Three-year-old male rabbit (Oryctolagus cuniculus).The animal presented two days of anorexia and lack of defecation. At physical examination, a single mass was detected by palpation at the right lumbar area. The presence of a round-shaped mass associated to the caudal pole of the right kidney was confirmed by ultrasonography. Clinicians suspected a neoplastic process, and a right nephrectomy was performed.

Gross Description:  

The complete right kidney was submitted for histopathologic evaluation. A well-circumscribed, oval white mass, 2x1.5 cm in diameter was observed at the caudal pole of the kidney. On section, its consistency was soft, and the cut surface was white and homogeneous.

Histopathologic Description:

Kidney: Replacing 50-75% of the renal tissue, there is a densely cellular, partially encapsulated but infiltrative nodular neoplasm which compresses adjacent parenchyma. The neoplasm is composed of a disorganized mixture of epithelial, mesenchymal, and blastemal components supported by an abundant fibrovascular stroma which, in some areas, is embedded in a loose, pale eosinophilic, collagenous matrix. The mesenchymal and blastemal components are predominant over the epithelial. Epithelial neoplastic cells are cuboidal to cylindrical and arranged in a tubular pattern. Occasionally, there are very scant tuft invaginations into the tubular lumen lined by flat epithelial cells (primitive glomerular structures). Those cells present well-defined cytoplasmic borders and moderate amount of bright eosinophilic cytoplasm. Nuclei are round, irregularly shaped, mostly basally located, with grossly stippled chromatin and less frequently, finely stippled chromatin with one basophilic nucleolus. There is low-grade anisokaryosis and anisocytosis, and low mitotic index (1/40X HPF). The mesenchymal component is arranged in a storiform pattern or disorganized bundles. Cells are fusiform, with an indistinct cytoplasmic border, scant eosinophilic cytoplasm, and fusiform centrally located nuclei with grossly stippled chromatin. There is a mild anisokaryosis and aniso-cytosis, and a low mitotic index (0-1/40X HPF). Some of these cells, organized in nest or ribbons, which are poorly differentiated are identified as possible blastemal cells. Multifocally, in the neoplastic mass there are areas of hypereosinophilia and loss of cytoplasmic and nuclear detail (coagulative necrosis) and mild lymphoplasmacytic inflammatory infiltrate is observed among the neoplasia. The adjacent renal parenchyma shows a moderate interstitial fibrosis, and intense congestion.

Morphologic Diagnosis:  

Renal nephroblastoma.

Lab Results:  




Contributor Comment:  

Nephroblastoma, or Wilms´ tumor, is the most common primary renal tumor of pigs and chickens, and occurs far less often in calves and dogs. It is frequently observed in young animals, although it may be seen in mature sows, and is more common in adult dogs than in pups. Clinically, it is usually an incidental finding except in dogs, in which some animals present with spinal dysfunction as result of compression of the spinal cord associated with neoplastic infiltration into the vertebral canal. Macroscopically, it is usually a solitary unilateral mass located at one pole of the kidney, but it can be multiple and/or bilateral. Nephroblastoma is a true embryonal tumor that arises from primitive metanephric blastema and exhibits blastemal, epithelial, and stromal components in variable proportions. Histologically, it is characterized by the presence of primitive glomeruli, abortive tubules, and loose spindle-cell stroma that may differentiate into a variety of mesen-chymal tissues.

Tubular and glomerular differentiation indicate a good prognosis, whereas anaplasia and sarcomatous stroma are associated with metastasis and a poor prognosis. In this case, the epithelial component is scant and poorly differentiated, and there is a clear predominance of undifferentiated mesen-chymal cells. These features, in combination with the neoplasm’s invasive growth pattern, suggest a poor prognosis. The differential diagnosis for renal neoplasia in a rabbit includes renal carcinoma and renal lymphosarcoma. To confirm the diagnosis of nephroblastoma, immuno-histochemistry was performed against Wilm's tumor  suppressor (WT1), which has proven efficacious in dogs. This immunohistochemistry was kindly provided by Dr. Joan Carles Ferreres, head of the Pathology Department at the Parc Taulí Sabadell University Hospital. In this case, positive nuclear immunoreactivity was observed in the mesenchymal and blastemal components, as well as endothelial cells.

