Histopathological Classification of Crescentic Glomerulonephritis

Primary Pathogenesis-Based Classification

The American Society of Nephrology recommends that crescentic glomerulonephritis be classified into three distinct pathogenic types based on immunofluorescence findings: Type I (anti-GBM disease with linear immunoglobulin deposits), Type II (immune-complex mediated with granular deposits), and Type III (pauci-immune with minimal or absent deposits) 1, 2, 3
The Renal Pathology Society consensus establishes that crescentic GN must be classified by etiology/pathogenesis rather than pattern alone, with Type I characterized by linear deposits of IgG and frequently C3 along the glomerular basement membrane on immunofluorescence 1, 2, 3, 4
Type I anti-GBM glomerulonephritis is confirmed by detection of circulating anti-GBM antibodies, and most active cases present with severe necrotizing and crescentic pattern 2, 3
Approximately 25% of patients with Type I have concurrent circulating ANCA (double-positive disease) 2, 3, 5
Type II immune-complex mediated crescentic GN includes diverse primary and secondary glomerular diseases complicated by crescent formation, such as lupus nephritis, IgA nephropathy, post-infectious GN, and cryoglobulinemic GN 1, 6
Type III pauci-immune crescentic GN is characterized by negative or minimal immunoglobulin deposits on immunofluorescence, with 80-90% of patients having serologic evidence of ANCA (MPO-ANCA or PR3-ANCA) 2, 3, 5

The KDIGO guidelines recommend the Berden/EUVAS histopathologic classification system for ANCA-associated crescentic GN, based on predominant glomerular phenotype, with classes including focal, crescentic, sclerotic, and mixed 7
The Berden/EUVAS system scores biopsies based on the proportion of globally sclerotic glomeruli, normal glomeruli, and glomeruli with cellular crescents, with the sclerotic class having ≥50% globally sclerotic glomeruli 7

Crescentic GN is defined as extracapillary proliferation (crescents) involving ≥50% of glomeruli, although this threshold may not apply to ANCA-GN and anti-GBM GN, where fewer than 50% of glomeruli may be involved by crescents while still warranting the diagnosis 8, 9

Cellular crescents are characterized by >50% of the lesion occupied by cells, with extracapillary proliferation >2 cell layers, while fibrocellular crescents have a mixed composition of cells and extracellular matrix, and fibrous crescents have >90% extracellular matrix, representing irreversible scarring 8, 9

The Mayo Clinic consensus explicitly states that a pattern diagnosis as the sole primary diagnosis is not recommended, and that crescentic GN should be classified by etiology/pathogenesis rather than pattern alone 1, 2, 4, 5
Segmental IgM and C3 staining in areas of segmental sclerosis should not be described using immunofluorescence pattern descriptors, as this represents nonspecific trapping 10

Type III involves ANCA-mediated small vessel vasculitis, with complement activation as a final common pathway 2, 3