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Kidney tumor - cysts, children, adult benign

Cystic non-neoplastic lesions

Nephronophthisis


Reviewers: Mandolin Ziadie, M.D. (see Reviewers page)
Revised: 30 December 2011, last major update December 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

General
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● Group of autosomal recessive disorders characterized by corticomedullary cysts, atrophy and interstitial fibrosis
● “Phthisis” (Greek): dwindling or wasting away
● Also referred to as juvenile nephronophthisis-medullary cystic kidney disease complex

Epidemiology
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● 1:50,000
● Most common genetic cause of pediatric end stage renal disease (ESRD)

Pathophysiology
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● Mutations in NPHP genes (produce nephrocystins in cilia / basal body structures, Eur J Hum Genet 2009;17:406, J Am Soc Nephrol 2007;18:1855), which cause defects in signaling mechanisms that result in defects of planar cell polarity and tissue maintenance (J Am Soc Nephrol 2009;20:23)

Clinical features
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Juvenile form: most common; presents in childhood with polyuria / polydipsia due to cortical and tubulointerstitial damage that progresses to chronic renal failure in 5-10 years; no gender preference; also anemia and growth retardation; 12% associated with retinitis pigmentosa
Adolescent form: similar to juvenile with later (mean, 19 years) presentation
Infantile: bilateral disease due to cortical cysts with renal failure by 3 years of age; may have extrarenal presentation including retinitis pigmentosa, hepatic fibrosis, skeletal / CNS malformations, situs inversus, etc.

Case reports
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● 4 year old girl with basal ganglia calcification and pancreatic lipomatosis (Arch Pathol Lab Med 1988;112:630)

Treatment
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● Renal transplant for ESRD (Pediatr Transplant 2008;12:878)

Gross description
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● Normal or small kidneys with firm, granular cortices and corticomedullary cysts
● Infantile forms have enlarged kidneys with cortical cysts

Gross images
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Cysts at corticomedullary junction, tubular cysts and interstitial infiltrate

Micro description
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● Severe tubular atrophy with thick basement membranes, interstitial fibrosis and chronic inflammation
● Minimal to advanced glomerulosclerosis
● Cysts at corticomedullary border lined by flattened or cuboidal epithelium
● Liver biopsy may show congenital hepatic fibrosis

Micro images
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Tubular basement membrane thickening and cystic tubular enlargement

Tubules with thickened basal membrane (PAS)

Dilated collecting ducts with thickened basal membrane (PAS)

Dilated tubules, thickened basal membrane (PAS)

Deformed tubules with thickened basal membrane in fibrotic stroma (PAS)

Dilated tubules with lymphocytic infiltrate (PAS)

End stage renal disease:
Extensive obliteration of glomeruli and sclerotic glomerli, interstitial fibrosis, atrophic tubules and chronic inflammation (PAS)

Preserved glomeruli with individual glomerular cysts, tubulointerstitial fibrosis, hypertrophic tubules, lymphocytic infiltrate #1, #2, #3 (PAS)

Tubulointerstitial fibrosis, tubular cysts and lymphocytic infiltrate (PAS)

Molecular description
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● Mutations in NPHP2 and NPHP3 genes (Kidney Int 2009;75:839), also associated with retinitis pigmentosa, mental retardation, cerebellar ataxia, bone anomalies and liver fibrosis
● Juvenile subtype associated with mutations in NPHP1 (OMIM 256100, chromosome 2q), 4 (chromosome 1p)
● Infantile subtype associated with NPHP2 (chromosome 9q)
● Adolescent subtype associated with NPHP3 (chromosome 3q)

EM description
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● Homogenously thickened tubular (NOT glomerular) basement membrane, split into thin lamellae, reticulated or disintegrated

EM images
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Tubules:
Atrophic tubules with partly thickened, partly missing basal lamina

Basal membrane shows thickening, splitting, grid like degeneration or complete absence

Grid like degeneration of tubular basement membrane

Thickened tubular basement membrane

Partially atrophic tubule with thickened basal membrane

Newly formed lamellar basal membrane

Cyst wall lined with collecting duct epithelium, basal membrane is lost

Collapsed glomeruli centrally, Bowman’s capsule is filled with amorphous material

Glomeruli:
Thickened glomerular basal membrane with lacuna, periglomerular fibrosis

Mild periglomerular fibrosis, thickened tubules with fragmented basal lamina, lymphocytes

End of Kidney tumor - cysts, children, adult benign > Cystic non-neoplastic lesions > Nephronophthisis


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