JPC Diagnosis:  

Kidney: Nephroblastoma, rabbit, Oryctolagus cuniculus.

Conference Comment:  

This case nicely demonstrates the blastemal, epithelial, and stromal components histologically characteristic for nephroblastomas. Conference participants readily identified the presence of scattered primitive glomeruli (formed by infolded papillary projections of polygonal cells within tubule lumina), as well as low numbers of tortuous, abortive tubules admixed with numerous blastemal cells and surrounded by an abundant loose spindle-cell stroma. Additionally, attendees noted several individualized well-differentiated renal tubules scattered throughout the neoplasm. Conference participants agreed that these likely represent entrapped non-neoplastic renal tubules within the neoplastic cell population rather than part of the epithelial component of the neoplasm. There is moderate slide variability, affecting the proportion of the three components present. When all three cell types are present in equivalent proportions, the neoplasm is referred to as triphasic or mixed;7 however, in this case there appears to be a preponderance of spindle-cell stromal and blastemal components. Although not a prominent feature in this case, the spindle-cell stroma can occasionally differentiate into various types of mesenchymal tissue, such as striated muscle, collagen, adipose tissue, bone, or cartilage.6,7

Nephroblastoma rarely causes clinical signs, although polycythemia is an infrequently reported paraneoplastic syndrome in rabbits.2 The vast majority of nephro-blastomas are considered incidental findings and are noted during necropsy as a solitary (or occasionally bilateral) renal masses.1 However, as mentioned by the contributor, when this neoplasm is characterized predominantly by a poorly differentiated sarcomatous stromal component, as in this case, it tends to metastasize to the lung and liver, portending an overall poor prognosis.7

While nephroblastomas are a relatively uncommon spontaneous neoplasm in pet rabbits, they can be rapidly induced at a high frequency in laboratory rabbits and rats after exposure to direct-acting alkylating carcinogens, such as dimethylnitrosamine.6 Dimethylnitrosamine has also been reported to experimentally induce triphasic nephro-blastomas in rainbow trout, similar to Wilm’s tumor in humans.3 Other than lymphoma, nephroblastomas are the most common primary renal neoplasm in a variety of species of freshwater fish, with the Japanese eel over-represented. Research is ongoing to determine if potential carcinogens in the water may be inducing nephroblastomas in wild fish, with a particular focus on fish commonly consumed by people.3


1. Cianciolo RE, Mohr FC. The urinary system. In: Maxie MG ed. Jubb Kennedy and Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:446-447.
2. Cooper TK, Griffith JW, et al. Spontaneous lung lesions in aging laboratory rabbits (Oryctolagus cuniculus). Vet Pathol. 2017; 54(1):178-187.
3. De Lorenzi D, Baroni M, Mandara MT. A true "triphasic" pattern: Thoracolumbar spinal tumor in a young dog. Vet Clin Pathol. 2007; 36:200-203.
4. Hassan J, Katic N, et al. Treatment of nephroblastoma with poly-cythemia by nephrectomy in a rabbit. Vet Rec. 2012; 170:465.
5. Lombardini ED, Hard GC, Hashbarger JC. Neoplasms in the urinary tract in fish. Vet Pathol. 2014; 51(5):1000-1012.
6. Meuten DJ. Tumours of the urinary system. In: Meuten DJ, ed. Tumors in Domestic Animals. Ames, IA: Iowa State Press; 2002:519-520.
7. Newman SJ. The urinary system. In: McGavin MD, Zachary JF, ed.  Pathologic Basis of Veterinary Disease. 5th ed. St Louis, MO: Elsevier Mosby; 2012: 643.

Click the slide to view.

4-1. Kidney, rabbit.

4-2. Kidney, rabbit.

4-3. Kidney, rabbit.

4-4. Kidney, rabbit.

4-5. Kidney, rabbit.

4-6. Kidney, rabbit.

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