IgG4-producing marginal zone B-cell lymphoma

Abstract

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. Little is known about lymphomagenesis in the context of IgG4-related disease, we recently first reported the ocular adnexal marginal zone B-cell lymphomas arising from IgG4-related disease. To the best of our knowledge, no existing study has ever established the neoplastic potential of IgG4-producing cells. In the present report, we describe the first IgG4-producing lymphoma. The patient was a 72-year-old male who was being followed for an asbestos-related pleural plaque. During follow-up, computed tomography revealed bilateral renal masses and multiple swollen retroperitoneal lymph nodes. A retroperitoneal lymph node biopsy was performed. Histologically, the interfollicular areas were expanded by medium to large plasmacytoid cells. These plasmacytoid cells showed nuclear pleomorphism and had prominent Russell bodies. Immunohistochemistry and double immunofluorescence staining of these cells revealed IgG4 positivity and monotypic lambda-light chain predominance. A portion of these cells were partially positive for CD20, negative for CD3, and somewhat faintly positive for CD138. In addition, serum IgG4 was elevated. Southern blot analysis of the lymph node specimen detected immunoglobulin heavy chain gene rearrangement. The present study indicates that, not only can malignant lymphomas occur in the setting of IgG4-related disease, but IgG4-producing cells can also be neoplastic.

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

“…We recently reported the first case of marginal zone B-cell lymphoma arising from ocular adnexal IgG4-related disease 7 and IgG4-producing marginal zone B-cell lymphoma. 32 However, the present series showed no immunoglobulin light-chain restriction and no immunoglobulin heavy chain gene rearrangement.…”

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.…”

“…Primary sites included skin (49), stomach (21), salivary gland (20), lymph node (20), intestine (12), eye (12), lung (12), soft tissue (11), breast (3), oropharynx/larynx (3), tonsil (3), thymus (2), and thyroid gland (1). All cases were reviewed with sections stained with hematoxylin and eosin, Giemsa, and periodic acid Schiff, and an appropriate panel of immunohistochemical stains to establish a diagnosis according to the WHO classification.…”

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.…”

“…Features of Rosai-Dorfman disease were not seen. Plasma cells were shown to be polyclonal in ten cases using in situ stains for kappa and lambda (Cases 1,5,8,9,11,13,14,18,25,27). Polyclonal kappa and lambda staining was demonstrated by immunohistochemistry in three cases (Case 24, 25, 27).…”