Bilateral ureteral obstruction in a cat due to a ureteral transitional cell carcinoma

Abstract

A 15-year-old cat was presented with a history of lethargy and vomiting. Serum biochemistry revealed severe azotemia. Ultrasonography revealed a small left kidney and hydronephrosis of the right kidney. There was an abdominal mass between the kidneys. Necropsy revealed a mass circumflexing both ureters and histopathology confirmed a diagnosis of transitional cell carcinoma.

A cute uremia is associated with high morbidity and mortality in small animals (1,2). There are numerous causes for acute uremia in dogs and cats. Recently, ureteral obstruction was reported as the most common cause of acute uremia in cats (3). Typically, 1 kidney is initially obstructed and undergoes fibrosis, if the obstruction is complete and static the other kidney undergoes compensatory hypertrophy. Acute uremia ensues when the second kidney becomes obstructed as well. Ureteral obstruction results most commonly from ureteral calculi; however, blood clots, inflammatory debris, and strictures may also obstruct the ureter (4). Neoplasia is a potential cause of ureteral obstruction in dogs and cats. Reported ureteral neoplasms in dogs include transitional cell carcinoma, leiomyoma, leimyosarcoma, mast cell tumor, and spindle cell sarcoma (5–7). Primary neoplasia or metastases have rarely been reported in cats. Unilateral ureteral obstruction due to leiomyosarcoma in the retroperitoneum has been reported in a cat (8), but this etiology has not been previously associated with bilateral ureteral obstruction. This case report describes a cat with acute uremia due to transitional cell carcinoma that originated from the left ureter and extended to the right ureter to cause bilateral ureteral obstruction.

Case description

A 15-year-old, 3.6 kg, spayed female Siamese cat, was referred to the Emergency Service of the Hebrew University Veterinary Teaching Hospital (HUVTH) with an 8-day history of anorexia, decreased water intake, lethargy, and several episodes of vomiting, 2 d prior to presentation. The cat had been treated symptomatically by the referring veterinarian with sub-cutaneous fluids (type and amount not specified) for 2 d prior to the referral but had shown no improvement. Upon physical examination the cat was well hydrated and lethargic; body temperature was 37°C, heart rate 168 beats/min, and respiratory rate 36 breaths/min. Abdominal palpation revealed a small, irregular left kidney and an enlarged, firm right kidney. Complete blood cell count disclosed mild leukocytosis [17.4 × 10³/μL, reference range (RR): 5 to 17 × 10³/μL], and normocytic normochromic anemia (hematocrit 22%, RR: 24% to 45%). Serum biochemistry revealed hypoalbuminemia (23 g/L, RR: 26 to 40 g/L), severe azotemia (creatinine 1563 μmol/L, RR: 38 to 122 μmol/L; urea 133.5 mmol/L, RR: 7.1 to 21.4 mmo/L), severe hyperkalemia (9.52 mmol/L, RR: 3.8 to 5.6 mmol/L), hyperphosphatemia (3.8 mmol/L, RR: 0.8 to 2.0 mmol/L), and hyperamylasemia (2438 U/L, RR: 340 to 800 U/L). Coagulation profile disclosed mild prolongation of prothrombin time (12.5 s, RR: 8.7 to 10.5 s) and activated partial thromboplastin time (26.8 s, RR: 12.3 to 16.7 s). Venous blood gas analysis revealed acidemia (pH 7.043, RR: 7.35 to 7.45), decreased bicarbonate concentration (8.7 mmol/L, RR: 22 to 26 mmol/L), and decreased partial pressure of venous CO₂ (32.7 mmHg, RR: 35 to 45 mmHg). Urinalysis showed that the urine specific gravity was 1.023, the pH was 5.0, and other features were unremarkable. An electrocardiogram revealed typical changes of hyperkalemia including flattening of the P-waves with wide QRS complexes and spiked T-waves.

Abdominal ultrasonography identified moderate abdominal effusion, a small left kidney (2.5 cm) with poor corticomedullary distinction, and a 5-cm right kidney with a 3-mm pelvic dilatation. A hypoechoic irregular abdominal mass was demonstrated between the left and the right kidneys. The mass seemed to originate from the caudal part of the left kidney, extending to the right kidney through the retroperitoneum and terminating 1 cm caudal to the right kidney. The reminder of the urinary system was unremarkable. No other ultrasonographic abnormalities were detected. Fine-needle aspiration of the abdominal mass was non-diagnostic. Abdominal fluid analysis revealed modified transudate (acellular, total solids 27 g/L), with creatinine and potassium concentrations of 893 μmol/L and 8.4 mmol/L, respectively.

