Chronic Myeloid Leukemia Presenting with Mixed Phenotype B/Myeloid Blast Phase: A Diagnostic Challenge

Abstract

Abstract Introduction/Objective Chronic myeloid leukemia (CML) is typically identified in chronic phase, however about 5% of cases present in a more advanced phase. In blast phase (BP), the blasts are most commonly of myeloid lineage, less commonly lymphoid, and rarely mixed lineage cases are encountered. A mixed phenotype at presentation raises the possibility of a de novo mixed phenotype acute leukemia (MPAL) with BCR::ABL1 fusion and requires careful correlation with ancillary studies to confirm the diagnosis. Methods/Case Report The patient is a 60-year-old man who presented with leukocytosis, anemia, normal platelet count, and blasts identified on peripheral blood smear examination. A bone marrow biopsy demonstrated hypercellular marrow and a dimorphic population of large and small blasts, comprising nearly 70% of cellularity. Flow cytometry demonstrated distinct myeloid and B-lymphoid blast populations, both of which expressed CD13 and TdT. Interphase fluorescence in situ hybridization (FISH) showed the BCR::ABL1 fusion in more than 90% of nuclei, including segmented nuclei, and conventional cytogenetic studies showed t(9;22)(q34.1;q11.2) in 19 of 20 metaphases. Molecular studies demonstrated the minor BCR::ABL1 p190 transcript, as well as ASXL1 and dual RUNX1 mutations. The discrepant number of BCR::ABL1 positive cells by FISH and conventional cytogenetic studies compared to the proportion of blasts, and its presence in segmented nuclei, enabled a diagnosis of CML with mixed phenotype blast phase despite absence of features such as basophilia or significant granulocytic left shift. Results (if a Case Study enter NA) NA Conclusion We share this case of CML in mixed phenotype blast phase to highlight the importance of careful evaluation in distinguishing this rare presentation from de novo MPAL, particularly with BCR::ABL1 fusion. Features such as a disproportionate number of nuclei or metaphases carrying the t(9;22) translocation on FISH or conventional cytogenetic studies and the presence of BCR::ABL1 in mature granulocytes can be helpful when other morphologic features of CML are absent.