Extensive Bone Marrow Involvement by

Background: Erdheim-Chester disease (ECD) is a recently recognized clonal hematopoietic neoplasm characterized by activating alterations in the MAPK pathway. It involves multi-organ accumulation of abnormal histiocytes, leading to nonspecific clinical manifestations due to inflammation and fibrosis caused by histiocytic infiltration. Case Presentation: We present a 45-year-old male with nonspecific clinical symptoms and progressive skin and abdominal lesions. Multiple tissue biopsies revealed fibrohistiocytic infiltration but provided an inconclusive diagnosis. Imaging studies showed extensive fibrosis in the perinephric regions on CT and sclerotic foci in long and pelvic bones on PET/CT. Bone marrow biopsy revealed abnormal histiocytes with multinucleated giant forms, prominent emperipolesis, active hemophagocytosis, and condensed hemosiderin deposition. Immunohistochemistry showed positive histiocytes for CD68, CD163, and partially for S-100. Molecular analysis confirmed the Conclusion: The case highlights the need to recognize that ECD diagnosis requires integrating histopathology with clinical and radiographic findings. It emphasizes the importance of awareness of mixed histiocytosis features and the role of detecting BRAF mutations, even through immunohistochemistry, in suspected histiocytic neoplasms. Extensive bone marrow involvement by ECD is rarely described. To our knowledge, there are no prior reports of bi-phenotypic (concurrent) ECD/RDD mixed histiocytosis affecting the bone marrow.