Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database

Am J Hematol. 2014 Mar;89(3):310-4. doi: 10.1002/ajh.23638. Epub 2014 Feb 19.


Approximately a third of the patients with diffuse large B-cell lymphoma present with extranodal involvement. Our study aims to identify primary extranodal sites of disease associated with prognosis in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. A secondary objective is to describe epidemiological and clinical characteristics of patients with extranodal DLBCL. We included adult patients from the Surveillance, Epidemiology and End Results (SEER) database (2004-2009) in whom DLBCL was the first malignancy diagnosed. Extranodal primary sites were divided into 12 groups according to the topography code reported by SEER. Multivariate overall survival (OS) analyses were performed using Cox proportional-hazard regression models adjusted for age, sex, race, and stage. From a total of 25,992 adult DLBCL patients included in our analysis, 32% presented with extranodal primary sites. Gastrointestinal tract (34%), head/neck (H&N; 14%), and skin/soft tissue (11%) were the most common. In comparison with nodal DLBCL, patients with extranodal involvement were older (with exception of skeletal sites) and presented with earlier stages. In the multivariate analysis, sites associated with worse OS rates were gastrointestinal (Hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.15-1.33; P <0.001), pulmonary (HR 1.59, 95% CI 1.38-1.83; P <0.001), and liver/pancreas (HR 1.58, 95% CI 1.35-1.85; P <0.001), whereas H&N was associated with better survival (HR 0.79, 95% CI 0.70-0.89; P <0.001). In this population-based study, primary extranodal sites of involvement are associated with distinct outcomes in patients with DLBCL. Gastrointestinal, pulmonary, and liver/pancreas sites had a significant worse outcome than nodal sites.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Ethnicity / statistics & numerical data
  • Female
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Lymphoma, Large B-Cell, Diffuse / pathology*
  • Male
  • Middle Aged
  • Organ Specificity
  • Prognosis
  • Proportional Hazards Models
  • Rituximab
  • SEER Program
  • United States / epidemiology
  • Young Adult


  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab