Classification

Etiology

Incidence

NHL is less common than HL and accounts for less than 5% of pediatric malignancies. NHL is more common in males. The male to female ratio of involvement is 3:1.

Children at any age can get NHL, but kids ages 7 to 11 are affected most often. NHL is rare at less than 5 years of age, with an incidence of 2.8 per million cases but increases dramatically after age 20.

The etiology of NHL is unknown. DNA and RNA viruses are thought to play an important role in the pathogenesis of NHL. The link between Epstein-Barr virus (EBV) and endemic forms of Burkitt's lymphoma observed in Africa and New Guinea is well known. EBV deoxyribonucleic acid (DNA) and nuclear antigens have been identified in 95% of African Burkitt's lymphoma tumor cells. A sporadic form of Burkitt's lymphoma occurs in Europe and America. Although histologically similar to the Burkitt's lymphoma of Africa, only 15% have tumors with identifiable EBV DNA. In addition, many cases of Burkitt's lymphoma have a translocation of a segment of the long arm of chromosome 8 containing the c-myc protooncogene.

The Epstein-Barr virus is also associated with other large-cell lymphomas found in immunosuppressed patients (HIV, Wiscott-Aldrich syndrome, Bloom syndrome, ataxia telangiectasia, X-linked lymphoproliferative syndrome and organ transplant recipients on immunosuppression).

In children with NHL, more than 90% of tumors belong to three histological subtypes:

v Lymphoblastic lymphoma;

v Small non-cleaved cell lymphoma (including Burkitt's and non-Burkitt's lymphomas);

v Large cell lymphoma (histiocytic).

Each of these categories is subdivided on the basis of histology and/or immunophenotype.

Lymphoblastic lymphomas account for 30% of childhood NHL and are mainly tumors of thymocytes (i.e., T-cell) origin. They consist of lymphoblasts that are morphologically identical to T-lymphoblasts of acute leukemia.

Small non-cleaved cell lymphomas (Burkitt's and non-Burkitt's) account for 40-50% of childhood NHL. Small noncleaved cell lymphomas originate from B-cells.

Large-cell lymphomas (LCL), formerly histiocytic lymphoma, account for 20-25% of childhood NHL. There are three subtypes based on reactivity to T- or B-cell antibodies: B-lineage, T-lineage, or indeterminate lineage.

B-lineage large-cell lymphoma is further divided into large cleaved, large noncleaved and immunoblastic lymphoma; although the distinction is probably not of major clinical significance. B-cell LCL is often immunotypically similar to small noncleaved lymphomas.

T-lineage large-cell lymphomas are divided into two groups: CD30 positive anaplastic LCL and other T-cell lymphomas. Over 90% of anaplastic large cell lymphomas are CD30 positive and the majorities are of T-cell immunophenotype.