Clinicopathological Analysis of Ocular Adnexal Extranodal Marginal Zone B-Cell Lymphoma with IgG4-Positive Cells

Abstract

This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%, p = 0.03) than IgG4-negative group with a median follow-up period of 38 months. A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure.

IgG4-producing lymphoma arising in a patient with IgG4-related disease

“…Since it is highly likely that this case of IgG4-producing marginal zone lymphoma occurred in a patient with IgG4-RD, a subset of IgG4-producing lymphomas might arise from pre-existing IgG4-RD. It is noted that the lymphoma in this case is distinct from previously described marginal zone B cell lymphomas with numerous non-neoplastic IgG4-positive cells [7][8][9]. Although both types apparently originate from pre-existing IgG4-RD, the IgG4-positive cells in our case had an atypical morphology and were neoplastic.…”

“…Several reports have shown that IgG4-RD produces chronic inflammation, which can promote the development of marginal zone B cell lymphomas [6][7][8][9]. In such cases, numerous non-neoplastic, IgG4-positive cells can be found among the malignant tumor cells.…”

Marginal zone B-cell lymphoma: lessons from Western and Eastern diagnostic approaches

“…5). 25,28,[82][83][84][85][86][87][88][89][90][91] MALT lymphoma is most common in the salivary glands, especially among patients with Sjögren syndrome, in which the risk of developing lymphoma is 5-20-fold higher than the general population. 92,93 Early MALT lymphoma lesions arising in the salivary glands consist of 'collars' of B-cells, often with a monocytoid appearance, arranged around frequently obliterated ducts; this feature is not observed in myoepithelial sialadenitis of Sjögren syndrome, when it is not associated with lymphoma.…”

Incipient Ocular Mucosa-associated Lymphoid Tissue Lymphoma in IgG4-related Orbital Disease

“…Certain autoimmune diseases and inflammatory disorders, such as rheumatoid arthritis, Hashimoto's thyroiditis, and Sjögren's syndrome, have been shown to be associated with lymphoma [1]. Although little is known about lymphomagenesis with regard to IgG4-RD, a few articles about orbital malignant lymphoma associated with IgG4-RD have been published [234]. However, most of these articles are related to ocular adnexal lymphoma in the lacrimal gland.…”

“…Recent studies suggest that IgG4+ plasma cells might be involved in the pathogenesis of MALT lymphoma [234]. Igawa et al [3] have suggested that some IgG4-producing lymphomas may be derived from pre-existing IgG4-RD.…”