Cellular Classification and Clinical Presentation
In children, non-Hodgkin lymphoma (NHL) is distinct from the more common forms of lymphoma observed in adults. While lymphomas in adults are more commonly low or intermediate grade, almost all NHL that occurs in children is high grade.[1,2,3] The World Health Organization (WHO) has classified NHL on the basis of the following: (1) phenotype (i.e., B-lineage and T-lineage or natural killer [NK] cell lineage) and (2) differentiation (i.e., precursor vs. mature). The incidence of NHL observed in children and adolescents varies depending on age, gender, and histology. Regardless of age or histology, males have a higher incidence than females. Burkitt lymphoma is much more common in males, with the highest incidence between the ages of 5 years and14 years. The incidence of diffuse large B-cell lymphoma (DLBCL) increases with age in both males and females. The incidence of lymphoblastic lymphoma remains relatively constant across ages for both males and females.
Table 1. Incidence and Age Distribution of Specific Types of NHLa
ALCL = anaplastic large cell lymphoma; DLBCL = diffuse large B-cell lymphoma; NHL = non-Hodgkin lymphoma.
a Adapted from Percy et al.
b In older adolescents, histologies more common in adult patients, such as low- or intermediate-grade NHL, are beginning to be found.
|�||Incidence of NHL per million person-years|
|Age (y)||<5||5-9||10-14||15-19||<5||5-9 ||10-14||15-19|
|Other (mostly ALCL)||2.3||3.3||4.3||7.8b||1.5||1.6||2.8||3.4b|
On the basis of clinical response to treatment, NHL of childhood and adolescence currently falls into three therapeutically relevant categories: (1) mature B-cell NHL (Burkitt and Burkitt-like lymphoma/leukemia and DLBCL); (2) lymphoblastic lymphoma (primarily precursor T-cell lymphoma and, less frequently, precursor B-cell lymphoma); and (3) anaplastic large cell lymphoma (ALCL) (mature T-cell or null-cell lymphomas). NHL associated with immunodeficiency generally has a mature B-cell phenotype and is more often of large cell than Burkitt histology. Posttransplant lymphoproliferative diseases (PTLDs) are classified according to WHO nomenclature as (1) early lesions, (2) polymorphic, and (3) monomorphic.
Other types of lymphomas are more commonly seen in adults and occur rarely in children. (Refer to the PDQ summaries on the treatment of Adult Non-Hodgkin Lymphoma, Primary CNS Lymphoma, and Mycosis Fungoides and the S�zary Syndrome for more information.)
Each type of childhood NHL is associated with distinctive molecular biological characteristics, which are outlined in the following table. The Revised European-American Lymphoma (REAL) classification and the WHO classification are the most current NHL classifications utilized and are shown below. The Working Formulation is also listed for reference. The WHO classification applies the principles of the REAL classification and focuses on the specific type of lymphoma for therapy purposes. The remainder of the categories, for the most part, do not pertain to pediatric NHL and are not shown.