Acute lymphoblastic leukemia followed by a clonally-unrelated EBV-positive non-Hodgkin lymphoma and a clonally-related myelomonocytic leukemia cutis.

Background: Complicating malignant hematopoietic proliferations might severely hamper the course of acute lymphoblastic leukemia (ALL) in patients with an otherwise good prognosis. It is important to distinguish whether such neoplastic proliferations represent ALL relapses or secondary treatment-related malignancies.

Procedure: We present an 11-year-old girl with precursor-B-ALL in whom maintenance treatment was complicated by an isolated ALL relapse in the brain, nodular lymphoproliferations in the liver, and an isolated myelo-monocytic leukemia cutis. All these hemato-oncologic malignancies occurred in the background of a secondary immunodeficiency, most likely caused by cytotoxic treatment.

Results And Conclusions: Using a stepwise molecular approach, we were able to demonstrate that the liver infiltrates were Epstein-Barr virus (EBV)-positive, contained monoclonal mature B-cells with immunoglobulin heavy chain gene (IGH) gene rearrangements unrelated to the primary ALL, and thus represented a true secondary non-Hodgkin lymphoma (NHL). In contrast, the skin infiltrates consisted of myelo-monocytic cells with clonal IGH and T-cell receptor gamma gene rearrangements, identical to the precursor-B-ALL blasts at diagnosis. Thus, the disease course of the precursor-B-ALL patient was complicated by two different isolated extramedullary relapses (brain and skin) and a secondary EBV(+) B-NHL.