Abstract
Background: Increased risk of developing cancer in patients with Immunoglobulin G4-related disease (IgG4-RD) have been reported. Association of malignancies and IgG4-related ophthalmic disease (IgG4-ROD), however, remains unclear. Methods: A retrospective review of medical records, orbital images and histopathology reports from 2005 to 2019 in a territory-wide, biopsy-proven cohort, fulfilling the “probable” or “definite” comprehensive diagnostic criteria of IgG4-RD. Findings: All 122 patients had biopsies taken from single or multiple ocular adnexal lesions including lacrimal glands (n=108), discrete orbital masses (n=30), infiltrated orbital fat (n=10), conjunctiva(n=2) or extraocular muscles (n=3). Totally 16 (13%) patients developed cancer over 73±48 months’ follow-up. 9 developed ocular adnexal lymphoma (OAL) and 7 had extra-orbital malignancies. The incidence of OAL was significantly higher (standardized incidence ratios (SIRs) =10.0, 95%CI=4.5-17.6) while that of extra-orbital malignancies was similar (SIRs=0.54, 95%CI=0.2-1.0) to the general population. The risk of OAL was highest within the first year of IgG4-ROD diagnosis (SIRs=46.7, 95%CI=18.5-87.6) as 7 of the 9 OAL were diagnosed concomitantly with IgG4-ROD. Patients who developed OAL or extra-orbital malignancies were older at the time of diagnosis of IgG4-ROD compared to the rest of the cohort (64.9±7.1 years and 68.3±8.5 years versus 55.2±15.0 years, both p<0.05). Radiologically, asymmetric lacrimal gland enlargement (78% versus 13%, p<0.05), lack of frontal (none versus 12%, p<0.05) or infraorbital nerve enlargement (none versus 36%, p<0.05) was associated with OAL. Pre-treatment serum IgG4 level or extraorbital involvement by IgG4-RD was not significantly different between patients with or without cancer. Interpretation: In this IgG4ROD cohort, 7% patients developed OAL, which is 10-fold that of the general population. Patients presenting with asymmetric lacrimal gland enlargement, lack of frontal or infraorbital nerves involvement radiologically were associated with OAL. Incidence of extraorbital malignancy was similar to that of the general population. Funding: None. Declaration of Interests: No conflicting relationship exists for any author. Ethics Approval Statement: Ethical approval was obtained from the Institutional Review Board (IRB) of each participating hospital.
Highlights
IntroductionIgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease characterized by tumefactive lesions with noticeable IgG4 + plasma cells infiltrating[1] into different organs including the hepatobiliary tree, pancreas, exocrine glands, kidneys, lungs, lymph nodes, meninges, aortas and prostate.[2,3,4,5] IgG4-RD was first recognized as a single disease entity, but some recent studies suggested several clinical phenotypes according to the affected organs. 6,7,8 While Lanzillotta et al[6] reported an increased prevalence of allergic manifestations in head and neck limited phenotype, Niwamoto et al[7] reported association between malignancies and specific phenotypes in IgG4-RD, especially IgG4-related autoimmune pancreatitis
Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with ocular adnexal lymphoma (OAL)
IgG4-related disease (IgG4-RD) was first recognized as a single disease entity, but some recent studies suggested several clinical phenotypes according to the affected organs. 6,7,8 While Lanzillotta et al[6] reported an increased prevalence of allergic manifestations in head and neck limited phenotype, Niwamoto et al[7] reported association between malignancies and specific phenotypes in IgG4-RD, especially IgG4-related autoimmune pancreatitis
Summary
IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease characterized by tumefactive lesions with noticeable IgG4 + plasma cells infiltrating[1] into different organs including the hepatobiliary tree, pancreas, exocrine glands, kidneys, lungs, lymph nodes, meninges, aortas and prostate.[2,3,4,5] IgG4-RD was first recognized as a single disease entity, but some recent studies suggested several clinical phenotypes according to the affected organs. 6,7,8 While Lanzillotta et al[6] reported an increased prevalence of allergic manifestations in head and neck limited phenotype, Niwamoto et al[7] reported association between malignancies and specific phenotypes in IgG4-RD, especially IgG4-related autoimmune pancreatitis. 6. In IgG4-related ophthalmic disease (IgG4-ROD), infiltration, fibrosis and dysfunction of the lacrimal glands, extraocular muscles, periorbital and optic nerves, the eyelid and orbital soft tissues have been reported.[9] Cheuk et al 10 first reported 6 patients with ocular adnexal lymphoma (OAL) associated with IgG4-ROD. The Japanese study group of IgG4-ROD showed that 9.8% of mucosa associated lymphoid tissue (MALT) orbital lymphoma in their multi-center cohort were IgG4-positive.[11] IgG4-ROD appeared to have a strong association with lymphoma, compared to other organ-specific phenotype of IgG4-RD.[12] In this study, we compare the incidence of malignancies in a well-characterized and biopsy-proven IgG4-ROD cohort with the local population, and we compare the clinical, serological and radiological features of patients who developed cancer at the time of or after the diagnosis of IgG4-ROD to those who did not
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