AFIP SYSTEMIC PATHOLOGY

JPC SYSTEMIC PATHOLOGY

URINARY

JANUARY 2018

U-N01

 

Signalment U-N01a (JPC 1759231): Pig

 

HISTORY: Tissue from a large abdominal mass found incidentally at the time of slaughter of a market pig.

 

HISTOPATHOLOGIC DESCRIPTION: Kidney (two sections): Within the cortex, compressing adjacent renal parenchyma and extending to cut borders is an encapsulated, partially lobulated, well-demarcated, expansile neoplasm composed of a disorganized mixture of three distinct cell populations: epithelial, mesenchymal and blastemal. The epithelial population is composed of cuboidal to columnar cells arranged in infolded tubules and occasionally projecting densely cellular tufts into lumina with cells lining a fibrovascular stalk (primitive glomeruli). These neoplastic cells have variably distinct cell borders, a moderate amount of eosinophilic fibrillar to foamy cytoplasm, irregularly round to oval nuclei with densely clumped chromatin and 1-2 generally distinct nucleoli. The mitotic rate is 2 per HPF. The mesenchymal population is composed of spindle cells loosely arranged in vague streams (embryonal mesenchyme). These neoplastic cells are stellate to spindle with variably distinct cell borders, a scant amount of eosinophilic fibrillar cytoplasm, oval to elongate nuclei with finely stippled chromatin and 1-2 variably distinct nucleoli. The mitotic rate is <1 per HPF. The blastemal population is composed of polygonal cells arranged in vague nests. These neoplastic cells have indistinct cell borders, a scant amount of eosinophilic fibrillar cytoplasm and a high nuclear to cytoplasmic ratio. Nuclei are irregularly round to oval with densely clumped chromatin and 1-3 variably distinct nucleoli. The mitotic rate is 1 per HPF. Multifocally there is scattered individual cell necrosis. Multifocally there are small aggregates of lymphocytes and plasma cells, which extend into the adjacent cortical interstitium. In the adjacent kidney there are multifocal areas of interstitial hemorrhage and tubular atrophy.

 

MORPHOLOGIC DIAGNOSIS: Kidney: Nephroblastoma, breed unspecified, porcine.

 

Signalment U-N01b (JPC 1923149): Pigtailed macaque.

 

HISTORY: Renal mass from a 6‑month‑old female pigtailed macaque.

 

HISTOPATHOLOGIC DESCRIPTION: Kidney: Within the cortex, compressing adjacent renal parenchyma and extending to cut borders is an encapsulated, well demarcated, lobulated, expansile neoplasm. In one lobe, the neoplasm is composed of a disorganized mixture of three distinct cell populations: epithelial, mesenchymal and blastemal. The epithelial population is composed of cuboidal to columnar cells arranged in infolded tubules and occasionally projecting tufts into lumina (primitive glomeruli). These neoplastic cells have variably distinct cell borders, a moderate amount of eosinophilic fibrillar to foamy cytoplasm, irregularly round to oval nuclei with densely clumped chromatin and 1-2 generally distinct nucleoli. The mitotic rate is 2 per HPF. The mesenchymal population is composed of spindle cells loosely arranged in vague streams (embryonal mesenchyme). These neoplastic cells are stellate to spindle with variably distinct cell borders, a scant amount of eosinophilic fibrillar cytoplasm, oval to elongate nuclei with finely stippled chromatin and 1-2 variably distinct nucleoli. The mitotic rate is <1 per HPF. The blastemal population is composed of polygonal cells arranged in vague nests. These neoplastic cells have indistinct cell borders, a scant amount of eosinophilic fibrillar cytoplasm and a high nuclear to cytoplasmic ratio. Nuclei are irregularly round to oval with densely clumped chromatin and indistinct nucleoli. The mitotic rate is 1 per HPF. The second lobe is composed of blastemal and mesenchymal cell populations. The blastemal population is composed of polygonal cells arranged in vague nests, ribbons, and solidly cellular areas. These neoplastic cells have indistinct borders, an abundant amount of eosinophilic to amphophilic, foamy to fibrillar cytoplasm, large, vesiculate nuclei with1-2 prominent nucleoli. Mitotic rate is 5 per HPF. There is moderate anisokaryosis and anisocytosis. Separating and surrounding the blastemal population is the previously described mesenchymal population producing distinctive streams of eosinophilic to fibrillar matrix that surrounds and separates nests of neoplastic cells. Multifocally there is individual cell necrosis and areas of coagulative and lytic necrosis. Multifocally, there is minimal to moderate dilatation of tubules (ectatic tubules).

 

MORPHOLOGIC DIAGNOSIS: Kidney: Nephroblastoma, Pigtailed macaque (Macaca nemestrina), non-human primate.

 

ETIOLOGY: Unknown; Wilms’ tumor locus has been mapped at the chromosome 11p13 as a tumor suppressor gene.

