Khối U Ác Tính Dưới Da: Góc Nhìn Phẫu Thuật (Cutaneous Malignancies)

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Cutaneous Malignancies
A Surgical Perspective
Brian R. Gastm an, MD
Director
Cleveland Clinic Foundation Melanoma Program
Associate Professor of Surgery
Cleveland Clinic Lerner College of Medicine
Cleveland Clinic
Cleveland, Ohio, USA
Sub-editor
Neilendu Kundu, MD
Medical Director
Plastic and Reconstructive Surgery
Mercy Health Physicians
Cincinnati, Ohio, USA
445 illustrations
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Names: Gastman, Brian R., editor.
Title: Cutaneous malignancies : a surgical perspective /
[edited by] Brian R. Gastman.
Description: New York : Thieme, [2018] |
Includes bibliographical references.
Identi ers: LCCN 2017038939 (print) | LCCN 2017039913 (ebook) |
ISBN 9781626231481 (e-book) | ISBN 9781626231474 (print)
Subjects: | MESH: Skin Neoplasms–surgery | Dermatologic Surgical
Procedures
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I would like to dedicate this book to my life partner and wife, Addie, whose love and support
have allowed me to focus on this important endeavor. To my children, Rachelli, Dovid,
Binyomen, and Esi, who I never see enough of but are growing up to be individuals any parent
would be proud of. I hope this book attests that my time away is for the best of causes.
As a simple servant of a higher power, I hope this book will help the few that are here on this
earth to help the many through the countless challenges of skin cancer.

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Contents
Video Contents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . viii
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
1.

Prevention of Future Skin Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Trevor Batty and Jerry D. Brewer
2.

Clinical Detection of Skin Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Michael Schowalter, Allison Vidimos, and Phillip L. Bailin
3.

Treatment of Squamous and Basal Cell Carcinoma of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Rogerio I. Neves and Morgan Brgoch
4.

Surgical Treatment of Cutaneous Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Andrea M. Abbott, Matthew P. Doepker, and Vernon K. Sondak
5.

Treatment of Rare Skin Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Karri Adamson and William W. Dzwierzynski
6.

Mohs Micrographic Surgery’s Role in the Treatment of Skin Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Charlene Lam, Christine Poblete-Lopez, and Elizabeth M. Billingsley
7.

Role of Radiotherapy in the Treatment of Skin Malignancies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Shlomo A. Koyfman, Bindu V. Manyam, Nikhil Purushottam Joshi, and Sue S. Yom
8.

Surgical Implications of Systemic Therapy for Skin Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158
Vadim P. Koshenkov, Oliver Eng, and Howard L. Kaufman
9.

Common Reconstructive Techniques after Facial Skin Cancer Excision . . . . . . . . . . . . . . . . . . . . . . . 168
Neilendu Kundu and Brian R. Gastman
10. Operative Lymphadenectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 192
Calvin J. Young, Amrita Pandit, and Deepak Narayan
11. Role of Dermatopathology in the Surgical Management of Skin Cancer . . . . . . . . . . . . . . . . . . . . . 212
Jennifer S. Ko, Eugen C. Minca, and Klaus J. Busam
12. High-Risk Cutaneous Malignancies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Sashank K. Reddy and Anthony P. Tufaro
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
vii

Video Contents
Cervicofacial Rotation Flap for a Cheek Defect
Completion Inguinal Lymphadenectomy
Multi-stage Nasal Defect Reconstruction
Sentinel Node Biopsy
viii

Preface
This book is designed to meet a growing need for the
modern surgeon treating skin cancer. Cutaneous malignan-
cies are currently treated by a variety of surgical specialties.
As a result, there lacks a strong uni ed description of how
these cancers should be approached. Additionally, many
recent developments in non-surgical therapies have been
developed, affecting surgeons who treat these pathologies.
Surgery is one aspect in the spectrum of cutaneous
malignancies treatment, beginning with prevention and
detection and ending with long-term follow-up and pos-
sibly systemic therapies. Any surgeon in the position of
handling any oncologic patients needs to have a robust
understanding of these important aspects of skin cancer
care. Often, the surgical interventions in this patient pop-
ulation are the least complex aspect of their treatment. In
the modern era, there exist many new aspects of these
cancers that may not be well known to all surgeons—for
example, the increasing use of immunosuppressive thera-
pies for transplantation and rheumatologic diseases,
which predisposes patients to these tumors. There are also
increasing numbers of lesser-known malignancies, such as
Merkel cell carcinoma and dermato brosarcoma protuber-
ans (DFSP), to name a few.
Many aspects of surgical care itself need to be considered
when contemplating comprehensive care for these
patients. This may include: Mohs surgery, sentinel node
biopsy, appropriate margin size, method of reconstruction,
and quality dermatopathology. Finally, increasing advances
in targeted therapy, immunotherapy, and radiotherapy are
affecting when, how, and even if a patient needs to undergo
surgery.
With a multitude of new advancements in cutaneous
cancers, especially for patients who progress after surgery,
this is a fortuitous time to complete a comprehensive book
on the management of these tumors. As national referral
patterns to surgeons are ever changing, having a reference
that can appeal to all types of surgeons is both timely and
essential. Nonetheless this book has been written in a
fashion that allows nonsurgical practitioners the ability to
understand the role surgeons play in these diseases, as well
as a substantial amount of information that will be bene-
cial for their practice. Thus, this can affect when and to
whom to refer these patients, as well as what a referring
physician should expect from the surgical consult. Finally,
for any physician—surgeon or not—who chooses to treat
these diseases,we hope this book will serve as an important
reference based on the newest standards of care derived
from many perspectives.
The development of a comprehensive text on the man-
agement of cutaneous cancers is overdue. This need is
derived from a combination of lack of consistency amongst
surgical specialties and a paucity of books devoted for the
modern surgeon treating skin cancer. By employing high-
volume surgeons and other skin cancer specialists who are
knowledgeable in both standard of care and cutting-edge
technologies, we fully expect that this book will serve as an
important reference that surgeons can utilize for years to
come.
ix

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Contributors
Andrea M. Abbott, MD, MS
Division of Oncologic and Endocrine Surgery
Medical University of South Carolina
Charleston, South Carolina, USA
Karri Adam son
PGY5 Resident
Plastic and Reconstructive Surgery
Medical College of Wisconsin
Milwaukee, Wisconsin, USA
Philip L. Bailin, MD
Dermatologist
Cleveland Clinic Dermatology
Cleveland, Ohio, USA
Trevor Batty, DO
Fourth Year Resident
Midwestern University
Rochester, Minnesota, USA
Elizabeth M. Billingsley, MD
Professor of Dermatology
Director
Mohs Micrographic Surgery & Dermatological Surgery
Penn State Hershey Dermatology
Hershey, Pennsylvania, USA
Jerry D. Brewer, MD
Associate Professor
Dermatology
Mayo Clinic
Rochester, Minnesota, USA
Morgan Brgoch, MD
Resident, PGY III
Division of Plastic Surgery
Penn State Health
Milton S. Hershey Medical Center
Hershey, Pennsylvania, USA
Klaus J. Busam , MD
Staff and Director, Dermatopathology
Department of Anatomic Pathology
Memorial Sloan Kettering Cancer Center
New York, New York, USA
Matthew P. Doepker, MD
Assistant Professor of Clinical Surgery/Surgical Oncology
Palmetto Health/USC Medical Group
Columbia, South Carolina, USA
William W. Dzwierzynski, MD, FACS
Professor and Program Director
Department of Plastic Surgery
Medical College of Wisconsin
Milwaukee, Wisconsin, USA
Oliver Eng, MD
PGY-4 Resident
Rutgers Robert Wood Johnson Medical School
New Brunswick, New Jersey, USA
Brian R. Gastm an, MD
Director
Cleveland Clinic Foundation Melanoma Program
Associate Professor of Surgery
Cleveland Clinic Lerner College of Medicine
Cleveland Clinic
Cleveland, Ohio, USA
Nikhil Purushottam Joshi, MD
Assistant Professor of Medicine
Department of Radiation Oncology
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, USA
Howard L. Kaufm an, MD, FACS
Professor and Chief
Division of Surgical Oncology
Chief Surgical Of cer
Associate Director for Clinical Science
Surgical Oncologist
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, USA
Jennifer S. Ko, MD, PhD
Dermatopathology Medical Director
Cleveland Clinic Central Biorepository
Department of Anatomic Pathology
Pathology and Laboratory Medicine Institute
Cleveland Clinic
Cleveland, Ohio, USA
Vadim P. Koshenkov, MD
Professor of Surgery
Rutgers Robert Wood Johnson Medical Group
The Cancer Institute of New Jersey
New Brunswick, New Jersey, USA
xi

Shlom o A. Koyfm an, MD
Assistant Professor of Medicine
Departments of Radiation Oncology and Bioethics
Cleveland Clinic Taussig Cancer Institute
Cleveland, Ohio, USA
Neilendu Kundu, MD
Medical Director
Plastic and Reconstructive Surgery
Mercy Health Physicians
Cincinnati, Ohio, USA
Charlene Lam , MD, MPH
Assistant Professor of Dermatology
Dermatology Department
Penn State Hershey
Hershey, Pennsylvania, USA
Bindu V. Manyam , MD
PGY-1 Resident
Radiation Oncology Department
Cleveland Clinic
Cleveland, Ohio, USA
Eugen C. Minca, MD, PhD
Department of Pathology
Pathology and Laboratory Medicine Institute
Cleveland Clinic
Cleveland, Ohio, USA
Deepak Narayan, MD
Professor
Plastic and Reconstructive Surgery
Yale University School of Medicine
New Haven, Connecticut, USA
Rogerio I. Neves, MD, PhD
Professor of Surgery, Dermatology, Pharmacology, and
Medicine
Melanoma and Cutaneous Malignancies Disease Team
Leader
Penn State Hershey Plastic Surgery
Hershey, Pennsylvania, USA
Am rita Pandit, MD
Research Fellow
Section of Plastic Surgery
Yale University School of Medicine
New Haven, Connecticut, USA
Christine Poblete-Lopez, MD
Vice-Chairman
Dermatology Department
Cleveland Clinic
Cleveland, Ohio, USA
Sashank K. Reddy, MD, PhD
Administrative Chief Resident
Department of Plastic and Reconstructive Surgery
Johns Hopkins School of Medicine
Baltimore, Maryland, USA
Michael Schowalter, MD
Dermatologist
Cleveland Clinic Dermatology
Cleveland, Ohio, USA
Vernon K. Sondak, MD
Chief of the Division of Cutaneous Oncology
Director of Surgical Education
H. Lee Mof tt Cancer Center and Research Institute
Tampa, Florida, USA
Anthony P. Tufaro, MD, DDS
Director
Head and Neck Program for General Surgery
Vice Chief
Plastic & Reconstructive Surgery
Associate Professor
Plastic and Reconstructive Surgery
Johns Hopkins Hospital
Baltimore, Maryland, USA
Allison Vidim os, RPh, MD, FACMS
Chairman
Department of Dermatology
Vice Chairman
Dermatology and Plastic Surgery Institute
Cleveland Clinic Professor of Medicine
Cleveland Clinic Lerner College of Medicine
Case Western Reserve University
Cleveland, Ohio, USA
Sue S. Yom , MD, PhD
Associate Professor
Departments of Radiation Oncology and Otolaryngology
Head and Neck Surgery
Helen Diller Family Comprehensive Cancer Center
UCSF
San Francisco, California, USA
Calvin J. Young MD, MHS
General Surgery Resident
Department of Surgery
Yale-New Haven Hospital
New Haven, Connecticut, USA
Contributors
xii

