Here, we report a 2-year-old boy, the youngest patient in the literature so far, who was diagnosed with concomitant BRAF mutation-positive LCH and ECD.
Identification of BRAF and other MAPK pathway mutations in biopsies improves ECD diagnosis, allows for development of targeted treatments, and demonstrates that ECD is a neoplastic disorder.
We collected CSF from patients with BRAFV600E or K-mutated melanoma (N=8) or BRAFV600E mutated Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS) involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or both.
Here, we retrospectively evaluated the clinical and pathologic characteristics, presence of the BRAFV600E mutation, treatment options, and outcomes of Chinese patients diagnosed with ECD at our center.
The coexistence of LCH and ECD in the same biopsy and the BRAF (V600E) mutation status in both histologic types support the recent re-classification of the histiocytic disorder into LCH, ECD, and "mixed histiocytosis", which reflects tumorigenesis for all three from a common progenitor cell.
A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD.
These results indicate that cfDNA BRAF(V600E) mutational analysis in plasma and urine provides a convenient and reliable method of detecting mutational status and can serve as a noninvasive biomarker to monitor response to therapy in LCH and ECD.
We performed molecular analysis of BRAF in the largest cohort of ECD patients studied to date followed by N/KRAS, PIK3CA, and AKT1 mutational analysis in BRAF wild-type patients.
Vemurafenib has been used for a small number of patients harbouring this mutation; inhibition of BRAF activation by vemurafenib was highly beneficial in these cases of severe multisystemic and refractory ECD.
The diagnosis of ECD was made by characteristic histopathologic features in addition to clinical-radiographic features and the typical immunoprofile (positive for cluster of differentiation 68 [CD68], CD163, and p16; negative forCD1a and S-100).