Original Article Histological diversity of vasculitic lesions in MPO–ANCA-positive autopsy cases Kenji Sano, 1 Nobuki Sakaguchi, 2 Makoto Ito, 2 Masamichi Koyama, 2 Motohiro Kobayashi 2 and Masao Hotchi 2 Departments of 1 Laboratory Medicine and 2 Pathology, Shinsu University School of Medicine, Matsumoto, Japan plete remission, and titers in patients in partial remission are usually very low. 3,4 ANCA-related vasculitis is now an established disease entity which has been reclassified from heterogenous vasculitides in old nomenclature. ANCA was originally identified by Davies et al. (1982) in eight patients who had necrotizing glomerulonephritis but no immune deposits or systemic vasculitis. 5 In 1985, van der Woude et al. generated substantial interest by suggesting that detection of ANCA was a useful diagnostic and prog- nostic marker for Wegener’s granulomatosis. 6 Subsequent studies revealed that ANCA was closely associated with three major categories of small-vessel vasculitis: Wegener’s granulomatosis, microscopic polyangitis, and Churg–Strauss syndrome. 2,7 Of several subclasses of ANCA, including anti-PR3 (cANCA), 8–11 anti-MPO (pANCA) 12 and other antibodies to lysosomal constituents, 13 cANCA has been demonstrated to correlate well with Wegener’s granulomatosis, whereas other ANCA subclasses are not specifically indicative of vasculitis. 3 pANCA appears in a variety of diseases such as inflamma- tory bowel disease, rheumatoid arthritis, infections and several types of vasculitis. 14,15 pANCA appears more often in several vasculitic disorders, such as microscopic polyarteritis nodosa (PN), Churg–Strauss syndrome and pulmonary– renal syndrome. 16,17 Since the introduction of tests for ANCA in patients who present with lung hemorrhage and nephritis, ANCA has been found more often than antiglomerular basement membrane antibodies (GBM). 18 The re-evaluation of anti-GBM anti- bodies, pANCA and cANCA using current methods for 88 patients with evidence of lung hemorrhage and nephritis, revealed that the major cause was an ANCA-associated con- dition. 19 Other causes of pulmonary–renal syndrome include anti-GBM-associated conditions, systemic lupus erythemato- sus, other collagen diseases, Henöch–Schönlein purpura, cryoglobulinemia and others. 20,21 These evaluations were made on the basis of biopsy analysis. pANCA-related vas- culitis mainly involves glomeruli and the alveolar septum, characterized by capillaritis of both of these tissues, with or Pathology International 2001; 51: 460–466 To investigate the variety of histological features of vas- culitic lesions in myeloperoxidase-specific antineutrophil cytoplasmic antibody (pANCA)-related vasculitis, retrospec- tive pathological analysis was done on 13 autopsy cases, collected from 1990 to 1998 at five hospitals. These cases were classified into three groups: (i) pulmonary–renal syn- drome characterized by capillaritis of lung and glomeruli with occasional small-vessel arteritis and/or phlebitis; (ii) glomerular capillaritis without pulmonary involvement asso- ciated with significant small-vessel arteritis; and (iii) exten- sive distribution of small-vessel arteritis with no capillary involvement. The results suggest that pANCA-related vas- culitis encompasses a wide variety of vasculitic syndromes, including pulmonary–renal syndrome, microscopic pol- yarteritis nodosa, and classic polyarteritis nodosa. pANCA may contribute to pathogenesis in all of these cases. Key words: myeloperoxidase–antineutrophil cytoplasmic antigen, diffuse alveolar hemorrhage, microscopic polyangitis, microscopic polyarteritis nodosa, necrotizing crescentic glomerulonephritis, pulmonary–renal syndrome Over the last decade (1980–1990), several lines of evidence have been collected on the close association between antineutrophil cytoplasmic antibody (ANCA) and the patho- genesis of small- to medium-vessel vasculitis. 1 Most patients with Wegener’s granulomatosis have antiproteinase-3 ANCA (PR3-ANCA which is also known as cytoplasmic ANCA; cANCA), whereas most patients with microscopic polyangitis or Churg–Strauss syndrome have antimyeloperoxidase ANCA (MPO–ANCA which is also known as perinuclear ANCA; pANCA). 2,3 cANCA titration depends upon the activity of Wegener’s granulomatosis. cANCA is detectable in almost 100% of patients with active, systemic disease, characterized by clinical symptoms due to small-vessel vasculitis, while it is not detectable in most patients in com- Correspondence: Kenji Sano, MD, Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. Email: kenjisa@sch.md.shinshu-u.ac.jp Received 29 August 2000. Accepted for publication 16 February 2001.