Unusual childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4-anaplastic lymphoma kinase gene fusion

This report describes an unusual extramedullary hematologic malignancy in a n 18-month-old child who presented with a capillary leak syndrome that evol ved into hyperleukocytosis with malignant cells. The circulating tumor cell s did not express an antigen profile typical of any subtype of leukemia com monly observed in children. Tumor cells were CD3(-)/CD56(+); had germline T CR genes; and strongly expressed CD30, epithelial membrane antigen, and ana plastic lymphoma kinase (ALK) consistent with a null cell anaplastic large cell lymphoma (ALCL). The malignant cells contained a t(2;19)(p23;p13.1) th at interrupted ALK and translocated it to the der(19). Reverse transcriptas e-polymerase chain reaction and nucleotide sequence analysis revealed fusio n of ALK to tropomyosin 4, an ALK fusion partner not described previously i n hematologic malignancies. The clinical presentation and phenotypic featur es of this malignancy were not typical for ALCL because tumor cells express ed both myeloid (CD13, CD33, HLA-DR) and natural killer (NK) cell antigens. The neoplastic cells most resembled NK cells because in addition to being CD3(-)/CD56(+) with germline TCR genes, these cells were CD25(+)/ CD122(+)/ granzyme B+ and possessed the functional properties of immature NK cells. T he unusual clinical presentation, immunophenotype, and functional propertie s of these neoplastic, cells suggest that this malignancy may be derived fr om the putative myeloid-NK precursor cell. Furthermore co-expression of NK and ALCL features supports the concept that a minority of null-ALCL may be derived from NK cells and expands the spectrum of phenotypes that can be se en in tumors produced by ALK fusion proteins.