1 Prevention of Future Skin Cancer
Trevor Batty and Jerry D. Brewer
1.1 Introduction
Nonmelanoma skin cancer (NMSC) is the most common malig-
nancy in humans. More than 3.5 million NMSCs in more than 2
million people are diagnosed in the United States annually.1 In
fact, the incidence of skin cancer is higher than new cases of
breast, prostate, lung, and colon cancer combined.2 Melanoma
incidence rates have been increasing over the past three deca-
des. Most recent data suggest an increase of 2.7% from 2006 to
2010.2 In 2014, melanoma is estim ated to be the third and
fourth most common cancer in men and women, respectively.2
The total estimated cost of treatment for skin cancer (including
melanoma, basal cell carcinoma [BCC]), and squamous cell car-
cinoma [SCC]) is $8.1 billion each year in the United States.3
Aside from treatment, cost due to lost workdays and restricted-
activity days is estimated at $106.2 million annually.2 The high
incidence of skin cancer—in addition to the cost and toll on
society—is astounding considering that an estimated daily
application of only sun protection factor (SPF) 15 in the first 18
years of life would reduce the lifetime incidence of NMSC by
78%.4 These statistics highlight the importance and beneficial
e ects of skin cancer prevention.
1.2 Role of Dermatology
1.2.1 Primary Prevention
Dermatologists have an opportunity to play an active role in the
prevention of skin cancer. Primary prevention, as defined by the
United States Preventive Services Task Force (USPSTF), involves
measures provided to individuals to prevent the onset of a tar-
geted condition, in this case skin cancer.5 Primary prevention
methods in general have included counseling patients, involving
other physicians, participating in community outreach pro-
grams, and endorsing school sun-safety programs and policy.
Chemoprevention is also considered a primary preventive meas-
ure and will be discussed in greater detail later in this chapter.5
Since NMSC and melanoma share the risk factors of exposure to
ultraviolet (UV) radiation and history of severe sunburns, follow-
ing primary preventive measures aimed at UV protective habits
can maximize great outcomes regarding skin cancer prevention.
Skin cancer prevention can be enhanced by dermatologists
asking patients if they are protecting themselves from the sun
and counseling them about the importance of sun protection.
The National Ambulatory Medical Care Survey found that only
1.6% of dermatologists reported mentioning sunscreen during
patient visits.6 The ability to counsel and distribute educational
pamphlets gives dermatologists the opportunity to change a
patient’s perspective and understanding of skin cancer. During
dermatologic examinations, it would be important to discuss
close monitoring and personal protective clothing with patients
who have exposure to known chemical risk factors for mela-
noma such as coal, tar, pitch, creosote, arsenic, radium, and pes-
ticides. It is important to educate patients during visits about
skin cancer warning signs and morphology for both melanoma
and NMSC. Cheng et al found 59% of self-detected melanomas
in situ had an established dermatologist, and many patients
attributed this to education obtained during a dermatology
appointment.7
Skin cancer prevention can be even more e ective in a multi-
disciplinary approach. Dermatologists have the opportunity to
enlist the help of fellow physicians, especially primary care pro-
viders, to emphasize the importance of the basics of skin cancer
prevention including sun and tanning bed avoidance, as well as
regular sunscreen use to their patients. The American Academy
of Dermatology (AAD) has created a free basic dermatology cur-
riculum that is available to the public (Table 1.1).8 This curric-
ulum is aimed toward physicians and students. Learning
modules include actinic keratosis (AK), SCC, BCC, evaluation of
pigmented lesions, and melanoma. These modules are very
helpful given they provide instruction and guidance on when to
assure or refer the patient. The USPSTF conducted a systematic
review of evidence on the e ectiveness -of behavioral counsel-
ing to prevent skin cancer and found in primary care settings
where counseling was given there was a decrease in intentional
Table 1.1 Helpful websites
Sponsor

URL

Information
American
Academy of
Dermatology

education/basic-
dermatology-curriculum
Basic dermatology
curriculum for
physicians and medical
students
The Skin
Cancer
Foundation

prevention
Educational links and
helpful tips for skin
cancer prevention
The Skin
Cancer
Foundation

get-involved
Ideas for getting
involved in fundraising,
advocacy, schools, and
your community
American
Academy of
Dermatology

spot-skin-cancer
Links to find a
dermatologist, free
cancer screening, and
educational information
The Ameri-
can Cancer
Society

healthy/morewaysacshel-
psyoustaywell/acs-skin-
cancer-prevention-activities
Skin cancer awareness
campaigns and
education resources
The Ameri-
can Cancer
Society

healthy/toolsandcalculators/
quizzes/sun-safety/index
Quiz on sun safety
Centers for
Disease
Control and
Prevention

dcpc/resources/features/
SkinCancer/
Facts about skin cancer,
educational links, and
sun-safety tips
National
Council on
Skin Cancer
Prevention
http://

org
News, ideas to get
involved, advocacy, and
educational links
Source:
Prevention of Future Skin Cancer
1

tanning and an increase in sun-protective behaviors.9 Another
finding of this review was that appearance-focused messages
were the most successful at reducing late-adolescent women’s
intent to pursue indoor training.9 Following this review, in May
2012, the USPSTF recommended counseling fair-skinned chil-
dren, adolescents, and young adults aged 10 to 24 years about
minimizing their exposure to UV radiation to reduce their risk
for skin cancer.9 The National Ambulatory Medical Care Survey
found that only 0.07% of patient visits had mention of
sunscreen and only 0.9% of patients with a history of skin dis-
ease were counseled on the importance of sunscreen.6 The
results of this survey demonstrate that dermatologists and
other health care providers can improve e orts to increase
awareness of the importance of skin cancer prevention.
Another responsibility of dermatologists is to promote skin
cancer prevention and awareness in our communities. National
surveys found that only 3 out of 10 adults practice routine sun
protection themselves, and approximately 60% of parents
applied sunscreen and 25% used shade to protect their chil-
dren.10 The results of this survey demonstrate the need to raise
community awareness of skin cancer by participating in
national or local sun protection campaigns. For example, the
American Cancer Society has a national skin cancer awareness
campaign called “Slip! Slop! Slap! and Wrap.” This slogan pro-
motes slipping on a shirt, slopping on sunscreen, slapping on a
hat, and wrapping on sunglasses to protect the eyes. The Amer-
ican Cancer Society has also designated the Friday before
Memorial Day as “No Fry Day.” Pool Cool is a sun-safety educa-
tion program with eight brief sun-safety lessons taught during
regular swimming lessons for children and parents.11 Pools that
use this program have been found to have better protected
pool environments and better sun protection habits among
swimmers and lifeguards that result in fewer sunburns.3 A
randomized controlled trial conducted in Australia showed that
a population screening that included melanoma awareness
campaign led to a decrease in thickness of the melanomas diag-
nosed during the campaign.12,13 A study done in 1999 evaluat-
ing the previous 20 years of primary health prevention
programs in Australia found a very large shift in knowledge,
attitudes, beliefs, and behaviors about sunlight exposure and
suntans.14 Participation and support of national campaigns,
such as these, could increase the community’s awareness and
application of sun-safety.
Studies of immigrants to Australia point to sun exposure dur-
ing childhood and adolescence as a major risk factor for devel-
oping NMSC.15,16 Sunburns in children are a risk factor for
development of skin cancer later in life, and it has been shown
that building healthier sun protection habits at an early age can
lead to better sun protection as adults.17,18 Dermatologists and
other health care providers have the opportunity to promote
formation of policy in local schools to educate students on
healthy sun protection habits. Dermatologists and other health
care providers can have a positive impact in school policy by
encouraging the creation of school sun-safety strategies such as
allowing students to apply sunscreen at school, having play
equipment in shaded areas, scheduling recess to avoid peak sun
intensity, and encouraging students to wear sun-protective
clothing such as hats, long-sleeved shirts, and pants. Sun-safety
curriculum has also been shown to play an important role in
skin cancer prevention. Such curriculums have been shown to
be e ective in school-aged children as early as preschool.19 A
randomized trial found that interactive multimedia programs
in conjunction with teacher instruction improved sun-safety in
primary school-aged children.20 Arizona was among the first to
require skin cancer prevention as part of their health education
curriculum. Since 2004, Arizona has implemented SunWise in
grades K-8 in all public schools.21 SunWise is a health and envi-
ronmental education program that o ers participants free
materials to promote cross-curricular learning about sun-safety,
UV radiation, and ozone science. The SunWise program has had
success in raising awareness and increasing sun-safety behav-
iors.22 This program has also been shown to prevent approxi-
mately 11,000 skin cancer cases among participants resulting in
saving $4 for every $1 spent.23 Involvement in endorsing local
school policy and curriculum that a ects younger individuals
has great potential to further decrease the incidence of skin
cancer.
Patients with previous solar damage and/or existing precan-
cerous lesions can be treated by several means to prevent
future skin cancer. The risks and benefits of the preventive
treatment should be discussed and agreed upon with the pa-
tient to encourage compliance and awareness. The subsequent
sections will discuss various methods of prevention and their
respective e cacy. Treatments include cryotherapy, light ther-
apy, topical medications, lasers, and chemical peels.
1.2.2 Chemoprevention
Chemoprevention is considered as primary prevention by the
USPSTF.5 The subject of chemoprevention is extensive and mul-
tiple methods deliver impressive e cacy.24 For the purposes of
this chapter, chemoprevention is the treatment of AKs. AKs
account for 5.2 million o ce visits per year and $920 million in
treatment.25 The progression of AKs to primary invasive or in
situ SCC was found to be 0.6% at 1 year and 2.57% at 4 years.26
Dodson et al estimated a 10-year risk of AKs transforming to
SCC to be around 6.1 to 10.2%.27 Hypertrophic AKs measuring
less than 1 cm in diameter located on the dorsum of the hand,
wrist, or forearm in white patients were found to have a trans-
formation rate of 50%.28 Criscione et al found that approxi-
mately 65% of primary SCC and 36% of BCC were originally
diagnosed as AKs.26 Treatment can be directed at single or mul-
tiple AKs. If multiple less well-defined AKs are present over
large areas, then field therapy can be very beneficial. Field ther-
apy targets clinically visible and subclinical AKs. Ultimately, the
choice of the method of chemoprevention should be individual-
ized to each patient.
Cryotherapy
Cryotherapy is the treatment of choice for individual AK
lesions.29 A multicenter study found a 67.2% clearance rate 3
months after treatment when lesions were frozen for at least 2
seconds, and greater than an 80% clearance rate when AKs were
frozen for at least 10 seconds.30 Krawtchenko and colleagues
reported 68% clinic clearance and 32% histological clearance 6
weeks after one or two treatments lasting 20 to 40 seconds for
each lesion.31 At a 12-month follow-up, 6% of patients who
were initially cleared remained clear,31 in contrast to a study
done by Lubritz and Smolewski that reports a cure of 98.8%
Prevention of Future Skin Cancer
2

