[Erdheim-Chester disease: a clinicopathological analysis of 16 cases]

Objective: To investigate the clinicopathological features, diagnosis, and prognosis of Erdheim-Chester disease. Methods: The clinical and imaging data of 16 patients with Erdheim-Chester disease diagnosed in the Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from August 2002 to July 2025 were retrospectively analyzed. A comprehensive evaluation was conducted on histopathology, immunophenotype, molecular characteristics, clinical treatment and follow-up outcomes, supplemented by a review of relevant literature. Results: There were 16 patients with Erdheim-Chester disease, including 7 males and 9 females. The age at onset ranged from 38 to 70 years, with an average age of 48.0 (43.5, 54.5) years. Two of the 16 cases were complicated by Langerhans cell histiocytosis. Isolated skeletal involvement was observed in 5 cases (most commonly affecting the long bones of the lower extremities), while skeletal involvement with extra-skeletal systemic manifestations (including pulmonary, pituitary, urinary system, pericardial, and aortic involvements) was identified in 11 cases. The characteristic imaging presentation consisted of bilateral symmetric, multifocal diffuse osteosclerosis predominantly involving the diaphyses and metaphyses of long bones. Bone scintigraphy revealed symmetrically increased radiotracer uptake. Magnetic resonance imaging showed hypointense signals on T1-weighted images and heterogeneously hyperintense signals on T2-weighted images, with significant enhancement observed after contrast administration. Histopathological examination revealed osteosclerosis accompanied by infiltration of abundant lipid-laden foamy histiocytes or small mononuclear histiocytes within the intertrabecular spaces. These cells exhibited uniformly eosinophilic, pale pink-stained cytoplasm and round to oval nuclei with inconspicuous nucleoli. The lesion was also characterized by variable numbers of Touton giant cells and varying degree of fibrosis. Immunohistochemical analyses demonstrated the expression of CD68, CD163, and PGM1, but no expression of S-100 or Langerin. BRAF V600E gene mutation was detected in five cases. Clinical management regimens encompassed curettage of intraosseous lesions, potentially combined with adjuvant therapies such as hormonal agents, chemotherapy, interferon-alpha, or BRAF V600E inhibitors. At the end of follow-up (ranging from 2 to 18 years), seven patients died of the disease, six survived with it, and three remained disease-free. Conclusions: Erdheim-Chester disease is a rare condition characterized predominantly by multifocal and symmetrical involvement of long bones, with the majority of patients presenting with systemic manifestations. Pathological examination combined with imaging studies aids in distinguishing it from inflammatory disorders and other histiocytic proliferative lesions. The overall prognosis is poor, especially in cases involving multiple bones and systemic involvement.