Nodal marginal zone B-cell lymphoma (MZL) is a clinically indolent neoplasm that involves lymph nodes. As defined in the World Health Organization (WHO) classification, this neoplasm histologically resembles extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and splenic MZL, but without evidence of extranodal or splenic disease (1). Currently, MZLs are distinguished, in large part, by clinical criteria because specific immunophenotypic or molecular markers for these neoplasms are largely unknown.

Monocytoid B-cell lymphoma (Kiel); parafollicular B-cell lymphoma (Lukes-Collins); small lymphocytic with plasmacytoid differentiation, diffuse small cleaved cell or diffuse mixed small and large cell (Working Formulation).

Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program collected from 1992 to 2001 and published in 2006, MZL represented 2.8% of all lymphomas in the United States. The incidence rate for MZL was 0.97 per 100,000 person-years (2). However, the category of MZL in the SEER data appears to include all types of MZL (nodal, splenic, and extranodal). Furthermore, the criteria for the diagnosis of MZL have evolved substantially since 1992. Mostly likely, a better measure of the relative frequency of nodal MZL is data from the Nebraska Non-Hodgkin Lymphoma Classification Project (3). In that study, nodal MZL represented 1.8% of all non-Hodgkin lymphomas. In other clinicopathologic studies from France and Japan, nodal MZL represented approximately 1% of all non-Hodgkin lymphomas (4,5).

The pathogenesis of nodal MZL is unknown, and the cell of origin is only postulated. Sheibani and colleagues (6), based on their observation that these neoplasms cytologically resemble reactive monocytoid B cells, coined the term monocytoid B-cell lymphoma. Monocytoid B cells are reactive lymphoid cells found in the lymph node sinuses of many lymphadenitides, and they are particularly prominent in Toxoplasma lymphadenitis (7,8). Similarly, a strong cytologic resemblance between nodal MZL and hairy cell leukemia (HCL) led to the suggestion that both neoplasms share a common cell of origin (9). Currently, a number of differences between the cells of nodal MZL and either reactive monocytoid B cells or HCL are recognized. Cousar and colleagues (10) suggested the term parafollicular B-cell lymphoma for this neoplasm. These authors considered parafollicular B cells to be a postgerminal center stage of B-cell maturation differentiating toward plasma cells (10,11). Essentially, this position is closest to our current understanding, except that parafollicular B cells are now thought to be nodal marginal zone B cells (1).

Nodal MZL is a disease of adults that occurs primarily in the sixth or seventh decades, but there is a wide age range. In a registry of 100 cases of what was then designated as monocytoid B-cell lymphoma, the median patient age was 64 years, with a range from 13 to 89 years. Women outnumbered men in a 2:1 ratio, and approximately 75% of patients had localized lymphadenopathy (12). The current problem with assessing the data in this registry is that patients with involvement of the spleen or other extranodal sites were included, as the definition of monocytoid B-cell lymphoma allowed at that time. Using the WHO classification, these patients are currently considered to have either splenic MZL or MALT lymphoma, respectively (1). Therefore, before the diagnosis of nodal MZL (as currently defined) can be established with certainty, all patients require staging to exclude occult splenic or extranodal disease (13).

In more recent studies of nodal MZL, the median age in various studies has ranged from 54 to 64 years of age (4,5,14,15,16,17). The sex ratio has been inconsistent in different studies (4,5,6,14,15,16,17). In the larger clinicopathologic studies, a slight female preponderance was noted (5,16). The clinical course of patients with nodal MZL is indolent, similar to that of patients with other types of clinically indolent B-cell lymphoma (14). Fever, weight loss, and night sweats (B-type symptoms) occur in approximately one-third of patients (3,4,6,14,15,16,17). However, in one Japanese study, fewer than 10% of patients had B symptoms (5). Serum lactate dehydrogenase (LDH) level is increased in 15% to 48% of patients, depending on the study (4,5,14,15,16,17). Patients present with localized or widespread lymphadenopathy that is usually peripherally based (3,4,5,6,14). The most common sites of peripheral lymphadenopathy, in order of frequency, are the neck, axilla, and inguinal/femoral region (14,15,16,17). In patients with localized disease, head and neck lymph nodes are most frequently involved (4,5,14). Para-aortic or mesenteric lymphadenopathy is also common, in approximately one-half of patients (4,14). Bone marrow involvement occurs, with an overall frequency ranging from 28% to 62%, depending on the study (4,12,13,14,15,16,17). A leukemic phase is uncommon (12,13). A monoclonal serum paraprotein, usually composed of immunoglobulin M (IgM), is present in a subset of patients (4,5,15,16,17), and in up to one-third of patients in the study by Traverse-Glehen and colleagues (4). Serologic evidence of hepatitis C infection was identified in 24% of patients in an Italian study (15) but was not detected in a study from France (4).

The assessment of prognosis is complicated by the small numbers of patients in most studies and the variable therapies employed (4,5,6,14,15,16,17). In a study by Nathwani and colleagues (14), the 5–year overall survival was 56%, and the
5–year failure-free survival was 28%. In a French study, 5–year overall survival was 70%, with a 5–year failure-free survival rate of 35% (4). Prognosis was best in a large Japanese study by Kojima and colleagues (5): the 5–year overall survival and failure-free survival were 85% and 65%, respectively. A subset of patients in these and other studies transformed into diffuse large B-cell lymphoma, and this development correlated with poorer prognosis (4,5,14,18).