BRAF V600E mutation in Juvenile Xanthogranuloma family neoplasms of the central nervous system (CNS-JXG): a revised diagnostic algorithm to include pediatric Erdheim-Chester disease

• DOI: 10.1186/s40478-019-0811-6
• Publication Date: 2019-11-04T12:03:24Z
• Authors: J. Picarsic; T. Pysher; H. Zhou; M. Fluchel; T. Pettit; M. Whitehead; L. F. Surrey; B. Harding; G. Goldstein; Y. Fellig; M. Weintraub; B. C. Mobley; P. M. Sharples; M. L. Sulis; E. L. Diamond; R. Jaffe; K. Shekdar; M. Santi
• Keywords: Juvenile xanthogranuloma; Erdheim–Chester disease

Abstract The family of juvenile xanthogranuloma neoplasms (JXG) with ERK-pathway mutations are now classified within the “L” (Langerhans) group, which includes Langerhans cell histiocytosis (LCH) and Erdheim Chester disease (ECD). Although BRAF V600E mutation constitutes majority molecular alterations in ECD LCH, only three reported JXG neoplasms, all male pediatric patients localized central nervous system (CNS) involvement, known to harbor mutation. This retrospective case series seeks redefine clinicopathologic spectrum CNS-JXG post-BRAF era, a revised diagnostic algorithm include ECD. Twenty-two lesions were retrieved from consult files 64% ( n = 14) having informative mutational testing (molecular and/or VE1 immunohistochemistry). Of these, 71% 10) cases (≤18 years) half 5) harbored As compared wild-type cohort (WT), had similar mean age at diagnosis [ V600E: 7 years (3–12 y), vs. WT: 7.6 (1–18 y)] but demonstrated stronger male/female ratio 4 vs 0.67), both more multifocal CNS 80% 20%) systemic 40% none). Radiographic features varied typically included enhancing mass lesion(s) associated white matter changes subset neoplasms. After clinical-radiographic correlation, was diagnosed cohort. Treatment options varied, including surgical resection, chemotherapy, targeted therapy BRAF-inhibitor dabrafenib one mutated case. appear gender aggressive presentation We propose for that an initial morphologic final integrated after order identify Future studies long-term follow-up required determine if positive distinct entity L-group category or represent expanded