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 are overlapping. 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 (e.g., Helicobacter pylori in the stomach) or an autoimmune disease (such as Sjögren syndrome or Hashimoto thyroiditis). SMZL accounts for approximately 20 percent of all marginal zone lymphomas, 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 percent of all marginal zone lymphomas and typically presenting with lymph node–based disease without splenic or extranodal site involvement.
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 (MALTs) 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 Tissues 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).1,1a In addition, three provisional entities are recognized by the current WHO classification: pediatric NMZL, splenic diffuse red pulp lymphoma, and hairy cell leukemia variant. The first is a separate variant of NMZL that mainly involves head and neck lymph nodes in male patients of pediatric age, with an indolent course and a remarkably better prognosis compared to NMZL. The last two represent subtypes of splenic lymphomas with features overlapping with those of MZL.1a
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; HCV, hepatitis C virus; Ig, immunoglobulin; IGHV, immunoglobulin heavy-chain variable region gene; IPSID, immunoproliferative small intestinal disease; LDH, lactate dehydrogenase; LPL, lymphoplasmacytic lymphoma; MALT, mucosa-associated lymphoid tissue; MZL, marginal zone lymphoma; NF-κB, nuclear factor kappa B; NMZL, nodal marginal zone lymphoma; PAX5, paired box gene 5; PIM1, protooncogene proteins pim; R-CHOP, rituximab, cyclophosphamide, doxorubicin (hydroxydaunomycin), vincristine (Oncovin), prednisone; R-CVP, rituximab, cyclophosphamide, prednisone; ROS, reactive oxygen species; SMZL, splenic marginal zone lymphoma; WHO, World Health Organization.