IgG4-related sclerosing disease is a recently recognized syndrome characterized by mass-forming lesions in exocrine glands or extranodal tissues due to lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and increased IgG4+ plasma cells in the involved tissues. We report the morphologic features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in patients with this syndrome. The patients presented with autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or chronic sclerosing sialadenitis. The histologic features of the lymph nodes could be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia, and interfollicular expansion by immunoblasts and plasma cells. The percentage of IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control lymph nodes comprising a wide variety of reactive conditions). We also report 6 cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma cells (mean 58%). These cases share many clinical and pathologic similarities with IgG4-related sclerosing disease. In fact, 2 of these patients developed lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland involvement during the clinical course. These cases therefore probably represent primary lymph node manifestation of the disease. The importance of recognition of the lymphadenopathic form of IgG4-related sclerosing disease lies in the remarkable response to steroid therapy, and the potential of mistaking the disease for lymphoma either clinically or histologically.

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.

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