title: Clinico-morphological features of BRAF inhibition-induced proliferative skin lesions in cancer patients.
abstract: BACKGROUND
  The use of BRAF inhibitors may lead to the development of cutaneous toxicities such as rashes, photosensitivity, alopecia, palmoplantar erythrodysesthesia, and proliferative skin lesions, including keratoacanthomas (KAs) and cutaneous squamous cell carcinomas (cuSCCs). The latter are noteworthy for their potential to exhibit malignant features, and they may necessitate invasive treatment. Their prompt identification is of primary importance for directing supportive care efforts and maintaining dose intensity while minimizing the morbidity associated with supportive care interventions. Because such lesions are less familiar to oncologists, this study was designed to characterize their clinico-morphological features, which have not been hitherto described.
  
  
  METHODS
  The clinical and dermoscopic characteristics and risk factors of new-onset proliferative skin lesions (benign verrucous lesions and KAs/cuSCCs) developing after the initiation of treatment with vemurafenib, dabrafenib, and XL281 were analyzed; the histopathological diagnoses were ascertained.
  
  
  RESULTS
  The majority of the lesions were benign verrucous lesions (78%, n = 87), whereas KAs/cuSCCs represented 22% (n = 25). The median times to biopsy for the initial verrucous lesions and KAs/cuSCCs were 4.8 and 10.5 weeks, respectively. The clinico-morphological features significant for KAs/cuSCCs included a larger size (P < .001), a nodular appearance (P < .001), a central keratin plug (P < .001), a central ulceration or crust (P = .04), an adherent scale (P = .02), an erythematous halo (P = .03), and a scaly ring (collarette; P < .001) at the periphery.
  
  
  CONCLUSIONS
  Our findings represent the first detailed description of the clinico-morphological characteristics that permit distinction between the benign and malignant skin lesions induced by BRAF inhibitors. They are valuable for the recognition of lesions that require intervention and/or a dermatology referral versus those that permit provisional monitoring.
authors.affiliation: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Viswanath Reddy
authors.initials: VR
authors.lastname: Belum
authors.forename: Alyx C
authors.initials: AC
authors.lastname: Rosen
authors.forename: Natalia
authors.initials: N
authors.lastname: Jaimes
authors.forename: George
authors.initials: G
authors.lastname: Dranitsaris
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Pulitzer
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Ashfaq A
authors.initials: AA
authors.lastname: Marghoob
authors.forename: Richard D
authors.initials: RD
authors.lastname: Carvajal
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.forename: Mario E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000009:adverse effects; D002219:Carbamates / Q000009:adverse effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects; D007211:Indoles / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010091:Oximes / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D012871:Skin Diseases / Q000139:chemically induced* / Q000150:complications / Q000473:pathology*; D013449:Sulfonamides / Q000009:adverse effects; D000077484:Vemurafenib
chemical_list: C000593770:BMS 908662; D001562:Benzimidazoles; D002219:Carbamates; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C561627:dabrafenib
keywords: BRAF; XL281; dabrafenib; keratoacanthoma; risk factors; skin neoplasms; squamous cell carcinoma; vemurafenib; verrucous lesion