Pathology in Practice

Samantha J. M. Evans 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Paula A. Schaffer 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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Kristi Sluiter 2VETMED Specialty Services, 20610 N Cave Creek Rd, Phoenix, AZ 85024.

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Amanda Simonson 3Norterra Animal Hospital, 2005 W Happy Valley Rd, Phoenix, AZ 85085.

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Paul R. Avery 1Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.

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History

A 6-month-old 25.5-kg (56.1-lb) spayed female Labrador Retriever was evaluated because of hematuria and hyporexia of 4 days' duration. Palpation of the dog's abdomen elicited signs of pain. Urinalysis revealed urine specific gravity of 1.011 with 3+ proteinuria, 4+ hematuria, and 1+ pyuria on a dipstick and a few bacteria. Treatment of the dog with cefpodoxime and carprofen for suspected urinary tract infection was initiated. Despite treatment, the dog's clinical signs persisted and over the next 2 days worsened to include stranguria, dysuria, and pollakiuria. The dog was referred to a specialty clinic.

Clinical and Clinicopathologic Findings

Clinicopathologic analyses performed at the specialty clinic revealed that the dog had mild normocytic, normochromic anemia (Hct, 35.4% [reference interval, 37.3% to 61.7%]) with evidence of mild regeneration (reticulocyte count, 148.5 × 103 reticulocytes/μL [reference interval, 10.0 × 103 to 110.0 × 103 reticulocytes/μL), mild hyperphosphatemia (7.2 mg/dL; reference interval, 2.5 to 6.8 mg/dL), and mildly high BUN concentration (31 mg/dL; reference interval, 7 to 27 mg/dL); creatinine concentration (1.7 mg/dL; reference interval, 0.5 to 1.8 mg/dL) was not abnormal. Repeated urinalysis (urine collected by cystocentesis) revealed urine specific gravity of 1.017 and marked proteinuria and hematuria without pyuria or detectable bacteria. Microbial culture of a urine sample yielded no growth. Abdominal radiography revealed a midabdominal mass that displaced the colon ventrally, and ultrasonography revealed gross bilateral renomegaly with distorted renal architecture and heterogeneous echotexture.

Cytologic Findings

Ultrasound-guided fine-needle aspirate specimens collected from both kidneys were examined microscopically (Figure 1). Slides were highly cellular with a thick background of RBCs, fibrin clots, and many free nuclei. Dense aggregates of unidentifiable cells were interpreted as possible glomerular or tubular structures. There were many clustered and individualized cells, which often appeared truly cohesive with pseudoacinar formations. Cells were round with large round nuclei and high nuclear-to-cytoplasmic ratio; they had a small amount of pale basophilic cytoplasm, often with punctate vacuolation, and rarely contained basophilic pigment globules. Nuclear chromatin was finely granular to homogeneous and smooth with variably distinct nucleoli. Admixed with this population was a less common spindle-shaped cell type with condensed oval nuclei; these cells were sometimes associated with pink extracellular matrix.

Figure 1—
Figure 1—

Cytologic preparations of fine-needle aspir ate specimens of bilater ally enlarged and irregular k idneys in a 6-month-old spayed female Labrador Retriever. A— Dense aggregates of cells, sometimes associated with pink extracellular matrix, are visible. Modified Wright-Giemsa stain; bar = 100 μm. B — In a higher-magnification view, many variably cohesive round cells with a high nuclear-to-cytoplasm ratio (reflective of large round nuclei and scant, occasionally vacuolated cytoplasm) are present. Some individualized round cells (asterisk) have transitioned into more cohesive clusters (arrow). Specimens from the left and right kidneys were cytologically similar. Modified Wright-Giemsa stain; bar = 20 μm. Inset—Higher-magnification view of a round cell with a lymphoid appearance. Modified Wright-Giemsa stain; bar = 10 μm.