 

SYNONYMS: Wilms’ tumor, embryonal or renal adenosarcoma, and embryonal nephroma

 

GENERAL DISCUSSION:

·  Embryonal malignancy (most tumors in swine occur in young animals (< 2 years); occurs more often in adult dogs than pups)

·  Nephroblastoma is the most common primary renal tumor of swine, chickens and fish and the second most common primary renal tumor in dogs and cats; less frequent in cattle

·  Metastasis is frequent in dogs and cats; rare in swine

 

PATHOGENESIS:

· Nephroblastomas are true embryonal tumors that arise from the metanephrogenic renal blastema, a group of pluripotent cells that normally develops into both the nephrons and the renal interstitial tissue

· In humans, mutation of the tumor suppressor gene WT1 (Wilm’s tumor gene located on chromosome 11p13) is a causative factor

· Prognosis considered good if more tubular and glomerular differentiation present; anaplasia and sarcomatous stroma associated with metastasis and poorer prognosis

 

TYPICAL CLINICAL FINDINGS:

· Signs may be absent

· Abdominal enlargement and hematuria have been reported

· Paraneoplastic syndrome: Polycythemia (due to erythropoietin) has been reported secondary to nephroblastoma in a dog

 

TYPICAL GROSS FINDINGS:

· Encapsulated white to tan, multilobulated, and firm mass with spongy and cystic areas, often with foci of necrosis and hemorrhage

· Usually located in the cortex, extending through the capsule

· Usually unilateral (with bilateral and extrarenal cases reported) and in one pole

· May be very large (up to 34 kg in swine)

· In dogs, metastases are most commonly reported in regional sublumbar and mesenteric lymph nodes, liver, lungs and the contralateral kidney

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

· A disorganized mixture embryonal epithelium and mesenchymal tissue is diagnostic; embryonic glomeruli tufts are an important feature

·      Epithelial component: Varies from glandular, tubular (abortive tubules) or glomeruloid structures (primitive glomeruli) that lack capillaries; occasionally the epithelial component becomes squamous and is keratinized

·      Mesenchymal component: May be arranged in undifferentiated lobules or streams or differentiated into smooth/skeletal muscle or less frequently fibrous, mucoid or adipose tissue, or, cartilage or bone

·      Blastemal cells: Found in clumps or dispersed between the epithelial and mesenchymal tissues with high nuclear to cytoplasmic ratio

·      Referred to as triphasic/mixed when all three elements present

· The proliferation rate and malignant potential of each element may vary even within a single tumor

· High mitotic activity, anaplasia, invasion and sarcomatous differentiation are associated with a greater likelihood of metastasis and a poorer prognosis

 

ADDITIONAL DIAGNOSTIC TESTS:

·      Cytology: Mononuclear cell tumor that resembles lymphoma; cells may be bimorphic

·      Immunohistochemistry:

·      Vimentin: Blastemal and stromal elements

·      Desmin: Stromal elements

·      Cytokeratin (CK19): Epithelial components

·      Wilm’s tumor gene product C19/ WT-1 stain: Successfully stains canine nephroblastomas, but not mesenchyme elements

·      GFAP: Negative

 

DIFFERENTIAL DIAGNOSIS:

· Renal adenoma

· Renal adenocarcinoma

· Renal carcinoma (for small papillary projections): Lack a blastemal cell population and embryonic mesenchymal tissue

 

 

COMPARATIVE PATHOLOGY:

· Reported in all major domestic animals and a variety of other animals and humans

· Rats: A subline of Sprague-Dawley rats (Upj:TUC(SD)spf.nb) has an incidence of 14%; often induced by carcinogens (e.g. dimethylnitrosamine)

·  Dogs: Thoracolumbar (T10-L3) spinal cord tumor of young dogs (ectopic nephroblastoma)

·      Seen most commonly in young German shepherds

·      Likely develop from remnants of renal rests trapped between the dura and the developing spinal cord

·      Form embryonic glomeruli, tubules and rosettes

·      Stain positive for Wilms’ tumor gene product (WT-1)

· Fish: Multiple species (Japanese eel, rainbow trout especially) can develop spontaneous or secondary to carcinogens; most commonly develop from the posterior aspect of the kidney

·      Chickens: Associated with an oncovirus (Avian leukosis virus)

 

References:

1.    Bailey GS, Willaims DE, Hendricks JD. Fish models for environmental carcinogenesis: the rainbow trout. Environ Health Perspect. 1996;104(suppl1):5-21.

2.    Breshears MA, Confer AW. Urinary system. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:664-665.

3.    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(5):618-624.

4.    Cianciolo RE, Mohr FC. The urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 2, 6th ed. St. Louis, MO: Elsevier Limited; 2016:446-447.

5.    Higgins RJ, Bollen AW, Dickinson PJ, et al. Tumors of the nervous system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, Iowa: Iowa State Press; 2017:863-864.

6.    Lombardini ED, Hard GC, Harshbarger JC. Neoplasms of the Urinary Tract in Fish. Vet Pathol. 2014;51:1000-1012.

7.    Mesfin GM. Intralobar nephroblastematosis: precursor lesions of nephroblastoma in the Sprague-Dawley rat. Vet Pathol. 1999;36:379-90.

8.    Meuten DJ, Meuten TLK. Tumors of the urinary system. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, Iowa: Iowa State Press; 2017:646-649.

9.    Nair V, Fadly AM. Neoplastic diseases: Leukosis/sarcoma group. In: Swayne DE, ed. Diseases of Poultry. 13th ed. Ames, IA: Wiley-Blackwell Publishing; 2013:578-582.

10. Rehulka J. Spontaneous nephroblastoma in a hatchery rainbow trout Oncorhynchuis mykiss. Disease of Aq Organ. 1992;14:75-79.

11. Terrell SP, Platt SR, Chrisman CL, et al. Possible intraspinal metastasis of a canine spinal cord nephroblastoma. Vet Pathol. 2000;37:94-97.

12. Traslavina RP, Aleman M, Affolter VK, et al. Pathology in practice. Spinal cord (ectopic) nephroblastoma in a dog. J Am Vet Med Assoc. 2013 Jun 15;242(12):1661-1663.

13. Zoller M, Matz-Rensing K, Fabrion A, Kaup F. Malignant nephroblastoma in a common marmoset (Callithrix jacchus). Vet Pathol. 2008:45:80-84.


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