Erdheim-Chester Disease Masquerading as Leukemia: Outwitting the Need for Transplant

Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, involves hyperproliferative histiocytes infiltrating multiple organs. Presentation is highly dependent on the organ system affected, often involving the long bones, central nervous system (CNS), skin, kidneys, and vasculature. Diagnosis is challenging due to diverse manifestations. We present a 54-year-old male with years of discordant symptoms, including psoriasiform lesions, xanthelasmas, recurrent abscesses, arthralgias, and pleural effusions, eventually presenting with diffuse bone pain. Initial evaluation revealed mild lymphocytopenia and monocytosis, prompting a bone marrow biopsy showing a KRAS mutation, raising concerns for chronic myelomonocytic leukemia (CMML). However, a skin biopsy revealed foamy histiocytic infiltration in a xanthelasma. The patient's constellation of symptoms, including skin manifestations, xanthelasmas, microabscesses, pleural effusions, and bone pain, in the context of potential malignancy, cytopenias, monocytosis, and KRAS mutation, suggested ECD. As a rare neoplasm with variable organ involvement, ECD poses a diagnostic challenge. This patient's atypical presentation included diffuse axial skeleton uptake on positron emission tomography (PET), bone pain, absence of bone marrow malignancy, fibrinous pleuritis, xanthelasmas with foamy histiocytes, and a KRAS mutation. While BRAF mutations are common in ECD, RAS isoforms occur in a smaller subset. This case highlights RAS-positive ECD, managed with KRAS pathway-targeted MEK inhibition, in line with the 2019 ECD Medical Symposium recommendations.