treated lesions with up to 8.5-year follow-up.32 Adverse e ects
include redness, blistering, crusting, oozing, and ulceration.29
Thai et al reported hypopigmentation resulted in up to 29% of
patients treated with a freeze time greater than 20 seconds.30
In a Cochrane review, cryotherapy was found to be significantly
inferior to 5-fluorouracil (5-FU) and aminolevulinic acid (ALA)
photodynamic therapy (PDT).24
Photodynamic Therapy
PDT involves the selective accumulation of photosensitizing
agents that generate reactive oxygen species when exposed to
light, which causes selective apoptosis in premalignant and/or
malignant cells. ALA and methyl aminolevulinic acid (MAL) are
topical photosensitizing agents that are applied for a certain
period prior to exposure to blue or red light. A Cochrane review
found that neither the topical photosensitizing agent nor the
type of light produced significantly di erent results.24 The
review did find that longer incubation periods of 4 hours with
ALA resulted in better outcomes compared to shorter incuba-
tion times of 0.5, 1, and 2 hours.24 In a randomized clinical trial,
PDT showed a 14% better chance of complete clearance com-
pared to cryotherapy after 3 months.33 A single application of
5-ALA patches applied 4 hours prior to light exposure resulted
in 89% clearance 12 weeks after treatment.34 At the 12-month
follow-up, this same treatment regimen was associated with
24% recurrent lesions.34 Common adverse events include pho-
tosensitivity, pain, erythema, and pruritus.33 PDT was found to
produce a better cosmetic outcome than cryotherapy and 5-
FU.24 Other than cosmetic outcome, PDT is a good choice for
patients where compliance may be an issue due to its single
application.
5-Fluorouracil
5-FU decreases cell proliferation and induces cell death by
interfering with deoxyribonucleic acid (DNA) and ribonucleic
acid (RNA) synthesis in cells with high mitotic rates.24 A Coch-
rane review found that the e cacy of 0.5 and 5% 5-FU was sim-
ilar when directly compared.24 The review also found that 5-FU
e cacy was similar to PDT and superior to cryotherapy.24 A
review of studies demonstrated an average complete clearance
of 52%.35 Treatment with 5% 5-FU applied twice a day for 4
weeks showed an initial clearance of 96% and a histological
clearance of 67%.31 At 12-month follow-up, 35% of the initially
clear patients remained clear.31 The Cochrane review found that
patients treated with 5-FU treatment experienced substantial
skin irritation, but in general was not cause for withdrawal
from treatment.24 Possible adverse e ects of 5-FU are eryth-
ema, erosions, edema, and dryness at the site of application.36,37
The recommended treatment and duration of 5-FU varies with
strength and location of application, but usually is between 1
and 4 weeks.
Diclofenac
Diclofenac is a nonsteroidal anti-inflammatory drug in a 2.5%
hyaluronic acid gel vehicle. Although the precise mechanism is
not understood, the current hypothesis is that the inhibition of
cyclooxygenase-2 (COX-2) leads to a decrease in prostaglandin
synthesis and may be responsible for inhibition of cell di eren-
tiation, induction of apoptosis, alteration of cell proliferation,
and inhibition of angiogenesis.38,39,40,41 A meta-analysis of three
studies that included 364 patients found cumulative and total
lesion scores of zero in 50% of patients treated for 90 days and
33% clearance of patients treated for 60 days.42 A study of six
organ transplant patients reported three out of the six com-
pletely cleared clinically and histologically after applying diclo-
fenac 3% twice a day for 16 weeks, while the rest achieved at
least 30% clearance.43 Akarsu et al reported a complete clear-
ance of 19.1% 24 weeks after starting diclofenac twice daily for
12 weeks, and reported no withdrawals from the study secon-
dary to adverse e ects.44 Common adverse e ects included
itching, scaling, dryness, rash, and erythema, and rarely pares-
thesia and hyperesthesia.44 One disadvantage of diclofenac is
the lengthy treatment period of twice daily application for 60
or 90 days.
Imiquimod
Imiquimod is an immune modulator that enhances innate and
acquired immune responses resulting in antiviral and antitu-
moral activity.45 A meta-analysis of four studies and 393 sub-
jects showed an average complete clearance of 70% in patients
treated with 5% imiquimod cream.35 Application of 5% imiqui-
mod three times weekly for 4 weeks and repeating this regimen
if initial lesions did not clear after a 4-week rest period pro-
duced a histological and clinical clearance of 73 and 86%,
respectively, 8 weeks after final treatment.31 Other studies
report a complete clearance rate ranging from 48.3 to 57.1%.46,
47,48 At a 12-month follow-up, 86% of patients who were ini-
tially clear showed sustained clearance.31 Patients with initial
clearance were found to have a 25% recurrence rate when
applying imiquimod three times per week and a 47% recurrence
rate with twice a week application at 16 months.49 Krawtch-
enko et al also reported that 81% of the patients treated with
imiquimod had an excellent cosmetic outcome.31 Complete
clearance rates are higher with 5% imiquimod versus 3.75%
imiquimod following 8 weeks of treatment.50,51 A Cochrane
review found treatment with 5% imiquimod resulted in more
participant withdrawal secondary to adverse e ects than
treatment with 2.5 and 3.75% imiquimod.24 Common adverse
events were erythema, scabbing, and flaking (Table 1.2).47
Chemical Peels
Chemical peels are another option for treating widespread AKs.
A variety of chemical peels can be used to treat AKs and should
be selected according to the histological level or severity of skin
pathology in order to achieve optimal results.61 Medium-depth
chemical peels such as 70% glycolic acid with 35% trichloroace-
tic acid (GA-TCA) and Jessner’s solution with 35% trichloroacetic
acid (JS-TCA) penetrate to the papillary dermis and can be used
to treat AKs.57 The exfoliative e ect of chemical peels stimulates
new epidermal growth and collagen formation.61 Chemical
peels have shown to alter the epidermis restoring a more nor-
mal pattern of columnar cells with increased polarity.61 JS-TCA
and GA-TCA at day 60 post peel showed a hyperplastic epider-
mis and an expanded papillary dermis.57 This study also
reported 7% of JS-TCA peels and 15% of GA-TCA peels developed
Prevention of Future Skin Cancer
3

new elastic fibers. In a split face study, JS-TCA was found to pro-
duce equivalent results when compared to 5-FU.53 Subjects in
this study had a 75% reduction in AKs and experienced no
recurrence of AKs for at least 1 year. In addition to treating AKs,
Abdel-Daim et al suggest chemical peeling with glycolic acid,
salicylic acid, and trichloroacetic acid could serve tumor pre-
vention by removing photodamaged cells.62 This was shown in
a study done by Hantash et al which demonstrated a 40-fold
lower rate of developing subsequent NMSC after treatment
with 30% trichloroacetic acid peel compared to 5-FU and Car-
bon dioxide (CO2) laser.54 This study also comments on the
excellent cosmetic results produced by trichloroacetic acid
peels. JS-TCA and GA-TCA peels resulted in erythema, crusting,
and swelling within 24 hours with crusting and swelling resolv-
ing by day 7.57 Medium- and deep-depth peels have been asso-
ciated with pigmentary changes for dark-skinned individuals,
infections, allergic reactions, improper healing, hypersensitiv-
ity, and disease exacerbation.55,56
Lasers
Di erent ablative laser systems are used to treat AKs. CO2
lasers work by collateral heat which causes collagen synthe-
sis and the sealing of blood vessels and nerve endings
leading to less pain and bleeding, whereas Erbium :yttrium
aluminum garnet (Er:YAG) lasers work w ith high water
absorption resulting in little collateral heat.63 Re-epitheliali-
zation and resolution of erythem a following Er:YAG
treatment occurred in 5 to 8 days and 3 to 6 weeks, respec-
tively.58 In comparison, re-epithelialization and resolution of
erythem a following CO2 laser treatment occurred on an
average of 7 days and 6 weeks, respectively.64 Jiang et al
treated five patients w ith a m ean of 24 lesions per patient
with the Er:YAG laser, resulting in a 93% reduction in AKs.58
In a retrospective study, Iyer et al treated 24 patients w ith
an Er:YAG or CO2 laser or a combination of the two lasers,
resulting in a 94% reduction of AKs.60 Also in a retrospective
study of 25 patients treated in the sam e m anner, Ostertag
et al found 80% of patients rem ained lesion free for 1 year,59
which is sim ilar to the 87% clearance reported by Iyer et
al.60 On average, 64% of recurrences occurred 32.7 m onths
after treatment.59 This study also failed to identify a statisti-
cal di erence in the apparatus used in relation to the recur-
rence. Histological studies 3 m onths after Er:YAG treatments
showed reversal of epiderm al actinic dam age, as well as an
increase in collagen form ation and decreased elastosis in the
superficial papillary dermis.58 Ablative laser treatm ent is
believed to provide prophylaxis against future keratosis and
Table 1.2 Common therapeutic options for skin cancer prevention in patients with actinic damage
Treatment modality
Length of treatment Initial clinical
clearance
Long-term efficacy Common adverse effects Comments
Photodynamic therapy Best results seen
with incubation
periods of 4 h24
86% complete
clearance52
24% recurrence at 12
mo34
Photosensitivity, pain,
erythema, and pruritus33
Better cosmetic outcome
compared to 5-FU and
cryotherapy24
5-fluorouracil (5-FU)

1–4 wk

52%35 compared to
96%31 complete
clearance
35% maintained
clearance at 12 mo31
Erythema, erosions,
edema, and dryness36,37
0.5 and 5% have similar
efficacy24
Diclofenac

60–90 d

50% when treated for
90 d, and 33% when
treated for 60 d42
19.1% complete
clearance at 24 wk44
Itching, scaling, dryness,
rash, and erythema44
Imiquimod

2–3 times/wk for 1
mo
86% complete clea-
rance31
25% recurrence 3
times/wk, 47%
recurrence 2 times/
wk49
Erythema, scabbing, and
flaking47
81% of patients reported an
excellent cosmetic
outcome31
Cryotherapy

Greater efficacy for
freezing lesion
longer than 10 s30
80% complete
clearance when
frozen for 10 s
compared to 67.2%
when frozen for 2 s30
631 to 98.8% com-
plete clearance32
Redness, blistering,
crusting, oozing, and
ulceration29
29% of patients experienced
hypopigmentation after
freeze times of 20 s or
longer30
Medium-depth chemi-
cal peels
One-time application 75% reduction in
AKs53
No recurrent AKs
after 1 y53
40-fold decrease in
developing
subsequent NMSC54
Pigmentary changes for
dark-skinned individuals,
infections, allergic
reactions, improper
healing, hypersensitivity,
and disease
exacerbation.55,56
Effective in treating
photodamage57
Laser ablation

One-time procedure 93% reduction in
AKs58
8059 to 87%60lesion
free for 1 y
Infection, pigmentary
changes, acne, milia, scar
formation, and atrophic
and/or easily bruising
skin59
On average 64% of
recurrences occur 32.7 mo
posttreatment59
Abbreviations: AKS, actinic keratoses; NMSC, nonmelanoma skin cancer.
Prevention of Future Skin Cancer
4

