Childhood Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Cellular Classification of Childhood NHL
Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa continued...
Involvement of the bone marrow may lead to confusion as to whether the patient has lymphoma with bone marrow involvement or leukemia with extramedullary disease. Traditionally, patients with more than 25% marrow blasts are considered to have leukemia, and those with fewer than 25% marrow blasts are considered to have lymphoma. It is not yet clear whether these arbitrary definitions are biologically distinct or relevant for treatment design.
Anaplastic large cell lymphoma
Anaplastic large cell lymphoma accounts for approximately 10% of childhood NHL. While the predominant immunophenotype of anaplastic large cell lymphoma is mature T-cell, null-cell disease (i.e., no T-cell, B-cell, or NK-cell surface antigen expression) does occur. The WHO classification system classifies anaplastic large cell lymphoma as a peripheral T-cell lymphoma. Many view ALK-positive anaplastic large cell lymphoma differently than other peripheral T-cell lymphoma because prognosis tends to be superior to other forms of peripheral T-cell lymphoma. All anaplastic large cell lymphoma cases are CD30-positive and more than 90% of pediatric anaplastic large cell lymphoma cases have a chromosomal rearrangement involving the ALK gene. About 85% of these chromosomal rearrangements will be t(2;5)(p23;q35), leading to the expression of the fusion protein NPM-ALK; the other 15% of cases are comprised of variant ALK translocations. Anti-ALK immunohistochemical staining pattern is quite specific for the type of ALK translocation. Cytoplasm and nuclear ALK staining is associated with NPM-ALK fusion protein, whereas cytoplasmic staining only of ALK is associated with the variant ALK translocations. There is no correlation between outcome and ALK translocation type. In a series of 375 children and adolescents with systemic ALK-positive anaplastic large cell lymphoma, the presence of a small cell or lymphohistiocytic component was observed in 32% of patients and was significantly associated with a high risk of failure in the multivariate analysis, controlling for clinical characteristics (hazard ratio, 2.0; P = .002).
Clinically, systemic anaplastic large cell lymphoma has a broad range of presentations, including involvement of lymph nodes and a variety of extranodal sites, particularly skin and bone and, less often, gastrointestinal tract, lung, pleura, and muscle. Involvement of the CNS and bone marrow is uncommon. anaplastic large cell lymphoma is often associated with systemic symptoms (e.g., fever, weight loss) and a prolonged waxing and waning course, making diagnosis difficult and often delayed. Patients with anaplastic large cell lymphoma may present with signs and symptoms consistent with hemophagocytic lymphohistiocytosis. There is a subgroup of anaplastic large cell lymphoma with leukemic peripheral blood involvement. These patients usually exhibit significant respiratory distress with diffuse lung infiltrates or pleural effusions and have hepatosplenomegaly. Most of these patients have an aberrant T-cell immunophenotype with frequent expression of myeloid antigens. Patients in this anaplastic large cell lymphoma subgroup may require more aggressive therapy.[37,38]