Clinical Images: Erdheim–Chester disease presenting with fever, enlarged lymph nodes, and monoallelic BRAF ( V600E ) mutation

The patient, a 66-year-old woman, presented with fever and was subsequently hospitalized. Clinical evaluation revealed cachexia, along with cervical and axillary lymphadenopathy. Laboratory investigations demonstrated electrolyte imbalances and elevated markers of inflammation, whereas antinuclear antibody, extractable nuclear antigen, and antineutrophil cytoplasmic antibody tests were negative. (A) 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography imaging identified multiple soft tissue and lymph node lesions distributed systemically, accompanied by abnormal bone marrow metabolism in the facial bones, long bones of the extremities, and multiple metatarsal and phalangeal bones of both feet. Histopathological analysis of (B) lymph node and (C) lower limb bone biopsies revealed sheets of “foamy” histiocytes interspersed with inflammatory cells, with immunohistochemical staining positive for CD163, CD68, and BRAF (V600E). Next-generation sequencing of lymph node tissue confirmed the presence of a BRAF (V600E) mutation, which was identified as a monoallelic genetic alteration. Erdheim–Chester disease (ECD) represents a rare form of non-Langerhans cell histiocytosis, characterized by both inflammatory and neoplastic features.1 Although there have been reports of a higher incidence of autoimmune diseases in this condition, our patient did not reveal any concurrent autoimmune disorders.2 The diagnosis of this disease primarily relies on existing genetic diagnostic technologies, yet the heterogeneity of its clinical manifestations and the incomplete understanding of its pathophysiologic mechanisms still pose significant diagnostic and therapeutic challenges. A multidisciplinary diagnostic approach, incorporating clinical, radiologic, and histopathological assessments, is typically required.1 PET imaging serves as a valuable tool for evaluating systemic disease involvement and activity. Histopathological examination often demonstrates the presence of “foamy” histiocytes and inflammatory cell infiltration, with immunohistochemical markers CD68 and CD163 typically positive in ECD cases. Molecular analyses, including genetic testing for mutations such as BRAF (V600E), play a crucial role in confirming the diagnosis and informing targeted therapeutic strategies. Supported by the Foshan 14th Fifth High-Level Key Specialty Construction Project (grant FSGSP145030).