Clinical Pearls & Morning Reports
Marginal-zone lymphomas (MZLs) comprise three subtypes: extranodal MZL of mucosa-associated lymphoid tissue (MALT lymphoma), splenic MZLs, and nodal MZLs. A premalignant condition described as clonal B-cell lymphocytosis of marginal-zone origin (CBL-MZ) may precede the onset of an overt MZL. Read the NEJM Review Article here.
Q: Is MZL a common type of B-cell non-Hodgkin’s lymphoma?
A: MZLs are the third most common type of B-cell non-Hodgkin’s lymphoma, after diffuse large B-cell lymphoma and follicular lymphoma. In the United States, from 2001 to 2017, the incidence of MZL increased 1.0% per year, which partly reflects improved diagnosis. Moreover, the representation of MZL subtypes has changed over time, with a relative reduction in cases of extranodal MZL and an increase in cases of splenic MZL. Differences in temporal and geographic features of MZLs may reflect modifications of predisposing conditions.
Q: What are some of the conditions that constitute predisposing factors for MZL?
A: A history of chronic infections and autoimmune conditions is strongly associated with MZLs. Chronic H. pylori gastritis is a predisposing factor for gastric MZLs. Other microorganisms have been associated with site-specific extranodal MZLs on the basis of strong, but not definitive, evidence, including Chlamydia psittaci for ocular adnexa MZLs, Borrelia burgdorferi for cutaneous MZLs, and Campylobacter jejuni for small-intestine MZLs. Hepatitis C virus infection, particularly when complicated by cryoglobulinemia, can precede nodal and splenic MZLs, as well as extranodal MZLs at selected sites. Sjögren’s syndrome and Hashimoto’s thyroiditis are predisposing factors for salivary gland and thyroid MZLs, respectively.
A: Clinical manifestations of MZLs are multifaceted. Patients with extranodal MZLs present with symptoms caused by the involvement of tissues at the affected site. Patients with gastric MZLs present with epigastric pain or other dyspeptic symptoms, weight loss, or gastrointestinal bleeding. Patients with ocular adnexa MZLs present with slowly growing masses or eye redness. Patients with salivary and thyroid gland MZL present with slowly growing and painless lumps. Cutaneous MZLs are manifested as reddish or violaceous skin papules, plaques, or nodules localized preferentially on the trunk or arms. Lung MZLs are generally asymptomatic and incidentally discovered as lung nodules on imaging studies. Diagnosis of extranodal MZL is made from a biopsy of the affected tissue. CBL-MZ, splenic MZL, and nodal MZL are usually disseminated disorders. Patients may be asymptomatic, with the disease discovered on an incidental finding of lymphocytosis, splenomegaly, or painless peripheral adenopathy. Serum immunoglobulin paraprotein is found in approximately 30% of patients with splenic MZL or CBL-MZ, and paraneoplastic autoimmune manifestations are present in 20% of patients with splenic MZL. Accordingly, splenic MZL and CBL-MZ should be suspected and investigated in patients presenting with paraproteinemias or paraneoplastic autoimmune manifestations.
A: The course of MZLs is generally indolent, particularly in patients with extranodal MZLs. Median survival exceeds 10 years, although the disease affects life expectancy. As compared with the matched general population, patients with nodal MZL have the lowest relative survival. Progression of disease within 2 years after initial treatment is the strongest prognostic biomarker of reduced survival. Patients with relapse or progression within 2 years (approximately 20% of patients with MZLs) have a median survival of only 3 to 5 years, whereas life expectancy for the remaining approximately 80% of patients appears to be similar to that of the age-matched general population.