential exposure.
What is the prognosis for transmissible venereal tumor in dogs?
The prognosis for complete remission of transmissible venereal tumor (TVT) in dogs is excellent with chemotherapy. Treatment with vincristine, vinblastine, and doxorubicin, or autohaemotherapy, has shown promising results in many cases.
Sources
- https://en.wikipedia.org/wiki/Canine_transmissible_venereal_tumor
- https://www.intechopen.com/chapters/82773
- https://vcahospitals.com/know-your-pet/transmissible-venereal-tumor
- https://juniperpublishers.com/ctoij/CTOIJ.MS.ID.555895.php
- https://link.springer.com/article/10.1023/A:1006491918910
- https://www.ivis.org/library/recent-advances-small-animal-reproduction/canine-transmissible-venereal-tumor-etiology
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