Transformed Nodal Marginal Zone Lymphoma versus Diffuse Large B Cell Lymphoma: The MicroRNA Aspect

tity still remains unanswered. All three entities share a common immunophenotype and some cytogenetic abnormalities, such as whole or partial gains of chromosomes 3, 12 and 18. However, certain differences indicate that NMZL differs biologically from SMZL and MALT lymphomas: the MALT-specific translocations and the SMZL-associated deletion of 7q are characteristically absent. Regarding the cell of origin, the normal counterpart of NMZL is considered an antigen-experienced, postgerminal center memory B cell that has not necessarily undergone germinal center transit. Findings from gene expression profiling studies point to a genetic similarity between NMZL and MALT lymphomas. However, nuclear factor-κB activation is less frequently encountered compared to MALT lymphomas [1, 2] . A third issue of interest is the invariable presence of scattered large cells (immunoor centroblasts) which may comprise >20% of the neoplastic cell population in up to half of all cases, in contrast to other low-grade B cell lymphomas. The importance of large cells has been a major debate between pathologists that has not been completely resolved even today. A threshold of >20 or >50% of large cells has been used as a cut-off for defining ‘transformed lymphoma’. Recently, in 2011, a consensus was reached to use the term ‘transformed NMZL’ only if Nodal marginal zone lymphoma (NMZL) is a very rare lymphoma subtype comprising less than 2% of all nonHodgkin lymphomas. It is one of the three well-recognized entities within the broad category of marginal zone lymphomas (MZL), together with splenic marginal zone (SMZL) and mucosa-associated lymphoid tissue (MALT) lymphomas [1] . There are several aspects of interest and unresolved issues regarding this relatively new entity. The first point of interest in NMZL is its diagnostic difficulty. Although NMZL is a separate entity, its recognition is rather challenging, at least at the histopathological level due to a lack of specific markers. Thus, the diagnosis of NMZL relies on clinical presentation in conjunction with a compatible histology/immunophenotype and requires lymph node involvement with concurrent absence of splenic and extranodal disease. Still, there are cases that are difficult to classify with certainty, such as disseminated disease at the time of diagnosis, cases with extranodal involvement and nonregional lymph nodes, or cases with prominent splenomegaly as the major finding combined with extensive abdominal or widespread lymphadenopathy and/or MALT-site involvement. A second point of interest focuses on the biologic similarity of NMZL to the other two entities of MZL. The question of whether NMZL truly represents a distinct enReceived: June 11, 2014 Accepted: June 28, 2014 Published online: November 4, 2014