Protein Kinase C-alpha Gene Fusions in Dendritic Cell Neurofibroma: Distinction From Conventional Neurofibroma.

Dendritic cell neurofibroma with pseudorosettes is an uncommon but distinctive variant of neurofibroma. The pseudorosette structures are formed by the circumferential arrangement of small, dark cells around an eosinophilic core at the center of which there is often a single larger and paler cell with slender dendrite-like projections. Dendritic cell neurofibroma often shows a multinodular architecture, which can cause confusion with plexiform neurofibroma. Since plexiform neurofibroma is essentially pathognomonic of Neurofibromatosis type I, such confusion could lead to unnecessary and costly clinical work-up. Since its description in 2001, there has been controversy as to whether dendritic cell neurofibroma represents a true subtype of neurofibroma, whose defining molecular feature is loss-of-function mutation in NF1. Here we show in a series of 9 cases that dendritic cell neurofibroma harbors recurrent gene fusions involving protein kinase c-alpha (PRKCA), including SLC44A1::PRKCA. Identical gene fusions are known to occur in a rare brain tumor known as papillary glioneuronal tumor, although this entity appears to be morphologically and clinically distinct from dendritic cell neurofibroma. Our results distinguish dendritic cell neurofibroma from conventional types of neurofibroma and raise consideration that dendritic cell neurofibroma may be better classified as a unique type of benign neural tumor.