Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy

Julia Dai; Christian A Kunder; Emily Y Chu; Edward F Chan; Christine L Egan; Roberto A Novoa

doi:10.1111/cup.13024

Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy

J Cutan Pathol. 2017 Dec;44(12):1053-1056. doi: 10.1111/cup.13024. Epub 2017 Sep 13.

Authors

Julia Dai¹, Christian A Kunder², Emily Y Chu³, Edward F Chan³, Christine L Egan³, Roberto A Novoa^{1

2}

Affiliations

¹ Department of Dermatology, Stanford University Medical Center, Stanford, California.
² Department of Pathology, Stanford University Medical Center, Stanford, California.
³ Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.

PMID: 28796396
DOI: 10.1111/cup.13024

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.

Keywords: BRAF inhibitor; RET; angiosarcoma; vemurafenib.

Publication types

Case Reports

MeSH terms

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 / genetics*
Hemangiosarcoma / pathology*
Hemangiosarcoma / radiotherapy
Humans
Indoles / administration & dosage*
Indoles / adverse effects*
Indoles / therapeutic use
Male
Melanoma / complications
Melanoma / pathology*
Melanoma / radiotherapy
Melanoma / surgery
Mitogen-Activated Protein Kinase 1 / drug effects
Mutation
Physicians
Positron Emission Tomography Computed Tomography / methods
Protein Kinase Inhibitors / adverse effects*
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins B-raf / genetics
Proto-Oncogene Proteins c-ret / genetics*
Skin Neoplasms / drug therapy
Skin Neoplasms / pathology*
Skin Neoplasms / radiotherapy
Sulfonamides / administration & dosage*
Sulfonamides / adverse effects*
Sulfonamides / therapeutic use
Vemurafenib

Substances

Enzyme Inhibitors
Indoles
Protein Kinase Inhibitors
Sulfonamides
Vemurafenib
Proto-Oncogene Proteins c-ret
RET protein, human
Proto-Oncogene Proteins B-raf
Mitogen-Activated Protein Kinase 1