IgG4-related Inflammation of the Orbit Simulating Malignant Lymphoma

Case Report

A 72-year-old female complained of bilateral eyelid swelling for three years. Since orbital tumors were detected at the initial clinic, she was referred to Hokkaido University Hospital on September 12th, 2011. She had a medical history of bronchial asthma, hypertension, and hyperlipidemia. The patient exhibited bilateral superior and inferior eyelid swelling (Figure 1 A). Multiple subcutaneous masses were palpable without pain. Laboratory tests showed high serum IgG4 and IgE concentrations, measuring 991 mg/dl and 389 U/ml, respectively, while serum IgG was almost normal (1.755 mg/dl). T2-Weighted magnetic resonance imaging (MRI) demonstrated massive bilateral lesions adjacent to the orbicularis oculi muscle of the eyelid extending to the deep orbit (Figure 1 B-D). There were two kinds of lesions, tumor type 1, presenting with a predominantly low density, and tumor type 2 with a relatively high density (Figure1 E).

Each orbital tumor tissue was partially removed to confirm the histopathological diagnosis following a subciliary cutaneous incision. During the operation, tumor type 1 was a hard whitish nodule, while tumor 2 was a soft pink nodule. Tumor type 1 histologically demonstrated cellular infiltration together with fibrosis and lymphoid follicle formation (Figure 2 A). At a high magnification, the tissue consisted of an aggregation of plasma cells and small lymphocytes admixed with blood vessels and fibroblasts (Figure 2B). Marked cluster of differentiation (CD) 138-positive plasma cells infiltrated outside the lymphoid follicle (Figure 2C). Marked IgG4 immunoreactivity was also detected in the tissue (Figure 2 D). Infiltrating small lymphocytes were CD20-positive B-cells, especially in the lymphoid follicle (Figure 2E). Orbital tissue from tumor 1 showed no IgH gene rearrangement as determined by Southern blot analysis (Figure 2 F). In contrast to tumor type 1, tumor type 2 histologically exhibited dense cellular infiltration without fibrosis or lymphoid follicle formation (Figure 2 G). At a high magnification, there was a collection of small-sized atypical lymphoid cells, which were CD20-positive (Figure 2 H and I), in the tissue. Several IgG4-positive plasma cells infiltrated the tissue (Figure 2 J). Southern blot analysis verified IgH gene rearrangement of the JH region in tumor type 2 tissues (Figure 2 K). Flow cytometry showed a large population of CD20-positive cells, comprising 52.1% in tumor 2 tissue compared to tumor type 1 (30.1%). Based on the pathological findings, tumor type 1 and 2 were diagnosed as IgG4-related inflammation and EMZL, respectively. A systemic survey showed no other lesions related to lymphoproliferative disorders except for ophthalmic regions. The patient initially received oral prednisolone at a dose of 30 mg/per day for three months, which was then tapered gradually. After starting oral prednisolone, a number of orbital masses were reduced; however, a few masses remained unchanged, being consistent with EMZL. The patient underwent 30-Gy X-ray irradiation in total to both eyes one month after starting prednisolone. After oral prednisolone at 5 mg had been administered, the bilateral tumors diminished. The patient is currently well with no recurrence or systemic involvement (Figure1 F).

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Figure 1.

Facial photograph before and after treatment (A and F, respectively), and magnetic resonance imaging (MRI) at the initial presentation (B-E). A: The patient exhibits bilateral superior and inferior eyelid swelling without pain. B-D: T2-Weighted MRI demonstrates massive bilateral orbital lesions from the subcutaneous layer to deep orbit with a low density. E: There are two kinds of lesion, one presenting with a low density (tumor type 1, T1) and are with relatively high density (tumor type 2, T2). F: Eyelid swelling completely resolved after treatment.

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Figure 2.

Pathological analyses of tumor type 1 (A-F) and tumor type 2 (G-K). Hematoxylin and eosin staining (A, B, G, H) and immunoreactivity for cluster of differentiation (CD) 138 (C), immunoglobulin (IgG) 4 (D, J), and CD20 (E, I), and immunoglobulin heavy chain (IgH) gene rearrangement (F, J). A: Tumor type 1 demonstrates cellular infiltration together with fibrosis and lymphoid follicle formation. B: At a high magnification, the tissue consists of an aggregation of small lymphocytes and plasma cells admixed with blood vessels and fibroblasts. C: Marked CD138-positive plasma cells infiltrate outside the lymphoid follicle (LF). D: IgG4 immunoreacitivty is strongly detected in the tissue. E: CD20-positive B-cell infiltration is observed. F: Orbital tissue from “tumor type 1 (T1)” shows no IgH gene rearrangement, determined by Southern blot analysis. G: Tumor 2 demonstrates marked cellular infiltration without fibrosis or lymphoid follicle formation. H: At a high magnification, there is an aggregation of small-sized atypical lymphoid cells. I: CD20-positive lymphoid cells are markedly observed in the tissue. J: Several IgG4-positive cells infiltrate the tissue. K: IgH gene rearrangement is detected in tumor type 2 (T2) tissues. (Original magnification: A, C, D, E, G, I, J ×40; B, H ×100).