E-Poster Presentation ESA-SRB-ANZBMS 2021

Background: Erdheim-Chester Disease (ECD) is a rare non-Langerhan’s histiocytic disorder. ECD usually manifests as sclerosis of the long bones. Multi-organ involvement is common including pituitary infiltration, retroperitoneal fibrosis, and pericardial disease [1]. In more than 50% of ECD cases, ECD histiocytes are known to harbour the BRAF-V600E mutation but the precise pathophysiology is unclear [2].  Targeted therapies have shown efficacy in BRAF-V600-mutant ECD [3].

Case Presentation: We describe a case of diffuse skeletal ECD in a 63-year old female who presented with pain in the low limbs on the background recently diagnosed breast cancer. A staging bone scan for skeletal metastases displayed increased 99mTc activity bilaterally in the long bones of the upper and lower limbs (Figure 1A). Bone biopsy of the proximal tibia demonstrated lipid-laden, foamy histiocytes (see arrow, Figure 1D) with associated fibrosis and sclerosis, supporting a diagnosis of ECD.

BRAF codon 600 sequencing demonstrated a positive V600E mutation, a characteristic finding in BRAF mutant histiocytes. Extraskeletal involvement was excluded by FDG-PET and targeted imaging modalities.

ECD histiocytes are known to upregulate RANKL and induce local increase in osteoclast-mediated bone resorption. Hence, a RANKL inhibitor denosumab was administered at 120 mg monthly. However no demonstrable change was seen on 99mTc-bone scan after 3 months of treatment (Figure 1B) and her pain persisted.

Given BRAF-V600E mutation positivity of our patient’s ECD, a novel combined treatment with a BRAF and MEK-inhibitor, dabrafenib and trametinib, was instituted. Pain improved within weeks and complete resolution in disease activity was demonstrated on serial bone scan after 6 months (Figure 1C).

Conclusion: This is the first case to describe the novel use of a BRAF and MEK inhibitor in the successful treatment and resolution of ECD confined to the skeleton. Treatment for ECD should be individualized based on organ involvement and molecular mutations.