Contemporary Perspectives on Primary Extramedullary Acute Promyelocytic Leukaemia: Expanding the Clinical Spectrum

Abstract

Acute promyelocytic leukaemia is a distinct subtype of acute myeloid leukaemia defined by the PML-RARA fusion gene and responsiveness to differentiation-based therapy with all-trans retinoic acid and arsenic trioxide. Although acute promyelocytic leukaemia typically presents with bone marrow involvement, cytopenias, and coagulation abnormalities, extramedullary manifestations have been increasingly described. Primary extramedullary acute promyelocytic leukaemia refers to leukaemic infiltration outside the bone marrow at diagnosis, with absent or minimal marrow involvement. This rare presentation may create diagnostic uncertainty because it can resemble solid tumours, lymphoma, infection, or inflammatory disease. This narrative review examines current evidence on the epidemiology, biological basis, clinical presentation, diagnosis, treatment, and follow-up of primary extramedullary acute promyelocytic leukaemia. The reviewed literature includes clinical studies, guidelines, reviews, and case reports, with attention to central nervous system, skin, lymph node, soft tissue, orbital, gastrointestinal, bone, and visceral involvement. Molecular confirmation of PML-RARA remains essential for diagnosis, irrespective of disease location. Histopathology, immunophenotyping, cytogenetic assessment, and molecular testing are therefore central to accurate recognition. Treatment evidence remains limited because most data derive from case reports and small series. Systemic all-trans retinoic acid- and arsenic trioxide-based therapy remains central, while chemotherapy, radiotherapy, intrathecal therapy, or site-directed intervention may be considered according to disease burden, anatomical site, and clinical risk. Long-term surveillance is important because isolated extramedullary relapse may occur after apparent remission.