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).
On the basis of clinical response to treatment, NHL of childhood and adolescence currently falls into the following three therapeutically relevant categories:
- Mature B-cell NHL (Burkitt and Burkitt-like lymphoma/leukemia and diffuse large B-cell lymphoma).
- Lymphoblastic lymphoma (primarily precursor T-cell lymphoma and, less frequently, precursor B-cell lymphoma).
- Anaplastic large cell lymphoma (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 are classified according to WHO nomenclature as (1) early lesions, (2) polymorphic, and (3) monomorphic. While the majority of posttransplant lymphoproliferative diseases are of B-cell phenotype, approximately 10% are mature (peripheral) T-cell lymphomas.
Other types of lymphoma, such as peripheral T-cell lymphoma, T/NK lymphomas, cutaneous lymphomas, and indolent B-cell lymphomas (e.g., follicular lymphoma), are more commonly seen in adults and occur rarely in children. Refer to the following PDQ summaries for more information:
- Adult Non-Hodgkin Lymphoma.
- Primary CNS Lymphoma.
- Mycosis Fungoides and the Sézary Syndrome.
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. For the most part, the remaining categories do not pertain to pediatric NHL and are not shown.
Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa
|Category (WHO Classification/ Updated REAL)||Category (Working Formulation)||Immuno-phenotype||Clinical Presentation||Chromosome Translocation||Genes Affected|
|CNS = central nervous system; ML = malignant lymphoma; REAL = Revised European-American Lymphoma; WHO = World Health Organization.|
|a Adapted from Percy et al.|
|Burkitt and Burkitt-like lymphomas||ML small noncleaved cell||Mature B cell||Intra-abdominal (sporadic), head and neck (non-jaw, sporadic), jaw (endemic), bone marrow, CNS||t(8;14)(q24;q32), t(2;8)(p11;q24), t(8;22)(q24;q11)||C-MYC,IGH,IGK,IGL|
|Diffuse large B-cell lymphoma||ML large cell||Mature B cell; maybe CD30+||Nodal, abdominal, bone, primary CNS (when associated with immunodeficiency), mediastinal||No consistent cytogenetic abnormality identified|
|Lymphoblastic lymphoma, precursor T-cell leukemia, or precursor B-cell lymphoma||Lymphoblastic convoluted and non-convoluted||Pre-T cell||Mediastinal, bone marrow||MTS1/p16ink4a; DeletionTAL1t(1;14)(p34;q11), t(11;14)(p13;q11)||TAL1, TCRAO, RHOMB1, HOX11 |
|Pre-B cell||Skin, bone, mediastinal|
|Anaplastic large cell lymphoma, systemic||ML immunoblastic or ML large||CD30+ (Ki-1+)||Variable, but systemic symptoms often prominent||t(2;5)(p23;q35); less common variant translocations involvingALK||ALK,NPM|
|T cell or null cell|
|Anaplastic large cell lymphoma, cutaneous||CD30+ (Ki-usually)||Skin only; single or multiple lesions||Lacks t(2;5)|