Eruptive Squamous Cell Carcinomas With Keratoacanthoma-like Features in a Patient Treated with Sorafenib

March 2011 | Volume 10 | Issue 3 | Case Reports | 308 | Copyright © March 2011

Michael C. Lynch BS,a Renee Straub MD,b David R. Adams MDb

aPennsylvania State University College of Medicine, Hershey, PA bDepartment of Dermatology, Milton S. Hershey Medical Center, Hershey, PA

Abstract
Sorafenib is a multikinase inhibitor that displays antiproliferative and antiangiogenic properties in the treatment of solid tumors. Commonly administered for the treatment of metastatic or unresectable hepatocellular carcinoma and advanced renal cell carcinoma, sorafenib has demonstrated remarkable survival benefits for those where curative surgery is not an option. Although generally having a mild side effect profile, sorafenib has been linked to a variety of dermatologic disorders, including most commonly acneiform rash, hand-foot-skin reactions, facial erythema, splinter subungual hemorrhages, alopecia or pruritus. The authors describe a case of sorafenib-induced eruptive squamous cell carcinomas with keratoacanthoma-like features in a patient with hepatocellular carcinoma. This case adds to the growing literature suggesting a strong correlation between sorafenib and non-melanoma skin cancers including keratoacanthoma and squamous cell carcinoma. Routine dermatologic monitoring of these patients to ensure early detection is highly recommended.

J Drugs Dermatol. 2011;10(3):308-310.

INTRODUCTION

Sorafenib (Nexavar), a multikinase inhibitor (MKI), is available for the treatment of metastatic or unresectable hepatocellular carcinoma (HCC), advanced renal cell carcinoma, and other solid tumors. Sorafenib inhibits cell proliferation, reduces angiogenesis, and promotes apoptosis in cancer cells.1,2 These effects are garnered by inhibition of several tyrosine kinase receptors involved in the RAF/MEK/ERK signaling pathway, an important intracellular pathway controlling cell growth and differentiation. Specifically, sorafenib inhibits Raf-1 and Braf, important mediators of tumor proliferation, vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptor β (PDGRFβ), receptors that regulate tumor angiogenesis, c-kit and RET.1,2 These varied targets make sorafenib a powerful antineoplastic agent that has revolutionized the treatment of these tumors.
Although widely tolerated with a minimal side effect profile, its usefulness in oncologic therapy is occasionally tempered by a variety of dermatologic conditions including acneiform rash, hand-foot skin reactions (HFSR), pruritus, facial erythema, splinter subungual hemorrhages, and alopecia.3–4 Rarely, psoriasiform eruptions, keratoacanthomas (KA), squamous cell carcinomas (SCC), or SCC with KA-like features have been described.5–8
In many cases, because other effective therapies are lacking, the benefits of sorafenib often outweigh the disadvantages of these dermatologic manifestations. In these patients, chemoprophylaxis of non-melanoma skin cancers has been reported by the use of systemic retinoids.9–11
Here, the authors present an 80-year-old white male treated with sorafenib for unresectable HCC who developed eight atypical squamous proliferations.

CASE REPORT

An 80-year-old man with longstanding alcoholic cirrhosis underwent abdominal magnetic resonance imaging (MRI) in late 2008 to rule out hepatocellular carcinoma (HCC). The MRI identified multiple lesions involving bilateral hepatic lobes and subsequent needle biopsy confirmed the diagnosis of HCC.