Canine Transmissible Venereal Tumors: These Tumors Can Be Spread

The probability is that you have never seen a tumor that can be spread from one individual to another. But did you know that there is a tumor that can be transmitted from dog to dog?

Transmissible Venereal Tumor (TVT) is a tumor of dogs that is surprisingly common and widely distributed. Canine TVT occurs primarily in dogs that are largely uncontrolled and allowed to breed indiscriminately. It also affects other canids such as coyotes, foxes and jackals.

Also known as infectious sarcoma, venereal granuloma, transmissible lymphosarcoma or Sticker tumor, this disease is a benign tumor that occurs primarily on the external genitals of both male and female dogs. It is one of a very few tumors that can be transmitted by direct contact. It acts like a freely living organism -- more a parasite than a cancer.

What does TVT look like?
Canine TVT is cauliflower-like, pedunculated, nodular, papillary, or multilobulated in appearance. It ranges in size from a small nodule (5 mm) to a large mass1. Finding a small nodule that bleeds and is located on the external genitalia is the most consistent symptom. The condition is transmitted during sexual contact and is most commonly seen in young, but mature, sexually active animals.

How does a dog become affected?
Transmission occurs during direct contact with other dogs2. Elizabeth Murchison, a cancer biologist at the Wellcome Trust Sanger Institute in Hinxton, UK says, “It’s the oldest continuously surviving cancer we know of in nature.” It first appeared in an ancient breed of dog, not unlike the Alaskan malamute, that was of medium to large size. TVT remained in an isolated population of dogs for most of its history, then something happened that allowed it to move into other dog populations and spread around the world3. “These tumors are masters at survival, at transmission and at invading new tissues,” says Hannah Siddle, a tumor immunologist at the University of Southampton, UK, who studies contagious cancers.

How is the TVT diagnosed?
Your veterinarian must perform a biopsy or examination of cells from the mass to be sure it's TVT.

What is the prognosis with TVT?
Initially, TVTs grow rather fast and more rapidly in neonatal and immuno-suppressed dogs. Metastasis (spreading) is uncommon (5%). Many cases resolve spontaneously and self cure. Complete surgical removal is difficult and recurrence is likely. Radiation therapy is effective but the tumor is very responsive to chemotherapy1. Currently a drug called Vincristine is helpful with a period of 6-7 weeks as the recommended treatment.

Is TVT transmissible to humans?
There is no risk of transfer of the tumor to humans.

Can the condition be prevented?
Since the method of transmission is direct sexual contact, prevention of coatis is the best means of prevention.

See your veterinarian right away for any lesions. An early diagnosis and prompt treatment reduces the course of most diseases.

If you have any questions or concerns, you should always visit or call your veterinarian -- they are your best resource to ensure the health and well-being of your pets.

1. "Overview of Canine Transmissible Venereal Tumor." Merck Veterinary Manual. Web.

2. "Canine Transmissible Venereal Tumor: A Review." Internet Scientific Publications. Web.

3. Borrell, Brendan. "How a Contagious Dog Tumor Went Global." Nature Publishing Group, 23 Jan. 2014. Web.

Canine Transmissible Venereal Tumors: These Tumors Can Be Spread - pets

Street dogs around the world have a constant battle against hunger, disease and indiscriminate breeding, resulting in unnecessary pain and suffering. Mayhew International believes free-roaming dogs should be able to live healthily side by side with people and our humane and sustainable projects work towards this goal.

A less well-known but common disease associated with free-roaming dogs worldwide is the Canine Transmissible Venereal Tumour (CTVT). Here in the UK, the condition disappeared during the 20 th century following the introduction of dog control laws, but in places like Afghanistan it can be found in as much as 10% of the dog population.

A CTVT is a naturally occurring sexually transmitted tumour that can be passed from dog to dog very easily. It is most common in young, unneutered dogs and free-roaming dogs are at the highest risk of contracting the disease. Sadly Mayhew’s team in Kabul, Afghanistan have seen several cases during their work in the field vaccinating against rabies in the city.

However, despite its prevalence, it is a preventable disease.

