How is Transitional Cell Carcinoma (TCC) Diagnosed?

 
 
 

1. Signs and Symptoms

Blood in the urine, straining to urinate, and frequent repeated attempts to urinate are the most common signs of TCC in dogs. A bladder infection, a bladder stone, or in cats a lower urinary tract disease would be more common and must be ruled out first. The average age at TCC diagnosis is 9-11 1 years and 15 years in cats 2 . Female dogs have an increased risk of TCC than male dogs, possibly because females do less urine marking and are thus possibly storing urinary toxins longer. In cats, males have an increased risk over females. Certain breeds of dogs have also shown to be at higher risk for TCC. Scottish Terriers have an 18-20 fold higher risk of TCC than other dogs. Shetland Sheepdogs, Beagles, West Highland White Terriers, and Wire Hair Fox Terriers are 3 to 5 times more likely to develop TCC than other dogs 1 . A seven fold increased risk of TCC was found in Scottish Terriers exposed to lawns or gardens treated with herbicides and insecticides or herbicides alone according to a study published in 2004. These findings indicate that Scottish Terriers, as well as other dogs of high-risk breeds for TCC, should be restricted from lawns treated with herbicides and pesticides 3 .

2. Urinalysis and Culture

Urinalysis and culture is typically the first step of diagnosis. A known infection does not rule out a tumor as tumors may easily become infected. About 30 percent of TCCs will shed tumor cells into the urine that may be identified as such on the urinalysis 2 . If an infection is found in the bladder, it may be worthwhile to simply treat it with the appropriate antibiotic and see if the clinical signs resolve. However, survival and remission is greatly enhanced if TCC is found early. Do not be afraid to request an ultrasound or Cadet BRAF urine test if your dog is a high risk breed or at an advanced age.

If no infection is found, if the urinalysis is normal despite obvious symptoms, if your veterinarian can feel a growth, or if there is some other reason to be suspicious of tumor, xrays and/or an ultrasound would be the next step 2 . The goal would be to rule out a bladder stone and this can be done with either xrays or ultrasound. Xrays are typically less expensive and more available than ultrasound. Most bladder stones are visible on xrays and as soon as they are identified, appropriate treatment can be initiated 2 .

3. Ultrasound

Ultrasound offers the ability to visualize soft tissue structures within the bladder, which xrays cannot 2 . Abdominal ultrasound is commonly used to evaluate the bladder wall, kidneys and ureters, as well as for possible metastatic spread within the abdominal cavity. If you have a high risk breed, it may be worthwhile to have an ultrasound performed to rule out bladder cancer. Survival and remission is greatly enhanced if TCC is found early.

4. CADET BRAF Mutation Urine Test

A non-invasive test for transitional cell carcinoma has been tested and confirmed for dogs. It has been found that 85 percent of canine transitional cell carcinomas have a mutation called the BRAF mutation, and it can be detected in a urine sample well before the tumor is visible via special imaging 2 . The Cadet BRAF test can be used to screen asymptomatic dogs of an at-risk breed or it can be used to determine a diagnosis for a dog with symptoms when there is a question of tumor. The test is not available for cats and it requires 30cc of urine (a relatively large sample) 2 . 15 percent of dogs with TCC do not express the BRAF mutation and will test negative. The Cadet BRAF-Plus assay was launched commercially in July 2018 and can be used as an add-on test when the initial BRAF test is negative. This assay detects a second signature in more than two-thirds of non-BRAF patients. The new test increases overall sensitivity for detecting TCC/UC from 85% to more than 95% 4 . This translates to 5% false negatives and 0% false positives.

5. Tissue Biopsy

Dr. Knapp at Purdue University believes "a definitive diagnosis of TCC is made with a tissue biopsy. Several other types of growths in the bladder, bladder infection, bladder stones, or bladder inflammation can cause similar symptoms as those in dogs with TCC. Some of these other conditions can also cause "masses" to be seen on radiographs or ultrasound, and these other conditions can cause abnormal cells in the urine, which can be mistaken for TCC. This is important because the treatment and prognosis depend entirely on exactly what is wrong with the bladder. A tissue biopsy can be obtained by surgery, cystoscopy (insertion of a fiberoptic scope into the bladder and biopsy through the scope), or in some cases with a urinary catheter" 5 .

If the canine patient has a growth in the bladder neck, this may be all the oncologist needs to know, but if there is any question about the status of the growth, tissue sampling is needed to confirm the diagnosis. Ultrasound guidance can allow a needle aspirate of the growth, but this is not recommended as the TCC is able to seed normal tissue with tumor as a needle is passed through it. More appropriate ways to get a sample include traumatic catheterization (where a sharp urinary catheter is passed and used to slice off or aspirate a piece of the growth; surgery (where the bladder is opened up and tissue is removed for evaluation); or cystoscopy (where a small camera is passed into the urinary tract and tiny instruments can sample the growth). This last option requires a large enough urinary tract opening to accommodate the equipment; male cats are not large enough 2 .


References (includes links to source documents):

  1. Knapp, Deborah & Ramos-Vara, José & Moore, George & Dhawan, Deepika & Bonney, Patty & Young, Kirsten. (2014). Urinary Bladder Cancer in Dogs, a Naturally Occurring Model for Cancer Biology and Drug Development. ILAR journal / National Research Council, Institute of Laboratory Animal Resources. 55. 100-18. 10.1093/ilar/ilu018.

  2. Brooks, W., 2018. Transitional Cell Carcinoma In Dogs And Cats - Veterinary Partner - VIN. [online] Vin.com. Available at: https://www.vin.com/veterinarypartner/default.aspx?pid=19239&id=4951982[Accessed 23 August 2020].

  3. Glickman, Larry & Raghavan, Malathi & Knapp, Deborah & Bonney, Patty & Dawson, Marcia. (2004). Herbicide exposure and the risk of transitional cell carcinoma in Scottish Terriers. Journal of the American Veterinary Medical Association. 224. 1290-7. 10.2460/javma.2004.224.1290.

  4. Sentinelbiomedical.com. 2020. [online] Available at: <https://www.sentinelbiomedical.com/brafplus-vets/> [Accessed 23 August 2020].

  5. Knapp, D., 2020. Urinary Bladder Cancer Research. [online] Purdue University College of Veterinary Medicine. Available at: <https://vet.purdue.edu/pcop/urinary-bladder-cancer-research.php#:~:text=The%20most%20common%20cancer%20of,cells%20that%20line%20the%20bladder.> [Accessed 23 August 2020].