Toward a global understanding of lymphoma: epidemiologic clues from the second most populous country

Abstract

Observations of global and regional geographic variation off er important clues to the etiology and, perhaps, biology of disease. In cancer, this is most explicitly seen in nonHodgkin lymphoma (NHL) where there is substantial variation in both incidence and histologic subtypes around the world. NHL comprises many clinically, histologically and biologically distinctive lymphoid malignancies. Th e highest incidence rates are observed in North America and Australia, followed by Europe, with lower rates reported in Asia [1]. From 2005 to 2009, the annual age-adjusted incidence rate in the United States was 19.6 per 100 000 persons, and although the overall incidence has been stable for the past decade, incidence patterns for specifi c subtypes vary [2]. In contrast, the overall incidence of lymphomas in Asian countries is lower, and ranges from 2.1 (China) and 2.4 (India) to 5.1 (Japan) per 100 000 persons [1]. Th ere are also marked diff erences in the distribution of lymphoma subtypes across geographic regions. Compared with North America and Western European countries, Asian countries tend to have higher incidences of mature T-/natural killer (NK)-cell lymphomas and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma) and lower rates of follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and Hodgkin lymphoma [3 – 7]. It has been proposed that some Epstein – Barr virus (EBV)-associated subtypes of T/NK-cell lymphomas are unique to Asian countries and do not exist in other locales. Th is geographic and ethnic heterogeneity is well recognized but remains unexplained, mainly because the etiology of lymphoma is largely unknown, although genetic, immune, infectious, environmental and lifestyle factors have been considered as potential risk factors [8]. Nevertheless, examining patterns of specifi c lymphoma subtypes across diff erent racial/ethnic groups or countries off ers important clues regarding the study of lymphoma etiology. In this issue of Leukemia and Lymphoma , Arora and colleagues [9] review the histological material of over 5000 patients with lymphoma seen at a tertiary care center in South India over a 10-year period of time (2001 – 2010). Th is is the fi rst large-scale catalog and description of lymphoma subtypes from the second most populous country in the world. Importantly, the authors describe the subtype distribution according to the most current classifi cation, the 2008 World Health Organization classifi cation of lymphoid neoplasms. In their series, 21.3% had Hodgkin lymphoma (HL) and 78.7% had NHL. For HL, in contrast to Western populations, the authors reported no bimodal age curve and a higher frequency of mixed cellularity (45%) than nodular sclerosis subtype (36%). Of the NHLs, about 79% were B-cell and 20% were T-cell/NK-cell. Th e most common NHL was diff use large B-cell lymphoma, which constituted 47% of NHLs, followed by follicular lymphoma (11%). Th e more common occurrence of aggressive lymphomas countered by decreased frequency of indolent lymphomas is consistent with observations from other Asian countries, and is possibly related to environmental and/or infectious factors. Extranodal primaries accounted for 33% of NHLs and most frequently involved the gastrointestinal tract. Th ere are several key strengths to this report, including the central review of slides by pathologists and additional immunostains in cases where there were disagreements on the original diagnosis. As mentioned above, this is an impressive and large series from a single tertiary care center in a country where subtypes of lymphoma, in comparison to other Asian countries, have not been well described. However, this strength also brings limitations, as a tertiary hospital population has inherent referral bias. Th e frequency of a specifi c lymphoma subtype may be distorted if its underlying pathogenesis is associated with socioeconomic status and environmental or lifestyle factors. In addition, this is a hospital-based analysis and not a population-based analysis. Consequently, a direct comparison of the distribution of subtypes across hospital-based series or diff erent ethnic/racial groups is diffi cult as the actual incidence rate is not available. Furthermore, the Indian population is a mix of several ancient ethnicities, with Indo-Aryan groups