CTVT is transmitted through direct contact with tumour cells from a diseased animal, usually during mating, but also through oral contact such as biting, licking or sniffing. It is spread by the transfer of living cancer cells between dogs and it presents as a red bulging mass on the surface of the genitals of both male and female dogs. The mass will be painful, uncomfortable and bleed easily, causing the dog to lick the affected area frequently. Un-neutered females are also at higher risk of developing fatal infections of the womb, known as pyometras, and cancerous mammary tumours from multiple litters of puppies. One female dog the team encountered, seen above with Mayhew Afghanistan Country Director, Dr Mohammadzai DVM, was suffering from TVT which had metastasized to a large mammary tumour and was causing the dog intense pain and discomfort. Sadly, there was nothing we could do to help this dog and the kindest thing was to put an end to her suffering.

Although owned dogs with CTVTs can be treated with chemotherapy, this option is simply not possible for the street dogs of Kabul. The best way to prevent them contracting and spreading this condition is to spay and neuter the dogs. Mayhew has long been an advocate of neutering as the most humane way to reduce the overpopulation of dogs, but it is also effective against reducing the risk of these sexually transmitted cancers and other diseases of the reproductive organs.

Mayhew Afghanistan is currently planning to implement a comprehensive neutering programme in Kabul to help control the free-roaming dog population, as well as combat the spread of CTVT and other diseases. This will ultimately reduce the suffering of street dogs in the city and start to build a healthier community. Our plan for 2019 is to neuter 6,400 dogs, which is 40% of the population, targeting primarily the female dogs.

Mayhew Afghanistan is also proud to be participating in a research programme with Cambridge University Vet School on the spread and development of CTVTs around the world.

We have calculated a cost of approximately £50 to Trap, Vaccinate, Neuter and Release (TVNR) one dog in Kabul, including catching the dog, bringing them to the clinic, pre and post-op care and 48-72 hours boarding, surgery, rabies vaccination, parasite treatment, identification and releasing them back to their own area.

Case description

A 1-year-old, 15-kg, intact, mixed breed, female dog was presented to St. George’s University Small Animal Clinic (SGU SAC) for evaluation of a suspected prolapse of her right third eyelid and unilateral ocular discharge. The dog had been adopted by a veterinary student 3 days earlier after it was found wandering the neighborhood. On presentation the right third eyelid was prominent, light pink in color with diffuse punctate, raised lesions. There was moderate, yellowish-brown crusting around the eye. A neuro-ophthalmic examination showed the eyes to be normal bilaterally. Tear production, intraocular pressures, and a fundoscopic examination were normal in both eyes. There was no corneal uptake of fluorescein stain bilaterally. Clavamox (Pfizer Animal Health, New York, New York, USA) 16 mg/kg body weight (BW) PO, q12h for 14 d, Rimadyl (Caplets and Chewables Pfizer Animal Health) 2.5 mg/kg BW PO, q12h for 5 d, and chloramphenicol ophthalmic ointment (Vetachloracin Ophthalmic Ointment 1% Dechra Veterinary Products, Overland Park, Kansas, USA) OD ¼ inch strip applied topically q12h for 7 d were prescribed. Despite these therapies chemosis of the right third eyelid worsened and the ocular discharge increased.

Three days later the dog was re-examined at the SGU SAC. The right third eyelid was noticeably more swollen with punctate hemorrhages, scalloped edges, and several lobulated masses evident. Blood-tinged epiphora with moderate brown-black crusting around the eye was seen ( Figure 1 ). The third eyelid mass was friable and bled when manipulated with a cotton tip applicator. The left eye was normal.

Ocular transmissible venereal tumor (TVT) of the right third eyelid and bulbar conjunctival tissue in a dog.

