Available online 30 January 2024

Author links open overlay panelAbstract

Orbital inflammatory diseases represent a heterogenous group of idiopathic, autoimmune-related, and sometimes neoplastic conditions with overlapping clinical and histopathologic features, as well as variable levels of IgG4-positive plasma cells detected within tissue biopsies. Some histopathologic features, especially in an appropriate clinical context, may point to a specific diagnosis in a given patient. Diagnoses of non-specific orbital inflammation, orbital inflammation related to autoimmune diseases such as granulomatosis with polyangiitis and IgG4-related disease, lymphoma, and xanthogranulomatous diseases are discussed, contrasted and illustrated.

Section snippetsIgG4-related disease (and potentially associated conditions)

In patients with pancreatic sclerosing pseudotumors, after cholangitis and lymph node involvement, salivary gland disease follows in prevalence.8 As the lacrimal gland is a predominantly serous, excretory, major salivary-type gland located within the orbit, it comes as no surprise that ophthalmologists are familiar with the diagnosis of IgG4-RD. The mass forming inflammatory pseudotumors of orbital IgG4-RD very often involve the lacrimal gland, but frequently extend out into the fibroadipose

Nonspecific (including autoimmune-related) orbital inflammation

Orbital pseudotumors have long been postulated to be associated with systemic autoimmune diseases, as many intraocular inflammatory (uveitic) syndromes are known to be.2,4 In many cases, the histopathology of autoimmune associated orbital inflammation is non-specific. In such patients, a history of systemic autoimmune disease may be elicited or suggested based on laboratory testing or other ophthalmic or systemic clinical features. Occasionally non-specific orbital inflammatory syndromes

Granulomatosis with polyangiitis (and other granulomatous orbital inflammatory diseases)

Granulomatosis with polyangiitis (GPA) is likely the most common mimicker of IgG4-RD in the orbit, particularly because in addition to some overlapping histopathologic and immunophenotypic features, GPA also quite frequently displays ophthalmic manifestations (about half of patients), either as ocular or ocular adnexal/orbital inflammatory disease.17 Further hindering one's ability to distinguish GPA from other inflammatory conditions is the fact that when disease is isolated to the head and

Reactive lymphoid hyperplasia and lymphoma

In terms of neoplasia, lymphoid tumors involving the orbit, many centered in the lacrimal gland, are much more common than solid tumors or metastatic disease. The majority are low-grade, extranodal B-cell lymphomas, as there are no lymph nodes within the orbit. In particular, extranodal marginal zone lymphoma (EMZL) represents the vast majority of orbital lymphomas; follicular lymphoma is also relatively common. In addition, florid reactive follicular lymphoid hyperplasia may present in a

Periocular and orbital xanthogranulomatous disease

Somewhat uniquely frequent in the ocular adnexa and orbit are a group of orbital inflammatory pseudotumors showing prominent xanthogranulomatous inflammation.27 In addition to the typical presenting features of orbital inflammatory disease, patients with orbital xanthogranuloma (XG) often display an unusual yellow-orange hue to the overlying edematous skin. Four clinical syndromes with somewhat overlapping histopathologic features may arise: adult-onset asthma and periocular xanthogranuloma

Conclusion

A significant number of cases historically categorized as orbital pseudotumors, including idiopathic orbital inflammation (IOI) and benign lymphoid hyperplasia, likely represent manifestations of orbital IgG4-RD. However, inflammatory conditions related to other systemic autoimmune diseases or neoplasia may show high levels of IgG4-positive plasma cells in tissue. Other histomorphologic features seen in biopsy specimens, together with clinical presentations (ophthalmologic and systemic), and

CRediT authorship contribution statement

Anna M. Stagner: Writing – review & editing, Writing – original draft, Formal analysis, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References (31)AJ Wong et al.IgG4 immunostaining and its implications in orbital inflammatory disease

PLoS One

(2014)

NH Andrew et al.An analysis of IgG4-related disease (IgG4-RD) among idiopathic orbital inflammations and benign lymphoid hyperplasias using two consensus-based diagnostic criteria for IgG4-RD

Br J Ophthalmol

(2015)

JT Geyer et al.IgG4-associated sialadenitis

Curr Opin Rheumatol

(2011)

AA McNab et al.IgG4-related ophthalmic disease. Part I: background and pathology

Ophthalmic Plast Reconstr Surg

(2015)

JA Ferry et al.IgG4-related Orbital Disease and Its Mimics in a Western Population

Am J Surg Pathol

(2015)

View full text

© 2024 Elsevier Inc. All rights reserved.