cancers.58,59,60,65
Im m unohistochem istry analysis 4 weeks
after treatment with a CO2 laser found a decrease in expres-
sion of p53 and Ki-67.63 A study reported a decrease in the
p53 m utation 6 m onths after CO2 laser treatm ent, and the
authors concluded this treatment theoretically could
decrease the risk of malignant transform ation.66 Ablative
laser techniques o er dramatic improvement of actinic dam -
age of the skin.59 A comparison study of 5-FU and Er:YAG
laser resurfacing found laser resurfacing to be m ore e ective
in relation to recurrence rates.67 The m ost comm on side
e ects of ablative lasers are infection, hypopigmentation,
hyperpigm entation, acne, milia, scar form ation, and atrophic
and/or easily bruising skin.59 Since Er:YAG lasers cause less
tissue damage, they have fewer associated side e ects such
as scarring and pigm entary changes, along w ith a decreased
recovery period.58
Cyclooxygenase-2 Inhibitors
Epidemiological studies suggest COX-2 may be involved in the
pathogenesis of NMSC.68,69,70,71,72,73,74,75 COX-2 is not constitu-
tively expressed in most tissues,76 but can be induced by UV
radiation.70,73,77 Celecoxib has been shown to be a selective
inhibitor of COX-2.78 Animal models have shown treatment
with celecoxib inhibits the development of UV-induced prema-
lignant skin papillomas in mice, which are believed to
correspond to AKs in humans.68,69,70,71,72,73 A randomized, dou-
ble-blind, placebo-controlled trial with oral celecoxib over 11
months in 240 subjects with biopsy-proven NMSC or AK
reported a decrease of 58% of NMSC in the treatment group, but
failed to show a decrease in AKs.79 Tang et al performed a trial
in which patients with basal cell nevus syndrome received cele-
coxib or a placebo, and found that the treatment group had 26%
fewer new BCCs compared to the placebo group at the end of 2
years.80
Antioxidants
Selenium is necessary for the functioning of glutathione peroxi-
dase,81 which acts to reduce DNA-damaging hydroxyl-free radi-
cals.82 Increased dietary selenium in mice has been shown to
provide protection from UV-induced skin tumors.83 A prospec-
tive study of 485 adults found patients with 1.3 to 2.8 µmol/L of
selenium had a decreased incidence of both BCC and SCC.84
However, no significant e ect to the incidence of BCC or SCC
was found in a randomized controlled trial of patients who
were treated with 200 µg/d of selenium for a mean of 4.5 years
and a total follow-up of 6.4 years.85 A Cochrane review that
included this study found the selenium group was 17% more
likely to develop NMSC, in particular SCCs.81 The review also
reported a 35% reduction in the risk of other cancer in the treat-
ment group.
Beta carotene has provitamin A (retinol) activity, and is an
antioxidant that may reduce free radical damage of DNA after
UV exposure.81 Beta carotene supplementation is believed to
work by reducing immunosuppression induced by UV radia-
tion.86 In a study of 1,805 patients with a recent history of
NMSC, patients received 50 mg of beta carotene daily for up to 5
years without a significant e ect on the incidence of new
NMSC.87 Oral vitamin A supplements, however, have been
shown to significantly reduce the 5-year probability of develop-
ing a new SCC.88
1.2.3 Dietary Modifications
Unsaturated fatty acids are major targets for free radical
attack81; therefore, it is possible that decreased dietary fats
could reduce free radical attack and carcinogenesis.89 A series
of animal studies showed a high level of dietary fats intake
markedly shortened the time between UV exposure and tumor
appearance, and increased the number of tumors that devel-
oped.90 Based on diet alone, patients on a higher fat diet were
found to be at 4.7 times greater risk for developing AKs during a
2-year period than those on a lower fat diet.89 A comparison
study of normal diet and a reduced fat diet over 24 months in
115 people with a history of no more than 2 NMSC found a
trend toward significant reduction in the incidence of NMSC at
2 to 5 years.91 Jaax et al further analyzed the results of the study
and found a significant di erence of new NMSC in subjects on a
low-fat diet compared to a normal diet.92
1.2.4 Chemoprevention in Organ
Transplant Recipients
Rates of developing AKs and Bowen’s disease in organ trans-
plant recipients (OTR) are 50 to 100 times higher than the gen-
eral population.93 OTRs are 250 and 10 times more likely to
develop SCC and BCC, respectively, than the general popula-
tion.94 SCC and BCC account for more than 90% of skin cancers
in transplant recipients.95,96,97,98 The incidence of skin cancer in
renal transplant patients increases with number of years post-
transplantation, starting at 7% after 1 year, and increasing to
45% after 11 years, and 70% after 20 years.97 In addition, the
incidence of skin cancer is related to age of transplantation with
a mean of 8 years posttransplant for those who received trans-
plants at approximately 40 years of age,99 and only 3 years for
patients who received transplants after the age of 60.95 Skin
cancer development is proportional to the level of immunosup-
pression.97 Significantly lower CD4 counts have been associated
with OTRs with cutaneous carcinomas compared to those with-
out skin lesions.100 SCCs appear to be more aggressive in
OTRs.101,102,103,104 This point is demonstrated in a study of car-
diac transplant recipients where 27% of all deaths 4 years post-
transplant were attributed to skin cancer.105 These studies
emphasize the importance of taking preventative measures in
this high-risk population to significantly impact morbidity and
mortality rates.
Systemic Retinoids
Retinoids are vitamin A derivatives that work by inhibiting cell
growth and inducing normal di erentiation in malignant
cells.106 Although indications for systemic retinoids are not con-
clusive, it has been suggested that retinoids are most e ective
in patients with a history of multiple NMSCs.107 Acitretin is a
retinoid and has been shown to be e ective in the prevention
of SCC in renal transplant recipients with a history of NSMC.108
A double-blinded placebo-controlled study demonstrated 42%
reduction in premalignant lesions and a 78% risk reduction in
developing NMSC within the first year of treatment of
Prevention of Future Skin Cancer
5

acitretin.109 In a crossover study, George et al reported an aver-
age increase of 42% of SCCs during drug-free period compared
to acitretin period.108 Studies have shown a statistically signifi-
cant decrease in skin cancers with a robust e ect in patients
with multiple prior NMSCs.109,110 Systemic low-dose retinoids
have been shown to significantly reduce the mean number of
SCCs for up to 3 years.111 Systemic retinoids can cause cheilitis,
headache, rash, photosensitivity, dry eyes, palmoplantar des-
quamation, epistaxis, elevate triglycerides, “stickiness,” aggra-
vation of existing musculoskeletal symptoms, nail changes,
gastrointestinal side e ects, and pruritus.108 A systematic
review of oral retinoids found that headaches, rash, musculos-
keletal symptoms, and hyperlipidemia were the most common
causes of withdrawal from treatment.112 No significant di er-
ence in adverse e ects was found when comparing 0.4 mg/kg/d
acitretin for 12 months versus 0.4 mg/kg/d for 3 months, then
0.2 mg/kg/d for the remaining 9 months.113 Retinoids are e ec-
tive only during treatment.111 A “rebound” e ect on the devel-
opment of SCCs when acitretin is discontinued has been
reported,107,108,109,111 and is most marked in patients taking ret-
inoids longer than 12 months.111 Continued use of systemic ret-
inoids can accelerate osteoporosis, calcification of tendons and
ligaments, osteophytes, and bone spurs around joints.114,115
Besides recom m ending treatments to prevent the transfor-
m ation of precancerous lesions, derm atologists also perform
skilled physical exams that allow for early detection of skin
cancers and educate patients on m ole m apping and self-skin
exams (SSE).
1.2.5 Secondary Prevention
The USPSTF defines secondary prevention as preventive meas-
ures that identify and treat asymptomatic persons who have
already developed risk factors or preclinical disease, but in
whom the condition has not become clinically apparent.5 Der-
matologists consistently perform secondary prevention meth-
ods in their practice by performing skin examinations, mole
mapping, and teaching patients how to perform skin self-
examinations. Since Breslow thickness is the strongest prognos-
tic indicator,116 it is important to detect melanoma at the ear-
liest stage possible.
Dermatologists have a positive impact on early detection of
melanoma with an increase in incidence of melanoma and a
decrease in mortality.117 This study found that the increase in
incidence was mostly due to an increase in the diagnosis of
stage I cancers.117 Authors attributed this finding to the ease of
access to health care due to the high ratio of dermatologists per
capita and increased public awareness.117 In addition, patients
with an established dermatologist were more likely to be given
a diagnosis of melanoma in situ and to have thinner invasive
melanoma.7
Although currently the USPSTF does not recommend SSE for
the general population,118 there is evidence that supports SSEs,
especially in high-risk groups. Risk factors for melanoma
include personal history of melanoma (5–8%),119,120 family his-
tory of melanoma in two or more family members,121 numer-
ous nevi and presence or history of atypical/dysplastic nevi,122,
123,124 fair skin (fourfold),125 red hair and blue eyes (twofold),126
history of NMSC (twofold to threefold),127,128 history of sun-
burns or excessive UV light exposure (twofold),129 and indoor
tanning (twofold to threefold).130 The National Comprehensive
Cancer Network (NCCN) recommends SSE in patients with a
history of melanoma and NMSC.37,131,132 It is estimated that 75%
of melanomas are detected by patients themselves or by
spouses, friends, or other lay persons.133,134,135,136,137 A retro-
spective cross-sectional study reported patients detected 41.7%
of melanomas in situ, 51% of melanomas, and 62.4% of invasive
melanomas.7 A study of 816 melanoma patients found patients
who conducted SSE were associated with early diagnosis.134 In
a separate study, patients who conducted SSE were found to
have significantly thinner melanomas.138 In a large study of
1,062 melanoma patients, 19% had a recurrence that was most
often self-detected.139 This study also observed that self-detec-
tion independently predicted survival. A literature review
showed a wide range of sensitivity and specificity for SSE rang-
ing from 25 to 88% sensitivity and 57 to 97% specificity.140 A
randomized controlled trial showed an increase in accuracy
and specificity of SSEs when patients received a leaflet with
photos of nevi, seborrheic keratoses, and early melanomas.141
Fig. 1.1 is taken from the AAD’s website demonstrating the
appropriate method to perform a SSE.142 The SSE can create a
feeling of joint responsibility with the dermatologist in early
detection of melanoma.143 It is recommended that SSEs be per-
formed frequently at first to become familiar with their nevi
and then monthly (Table 1.3).143
Patients with multiple nevi are at increased risk for develop-
ing melanoma compared to the general population. A study
found a relative risk of 1.6 for patients with 11 to 25 nevi, 4.4
for 26 to 50 nevi, 5.4 for 51 to 100 nevi, and 9.8 for patients
with more than 100 nevi.147 Patients with atypical nevi are also
at high risk. The same study reported relative risks of 3.8 and
6.3 for patients with 1 to 5 atypical and more than 6 atypical
nevi, respectively.147 It is estimated that 22 to 50% of melano-
mas show nevus origin.123,148,149 Mole mapping is especially
helpful in these individuals. Simply drawing a mole on a mole
diagram improved accuracy of reporting new lesions on SSE.150
The ADD has provided an excellent mole map with a lesion log
that is demonstrated in ( Fig. 1.2).142 Other studies have dem-
onstrated that the use of digital photography increases the diag-
nostic accuracy of SSEs.150,151,152 Total nevus number usually
peaks by the third decade of life and declines in the seventh or
eighth.153 With this in mind, dermatoscopic monitoring can be
performed for concerning lesions in younger individuals and
total body photography to monitor for new lesions in the
elderly.143
1.3 When to Treat
1.3.1 Nonmelanoma Skin Cancer
The primary goal of treatment of BCC is the cure of the tumor
along with maximal preservation of function and cosmesis. In
order to achieve this goal, each case should be individualized
based on treatment cure rate, preservation of function and
cosmesis, and patient’s preference. Tumors with low-risk char-
acteristics and uncomplicated high-risk patients can be e ec-
tively treated by dermatologists. Indications, risks, and benefits
for di erent treatment modalities will be discussed later in the
book, so this section will focus on characteristics of low-risk
tumor characteristics found in Table 1.4.
Prevention of Future Skin Cancer
6

Fig. 1.1 Self-skin exam. (Reproduced with permission from the American Academy of Dermatology.142 Copyright ©2015. All rights reserved.)
Table 1.3 Risk factors for cutaneous melanoma
Risk factor

Odds ratio

Information
Personal history of melanoma

Standardized incidence ratio 4.5–25.6
Family history of melanoma

1.8
11–50 common moles >2 mm

1.7–1.9
55–100 common moles >2 mm

3.2–3.7
>100 common moles >2 mm

7.6–7.7
1–4 atypical nevi

1.6–7.3
Atypical moles: ill-defined or irregular border; irregular pigmentation;
diameter >5 mm; erythema (blanchable in lesion or at edge);
accentuated skin markings
Reported growth of a mole

2.3
Giant congenital melanocytic

Relative risk range 239–1,224 for nevi>20 cm in diameter extra
cutaneous as well as cutaneous melanoma
Skin that does not tan easily

1.98
Light-colored Skin

1.40–1.42
Light-colored eyes

1.55–1.60
Red or light-colored hair

1.4–3.5
Presence of actinic lentigines

1.9–3.5
History of nonmelanoma skin cancer

Twofold to threefold increased risk127,128
Female

Female:male standardized incidence ratio is 1.3:1
Prevention of Future Skin Cancer
7