A complete blood (cell) count (CBC), serum biochemistry profile, and analysis of urine collected by cystocentesis were performed along with a Snap 4Dx test (IDEXX Laboratories, Westbrook, Maine, USA) to screen for vectorborne disease agents Dirofilaria immitis (heartworm disease), Ehrlichia canis (ehrlichiosis), Anaplasma phagocytophilum (anaplasmosis), and Borrelia burgdorferi (Lyme disease). In addition, impression smear cytology of the third eyelid mass was done. The CBC revealed a mild non-regenerative anemia [hematocrit (HCT) 34% reference interval (RI): 37% to 55%, reticulocyte count 1.5%)] and marked thrombocytopenia (36 × 10 9 /L RI: 175 to 500 × 10 9 /L). The serum biochemistry profile revealed mild hyperphosphatemia (2.45 mmol/L RI: 0.81 to 2.2 mmol/L), and moderate hyperproteinemia (93 g/L RI: 52 to 82 g/L) characterized by a hyperglobulinemia (63 g/L RI: 25 to 45 g/L). The urine specific gravity was 1.045 and the urine sediment examination was unremarkable. The dog was positive for D. immitis, E. canis, and A. phagocytophilum and negative for B. burgdorferi on the IDEXX 4Dx Snap test. Impression smear cytology of the right third eyelid mass using Giemsa stain revealed a neoplastic round cell population with some inflammatory cells (75% neutrophils and 25% macrophages). Features of malignancy in the round cell population included mild to moderate anisocytosis, anisokaryosis, numerous mitotic figures, and abundant faint basophilic cytoplasm. The cells had an increased nuclear to cytoplasmic ratio and the cytoplasm contained 3 to 4 distinct vacuoles characteristic for transmissible venereal tumor (TVT) ( Figure 2 ). Given the findings consistent with TVT a vaginal examination was performed. No vaginal mass was visualized or palpated.

Impression smear cytology of the third eyelid transmissible venereal tumor (TVT) revealing characteristic features of a TVT showing a round cell population with mild to moderate anisocytosis, anisokaryosis, a few mitotic figures and abundant faint basophilic cytoplasm with characteristic cytoplasmic vacuoles. Image courtesy of Dr. Kumthekar.

Treatment with doxycycline (Westward Pharmaceutical Corp, Edmonton, New Jersey, USA), 10 mg/kg BW, PO q12h for 30 d, for ehrlichiosis and anaplasmosis was initiated. In addition, Iverhart Max Chewable tablet containing ivermectin 136 μg, PO, q30d, pyrantel pamoate 114 mg, and praziquantel 114 mg (Virbac Animal Health, Fort Worth, Texas, USA) were prescribed for heartworm and intestinal parasites. For the TVT, treatment with vincristine sulfate (Hospira, Lake Forest, Illinois, USA), 0.025 mg/kg BW, IV, q7d for a total of 6 treatments was initiated. Due to financial limitations of the owner the dog was monitored with a CBC every other week instead of every week.

Photographs of the right nictitating membrane lesion were taken at each follow-up visit to monitor progress ( Figures 3a, b ). After the first vincristine treatment only minimal improvement was noted. A CBC performed prior to the second vincristine treatment revealed no improvement in the anemia (HCT 34%), a persistent but improved thrombocytopenia (162 × 10 9 /L RI: 175 to 500 × 10 9 /L), and a mild eosinophilia (1.7 × 10 9 /L RI: 0.5 to 1.5 × 10 9 /L).

A — Partial resolution of the third eyelid transmissible venereal tumor (TVT) in a dog after 3 weekly vincristine sulphate treatments (left), and B — Complete resolution of the third eyelid TVT in a dog after 6 weekly treatments with vincristine sulfate (right).

By the third week the right third eyelid mass had decreased dramatically in size. By the fourth week only a small remnant of the mass was visible ( Figure 3a ) and by week 6, the mass was no longer evident without exteriorization of the third eyelid. However, marked thrombocytopenia (25 × 10 9 /L) persisted, along with a now regenerative anemia (HCT 35.9%). A manual platelet count with only 1 platelet seen per high power field (hpf ) confirmed the thrombocytopenia. Because the thrombocytopenia was attributed to bone marrow suppression from the vincristine the sixth, and final vincristine treatment, was postponed by a week. Prior to the sixth treatment a recheck CBC revealed normalization of the platelet count (200 × 10 9 /L RI: 175 to 500 × 10 9 /L) and resolution of the anemia (HCT 37.5%). At this time the dog was sedated with Propofol (PropoFlo Abbot Laboratories, Abbott Park, Illinois, USA), 0.2 mg/kg BW, IV and her right third eyelid was everted to permit examination. Only a very small remnant of the mass was still visible. Complete resolution was evident 1 week later after the final treatment ( Figure 3b ). With resolution of the ocular TVT, heartworm adulticide treatment was initiated and was well-tolerated with no complications. Eighteen months after initial presentation, there was no visible recurrence of the dog’s TVT.

