Atypical marginal zone hyperplasia of tonsil with immunoglobulin light chain restriction
Authors: Prabhjot Kaur, Norman B. Levy
Journal: American Journal of Hematology (2011)

This is a case of tonsillar enlargement in an immune compromised, 9-year-old child with aplastic anemia. The tonsil showed florid follicular and interfollicular hyperplasia ( Image 1A). The expanded marginal zones contained a mixture of small centrocyte-like cells, monocytoid cells, and numerous transformed large lymphocytes (Image 1B). The CD20 positive B lymphocytes (Image 1C) were negative for epstein-barr virus (EBV). The germinal center lymphocytes were positive for CD10 (Image 1D) and negative for Bcl2 (Image 1E). Flow analysis detected a B-cell population with lambda Ig light chain restriction (Image 1F). Molecular studies, however, showed a polyclonal B-cell population (Image 1G). Differential diagnosis included atypical marginal zone B-cell hyperplasia, marginal zone B-cell lymphoma, and immunodeficiency-associated B-cell lymphoproliferative disorder. Because of the absence of B-cell clonality by molecular analysis along with the absence of EBV infection by EBV-encoded RNA (EBER)-in situ hybridization studies, and a prior report by Attygalle et al. [1], the diagnosis of atypical marginal zone hyperplasia was rendered. In 2004, Attygalle et al. [1] reported a retrospective study which included six childhood cases, between the ages of 3 and 11, with tonsillar and appendiceal marginal zone proliferations displaying a naïve B-cell phenotype and lambda light chain restriction. All cases were found to be polyclonal by molecular analysis. No lymphoma-directed therapy was given to these children, and none of the children developed recurrent or new lesions after a follow-up of 3–13 years [2]. Similar cases have been described by Taddesse-Heath et al. [3]. Swerdlow reported a similar case in the adenoid of an 8-year-old girl but with monoclonal heavy chain VJ gene rearrangements [4]. These marginal cell proliferations are rare, and there is confusion on whether these are atypical hyperplasias or marginal zone lymphomas and if lymphomatous whether of mucosa associated lymphoid tissue type (MALT lymphoma) or nodal type [3, 5]. Marginal zone lymphoma of MALT lymphoma are extremely rare in native MALT sites of tonsil, adenoids, Peyer's patches and appendix [6] especially in children [3, 4, 7] and occur usually outside of the native MALT sites, like the parotid MALT lymphomas in human immunodeficiency virus patients and Helicobacter pylori infection-associated gastric MALT lymphomas, followed by orbital and skin sites [7]. (A) Tonsil with follicular hyperplasia and expanded marginal zones (hematoxylin–eosin, original magnification: 20×). (B) Marginal zones contain a mixture of small centrocyte-like cells, monocytoid cells and numerous transformed lymphocytes (original magnification: 400×). (C) CD20, also seen in intraepithelial B lymphocytes (original magnification: 20×). (D) The germinal center lymphocytes are positive for CD10 (original magnification: 20×). (E) The germinal center lymphocytes are negative for Bcl2 (original magnification: 20×). (F) Flow analysis showing lambda Ig light chain restriction. (G) Molecular studies showing polyclonal B-cell IgH gene rearrangement. These marginal zone proliferations in native MALT sites usually present as localized disease and behave in an indolent fashion [1-4]. They may be managed, conservatively, with a watch and wait approach. Interestingly, similar lesions showing discordance between immunophenotypic and molecular analysis of clonality has been found in localized lambda restricted plasmablastic proliferations of multicentric Castleman's disease [8]. Of note, our patient has been followed for the last 3 years, and there has been no recurrence at tonsillar sites or new adenopathy.