Genomics of anaplastic large cell lymphoma

While mature T cell is the predominant immunophenotype of anaplastic large cell lymphoma, null-cell disease (i.e., no T-cell, B-cell, or natural killer-cell surface antigen expression) does occur. The World Health Organization (WHO) classifies anaplastic large cell lymphoma as a subtype of peripheral T-cell lymphoma.[14,60]

All anaplastic large cell lymphoma cases are CD30-positive. 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 NPM::ALK fusion protein. The other 15% of cases are composed of variant ALK translocations.[61] The 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 proteins, whereas cytoplasmic staining of ALK is only associated with the variant ALK translocations, as shown in Table 4.[62]

In adults, ALK-positive anaplastic large cell lymphoma is viewed differently from other peripheral T-cell lymphomas because prognosis tends to be superior.[63] Also, adult patients with ALK-negative anaplastic large cell lymphoma have an inferior outcome compared with patients who have ALK-positive disease.[64] In children, however, this difference in outcome between ALK-positive and ALK-negative disease has not been demonstrated. In addition, no correlation has been found between outcome and the specific ALK-translocation type.[65-67]

One European series included 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 it was significantly associated with a high risk of failure in the multivariate analysis, controlling for clinical characteristics (hazard ratio, 2.0; P = .002).[66] The prognostic implication of the small cell variant of anaplastic large cell lymphoma was also shown in the COG-ANHL0131 (NCT00059839) study, despite using a different chemotherapy backbone.[67]

For information about the treatment of childhood anaplastic large cell lymphoma, see Childhood Non-Hodgkin Lymphoma Treatment.