Orbital granulomatosis with polyangiitis (Wegener granulomatosis): clinical and pathologic findings

Abstract

The pathology of granulomatosis with polyangiitis (GPA), formerly Wegener granulomatosis, typically features a granulomatous and sometimes necrotizing vasculitis targeting the respiratory tract and kidneys. However, orbital involvement occurs in up to 60% of patients and is frequently the first or only clinical presentation in patients with systemic or limited forms of GPA. Orbital GPA can cause significant morbidity and potentially lead to complete loss of vision and permanent facial deformity. Fortunately, GPA is highly responsive to medical treatment with corticosteroids combined with cyclophosphamide or, more recently, rituximab. Therefore, it is imperative for this disease to be accurately diagnosed on orbital biopsy and distinguished from other histologically similar orbital lesions. Herein, we review the clinical and pathologic findings of orbital GPA, focusing on the differentiation of this disease from other inflammatory orbital lesions.

Figure 1

Histopathology of orbital granulomatosis with polyangiitis (GPA). A, A noncontrast coronal computed tomography image of the paranasal sinuses demonstrates bilateral lobulated soft tissue within the nasal cavity extending through the medial orbital walls (red arrows) to bilateral retrobulbar extraconal orbital spaces in a patient with GPA. B, A micrograph of an orbital lesion biopsy depicts collections of epithelioid histiocytes (granulomas) surrounding small vessels (hematoxylin-eosin, original magnifications ×200 and ×400 [inset]). C and E, Shown are small vessels (black arrow) with necrotizing and granulomatous inflammatory infiltrate composed of epithelioid histiocytes, neutrophils, lymphocytes, scattered eosinophils, and karyorrhectic debris. Adjacent vessels with less inflammation are also shown in C (*) (hematoxylin-eosin, original magnifications ×200 [C] and ×400 [E]). D and F, Micrographs of CD34 immunostains highlight disrupted and reactive endothelium in a small, central vessel with vasculitis (black arrow). Multiple adjacent uninvolved vessels show confluent CD34 endothelial staining in D (*) (anti-CD34, original magnifications ×200 [D] and ×400 [F]). G, Many vessels are surrounded by a rich polymorphic inflammatory infiltrate (hematoxylin-eosin, original magnification 3400). H, This area shows chronic vasculitis with fibrinoid change in the vessels (hematoxylin-eosin, original magnifications ×200 and ×400 [inset]). A full workup, including histochemical stains and immunostains, reveal no fungal or bacterial microorganisms and no evidence of increased IgG4- positive plasma cells. Of note, the patient’s serum cytoplasmic and perinuclear antineutrophil cytoplasmic antibody titers were both increased to 1:160.