Mantle Cell Lymphoma With Mantle Zone Growth Pattern

A Clinicopathologic Study of 35 Cases

Ji Yuan, MD, PhD; Shaoying Li, MD; Xin Liu, MD, PhD; Ruijun Jeanna Su, MD, PhD; Mingyi Chen, MD, PhD; Xiaojun Wu, MD; Gang Zheng, MD, PhD; Lynette M. Smith, PhD; Lifu Wang, MD; Yanxia Li, MD, PhD; Cynthia Liu, MD, PhD; Jiehao Zhou, MD, PhD; Qi Shen, MD, PhD; Linsheng Zhang, MD, PhD; Endi Wang, MD, PhD; Mina L. Xu, MD; Zenggang Pan, MD, PhD

Disclosures

Am J Clin Pathol. 2019;152(2):132-145. 

In This Article

Abstract and Introduction

Abstract

Objectives: To characterize the clinical and pathologic features of mantle cell lymphoma with mantle zone growth pattern (MCL-MZGP).

Methods: The clinicopathologic data from 35 cases of MCL-MZGP obtained in 12 centers were analyzed.

Results: The patients with MCL-MZGP typically sought treatment at high clinical stages (81%). Intriguingly, 40% (14/35) of cases were incidentally noted. The lymph nodes with MCL-MZGP showed preserved architecture and expanded mantles containing lymphoma cells with classic or small cell cytology. MCL-MZGP was positive for BCL2 (96%, bright), CD5 (82%, moderate), cyclin D1 (100%), and SOX11 (89%). Clinically, our study revealed no significant difference in the overall survival between patients managed with observation alone and those who received chemotherapy.

Conclusions: MCL-MZGP was often incidentally identified and resembled reactive mantles. Therefore, recognition of this unusual morphology emphasizes the utility of cyclin D1 immunostain in the cases with suspicious morphology. However, the clinical significance of these findings is still unclear.

Introduction

Mantle cell lymphoma (MCL) accounts for 5% to 6% of non-Hodgkin lymphomas, which characteristically overexpresses cyclin D1 due to t(11;14)(q13;q32) translocation involving CCND1-IGH gene rearrangement. Patients with MCL usually seek treatment at advanced stages with an aggressive clinical course. Despite significant improvement in the management over the years, the long-term prognosis remains poor, with a median overall survival of 3 to 5 years.[1] In addition, MCLs show a broad spectrum of morphologic characteristics with variable architectural patterns and cytologic features, which are associated with heterogeneous clinical behaviors.[2–4] There are three major architectural patterns, including diffuse, nodular, and mantle zone. The diffuse pattern is most commonly encountered (~80%), followed by the nodular growth (~18%), which has a slightly better prognosis.[3] Mantle zone growth is observed as the predominant pattern in less than 2% of MCL cases, in which the lymphoma cells grow in the mantles around preexisting germinal centers.[3,4]

Several cytologic variants of MCL have been recognized, including classic, small cell, pleomorphic and blastic, the latter two of which are grouped by some pathologists as the "blastoid variant."[3,4] The classic cytology is observed in approximately 88% of cases, and the lymphoma cells are small to medium sized with irregular nuclei, moderately dispersed chromatin, and inconspicuous nucleoli.[3–5] The small cell subtype accounts for only 2% to 4%, which closely resembles small lymphocytic lymphoma with small round or slightly irregular nuclei and condensed chromatin. Clinically, this variant is indolent and has a higher 5-year survival rate than the classic type.[3,6] The MCLs with pleomorphic and blastic morphology (~10% combined) are reminiscent of diffuse large B-cell lymphoma and lymphoblastic lymphoma, respectively; both cytologic variants are associated with a high proliferation rate and a poor outcome.[3,5]

Although patients with MCL are usually treated aggressively, approximately 15% have an indolent clinical course with an overall survival of 7 to 10 years, resulting in the term indolent MCL.[3,7–11] Patients with indolent MCL may defer treatment for a long period with no apparent adverse effects on the outcome. Therefore, it is of paramount importance to identify the different prognostic subgroups of MCL and allow risk-adjusted therapeutic approaches in these patients.

Mantle cell lymphoma with mantle zone growth pattern (MCL-MZGP) is of particular interest. While the diagnosis of MCL with diffuse and/or nodular patterns is usually straightforward, recognition of MCL-MZGP can be problematic due to its rarity and significant morphologic overlaps with reactive mantle zones. Therefore, the pathologic changes could potentially be overlooked even with careful morphologic examination. In addition, the tumor cells may only account for a minute proportion of cells in the lymph node, which may not be readily sampled or detected by flow cytometry. Moreover, the definition of MCL-MZGP remains to be further clarified. Recently, we encountered several cases of incidental MCL-MGZP in the lymph nodes dissected for carcinoma staging, which were very challenging to diagnose without ancillary flow cytometric and cytogenetic studies. Hence, there is a need to identify important morphologic clues that can trigger the suspicion for MCL-MZGP to initiate appropriate further workup.

Prior studies with limited cases suggested that MCL-MZGP was associated with a better prognosis than conventional MCL.[6,8,12] However, it is still not certain whether MCL-MZGP belongs to the category of indolent MCL or represents the early phase of MCL with nodular and/or diffuse patterns. Therefore, in this study, we assessed a large series of cases previously diagnosed as "MCL-MZGP" to extract the important clinical, morphologic, and immunophenotypic features, which may assist in the accurate diagnosis of this entity and the selection of optimal management.

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