The owner expressed concern that the cat had lost weight over the past several months, though the cat had previously been overweight. The cat's appetite seemed unchanged, there were no other systemic signs of disease such as polyuria or polydipsia, and there was no history of inappropriate urination. Multiple cats lived in the household, and they were all housed strictly indoors and fed a commercial feline kibble, but the owner did not closely observe their food consumption and litter box habits.
On physical examination, the cat's body condition score was 3 (on a scale of 5) with no muscle atrophy. No abnormalities were noted apart from Stage 3 periodontal disease and findings indicative of feline odontoclastic resorptive lesions on the mandibular molars. The cat's weight loss was attributed to probable reluctance to eat because of oral pain. Rabies, feline viral rhinotracheitis, calicivirus, and feline panleukopenia virus vaccinations were given, and the cat was scheduled for a dental examination, radiography, and prophylaxis with extractions as necessary.
Initial dental treatment and additional test results
No growth was present on bacterial culture of the urine. The bacteriuria was attributed to misidentification of fat droplets or other debris in the sediment, particularly since the cat had not been receiving antibiotic therapy at the time of sample collection. The results of the renal cytologic examination revealed a highly cellular sample that was compatible with a diagnosis of primary renal cell carcinoma (Figure 2), although this tumor is relatively rare in cats.
The cat was anesthetized for an exploratory celiotomy. The anesthesia protocol included premedication with midazolam and buprenorphine, induction with propofol, and maintenance with sevoflurane in oxygen. Ongoing analgesia was provided by a constant-rate infusion of fentanyl and lidocaine. Indirect Doppler blood pressure measurements were obtained intermittently, and continuous electrocardiographic and temperature readings were obtained. Perioperative intravenous crystalloid fluids were supplemented by a single bolus of intravenous hetastarch to treat an episode of hypotension during the procedure.
The right kidney was an irregular mass that appeared contained within the renal capsule. The remainder of the abdominal organs appeared grossly normal. A right nephrectomy was performed, and the cat recovered without complications.
The cat was admitted to the hospital for overnight monitoring and was treated with intravenous hydromorphone for analgesia and lactated Ringer's solution with supplemental potassium chloride. Urine output was estimated to be normal.
On the day after surgery, a renal biochemical profile (BUN, creatinine, calcium, phosphorus, magnesium, total protein, albumin, globulin, sodium, chloride, potassium, bicarbonate, osmolality, creatine kinase, glucose, and cholesterol) revealed the cat had mild hypoproteinemia (total protein 5.6 = g/dl; reference range = 5.9 to 8.2 g/dl) and mild hyperkalemia (potassium = 5.5 mmol/L; reference range = 3.9 to 5.3 mmol/L). The mild hypoproteinemia and hyperkalemia were attributed to the intraoperative and postoperative intravenous fluid therapy.
The cat was discharged the day after surgery with buprenorphine (0.03 mg given sublingually twice daily), and the owner was told to bring in the cat for a renal biochemical profile and urinalysis two to three weeks after discharge.
Follow-up evaluations and treatment
The referring veterinarian evaluated the cat 11 days after surgery. The cat was doing well and had an improved appetite and normal activity level. The incision had healed. A renal biochemical profile revealed persistent, mild hyperkalemia (potassium = 5.5 mmol/L; reference range = 3.3 to 5.4 mmol/L). Urinalysis revealed concentrated urine with a specific gravity greater than 1.040, trace proteinuria, and an inactive sediment (Table 2).
On Day 83 after surgery, the cat was presented to the University of Minnesota for evaluation of ocular problems. Horner's syndrome was noted in the left eye, but the cat's vision was apparently unaffected, and the globe and fundus examination results were normal. There were no other neurologic deficits. On physical examination, the cat was thin and had lost another 1.5 lb (0.68 kg) since its last visit (on Day 69 after surgery), for a total loss of 2.5 lb (1.14 kg), or 22.8% of body weight, since the second mitoxantrone treatment on Day 48 after surgery. The differential diagnoses for the Horner's syndrome were metastatic neoplasia affecting the vagosympathetic trunk, spinal cord, or brainstem or an idiopathic cause (due to the lack of other concurrent neurologic clinical signs).