History of Dogs Tracked Through Contagious Canine Cancer

Around 11,000 years ago, a dog became immortal. One of its cells started growing and dividing uncontrollably, giving rise to a tumour. And one of the cells from that tumour became contagious. It gained the ability to leave its original host and infect new ones. It jumped into another dog, and another, and another, creating a fresh tumour in each new host. That original dog is long dead, but in a way, it lives on in the contagious cancer that it spawned.

That cancer, now known as canine transmissible venereal tumour (CTVT), has since travelled across six continents, spreading from dog to dog by sex or close contact. It’s a global parasite. It’s also the oldest living cancer.

A Russian veterinarian named Mstislav Novinski first described this contagious cancer in the 1870s, but it took till 2006 for Robin Weiss and Claudio Murgia from University College London to discover its true nature. By comparing tumour samples from 40 dogs across the world, the team showed that CTVT tumours are more closely related to each other than to cells from their host dogs. In other words, they hadn’t arisen independently in each host. They were all descendants of that same original contagious cancer.

And this cancer hasn’t gone unchanged during its travels. On occasion, it has swapped out its batteries.

Our cells are powered by tiny bean-shaped structures called mitochondria. These are passed down from mother to daughter, and they have their own small independent genomes. This should mean that all the mitochondria in every CTVT cell descends from that ancestral tumour, and that it should be possible to map their genomes only to a single exclusive family tree.

It’s not. In 2011, Clare Rebbeck analysed mitochondrial genomes from 37 tumour samples and found that they belonged to two main lineages, each of which clustered with a different group of dogs. This strongly suggested that the contagious cancers occasionally pick up new mitochondria from their hosts.

How many times has this happened? At least five, according to Andrea Strakova and Máire Ní Leathlobhair from the University of Cambridge. They got that number through the biggest survey yet of CTVT—a whopping 449 tumours from 39 countries. They showed that the mitochondria of these tumours group into five different lineages, implying five replacement events.

All of these lineages are younger than 1,700 years, and CTVT itself is at least 11,000 years old. This means that the original mitochondria from the founder dog that first spawned these tumours are no more. They were replaced.

No one knows how these mitochondrial swaps occur. Tumour cells might grab the mitochondria of new hosts by fusing with their cells. Alternatively, “it’s possible that little tubules form between the tumour and host cells,” says Elizabeth Murchison, who led the new study. Mitochondria then travel along these bridges.

It’s also unclear why this happened. “That it happened five times suggests that it conferred some kind of advantage,” says Murchison. Mitochondria burn a lot of energy and their DNA has a habit of changing quickly. Many of these changes will be harmful. But as the CTVT cells go on the move, they can swap their worn-out batteries with fresh ones from new hosts.

Supporting this idea, Murchison’s team found an unusually low number of disruptive mutations among their mitochondrial genomes. “In cancer, that’s not usually the case cancer cells aren’t very good at protecting essential genes,” she says. “This suggests that the mitochondrial DNA is probably quite important for the viability of CTVT.”

There are also four other transmissible tumours: two that affect Tasmanian devils, one in shellfish, and another in captive Syrian hamsters. Studying these unusual cancers, Murchison says, gives us clues about the biology of normal ones that don’t spread between hosts.

For example, the team found signs that the mitochondria of CTVT cells can sometimes shuffle their DNA with the mitochondria of their hosts. This is called recombination, and it has never been seen in cancer cells before. This could be happening in human cancers and we’d never know because the mixing mitochondria would have nigh-identical genomes. But if it did happen, “it may be important for maintaining and repairing mitochondrial DNA,” Murchison says. “

Contagious cancers can also be informative in unexpected ways. For example, the history of the five contagious cancer lineages reveals the history of dogs, which in turn reveals the history of humans. One lineage is widespread throughout Eurasia, but only reached the Americas around 500 years ago, reflecting Europe’s colonisation of the New World. Another lineage seems to have spread through trade routes across the Atlantic and Indian oceans. As humans criss-crossed the world, we took our dogs with us—and their contagious tumours followed.

It is sobering to think that this rogue cancer—this immortal dog—will likely outlive you, me, and everyone who currently studies it.