Table 1.3 continued
Risk factor

Odds ratio

Information
Age

Melanoma is rare in childhood and adolescence but risk increases with
age
Affluence

Relative risk approximately of 3 for least deprived compared to most
deprived on Carstairs deprivation category
Unusually high sun exposure

2.6
Indoor tanning

A single session can increase the risk of melanoma by 20%144
Occupational exposure to coal tar, pitch, creosote,
arsenic, or radium145
Pesticide use more than two times per year145
Source: Modified from Scottish Intercollegiate Guidelines Network 2004.146
Fig. 1.2 Mole map and log example. (Reproduced with permission from the American Academy of Dermatology.142 Copyright ©2015. All rights reserved.)
Prevention of Future Skin Cancer
8

1.3.2 Melanoma
Understanding when to treat or when to refer melanoma can
be di cult since there are no hard and fast rules. Dermatolo-
gists can perform a wide local excision on lesions with a Bres-
low depth of less than 1 mm and less aggressive histological
features. Ulceration and mitoses are also important to consider.
A T1b melanoma can be referred to a general surgeon for senti-
nel lymph node biopsy and/or a medical oncologist for further
work-up. Tumor, node, metastasis (TNM) staging criteria are
listed in Table 1.5.154
1.4 When to Refer
1.4.1 Nonmelanoma Skin Cancer
The NCCN recommends that complicated high-risk tumors,
regional recurrence, or the development of distant disease be
managed by a multidisciplinary tumor board.131 Characteristics
of high-risk basal and squamous cell tumors can be found in
Table 1.6. Metastasized SCC to regional lymph nodes has been
associated with lymphovascular invasion, poor di erentiation,
and perineural invasion.155 In addition, patients with regional
Table 1.4 Characteristics of low-risk recurrence
Basal cell cancer

Squamous cell cancer142
Area <20 mm on trunk and
extremities (excluding pretibia,
hands, feet, nail units, and ankles)
Area <20 mm on trunk and
extremities (excluding pretibia,
hands, feet, nail units, and ankles)
Area <10 mm on cheeks, forehead,
scalp, neck, and pretibia
Area <10 mm on cheeks, forehead,
scalp, neck, and pretibia
Area <6 mm on central face,
eyelids, eyebrows, periorbital,
nose, lips, chin, mandible, preau-
ricular and postauricular skin/sulci,
temple, ear, genitalia, hands, and
feet (location independent of size
may constitute high risk in certain
clinical settings).
Area <6 mm on central face,
eyelids, eyebrows, periorbital,
nose, lips, chin, mandible, preau-
ricular and postauricular skin/sulci,
temple, ear, genitalia, hands, and
feet (location independent of size
may constitute high risk in certain
clinical settings).
Primary tumor

Primary tumor
Not a site of prior radiation therapy Not a site of prior radiation therapy
or chronic inflammatory process
Immunocompetent

Immunocompetent
Well-defined borders

Well-defined borders
Nodular, superficial, keratotic,
infundibulocystic, and
fibroepithelioma of Pinkus
Well or moderately differentiated
on pathology
Absence of perineural involvement Absence of perineural or vascular
involvement
Slow-growing tumor
Absence of neurologic symptoms
Thickness <2 mm or Clark levels I,
II, III
Source: Modified from National Comprehensive Cancer Network
2014.131
Note: Risk factors are also increase likelihood metastasis.
Table 1.5 AJCC TNM criteria for cutaneous melanoma
Tis

Thickness

Ulceration
status/mitosis
T1

N/A

N/A
≤1 mm

a: w/o ulceration and
mitosis <1/mm 2
b: with ulceration and
mitoses ≥1/mm2
T2

1.01–2 mm

a: w/o ulceration
b: with ulceration
T3

2.01–4 mm

a: w/o ulceration
b: with ulceration
T4

>4 mm

a: w/o ulceration
b: with ulceration
N classification

Number of metastatic
nodes
Nodal metastatic mass
N0

0 nodes

N/A
N1

1 node

a: Micrometastasisa
b: Macrometastasisb
N2

2–3 nodes

a: Micrometastasisa
b: Macrometastasisb
c: In-transit met(s)/
satellite(s) without
metastatic nodes
N3

4 or more metastatic
nodes, or matted
nodes, or in-transit
met(s)/satellite(s) with
metastatic node(s)
M classification

Site

Serum LDH
M0

0 sites

N/A
M1a

Distant skin, subcuta-
neous, or nodal
metastases
Normal
M1b

Lung metastases

Normal
M1c

All other visceral
metastases
Normal
Abbreviation: AJCC, American Joint Committee on Cancer; LDH, lactate
dehydrogenase; TNM, tumor, node, metastasis.
Source: Modified from Balch et al 2010.154
aMicrometastases are diagnosed after sentinel lymph node biopsy and
completion lymphadenectomy (if performed).
bMacrometastases are defined as clinically detectable nodal metastases
confirmed by therapeutic lymphadenectomy or when nodal metastasis
exhibits gross extracapsular extension.
Prevention of Future Skin Cancer
9

nodal involvement are at a significant increased risk for recur-
rence and mortality.156 The NCCN recommends patients with
palpable lymph nodes or suspicious lymph nodes on imaging
receive a fine needle or core biopsy, and that negative findings
be confirmed by re-biopsy and/or re-evaluation.131 In the rare
instance of metastasized cutaneous BCC, the NCCN suggests
that a trial of vismodegib may be helpful even in the case of
metastatic basosquamous carcinoma.131 In the case of meta-
static SCC, the NCCN recommended cisplatin monotherapy, cis-
platin plus 5-FU, epidermal growth factor inhibitors, or clinical
trials.131
1.4.2 Melanoma
In general, tumors with a Breslow depth of greater than 1 mm
should be referred to a surgeon for sentinel lymph node biopsy.
It is also important to discuss a general surgeon referral with
patients who have T1b cancers and/or a Breslow depth between
0.75 and 1 mm with 1 or more mitoses/mm 2. A medical oncolo-
gist is an important part of patient care for those with stage II
melanoma that exhibits aggressive features such as micrometa-
stases and a deep Breslow depth, or greater than stage III
cancer.
1.5 Follow-Up
1.5.1 Nonmelanoma Skin Cancer
It is estimated that 30 to 50% of patients with NMSC will
develop another NMSC within 5 years.157 In addition to a
10-fold increased risk of developing a subsequent NMSC
compared to the general population,158 they are also at
increased risk for developing cutaneous m elanom a.159 Nearly
70 to 80% of all cutaneous SCC recurrences develop within
2 years of initial treatm ent.160 Consequently, it is important
to closely follow these patients.
NCCN recommendations for nonmelanoma
skin cancer
● Complete skin exam every 6–12 months for life in patients
with a history of BCC.
● Complete skin and regional lymph node exam every 3–12
months for 2 years, then every 6–12 months for 3 years,
then annually for life for patients with a history of local SCC.
● Complete skin exam with regional lymph node exam every
1–3 months for 1 year, then every 2–4 months for 1 year,
then every 4–6 months for 3 years, then every 6–12 months
annually for life for patients with regional SCC.
● Patient education on sun protection and self-skin examina-
tion regardless of type of skin cancer.
Abbreviations: BCC, basal cell carcinoma; SCC, squamous cell
carcinoma.
Source: Modified from National Comprehensive Cancer Net-
work 2014.131
1.5.2 Melanoma
Approximately 30% of stage I to III melanomas that are com-
pletely resected will develop a recurrence.161,162,163 The recur-
rence rate of melanoma is highest in the first 2 to 3 years after
treatment.164,165 Recurrence rates of 5.2% with stage IA, 18.4%
with stage IB, 28.7% with stage IIA, 40.6% with stage IIB, and
44.3% with stage IIC have been reported.166 An overall 5-year
relapse-free survival for stage IIIA, IIIB, and IIIC patients was 63,
32, and 11%, respectively.167 Another study found the site of
first recurrence with stage I to III melanoma was local in 13% of
patients, in-transit in 17%, regional lymph nodes in 46%, and
distant in 24%.168 Among 340 relapsing stage III patients, 28%
had local/in-transit recurrence, 21% had regional node recur-
rence, and 51% had systemic recurrence.167 The risk of recurrent
disease makes appropriate follow-up essential. Unfortunately,
due to the absence of clear data, there are various opinions for
appropriate follow-up of patients with melanoma.132
Table 1.6 Characteristics of high-risk recurrence
Basal cell cancer

Squamous cell cancer
Area ≥20 mm on trunk and
extremities (excluding pretibia,
hands, feet, nail units, and ankles)
Area ≥20 mm on trunk and
extremities (excluding pretibia,
hands, feet, nail units, and ankles)
Area ≥10 mm on cheeks, forehead,
scalp, neck, and pretibia
Area ≥10 mm on cheeks, forehead,
scalp, neck, and pretibia
Area >6 mm on central face,
eyelids, eyebrows, periorbital,
nose, lips, chin, mandible,
preauricular and postauricular skin/
sulci, temple, ear, genitalia, hands,
and feet (location independent of
size may constitute high risk in
certain clinical settings)
Area >6 mm on central face,
eyelids, eyebrows, periorbital,
nose, lips, chin, mandible,
preauricular and postauricular skin/
sulci, temple, ear, genitalia, hands,
and feet (location independent of
size may constitute high risk in
certain clinical settings)
Recurrent tumor

Recurrent tumor
Site of prior radiation therapy

Site of prior radiation therapy or
chronic inflammatory process
Immunosuppressed

Immunosuppressed
Poorly defined borders

Poorly defined borders
Pathology showing morpheaform,
basosquamous (metatypical),
sclerosing, mixed infiltrative, or
micronodular features in any
portion of the tumor
Poorly differentiated on pathology
Perineural involvement
Adenoid (acantholytic),
adenosquamous (showing mucin
production), or desmoplastic
subtypes
Rapidly growing tumor
Neurologic symptoms
Thickness or Clark level≥2 mm or
IV, V
Perineural or vascular involvement
Source: Modified from National Comprehensive Cancer Network 2014.131
Prevention of Future Skin Cancer
10

