Pathophysiology of Langerhans Cell Histiocytosis

Molecular Basis

• Langerhans cell histiocytosis is fundamentally a clonal neoplastic disorder driven by activating mutations in the MAPK/ERK pathway, most notably BRAFV600E, rather than a reactive inflammatory process 1
• MAPK pathway mutations, including BRAF V600E, occur in over 90% of LCH cases and represent the primary oncogenic driver, according to the Mayo Clinic Proceedings 1, 2

Cellular Phenotype

• LCH cells show Langerhans cell differentiation markers: S100+, CD1a+, and Langerin+ by immunohistochemistry, as reported by the Mayo Clinic Proceedings 1, 3
• BRAF V600E mutation can be demonstrated by immunohistochemistry in affected tissues, as noted by the Mayo Clinic Proceedings 1, 3