Introduction

Primary renal tumors are uncommon in dogs.¹ However, the most common renal tumor in dogs is renal cell carcinoma.² Nephroblastoma is a rare malignancy that is usually found in juvenile dogs, but it can occur at any age.^3–5 Malignancy develops from nephrogenic rests, which are remnants of immature tissue that occur during renal development. In human medicine, nephroblastoma occurs typically in children and rarely in adults, and it represents the second most common childhood abdominal malignancy.⁶ Nephrectomy, with or without adjuvant chemotherapy, is the treatment of choice for unilateral renal nephroblastoma in both veterinary and human medicine.^2,7 The case reported here is unusual for several reasons. Most cases reported in the literature have been in large-breed dogs. Paraneoplastic polycythemia and hypoglycemia have only been reported in one dog each.⁸ This is the first reported case of renal nephroblastoma with polyuria and polydipsia. To the best of our knowledge, this is the longest survival time reported with nephrectomy alone in a dog with primary nephroblastoma.

Case Report

A 17 mo old, 5.1 kg, intact female Jack Russell terrier presented with a 2 wk history of polyuria and polydipsia. The dog had been anorexic and weak for 2 days. The physical examination revealed mildly depressed mentation and hyperemic mucosal membranes. The remainder of the physical examination was unremarkable. A complete blood count revealed erythrocytosis with an increased red blood cell count (13.85 × 10¹²/L; reference range 5.5–9.3 × 10¹²/L), increased hemoglobin (285 g/L; reference range 120–201 g/L), and increased hematocrit (84%; reference range 35–58%). The absolute reticulocyte count was 68.2 × 10⁹/L. The serum biochemistry profile revealed slight hypoglycemia (56 mg/dL; reference range 68–118 mg/dL). Urinalysis showed low urine specific gravity (1.014; reference range >1.030). Arterial blood gas analysis revealed that the partial pressure of oxygen was within the reference range (94.6 mmHg; reference range 85–95 mmHg); therefore, systemic hypoxia was excluded. Venous blood gas analysis and a three-view thoracic X-ray examination (right and left lateral views, ventrodorsal view) yielded unremarkable results. On the two-view abdominal X-ray examination (right lateral and ventrodorsal views), the right kidney was not definable. Abdominal ultrasonography was performed. Both kidneys were ∼4.5 cm in length, 2.5 cm in height, and 3 cm in width. The left kidney appeared normal in structure, size, and echogenicity. At the cranial pole of the right kidney, a large mass (∼2.4 × 2.4 × 2.4 cm) was observed. About one-third of the mass protruded beyond the normal margins of the kidney cranially. The mass was well defined and heterogeneously structured with a predominantly hyperechoic appearance. The mass involved part of the kidney cortex and medulla at its cranial aspect. With Doppler examination, the mass showed only mild vascularization. The remaining part of the right kidney had a normal appearance. Whole-body MRI was performed. The renal mass was isointense with the renal cortex in T1-weighted and T2-weighted images and showed a mildly heterogeneous structure. After intravenous contrast application^a (0.15 mmol/kg), normal renal enhancement was found to be present within both kidneys, and the mass showed a hypointense, less-enhanced appearance compared with the renal cortical parenchyma (Figure 1). The mass showed additional faint ring enhancement. Both renal capsules were intact. Spinal cord involvement was excluded. The remainder of the MRI examination was unremarkable. The serum erythropoietin level was above the reference range (29 mU/mL; reference range 8.4–28 mU/mL). Based on the diagnostic results, renal neoplasia with inappropriate secondary polycythemia was suspected. The polyuria, polydipsia, and mild hypoglycemia were thought to be consequences of the polycythemia. Therapeutic phlebotomy was performed three times, and infusion therapy was initiated to replace the removed volume (an isotonic solution of sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, sodium acetate trihydrate, and malic acid in water^b, 10 mL/kg IV over 2 hr). A hematocrit of 55–60% was considered optimum. Renal parameters and blood glucose were measured. Slight hypoglycemia was evident, but the dog remained clinically stable. Therefore, the patient was referred for surgery without further management.

