ALK-Positive Plasmablastic B-Cell Lymphoma with Expression of the NPM-ALK Fusion Transcript: Report of Two Cases

2 ABSTRACT While most ALK-positive Non-Hodgkin lymphomas (NHL) are of T-cell lineage, a small number of B-lineage tumors with plasmablastic morphology and expression of the full-length ALK protein have been described in the literature. All of these reported tumors lacked the NPM-ALK fusion transcript. There is controversy regarding the existence of ALK fusion-positive B-cell NHL, many investigators contending that ALK fusions are expressed uniquely in T-or null-cell lymphomas. Here we describe two well-characterized cases of ALK-positive B-cell lymphoma expressing the NPM-ALK fusion. Both tumors occurred in pediatric patients and showed poor response to chemotherapy. Each had plasmablastic morphology, showed IgA restriction, and was ALK-positive and CD30-negative by immunohistochemistry. One tumor showed the t(2;5)(p23;q35) chromosomal translocation by conventional cytogenetics. Both were positive for NPM-ALK by RT-PCR. Thus, ALK-positive plasmablastic B-cell lymphomas are more heterogeneous at the molecular level than previously recognized.