Pathology in Practice

Ryan P. Traslavina Departments of Pathology, Microbiology, and Immunology, University of California-Davis, Davis, CA 95616.

Search for other papers by Ryan P. Traslavina in
Current site
Google Scholar
PubMed
Close
 DVM
,
Monica Aleman William R. Pritchard Veterinary Medical Teaching Hospital, University of California-Davis, Davis, CA 95616.

Search for other papers by Monica Aleman in
Current site
Google Scholar
PubMed
Close
 MVZ, PhD, DACVIM
,
Verena K. Affolter Departments of Pathology, Microbiology, and Immunology, University of California-Davis, Davis, CA 95616.

Search for other papers by Verena K. Affolter in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
Richard A. LeCouteur Surgical and Radiological Sciences, University of California-Davis, Davis, CA 95616.

Search for other papers by Richard A. LeCouteur in
Current site
Google Scholar
PubMed
Close
 BVSc, PhD, DACVIM
,
Rajendra Ramsamooj School of Veterinary Medicine, and the Department of Pathology, School of Medicine, University of California-Davis, Davis, CA 95616.

Search for other papers by Rajendra Ramsamooj in
Current site
Google Scholar
PubMed
Close
 MD
, and
Robert J. Higgins Departments of Pathology, Microbiology, and Immunology, University of California-Davis, Davis, CA 95616.

Search for other papers by Robert J. Higgins in
Current site
Google Scholar
PubMed
Close
 BVSc, PhD, DACVP

Click on author name to view affiliation information

History

A 1.5-year-old 40.5-kg (89.1-lb) castrated male hound and German Shepherd Dog cross was brought to the University of California-Davis William R. Pritchard Veterinary Medical Teaching Hospital for evaluation of bilateral pelvic limb weakness of 2 weeks’ duration. Initial neurologic signs had appeared at 7 months of age and lasted for 2 months but resolved without treatment until this last episode.

Clinical and Intraoperative Findings

On neurologic examination, the dog was ambulatory with asymmetric paraparesis (worse in the left pelvic limb). Postural reactions were considered normal in the thoracic limbs and absent in both pelvic limbs. No signs of pain were elicited during palpation of the vertebral column and limbs. The neuroanatomic diagnosis was myelopathy at the T3 to L3 region of the spinal cord. At the level of the T13-L1 intervertebral space, MRI revealed an intradural extramedullary mass on the left side that was iso- to hyperintense on T1-weighted images and hypointense on T2-weighted images and severely displaced and compressed the spinal cord. The dog underwent surgery, during which a dark red, multilobular, firm, intradural extra- and intramedullary (1 × 1 × 0.6-cm) mass was almost completely removed from the T13-L1 spinal cord segment (Figure 1). Tissue from the mass was submitted for histologic evaluation.

Figure 1—
Figure 1—

Intraoperative photograph of the thoracolumbar portion of the spinal cord of a 1.5-year-old castrated male hound and German Shepherd Dog cross that had bilateral pelvic limb weakness of 2 weeks’ duration. Previous history included initial appearance of neurologic signs at 7 months of age; signs were evident for 2 months but resolved without treatment. Notice the distorted spinal cord (arrowhead) and dark red intramedullary mass (arrow).

Citation: Journal of the American Veterinary Medical Association 242, 12; 10.2460/javma.242.12.1661

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

Histopathologic Findings

Histologically, the submitted mass was unencapsulated, expansile, and densely cellular. The mass was partly attached to dura mater and composed of a disorganized mixture of 3 neoplastic cell populations (Figure 2). The first cell population was composed of cuboidal to columnar epithelial cells arranged in tangles of branching and infolded tubules with projecting tufts resembling primordial renal glomeruli (Figure 3). Cells had distinct cellular borders, moderate to scant amount of eosinophilic foamy cytoplasm, round to oval basilar nuclei with densely clumped chromatin, and 1 to 2 distinct nucleoli. Flat attenuated tubules filled with foamy eosinophilic material appeared similar to medullary collecting ducts. The second cell population was composed of polygonal (blastemal) cells with large angular hyperchromatic nuclei, indistinct nucleoli, and scant cytoplasm with a high nuclear-to-cytoplasmic ratio; these cells formed dense nests. The third cell population was composed of spindloid cells with indistinct cell borders that formed haphazard sheets and streams, occasionally admixed with islands of cartilage. As many as 40 mitotic figures were counted in ten 400× fields and predominated in epithelial components. There was both moderate single cell and coalescing areas of necrosis.

Figure 2—
Figure 2—

Photomicrograph of a section of the intramedullary mass in the dog in Figure 1. Notice the tubules (arrowhead) and a primordial renal glomerulus (arrow) formed by the epithelial cell population admixed with spindle cells and dense nests of polygonal cells (asterisk). H&E stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 242, 12; 10.2460/javma.242.12.1661

Figure 3—
Figure 3—

Photomicrograph of a section of the intramedullary mass in the dog in Figure 1. Within a primordial renal glomerulus, there is a projecting tuft of cells (black arrow). H&E stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 242, 12; 10.2460/javma.242.12.1661

Immunocytochemical staining of formalin-fixed paraffin-embedded sections of the mass tissue was performed with primary mono- or polyclonal antibodies and aminoethyl carbazol as the chromogen, as recommended by the manufacturer. Primary antibodies against high- and low-molecular weight cytokeratins (Lu-5),a vimentin,b Ki-67 antigen (MIB-1),c glial fibrillary acidic protein (GFAP),c and human Wilms tumor-1 proteinc (WT-1, clone 6F-H2, with neonatal canine kidney as a positive control) were used. The epithelial cell population had strong membranous immunoreactions with antibody against the high- and low-molecular weight cytokeratins (Figure 4). In both epithelial and blastemal cell populations, a nuclear immunoreaction with anti-WT-1 antibody was evident. Both mesenchymal and blastemal cell populations were immunoreactive with anti-vimentin antibody. Neoplastic cells of all 3 populations were negative for GFAP. Nuclear staining with MIB-I (for Ki-67 antigen) revealed a considerable difference in proliferative index (ratio of Ki-67 antigen-positive cells to total number of tumor cells) between the epithelial (50%) and mesenchymal (5%) components.

