ABSTRACT
Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma 6 months after initiation of vemurafenib therapy. Next-generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.
Subject(s)
Hemangiosarcoma/genetics , Hemangiosarcoma/pathology , Indoles/administration & dosage , Indoles/adverse effects , Melanoma/pathology , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins c-ret/genetics , Skin Neoplasms/pathology , Sulfonamides/administration & dosage , Sulfonamides/adverse effects , Aged , Awareness , Carcinogenesis/drug effects , Carcinoma, Squamous Cell/genetics , Disease Progression , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Fatal Outcome , Hemangiosarcoma/drug therapy , Hemangiosarcoma/radiotherapy , Humans , Indoles/therapeutic use , Male , Melanoma/complications , Melanoma/radiotherapy , Melanoma/surgery , Mitogen-Activated Protein Kinase 1/drug effects , Mutation , Physicians , Positron Emission Tomography Computed Tomography/methods , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/drug therapy , Skin Neoplasms/radiotherapy , Sulfonamides/therapeutic use , VemurafenibABSTRACT
BACKGROUND: Studies suggest that the Thin-Layer Rapid-Use Epicutaneous Test (TRUE Test) may be inadequate to completely diagnose a significant number of patients with allergic contact dermatitis (ACD). OBJECTIVE: To study the usefulness of the TRUE Test as a triage tool in a private practice setting. METHODS: A retrospective chart review of patients who were patch-tested with the TRUE Test between July 1, 2000, and June 30, 2004, in four private dermatology practices was conducted. RESULTS: Of the 183 patients evaluated, 50.8% had at least one positive reaction, 31.7% had a diagnosis of ACD, and 24.0% were suspected to have ACD from other allergens. Of the patients with positive reactions, 62.4% were determined to have reactions that were of present relevance. CONCLUSIONS: The TRUE Test allows patients with dermatitis to be triaged systematically in a private practice setting. It is important to supplement patch testing with the patients' personal products, especially in cases of facial or periorbital dermatitis, and to be aware of potential false negatives, particularly with fragrance and rubber additives.
