Clonal evolution of chronic lymphocytic leukemia to Langerhans cell histiocytosis: a case report.

The traditional concept of unidirectional maturation of hematopoietic cells has been called into question due to the recognition of lineage plasticity, which is increasingly found also in the clonal evolution of hematopoietic and lymphoid malignancies. Here we present an unusual case of a patient with TP53-mutated chronic lymphocytic leukemia (CLL) treated with a PI3Kδ inhibitor evolving to clonally related Langerhans cell histiocytosis (LCH) with acquired BRAF V600E and STK11 mutations and loss of expression of PAX-5 and other examined B cell markers. In indolent B cell lymphoma, transformation to a more aggressive high-grade lymphoma occurs frequently during the course of disease and is thought to be caused by clonal evolution. Our case further supports the concept of significant lineage plasticity in lymphomas and raises the question of a potential role of novel pharmacologic agents in clonal evolution.