Antineutrophil Cytoplasmic Autoantibody in the Absence of Wegener's Granulomatosis or Microscopic Polyangiitis: Implications for the Surgical Pathologist

Abstract

Antineutrophil cytoplasmic antibodies (ANCA) are useful serologic markers for the diagnosis and management of patients with Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). However, problems in diagnosis and classification may occur when patients with other disorders develop ANCA. A 7-year review (1993-1999) disclosed 247 patients whose sera tested positively for ANCA by an indirect immunofluorescence method: 166 patients for cytoplasmic-ANCA (C-ANCA) and 81 patients for perinuclear-ANCA (P-ANCA) Twenty-seven patients had active pulmonary disease and underwent openlung biopsy or transbronchial biopsy. Eight patients (30%) had a disease other than WG or MPA, and their clinical, pathological, and serological findings were reviewed. The patients, all women, ranged in age from 28 to 77 years (median, 37 y). Dyspnea (n ‫؍‬ 6), cough (n ‫؍‬ 6), chest pain (n ‫؍‬ 2), and/or hemoptysis (n ‫؍‬ 2) were present. The duration of symptoms lasted from 3 weeks to 6 years (median, 6 mo). ANCA titers were C-ANCA (n ‫؍‬ 4; range, 1:40 -1280) or P-ANCA (n ‫؍‬ 4; range, 1:40 -640). The lung biopsies disclosed nonspecific interstitial pneumonia (n ‫؍‬ 4), bronchiolitis obliterans organizing pneumonia (n ‫؍‬ 1), diffuse alveolar damage (n ‫؍‬ 1), organizing diffuse alveolar hemorrhage without capillaritis (n ‫؍‬ 1), and necrotic granuloma (n ‫؍‬ 1). No cases showed characteristic histology for WG or MPA. The final diagnoses were various connective tissue disorders (n ‫؍‬ 5), chronic hypersensitivity pneumonia (n ‫؍‬ 1), postinfectious bronchitis/bronchiectasis (n ‫؍‬ 1), and ulcerative colitis-related lung disease (n ‫؍‬ 1). Surgical pathologists should be aware that significantly elevated ANCA titers may be associated with diverse forms of pulmonary disease. ANCA positivity alone, in the absence of appropriate clinical or pathologic findings, should not be used to substantiate a diagnosis of WG or MPA.

Auto-Antibodies and Their Association with Clinical Findings in Women Diagnosed with Microscopic Colitis

“…In CC, a tendency to increased anti-nuclear antibodies (ANA) was seen in one study, whereas increased levels of ANA, ANCA, and ASCA were seen in others [3], [4], [7]. One confounding factor may be that the level of auto-antibodies correlates with disease activity, and high values may only be detected in the active disease [10].…”

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis

“…6 A previous report demonstrated that chronic interstitial lesions are common histologic features in patients with MPO-ANCA based on the pathologic reviews. 7,8 Thus, pulmonary fibrosis is now a recognized manifestation of MPA. Nada et al reported three patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) that developed pulmonary-renal vasculitis.…”

Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody-Positive Interstitial Pneumonia Associated with Granulomatosis with Polyangiitis Diagnosed by Surgical Lung Biopsy

“…Moreover, when ANCA is detected in IP with other organ involvement, it may be relatively easy to diagnose the disease as systemic vasculitis, such as GPA, MPA, and eosinophilic GPA [21,22]. In cases where the disease is limited to the lung, it is difficult to differentiate between ANCA-positive IP caused by the other etiology and GPA/MPA without surgical lung biopsy [23,24,25]. This has been proved by the following studies.…”

“…This has been proved by the following studies. First, 30% of the patients who had both positivity for MPO-ANCA or PR3-ANCA in sera test and active pulmonary disease underwent lung biopsy and were finally diagnosed with a disease other than GPA or MPO [25]. Second, separation of GPA from MPA is controversial [26].…”