An Unusual Presentation of Philadelphia Chromosome Positive B-Cell Acute Lymphoblastic Leukemia With Isolated...

Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph + B-ALL) is a high-risk subtype of ALL characterized by the presence of the BCR-ABL1 fusion gene and typically presents with diffuse bone marrow involvement, circulating blasts, and systemic symptoms. While extramedullary disease may occur, it is rarely the dominant or sole feature at diagnosis. Isolated skeletal involvement with a normal bone marrow evaluation is exceedingly rare and diagnostically challenging.

We report the case of a 56-year-old Caucasian female who presented with progressive left hip pain and extensive lytic skeletal lesions, initially raising concern for multiple myeloma or metastatic cancer. Imaging revealed multifocal FDG-avid lesions in the skeleton without evidence of a systemic disease. Bone biopsy confirmed precursor B-lymphoblastic leukemia with expression of CD45, CD34, CD79a, TdT, and CD99, and eventually detection of BCR::ABL1 p190 transcript, consistent with Ph + B-ALL. Surprisingly, bone marrow aspirate and biopsy showed normocellular trilineage hematopoiesis without morphologic or immunophenotypic evidence of leukemia. The patient was treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine (HyperCVAD/MA) plus dasatinib followed by allogeneic stem cell transplantation, achieving complete molecular and metabolic remission.

This case highlights an atypical presentation of Ph + B-ALL with isolated extramedullary skeletal involvement and a normal bone marrow at diagnosis. Such presentations, although rare, underscore the importance of maintaining a broad differential diagnosis in patients with unexplained lytic bone lesions and unremarkable hematologic findings. Early biopsy and appropriate molecular testing of affected tissue are essential for timely diagnosis and initiation of appropriate targeted therapy.