RPS Case of the Month
George Terinte-Balcan, Irshadjahan Malek, Harsharan K. Singh
Division of Nephropathology, Department of Pathology and Laboratory Medicine,
The University of North Carolina
Chapel Hill, NC., United States of America
A 28 year old Caucasian female with a past medical history of systemic lupus erythematous for approximately 2 years presented with a serum creatinine of 1.5 mg/dl and serum albumin of 3.5 g/dl. She was taking plaquenil. Her complement levels were normal. She had 3+ hematuria and 1+ proteinuria. A kidney biopsy was performed in order to reveal the cause of the renal failure.
KIDNEY BIOPSY FINDINGS
Light Microscopy: The tissue was examined at 10 levels with H&E, PAS, trichrome, and Jones silver stains. The up to 89 glomeruli demonstrated 48 with global sclerosis and 14 others with segments of tuft sclerosis and adhesions to Bowman’s capsule. 14 glomeruli had cellular to focal fibrocellular crescent formation with associated karyorrhectic debris in some glomeruli 9. In focal glomeruli there was mesangial and endocapillary hypercellularity (Figure 1A). There was diffuse mild interstitial fibrosis and tubular atrophy. Arterioles were unremarkable. Arteries revealed mild fibroelastosis.
Immunofluorescence Microscopy: 15 glomeruli were available for evaluation of which 9 were globally sclerosed. There was granular glomerular mesangial and focal capillary wall staining with antisera specific for IgG 2+, IgA 2+, IgM 1+, C3 2+ and kappa and lambda light chains 2+.
Electron Microscopy: The semithin sections of the tissue processed for electron microscopy demonstrated 2 glomeruli out of which 1 was globally sclerosed. Segmental endocapillary hypercellularity was seen in the inflated glomeruli. Electron microscopic examination showed glomerular basement membranes of variable thickness with areas of remodeling and with segmental effacement of the overlying foot processes. There were characteristic immune complex type electron dense deposits within mesangial, a few paramesangial and rare subendothelial regions (Figure 1B). In addition, in some mesangial regions, there were randomly arranged nonbranching fibrils measuring 18-20 nm in diameter (Figure 1C).
Immunohistochemistry: An immunohistochemical stain for DNAJB9 was performed and showed positive mesangial staining in some glomeruli (Figure 1D).
Figure 1. Kidney biopsy findings. (A) Light microscopy image showing a glomerulus with segmental endocapillary hypercellularity (black arrow) and fibrocellular crescent formation (red arrow). PAS stain, 200X. (B) Electron microscopy image showing immune complex type electron dense deposits located in the paramesangium. (C) Electron microscopy image showing a mesangial area that demonstrates nonbranching randomly arranged fibrils. (D) Light microscopy image of DNAJB immunostain that shows almost global positivity in the glomerulus.
Sclerosing and active immune complex mediated glomerulonephritis with approximately 15% cellular to fibrocellular crescent formation with combined features of fibrillary glomerulonephritis and diffuse lupus nephritis (ISN/RPS class IV).
Fibrillary Glomerulonephritis (FGN) is rare and seen in 0.6 and 1% of all kidney biopsies in large series of cases [1-3]. The diagnosis is based on electron microscopy with the finding of characteristic and diagnostic randomly arranged, non-branching fibrils with size ranging between 12-24 nm . In recent years, the diagnosis can be confirmed by DNAJB9 immunohistochemical staining with positivity detected within the glomeruli . These deposits are Congo-red negative .
The morphologic patterns seen by light microscopy can be varied, with the most common being either a mesangioproliferative or a membranoproliferative pattern [1, 2]. Crescent formation can be seen in 17 to 31% of biopsies [2, 3]. Immunofluorescence microscopy typically shows polyclonal IgG and complement deposition . Electron microscopy demonstrates randomly arranged non branching fibrils that have a diameter between 12 and 22 nm .
There is no known therapy for FGN and the prognosis is usually poor, with end stage renal disease in 2-5 years in approximately 45% of cases [1, 3]. The patients that have a sclerosing, diffuse proliferative or membranoproliferative pattern on light microscopy are the ones that progress the fastest towards ESRD .
FGN has been diagnosed in patients that also had malignancies, autoimmune diseases, chronic hepatitis C infection, diabetes and hypertension [1, 2]. There are very few reports of patients that suffered from lupus nephritis and also had FGN [2, 3, 5, 6]. The long term prognosis of these patients is difficult to estimate given the few cases that are published.
1. Iskandar, Samy S., Ronald J. Falk, and J. Charles Jennette. "Clinical and pathologic features of fibrillary glomerulonephritis." Kidney international 42.6 (1992): 1401-1407.
2. Nasr SH, Valeri AM, Cornell LD, et al. Fibrillary glomerulonephritis: a report of 66 cases from a single institution. Clin J Am Soc Nephrol. 2011;6(4):775-784. doi:10.2215/CJN.08300910
3. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D'Agati VD. Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features. Kidney Int. 2003 Apr;63(4):1450-61. doi: 10.1046/j.1523-1755.2003.00853.x. PMID: 12631361.
4. Nasr SH, Vrana JA, Dasari S, Bridoux F, Fidler ME, Kaaki S, Quellard N, Rinsant A, Goujon JM, Sethi S, Fervenza FC, Cornell LD, Said SM, McPhail ED, Herrera Hernandez LP, Grande JP, Hogan MC, Lieske JC, Leung N, Kurtin PJ, Alexander MP. DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary Glomerulonephritis. Kidney Int Rep. 2017 Aug 8;3(1):56-64. doi: 10.1016/j.ekir.2017.07.017. PMID: 29340314; PMCID: PMC5762944.
5. Bhat ZY, Zeng X, Hingorani J, Khan S, Mohanty MJ. Fibrillary glomerulonephritis in a patient with systemic lupus erythematosus: a rare association. Int Urol Nephrol. 2013 Feb;45(1):281-4. doi: 10.1007/s11255-011-0073-0. Epub 2011 Nov 19. PMID: 22102086.6. Menon S, Zeng X, Valentini R. Fibrillary glomerulonephritis and renal failure in a child with systemic lupus erythematosus. Pediatr Nephrol. 2009 Aug;24(8):1577-81. doi: 10.1007/s00467-009-1168-z. Epub 2009 Mar 24. PMID: 19308460.
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