Case Report Unusual B-Lymphoid Blastic Crisis as Initial Presentation of Chronic Myeloid Leukemia Imposes Diagnostic Challenges Nouran Momen, 1 Bora Baysal, 2 Sheila Jani Sait, 2 Joseph Tario, 2 and You-Wen Qian 2 1 Clinical & Chemical Pathology Department, Cairo University, Giza, Egypt 2 Department of Pathology, Roswell Park Cancer Institute, 665 Elm Street, Buffalo, NY 14203, USA Correspondence should be addressed to You-Wen Qian; you-wen.qian@roswellpark.org Received 30 March 2022; Accepted 3 June 2022; Published 25 June 2022 Academic Editor: Massimo Breccia Copyright © 2022 Nouran Momen et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder, characterized by reciprocal translocation t(9,22) (q34; q11), leading to increased myeloid proliferation. Most cases are diagnosed in the chronic phase (CP). However, a minority of cases can be present in the blastic phase (BP). In most patients with CML-BP, the blasts have a myeloid phenotype, however, in 20–30% of cases, the blasts have a lymphoid phenotype, mostly a B-cell phenotype. It is challenging to differentiate CML B-lymphoblastic phase (CML-BLP) from Ph + primary B-acute lymphoblastic leukemia (B-ALL) especially when the CML-BLP is the initial presentation of the disease, which is uncommon. We report here an unusual case of CML-BLP as an initial presentation of the disease without typical CML morphological findings. is case demonstrates diagnostic challenges and emphasizes the importance of an integrated approach using morphology, multiparametric flow cytometry, cytogenetic studies, and molecular studies to render an accurate diagnosis. 1. Introduction Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia (Ph) chromosome generated by the reciprocal translo- cation t(9,22) (q34; q11), leading to the proliferation of granulocytes and their precursors. Around 50% of newly diagnosed CML patients are asymptomatic and are usually diagnosed when a white blood cell (WBC) count is found to be elevated during a routine medical examination [1]. Detection of BCR-ABL1 fusion is required for the diag- nosis of CML. Meanwhile, Ph chromosome/BCR-ABL1 fusion is also the most common recurrent cytogenetic abnormality in B-lymphoblastic leukemia (B-ALL) in adults, representing around 25–30% of adult B-ALL cases [2]. Different fusion proteins are produced from different BCR-ABL1 fusion transcripts depending on the break- points within the breakpoint cluster region (BCR). e most common fusion proteins are p210 and p190, in which the breakpoints are located within the major BCR (M-BCR) and minor BCR (m-BCR), respectively. In CML, almost all cases are associated with the p210, and p190 is rarely detected, whereas in Ph + B-ALL, almost all cases are associated with p190, and p210 is detected in a mi- nority of adult cases [3]. e natural progression of the disease usually follows a triphasic course; a chronic phase (CP), an accelerated phase (AP), and a blastic phase (BP). Most CML cases are diag- nosed in the CP. Patients in AP have a blast count of 10–19% in the blood or bone marrow, and BP is characterized by more than 20% blasts in the blood or bone marrow. In most patients with CML-BP, the blasts show a myeloid phenotype, however, in 20–30% of cases the blasts show a lymphoid phenotype, usually B-lymphoblasts [4]. e BP can be the initial presentation of the disease in approximately 15% of adults and 5% of children, with blasts expressing a lymphoid phenotype in 20 to 30% of these cases [5], with rare T or mixed phenotypes [6]. In those cases, with AP or BP as the initial presentation with no prior history of CML, the presence of basophilia, myeloid hyperplasia, and Hindawi Case Reports in Hematology Volume 2022, Article ID 9785588, 8 pages https://doi.org/10.1155/2022/9785588