Leukemia Cutis at Initial Diagnosis of Acute Myeloid Leukemia Consistent With Therapy-Related Disease After Lung Cancer Chemotherapy: A Case Report.

Introduction: Leukemia cutis (LC) is characterized by dermal infiltration of leukemic blasts and typically occurs in patients with known leukemia. Rarely, LC is identified at the time of initial diagnosis of systemic disease, especially acute myeloid leukemia (AML). We describe a case of LC identified at the initial diagnosis of AML consistent with therapy-related disease in a patient with metastatic non-small-cell lung cancer (NSCLC) previously treated with cytotoxic chemotherapy and immunotherapy. Case Presentation: A 78-year-old woman with Stage IV NSCLC (adenocarcinoma, no actionable mutations, PD-L1 negative) initially received carboplatin, pemetrexed, and pembrolizumab, complicated by neutropenic fever. She later enrolled in the SHERLOC trial (MM-121 + docetaxel), discontinued due to colitis and neutropenia. Maintenance therapy with pembrolizumab was continued intermittently alongside stereotactic body radiation and cryoablation. After several years of disease control, follow-up PET/CT demonstrated new adrenal and iliac bone lesions concerning for progression. Shortly thereafter, she developed multiple pruritic, erythematous plaques on her extremities, accompanied by fatigue, weight loss, and cytopenias. Laboratory evaluation showed leukocytosis, macrocytic anemia, and severe thrombocytopenia, with peripheral smear revealing 72% circulating blasts. Punch biopsy confirmed LC, demonstrating dermal infiltration by myeloid blasts (CD4, CD43, CD68, and MPO positive). Flow cytometry and bone marrow biopsy established AML with > 75% myeloblasts. Next-generation sequencing identified DNMT3A, U2AF1, and PPM1D mutations. Conventional cytogenetic analysis was noninformative because no metaphase cells were obtained, AML FISH was normal, and PML-RARA FISH was negative, findings consistent with therapy-related AML. Interventions and Outcomes: The patient received hydroxyurea, transfusion support, and tumor lysis prophylaxis. Given her age, ECOG 1, adverse-risk mutations, and personal preference, she declined further chemotherapy and transitioned to hospice. Conclusion: LC at the time of initial AML diagnosis is uncommon and portends poor prognosis. Clinicians should remain vigilant for new skin lesions and cytopenias in cancer survivors previously exposed to chemotherapy, as early recognition of extramedullary AML may expedite timely diagnosis and care planning.