ANCA-associated vasculitis (Part I)


Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Milan, Italy


"ANCA-associated vasculitis" are Wegener's Granulomatosis, Micropolyarteritis and its renal-limited variant (previously called idiopathic necrotizing glomerulonephritis).

According to the "Chapel Hill Consensus Conference" classification, ANCA-associated vasculitis is characterized by prevalent involvement of small-size vessels, whereas medium and large-size artery  involvement is the marker of Polyarteritis Nodosa. 

However,  the vessel size-based classification is not always powerful enough, because also in ANCA-associated vasculitis the involvement of medium and large-size arteries is possible. Therefore, the presence of necrotizing extracapillary glomerulonephritis that is always absent in Polyarteritis Nodosa has become the distinctive marker of ANCA-associated renal vasculitis.

Small vessel vasculitis is morphologically defined by massive necrosis of the vascular wall with endo- and peri-vascular inflammatory infiltrates. This lesion should be the diagnostic hallmark of the disease, but is histologically detected in only 20-30% of cases, confirming the diagnostic importance of necrotizing extracapillary nephritis. Furthermore, a similar arteritis can be found in other diseases, such as anti-GBM antibody disease, HS nephritis, cryoglobulinemic nephritis and lupus nephritis.


Focal or diffuse necrotizing extracapillary glomerulonephritis is the histological hallmark of ANCA-associated Vasculitis. It is noteworthy that Wegener’s Granulomatosis, Micropolyarteritis and its renal-limited variant share similar morphological lesions and are therefore considered as one pathological entity with different systemic involvement.



Tuft necrosis and extracapillary proliferation are very variable in intensity and diffusion, even among glomeruli of the same biopsy. Some cases show isolated segmental necrosis of the glomerular tuft without extracapillary reaction.



A segmental extracapillary reaction in close proximity of the necrotizing lesion is more frequently present. The remaining part of the tuft, not affected by the lesion, appears completely normal.




Although segmental, the necrotizing extracapillary lesion can be larger and involve a higher percentage of glomeruli.




Massive necrosis is usually associated to diffuse circumferential extracapillary proliferation. From a clinical point of view, the patient is affected by rapidly progressive renal failure.




Periglomerular leukocyte infiltration is another distinctive feature of ANCA-associated renal vasculitis. The entity of leukocyte infiltration is variable, but leukocytes always localize in close proximity of the necrotizing extracapillary lesion. A rupture of the Bowman’s capsule can be commonly observed.




Extensive ruptures of the Bowman's capsule make it difficult to discriminate between extracapillary proliferation and periglomerular infiltration. 



The massive circumferential leukocyte infiltration gives a picture of "glomerular granuloma-like lesion." This feature is not exclusively found in Wegener's granulomatosis, but can be observed in cases of Micropolyarteritis and even in its renal-limited variant. A similar lesion can be found in anti-GBM antibody disease.




It is noteworthy that these granulomatous reactions in ANCA-associated vasculitis are mainly glomerular, as witnessed by the presence of "glomerular remnants" in the middle of the lesion.




The simultaneous presence in the same biopsy of active and sclerotic lesions is the expression of repeated ‘poussées’ of necrotizing extracapillary damage.




Besides the typical periglomerular localization, a diffuse interstitial leukocyte infiltration is very common in ANCA-associated vasculitis. 




When interstitial leukocyte infiltration is massive, "tubulitis" is frequently observed, with tubular basement membrane rupture and both endo- and peri-tubular infiltration. 




ANCA-associated renal vasculitis are by definition "pauci-immune" glomerulonephritis. Immunofluorescence can be either negative or characterized by scattered C3 granular deposition. 




Instead, in 20% of cases, a more consistent mesangial and parietal deposition of IgG and C3 can be observed. It is still controversial whether cell-mediated immune mechanisms or immune-complex deposition are at the basis of ANCA-associated vasculitis.  




In active lesions, fibrin deposition is invariably present and its entity and distribution are related to the entity of glomerular damage. Focal and segmental forms show fibrin deposition in segmental well delineated areas of the tuft. This aspect is shared by other segmental necrotizing diseases, such as anti-GBM antibody disease, lupus nephritis, HS nephritis, and necrotizing IgA GN. 




Bowman's capsule ruptures are accompanied by fibrin deposition not only in the glomerulus but also in periglomerular areas.






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