7 December 2005 Case of the Week #30
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We thank Dr. Dylan Miller, Mayo Clinic, Rochester, Minnesota (USA) for contributing this case. We invite you to contribute a Case of the Week by sending an email to NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case. Please only send cases with a definitive diagnosis.
Case of the Week #30
Clinical History
A 41 year old man with diabetes presented with renal failure one week after an upper respiratory infection. A renal biopsy was obtained, and processed for H&E and electron microscopy.
Micro description: H&E, PAS stain, Jones methenamine silver
Electron microscopy: image (m: mesangial nodule, arrow: subepithelial hump)
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Diagnosis
Diabetic nodular glomerulosclerosis with superimposed post-infectious glomerulonephritis.
Discussion
This case features two distinct lesions consistent with the patients history of diabetes and streptococcal infection (an ASO titer was elevated).
Patients with diabetes have numerous renal lesions, including nodular glomerulosclerosis, also called intercapillary glomerulosclerosis or Kimmelstiel-Wilson disease. These are ovoid, spherical, laminated hyaline masses in the periphery of the glomerulus that are PAS positive (additional image #1). They may eventually obliterate the glomerular tuft, causing end stage renal disease. They are relatively specific for diabetes, but may also be found in membranoproliferative glomerulonephritis, light-chain disease and amyloidosis.
Other
microscopic diabetic renal lesions include (a) basement membrane thickening and
increased mesangial matrix, in all patients; (b) diffuse glomerulosclerosis,
identified by an increase in PAS+ mesangial matrix associated with basement
membrane thickening, that eventually obliterates mesangial cells; (c) profound
hyalinization of afferent arterioles (insudative lesion-intramural), which is specific
for diabetes at this site (image);
(d) organizing fibroepithelial crescents, associated with an aggressive
clinical course; and (e) diffuse thickening of the tubular basement membrane,
tubular atrophy and interstitial fibrosis.
Post-streptococcal
glomerulonephritis is a diffuse type of
endocapillary proliferative glomerulonephritis. It is also called post-infectious
glomerulonephritis, because similar histologic findings are seen with endemic
malaria, toxoplasmosis, hepatitis B and C, HIV, varicella, spirochetes,
staphylococci, meningococci and other bacteria. The deposition of immune
complexes from antibodies against organisms elicits an acute inflammatory
response and nephritic syndrome. Post-streptococcal disease is decreasing in the
US, where post-Staphylococcal aureus infection is more frequent, but it
is common elsewhere. Histologically, the glomeruli are globally and diffusely
enlarged and hypercellular due to neutrophils and macrophages, and the proliferation
of mesangial and endothelial cells. Capillary lumina are obstructed by swollen
endothelial cells and inflammatory cells. Immunofluoresence shows a granular
(lumpy-bumpy) deposition of IgG, IgM and C3 in peripheral glomerular loops. EM
shows subepithelial humps (finely granular, dome-shaped, electron dense
material, representing immune complex deposits), and the obliteration of
epithelial cell foot processes. A case
of IgA dominant, post-staphylococcal
glomerulonephritis complicating diabetic nephropathy has been reported (Hum
Path 2003;34:1235). Additional
references: Hum Path 1993;24:77 (pathogenesis of
Kimmelstiel-Wilson nodule).
Also see our Kidney-Non tumor chapter (click here) Nat
Pernick, M.D.
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