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Nephrectomy was performed on the third day of hospitalization when the hematocrit was 60%. The kidney was approached through a ventral midline incision, which extended from the xiphoid to two-thirds of the distance to the pubis. The abdomen was explored, and both kidneys were evaluated. The left kidney and all other abdominal organs appeared normal in size, color, and localization. The intestines were covered with protective moistened pads and were retracted to the left side. The right kidney was freed from its retroperitoneal attachments by using sharp and blunt dissection. Hemorrhage from the capsular vessels was controlled by using electrocoagulation. A greyish-brown mass was situated at the cranial pole of the right kidney, and its size and localization correlated with the findings from diagnostic imaging (Figure 2). The perirenal fat was separated from the renal hilus, and the renal vessels were identified. Two sutures of polyfilament absorbable suture (polyglactin 910 2-0^c) were placed separately around the renal artery and vein, with the renal artery being ligated first. The vessels were subsequently transected, and the kidney was dissected from the remaining perirenal tissue. The ureter was freed from its retroperitoneal position and was ligated close to the bladder by using the same suture material used for the vessels. After transection of the ureter, the renal fossa was inspected for any remaining hemorrhage. Abdominal lavage with sterile, body-temperature, saline solution was initiated. The linea alba was closed with a continuous suture of monofilament absorbable material (polydioxanone 2-0^d), and the subcutis was closed by using a faster absorbable material (poliglecaprone 25 3-0^e). The skin was apposed with interrupted sutures of monofilament, nonabsorbable material (polypropylene 3-0^f). Plaster was used to protect the wound, and an Elizabethan collar was applied. Postoperatively, infusion therapy (an isotonic solution of sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, sodium acetate trihydrate, and malic acid in water^b, 2 mL/kg IV per hour) and antibiotic treatment with amoxicillin/clavulanic acid^g (15 mg/kg IV q 12 hr) were initiated. For postoperative pain management, buprenorphine^h (0.01 mg/kg IV q 6 hr) and metamizoleⁱ (25 mg/kg subcutaneously q 8 hr) were given.

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On histopathological examination of the removed kidney, the renal tissue was observed to be effaced by a well-demarcated, nonencapsulated proliferation of cuboidal cells, with little cytoplasm and large ovoid nuclei with clumped chromatin. Segments of these cells formed rows and cords and, rarely, glomeruloid structures. In other areas, sheets of less differentiated, round to ovoid cells were apparent. Marked anisocytosis and anisokaryosis were observed. The mitotic index was 5 per 40× high-power field. Small foci of necrosis and scattered lymphocytes and neutrophils were observed. A diagnosis of nephroblastoma was made.

Complete blood count and serum parameters (blood glucose, creatinine, and urea) were rechecked on a daily basis. Urine specific gravity was checked after IV fluid therapy was stopped. The hematocrit and urine specific gravity returned to the reference range 6 days after nephrectomy. The blood glucose was in the reference range 2 days after nephrectomy, and the renal values remained within the normal range at all times. The dog was discharged at postoperative day 7 in a good overall condition. The dog was presented for follow-up and suture removal 12 days after surgery. The clinical examination results and laboratory parameters were unremarkable. Chemotherapy was not recommended because diagnostic imaging and histopathology revealed stage I disease and a favorable histologic variant. Complete blood count, serum biochemistry profile, and urinalysis were performed at 4 wk and again at 1 yr after surgery, whereupon no abnormalities were noted. Complete restaging, based on three-view thoracic radiography and abdominal ultrasound, was performed 2 yr after diagnosis. Both examinations yielded unremarkable results.

Discussion

The diagnosis of renal nephroblastoma was made for the case presented herein. Additionally, polycythemia as a result of the renal neoplasia, with secondary polyuria, polydipsia, and hypoglycemia, was present. Paraneoplastic polycythemia is often associated with renal neoplasia, and this condition can be attributed to increased erythropoietin production by the tumor or a hypoxic stimulus caused by compression of the normal kidney tissue by the adjacent tumor mass.⁹ Bryan et al. reported three dogs with polycythemia, all of whom had renal carcinoma.¹ Polycythemia has been reported in one case of canine primary nephroblastoma, in addition to the current case.¹⁰ In contrast to the current case, polyuria and polydipsia were not present in the previously reported case. The hallmarks of polycythemia are blood volume expansion and hyperviscosity. Increased blood volume can lead to atrial stretch and an increased release of atrial natriuretic peptide. This may result in polyuria and polydipsia because atrial natriuretic peptide inhibits both vasopressin release from the pituitary gland and the response of the renal collecting duct to vasopressin.¹¹ In the case described here, the polycythemia and consequent polyuria and polydipsia resolved after nephrectomy. Hypoglycemia can be associated with severe erythrocytosis because of increased glucose use and depletion of hepatic glycogen stores by increased red blood cell mass.¹¹ Paraneoplastic hypoglycemia in canine primary nephroblastoma has been reported in two cases, including the dog in the current case. Coleman et al. reported hypoglycemia in a young female beagle with nephroblastoma.⁸ As in the current case, hypoglycemia resolved after nephrectomy.

Nephroblastoma can occur as a primary renal tumor or may be located in the thoracolumbar portion of the spinal cord.¹² Malignancy develops from remnants of immature tissue during embryogenesis of the kidney. In the current case, nephroblastoma was confined to the right kidney. Primary renal nephroblastoma is rarely reported in the veterinary literature. Although most of the dogs diagnosed with this tumor are young, the tumor can occur at any age. A retrospective study by Bryan et al., which concerned primary renal neoplasia in dogs, reported five cases of nephroblastoma.¹ The mean age was 5.2 yr (range 1–12 yr). In several single case reports of canine renal nephroblastoma, the ages ranged from 3 mo to 8 yr. Jack Russell terrier is an unusual breed for nephroblastoma because large-breed dogs tend to be predisposed to develop this kind of tumor.¹² In the published cases, the affected breeds were an individual case each of golden retriever, Labrador retriever, mastiff, Bernese mountain dog, beagle, mix-breed, fox terrier, and whippet. Although the breeds were not stated in the study by Bryan et al., the mean body weight was 40.4 kg (range 9.3–53 kg).¹ Without adequate therapy, the survival of dogs with primary nephroblastoma is very short. Nephrectomy is the treatment of choice in dogs with unilateral renal tumors.² Michael et al. reported a case of a 16 wk old whippet for whom the owner refused nephrectomy, and the dog was euthanized 4 wk after diagnosis because of pain when defecating.¹³ Therefore, in the current case, the decision for nephrectomy was made.

In human medicine, the treatment of choice for unilateral renal nephroblastoma is nephrectomy with or without adjuvant chemo- or radiation therapy. The decision to give adjuvant therapy depends on histopathologic classification and tumor stage. The National Wilms’ Tumor Study Group has developed a staging system that takes clinical, surgical, and pathological information into account. In children, histology is the most important factor in determining outcome.⁷ Anaplastic appearance, rhabdoid tumor of the kidney, and clear cell sarcoma are unfavorable histologic variants.⁷ In children, risk stratification is an important basis for deciding to possibly forego adjuvant treatments such as chemo- or radiation therapy.¹⁴ Stage I favorable histology tumors that weigh <550 g and occur in children under 24 mo of age can be managed with surgery alone.^14,15 In the veterinary literature, 13 out of 14 of the reported cases of dogs with primary renal nephroblastoma, including the current case, were treated with nephrectomy, and 10 out of 13 of these cases, including the current case, were reported in dogs who underwent nephrectomy without adjuvant chemotherapy. In the retrospective study by Bryan et al., 5 dogs with primary nephroblastoma were included and the median survival was 6 mo.¹ Staging, according to human Wilms’ tumor classification, was not reported. In 4 other single case reports, the dogs were treated with nephrectomy without adjuvant chemotherapy. One case involved an 8 mo old beagle with stage II Wilms’ tumor and unfavorable histologic variant. The dog developed lung metastases after a disease-free interval of 1.5 mo.⁸ Three case reports described dogs with stage II Wilms’ tumor and favorable histology, with disease-free intervals of 8, 4, and >19 mo.^10,16,17 In the veterinary literature, 3 out of 13 dogs were treated with adjuvant chemotherapy. The treatment protocols consisted of vincristine and doxorubicin, actinomycin D only, or vincristine, actinomycin D, and doxorubicin.^5,18,19 The median survival times were 25, 4, and 15 mo, respectively.

In the current case, a diagnosis of stage I, low-risk nephroblastoma was made because the tumor was confined to the kidney, the renal capsule was intact, the tumor did not show extension to the renal sinus, and anaplasia was not present. Therefore, adjuvant chemotherapy was not recommended.

Conclusion

To the best of our knowledge, this is the first case involving a young, small-breed dog presenting with polycythemia as a result of primary renal nephroblastoma, with secondary polyuria, polydipsia, and hypoglycemia; treated with nephrectomy alone; and with a disease-free survival of >30 mo. Staging and histologic grading are very important for treatment planning. Lower stages have more favorable prognoses and might be treated without adjuvant chemotherapy. Human Wilms’ tumor classification might be applicable to dogs with primary renal nephroblastoma and be helpful in the decision-making process concerning treatment.