Case Presentation: A 56-year-old Caucasian male with no pertinent medical history presented with 4 months of progressive left lower extremity weakness, gait instability, headache, and an 8-lb weight loss. Physical exam was notable for left leg spasticity, positive left Babinski sign, and asymmetric dysmetria on heel to shin on his left compared to his right lower extremity. CT head showed a grapelike cluster of peripherally enhancing lesions in the right parietal lobe with vasogenic edema. CT abdomen showed a pleural-based soft tissue mass in the right lower lobe, a right perinephric soft tissue mass, and a proximal left femur mass. No infectious etiology was found. Biopsy of the masses showed xanthomatous histiocytes positive for CD163 and negative for S100 and BRAF2, and a diagnosis of Erdheim-Chester disease was made.
Discussion: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytic disorder with approximately 500 cases reported in the literature. Its characteristic manifestations are caused by neoplastic proliferation of histiocytes, leading to inflammatory infiltration and thickening of affected tissues. Patient presentations are highly variable and symptoms are often nonspecific; back or bone pain, constitutional symptoms, or ataxia are common and the extent of involvement may range from subclinical infiltration of target organs to obvious masses. Despite its protean nature, ECD is associated with certain clinical findings, including long bone osteosclerosis, periarterial thickening, pericardial thickening with or without tamponade, retroperitoneal fibrosis, and primary diabetes insipidus due to hypothalamic or pituitary infiltration.
ECD is diagnosed with tissue biopsy of an affected area. Biopsy typically reveals xanthomatous histiocytes with a background of fibrosis. Like Langerhans cell histiocytosis, cells stain positive for CD163; however in ECD, stains for S100 and Langerin (CD207) are negative.
Due to its rarity and paucity of data regarding treatment, the prognosis of ECD has historically been poor, with as few as 43% of patients alive at 32 months post-diagnosis. Accordingly, treatment previously relied largely on untargeted therapies, such as interferon-alpha, IL-1 antagonists, corticosteroids, and cytotoxic chemotherapy. However, with the entrance of molecular markers, the treatment paradigm has shifted in favor of targeted therapies. The BRAF V600E proto-oncogene has been identified in more than 50% of ECD cases. Treatment with vemurafenib, a BRAF inhibitor, has resulted in dramatic improvement clinically and radiologically. In addition, tyrosine-kinase inhibitors are often used when mutations in C-KIT and BCR-ABL are identified.
Conclusions: Although exceedingly rare, ECD should be considered in a patient with constitutional symptoms and long bone or extra-skeletal inflammatory changes. Furthermore, ECD is an example of how molecular markers allow for targeted treatment of rare malignancies.