Vol. 29. No. 3


The proper diagnosis and management of pigmented lesions and melanoma can be extremely challenging, but significant strides have been made on multiple fronts in our understanding of the best approaches to these lesions. In this issue, Arthur Sober and his colleagues describe the new changes to the AJCC staging system, Beth Ruben discusses the issues surrounding pigmented lesions of the nail, Kara Shah examines the risk of melanoma and neurocutaneous melanosis in congenital nevi, and Rossitza Lazova and Maria Miteva review the difficulties associated with management of Spitz nevi and the “atypical Spitzoid neoplasm.” Steven Wang and Pantea Hashemi review different imaging modalities, and Suephy Chen and her colleagues discuss the literature surrounding photoprotection measures and serum vitamin D levels. Hensin Tsao and his colleagues describe our current knowledge of the genetic determinants of melanoma predisposition, and the issue concludes with Keith Flaherty and Igor Puzanov’s review of the latest information regarding targeted therapy for metastatic melanoma. I hope that the reader will find the authors’ insights to be helpful when faced with similar situations in daily practice, and I thank all the authors for sharing their expertise. This issue is dedicated to Marie-France Demierre, who was to have been a contributor to this issue before her untimely passing. She was not only an excellent clinician, researcher, and teacher, but also a wonderful colleague and friend, and she is missed.

Vitamin D Levels, Dietary Intake, and Photoprotective Behaviors Among Patients With Skin Cancer

Bryan Gammon, MD | Laura K. DeLong, MD, MPH | Meena Kumari, MD | Nikki Hill, MD | Sarah Wetherington, BS | Scott Dunbar, MD | Suephy C. Chen, MD, MS | Vin Tangpricha, MD, PhD

Photoprotection against ultraviolet light is an important part of our armamentarium against
actinically derived skin cancers. However, there has been concern that adherence to
photoprotection may lead to low vitamin D status, leading to negative effects on patients’
health. In this work we discuss previous findings in this area, which do not give a clear
picture as to the relationship between vitamin D levels and photoprotection measures, as
well as research performed by the authors, who did not detect a relationship between
serum 25(OH)D levels and adherence to photoprotection measures in subjects with skin
cancer, as assessed by the use of sunscreen, clothing, hats, sunglasses, and umbrellas/
shade through the Sun Protection Habits Index. Subjects who took vitamin D oral supplementation
had greater serum 25(OH)D levels than those who did not, whereas dietary
intake through foods did not predict 25(OH)D levels in the authors’ study. However, there
was a high prevalence of vitamin D insufficiency and deficiency in the authors’ study
population, highlighting the importance of assessing vitamin D status and recommending
oral vitamin D supplementation when indicated.
Semin Cutan Med Surg 29:185-189 Published by Elsevier Inc.


Genetic Determinants of Cutaneous Melanoma Predisposition

Bisundev Mahato | Durga Udayakumar, PhD | Hensin Tsao, MD | Michele Gabree, MGC

In the last 2 decades, advances in genomic technologies and molecular biology have
accelerated the identification of multiple genetic loci that confer risk for cutaneous melanoma.
The risk alleles range from rarely occurring, high-risk variants with a strong familial
predisposition to low-risk to moderate-risk variants with modest melanoma association.
Although the high-risk alleles are limited to the CDKN2A and CDK4 loci, the authors of
recent genome-wide association studies have uncovered a set of variants in pigmentation
loci that contribute to low risk. A biological validation of these new findings would provide
greater understanding of the disease. In this review we describe some of the important risk
loci and their association to risk of developing cutaneous melanoma and also address the
current clinical challenges in CDKN2A genetic testing.
Semin Cutan Med Surg 29:190-195 © 2010 Elsevier Inc. All rights reserved.


Targeted Molecular Therapy in Melanoma

Igor Puzanov, MD, MSCI | Keith T Flaherty, MD

Immunotherapy and chemotherapy benefit few patients with metastatic melanoma, and
even fewer experience durable survival benefit. These poor results may come from treating
all melanomas as though they are biologically homogeneous. Recently, it has been shown
that targeting specific activated tyrosine kinases (oncogenes) can have striking clinical
benefits in patients with melanoma. In 2002, a V600E mutation of the BRAF serine/
threonine kinase was described as present in more than 50% of all melanomas. The
mutation appeared to confer a dependency by the melanoma cancer cell on activated
signaling through mitogen-activated protein kinase pathway. The frequency and focality of
this mutation (>95% of all BRAF mutations being at V600 position) suggested its importance
in melanoma pathophysiology and potential as a target for therapy. The recent results
of a phase 1 study with PLX4032/RG7204, a small molecule RAF inhibitor, confirm this
hypothesis. Mucosal and acral-lentiginous melanomas, comprising 3% of all melanomas,
frequently harbor activating mutations of c-kit and drugs targeting this mutation seem to
confer similar benefits for these types of tumors. Here we provide an overview of the
targeted therapy development in melanoma with emphasis on BRAF inhibition because of
its prevalence and possibility of transforming the care of many melanoma patients.
Semin Cutan Med Surg 29:196-201 © 2010 Elsevier Inc. All rights reserved.