Elsevier

Human Pathology

Volume 44, Issue 12, December 2013, Pages 2658-2667
Human Pathology

Original contribution
Clonally related composite follicular lymphoma and mantle cell lymphoma with clinicopathologic features and biological implications,☆☆

https://doi.org/10.1016/j.humpath.2013.07.007Get rights and content

Summary

Composite lymphoma with follicular lymphoma (FL) and mantle cell lymphoma (MCL) components is rare and can pose a substantial diagnostic challenge. We report two cases of composite lymphoma with FL and MCL components occurring in lymph nodes. Both cases showed near total effacement of the lymph node architecture by grade 1 FL (CD10+ and BCL2+) with accompanying in situ MCL component (CD5+ and cyclin D1+) surrounding neoplastic follicles. The diagnosis of composite FL and MCL was confirmed by detecting the t(14;18)(q32;q21) and t(11;14)(q13;q32) in the FL and MCL components, respectively. Immunoglobulin heavy chain fragment length analysis in both cases showed identical dominant monoclonal peaks in microdissected neoplastic lymphoid cells from FL and MCL components. These findings suggest a common clonal origin for the FL and MCL components in both cases.

Introduction

Composite lymphoma is defined as two or more morphologic and immunophenotypic types of lymphoma involving the same anatomical site [1]. Traditionally, based on disparate morphologic features, it was presumed that the two components of composite lymphoma are unrelated [1]. However, with the advent of molecular analysis, it has become clear that the components of composite lymphoma can share a common clonal origin suggesting derivation from a common precursor cell in a subset of cases [2]. The origin of composite lymphoma therefore is complex, and there are likely a number of pathogenetic pathways that can result in composite lymphoma.

The diagnosis of small B-cell lymphoma has gone through a number of changes in the past two decades, resulting in several types of small B-cell lymphoma as defined in the most recent World Health Organization classification [3]. Small B-cell lymphomas are characterized by distinctive clinical, morphological, immunophenotypic and genetic features. With the increasing use of comprehensive panels of immunophenotypic markers and the development of newer markers for the diagnostic evaluation of small B-cell lymphomas in routine practice, more cases of composite B-cell lymphomas (including in situ variants) are likely to be diagnosed in the future. The diagnosis of cases of composite small B-cell lymphoma can be challenging, and molecular studies are proving to be invaluable in the workup of composite small B-cell lymphomas.

Cases of composite lymphoma with follicular lymphoma (FL) and mantle cell lymphoma (MCL) have been reported rarely in the literature, mostly in the form of case reports [4], [5], [6], [7], [8], [9], [10]. Molecular studies to assess clonal relatedness have been performed in five cases of composite FL and MCL. Two cases were clonally distinct or biclonal [4], [6], one case was inconclusive [7] and the remaining two cases appeared to be clonally related [5], [8]. Additional case reports and molecular analysis of these rare tumors are needed to better understand the pathogenesis of composite FL and MCL.

In this study, we present 2 cases of composite FL and MCL occurring in lymph nodes. Molecular analysis using PCR-based methods to assess clonality showed that the two components were clonally related in both cases.

Section snippets

Case 1

An 80-year-old man presented with right neck cervical lymphadenopathy. On admission, the complete blood count showed a hemoglobin level of 13.6 g/dL (normal range, 13.5-17.5 g/dL for males). Examination of a peripheral blood smear was normal. The serum lactate dehydrogenase level was 273 IU/L (normal range, 100-220 IU/L). A computed tomographic scan showed lymphadenopathy mostly confined to the right neck and mild splenomegaly. Excisional biopsy of a right neck lymph node was performed, and the

Histologic and immunohistochemical studies

Both lymph node specimens were fixed in 10% neutral buffered formalin and embedded in paraffin. Sections 4-μm thick were cut and stained with hematoxylin and eosin for routine histological evaluation.

Immunohistochemical studies were performed using formalin-fixed, paraffin-embedded tissue sections. Briefly, tissue sections were deparaffinized in xylene and rehydrated in graded alcohols. Endogenous peroxidase was blocked with 3% hydrogen peroxide. During antigen retrieval, tissue sections were

Case 1

The right cervical lymph node showed near total effacement of the architecture by numerous neoplastic follicles in a crowded back-to-back arrangement (Fig. 1A). The neoplastic follicles lacked polarity and tingible body macrophages (Fig. 1B and C) and were composed predominantly of small centrocytes with a few centroblasts (≤5 per 10 hpf). Some of the neoplastic lymphoid follicles were rimmed by normal to mildly thickened mantle zones (Fig. 1B and C). There was no significant merging of the

Discussion

Composite B-cell lymphomas are defined as two morphologically and immunophenotypically distinct neoplastic B-cell lymphomas occurring in the same anatomical site. Traditionally, it was presumed that the two components were not clonally related based on their disparate morphologic and immunophenotypic features. With the advent of molecular testing, however, it has become recognized that in some cases of composite lymphoma, the two components are clonally related, suggesting origin of each

Acknowledgment

Shi Wang is an honorable visiting scholar supported by the National University Hospital, Singapore. Z.Y.X.-M. is a recipient of Shannon Timmins Leukemia Endowment Fellowship and Harold C. and Mary L. Daily Endowment Fellowship Awards at The University of Texas MD Anderson Cancer Center. A.T. is a recipient of the Stiftung zur Krebsbekaempfung Zurich Grant 269 award. K.H.Y. is supported by The University of Texas MD Anderson Cancer Center Institutional R & D Fund, Institutional Research Grant

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    Author Contributions: Conception and design: S.W., A.T., K.H.Y.; performing research: S.W., A.T., K.H.Y.; provision of study materials, key reagents, technology and resource: S.W., A.T., Z.Y.X.M., S.H., S.A.W., K.L.R., S.Z., J.W.S., L.J.M., K.H.Y.; collection and assembly of data under approved institutional review board: S.W., A.T., Z.Y.X.M., S.H., K.L.R., S.Z., J.W.S., K.H.Y.; data analysis and interpretation: S.W., A.T., L.J.M., K.H.Y.; manuscript writing: S.W., L.J.M., K.H.Y.; final approval of manuscript: all authors.

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    Disclosure of Conflicts of Interest: The authors declare no conflicts of interest.

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