Figure 4—
Figure 4—

Photomicrographs of sections of the intramedullary mass in the dog in Figure 1 following immunohistochemical staining. A—Glomerular primordia and tubules react strongly with antibodies against high- and low-molecular weight cytokeratins. B—Strong immunoreactivity against vimentin is evident in clumped polygonal cells and stroma elements. Tubules of the epithelial component are not vimentin immunoreactive. C—Strong nuclear immunoreactivity for Wilms tumor-1 protein (WT-1) is present in glomerular structures. D—Results of staining for Ki-67 antigen. The proliferation index (ratio of Ki-67 antigen-positive cells to total number of tumor cells) is as high as 50% in epithelial components. In panels, A, B, C, and D, Lu-5, anti-vimentin antibody, anti-WT-1 (clone 6F-H2) antibody, and MIB-1 staining, respectively; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 242, 12; 10.2460/javma.242.12.1661

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: spinal cord (ectopic) nephroblastoma in a dog.

Comments

Ectopic nephroblastomas of the spinal cord in dogs are distinct and independent of primary renal nephroblastomas.1 To our knowledge, only 1 report details the metastatic spread of a primary nephroblastoma to the spinal cord.2 Ectopic nephroblastomas are common in young dogs < 3 years of age and are believed to originate from renal progenitors that are trapped intradurally and extramedullary during development, most frequently at the thoracolumbar junction.1,2 As such, this neoplasm was once called thoracolumbar tumor of young dogs.3 Historically, these tumors were considered to be most prevalent in German Shepherd Dogs but recently have been identified in a variety of other purebred large-breed and crossbred dogs.1,2

A mutation in the Wilms tumor gene on chromosome 11, which encodes the zinc finger protein WT-1, is associated with nephroblastomas in humans.4,5 Wilms tumor-1 protein orchestrates the transition from epithelial to mesenchymal tissue during nephrogenesis.4 In 1 study,5 up to 56% of human nephroblastomas (n = 60) were immunopositive for WT-1. Similarly, 9 of 11 ectopic nephroblastomas in dogs were positive for this marker.1 In addition to being immunopositive for WT-1, the mass in the dog of the present report was immunoreactive against certain epithelial and mesenchymal markers as previously described.1,3 The mitotic activity and proliferation index were the highest in the epithelial components, including tubules and glomerular primordia, similar to findings of an immunocytochemical study6 of nephroblastomas in humans.

The prognosis for dogs with spinal cord nephroblastomas is variable. One study1 found that the mean survival time of 11 affected dogs that underwent cytoreductive surgery was 70 days. In another study,3 the median survival time was 374 days with only cytoreductive surgery (n = 6) or radiation (1) and 55 days in dogs that underwent palliative treatment, including administration of prednisone and gabapentin (3). Within the same study,3 dogs with a presumptive or definitive diagnosis of intramedullary nephroblastoma had a shorter median survival time (140 days) than did dogs with tumors restricted to the intradural space (median survival time, 380 days).3 In another report,7 a dog with an intra-dural extramedullary tumor lived 5.5 years after cytoreductive surgery and radiation therapy. The dog of the present report had an intramedullary tumor and was treated with cytoreductive surgery and external beam radiation therapy (total dose, 40 Gy [20 fractions; 2 Gy/fraction). At 1 year and 2 months after surgery, the dog was strongly ambulatory, with mild paraparesis and delayed proprioception of the left pelvic limb but normal proprioception of the right pelvic limb.

a.

Boehringer Mannheim, Indianapolis, Ind.

b.

ICN Biochem, Lisle, Ill.

c.

DakoCytomation, Carpinteria, Calif.

References

  • 1. Brewer DM, Cerda-Gonzalez S, Dewey CW, et al. Spinal cord nephroblastoma in dogs: 11 cases (1985–2007). J Am Vet Med Assoc 2011; 238: 618624.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Gasser AM, Bush WW, Smith S, et al. Extradural spinal, bone marrow, and renal nephroblastoma. J Am Anim Hosp Assoc 2003; 39: 8085.

  • 3. Fanni D, Fanos V, Monga G, et al. Expression of WT1 during normal human kidney development. J Matern Fetal Neonatal Med 2011; 24(suppl 2):4447.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Ghanem MA, Van der Kwast TH, Den Hollander JC, et al. Expression and prognostic value of Wilms' tumor 1 and early growth response 1 proteins in nephroblastoma. Clin Cancer Res 2000; 6: 42654271.

    • Search Google Scholar
    • Export Citation
  • 5. Liebel FX, Rossmeisl JH, Lanz OI, et al. Canine spinal nephroblastoma: long-term outcomes associated with treatment of 10 cases (1996–2009). Vet Surg 2011; 40: 244252.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Diniz G, Aktas S, Turedi A, et al. Telomerase reverse transcriptase catalytic subunit expression and proliferation index in Wilms tumor. Tumour Biol 2011; 32: 761767.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Dickinson PJ, McEntee MC, Lipsitz D, et al. Radiation induced vertebral osteosarcoma following treatment of an intradural extramedullary spinal cord tumor in a dog. Vet Radiol Ultrasound 2001; 42: 463470.

    • Crossref
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 112 0 0
Full Text Views 607 569 267
PDF Downloads 99 63 4
Advertisement