NCCN recommendations for melanoma skin
cancer
● At least annual skin exam for life.
● Radiologic imaging for specific signs and symptoms.
● Regional lymph node ultrasound may be considered for equiv-
ocal lymph node physical exam, patients who were o ered but
did not undergo sentinel lymph node biopsy, or patients with a
positive sentinel lymph node biopsy who did not undergo com-
plete lymph node dissection. However, nodal basin ultrasound
is not a substitute for sentinel lymph node biopsy.
● Risk of recurrence, prior primary melanoma, family history of
melanoma, atypical moles, and patient/physician concern
should influence follow-up schedule.
Source: National Comprehensive Cancer Network 2014.132
The NCCN recommendations for follow-up for all patients
regardless of stage of melanoma can be found above. The NCCN
also recommends a skin and lymph node exam for patients with
stage IIB to IV melanoma every 3 to 6 months for 2 years, then
every 3 to 12 months for 3 years, then annually as clinically nec-
essary.132 It is important to consider performing a chest X-ray,
computed tomography (CT), and/or positron emission tomogra-
phy (PET)/CT scan every 4 to 12 months to screen for recurrent/
metastatic disease, and possibly more frequently in patients who
are at higher risk.132 Since there is a 13% risk of stage IIIC mela-
noma patients to have brain metastasis,167 an annual brain mag-
netic resonance imaging (MRI) can be considered.132 Routine
radiologic screening for asymptomatic recurrent/metastasis is
not recommended after 5 years.132
1.5.3 Family History of Melanoma
A single first-degree relative with melanoma nearly doubles
one’s risk for developing melanoma.126 A positive family history
has been associated with younger age of diagnosis of melanoma
with 68.6% being diagnosed at 45 years of age or younger.169
Patients with a family history of melanoma are more likely to
have multiple atypical nevi.169,170 Screening those with a
known family history have produced thinner melanomas.171,172,
173,174 A study suggested patients with a family history of mela-
noma would benefit from targeted dermatologic care.169 This is
in accord with a literature review that found 27% of the
reviewed guidelines recommended targeted monitoring.175
1.5.4 Familial Atypical Multiple Mole
Melanoma Syndrome
The median age of melanoma incidence in patients with familial
atypical multiple mole melanoma syndrome (FAMMS) that
carry the CDK2NA mutation has been reported to be between
33 and 45,176,177 but cases of melanoma have also been reported
in early teens and twenties.178 Screening for melanoma patients
with FAMMS should begin at age 10 with a baseline full-body
exam including oral mucosa and genital area.179,180,181,182 This
screening should also be o ered to all first- and some second-
degree relatives.183 It has been suggested FAMMS patients be
examined by a health care provider every 6 months to ensure
nevi stability.183 After this is established, patients should be
educated on the performance and importance of SSE, and sub-
sequent visits can be performed annually or as needed.183
1.5.5 Genetic Testing
FAMMS is a autosomal dominant with variable expressivity
and penetrance that typically presents as more than 50
moles.183 Typical germline mutations of the CDKN2A gene
are missense or nonsense mutations in p16(INK4), P15
(INK4b), or p18(INK4c).183 The Melanoma Genetics Consor-
tium (GenoMEL) has issued statements that genetic testing
for CDK2NA is premature citing varying penetrance and fam-
ily members with a negative genetic test are still at higher
risk than general population giving them a false security.182
Instead, it is recommended that first-degree relatives of indi-
viduals at high risk be engaged in the same programs of mel-
anoma prevention and surveillance irrespective of the results
of any genetic testing.182
1.5.6 Nevoid Basal Cell Carcinoma
Syndrome
Patients with nevoid basal cell carcinoma syndrome (NBCCS)
usually develop BCCs in the third decade of life with a median
age of 25.184 At the age of 20, the cumulative incidence of BCC is
14% in males and 12% in females. By 50 years of age, 77% of
females and 80% of males have been diagnosed with BCC.185
Approximately 90% of Caucasians with NBCCS develop BCCs,
compared to only 40% of African Americans. It has been sug-
gested patients have annual skin examinations.184
Genetic Testing
NBCCS is an autosomal dominant disorder.184 It is estimated
that 70 to 80% of mutations are inherited from a parent, while
the remaining 20 to 30% are new mutations.184 Evans and Farn-
don cited the need for surveillance for complications of NBCCS,
such as medulloblastoma in children and jaw cysts and BCCs in
adults.184 Genetic testing for at-risk relatives, including chil-
dren, may also be appropriate.184
1.5.7 Xeroderma Pigmentosum
Xeroderma pigmentosum (XP) is an example of how both
genetic and environmental interactions influence the course of
disease.186 XP patients develop AKs at an early age.187 If XP is
diagnosed at 20 years of age or earlier, there is a 10,000-fold
increased risk for developing NMSC on sun-exposed sites, and
greater than 2,000-fold increased risk for developing cutaneous
melanoma.187 The median onset of NMSC is 9 years of age, and
the median age for cutaneous melanoma is 22.187 Both BCC and
SCC can grow quickly and behave aggressively.188 Complete skin
examination with clinical color photographs of the entire skin
surface and close-ups (including a ruler) of individual lesions is
the suggested management plan.187 Depending on severity of
skin disease, frequent skin examinations approximately every 3
to 12 months are recommended.186 In addition to regular skin
Prevention of Future Skin Cancer
11

examinations, periodic routine eye and neurologic examina-
tions and audiograms are included in the management plan.187
Patients or parents should be instructed on morphology of BCC,
SCC, and abnormal pigmented lesions in order to perform fre-
quent skin exams.186
Genetic Testing
XP is an autosomal recessive mutation of nucleotide excision
repair.187 The diagnosis of XP is based on clinical findings and
family history.187 Functional testing to screen cells for abnor-
malities in DNA repair is the preferred laboratory diagnostic
method.187 XP patients with XP-A, B, D, F, and G mutations
experience severe sunburn after minimal sun exposure.186 Car-
rier testing for at-risk individuals and prenatal diagnosis are
available.187
1.5.8 Consolidation of Medications
Adverse drug reactions reported to the Norwegian Medicine
Control Authority from 1970 to 1994 reported photo-induced
drug eruptions represented 8% of cutaneous adverse events.189
The proposed mechanism involves a systemic/cutaneous drug or
its metabolites present in the skin and exposed to UV light.190
Photosensitive reactions are classified as either the more com-
mon phototoxic response or the less common photoallergic reac-
tions.191 Phototoxic eruptions are not immune mediated and
occur in all individuals with high doses of exposure of the culprit
drug and radiation at the appropriate wavelengths.190 Intensity
of responses are dependent on the dose of the photosensitizer
and sunlight.191 Photoallergic reactions are immune mediated
and do not occur in all individuals exposed to the drug and radi-
ation.190 There have been case reports of patients on known
photosensitive drugs for a prolonged period that develop cancer.
McCarthy et al report a patient with chronic granulomatous dis-
ease on long-term voriconazole that led to multifocal facial
SCC.192 Individuals are more prone to developing SCCs while on
photosensitizing drugs and being immunosuppressed.193,194,195
Miller et al reported two patients on long-term voriconazole that
developed five in situ melanomas.196 A review of 1,380 patients
treated with psoralen plus UV-A phototherapy (PUVA) found an
increased risk of melanoma in patients receiving more than 250
treatments with the most pronounced risk occurring 15 years
from initial treatment.197 It is important to be mindful of the
increased risk of skin cancer long-term therapy with photosensi-
tive drugs poses. Table 1.7 was modified from Moore and con-
tains common photosensitive drugs.191
1.6 High-Risk Groups
1.6.1 Outdoor Workers
Outdoor workers have been identified as at-risk group for the
development of NMSC due to the nature of their work and high
levels of UV exposure.198 The term “outdoor worker” typically
includes individuals who work outdoors for 3 or more hours on
a usual workday.199 Sunburn rates among construction workers
has been estimated to be 50 to 80%.200 Not only do individuals
who work outside spend more time in the sun at work, but sev-
eral studies also show they spend a significant amount of time
outside during nonwork hours.201,202 Studies using dosimetry
methods to objectively quantify UV radiation exposure demon-
strate that outdoor workers receive higher than recommended
doses.203,204,205,206 Two separate meta-analyses have shown a
clear association between occupational UV exposure and
increased risk of developing SCC207 and BCC.208 The association
between occupational UV exposure and melanoma is less
clear.209 A systematic review of 29 published case-control stud-
ies revealed a significant positive risk for intermittent sun
Table 1.7 Drugs with reported photosensitivity
Diuretic agents

Antimicrobials
Hydrochlorothiazide, furosemide
(frusemide), chlorothiazide,
bendroflumethiazide, benzthiazide,
cyclothiazide, hydroflumethiazide,
methyclothiazide, trichlormethiazide,
polythiazide, amiloride,
ethacrynic acid, triamterene,
spironolactone, acetazolamide,
metolazone, quinethazone
Demeclocycline, nalidixic acid,
sulfamethoxazole, sulfasalazine,
ciprofloxacin, enoxacin,
lomefloxacin, ofloxacin,
norfloxacin, oxytetracycline,
tetracycline, doxycycline,
methacycline, minocycline,
trimethoprim, isoniazid,
sulfamethizole, gentamicin,
clofazimine, griseofulvin,
nitrofurantoin
Nonsteroidal anti-inflammatory
drugs
Antipsychotic drugs
Naproxen, ketoprofen, suprofen,
tiaprofenic acid, piroxicam,
diflunisal, diclofenac, mefenamic
acid, nabumetone, sulindac,
phenylbutazone, indomethacin,
ibuprofen
Chlorpromazine, trifluoperazine,
prochlorperazine, thioridazine,
chlorprothixene, promethazine,
perphenazine, fluphenazine,
promazine, haloperidol,
thiothixene, triflupromazine,
trimeprazine
Antidepressants

Cardiovascular drugs
Amitriptyline, trimipramine,
nortriptyline, protriptyline,
desipramine, amoxapine,
imipramine, doxepin
Amiodarone, nifedipine, quinidine,
captopril, enalapril, fosinopril,
ramipril, disopyramide,
hydralazine, clofibrate, simvastatin
Antimalarials

Hypoglycemics
Chloroquine, quinine,
pyrimethamine, mefloquine
Glibenclamide (glyburide),
tolbutamide, glipizide, tolazamide,
chlorpropamide, acetohexamide
Antihistamines

Cytotoxic drugs
Cyproheptadine, diphenhydramine,
brompheniramine, triprolidine,
loratadine
Fluorouracil, vinblastine,
dacarbazine, procarbazine,
methotrexate
Anticonvulsants

Hormones
Carbamazepine, lamotrigine,
phenobarbital (phenobarbitone),
phenytoin
Corticosteroids, estrogens,
progesterones, spironolactone
Systemic dermatological agents

Miscellaneous
Isotretinoin, methoxsalen

Gold salts, azathioprine,
hematoporphyrin
Note: Drugs are listed by therapeutic class and generic name. The drugs
are listed within each grouping in approximate order of frequency of
incidence of reports.
Source: Modified from Moore 2002.191
Prevention of Future Skin Cancer
12

