Lung cysts, a common feature found in patients with hairy cell leukemia and Langerhans cell histiocytosis

Extract Hairy cell leukaemia disorders, including classical HCL and HCL variant (HCL-V), are a heterogeneous group of mature B-cell lymphoid malignancies characterized by the presence of “hairy” cells, specific genetic abnormalities, and distinct clinical behaviours. Classical HCL is universally driven by the BRAFV600E mutation in more than 95% of cases 1, leading to constitutive activation of the MEK–ERK pathway. In contrast, HCL-V is a distinct entity associated with a poorer prognosis and defined by cells with absence of both CD25 expression and BRAFV600E mutation. Instead, MAP2K1 mutations, affecting the kinase directly downstream of BRAF, are frequent in HCL-V 2. This genomic landscape is shared with Langerhans cell histiocytosis (LCH) 3, 4 and Erdheim–Chester disease 5 (ECD), two myeloid disorders affecting multiple organs, including the lungs. Notably, pulmonary involvement is particularly frequent in LCH. Pulmonary LCH (PLCH) primarily affects young smokers of both sexes. Genetically, the BRAFV600E mutation is found in 57% of LCH cases 3, while MAP2K1 mutations are present in 42% of patients 4. High-resolution chest computed tomography (HRCT), crucial for diagnosis, typically reveals small nodules, cavitated nodules, and thick- and thin-walled cysts predominantly in the upper and middle lung fields, while the lung bases remain relatively spared. These lesions appear focal, interspersed with seemingly normal parenchyma, and involve both peripheral and central regions of the lungs 6, 7. Considering the shared genetic background, we asked whether the BRAFV600E and MAP2K1 mutations might be associated with lung cysts detected on HRCT in patients with HCL disorders.