Histopathological Classification of Crescentic Glomerulonephritis
Crescentic glomerulonephritis is 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
Primary Pathogenesis-Based Classification
The Mayo Clinic/Renal Pathology Society consensus establishes that crescentic GN must be classified by etiology/pathogenesis rather than pattern alone 1:
Type I: Anti-GBM Glomerulonephritis
- Characterized by linear deposits of IgG and frequently C3 along the glomerular basement membrane on immunofluorescence 1
- Confirmed by detection of circulating anti-GBM antibodies 1
- Most active cases present with severe necrotizing and crescentic pattern 1
- Approximately 25% of patients have concurrent circulating ANCA (double-positive disease) 1
Type II: Immune-Complex Mediated Crescentic GN
- Characterized by granular deposits of immunoglobulins and complement in glomeruli 2
- Includes diverse primary and secondary glomerular diseases complicated by crescent formation 2
- Examples include lupus nephritis, IgA nephropathy, post-infectious GN, and cryoglobulinemic GN 1
- ANCA can be detected in 25.6% of Type II cases, creating diagnostic complexity 3
Type III: Pauci-Immune Crescentic GN (ANCA-Associated)
- Characterized by negative or minimal immunoglobulin deposits on immunofluorescence 1
- 80-90% of patients have serologic evidence of ANCA (MPO-ANCA or PR3-ANCA) 1
- Remaining 10-20% are ANCA-negative but share identical histologic features 1
- Most common type in Northern China (43.4% of cases) 3
Histologic Prognostic Classification for ANCA-GN
For ANCA-associated crescentic GN specifically, the KDIGO 2024 guidelines recommend the Berden/EUVAS histopathologic classification system based on predominant glomerular phenotype 1:
- Focal class: ≥50% normal glomeruli 1
- Crescentic class: ≥50% glomeruli with cellular crescents 1
- Sclerotic class: ≥50% globally sclerotic glomeruli 1
- Mixed class: Biopsies not fitting into other categories based on predominant phenotype 1
This prognostic classification should be scored in order: first globally sclerotic glomeruli, then normal glomeruli, then glomeruli with cellular crescents 1.
Definition of Crescentic GN
Crescentic GN is defined as extracapillary proliferation (crescents) involving ≥50% of glomeruli 1, 4, 2. However, this 50% threshold applies primarily to immune-complex GN and C3 glomerulopathy; for ANCA-GN and anti-GBM GN, fewer than 50% of glomeruli may be involved by crescents while still warranting the diagnosis 1.
Types of Crescents by Stage
Crescents are classified by composition, reflecting disease stage 1:
- Cellular crescents: >50% of lesion occupied by cells, extracapillary proliferation >2 cell layers 1
- Fibrocellular crescents: Mixed cells and extracellular matrix, <50% cells and <90% matrix 1
- Fibrous crescents: >90% extracellular matrix, representing irreversible scarring 1
Critical Diagnostic Pitfalls
A common error is reporting pattern alone without identifying the underlying pathogenic type 1. The Mayo Clinic consensus explicitly states that "a pattern diagnosis as the sole primary diagnosis is not recommended" 1.
Segmental IgM and C3 staining in areas of segmental sclerosis should not be described using immunofluorescence pattern descriptors (granular, linear, etc.), as this represents nonspecific trapping 1.
In Type II crescentic GN, ANCA-positive patients are older, have more multi-system involvement, and demonstrate more fibrinoid necrosis than ANCA-negative patients, indicating significant heterogeneity within this category 3.
Pathophysiologic Mechanisms
Crescent formation requires vascular injury causing ruptures in the glomerular basement membrane, triggering plasmatic coagulation within Bowman's space 5. Cellular crescents develop from activated parietal epithelial cells along Bowman's capsule 5. When multilevel growth associates with epithelial-mesenchymal transition, fibrous crescents form and become irreversible in terms of GFR recovery 5.
The upstream mechanisms differ by type but all share complement activation as a final common pathway 5. Type I involves anti-GBM antibodies, Type II involves immune complex deposition 6, and Type III involves ANCA-mediated small vessel vasculitis 1.