The BRAF inhibitor vemurafenib is approved by the U.S. Food and Drug Administration (FDA) for patients with ECD harboring a <i>BRAF</i> V600E mutation.
This retrospective case series seeks to redefine the clinicopathologic spectrum of pediatric CNS-JXG family neoplasms in the post-BRAF era, with a revised diagnostic algorithm to include pediatric ECD.
The <i>BRAF</i><sup>V600E</sup> mutation and BRAF inhibitor responsiveness characterize ∼50% of patients with the non-Langerhans cell histiocytosis (non-LCH) Erdheim-Chester disease (ECD).
BRAFV600E is the predominant oncogenic driver of L-group histiocytoses, which includes Erdheim-Chester disease (ECD); however, limited data exist on the prevalence of this mutation in sporadic XG family lesions.
IMPLICATIONS FOR PRACTICE: Vemurafenib, an oral monotherapy targeting a mutation in BRAF, is the first U.S. Food and Drug Administration approval for the treatment of Erdheim-Chester disease (ECD).
In addition, we identified the BRAF status and the HDL phenotype as independent determinants of the aortic involvement in ECD with a potential role of HDL in modulating the infiltration of blood CD14<sup>+</sup> cells into the aorta.
Patients with BRAF V600-mutant ECD or LCH were enrolled in an "other solid tumor" cohort of the VE-BASKET study, and they were enrolled in the present study.
Underlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments.
• To assess the degree of thoracic involvement in ECD with CT. • BRAF <sup>V600E</sup> mutation has a high association with right coronary artery sheathing.
Therefore, the patient was determined to have ECD with a typical BRAFV600E mutation, as well as primary myelofibrosis, with the latter diagnosis manifesting clinically over one year after the JAK2 V617F was first detected in ctDNA.
Finally, droplet digital PCR using a probe specific for this novel mutation detected the complex BRAF mutation in both the 2000 and 2008 lesions, indicating this case to be ECD with a novel underlying BRAFp.Thr599_Val600delinsArgGlu mutation.
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.