Patients with extranodal marginal zone lymphomas (EZML) with multiple mucosal sites (MMS) at presentation may have a poor prognosis, increased incidence of higher grade transformation (HGT), and decreased progression-free survival (PFS) and overall survival (OS) compared with patients without MMS, according to a study published in the American Journal of Hematology.

Poor prognostic factors for patients with EMZL include age greater than 70 years, advanced Ann Arbor stage, and elevated lactate dehydrogenase (LDH). However, the prognostic role of factors such as MMS involvement and monoclonal gammopathy have not been established, with studies reporting conflicting results.

In this study, researchers examined the incidence of MMS presentation and monoclonal gammopathy and the association of these factors with clinical progression and prognosis in patients with EMZL. They also evaluated the relationships between HGT and MMS and between early disease progression and survival.

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A total of 405 patients with EMZL were enrolled, with a follow-up time of 22.3 years. Ann Arbor stage was assessed via physical, hematologic, and chemical examination (including LDH levels) and computerized tomography of the chest. Biopsies were conducted in suspected cases of HGT. MMS involvement was defined as the presence of EMZL in 2 or more anatomical organs other than the spleen and bone marrow.

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A total of 43 patients had MMS at presentation, 5 of whom also presented with monoclonal gammopathy. Of patients with MMS, 17 had high LDH levels, 9 had anemia, and 9 had bone marrow involvement.

Patients with MMS had significantly shorter PFS and OS (P <.001 for both) compared with patients without MMS. The 10-year OS of patients with MMS presentation was 40.5% (95% CI: 20.7%-59.5%), while the 10-year OS of patients without MMS presentation was 81.1% (95% CI: 75.1%-85.5%).

Progression after diagnosis and therapy was observed in 37 patients with MMS. Patients with MMS showed higher incidence of HGT (25.6%) compared with patients with a single mucosal site (P <.001).

Disease progression within 2 years was found to be associated with shorter survival (hazard ratio, 6.79; P<.001). Of 332 patients who received treatment, 21.7% progressed within 2 years.

The authors noted this was the first large study showing statistically significant associations between MMS in EZML, HGT, and resulting clinical outcomes. Further studies are warranted to better understand the mechanisms of high-risk EZML and develop alternative treatment strategies.


  1. Alderuccio JB, Zhao W, Desai A, et al. Short survival and frequent transformation at extranodal marginal zone lymphoma with multiple mucosal site presentations [published online February 19, 2019]. Am J Hematol. doi: 10.1002/ajh.25446