NRAS Mutations May Be Involved in the Pathogenesis of Cutaneous Rosai Dorfman Disease: A Pilot Study.

BACKGROUND

Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD.

METHODS

We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog () Kirsten rat sarcoma 2 viral oncogene homolog (), and v-raf murine sarcoma viral oncogene homolog B1 () in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing.

RESULTS

Seven patients with cutaneous RDD were recruited with nine biopsy specimens. The median age was 46 years (range: 17-62 years). Four of seven patients (57.1%) received tumor excision, while the other three chose oral and/or topical or intralesional steroids. mutation was detected in 4 of 7 cases (4/7; 51.7%), and A146T was the most common mutant point ( = 4/7), followed by G13S ( = 2/7). There is no or mutation detected.

CONCLUSIONS

We report the mutation is common in cutaneous RDD, and A146T was the most frequent mutation in this cohort. Mutations in the gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD.