Acute Myeloid Leukemia With KMT2A Rearrangement Presenting as Skin Hyperpigmentation

Leukemia cutis (LC) is a rare extramedullary manifestation of leukemia, most commonly associated with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). The classic clinical presentation of LC usually includes various cutaneous lesions such as papules, nodules, and plaques. There are limited case reports describing a primary presentation with hyperpigmented macules and patches. This case report describes a 29-year-old male, diagnosed with AML, who initially presented with extremity skin dyspigmentation, unexplained lymphadenopathy, and fatigue. A skin biopsy revealed a dense periadnexal and perivascular infiltrate of atypical blastoid cells. Special stains for melanin (Fontana Masson) and iron were negative for abnormal deposition. Immunohistochemical stains showed scattered immature leukocytes (myeloperoxidase-positive), CD4-positive cells consistent with flow cytometry, and weak CD56 staining of admixed cells within the dense infiltrates. The patient was diagnosed with AML with an 11q23 KMT2A::AFF1 gene rearrangement-a mutation increasingly associated with a poor prognosis. This case underscores the importance of recognizing hyperpigmentation as a rare but potential manifestation of LC, especially in younger patients, and highlights the need for prompt diagnosis and intervention to improve patient outcomes.