On Day 90 after surgery, the cat received a fourth dose of mitoxantrone. The Horner's syndrome persisted, and a topical 10% phenylephrine test revealed a partial response, with some resolution of the miosis in the left eye at 10 minutes and then no further change out to 60 minutes. Physical examination findings were unchanged from the previous visit. The results of a CBC were within reference ranges (Table 1), and the results of feline immunodeficiency virus antibody and feline leukemia virus antigen tests were negative.
Three-view thoracic radiographs revealed a left-sided soft tissue mass in the cranial mediastinum near the thoracic inlet (Figure 5). The most likely differential diagnosis for this mass was metastatic spread of the primary renal transitional cell carcinoma. The mediastinal mass was thought to be the most likely cause of the cat's Horner's syndrome. Additionally, there was a moderate, diffuse bronchial pattern not seen on the previous radiographs. The bronchial pattern was consistent with moderate to severe bronchial disease, although an atypical presentation for metastasis could not be ruled out.
Feline renal transitional cell carcinoma and feline renal cell carcinoma exhibit distinct biologic behaviors. Renal carcinomas are less likely to metastasize, with only five cases of confirmed metastasis noted in 13 cats with the disease,1 so surgical excision of a unilateral tumor may prolong survival. Like the cat described here, all previously reported cases of feline renal transitional cell carcinoma have developed distant metastases. Sites of metastasis include the sublumbar or tracheobronchial lymph nodes, contralateral kidney, liver, spleen, adrenal glands, omentum, mesentery, lungs, eyes, skeletal muscles, and meninges.3
This cat displayed some of the most common signs of a feline primary renal tumor: decreased appetite, weight loss, and a palpable abdominal mass. Less common signs include hematuria, abdominal pain, abdominal distention, dyspnea, systemic hypertension, and blindness or other neurologic signs.1,3 Although pyuria has not been specifically reported in cases of feline primary renal tumors, it was a prominent feature in this cat's initial presentation and persisted until nephrectomy. In the absence of a urinary tract infection, the differential diagnoses for pyuria in a sample obtained by cystocentesis are noninfectious inflammatory conditions of the urinary tract, including urolithiasis, trauma, chemical irritation, and neoplasia.5 In this cat, multiple negative bacterial culture results ruled out a urinary tract infection, and the pyuria was considered to be due to inflammation caused by the tumor.
A feline renal tumor can be diagnosed with a physical examination along with an abdominal radiographic examination, ultrasonographic examination, or both. Cytologic examination can help determine whether neoplasia is present and often indicates a general tumor type, but histologic examination is needed to make a definitive diagnosis. Because primary renal epithelial tumors are rare in cats and the cytologic appearance can be similar, pathologists may have difficulty in distinguishing among specific types. Two of the three tumors diagnosed as renal transitional cell carcinoma on final histologic review in a recent study were initially identified as other renal epithelial tumors.1 Overall, eight of 19 feline primary renal tumors were reclassified after histologic verification in that study.1 As the metastatic potential for renal transitional cell carcinoma is higher than for other renal epithelial tumors, histologic confirmation of tumor type should be sought after definitive surgery. In this cat, the initial cytologic diagnosis suggested a renal cell carcinoma, but histologic evaluation of both the surgical biopsy and necropsy samples confirmed renal transitional cell carcinoma.
Before determining a treatment plan, an overall health assessment and complete staging of feline primary renal tumors should include thoracic radiography (three-view), a CBC, a serum chemistry profile, a total T4 measurement, urinalysis, and feline leukemia virus and feline immunodeficiency virus serology.
In the absence of evident metastatic disease, the preferred treatment for feline primary renal tumors is removal of the affected kidney. For low-grade renal cell carcinoma or renal sarcoma, this approach may be curative provided renal function remains adequate. Surgical excision is thought to prolong survival in cats with renal cell carcinoma because of the tumor's lower metastatic rate compared with renal transitional cell carcinoma. However, for renal transitional cell carcinoma and most renal cell carcinomas, the long-term prognosis is guarded because of local tumor recurrence or metastasis.3
Adjuvant chemotherapy has been proposed for renal transitional cell carcinoma and renal cell carcinoma, but no standard protocols exist for either of these rare feline tumors. Mitoxantrone chemotherapy caused a partial remission of 60 days in a cat with urinary bladder transitional cell carcinoma.6 Carboplatin is safe in cats and has been suggested as an adjuvant treatment for bladder transitional cell carcinoma in cats, although no reports support this use.3 Piroxicam has been used in dogs to successfully treat bladder transitional cell carcinoma, but there are no reports of its use in cats for this purpose.3 These options were considered, and single-agent mitoxantrone chemotherapy was selected for adjuvant treatment of this cat's renal transitional cell carcinoma.