Citation: Journal of the American Veterinary Medical Association 256, 4; 10.2460/javma.256.4.435

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Histopathologic Findings

On the basis of the cytologic findings, a malignant neoplasm, most likely nephroblastoma, was considered. Lymphoma was considered far less likely because of the presence of cohesion and lack of cytoplasmic fragments consistent with lymphoglandular bodies; however, because of the bilateral renal involvement and the individualized lymphoid appearance of the cells in some fields of view, a PCR assay for antigen receptor rearrangement testing was suggested but not performed. Owing to the dog's grave prognosis and precipitously deteriorating quality of life, the dog was euthanized 19 days following the initial evaluation at the primary care clinic. Wedge sections of both kidneys were obtained following euthanasia and examined histologically (Figure 2). Sections from both kidneys contained all 3 components characteristic for nephroblastoma, namely haphazardly arranged tubules, primitive glomeruli, and acini (epithelial component); a low number of spindle-shaped cells (mesenchymal component); and densely cellular regions of undifferentiated cells (blastemal component). A complete necropsy was not performed.

Figure 2—
Figure 2—

Photomicrographs of a section of kidney tissue from the dog in Figure 1. A—Expanding and replacing the renal parenchyma is a large tumor mass. H&E stain; bar = 1 mm. B—Higher-magnification view of the image in panel A. H&E stain; bar = 500 μm. C—The tumor is composed of epithelial (black arrows), mesenchymal (white arrow), and blastemal (asterisks) components in varying proportions. Left and right kidneys were histologically similar. H&E stain; bar = 100 μm. D—Higher-magnification view of the image in panel C. H&E stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 256, 4; 10.2460/javma.256.4.435

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: bilateral renal nephroblastoma in a dog.

Comments

Nephroblastoma (termed Wilms tumor in human medicine) arises in the primitive nephrogenic blastema and in foci of renal dysplasia. It is the most common primary renal tumor of pigs and chickens, relatively uncommon in calves and dogs, and rare in sheep, horses, and cats.1 Wilms tumor is the most common genitourinary malignant tumor in children, and bilateral disease has been reported for up to 5% of affected children.2 Bilateral nephroblastoma has been identified in pigs.1 Occasionally, rests of embryonic renal tissue fail to migrate during development, such that nephroblastomas may develop within or adjacent to the vertebral column or spinal cord. The cytologic and histologic features of renal3 and spinal4 nephroblastoma include variable proportions of the characteristic tubular elements, glomeruloid bodies, spindle-shaped mesenchymal cells, and prominent blastemal cells.

Some canine nephroblastomas are immunochemically reactive for the human Wilms tumor marker WT1 in tissue sections,1 but immunocytochemical staining for WT1 in canine nephroblastomas has not been reported. A recent study5 found ubiquitous immunohistochemical expression of WT1 in canine lymphomas, indicating that WT1 expression is not useful for distinguishing nephroblastoma from lymphoma. Therefore, antigen receptor rearrangement testing or immunocytochemical analyses for B- and T-cell markers may be most valuable when faced with a cytologic sample for which lymphoma and nephroblastoma are considered differential diagnoses. There are too few reports available to make definitive treatment recommendations for dogs with renal nephroblastoma; however, treatment of unilateral disease with excision alone6 or with a combination of nephrectomy and administration of chemotherapeutic agents (eg, vincristine, actinomycin D, or doxorubicin7,8) has been attempted with variable success. Nephrectomy was not an option in the case described in the present report because both kidneys were affected.

Nephroblastoma is an important differential diagnosis for young dogs with unilateral or bilateral renomegaly with or without renal insufficiency. For the dog of the present report, cytologic examination of fine-needle aspirate specimens provided evidence of a malignant neoplasm, for which the top differential diagnosis was nephroblastoma; bilateral renal nephroblastoma was confirmed on the basis of histologic findings. There is a previous report9 of a young dog with a very large (20 × 15 × 10-cm) nephroblastoma involving both kidneys, the omentum, intestinal mesentery, and urinary bladder, but that was described as a single mass rather than independent neoplastic disease in both kidneys. For the dog of the present report, the bilateral nature of the neoplastic disease and the discrete cytologic appearance of some cells contributed to the diagnostic challenge by introducing lymphoma as an important diagnostic rule-out.

References

  • 1. Maxie MG, Newman SJ. The urinary system. In: Maxie MG, ed. Jubb, Kennedy & Palmer's pathology of domestic animals. Philadelphia: Saunders Ltd, 2015:501502.

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  • 2. Lopes RI, Lorenzo A. Recent advances in the management of Wilms' tumor. F1000Res 2017;6:670.

  • 3. Michael HT, Sharkey LC, Kovi RC, et al. Pathology in Practice. Renal nephroblastoma in a young dog. J Am Vet Med Assoc 2013;242:471473.

