title: Genetic and morphologic features for melanoma classification.
abstract: Melanoma is comprised of biologically distinct subtypes. The defining clinical, histomorphologic, and molecular features are not fully established. This study sought to validate the association between genetic and histomorphologic features previously described and to determine their reproducibility and association with important clinical variables. Detailed clinical and histomorphologic features of 365 primary cutaneous melanomas were assessed by 11 pathologists and correlated with mutation status of BRAF and NRAS. There was substantial agreement in the quantitative assessment of histomorphologic features showing similar or better interobserver reproducibility than the established World Health Organization classification scheme. We confirmed that melanomas with BRAF mutations showed characteristic morphologic features (P < 0.0001) and metastasized more frequently to regional lymph nodes (P = 0.046). Importantly, melanomas without mutations were a heterogeneous group, with a subset having very similar clinical and morphological features as those with BRAF mutation raising the possibility that they are biologically related. Our study confirms an association between histomorphologic features, mutation status, and pattern of metastasis, providing criteria for a refined melanoma classification aimed at defining biologically homogeneous disease subgroups.
authors.affiliation: Department of Dermatology, University of California San Francisco, 1701 Divisadero St, San Francisco, CA 94115, USA.
authors.forename: Sigrid M C
authors.initials: SM
authors.lastname: Broekaert
authors.forename: Ritu
authors.initials: R
authors.lastname: Roy
authors.forename: Ichiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Joost
authors.initials: J
authors.lastname: van den Oord
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Barnhill
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Cochran
authors.forename: Martin G
authors.initials: MG
authors.lastname: Cook
authors.forename: David E
authors.initials: DE
authors.lastname: Elder
authors.forename: Stanley W
authors.initials: SW
authors.lastname: McCarthy
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Alan
authors.initials: A
authors.lastname: Spatz
authors.forename: Boris C
authors.initials: BC
authors.lastname: Bastian
mesh_terms: D000368:Aged; D000465:Algorithms; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D014944:World Health Organization
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf