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.