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.
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: Daniel N Cohen; Steven K Lawson; Aaron C Shaver; Liping Du; Harrison P Nguyen; Qin He; Douglas B Johnson; Wilfred A Lumbang; Brent R Moody; James L Prescott; Pranil K Chandra; Alan S Boyd; Jeffrey P Zwerner; Jason B Robbins; Stephen K Tyring; Peter L Rady; James D Chappell; Yu Shyr; Jeffrey R Infante; Jeffrey A Sosman Journal: Clin Cancer Res Date: 2015-02-27 Impact factor: 12.531
Authors: A Boada; C Carrera; S Segura; H Collgros; P Pasquali; D Bodet; S Puig; J Malvehy Journal: Clin Transl Oncol Date: 2018-05-24 Impact factor: 3.405
Authors: Edward J Hartsough; Curtis H Kugel; Michael J Vido; Adam C Berger; Timothy J Purwin; Allison Goldberg; Michael A Davies; Matthew J Schiewer; Karen E Knudsen; Gideon Bollag; Andrew E Aplin Journal: Mol Cancer Ther Date: 2017-11-13 Impact factor: 6.261
Authors: Azael Freites-Martinez; Bernice Y Kwong; Kerri E Rieger; Daniel G Coit; A Dimitrios Colevas; Mario E Lacouture Journal: JAMA Dermatol Date: 2017-07-01 Impact factor: 10.282
Authors: Francis Worden; Martin Fassnacht; Yuankai Shi; Tatiana Hadjieva; Françoise Bonichon; Ming Gao; Laura Fugazzola; Yuichi Ando; Yasuhisa Hasegawa; Do Joon Park; Young Kee Shong; Johannes W A Smit; John Chung; Christian Kappeler; Gerold Meinhardt; Martin Schlumberger; Marcia S Brose Journal: Endocr Relat Cancer Date: 2015-12 Impact factor: 5.678