Classification of Non-Hodgkin Lymphoma in Seven Geographic Regions Around the World: Review of 4539 Cases from the International Non-Hodgkin Lymphoma Classification Project

INTRODUCTION

The distribution of non-Hodgkin lymphoma (NHL) subtypes varies around the world, but a large and systematic comparative study has not been done. This study is first to evaluate the relative frequencies of NHL subtypes in seven regions of the world.

METHODS

Five expert hematopathologists classified 4848 consecutive cases of NHL from 25 countries in seven regions, including North America, Central/South America, Western Europe, Southeastern Europe, Southern Africa, the Middle East/North Africa, and the Far East, using the WHO classification. Data from the developed world (North America and Western Europe) was compared to the developing world (all other regions combined).

RESULTS

Among the 4848 cases reviewed, 4539 (93.6%) were confirmed to be NHL, whereas the other 309 (6.4%) had diagnoses other than NHL and were excluded from further analysis. A significantly higher male to female ratio was found in the developing regions (1.4:1) compared to the developed world (1:1; p<0.05). The median age at diagnosis was significantly lower for both low grade (LG) and high grade (HG) B-NHL in the developing regions (59 and 54 yrs, respectively) compared to the developed world (62 and 64 yrs, respectively). The developing regions had a significantly lower frequency of B-NHL (86.6%) and a higher frequency of T-NHL (13.4%) compared to the developed world (90.7% and 9.3%, respectively). Furthermore, the developing regions had significantly more cases of HG B-NHL (58.7%) compared to the developed world (43.9%).  Among B-cell lymphomas, diffuse large B-cell lymphoma (42.5%) and Burkitt lymphoma (2.2%) were significantly more common in the developing regions, compared to the developed world (28.9% and 0.8%, respectively). Follicular lymphoma (15.3%), mantle cell lymphoma (3.8%), marginal zone lymphoma of mucosa-associated lymphoid tissue (5.2%), and lymphoplasmacytic lymphoma (0.3%) were significantly less common in the developing regions, compared to the developed world (25.5%, 7.8%, 8.8%, and 1.4%, respectively). Among T-cell lymphomas, precursor T-lymphoblastic lymphoma (2.9%) and nasal NK/T-cell lymphoma (2.2%) were more common in the developing regions, compared to the developed world (1.3% and 0.3%, respectively).

CONCLUSION

Our study is the first to systematically compare the relative frequencies of NHL subtypes in different regions around the world, and provides new evidence of significant geographic differences. Our findings suggest that differences in etiologic and/or host risk factors are likely responsible, and more detailed epidemiologic studies are needed to better understand these differences.