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  • 4. De Lorenzi D, Baroni M, Mandara MT. A true “triphasic” pattern: thoracolumbar spinal tumor in a young dog. Vet Clin Pathol 2007;36:200203.

    • Crossref
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  • 5. Sakai O, Sakurai M, Sakai H, et al. Molecular cloning of canine Wilms' tumor 1 for immunohistochemical analysis in canine tissues. J Vet Med Sci 2017;79:12721277.

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  • 6. Montinaro V, Boston SE, Stevens B. Renal nephroblastoma in a 3-month-old Golden Retriever. Can Vet J 2013;54:683686.

  • 7. Frimberger AE, Moore AS, Schelling SH. Treatment of nephroblastoma in a juvenile dog. J Am Vet Med Assoc 1995;207:596598.

  • 8. Seaman RL, Patton CS. Treatment of renal nephroblastoma in an adult dog. J Am Anim Hosp Assoc 2003;39:7679.

  • 9. Baskin GB, De Paoli A. Primary renal neoplasms of the dog. Vet Pathol 1977;14:591605.

Contributor Notes

Dr. Evans' present address is Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Address correspondence to Dr. Evans (evans.2608@osu.edu).
  • Figure 1—

    Cytologic preparations of fine-needle aspir ate specimens of bilater ally enlarged and irregular k idneys in a 6-month-old spayed female Labrador Retriever. A— Dense aggregates of cells, sometimes associated with pink extracellular matrix, are visible. Modified Wright-Giemsa stain; bar = 100 μm. B — In a higher-magnification view, many variably cohesive round cells with a high nuclear-to-cytoplasm ratio (reflective of large round nuclei and scant, occasionally vacuolated cytoplasm) are present. Some individualized round cells (asterisk) have transitioned into more cohesive clusters (arrow). Specimens from the left and right kidneys were cytologically similar. Modified Wright-Giemsa stain; bar = 20 μm. Inset—Higher-magnification view of a round cell with a lymphoid appearance. Modified Wright-Giemsa stain; bar = 10 μm.

  • Figure 2—

    Photomicrographs of a section of kidney tissue from the dog in Figure 1. A—Expanding and replacing the renal parenchyma is a large tumor mass. H&E stain; bar = 1 mm. B—Higher-magnification view of the image in panel A. H&E stain; bar = 500 μm. C—The tumor is composed of epithelial (black arrows), mesenchymal (white arrow), and blastemal (asterisks) components in varying proportions. Left and right kidneys were histologically similar. H&E stain; bar = 100 μm. D—Higher-magnification view of the image in panel C. H&E stain; bar = 100 μm.

  • 1. Maxie MG, Newman SJ. The urinary system. In: Maxie MG, ed. Jubb, Kennedy & Palmer's pathology of domestic animals. Philadelphia: Saunders Ltd, 2015:501502.

    • Search Google Scholar
    • Export Citation
  • 2. Lopes RI, Lorenzo A. Recent advances in the management of Wilms' tumor. F1000Res 2017;6:670.

  • 3. Michael HT, Sharkey LC, Kovi RC, et al. Pathology in Practice. Renal nephroblastoma in a young dog. J Am Vet Med Assoc 2013;242:471473.

    • Search Google Scholar
    • Export Citation
  • 4. De Lorenzi D, Baroni M, Mandara MT. A true “triphasic” pattern: thoracolumbar spinal tumor in a young dog. Vet Clin Pathol 2007;36:200203.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Sakai O, Sakurai M, Sakai H, et al. Molecular cloning of canine Wilms' tumor 1 for immunohistochemical analysis in canine tissues. J Vet Med Sci 2017;79:12721277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Montinaro V, Boston SE, Stevens B. Renal nephroblastoma in a 3-month-old Golden Retriever. Can Vet J 2013;54:683686.

  • 7. Frimberger AE, Moore AS, Schelling SH. Treatment of nephroblastoma in a juvenile dog. J Am Vet Med Assoc 1995;207:596598.

  • 8. Seaman RL, Patton CS. Treatment of renal nephroblastoma in an adult dog. J Am Anim Hosp Assoc 2003;39:7679.

  • 9. Baskin GB, De Paoli A. Primary renal neoplasms of the dog. Vet Pathol 1977;14:591605.

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