Clinicopathologic Characterization of Membranous Glomerulonephritis with Crescents
Caroline Barrett, Donald Houghton, Megan Troxell. OHSU, Portland, OR
Background: Membranous glomerulonephritis (MGN) infrequently presents with glomerular crescents and necrosis (NCGN), except in lupus nephritis. This combination of glomerular lesions may represent a coincidental occurrence of two disease processes, or may be related to each other, or to a common pathophysiologic process. We reviewed our institution's experience with non-lupus MGN-NCGN, including IgG subclass staining, in order to further address this question.
Design: Renal biopsies with both MGN and NCGN were identified by searching the pathology database (2000-2011). Lupus nephritis cases were excluded, yielding 12 cases. Biopsy pathology was reviewed, and correlated with available patient history at presentation, treatment, and followup. In addition, immunofluorescent staining for IgG subclasses was performed on 6 cases with archival frozen tissue (antibodies from The Binding Site).
Results: MGN-NCGN was seen in biopsies from 2 children and 10 adults (6 patients >70 years old). ANCA serologies were positive in 7/10 patients (all MPO/P-ANCA); none had evidence of anti-GBM disease. ANA was positive in 5/10 patients, none with subsequent clinical evidence of lupus. Two patients had active malignancy (ovarian cancer, CLL, with CLL focally present in renal biopsy). One patient each had a history of treatment with hydralazine and gold (remote), and one reported infrequent NSAIDs use. Hepatitis serologies were negative in all cases with available data.
In MGN-NCGN biopsies, cellular or fibrocellular crescents were present in a mean of 26% of glomeruli (range 3-70%). Five biopsies had minor mesangial or endocapillary hypercellularity. Five of 12 cases had >50% interstitial fibrosis and tubular atrophy at biopsy. One biopsy had C3-only capillary wall deposits; none had immune deposits other than typical MGN pattern. Of six tested cases, 4 showed no IgG4 in the IgG deposits, while in 2 cases IgG4 staining was co-dominant with IgG1. IgG4 staining was negative in the patient with concurrent ovarian cancer.
Conclusions: Review of MGN-NCGN cases at our center revealed evidence of heterogeneous pathogenesis. A substantial subgroup of patients (7) was positive for MPO/P-ANCA, the majority of whom were negative for IgG4 (3 negative of 4 tested), a staining pattern not typical of idiopathic MGN. At least 2 patients were likely to have paraneoplastic MGN. Based on history of concurrent neoplasm, and/or lack of IgG4 staining, at least 5/12 cases of MGN-NCGN likely represent secondary MGN. This finding suggests that MGN and pauci-immune NCGN, when they coexist in a non-lupus patient, may relate to each other or to a common cause.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 262, Wednesday Afternoon