A positive contrast nephropyelogram of the right kidney confirmed a complete proximal ureteral obstruction and pelvic dilatation. Following the radiologic work-up, the assessment was a chronic obstruction of the left ureter by a space-occupying mass, resulting in left kidney atrophy and fibrosis, and an acute right ureteral obstruction due to extension of the mass to the right ureter.

Initial treatment for the hyperkalemia at the Emergency Service included dextrose bolus (2 g, IV over 10 min), IV fluids (0.9% NaCl at 2 mL/kg per hour supplemented with 5% dextrose), regular insulin (Actrapid; Novo Nordisk, Bagsvaerd, Denmark), 1U IM, calcium-gluconate (Calcium gluconate 10%; Melsungen, Germany), 400 mg slow IV over 20 min, and sodium bicarbonate (Sodium bicarbonate 8.4%; Melsungen, Germany), 15 mEq, IV, diluted in 0.9% NaCl over 6 h. Additional treatment was directed to control clinical signs of uremia and to promote urine production and consisted of ranitidine (Zantac; Novolog, Verona, Italy), 2 mg/kg body weight (BW), slow IV, q24h, constant rate infusion of metoclopramide (Pramin; Rafa, Jerusalem, Israel), 0.04 mg/kg BW per hour, dexamethasone (Dexacort; Teva, Petach, Tikva, Israel), 0.2 mg/kg BW, and furosemide (Fusid; Teva, Petach Tikva, Israel), 2 mg/kg BW, IV followed by a constant rate infusion at 1 mg/kg BW per hour. Butorphanol (Torbugesic, Fort Dodge, Fort Dodge, Iowa, USA) was administered for pain relief at 0.4 mg/kg BW, SQ, q6h. Despite the medical treatment the cat remained completely anuric, the hyperkalemia and azotemia persisted, and 24 h after presentation the cat had cardiopulmonary arrest.

On necropsy a 7.5-cm long, firm mass was observed between the right and left kidneys (Figure 1). The mass circumflexed the proximal part of both ureters, but was more prominent on the left side, in which a normal ureter could not be identified within the mass. Bilateral ureteral retrograde injection of new methylene blue demonstrated a complete obstruction of the left ureter and a partial obstruction of the right ureter (Figure 1). The left kidney was small and irregular with no distinct separation between the cortex and the medulla and the right kidney was enlarged with pelvic dilatation. The remainder of the urinary tract was unremarkable. There were no other findings on necropsy.

Figure 1.

a. The urinary system after dissection. The right kidney is enlarged (5 cm, black arrowhead) with pelvic dilatation, while the left kidney is small and firm (2.5 cm, black arrow). Note that the mass surrounds the proximal portion of the left ureter, making the left kidney appear larger than its actual size. b. Retrograde injection of new methylene blue to the right ureter, demonstrating the right ureter (white arrow) up to the level of the right renal pelvis. The right ureter was patent when sufficient pressure was applied. c. The left fibrotic kidney (black arrow) surrounded by the mass, which involves the proximal part of the left ureter (white arrowheads).

Histopathology showed that the right kidney had mild lymphocytic plasmacytic infiltration, but was otherwise unremarkable, whereas the left kidney had a complete loss of the normal architecture with severe diffuse fibrosis and mild lymphocytic plasmacytic infiltration. The mass consisted of a large, poorly demarcated, unencapsulated, highly infiltrative moderately to densely cellular neoplastic cell proliferation. The cells were cuboidal to polygonal and were arranged as solid sheets to cords with occasional tubule formation. Cell borders were variably distinct. The cytoplasm was moderate in amount, eosinophilic, and slightly vacuolar. The nuclei were large, centrally located, had coarsely clumped chromatin with 1 to 3 prominent nucleoli. There was marked anisokaryosis with nuclear atypia. Mitotic index was 20 mitotic figures per 10 high power fields with occasional bizarre mitoses. The neoplastic cells were surrounded by abundant haphazardly arranged dense fibrous connective tissue (desmoplasia). A diagnosis of transitional cell carcinoma was made, suspected to originate from the left ureter. Histopathology of other organs (including the urinary bladder and the urethra) was unremarkable.

Discussion

Primary ureteral tumors are rare in companion animals and in humans (9). They are not commonly reported in dogs and only 1 case describing unilateral ureteral leiomyosarcoma has been reported in a cat (5,7,10–13).This is the first case of bilateral ureteral obstruction due to a ureteral neoplasia in a cat.