exposure and a significantly reduced risk for heavy occupa-
tional exposure.129 These findings are supported by a meta-
analysis of 41 published studies that demonstrated a positive
association for intermittent exposure and an inverse association
with high continuous sun exposure and melanoma.210 Some
believe there is su cient evidence to consider skin cancer as an
“occupational disease.”198
Occupational sun exposure can be minimized or avoided by
following recommended sun-protective strategies such as wear-
ing wide-brimmed hats, long-sleeved shirts and pants, sun-
glasses, regular sunscreen use, seeking shade, and rescheduling
work tasks that are during peak UV time (10 a.m.–3 p.m.).199
Studies have shown low uptake of sun-protective strategies
among outdoor workers.206,211,212
A systematic review of
34 cross-sectional and interventional studies reported that many
outdoor workers never or only rarely wore long-sleeved shirt
(50–80%), sun-protective headgear (30–80%), and sunscreen
(30–100%).200 It has been shown that employees working under
mandatory sun protection policy have fewer solar keratoses and
less self-reported skin cancer excisions compared to employees
under voluntary sun protection policy.202 Several methods and
interventions have been shown to increase the application of
sun protection. Randomized trials incorporating education and
awareness about skin cancer protection demonstrated long-term
e cacy of workplace-based interventions. The first trial used a
UV photograph and/or video about skin cancer that resulted in a
significant increase in sun protection behavior for 12 months.213
Another trial incorporated communication strategies in the Go
Sun Smart Health Communication Campaign for ski area
employees that led to improved sunscreen and protective cloth-
ing use.214 The third trial involved the SunWise program and the
provision of hats and sunscreen for postal workers that also led
to improved sunscreen and protective clothing use.215 Provision
of personal protective equipment and education has also been
shown to increase sun protection in Israeli workers.216 Other
environmental considerations such as a workplace culture that
values sun protection217,218 and social norms219 have shown a
positive association with sun-safety behaviors.
1.6.2 Pilots
Flight personnel have been reported to have an increased inci-
dence of skin cancer.220 Aircraft windows block UV radiation
and measurements within the cockpit at high cruise altitudes
reveal only minimal exposure,221 but flight personnel are regu-
larly exposed to cosmic radiation that is composed of mainly
gamma and neutron radiation.222 This type of radiation can
easily penetrate the body and has been linked to multiple types
of cancer ranging from melanoma to brain cancer.220 Annual
radiation dose estimates vary depending on several occupa-
tional factors. With factors, such as the worker’s job (cockpit or
cabin crew), type of flights (long or short haul), and number of
hours flown, it is estimated that flight personnel receive an
annual radiation dose between 0.2 and 9.1 mSv/y.223 This is
higher than the average annual dose of most nuclear workers,
radiologic technologists, and industrial radiographers.224 It has
been estimated that airline pilots are exposed to 2 to 6 mSv/y of
ionizing radiation, and approximately 1 mSv of background
gamma radiation.222 A review of cosmic radiation exposure and
cancer risk revealed a risk estimate of 1.6 to 2.5 for developing
NMSC among airline crew members.220
The review also
reported a risk estimate for developing melanoma ranging from
1.8 to 10.2 in airline pilots and 0.4 to 3.7 in flight attendants.
Although higher incidence of skin cancer has been reported,
several confounding factors make a clear association challeng-
ing.220 This unclear association makes an approach to skin can-
cer prevention in this group di cult.
1.6.3 Tanning Beds
Indoor tanning has been labeled as a class I carcinogen by the
International Agency for Research on Cancer.225 One minute in the
average indoor tanning machine is estimated to be twice as carci-
nogenic as 1 minute in the midday Mediterranean sun.226 Individ-
uals who have used indoor tanning under the age of 25 are at a
higher risk for NMSC.227 The National Health Interview Survey
found indoor tanners tended to be non-Hispanic white females,
and of those females 62% were 25 or younger.228 The United States
attributable risk fraction was estimated to be 8.2% for SCC and
3.7% for BCC corresponding to approximately 170,000 cases of
NMSC associated with indoor tanning.227 In 2014, estimates of
NMSC linked with tanning beds rose to 419,000.229 A single
indoor tanning session has been associated with an increased risk
of 67% and 29% for SCC and BCC, respectively.229 Six tanning ses-
sions per year in a high school and college-aged individual
increases the risk developing BCC by 73%.230 It is estimated that of
melanoma cases in patients 18 to 29 years, 765 are linked to tan-
ning bed use.231 Nearly 25% of early-onset BCC could have been
avoided if individuals never tanned indoors.232 Approximately
3,438 cases of melanoma in Europe can be attributed to tanning
bed use.144 About 10,000 cases of melanoma are linked to indoor
tanning in the United States, Europe, and Australia.229 In a system-
atic review and meta-analysis, first tanning bed use before the age
of 35 was associated with a relative risk of 1.87 for developing
melanoma.144 The review also reported a dose response of 1.8%
increased risk of melanoma for each additional indoor tanning
session per year.144 Just one tanning session can increase the
user’s risk of developing melanoma by 20% and each additional
session during the same years increases the risk by another 25.144
According to the Youth Risk Behavior Surveillance System, 13% of
all high school students, 21% of high school girls, 32% of girls in
the 12th grade, and 29% of white high school girls use indoor tan-
ning beds.233 States including California, Hawaii, Illinois, Louisiana,
Minnesota, Nevada, Oregon, Texas, Vermont, and Washington
have passed laws against indoor tanning by minors.234 It has also
been reported that newer tanning beds are not safer than older
models,235 and since September 2014, the Food and Drug Admin-
istration required tanning beds to carry a class II (moderate- to
high-risk) warning.236
1.7 Sun Protection Methods
The International Agency for Research and Cancer has classified
UV radiation as a carcinogen.237 Survey results from the Center of
Disease Control demonstrated that although protective behaviors
such as sunscreen use, shade use, and wearing long clothing to
the ankles have increased in recent years, sunburn prevalence
remains high, with 50.1% of all adults and 65.6% of whites aged
18 to 29 years reporting at least one sunburn in a 1-year
period.238 A survey review showed the highest incidence of
Prevention of Future Skin Cancer
13

sunburns were among men, non-Hispanic whites, young adults,
and high-income groups, while women and older adults took
more precautions.10 Sunburns are more common among persons
aged 18 to 29 years compared with older adults.238 It is estimated
that less than 40% of adolescents use sun protection.10 Female
adolescents have been reported to use sunscreen more readily, in
a wider range of situations, and reapply sunscreen more often
when compared to adolescent males.239 In addition, more female
adolescents were found to receive encouragement to use
sunscreen from their mothers and peers.239 As stated previously
in the chapter, approximately 60% of parents apply sunscreen.10
Despite the more sensitive nature of infant and toddler skin, there
is evidence suggesting not only that the skin’s barrier protection
remains immature throughout at least the first 2 years of life, but
also that accumulation of UV radiation-induced changes in the
skin may begin as early as the first summer of life.240 A survey of
4,000 elementary students in Florida demonstrated that 51.3% of
non-Hispanic white students reported use of SPF 15 or greater
sunscreen “most of the time or always” compared with 35.3% of
Hispanic and 13.4% of non-Hispanic black students.241 According
to the National Ambulatory Medical Care Survey, children were
the population that received the fewest mentions of sunscreen
during their appointment.6 In this section, basic sun protection
methods will be discussed, which includes sunscreen, plant phe-
nols, SPF clothing, hats, and sunglasses.
1.7.1 Sunscreen
Sunscreen is one of the most common methods of sun protec-
tion used by Americans.238
The amount of UV radiation
required to produce a sunburn with sunscreen applied to the
skin in relation to the amount required to produce a sunburn
on unprotected skin is known as SPF.3 As the SPF increases, the
amount of protection increases.3 SPF 30 sunscreen absorbs
96.7% of the erythemogenic UV rays, whereas a SPF 60
sunscreen absorbs 98.3%, which is to say that a sunscreen of SPF
60 prevents almost twice the erythemogenic UV rays from
reaching the skin compared to an SPF 30 sunscreen.242 Most
people only use 25 to 50% of the recommended 2 mg/cm 2 of
sunscreen, resulting in less sun protection.243
Sunscreen is composed of organic and inorganic filters.
Organic filters are aromatic compounds that work by absorbing
UV light, and inorganic filters can absorb, reflect, and scatter UV
light.244 These filters absorb energy and electrons jump to an
excited state, and on return to ground state, release their energy
in the form of heat or light in longer wavelength.245,246,247
Para-aminobenzoic acid (PABA) derivatives, cinnamates, ben-
zophenones, and octocrylene are examples of organic filters that
have been described to cause photoallergy.248 Approximately less
than 1% of allergic contact dermatitis reactions in North America
are from sunscreens, but it is the most common cause of
photoallergy.249 The first UV filter available in the United States
was p-Aminobenzoic acid,244 but it also has the potential to
cause photoallergy, contact dermatitis, and stain clothes.250 A
cross-sectional analysis of 23,908 patients found the top three
most frequent allergens in sunscreens were benzophenone-3
(70.2% for 10% concentration, 64.4% for 3% concentration), DL-
alpha-tocopherol (4.8%), and fragrance mix I (4%).251
Titanium dioxide (TiO2) and zinc oxide (ZnO) are frequently
employed in sunscreens as inorganic physical sun blockers.252
Early generations of TiO2 and ZnO contained larger particles with
higher refractive indices, resulting in a thick, white coat with poor
particle dispersion and comedogenic potential.253 Recently, manu-
facturers have modified these minerals to micro and nano sizes,244
which scatter less visible light and have more transparent films
with improved cosmetic appearance.254 As TiO2 is more e ective
in UVB and ZnO in the UVA range, the combination of these par-
ticles assures a broadband UV protection.252 Compared to organic
filters, inorganic filters are less susceptible to degradation from
UV exposure and have a lower potential of causing allergic reac-
tions.253 Table 1.8 has the approved sunscreen ingredients and
their approximate UVcoverage.255
Sunscreens are meant to protect against the adverse e ects
of UV-B (290–320 nm) and UV-A (320–400 nm) radiation.252
UV-A and UV-B are both immunosuppressive.256 UV-A can pen-
etrate deeper into the skin reaching the dermis.244 High-energy
UV-B rays can create covalent bonds between pyrimidine bases
causing direct DNA damage.257,258 Both UV-A and UV-B can
cause indirect damage resulting in the formation of reactive
oxygen species, oxidative DNA damage, and activation of
Table 1.8 Approved sunscreen ingredients with absorption range
Type

Absorption rangea (shaded area)
UV-B
(290–320 nm)
UV-A2
(320–340 nm)
UV-A1
(340–400 nm)
Chemical
sunscreens
(organic
compounds)
Cinoxate
Ensulizole
Homosalate
Octinoxate
Octisalate
Octocrylene
Padimate O
Para-
aminobenzoic
acid (PABA)
Trolamine
ü
Dioxybenzone
Oxybenzone
Sulisobenzone

ü

ü
Ecamsule
Meradimate

ü
Avobenzoneb
ü
Physical
sunscreens
(inorganic
compounds)
Titanium dioxide
ü

ü
Zinc oxide
ü

ü

ü
Source: Modified from Joe et al 2012.255
aThe ranges are approximations; each sunscreen may not block the entire
range of ultraviolet (UV) radiation listed.
bCombined with octocrylene to ensure stability.
Prevention of Future Skin Cancer
14

