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C H A P T E R 84

MALIGNANT LYMPHOMAS IN CHILDHOOD

Kara M. Kelly, Birgit Burkhardt, and Catherine M. Bollard

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Malignant lymphomas are the third most common malignancy among histologic subtype in both equatorial Africa and northeastern Brazil.
1–3
children and adolescents. Among children <15 years of age, non- There are also geographic differences in both the clinical and biologic
Hodgkin lymphoma (NHL) is more frequent; however, in patients up features of certain NHL subtypes. 7,8
to 18 years of age, Hodgkin lymphoma (HL) is predominant. NHLs
in children are usually extranodal, diffuse, high-grade tumors, whereas
low- and intermediate-grade nodal lymphomas predominate in adults. Classification
These differences are speculated to reflect maturational changes in the
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function and composition of the immune system. The different After Thomas Hodgkin described the disease bearing his name in
histologies explain in part the differing clinical features, disease course, 1832, various schemes emerged to classify the tumors now collectively
and treatment strategies used in adults and children. referred to as the NHLs. Several classification schemes were developed
The differences in treatment approach and disease subtypes are on the basis of histopathologic features and the putative cell of origin.
less striking in adults and children with HL. However, there are In an attempt to reduce the confusion of multiple classification
significant challenges in the management of children with HL. schemes, the National Cancer Institute (NCI) sponsored a workshop
These primarily comprise the sequelae of therapy, such as radiation- to design a single classification scheme for clinical use. This scheme,
induced bone growth abnormalities, endocrine dysfunction, and published in 1982 and referred to as the NCI Working Formulation,
chemotherapy-related sterility. Of greater concern are the radiation- was widely accepted for almost two decades. In the Working Formu-
and chemotherapy-related second malignancies and late cardiac lation, the NHLs of childhood are predominantly diffuse high-grade
deaths. Current trials are examining ways to reduce the toxicity tumors and can be divided among three major subgroups: lympho-
of therapy without compromising the excellent outcome generally blastic, small noncleaved cell, and large-cell lymphomas.
achieved. In the past decade, additional classification schemes were designed
to improve upon the NCI Working Formulation. Because of the
problems associated with attempts to classify lymphoid neoplasms
NON-HODGKIN LYMPHOMA into categories based on presumed normal cell counterparts, the
International Lymphoma Study Group proposed a classification
Epidemiology system for lymphoid neoplasms predicated on a practical approach
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to categorizing these diseases using available immunologic and
The incidence of NHL increases steadily throughout life, in contrast molecular genetic techniques in addition to the standard morphologic
to Hodgkin disease, which has a bimodal age distribution peaking in criteria. This Revised European-American Classification of Lymphoid
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early and late adulthood. Although NHLs may occur at any age in Neoplasms (REAL Classification) has been endorsed by many of the
childhood, they are infrequent among children younger than 3 years world’s leading lymphoma pathologists and has served as the basis for
of age; the median age at presentation is approximately 10 years. the World Health Organization (WHO) classification of hematopoi-
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NHL is two to three times more frequent in boys than in girls and etic and lymphoid tumors. Both the REAL and WHO classification
is almost twice as common in whites as in African Americans. The systems include related lymphoid leukemias and recognize that NHL
reasons for these differences have yet to be determined. 4 and acute lymphoblastic leukemia (ALL) represent different stages of
Specific populations at risk for the development of NHL include evolution within specific morphologically and immunologically
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those with either congenital or acquired immunodeficiency conditions. defined disease categories, an observation recognized by clinicians
Inherited immunodeficiency syndromes include Wiskott-Aldrich caring for children with lymphoid neoplasms and reflected in current
syndrome, X-linked lymphoproliferative syndrome (XLP), and ataxia clinical practice, which prescribes similar therapies for lymphomas
telangiectasia (AT). The recognition of these syndromes in children and leukemias of related phenotype.
with newly diagnosed NHL is important for appropriate therapeutic In the REAL and WHO classification systems, NHLs are classified
design. For example, involved field irradiation and radiomimetics on the basis of phenotype (B lineage vs. T lineage vs. natural killer
should be avoided in children with AT. Additionally, children with [NK] cell lineage) and differentiation (precursor vs. mature). Hence,
AT are at increased risk for the development of cyclophosphamide- NHLs that occur commonly in children appear in three major catego-
induced hemorrhagic cystitis; therefore, they should receive vigorous ries: lymphoblastic lymphoma (LBL; precursor B-cell lymphoma and
hydration and uroprotectants (e.g., mesna) when administering any precursor T-cell lymphoma), mature B-cell NHL (Burkitt and
dose of cyclophosphamide. XLP should be considered in any male Burkitt-like lymphoma and diffuse, large B-cell lymphoma [DLBCL]),
with a high-grade B-cell lymphoma who either develops a late recur- and anaplastic large-cell lymphoma (ALCL; mature T-cell or null-cell
rence (second occurrence) of a high-grade B-cell lymphoma or has a types). The current version of the WHO classification introduced
brother with either a high-grade B-cell lymphoma or fatal infectious pediatric follicular lymphoma, marginal zone lymphoma, and gray
mononucleosis. Children with acquired immunodeficiency conditions zone lymphoma. The clinical and biologic characteristics of NHL in
predisposing them to the development of NHL include those who children are summarized in Table 84.1 and illustrated in Fig.
have received posttransplant immunosuppressive therapy and those 84.1A–C.
with acquired immunodeficiency syndrome (AIDS).
There are differences in both the incidence and proportion of
histologic subtypes in different parts of the world. For example, the Lymphoblastic Lymphoma
NHLs are very rare in Japan but occur quite frequently in equatorial
Africa. Burkitt lymphoma, which accounts for about one-half of all Whether LBL and ALL are two clinical presentations of the same
childhood cancers in equatorial Africa, is the predominant NHL disease or two different diseases is the subject of ongoing discussion.

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