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Int J Clin Exp Pathol 2012;5(7):684-689

Original Article
Histopathological features predictive of a clinical diagnosis of ophthalmic granulomatosis
with polyangiitis (GPA)

Hazlita Isa, Sue Lightman, Philip J Luthert, Geoffrey E Rose, David H Verity, Simon RJ Taylor

Multidisciplinary Vasculitis Clinic, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; UCL Institute of Ophthalmology, 11-43 Bath
Street, London EC1V 9E, UKL; Department of Ophthalmology, Medical Faculty, University Kebangsaan Malaysia, 56000 Kuala Lumpur,
Malaysia; Orbital Clinic, Moorfields Eye Hospital, City Road, London EC1V 2PD; Division of Immunology & Inflammation, Faculty of Medicine,
Imperial College London, London, UK

Received July 14, 2012; Accepted Augest 2, 2012; Epub September 5, 2012; Published September 15, 2012

Abstract: Background: The limited form of Granulomatosis with Polyangiitis (GPA), formerly known as Wegener’s Granulomatosis (WG)
primarily involves the head and neck region, including the orbit, but is often a diagnostic challenge, particularly as it commonly lacks positive
anti-neutrophil cytoplasm antibody (ANCA) titres or classical features on diagnostic orbital biopsies. The purpose of this study was to relate
biopsy findings with clinical outcome and to determine which histopathological features are predictive of a clinical diagnosis of GPA. Methods:
Retrospective case series of 234 patients identified from the database of the UCL Institute of Ophthalmology Department of Eye Pathology as
having had orbital biopsies of orbital inflammatory disorders performed between 1988 and 2009. Clinical records were obtained for the
patients and analysed to see whether patients had GPA or not, according to a standard set of diagnostic criteria (excluding any
histopathological findings). Biopsy features were then correlated with the clinical diagnosis in univariate and multivariate analyses to determine
factors predictive of GPA. Results: Of the 234 patients, 36 were diagnosed with GPA and 198 with other orbital pathologies. The majority of
biopsies were from orbital masses (47%). Histology showed a range of acute and chronic inflammatory pictures in all biopsies, but the
presence of neutrophils (P<0.001), vasculitis (P<0.001), necrosis (P<0.001), eosinophils (P<0.02) and macrophages (P=0.05) were
significantly associated with a later clinical diagnosis of GPA. In a multivariate analysis, only tissue neutrophils (OR=3.6, P=0.01) and vasculitis
(OR=2.6, P=0.02) were independently associated with GPA, in contrast to previous reports associating eosinophils and necrosis with the
diagnosis. Conclusions: Neutrophil, eosinophil and macrophage infiltration of orbital tissues, together with vasculitis and necrosis, are all
associated with a clinical diagnosis of GPA, but only neutrophil infiltration and vasculitis are independently associated with this diagnosis.
These features may assist in the establishing the diagnosis of limited GPA among patients with early orbital disease, particularly in the
absence of positive serum ANCA titres. (IJCEP1207008).

Keywords: Granulomatosis with polyangiitis, histopathology, eosinophils, nuclear dust


Address all correspondence to:
Simon RJ Taylor, PhD
Imperial College London
Faculty of Medicine
5th Floor Commonwealth
Building, Hammersmith Hospital
London W12 0NN.
Tel: +44 (0) 20 8383 2306; Fax: +44 (0) 20 7566 2266
E-mail: s.r.taylor@imperial.ac.uk