Philadelphia Chromosome-Negative Hyperdiploid B-cell Acute Lymphoblastic Leukemia Presenting As Hemophagocytic...

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory syndrome that can mask underlying malignancies. We report a 22-year-old woman who presented with fatigue, night sweats, pancytopenia, hyperferritinemia, and abnormal liver function tests, without peripheral blasts. Imaging revealed no organomegaly or significant lymphadenopathy. Initial evaluation suggested HLH or severe infection. Bone marrow biopsy confirmed Philadelphia chromosome-negative, hyperdiploid B-cell acute lymphoblastic leukemia (B-ALL). The patient received supportive care with intravenous antibiotics, growth factor support, and tumor lysis prophylaxis. She commenced induction chemotherapy with the UKALL14 Regimen B protocol. Hyperinflammation was controlled with corticosteroids, and she remained clinically stable during induction. This case highlights the diagnostic challenge of malignancy-associated HLH, particularly when peripheral blasts are absent and imaging is non-specific. Masked leukemia presentations can delay recognition of the underlying cancer, leading to treatment delays. High hyperdiploidy usually confers a favorable prognosis, but its association with HLH is rare. Clinicians should consider early bone marrow evaluation in young adults with unexplained cytopenias, systemic inflammation, and markedly elevated ferritin, even in the absence of peripheral blasts. Prompt diagnosis and timely initiation of chemotherapy are critical to improve outcomes.