Monday, January 27, 2014

Canine transmissible venereal tumour sequenced - and a great dane puppy

We made a new friend on our walk this weekend. Sonny (left) is 20 weeks old. Look at the size of those paws!!! 


This year SAT will be discussing oncology a little more as we're currently undertaking a distance education program on small animal clinical oncology through the Centre for Veterinary Education. (The course hasn't officially begun yet but the reading is fascinating and full of new and very useful information about how to help dogs and cats with benign and malignant tumours).

Anyway, naturally our ears pricked up when we read that the genomes of two canine transmissible venereal tumours (CTVTs) had been sequenced

WARNING: If you scroll down you will see two images of CTVTs - they often appear very inflamed and ulcerated and as the name suggests they have a predilection for the genitalia of dogs. The photos were taken as clinical records and not arranged in the nice neat way you see in medical journals. Apologies in advance. Both patients were sedated but they were sedated "in the field".

Before that, though, this is a photo of my paw beside Sonny's pawprint. Big, huh?

I first encountered CTVTs in the Northern Territory in a remote Indigenous community. I've also seen them in Papua New Guinea. They are remarkable in that these cancers are contagious (and a very good reason for desexing dogs as one mode of transmission is sexual) but they are also highly treatable if the funds and resources are available.

The team who sequenced the CTVTs estimate that they arose around 11,000 years ago. They worked this out by comparing the rate of mutations in these tumours to the rate of mutations in human medulloblastoma.

Since it arose, CTVT has collected 1.9million mutations (typical human tumours acquire 1-5K). Incredibly, now it is pretty stable. So the question is - do cancers go through a mutation phase and eventually stablise and become more amenable to treatment? Of course no cancer patient has 11,000 years to kill. But understanding tumour biology is the key to effective treatment.

A canine transmissible venereal tumour (CTVT) on the vulva of a dog in Port Moresby. The dog is sedated to facilitate examination and sample collection.
CTVTs, along with Tasmanian Devil Facial Tumour Disease (DFTD) are the only known clonally transmissible cancers, transmitted by physical transfer of tumour cells. 

The prevalence of CTVTs in Australia is unknown but they are more common in the tropical North. In overseas studies affected dogs are around 4-5 years old or older (in very young or immunosuppressed dogs the tumour grows rapidly and metastasizes early).

Clinical signs

CTVTs are most likely to affect entire females but they can be transmitted by sniffing or inoculation of tumour cells into the skin. For this reason they sometimes occur on the lips, tongue, pharynx or tonsils, as well as the nasal passages. They can also spread haematogenously, or via lymphatics, to regional lymph nodes, intestine, the liver, spleen, lungs and central nervous system.

Affected animals may have a bulge in the perineal region, or apparent prolapsed tissue from the vulva. Other clinical signs include urogenital discharge, dysuria, pollakiuria, tenesmus and urinary incontinence. Affected animals have a high rate of bacterial urinary tract infection, possibly secondary to partial urethral obstruction by tumour tissue.

A CTVT in a male dog anaesthetised for examination during a dog program. Note haemorrhagic discharge and marked swelling of the prepuce and penis. (Apologies for the grubby hand, lifting the dog on the table was a little messy but the hand is in the photo for scale).
If extragenital sites are involved, signs might include nasal discharge, sneezing, lymphadenomegaly, cutaneous or subcutaneous swelling, dysphagia or facial deformation.

They are uncomfortable, painful and always inflamed.

Diagnosis

Diagnosis in the late stages is reasonably easy as most lesions are visible, often ulcerated and very friable. Masses can be solitary or multiple, a bit cauliflower like, pedunculated, nodular, papillary or multilobulated (in other words pretty gross).

But in the early stages may require vaginal/rectal palpation, contrast vaginoscopy and cytology (CTVTs are an undifferentiated round cell tumour of reticuloendothelial origin. They exfoliate well but inflammatory cell infiltrates are common, nonethless they are easily diagnosed on cytology). Thoracic and abdominal imaging is recommended to screen for mets. 

Some of these tumours regress spontaneously after about six months, probably thanks to effective cell mediated immunity.

Treatment
Surgical excision of these tumours tends to be unsuccessful. They have a high local recurrence rate (up to 68%) but they also tend to be huge, located in surgically awkward sites and so friable that seeding from the tumour is highly likely.

Chemotherapy with vincristine weekly is very successful and curative of many patients (39 out of 41 in one study) - even those with metastatic disease. Vincristine resistant CTVTs may be treated with doxorubicin.

Reference
Rogers KS (1997) Transmissible venereal tumour. Compendium on Continuing Education 19(9):1036-1045.

Withrow SJ, Vail DM & Page RL (eds) Withrow & MacEwen's Small Animal Clinical Oncology: 5th edition. St Louis: Elsevier.

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