Non-MALT marginal zone lymphomas.

The concept of marginal zone B-cell lymphomas was developed in the 1990s for lymphomas whose cells originate from B lymphocytes normally present in a distinct anatomical location, the so-called ‘marginal zone’ (MZ). MZ has been described in the lymphoid organs—spleen and lymph nodes—and in nonlymphoid organs—mucosa-associated lymphoid tissue (MALT) or non-mucosal tissue such as skin, orbit and dura—as micro-anatomical sites situated around the mantle zone at the periphery of the splenic white pulp and at the periphery of lymphoid follicles. It was ascribed to the location of memory B cells at the end of the 1980s [1, 2]. Different entities of B-cell lymphomas are supposed to derive also from the cells of MZ. The International Lymphoma Study Group has individualized three distinct subtypes of MZL: (i) extranodal MZL of MALT type, (ii) splenic MZL (with or without villous lymphocytes) and (iii) nodal MZL (with or without monocytoid B cells) [3, 4]. In addition, entities with overlapping clinical, morphological and phenotypical features have been reported, including Waldenström macroglobulinemia/lymphophasmacytic lymphoma (WM/ LPL) [5, 6], splenic red pulp lymphoma with villous lymphocytes [7] and hairy cell leukemia variant [8]. In spite of multifaceted phenotypic characterization, the absence of a clear consensus for diagnosis coming from the lack of typical markers and recurrent molecular abnormalities makes the identification of these entities difficult and are obstacles to conducting epidemiological surveys and to describing clinical features and outcomes, particularly for splenic MZL and nodal MZL. Moreover, few prospective studies on large series have been published to date, making therapeutic decisions difficult. Data regarding clinical and biological prognostic markers are limited, and it is therefore difficult to predict those in whom the disease will be more aggressive. This review will present recent data describing the epidemiology, pathogenesis, clinical features, staging and therapy of non-MALT MZL.