Erdheim-Chester Disease: The Importance of Information Integration

Abstract

Background: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis disorder that utilizes the RAS-RAF-MEK-ERK pathway. It has a highly variable clinical presentation, where virtually any organ can be involved, thus having the potential of posing a great diagnostic challenge. Over half of the reported cases have the BRAF V600E mutation and have shown a remarkable response to vemurafenib.

Case presentation: We describe herein a patient with a history of stroke-like symptoms and retroperitoneal fibrosis that on initial pathology raised the possibility of IgG4-related disease. However, the patient was refractory to high-dose steroids and progressed further, developing an epicardial soft tissue mass and recurrent neurological symptoms. Integration of the above findings with new information at another hospital about a radiological history of symmetrical lower extremities long bone lesions raised the differential diagnosis of ECD. Molecular analysis of formalin-fixed paraffin-embedded tissue of both of the patient's retroperitoneal biopsies (the second one of which had shown a small focus of foamy histiocytes, CD68+/CD1a-) was positive for BRAF mutation, confirming the diagnosis of ECD. The patient demonstrated a dramatic and sustained metabolic response to vemurafenib on follow-up positron emission tomography scans.

Conclusion: This case highlights the need for developing a high index of suspicion for presentations of retroperitoneal fibrosis that could represent IgG4-related disease but fail to respond to steroids. When unusual multisystem involvement occurs, one should consider a diagnosis of a rare histiocytosis. Vemurafenib appears to be an effective treatment for even advanced cases of both ECD and Langerhans histiocytosis bearing the BRAF V600E mutation.

Keywords: BRAF V600E; Erdheim-Chester disease; IgG4-related disease; Vemurafenib.

Fig. 1

Photomicrograph of the patient's second biopsy. Hematoxylin and eosin-stained section, at 5× (a) and 20× (b) magnifications. The asterisk in a represents the magnified area seen in b; the arrowhead in b points to a representative foamy histiocyte.

Fig. 2

FDG PET maximum intensity projection images at baseline (a) and 3 months after treatment (b). Black arrowheads show the right atrium, white arrowheads show the pelvic and femoral bone lesions.