Treatment of Transmissible Venereal Tumors in Dogs with Intratumoral Interleukin-2 (IL-2). A Pilot Study

Aim: To improve the treatment of transmissible venereal tumors (TVTs) in dogs with intratumoral injections of interleukin-2 (IL-2). Patients and Methods: We treated 13 dogs with 18 natural TVTs with IL-2. The tumors were treated with intratumoral application of 2×10 6 units IL-2. Results: Three months after injection of IL-2, the tumors in 2/13 dogs had regressed completely, those in 1/13 had regressed partially, and 4/13 dogs had stable disease. Conclusions: Local IL-2 treatment of TVT is therapeutically effective, as indicated by complete regression (CR), partial regression (PR) and stable disease (SD) of the tumors of 7 out of 13 dogs. In addition, we observed that the intratumoral treatment with IL-2 did not cause any toxic side-effects.

Transmissible Venereal Tumors (TVTs) were first described by Nowinsky in 1876 (1). TVTs most frequently occur in dogs in tropical and sub-tropical countries. TVTs are usually transmitted from dog to dog during mating when abraded skin is exposed to the tumor of an infected dog (2, 3). Consequently, the tumors grow mainly on the genitals. The literature on TVTs is often confusing and contradictory as there are two forms of TVTs: natural and experimental TVT that, however, are not always recognized (4). Many studies focus on experimentally-transplanted or injected TVTs, which have a different disease course than naturally transmitted TVTs. This difference is probably related to differences in antigen presentation after disease transfer by contact via the epithelial cells or sub-epithelial cells. An experimental TVT is usually transferred by subcutaneous injection of TVT cells. After transplantation, there is usually first a progressive growth phase during 5-7 weeks followed by a static phase and a regression phase (3, 5-7). After three to nine months, the transplanted TVT is rejected by the immune system. The natural disease is transmitted by sexual intercourse or other close contact between dogs. Authors often stress that natural TVT can be transmitted because these tumor cells do not induce an immune reaction. Natural TVT does not regress spontaneously these tumors grow or are in steady state. In immunologically incompetent or compromised hosts the tumor progresses to ulceration and metastasis (8) in about 5 % of the cases (9). This is in line with Murchison (10) and Purohit (11) who stress that spontaneous regression has not been well-documented in natural TVT.

The tumor is transmitted by viable tumor cells but not by dead tumor cells, viruses or cell-free filtrates (12). The origin of TVTs is not yet clear but, at present, most authors conclude that TVT has a histiocytic origin (3, 13-15). TVT should be differentiated from mastocytoma and malignant lymphoma (14). TVT grows as a homogeneous population of large round cells with distinctive centrally located nucleoli (3).

The infectious nature of TVT may be surprising, but TVT is not the only tumor that is spread by contact between a tumor bearer and a healthy recipient as a similar disease occurs in the Tasmanian Devil, a marsupial in Tasmania. Devil facial tumor disease (DFTD) affects the face of animals due to tumor cell transfer during fighting (10). This tumor often kills the host within 6 months (6) and is considered a threat to the endangered species.

Both DFTD and TVTs have a chromosomal abnormality (10, 14). Somatic cells in dogs have 78 chromosomes but TVTs have 57-64 chromosomes (17, 18). TVT is thought to be a single clone (14) that emerged either about 250-2,500 or 7,800-78,000 years ago (14). DFTD tumor in Tasmanian devils emerged recently, probably some decades ago as an aggressive facial tumor (10). In most cases the tumor does not metastasize but it grows and bleeds. Dogs suffering from TVTs often exude serosanguineous fluid from their TVTs, thereby infecting other dogs and soiling their living area. The predilection site of the tumor for genitals often inhibits complete surgical removal of the tumor (5). A major problem of surgery, therefore, is that most tumors recur. As such, if complete surgery is impossible, chemotherapy is considered the treatment of choice. Usually, the dogs are treated with intravenously-applied vincristine sulphate (0.5-0.7 mg/m 2 ). Intravenous application once weekly for 3-6 weeks is usually effective (6, 19). However, as it is undesirable to come into contact with spilt vincristine (especially children and pregnant women) a non-toxic replacement drug is needed.

Watch the video: Infectious Cancers in Tasmanian Devils (May 2021).