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A male in his 50s presented with profound leucocytosis, systemic symptoms and marked hepatosplenomegaly. Initial workup with peripheral blood flow cytometry suggested T-cell prolymphocytic leukaemia as the most likely diagnosis. However, bone marrow biopsy with comprehensive immunogenetic testing ultimately identified anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in its leukemic phase. The treatment course was with targeted agents with less immunosuppressive risk, after taking into consideration that he was a Jehovah’s Witness, who would not be able to receive blood products. Despite a transient response, the disease progressed rapidly. This case underscores the importance of a broad differential diagnosis, judicious use of advanced diagnostics and individualised treatment planning, particularly in rare and aggressive lymphoproliferative disorders.