Lymphadenopathy of IgG4-related Sclerosing Disease

Abstract

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.

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

“…Concomitant lymphadenopathy is common in patients with IgG4RD, and there have been several reports dealing with the morphological and immunohistological findings of lymph node lesions [55–57]. Although IgG4-related lymphadenopathy is occasionally characterized by systemic lymphadenopathy, polyclonal hyperimmunoglobulinemia, especially elevated IgG and IgE concentrations, and positivity for various autoantibodies, patients with IgG4RD with generalized lymphadenopathy should only be evaluated for lymphoma, sarcoidosis, multicentric Castleman’s disease, and other malignancies.…”

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease

“…Such abnormalities include an elevated serum IgG4 level and numerous IgG4-positive plasma cells infiltrating the affected tissue, and these disorders are classified as IgG4-related diseases. [1][2][3][4][5][6][7][8][9][10][11] Castleman's disease is a rather rare atypical lymphoproliferative disorder 12 classified according to the histopathologic findings of the affected lymph nodes as plasma cell type, hyaline-vascular type or a mixed-type variant of the two. 13,14 Patients with the plasma cell or the mixed-type variant frequently have systemic manifestations (so-called multicentric Castleman's disease), such as low-grade fever, fatigue, loss of appetite, and weight loss.…”

“…17,18 Multicentric Castleman's disease exhibits an aggressive and usually fatal disease course associated with infectious complications and risk of malignant tumors; one-third of such patients develop Kaposi sarcoma or B-cell lymphoma. 17,18 IgG4-related disease sometimes involves regional and/or systemic lymph nodes, 3,4,11 and is often clinically and/or histologically suspected to be multicentric Castleman's disease and/or malignant lymphoma. 5,6,11 However, systemic IgG4-related lymphadenopathy is either not mentioned or only briefly alluded to in previous reports.…”

“…17,18 IgG4-related disease sometimes involves regional and/or systemic lymph nodes, 3,4,11 and is often clinically and/or histologically suspected to be multicentric Castleman's disease and/or malignant lymphoma. 5,6,11 However, systemic IgG4-related lymphadenopathy is either not mentioned or only briefly alluded to in previous reports. 3,11 In this study, we examined systemic IgG4-related lymphadenopathy in detail, and its differences from multicentric Castleman's disease, with specific reference to clinical and pathologic findings.…”

“…5,6,11 However, systemic IgG4-related lymphadenopathy is either not mentioned or only briefly alluded to in previous reports. 3,11 In this study, we examined systemic IgG4-related lymphadenopathy in detail, and its differences from multicentric Castleman's disease, with specific reference to clinical and pathologic findings.…”