Abstract
A 59-year-old woman with persistent lower-leg erythema and pain, initially misdiagnosed as cellulitis, was later diagnosed with erythema nodosum (EN) and acute myeloid leukemia (AML), French-American-British (FAB) subtype M2, carrying a FLT3-internal tandem duplication (ITD) mutation. FLT3 mutations, common in AML-M2 and M4, activate PI3K/AKT and STAT5 pathways, driving cytokine production (tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF)) and contributing to EN as a paraneoplastic phenomenon. This case highlights the role of FLT3 mutations in AML-associated inflammation and the importance of distinguishing paraneoplastic from drug-induced EN to guide treatment strategies.