the rare disease now known as primary lymphoma of bone ( plb ) was initially described by oberlin . parker and jackson later described plb as a distinct entity , which is understood to be a malignant lymphoid infiltrate of bone . while this may include cortical or soft tissue invasion , the diagnosis generally excludes lymph node or distant visceral involvement to be considered a primary lymphoma of bone . this definition has been contended throughout the literature , with some authors permitting lymph node involvement [ 57 ] , though most authors recognize the disease as lymphoma localized only to bone upon diagnosis . previous studies have suggested plb comprise 5% of all extranodal lymphomas , and 3% of all bone malignancies . due to the low incidence of plb , most prior studies have been from a single - institution , and have had small sample sizes [ 1015 ] . the surveillance , epidemiology , and end results ( seer ) database is a publically available database created for the purpose of collecting demographic , clinical , and outcome data for cancer patients in the united states . the purpose of this population - based study was to identify prognostic factors for survival in patients with plb , in order to determine whether disparities in survival exist between demographic cohorts . in doing so , the current study aimed to determine the prognostic significance of different tumor - specific and anatomic considerations that may influence overall survival from this disease . the authors chose to limit this study to adult patients , because plb in children is often considered and treated as a systemic disease . the seer database collects data from 18 geographic registries , covering approximately 28% of the u.s . md ) was used to identify 997 adult patients diagnosed with primary lymphoma of bone during a 15-year period from 1989 to 2003 . histology was selected by using icd - o-3 codes 9590/3 , 9591/3 , 9670/3 , 19671/3 , 9675/3 , 9680/3 , and 9684/3 . primary site was selected as c40.0 , c40.1 , c40.2 , c40.3 , c40.8 , c40.9 , c41.2 , c41.3 , c41.4 , and c41.9 . exclusion criteria included lesions of the skull and face , t - cell lymphoma , and cases without follow up data , yielding a final study population of 692 patients . the scapula was considered to be part of the appendicular skeleton , while the pelvic bones were considered to be part of the axial skeleton . marital status was categorized as single , married , or other ( including separated , divorced or widowed ) . rural  urban continuum code was collapsed into a binary variable : metro county or non - metro county , using guidelines by seer and the economic research service . seer registry region was aggregated into regions ( northeast , south , southwest , midwest , and west ) . age was considered as a categorical variable ( < 30 years , 3059 years , 60 years ) . statistical analysis was performed in sas version 9.3 ( sas institute , cary , nc ) . the effects of categorical variables on survival were assessed by computing kaplan  meier product limit curves and compared using the log - rank test . factors that appeared to be significantly associated with survival in the univariate analysis were considered for inclusion in the final multivariable cox proportional hazards regression model . incidence rates were age - adjusted to the 2000 us standard population , with confidence intervals calculated using the tiwari modification . the final analysis included 692 patients , whose demographic and clinical characteristics are presented in table 1 . the majority of patients were white ( 89.0% ) , non - hispanic ( 91.3% ) , and lived in metropolitan counties ( 87.4% ) . the majority of patients were over the age of 60 years ( 55.6% ) , and diffuse large b - cell lymphoma was the most common histologic classification ( 71.2% ) . the western region of the united states contributed the largest proportion of patients to the study population ( 56.5% ) . the estimated overall survival of patients for all patients in this study was 49.6% at 5-years , and 30.2% at 10-years ( fig . the incidence of plb during the 15-year study period ranged from 0.1/100,000 to 0.3/100,000 ( fig . the annual percent change for this time period was non - significant , suggesting a stable incidence over the study period . in univariate analysis , significant factors for overall survival included age ( p<0.0001 ) , marital status ( p<0.0001 ) , anatomic location of tumor ( p<0.0001 ) , geographic region ( p=0.02 ) , and tumor grade ( p=0.01 ) . after bonferroni adjustment , tumor grade was no longer a significant prognostic indicator for overall survival . furthermore , after bonferroni adjustment for multiple comparisons , tumor grade and geographic region were not statistically significantly associated with overall survival . the final multivariable model demonstrated that age ( p<0.0001 ) , marital status ( p=0.02 ) , and appendicular or axial tumor location ( p=0.004 ) remained significant independent prognostic variables for overall survival ( table 3 ) . the mortality rate for plb patients in the 3059 age group is estimated to be 4.4 times that for those patients in the < 30 age group , after adjusting for marital status and tumor location ( ci : 1.711.2 ; p=0.002 ) . furthermore , patients aged 60 or older are estimated to have a mortality rate 12.8 times that for < 30 year - old patients , after adjusting for tumor location and marital status ( ci : 5.132.3 ; p<0.0001 ) , though this finding is potentially influenced by medical comorbidities . the multivariable cox regression model also showed that patients who were divorced , separated , or widowed had a significantly worse outcome than patients who were married or single ; the mortality rate for divorced , separated or widowed plb patients was estimated to be 1.4 times that for married patients , after adjusting for tumor location and age ( ci : 1.11.8 ; p=0.006 ) . the hazard ratio for comparing single with married patients was non - significant , however ( p=0.69 ) . anatomical location of the primary tumor was also a significant factor in overall survival . patients with an appendicular lesion had significantly better prognosis than patients with a primary axial lesion ( fig . the mortality rate for plb patients with axial - located disease is estimated to be 1.4 times that for those patients with appendicular - located disease , after adjusting for marital status and age ( ci : 1.21.8 ; p=0.004 ) . the current study presents a population - based analysis of the effects of demographic factors on overall survival from primary lymphoma of bone . in order to account for the various clinical indicators , this study utilized the large patient population to better analyze the relative prognostic significance of patient- and tumor - related predictors of overall survival from the disease . to our knowledge , this is one of the largest studies of patients with primary lymphoma of bone published in the english language medical literature . among the strengths of a large , population - based study is the inclusion of a larger collection of patients than would be feasible for a single institution study of such a rare disease , as well as the ability to sample a cross - section of the united states population . single institution studies have been published on individual chemotherapy regimens , as well as the individual prognostic potentials of several laboratory values ( i.e. lactate dehydrogenase ) . however , the seer database does not include data on chemotherapy , thus the relative effect of chemotherapy treatment regimens could not be evaluated in our analysis . we addressed the concern over evolving chemotherapy protocols by limiting the study to a 15-year period . while the authors recognize that significant improvements in imaging , staging , and clinical care have been made over the study period , there was no significant change in the incidence or overall survival over the course of this study , thereby supporting a stable clinical period for analysis . limiting the years of the study also helped control for the changes in classification and categorization of the disease , while allowing for long - term follow - up for overall survival . we found that appendicular tumor location is an independent predictor of survival in multivariable analysis when compared with axial location . while this has been suggested by previous authors , other relatively large studies investigating plb have not yielded significant prognostic importance for overall survival , when considering confounding variables . age at time of diagnosis was also an independent predictor of survival , which has been consistently demonstrated in prior analyses . age over 60 years has previously been shown to influence both overall and disease - specific survival , so these findings are not entirely related to mortality from unrelated conditions . however , the ability to endure chemotherapy due to age and comorbidities may plan a significant role in considering treatment options . in the current study , multivariable analysis demonstrated that divorced , separated , or widowed patients have a significantly poorer prognosis than married patients , independent of age . there was insufficient data available from the seer database to elucidate the cause of this finding . , also demonstrated that marital status was an independent predictor of survival following oncologic diagnoses . they reported that the survival benefit associated with marriage was larger than the published survival benefit of chemotherapy for prostate , breast , colorectal , esophageal and head / neck cancers . marital status was associated with lower stage at presentation in that study , suggesting that these findings may be due to lead time bias of earlier detection in married patients , rather than a true reflection of improved mortality . in conclusion , there is evidence to suggest that socioeconomic factors , as well as clinical factors , contribute to the overall survival in patients with primary lymphoma of bone . younger age , appendicular tumor location , and being married appear to be good prognostic factors for survival among patients with plb .
backgroundprimary lymphoma of bone ( plb ) is a rare disease , comprising a malignant lymphoid infiltrate of bone . 
 the goal of this study was to identify socioeconomic , demographic , and anatomic factors as prognostic indicators of survival for this disease using the surveillance , epidemiology , and end results ( seer ) database.methodsthe seer database was used to identify a study population of 692 patients diagnosed with plb in the united states from 1989 to 2003 . 
 survival was analyzed using the kaplan  meier method , with effects of potential prognostic factors on survival analyzed using the log - rank test . 
 multivariable analysis was performed by cox proportional hazards regression.resultsthe overall 5-year survival rate was 49.6% , with a 10-year survival rate of 30.2% . 
 median overall survival was 4.9 years ( 95% ci : 3.9 , 6.1 ) . 
 in multivariable analysis , age ( p<0.0001 ) , marital status ( p=0.006 ) , and appendicular vs. axial tumor location ( p=0.004 ) were found to be independent predictors of survival.conclusionsthis population - based study of plb identified age , marital status , and tumor location as independent indicators of prognosis . 
 this finding supports the clinical suspicion that an appendicular tumor location confers a better prognosis than an axial tumor location .