Ocular Adnexal IgG4-related Disease: Comparative Analysis With Mucosa-associated Lymphoid Tissue Lymphoma and Other Chronic Inflammatory Conditions

1. Ho-Kyung Choung¹
2. Sang-won Hwang²
3. Yoon Kyung Jeon³
4. Min Joung Lee⁴
5. Nam Ju Kim⁵
6. Sang In Khwarg⁶

¹Seoul National University Boramae Medical Center, Seoul, Republic of Korea
²Dongguk University International Hospital, Ilsan, Republic of Korea
³Department of pathology, Seoul National University Hospital, Seoul, Republic of Korea
⁴College of Medicine, Seoul National University, Seoul, Republic of Korea
⁵Seoul National University Bundang Hospital, Seongnam, Republic of Korea
⁶Seoul National University Hospital, Seoul, Republic of Korea

Purpose: To determine the clinicopathological characteristics of ocular adnexal IgG4-related disease, and compare these with ocular adnexal MALT lymphoma and other types of chronic inflammatory lesions, particularly immunohistochemical and genetic features.

Methods: We investigated the immunohistochemistry, immunoglobulin heavy chain gene rearrangement, immunoglobulin light chain restriction, and fluorescence in situ hybridization in 14 cases of IgG4-related disease, 9 MALT lymphomas and 12 other chronic inflammations involving the lacrimal gland and orbit. Clinical characteristics were also collected and compared among these diseases.

Results: Bilateral involvement was frequent in IgG4-related diseases. The number of IgG4-positive cells and the ratio of IgG4/IgG-positive cells were higher in patients with IgG4-related disease, as compared to those with MALT lymphoma (p=0.016; p=0.000) and other inflammations (p=0.000; p=0.000). Monoclonality was observed in 14.3% (n=2) of IgG4-related diseases. One patient also displayed monomorphous features suggesting secondary MALT lymphoma. In the other case, κ chain restriction in IgG4-positive cells was observed, raising the possibility of IgG4-producing MALT lymphomas. Trisomy 3, 18 or MALT1 translocation was observed in none of the IgG4-related diseases. Regulatory T-cells infiltration was higher in IgG4-related diseases, as compared to MALT lymphomas (p=0.000) and other inflammations (p=0.006).

Conclusions: Ocular adnexal IgG4-related disease is a distinct condition that has unique clinicopathological features, as compared to MALT lymphoma or other chronic inflammatory conditions. Some genetically and morphologically complicated cases emphasize the need for in-depth studies to differentiate this disease from MALT lymphoma, and to exclude secondary lymphoma.