Co-occurrence of immature T-lymphoblastic lymphoma and acute myeloid leukemia—microenvironment-dependent lineage differentiation derived from a common progenitor?

Mixed phenotype acute leukemia (MPAL) is an uncommon disease characterized by currently only limited knowledge concerning biology, clinical presentation, and treatment outcome. We here describe a most unusual case of simultaneous occurrence of T-lymphoblastic lymphoma in cervical and mediastinal lymph nodes and acute myeloid leukemia in the bone marrow (BM) successfully treated with allogeneic stem cell transplantation (SCT). Although the blasts in both locations showed additional aberrant expression of other lineage markers (even B-cell markers), diagnostic criteria of MPAL were not fulfilled either in the LN or in the BM. We performed next generation sequencing (NGS) with the objective to look for common genetic aberrations in both tissues. Histology, immunohistochemistry, flow cytometry, AML-associated genetic alterations (FLT3, NPM1, KIT D816V, CEPBA), and clonal T-cell receptor β and γ gene rearrangements were performed according to routine diagnostic workflows. Next generation sequencing and Sanger sequencing were additionally performed in BM and LN. Somatic mutation in the EZH2 gene (p.(Arg684Cys)) was detected in the BM by NGS, and the same mutation was found in the LN. Since an identical genetic aberration (EZH2 mutation) was detected in both locations, a common progenitor with regional dependent differentiation may be involved.