A challenging case: A cat with weight loss and an abdominal mass

A 7-YEAR-OLD 11-lb (5-kg) neutered male domestic longhaired cat was presented to its regular veterinarian for vaccinations and a wellness examination. The cat had not received veterinary care in the previous three years. The cat had been vaccinated against rabies and feline viral rhinotracheitis, calicivirus, and panleukopenia at 8 months of age but had not received any vaccinations since then. The results of a feline leukemia virus antigen test had been negative at that time. The owner had adopted the cat when it was 6 weeks old and reported that it had generally been healthy.

Vital Stats

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.

Initial assessment

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.

Preanesthetic evaluation

One week later, the cat was admitted to the clinic for the dental procedures. The results of a preanesthetic complete blood count (CBC) (Table 1) and an activated partial thromboplastin time were normal. A preanesthetic serum chemistry profile revealed one abnormality—a low blood urea nitrogen (BUN) concentration (14.6 mg/dl; reference range = 16 to 36 mg/dl). This abnormality could be caused by decreased protein intake, polyuria and polydipsia, or hepatic insufficiency. In this case, decreased protein intake was considered most likely.

Figure 1. Longitudinal ultrasonograms of the right (A) and left (B) kidneys at initial presentation. The normal architecture of the right kidney has been disrupted and appears to be a mass of mixed echogenicity; it is markedly enlarged compared with the normal left kidney.

On physical examination, a cranial abdominal mass was palpated. An abdominal ultrasonographic examination revealed a normal liver, gallbladder, spleen, left kidney, and urinary bladder and normal intestines. The right kidney was markedly enlarged and irregular. The normal renal architecture of the cortex, medulla, and pelvis had been effaced by an irregular mass that had mixed echogenicity (Figure 1). Urinalysis of a sample obtained by cystocentesis revealed marked hematuria, pyuria, and cocci. The urine was submitted for bacterial culture (Table 2). Fine-needle aspirates were obtained from the right kidney with ultrasound guidance and were submitted for cytologic evaluation.

Table 1 Complete Blood Count Results

Because of the right kidney's ultrasonographic appearance and the lack of urinary-specific clinical signs (e.g. pollakiuria, stranguria), the primary differential diagnosis for the renal mass was neoplastic disease. Primary renal lymphoma was considered most likely because of the cat's age, but primary renal carcinoma, transitional cell carcinoma, and metastatic neoplasia were also possible. Granulomatous disease such as noneffusive feline infectious peritonitis was also considered but was thought to be less likely given the cat's signalment and lack of abnormal findings on the CBC and serum chemistry profile (e.g. lymphopenia, nonregenerative anemia, neutrophilia with a left shift, hyperglobulinemia). Any of these differential diagnoses could result in generalized weight loss over several months and might not be associated with specific clinical signs.

Table 2 Urinalysis and Urine Culture Results

Initial dental treatment and additional test results

The owner elected to proceed with the scheduled dental procedures because the cytology results would not be immediately available, and he felt in retrospect that the dental disease might have been affecting the cat's appetite and quality of life. The cat was anesthetized for dental examination, radiography, and routine prophylaxis. Feline odontoclastic resorptive lesions were confirmed; one extraction and two crown amputations were performed on the affected teeth, and the cat recovered well. The cat received buprenorphine for analgesia and amoxicillin trihydrate-clavulanate potassium to prevent infection after the dental procedures and for a presumed urinary tract infection, pending urine culture results.

Figure 2. Cytologic examination of an aspirate from the right kidney revealed irregular clusters of malignant epithelial cells with marked anisocytosis and anisokaryosis. Individual cells showed hyperchromatic staining and a single, prominent nucleolus (Wright's-Giemsa stain; 100X).

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.

Referral examination

The cat was referred to the University of Minnesota Veterinary Medical Center for further evaluation and likely nephrectomy 11 days later. A physical examination revealed a palpably large right kidney but was otherwise unremarkable. Three-view thoracic radiographs showed no evidence of pulmonary metastases; a mass involving the right kidney was noted on the ventrodorsal view (Figure 3). The results of a CBC and serum chemistry profile were within reference ranges. Urinalysis revealed concentrated urine with a specific gravity of 1.035, proteinuria, marked pyuria and hematuria, and normal epithelial cells (unspecified type) (Table 2). No bacteria were seen, and the results of a second urine culture were negative. A serum thyroxine (T4) concentration was within the reference range.

Figure 3. Ventrodorsal (left) and right lateral (right) thoracic radiographs obtained at the initial presentation to the University of Minnesota. The thoracic structures are normal, but the right kidney is markedly enlarged (arrow).

Surgery

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.

Definitive diagnosis

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.

Histologic examination of the right kidney and associated mass revealed neoplastic transitional cells that had infiltrated the kidney (especially the medulla) and marked reactive fibrosis (Figure 4). The diagnosis was transitional cell carcinoma, likely originating from the transitional epithelium lining the renal pelvis.

Figure 4. Histologic examination of the right kidney obtained by surgical biopsy revealed nests of neoplastic epithelial cells resembling transitional epithelium that infiltrated the renal medulla. The tumor cells are fairly well differentiated and have uniform nuclei with dispersed chromatin and one prominent nucleolus. A marked reactive fibrosis is associated with the nests of tumor cells (hematoxylin-eosin stain; 2X [inset 10X]).

