Ocular Adnexal Lymphoma Associated With IgG4+ Chronic Sclerosing Dacryoadenitis: A Previously Undescribed Complication of IgG4-related Sclerosing Disease

Abstract

IgG4-related sclerosing disease is a recently recognized inflammatory lesion frequently involving pancreas, submandibular gland, lacrimal gland, and lymph node. We report 3 cases of ocular adnexal lymphoma arising in IgG4-related chronic sclerosing dacryoadenitis, a phenomenon that has not been previously reported. The patients presented with bilateral or unilateral ocular adnexal mass usually present for many years. One patient also had asymptomatic diffuse lymphadenopathy. Two patients had biopsy-proven IgG4-related chronic sclerosing dacryoadenitis before the current presentation, and 1 had systemic involvement by IgG4-related sclerosing disease as evidenced by increased IgG4+ cells in a prior nasopharyngeal biopsy. Two cases showed features of extranodal marginal zone lymphoma of mucosa-associated lymphoid-tissue type (1 with large cell transformation) and 1 follicular lymphoma. Thus, the lymphoid hyperplasia of IgG4-related sclerosing disease can provide a substrate for the emergence of lymphoma. In addition, we report 3 cases of ocular adnexal extranodal marginal zone B-cell lymphoma that show sclerosing inflammation in the background and numerous IgG4+ monotypic plasma cells. In the absence of prior biopsies or information on serum IgG4 titer, it is unclear whether these cases represent lymphoma complicating IgG4-related sclerosing disease or de novo lymphoma. Nonetheless, these cases are distinctive in that the neoplastic cells express IgG4 (light chain restricted), whereas unselected cases of ocular adnexal lymphomas do not show IgG4 expression.

Primary cutaneous marginal zone lymphomas with plasmacytic differentiation show frequent IgG4 expression

“…Although IgG4 expression has been described in a single case of a nodal marginal zone lymphoma, 21 few cases of ocular adnexae marginal zone lymphomas, [17][18][19]22 as well as in a subset of marginal zone lymphomas of the dura, 16 the rate of 39% IgG4-positive cases among our primary cutaneous marginal zone lymphomas is striking. Only two IgG4-rearranged primary cutaneous marginal zone lymphomas, identified by RT-PCR, were previously reported.…”

“…9 As morphologic and environmental features did not differ between IgG4-positive primary cutaneous marginal zone lymphomas and the remaining class-switched cases in our series, the pathogenetic consequences of IgG4 expression remain unclear at present. Although few ocular marginal zone lymphomas may show an association with an underlying IgG4-related disease, 17,23 there is little evidence that this is the case for dural marginal zone lymphomas in the published series. 16 Similarly, it is very unlikely that IgG4-related disease is associated with the respective subgroup of primary cutaneous marginal zone lymphomas in our cohort.…”

“…This scenario raises the question of a secondary skin involvement by an originally noncutaneous marginal zone lymphoma. 2,6 Given some recent reports that particular subsets of marginal zone lymphomas, specifically epidural and ocular marginal zone lymphomas, [16][17][18][19] show increased frequencies of IgG4 expression and based on the known fact that primary cutaneous marginal zone lymphomas predominantly express IgG in contrast to other marginal zone lymphomas, we were interested to study the prevalence of IgG4 expression in primary cutaneous marginal zone lymphomas in comparison with various noncutaneous marginal zone lymphomas. The concept of IgG4-related diseases has attracted major attention in recent years comprising an ever increasing amount of manifestations of various organs (autoimmune pancreatitis type 1, Mikulicz's disease, Kuttner's tumor, and retroperitoneal fibrosis).…”

Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells

“…There are increasing numbers of reports of lymphoma associated with IgG4 production. 12,13 Most of these have been marginal zone lymphomas with IgG4-positive clonal plasma cells. The relationship between IgG4-positive benign disorders and the subsequent development of IgG4-positive lymphomas has not been thoroughly evaluated at this point.…”

A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details

“…At this point, it is unclear whether the pathogenetic mechanism of this disease is systemic or whether it consists of manifestations in individual organs. In addition, several reports have described patients with IgG4-associated conditions concomitant with malignant tumors such as pancreatic [25, 26] and salivary [27] carcinomas, and ocular adnexal lymphoma [28]. Therefore, using the term ‘systemic’ may lead to an incorrect diagnosis of an IgG4-related condition in a patient with malignant tumors in other organs.…”