Mitoxantrone is an antitumor antibiotic chemically related to doxorubicin that has been used to treat lymphoma, mammary adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma in dogs and cats. Its mechanism of action is to inhibit topoisomerase II activity,7 and its pharmacokinetics has been described in cats.8 One study evaluated the toxicoses and efficacy associated with administering mitoxantrone in cats with various malignant tumors.6 Including the partial remission of a cat with bladder transitional cell carcinoma already mentioned, the overall remission rate (complete and partial) for carcinomas was about 18% (nine of 51 cats) in that study. A typical feline treatment regimen is to administer 6 to 6.5 mg/m2 intravenously every three weeks. In cats, gastrointestinal side effects were most common. Other reported side effects were myelosuppression, seizures, and secondary sepsis.
Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) frequently used as an antitumor agent in dogs, particularly in treating transitional cell carcinoma. The single-dose pharmacokinetics of piroxicam in cats has been described.9 While cats tolerated the medication well and no adverse effects were noted, the study only evaluated single-dose administration, which would be ineffective for tumor control.
Horner's syndrome is a common peripheral neuropathy with many possible causes, including otitis media or interna, trauma, brachial plexus root avulsion, and cranial mediastinal lesions.10,11 Pharmacologic testing has been described to help localize the lesion in animals with acute Horner's syndrome. When a dilute, direct-acting sympathomimetic agent (e.g. phenylephrine at concentrations of 1% to 10%) is applied topically to the eye, lack of pupillary dilation suggests a preganglionic lesion such as intracranial disease, a C1-T3 myelopathy, or thoracic disease. A positive test result (resolution or improvement of miosis within 20 minutes) should indicate a postganglionic lesion because of the increased sensitivity of local adrenergic nerves after sympathetic denervation.12 Although as described, pharmacologic testing should be helpful in localizing the site of neuron injury, the specificity of the test has not been reported.10 For example, in this cat a partial response to dilute phenylephrine suggested a postganglionic lesion. But at necropsy, the cat was found to have tumor metastasis involving the thoracic sympathetic trunk, with no evidence of postganglionic disease.
Pulmonary metastatic disease in dogs and cats typically appears as well-circumscribed, interstitial nodules. However, it has been suggested that cats are more likely to have an atypical pattern of metastasis on thoracic radiographs, and in one study, seven of 25 cats with pulmonary metastases showed a diffuse pattern; all had epithelial tumors, although none had transitional cell carcinoma.13 The cat described here developed a diffuse bronchial pattern that was seen on thoracic radiographs at Day 90 after surgery, and at necropsy the cat was found to have numerous small pulmonary metastases with no evidence of bronchial disease. CT provides additional information when compared with thoracic radiographs alone in both dogs and cats.14,15 In this cat, the thoracic CT scan identified thoracic lymphadenopathy that was not evident on plain radiographs. Interestingly, the pulmonary parenchyma was interpreted as normal on the CT scan, which brings into question whether the bronchial change interpreted on plain radiographs represented the pulmonary metastases that were demonstrated postmortem.
Renal transitional cell carcinoma is a rare tumor in cats that has aggressive biologic behavior but can initially present with vague, nonspecific signs. Generally, the clinical signs are decreased appetite, weight loss, hematuria, or pyuria. Once a renal mass is recognized, initial diagnosis of renal tumors can be made by fine-needle aspirate cytology. This simple procedure can help identify cats that may benefit from nephrectomy. However, histologic confirmation should always be obtained after surgery, as the long-term prognosis varies with specific tumor type.
Andrew R. Lie, DVM*
Blaine Area Pet Hospital
11844 Aberdeen St. NE
Blaine, MN 55449
Cheri Nielsen, MS, DVM**
Department of Veterinary Clinical Sciences
College of Veterinary Medicine
University of Minnesota
St. Paul, MN 55108
*Mission Pet Hospital
720 Valencia St.
San Francisco, CA 94110
**Pet Emergency and Specialty Center of Marin
901 E. Francisco Blvd., Suite C
San Rafael, CA 94901
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