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 27 after surgery, the cat began receiving adjuvant chemotherapy at the University of Minnesota. Mitoxantrone (1.75 mg [6 mg/m2 ] intravenously) was administered on Days 27, 48, 69, and 90 after surgery. A CBC performed about seven days after each mitoxantrone treatment revealed leukopenia after the first two treatments (Table 1); each time the cat was given prophylactic oral amoxicillin trihydrate-clavulanate potassium (62.5 mg orally twice daily for seven days) and metoclopramide (2.5 mg orally three times daily, as needed) and did not develop clinical signs associated with the low white blood cell counts. The cat tolerated the mitoxantrone well with no reported adverse effects, although it lost 1 lb (0.45 kg) between the second and third treatments. The client did not mention any change in the cat's appetite. Possible causes for the weight loss would be decreased appetite (e.g. secondary to the medications) or cancer cachexia.

5. Ventrodorsal (left) and right lateral (right) thoracic radiographs taken on Day 90 after surgery. A diffuse bronchial pattern is present, and a large soft tissue density mass in the cranial mediastinum (arrow) is most apparent in the lateral view. Surgical clips from the previous nephrectomy are noted within the abdomen just cranial to the remaining kidney (arrowhead), which appears radiographically normal.

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.

On Day 101 after surgery, the cat was anesthetized for a computed tomography (CT) scan of the brain and thorax to further evaluate the Horner's syndrome and characterize the extent of any metastatic disease. A mild patchiness to the cerebral parenchyma was present, but this change was considered unlikely to be clinically relevant and possibly artifactual. No structural abnormalities in the brain were seen. A large (3-x-3-x-5-cm), lobulated, cranial mediastinal mass was present immediately ventral to the trachea and esophagus; it exhibited complex contrast enhancement (Figure 6). Moderate sternal lymphadenopathy was also present. The most likely differential diagnosis was metastasis from the primary renal transitional cell carcinoma. The pulmonary parenchyma was unremarkable, with no evidence of nodular or diffuse metastases. Based on these findings and the cat's recent weight loss, the owner declined further diagnostic testing or treatment and elected euthanasia.

Figure 6. A transverse CT image through the cranial mediastinum obtained on Day 101 after surgery (soft tissue window). A large, lobulated mass with complex contrast enhancement (short arrow) is seen immediately ventral to the trachea (long arrow) and esophagus (arrowhead).

Additional findings

A complete necropsy was performed. The cat had a body condition score of 2/5. Minimal autolysis had occurred. A firm, nodular, left-sided mass (1 x 1 x 2 cm) at the thoracic inlet compressed the esophagus and surrounded the vagosympathetic trunk. This mass invaded the musculature on the left side of the vertebrae. Two similar masses were found within the mediastinum, near the heart base and close to the trachea. The hilar lymph nodes were moderately enlarged and firm. The left kidney was moderately enlarged but otherwise grossly normal. Dense fibrotic tissue was present near its cranial pole and surrounded the left adrenal gland. The urinary bladder and urethra were normal. No marked macroscopic abnormalities were present in the vertebral column, spinal cord, brain, heart, lungs, spleen, skin, eyes, gastrointestinal tract, urinary bladder, or urethra.

Figure 7. Histologic examination of the cranial mediastinal mass revealed a sclerotic tumor with bands of fibrous tissue surrounding islands (arrows) of neoplastic epithelial cells (hematoxylin-eosin stain; 10X).

Tissue samples were fixed in neutral-buffered 10% formalin, routinely processed, cut to 5-µm thickness, and stained with hematoxylin and eosin for examination by light microscopy. Histologic examination of the cranial mediastinal mass revealed a sclerotic tumor with small, scattered clusters of neoplastic epithelial cells surrounded by large amounts of fibrous tissue (Figure 7). Several nerves were identified within the tumor. The other mediastinal masses and the hilar lymph node showed similar morphology. The tissue near the cranial pole of the left kidney was composed of similar sclerotic tumor with large lymph vessels filled by metastases, surrounding a normal adrenal gland (Figure 8). The sublumbar lymph nodes contained large metastases within the medulla. Histologic examination of the lungs revealed numerous small metastases in the subserosa and around large blood vessels (Figure 9). Mild lymphocytic inflammation was present in the lamina propria of the left third eyelid. No microscopic abnormalities were found in the brain. The final diagnosis was widely metastatic transitional cell carcinoma arising from the right kidney.

Figure 8. Histologic examination of the left adrenal gland and surrounding tumor mass revealed large lymph vessels (long arrow) filled with metastases within the sclerotic tumor tissue that extends to the normal adrenal tissue (short arrow) (hematoxylin-eosin stain; 10X).

Discussion

Primary renal tumors are rare in companion animals. In cats, the most common primary renal tumor is lymphoma,1,2 and in dogs, metastatic neoplasia most commonly occurs in the kidneys.2 A retrospective study of feline primary renal tumors (excluding lymphoma) identified only 19 cases in a period of six years from four veterinary colleges and one private specialty clinic.1 In both cats and dogs, most primary renal tumors are epithelial in origin, and benign tumors are rare.1-3 Feline renal transitional cell carcinoma is nearly as common as feline renal cell carcinoma.3 This is in contrast to dogs, in which renal cell carcinoma is most common2 and renal transitional cell carcinoma, although reported,4 is rare.

Figure 9. Histologic examination of lung tissue obtained at necropsy revealed numerous small metastases in the subserosa (arrow) (hematoxylin-eosin stain; 10X [inset 20X]).

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.

Conclusion

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

Current addresses:

*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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