Leukemia Cutis in T-Cell Prolymphocytic Leukemia with KDM6A Mutation: A Case Report

Summary: T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive mature T-cell neoplasm with systemic manifestations such as lymphocytosis, hepatosplenomegaly, and bone marrow involvement. Cutaneous infiltration, termed leukemia cutis (LC), is infrequent and signifies advanced disease. We present a 49-year-old female with T-PLL, diagnosed 4 years previously, who developed progressive erythematous and violaceous plaques on the abdomen and extremities. Skin biopsy revealed a dense dermal infiltrate of atypical T cells expressing CD3, CD4, CD5, CD8, and Ki67 (60–70%) with negative CD20 and CD56, confirming LC. Peripheral blood flow cytometry demonstrated a clonal T-cell population with CD3, CD4, CD5, CD7, and dual CD4/CD8 co-expression. Bone marrow biopsy showed >95% infiltration by leukemic T-cells. Molecular analysis detected TCL1A rearrangement (45% of nuclei), trisomy/tetrasomy 8 with MYC gain, and a KDM6A mutation, highlighting an aggressive molecular profile. Despite treatment with Alemtuzumab, Venetoclax/Cladribine combinations, radiotherapy, and two allogeneic hematopoietic stem cell transplants, the disease progressed with extramedullary involvement, including LC, and resistance to therapies. The discovery of a KDM6A mutation underscores its potential as a biomarker for pathogenesis and targeted therapy in T-PLL. This case highlights the diagnostic and therapeutic challenges in T-PLL with LC and the need for novel, multidisciplinary management strategies.