CRP-03
CRP-03
Clinical History
The patient is a 52 year old white male.
The patient is hepatitis C positive with a history of hepatorenal syndrome. Status post liver transplant for cirrhosis. Now with nephrotic range proteinuria. BUN 57, creatinine 4.5, BP 150/98. Clinical impression: membranous nephropathy, rule out cryoglobulinemia.
Gross Description
Received in transport media are two cores of renal tissue measuring 8 mm and 2.3 cm in length and 1 mm in diameter. The 8-mm core is submitted for immunofluorescence. Three 1-mm pieces are taken from the other core for EM, and the remaining tissue is processed for light microscopy.
Pathology
Case CRP-003 H&E
Case CRP-003 PASH
Case CRP-003 Silver
Microscopic Description
Light Microscopy
The specimen consists of two fragments of renal cortex and medulla that contain 51 glomeruli in the three levels examined. Twelve of these are obsolete, and seven others demonstrate segmental sclerosis with hyalinosis. The remaining glomeruli are similar and show diffuse mesangial expansion, as well as mesangial and epithelial hypercellularity. The lobular architecture of the glomeruli is clearly accentuated. One small epithelial crescent is identified, but most of the epithelial cell proliferation is visceral rather than parietal epithelium. Silver stain demonstrates duplication of the basement membranes focally, but no spikes are identified along the epithelial surfaces. No segmental areas of necrosis are identified, and no glomerular thrombi are noted. There is diffuse moderate interstitial fibrosis with corresponding tubular atrophy. Many of the remaining tubules demonstrate epithelial simplification and irregular dilatation. The interstitium is quite active, with numerous lymphocytes scattered throughout the cortex. However, no tubulitis is identified. The large arteries at the corticomedullary junction show marked intimal fibrosis. The arterioles show moderate to marked thickening with hyaline deposition. No vasculitis is identified, and none of the arterioles or small arteries demonstrate thrombi.
Immunofluorescence
There are fourteen glomeruli in the sections. Three of these are obsolete, but the remaining glomeruli appear to be hypercellular with thickened glomerular basement membranes. There is diffuse capillary and mesangial staining that is graded 3+ for C3 and l+ for IgG. IgM, IgA and light chains. There is no staining for Clq. The staining is generally granular, and some of the granules are quite large. The capillary loop staining appears to be subendothelial and intramembranous. There is no staining of tubules or blood vessels. No thrombi are identified.
Electron Microscopy
Three thick sections containing a total of three glomeruli are available. These are similar to those described under light microscopy. Ultrastructural examination of one glomerulus confirms the marked mesangial expansion and hypercellularity. Occasional mesangial electron dense deposits are identified. The capillary basement membranes are markedly thickened, and occasional examples of mesangial interposition and formation of new basement membrane are noted. There is diffuse fusion of the visceral epithelial cell foot processes. Numerous electron dense deposits are identified in subepithelial and intramembranous locations. Some of the intramembranous deposits appear to be undergoing resorption. Only rare, small subendothelial deposits are noted.
These combination of light, IF and EM findings suggest two different lesions. Most of the glomerular basement membranes deposits are subepithelial and intramembranous, which is more typical of membranous glomerulonephritis. Similarly, the IF findings suggest long standing membranous glomerulonephritis. However, the glomerular histology is typical of type I membranoproliferative glomerulonephritis, and the focal examples of mesangial interposition are not characteristically seen in membranous glomerulonephritis. Both of these lesions (membranous and membranoproliferative glomerulonephritis) have been described in conjunction with hepatitis C infection, and it is tempting to speculate that the patient has had membranous glomerulonephritis for a long time, and now he has progressed to a more active form of glomerulonephritis. There is no evidence of cryoglobulinemia in this biopsy.