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Overview

When Zack, a beagle, presented for his annual wellness examination, his veterinarian had lab work performed — including a CBC, chemistry, and urinalysis — as part of his minimum database. Given Zack’s unexpected results, he was referred to a specialist for further testing and a definitive diagnosis.

Case Details

Zack: 12-year-old male neutered beagle

Background: Zack and his family visited his veterinarian for a wellness appointment. Zack’s owners reported that he was doing great at home, no abnormalities since his last appointment a year prior when he’d had a dental cleaning at 11 years old. Being responsible and caring pet owners, they asked whether Zack was due for another dental cleaning. The veterinarian did her physical examination and noted return of his dental tartar, as well as lenticular sclerosis, and arthritis — older dog types of changes. The veterinarian agreed that a dental cleaning was warranted and, in preparation, the doctor sent a CBC, chemistry, and urinalysis to Antech Reference Lab (ARL) as part of a senior wellness panel. Urinalysis is often the forgotten portion of the minimum data baseline but it’s imperative for proper interpretation of the CBC and the biochemistry profile, and it also provides the health care team important information on the upper and lower urinary tract.

Antech Reference Lab Diagnostics

• Zack’s CBC and biochemical profile results from ARL did not reveal any significant abnormalities There was a mild elevation in the alkaline phosphatase (ALP), which had previously been noted for him, so it was not considered of clinical concern.
• Zack’s urinalysis, however, identified increased red blood cells and white blood cells, as indication of inflammation and bleeding. Concerningly, the technologist at ARL also noted atypia in the epithelial cells and flagged it, elevating the urine sediment review to a pathologist.
• An Antech board-certified clinical pathologist reviewed the specimen and confirmed the epithelial cell atypia that was concerning for underlying urothelial or transitional cell carcinoma. The possibility for underlying urothelial cell cancer came as a total surprise to both the veterinarian and owner, as Zack was not showing overt clinical signs at home. Zack was referred to a specialist for further workup.
• At Zack’s referral appointment, the bladder was imaged on ultrasound. Moderate thickening of the bladder wall was noted, but there was no discernible mass.
• Ultrasound imaging of the prostate gland, however, showed enlargement and mixed echogenicity, including a central hyperechoic focus consistent with mineralization which is unexpected in a neutered male dog — especially one neutered before sexual maturity like Zack — adding further concern for underlying carcinoma and the suspected source of the epithelial atypia seen in the urine sediment review at the reference lab.

Now there are two concerning changes for underlying carcinoma and Zack’s health care team needed a definitive diagnosis.

• At the time, it was common practice for this particular specialist to perform fine needle aspiration of suspected urothelial cell carcinomas for cytologic evaluation by a clinical pathologist. In this case, expert review of the cytology preparation confirmed the diagnosis of urothelial cell carcinoma (formerly transitional cell carcinoma).
• Interpretation of cytologic preparations in such cases, however, is commonly confounded by concurrent inflammation and poor cell preservation. Additionally, some practitioners may lack the skill to perform ultrasound-guided aspirates or be reluctant because of possible risks, particularly of potentially seeding the needle track with neoplastic cells.
• The gold standard for diagnosis of urothelial carcinoma is histopathology, which requires a biopsy of the mass, an invasive procedure requiring specialized equipment and training, all of which is expensive for the owners, and in Zack’s case potentially causing a patient that’s not experiencing any signs to then have those things occur because of the procedure.
• Through Antech, there is another, less-invasive option.

Antech Canine Cancer Diagnostics

Studies have shown that 80% to 85% of canine urothelial carcinomas share a specific mutation in the BRAF gene that leads to uncontrolled cell growth, and this mutation can be used as a marker in urine for urothelial carcinomas. Antech Reference Lab offers the CADET™ BRAF PCR test that’s very sensitive and specific for the BRAF mutation.

• The test is done on free-catch urine samples, allowing for sampling and investigation of the entire urinary tract. Over a period of 2-3 days, 40 mls of urine can be collected and pooled from multiple samples. Within 15 minutes of collection, each sample must be transferred into a urine collection cup, supplied by Antech, that contains a preservative and protects the urine from light.
• Given that the BRAF mutation is only present in up to 85% of urothelial carcinomas, if the CADET BRAF test is negative and there is adequate cellularity, the sample is automatically reflexed to the CADET™ BRAF-PLUS test. The BRAF-PLUS looks for a copy number mutation that’s present in another subset of the urothelial carcinomas that lack the BRAF mutation, increasing the sensitivity of the CADET BRAF test.

 

Case Impact

Zack’s case highlights the importance of wellness testing as part of preventive care, and the opportunity to uncover occult disease. In doing so, and by incorporating advanced diagnostics like CADET BRAF testing, veterinary teams are able to identify diseases earlier, sometimes before they cross the clinical threshold. Earlier diagnosis allows for earlier treatment and the opportunity to afford pets longer healthier lives.