The cat in the present report was suspected to have transitional cell carcinoma originating from the left ureter and extending to the right ureter, resulting in bilateral ureteral obstruction. Both on ultrasound and postmortem examinations there was no involvement of the renal pelvices, renal parenchyma, urinary bladder, or urethra, thus eliminating the possibility that these were the origin of the neoplasia. Metastatic carcinoma was considered less likely as no primary tumor was found elsewhere on necropsy. Bilateral primary ureteral neoplasia has rarely been reported in humans (14), but was considered less likely in this case, as the mass extended from the left ureter to the right ureter through the retroperitoneum.

The clinical presentation of the cat was similar to the presentation of cats with ureteroliths, which has become the most common cause of acute uremia in recent years in the United States (3,4,15). In this presentation 1 of the ureters is typically obstructed, most commonly by calcium oxalate containing ureteroliths (4). Ureteral obstruction may be complete or partial, and when caused by ureteroliths, may also be static or dynamic. If the obstruction is complete and static, the kidney will undergo fibrosis (16). Clinical signs of unilateral obstruction are often non-apparent or non-specific, and may be associated with pain, which results from dilatation of the collecting system and the renal capsule. The contralateral kidney undergoes compensatory hypertrophy. Acute uremia may result if the contralateral hypertrophic kidney becomes obstructed as well. At presentation, such cats have 1 fibrotic small kidney and 1 enlarged hypertrophic kidney, thus this syndrome is referred to as “big kidney little kidney syndrome” (17). We suspect that similar events took place in this case, but the etiology was neoplasia rather than ureteroliths. It is likely that the mass initially obstructed the left ureter and consequently the left kidney underwent fibrosis. Despite the old obstruction of the left ureter (as implied by the advanced chronic changes of the left kidney) the cat’s owner did not report any clinical signs in the cat’s history. As the mass extended to the right ureter, the right kidney became obstructed as well, and clinical signs became apparent.

Treatment of cats with bilateral ureteral obstruction is challenging and often necessitates advanced technologies (such as dialysis) and specialized surgical skills. There is no readily available method to assess the function of the obstructed kidney, until the obstruction is relieved. When an ureterolith is obstructing the ureter, normograde movement of the ureterolith may occur, and the obstruction may resolve spontaneously; however, when neoplastic tissue is obstructing the ureter, as in the current case, spontaneous resolution cannot occur, thus surgery might be a valid treatment option. Ureteronephrectomy is often the treatment for renal or ureteral neoplasia (18), but can be performed only if the contralateral kidney has enough residual function (19). As the contralateral kidney in this case was small and fibrotic, and thus was assessed to have low residual function, ureteronephrectomy was not regarded as a valid treatment option. Ureteroneocystostomy and ureteral resection and anastomosis are other surgical options in cases of ureteral obstruction, but could not have been performed in this case as the neoplasia involved the proximal ureter. The recovery of renal function after alleviation of the obstruction depends on the nature of the obstruction (complete versus partial) and its duration (16).

Due to the severity of azotemia and hyperkalemia in this cat, the first treatment option that should have been considered was urine diversion or dialysis. The latter would have been a temporary treatment because the obstruction was static and was not expected to resolve spontaneously, as may occur in some cases of ureteroliths.

Urine diversion can be achieved using methods such as surgery, nephrostomy tube placement, and stents (20,21). Nephrostomy tube placement can allow urine drainage and assessment of the glomerular filtration rate (GFR) of the obstructed kidney; however, its placement may be associated with morbidity and mortality (15). Nonetheless, nephrostomy tube placement was considered a valid option in this case as nephrostomy tubes can be placed readily with ultrasound guidance avoiding the risk of prolonged surgery and anesthesia (21). Another alternative that was not attempted in this case, but could be considered in cases of ureteral obstruction, is stent placement from the renal pelvis to the urinary bladder (for example, double pigtail ureteral stent). This has been recently shown to be feasible and effective in dogs and cats with ureteral obstruction (20,22). These palliative solutions facilitate urine drainage from the obstructed kidney, restore GFR, and eliminate clinical signs, depending on the remaining function of the obstructed kidney (23). Chemotherapy or radiation therapy should be considered as other treatment options for dogs and cats with ureteral neoplasia; however, they should be considered in azotemic animal patients only after initial stabilization and urine diversion (24).

In summary, ureteral obstruction due to transitional cell carcinoma that extended from 1 ureter to the other should be included in the differential diagnoses of cats presenting with “big kidney little kidney syndrome.” Treatment is challenging, as spontaneous resolution cannot occur. Ureteral stents and nephrostomy tubes may be considered as potential palliative and temporary treatment options in the absence of a healthy proximal ureteral segment to allow surgical intervention. CVJ