Mixed Erdheim–Chester disease with thoraco-abdominal involvement

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis. Mixed ECD-Langerhans cell histiocytosis (LCH) is uncommon, with fewer than 200 cases reported. Diagnosis is challenging and relies on clinical, radiological, and histopathological correlation. We present the case of a 61-year-old man with night sweats, weight loss, and recently diagnosed type 2 diabetes. Imaging revealed cystic lung lesions, perirenal infiltration, and circumferential aortic wall thickening. FDG PET-CT demonstrated multifocal hypermetabolism involving lymph nodes, perirenal soft tissues, and the aortic wall, but no bone involvement. These lesions were shown to progress on subsequent imaging. A lymph node and perirenal biopsies confirmed a mixed form of ECD-LCH with BRAFV600 E mutation and associated chronic myelomonocytic leukemia. The patient was started on targeted therapy with cobimetinib, a MEK inhibitor. Mixed ECD-LCH is a rare entity that typically demonstrates more frequent and widespread organ involvement, particularly affecting the lungs. Its clinical and radiological presentation can have features of both disorders, such as bone, lung, kidney, and vascular involvement. The diagnosis is challenging and requires biopsy with histopathology and genetic testing to be confirmed. Treatment is generally targeted therapy guided by the driver mutations that are identified. We present a rare case of mixed ECD-LCH with thoraco-abdominal and pulmonary involvement. Comprehensive diagnostic workup including histopathology and molecular profiling is crucial for accurate diagnosis and initiation of targeted therapy.