title: Rosai-Dorfman Disease Harboring an Activating KRAS K117N Missense Mutation.
abstract: Rosai-Dorfman disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare histiocytic proliferation that is generally considered to be reactive with a benign clinical course. The etiology of RDD is very poorly understood. Recent studies have shown frequent BRAF, NRAS, KRAS, and PIK3CA activating mutations in several histiocytic neoplasms highlighting the emerging importance of the RAF/MEK/ERK pathway in the pathogenesis of these diseases. Here we report a case of Rosai-Dorfman disease involving the submandibular salivary gland with a KRAS K117N missense mutation discovered by next-generation sequencing. These results suggest that at least a subset of RDD cases may be clonal processes. Further mutational studies on this rare histiocytic disease should be undertaken to better characterize its pathogenesis as well as open up potential avenues for therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine - Qatar, Education City, PO Box 24144, Doha, Qatar. vis2018@qatar-med.cornell.edu.
authors.forename: Vignesh
authors.identifier: http://orcid.org/0000-0002-2005-9080
authors.initials: V
authors.lastname: Shanmugam
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Margolskee
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kluk
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Giorgadze
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY, 10065, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D015618:Histiocytosis, Sinus / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Clonality; Histiocytosis; Next generation sequencing; Pathogenesis; Rosai–Dorfman disease; Sinus histiocytosis with massive lymphadenopathy