Unilateral renal cell carcinoma in a Labrador retriever

Abstract

A 7-year-old, neutered male, Labrador retriever was presented with a history of hematuria. Radiographic and ultrasonographic studies led to a presumptive diagnosis of unilateral renal neoplasia. Unilateral nephroureterectomy was performed. Histopathologic examination of the resected mass confirmed the diagnosis of renal cell carcinoma. Six weeks postoperatively, the dog was well.

A 7-year-old, neutered male, Labrador retriever with a 1-month history of intermittent hematuria and a palpable abdominal mass was referred to the Western College of Veterinary Medicine for additional diagnostic tests and treatment. On physical examination, the dog was bright, alert, and responsive. A large mass could be palpated on both sides of the abdomen, caudal to the ribs. Radiographs taken by the referring veterinarian revealed a large oval mass in the area of the left kidney. Mucous membranes were mildly hyperemic.

As part of the diagnostic work-up, a complete blood (cell) count (CBC), biochemical panel, urinalysis (sample obtained by cystocentesis), and urine culture were performed. Hematologic abnormalities included a high red blood cell (RBC) count (9.05 × 10¹²/L; reference range 5.2 to 8.2 × 10¹²/L), a high hemoglobin concentration (205 g/L; reference range 128 to 196 g/L), and a high hematocrit (0.61 L/L; reference range 0.37 L/L to 0.57 L/L). The total plasma protein concentration (63 g/L; reference range 55 to 71 g/L) was normal, indicating that the dog had an absolute erythrocytosis, which was likely due to increased erythropoeitin production by the renal mass. Results of the biochemical panel showed a mild hypoalbuminemia (27 g/L; reference range 28 to 38 g/L), likely due to decreased hepatic production or increased renal losses. There was also an elevation in gamma glutamyl transferase (GGT) (42 U/L; reference range 0 to 8 U/L), possibly of renal origin, or due to cholestasis or steroid induction. Urinalysis revealed turbid brown urine with 4 + protein, 4 + blood, and 20 to 30 RBC/hpf (100 ×). Urine culture was negative.

Plain view thoracic radiographs were taken and an abdominal ultrasonograph performed. The thoracic radiographs showed no evidence of pulmonary metastases. The abdominal ultrasonograph revealed a large oval-shaped mass in the left renal field. The interior of this mass was irregular and somewhat cavitated. The extent of the mass caused the intestines to be displaced to the right side of the abdomen and the spleen to be displaced ventrally and caudally. A normal left kidney could not be identified. The right kidney, however, was recognizable; it appeared normal with respect to architecture and echogenicity. A presumptive diagnosis of unilateral renal neoplasia was made.

Surgery was performed on the 3rd day following admission. Prior to surgery, blood pressure, prothrombin time, and partial thromboplastin time were measured; these were within normal limits. On the day of surgery, the dog was premedicated with hydromorphone (Hydromorphone HP; Sabex, Boucherville, Quebec), 0.1 mg/kg BW, IM, and acepromazine (Atravet; Ayerst Veterinary Laboratories, Guelph, Ontario), 1.25 mg/kg BW, IM. He was induced with propofol (Propofol Injection; Abbott Laboratories, Saint-Laurent, Quebec), 4 mg/kg BW, IV, and maintained on isoflurane (IsoFlo; Abbott Laboratories). A morphine (Morphine HP; Sabex) epidural anesthetic was administered prior to surgery. One dose of cefazolin (Cefazolin for Injection; Novopharm, Toronto, Ontario), 25 mg/kg BW, IV, and 2 separate doses of fentanyl (Fentanyl Citrate Injection USP; Sabex), 0.5 mL, IV, were delivered intraoperatively.

An exploratory laparotomy and nephroureterectomy were performed, via a midline approach, to search for metastases and to remove the renal mass. A retractor was placed to maintain exposure of the abdominal cavity. A large, heterogeneous mass was immediately visible. The mass was confirmed to be the left kidney and it measured approximately 25 cm in diameter when removed. Externally, it appeared to be nodular and highly vascularized. The extent of the mass limited initial examination of abdominal organs to liver, stomach, intestines, pancreas, and bladder. These were assessed for abnormalities; none were found. The peritoneum was carefully dissected away from the left kidney; bleeding was controlled by electrocautery. The left ureter was then identified, dissected out, ligated with 2-0 polydioxanone suture (PDSII; Ethicon, Peterborough, Ontario), as close to the bladder as possible, and transected. The left kidney was elevated to expose the renal blood vessels. The renal artery was ligated first, followed by the renal vein with 2-0 polydioxanone suture. Both vessels were transected and the kidney removed.

Removal of the kidney and its associated mass permitted a more thorough exploration of the abdomen. No gross abnormalities were noted in any of diaphragm, liver, gall bladder, stomach, intestines, pancreas, adrenal gland, bladder, and prostate. The guillotine method (1) was used to take a liver biopsy to further investigate the elevated GGT. The linea alba and subcutaneous tissue were closed in a simple continuous pattern using 0 polydioxanone (PDSII; Ethicon) suture. Staples were used to close the skin. The liver biopsy and resected kidney were submitted for histopathologic examination. Hydromorphone (Hydromorphone HP; Sabex), 0.025 mg/kg BW, IV, q24h, was administered postoperatively for pain control.

Recovery from anesthesia was uneventful. Postoperative fluids and pain medication were administered. Histopathologic examination of the renal mass confirmed the diagnosis of renal carcinoma. No metastases were identified in the liver biopsy. Six weeks after surgery, the dog was doing well. There were no signs of metastasis and both the hematuria and polycythemia had resolved (hematocrit had dropped to 0.44 L/L).

Primary renal tumors occur uncommonly in dogs, with a prevalence rate of approximately 1% (2–5,8,9,11,14). Of these, renal carcinoma is the most common type (2,4,7–9,11,12,14,15). Renal carcinomas are believed to originate from the epithelium of proximal convoluted tubules (2,5,9,14). Middle-aged and older dogs (average age, 8 y) are more likely to be affected, although renal carcinoma has been reported in dogs as young as 1 y of age (2,7,9,11,14,15). As is the case in humans, there is a gender predilection for renal carcinoma, with males diagnosed with it roughly twice as frequently as females (2,4,5,8,9,11,14,15). No breed predilection has been identified (3–5,8,9,14).

Research in human medicine has lent support to the theory that renal carcinoma is a hormonally-induced tumor (3,7,11,12): some patients treated with progestins experienced regression of their renal tumors (11).

Dogs with renal carcinoma tend to present with a variety of vague, nonspecific signs of chronic duration (3,4,7,15). Polysystemic signs not related to the urinary system, such as anorexia, depression, and weight loss, frequently are the first signs reported (4,7,12,15). Anemia, hematuria, and fever are common but are rarely present concurrently (11). Absence of overt clinical signs may delay diagnosis until late in the clinical course of disease, by which time the tumor has metastasized (7,11,12,14). A palpable abdominal mass is a common finding on physical examination, and its presence in conjunction with any of weight loss, anorexia, and hematuria should suggest renal tumor as a differential diagnosis (2,3,5,7–9,11,14).

Paraneoplastic syndromes occur commonly in humans with kidney tumors and have also been reported in dogs with renal neoplasia (11). Of these, fever and anorexia are the 2 most commonly reported disorders (8); others include polycythemia, hypertrophic osteopathy, and hypercalcemia (3,8,11,12). Clinical signs associated with polycythemia are erythema of skin and mucous membranes, polyuria and polydipsia, and occasionally neurological signs (15). The pathogenesis of secondary polycythemia induced by excess erythropoietin production by tumor tissue remains unclear (15). Two theories have been put forth. The first is that the renal tumor independently produces and secretes excess erythropoietin. Alternatively, the tumor induces tissue hypoxia via compression of normal kidney parenchyma, impairment of renal blood flow, or both, to the point that normal renal erythropoietin-producing cells amplify erythropoietin production (15).

A presumptive diagnosis of a primary renal tumor can often be made based on history and findings on physical examination, laboratory analysis of blood and urine, and imaging studies (11,12). Complete blood (cell) count and biochemical panel results are often within normal limits, especially if the tumor is unilateral (12,15). Even in bilateral cases, signs of renal failure may not be present, as adequate kidney function requires only 25% of the parenchyma to be normal (12). Nonregenerative anemia or erythrocytosis may be present (11,12). Urinalysis may be normal, or proteinuria and gross or microscopic hematuria, or both, may be present (11,12). It has been suggested that antemortem diagnosis of renal carcinoma can be made upon detection of neoplastic cells in urine sediment (7,12); another source believes this to be a fruitless practice (14). Radiographs are an excellent screening procedure (3). Abdominal radiographs aid in identifying the organ(s) primarily involved, the size and location of the neoplasm, and metastatic foci (11). Thoracic radiographs aid in identification of pulmonary metastases, a finding that may influence treatment protocol (11). Performing abdominal ultrasonography or intravenous urography in addition to radiography will increase diagnostic specificity (3). These techniques will identify an abdominal mass and recognize it as the kidney more reliably than radiography alone (12). Intravenous urography is particularly useful for estimating the extent of renal parenchymal involvement (7,12). Definitive antemortem diagnosis requires microscopic identification of neoplastic cells in the affected tissue (7,12). As nephroureterectomy is the mainstay of treatment for unilateral renal carcinoma (11,15), percutaneous biopsy of the mass is neither necessary nor recommended, especially given the potential for iatrogenic metastasis along the needle tract (3,7,12). Percutaneous biopsy is indicated, however, when bilateral involvement is detected (7).

Nephroureterectomy is indicated in cases of unilateral renal carcinoma where the contralateral kidney is functional and where metastases are not grossly evident (7,11,12). Preoperatively, the mass should be palpated to a minimal extent to prevent tumor rupture and consequent seeding of neoplastic cells into the abdomen (7,12). To minimize tumor emboli during surgery, the mass should be handled carefully and adequately exposed. Renal vessels should be ligated early on in the procedure (3,7,12). In most cases of renal carcinoma, the renal capsule is intact at the time of surgery, making complete resection of the mass possible (11). Invasion into surrounding structures (caudal vena cava, lumbar musculature, adrenal glands) can occur, however, making complete excision of the tumor difficult (9,11). Chemotherapy and irradiation therapy for renal carcinoma have received little attention in the veterinary literature, possibly because of their limited success in human medicine (7,12). However, in cases of highly aggressive or invasive renal carcinoma, cytotoxic chemotherapy should be considered as adjunctive therapy to surgery (11).

If secondary polycythemia is present, phlebotomy prior to surgery should be considered, as small increases in hematocrit above 60% translate into considerable increases in blood viscosity (15). Phlebotomy may lessen the risk of thrombosis and excessive hemorrhage (15).

The fact that renal carcinomas are usually advanced at the time of presentation (3,7,11) does not necessarily preclude a good prognosis, especially where no other evidence of malignant disease exists (4). A guarded to good prognosis is warranted if complete resection of a unilateral malignant neoplasm is achieved (7). Nephroureterectomy has been associated with a mean survival time of 6.8 mo (12), although postoperative survival time of 4 y has been reported (4,8). Prognosis worsens if involvement is bilateral, the tumor has invaded vital structures, there is evidence of chronic renal failure or metastases, or no treatment is provided (3,7,12).