Page 80 - Haematologica Atlas of Hematologic Cytology

AB
CD
Figure . Myeloid/lymphoid neoplasm with FGFR1 rearrangement. (A and B) The same bone marrow smear as in Figure 5 shows, at higher magnification, normal morphology of eosinophils; blast cells are medium-sized, with agranular cytoplasm, high nuclear:cytoplasmic ratio, rather condensed chromatin, and irregular nuclear shape. Blasts showed immature T-cell immunophenotype: CD1a, CD2, CD3, CD45, CD99 and TdT positive, CD7, CD10, CD14, CD20, CD68, CD79a, myeloperoxidase and lysozyme negative. (C and D) Aspiration cytology of a cervical lymph node revealing mature lymphocytes, many blasts similar to bone marrow blasts, and scattered eosinophils and precursors. Lymph node blast immunophenotype was identical to that of bone marrow blasts suggesting a diagnosis of precursor T-lymphoblastic leukemia/lymphoma. The cytogenetic analysis of peripheral blood and bone marrow showed a reciprocal balanced translocation (8;13)(p11; q12), whereas molecular analysis demonstrated the fusion of the ZMYM2 gene at 13q12.1 to the entire catalytic domain of fibroblast growth factor receptor 1 (FGFR1) at 8p11.2. On the basis of these findings, myeloid/lymphoid neoplasm with FGFR1 rearran- gement was diagnosed. This disorder arises from a pluripotent stem cell able to differentiate into B- and T-lym- phoid lineages, as well as myeloid lineages. It is characterized by the association of lymphoblastic lymphoma, usually of the T lineage but, although rarely, also of the B lineage, a myeloproliferative disorder with eosinophilia and a chromosomal translocation with an 8p11-12 breakpoint. Characteristic clinical features include systemic symptoms, diffuse lymphadenopathies in the absence of a mediastinal mass, frequent splenomegaly, and leu- kocytosis with neutrophilia, eosinophilia, monocytosis, and circulating myelocytes and metamyelocytes. Survival is usually short, because the disorder evolves into acute myeloid leukemia within 1 or 2 years of diagnosis. Since chemotherapy alone cannot eradicate the neoplastic clone, only allogeneic stem cell transplantation appears to offer a chance of cure. The molecular abnormalities caused by t(8;13) and by variant translocations have been identified. The FGFR1 gene is constantly disrupted. The products of the fusion genes show constitutive tyrosine kinase activity, activate multiple pathways of signal transduction, and may play an essential role in the pathoge- nesis of the disorder.
67