Indolent B-cell lymphomas deriving from the marginal zone include three specific entities: extranodal marginal zone (or mucosa-associated lymphoid tissue) lymphoma (EMZL), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). The clinical and molecular characteristics are distinctive for each of these entities, although some phenotypic and genetic features overlap. EMZL is the most common entity, arising at virtually any extranodal site, commonly associated with chronic antigenic stimulation either as a result of an external infection (eg, Helicobacter pylori in the stomach) or an autoimmune disease (eg, Sjögren syndrome or Hashimoto thyroiditis). SMZL accounts for approximately 20% of all marginal zone lymphomas (MZLs), with patients typically presenting with an enlarged spleen and involvement of marrow and splenic hilar lymph nodes. NMZL is the least common entity, representing approximately 10% of all MZLs and typically presenting with lymph node–based disease without splenic or extranodal site involvement.
Acronyms and Abbreviations
AKT1, protein kinase Bα; BCL6, B cell CLL/lymphoma 6 gene; BCL10, B cell CLL/lymphoma 10 gene; BCR, B cell receptor; BTK, Bruton tyrosine kinase; CD, cluster of differentiation; EMZL, extranodal marginal zone lymphoma; HBV, hepatitis B virus; HCV, hepatitis C virus; IELSG, International Extranodal Lymphoma Study Group; Ig, immunoglobulin; IGHV, immunoglobulin heavy-chain variable region gene; KLF2, Krüppel-like factor 2; LDH, lactate dehydrogenase; LPL, lymphoplasmacytic lymphoma; MALT, mucosa-associated lymphoid tissue; MYD88, myeloid differentiation primary response 88; MZL, marginal zone lymphoma; NF-κ B, nuclear factor-kappa B; NHL, non-Hodgkin lymphoma;NMZL, nodal marginal zone lymphoma; PAX5, paired box gene 5; PI3K, phophoinositide 3-kinase; PIM1, protooncogene proteins pim; PTPRD, protein tyrosine phosphatase receptor type D; R-CHOP, rituximab, cyclophosphamide, hydroxydaunorubicin [Adriamycin], vincristine [oncovin] and prednisone; R-CVP, rituximab cyclophosphamide, vincristine and prednisone; ROS, reactive oxygen species; SMZL, splenic marginal zone lymphoma; TNF, tumor necrosis factor; TNFAIP3, tumor necrosis factor alpha-induced protein 3; WHO, World Health Organization.
INTRODUCTION AND CLASSIFICATION
Marginal zone lymphomas (MZLs) represent a heterogeneous group of indolent lymphoproliferative disorders originating from memory B lymphocytes, which are normally present in the marginal zone—that is, the outer part of the mantle zone—of the secondary lymphoid follicles. The spleen and the mucosa-associated lymphoid tissues (MALT) are the most frequently involved anatomic compartments; lymph nodes may also be involved, albeit rarely.
The 2016 revision of the World Health Organization (WHO) Classification of Tumours of Haematopoietic and Lymphoid Tissue identifies three distinct subtypes of MZL based on the involved site, the clinical presentation, and course of the disease, as well as the molecular profiles, namely, extranodal MZL of MALT type (also termed extranodal marginal zone lymphoma [EMZL]), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). In addition, three provisional entities are recognized by the current WHO classification: pediatric nodal MZL, splenic diffuse red pulp lymphoma, and hairy-cell leukemia variant. The former is a separate variant of NMZL that mainly involves head and neck lymph nodes ...