Congenital histiocytosis with central nervous system involvement and a novel PTPRJ::RASGRF1 fusion

Abstract

Histiocytic neoplasms are rare diseases characterized by clonal expansions of cells with a macrophage or dendritic cell phenotype. They are driven by mutations activating the MAPK pathway and may involve diverse organs, including the central nervous system (CNS). We describe a newborn with congenital histiocytosis affecting the CNS, skin, lungs, lymph nodes, thyroid, fingernail, and soft tissues – including a tumor originating from the tongue obstructing the upper airway. Histopathology revealed an atypical histiocytosis with strong CD1a and variable Langerin expression; post-mortem transcriptome sequencing identified a novel PTPRJ::RASGRF1 fusion. This case expands the molecular landscape of histiocytic neoplasms, highlighting the value of comprehensive genomic profiling.