inflammatory cytokines.259,260,261 Eventually, these insults can
result in sunburns, pigment darkening, premature aging, and
photocarcinogenesis.262,263,264 UV-B sunscreen failed to protect
from solar-simulated radiation-induced immunosuppression,
whereas a broad-spectrum sunscreen with the same SPF and a
higher protection in the UV-A range significantly reduced local
UV-induced immunosuppression.265 A greater average immune
protection with UV-A/UV-B sunscreens was seen in 211
volunteers using contact sensitivity as a model.266 The amount
of UV-A protection is also important in preventing local immu-
nosuppression as demonstrated by a study that demonstrated a
UV-A protection factor of 14 produced no local immunosup-
pression, whereas a UV-A protection factor of 6 failed to pre-
vent local immunosuppression.265 Also, sunscreens with UV-A
absorbers have been shown to significantly reduce the forma-
tion of pyrimidine dimers and p53 accumulation.267
Sunscreen should be used daily throughout the year since
80% of UV light passes through cloud cover, and approximately
25 and 80% is reflected by sand and snow, respectively.255
Sunscreen should also be applied 15 to 30 minutes before sun
exposure, applying it to common areas of NMSC such as the
face, ears, hands, arms, and lips.255 In addition, current recom-
mendations also state that sunscreen should be reapplied every
2 hours and after swimming, sweating, and toweling o .3
Health Benefits
When broad-spectrum sunscreen with an SPF of 15 or greater is
used as directed with other sun protection measures, sunburns
can be prevented with decreased risk of early skin aging and skin
cancer (melanoma and SCCs).268,269,270,271,272
Since 2011,
sunscreens that are broad-spectrum SPF≥15 can now include this
statement: “If used as directed with other sun protection meas-
ures, decreases the risk of skin cancer and early skin aging caused
by the sun.”273 Also in 2011 sunscreens that are not broad spec-
trum and have an SPF of less than 15 have the following state-
ment: “Spending time in the sun increases your risk of skin
cancer and early aging.”273 Even suberythemal doses of UV light
have been shown to increase thymine dimers, p53 expression,
and loss of Langerhans cells.274 A broad-spectrum sunscreen with
an SPF of 8 was shown to reduce these e ects as well as decrease
the number and size of melanocytes and lower the lysozyme-to-
elastin ratio.275 It is estimated that daily broad-spectrum SPF 15
or greater sunscreen use in a 5-year period could prevent 11 BCCs,
24 SCCs, and 838 AKs along with saving $88,203.276
Photoaging
Photoaging is a complex and progressive process that is exacer-
bated by UV exposure, and sunscreens are considered to be the
most e ective method of prevention.244 A randomized, double-
blind, placebo-controlled trial of 53 adults with previously
diagnosed skin cancer or AKs or both demonstrated that partic-
ipants that applied UV-A/UV-B sunscreen for 24 months had
less solar elastosis on biopsy.277 Application of a broad-spec-
trum sunscreen for 6 weeks in 12 French volunteers was shown
to minimize or prevent epidermal thickening, decreased procol-
lagen expression, and higher lysozyme-to-elastin ratio.275 The
Nambour Skin Cancer Prevention Trial assigned microtopogra-
phy grades to participants’ left dorsal hands after using a
sunscreen of SPF 16. A unit increase in a microtopography grade
is associated with deterioration of skin texture, increased visi-
ble blood vessels, increased comedones on the face, and
increased risk of developing AKs and NMSC.16,278,279 Results
showed daily sunscreen use reduced the likelihood of having
higher microtopography grades and also decreased the risk of
developing AKs and skin cancer.272
Prevention of AKs
AKs have been associated with high-dose cumulative UV
exposure.280 A randomized controlled trial gave participants
a broad-spectrum SPF 17 sunscreen to be applied daily, and
over a 7-m onth period the sunscreen group showed reduced
em ergence of new lesions, decreased total AKs, and greater
rem ission rates in a dose-dependent m anner.281 Daily use of
a broad-spectrum SPF 16 sunscreen led to a 24% reduction
in AK development.282
Prevention of Squamous Cell Carcinoma
SCC has also been associated with high-dose cumulative UVexpo-
sure.280 In a 4.5 year span, application of a broad-spectrum SPF
16 sunscreen 3 to 4 days a week showed a 40% reduction in the
development of SCC.283 After an 8-year follow-up, daily sunscreen
users continued to have a 40% lower incidence rate of SCC.271
Prevention of Melanoma
Melanoma results from a multifactorial process, and UV expo-
sure has been identified as a modifiable risk factor.268 Dennis et
al demonstrated that high-dose intermittent sun exposure asso-
ciated with sunburns has a lifetime relative risk of 1.6 in all age
groups.284 Even though UV exposure has been established as a
risk factor, evidence to support sunscreen as a preventative
method has been ambiguous and controversial.285,286 A slight
decrease in new nevi in children with freckles using a broad-
spectrum SPF 30 sunscreen was shown in a randomized con-
trolled trial.287 However, sunscreen was associated with more
nevi compared to the use of clothing in a European study of
white school-age children.288 Physical barriers and sunscreens
can partially prevent UV-B e ects on nevi, but sunscreens were
not quite as e ective as physical barriers in the prevention of
inflammatory changes induced by UV-B light.289 A meta-analysis
of cohort and case-control studies from 1966 to 2003 revealed
there was no protective or harmful association with melanoma
and sunscreen use.290 One study showed a 50% reduction in new
primary melanomas and a 73% reduction in invasive melanoma
after a 5-year trial period of daily broad-spectrum SPF 16
sunscreen use and a 10-year follow-up.268 A limitation to this
study is the intervention sites excluded the trunk and lower
extremities, and the entire body was analyzed for melanomas.291
Sunscreens and Basal Cell Carcinoma
Sun exposure has been identified as a risk factor for BCC,1 but
only about two-thirds of BCCs develop on sun-exposed areas.292
Eight years after the initial trial of daily broad-spectrum SPF 16
sunscreen, van der Pols et al found a 25% reduction in BCC inci-
dence in the sunscreen group that was found to be statistically
insignificant.271 This may be attributed to the latency period
described by Situm et al, which suggested that BCC has a
latency period of more than 20 years from the time of UV dam-
age to clinical onset.292
Prevention of Future Skin Cancer
15

1.7.2 Green Tea
The health benefits of green tea are attributed to the presence
of polyphenols. The most e ective and major polyphenol is epi-
gallocatechin-3-gallate (EGCG).293 There have been studies that
have shown polyphenols possess antioxidant, anti-inflamma-
tory, and anticarcinogenic activities in several in vitro and in
vivo systems.294,295 A significant reduction in UV-B–induced
DNA damage was shown with topical green tea phenols (GTP)
on mouse skin.296,297 Similarly, topical treatment of human skin
with GTPs prior to UV exposure resulted in a dose-dependent
repair of cyclobutane pyrimidine dimers.298 Topical application
of green tea or white tea extracts has been shown to provide
human skin protection from solar-simulated UV light.299 Oral
GTP300 and topical EGCG301 lead to significant reduction in
tumor incidence, tumor multiplicity, and tumor size in mice.
1.7.3 Protective Clothing
In the Surgeon General’s Call to Action to Prevent Skin Cancer,
it is recommended that long-sleeved shirts and long pants and
skirts been worn to provide maximal UV protection.3 The Sur-
geon General also states that tightly woven fabric and darker
colors may also provide more protection. Fabric porosity, type,
color, weight, and thickness influence UV protection.302 A UV-
protection factor of over 500 was assigned to jeans, tracksuits,
sweatshirts, pullovers, and tights.303 The investigators also sug-
gested layering of fabrics increases the protective e ect. The
application of UV absorbers into fabrics significantly improves
the UV protection factor.302 Wet cotton fabrics and polyester
with TiO2 showed significantly decreased UV protection com-
pared to their dry counterparts, whereas in wet modal with
TiO2 and polyester crepe with TiO2, the UV protection was sig-
nificantly increased compared to their dry counterparts.304
1.7.4 Hats
The Surgeon General recommends wide-brimmed hats made of
tightly woven fabric that shade the face, ears, and back of the
neck over straw hats or other porous fabrics.3 This study sug-
gests darker hats may provide better protection. The American
Cancer Society recommends wide-brimmed hats with a nonre-
flective underside or a shade cape.305
1.7.5 Sunglasses
Sunglasses are important for the skin around the eye, as well as
the eyes themselves.305 The American Cancer Society describes
the ideal sunglasses as blocking 99 to 100% of UV-A and UV-B
rays, and sunglasses labeled as “cosmetic” only block about 70%
of UV rays.305 Invisible chemicals that provide UV protection
can be applied to the lenses, so it is important to check labels
looking “Meets ANSI UV requirements.”305 Large-framed sun-
glasses with a wraparound frame are ideal and provide protec-
tion from light coming from multiple directions.305
Play
sunglasses for children are not su cient.305
1.7.6 Seek Shade
UV light is the strongest between 10 a.m. and 4 p.m .305 The
strength of UV light depends on the tim e of year and other
factors.305 The Surgeon General warns shade does not block
all UV radiation given it does not protect against scattered
UV rays.3 Di erent surfaces have di erent reflectivity. Snow
can reflect 80 to 90%306 of UV radiation, sand 20 to 30%,306
water 5 to 7%,306 concrete 14 to 17%,307 and grass 1 to 2%.307
Windows usually block most UV-B rays, but allow a sm all
portion of UV-A rays.305
1.8 Conclusion
Skin cancer is a rising concern 2 and economic burden,3 making
action toward its prevention necessary. Dermatologists play a
central role in promoting and preventing skin cancer. In order
to maximize skin cancer prevention, a multifaceted approach is
best. Raising public awareness and increasing patient education
e orts on sun-protective measures, early detection, and treat-
ment of precancers and early forms of skin cancer are key to
skin cancer prevention and successful management.
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Prevention of Future Skin Cancer
22

2 Clinical Detection of Skin Cancer
Michael Schowalter, Allison Vidimos, and Philip L. Bailin
Skin cancer is a broad term that encompasses all malignant
entities of the skin from common carcinomas of the surface epi-
thelium to rare tumors involving skin adnexal structures or
appendages such as sweat ducts, sebaceous glands, or hair fol-
licles. This chapter will focus on the clinical detection of com-
monly encountered skin cancers.
2.1 Basal Cell Carcinoma
2.1.1 Introduction
In practice, cutaneous malignancy is commonly broken down
into the melanoma and nonmelanoma skin cancers (NMSC).
NMSC represents the largest category of malignancies in the
United States, occurring on the order of 3.5 million times per
year in approximately 2.2 million patients.1 NMSC can be fur-
ther subdivided into basal cell carcinoma (BCC) and squamous
cell carcinoma (SCC). BCCs make up the majority of NMSC and
are the most common skin cancer in the United States as well
as globally. BCC is a malignancy of the basal keratinocyte. Most
tumors are sporadic, but patients with certain hereditary disor-
ders are at an increased risk of developing numerous BCCs. BCC
represents a large group with numerous subtypes, and as such
the presentation and clinical detection of individual tumors
varies and will be discussed separately.
2.1.2 History and Physical Exam
Sporadic BCCs are tumors primarily produced by ultraviolet
(UV) radiation. As such, tumors concentrate to areas of high
sunlight exposure. Careful examination of the head, face, neck,
arms, and dorsal hands should be conducted. Specifically on the
head, areas of higher UV exposure include nose, scalp, eyelids,
ears, and lips. Clinicians should ask historically about new
growths or persistent ones that may bleed or scab unprovoked.
BCCs are variably painful or itchy. Thorough history includes
questioning the nature of past UV radiation exposure such as
tanning bed use, intense sun exposure leading to blistering sun
burns, or therapeutic UV radiation such as psoralen and ultra-
violet A radiation (PUVA). In patients with personal and family
history of numerous BCCs, appropriate evaluation for genetic
syndromes should be conducted. Patients with Gorlin’s syndro-
me or BCC nevus syndrome (BCCNS) carry germline mutations
in the PTCH1 gene, vastly increasing their susceptibility to the
tumors. A review of medical history and medications for evi-
dence of iatrogenic immunosuppression is essential.
2.1.3 Nodular Basal Cell Carcinoma
Nodular or “classic” BCC is the most commonly encountered
type, comprising 60 to 80% of all BCC. Nodular BCC appears as
pink or red papules concentrated mainly to the head and neck.
These papules may have a pearly, waxy, or translucent appear-
ance. Many have grossly apparent telangiectasias coursing
through the lesion. Tumor borders may be rolled forming a cen-
tral area of depression (Fig. 2.1). Nodular BCCs are an indolent
subtype that slowly enlarge and may ultimately ulcerate and
bleed unprovoked, which leads to the formation of an adherent
crust overlying the lesion. Typically, nodular BCCs are not pain-
ful lesions unless neglected, large, and ulcerated.
2.1.4 Superficial Basal Cell Carcinoma
Superficial BCC is the next most common subtype, making up
approximately 15 to 20% of diagnosed BCCs. This subtype classi-
cally involves trunk and extremities, and tumor characteristics
are distinct from other BCC subtypes. Lesions are characterized
as slow growing, flat, or minimally elevated pink to red scaly
plaques, and may be quite subtle ( Fig. 2.2). The tumor may
focally have superficial erosions or ulcerations with formation
of crust. Borders are well defined and may be raised from the
adjoining normal skin. These tumors may mimic inflammatory
skin conditions such as atopic dermatitis, tinea infections, or
psoriasis. Clinicians should be wary of dismissing superficial
BCC as a nonmalignant entity in those patients with no prior
history of inflammatory skin conditions or when lesions appear
in atypical locations such as upper back or extremities distant
from joints. These tumors are similarly not painful or pruritic,
which may help di erentiate these tumors from inflammatory
skin conditions. Superficial BCCs are more common in men
than in women.
Fig. 2.1 Nodular basal cell carcinoma. Characteristic pearly or trans-
lucent appearance, rolled borders, focal ulceration, and overlying crust
on the left ear of an elderly, fair-skinned man.
Clinical Detection of Skin Cancer
23

2.1.5 Pigmented Variants
Pigmented BCCs are a variant of nodular and superficial BCC in
which there is variably retained melanin in the malignant basal
cell population (Fig. 2.3). These variants are common in
patients with skin of color. Tumors otherwise retain their pri-
mary characteristics. These entities may represent a pitfall in
clinical diagnosis of skin cancer and as such should be consid-
ered when evaluating pigmented lesions.
2.1.6 Morpheaform and Infiltrative
Basal Cell Carcinoma
Morpheaform and infiltrative BCCs are rare, clinically similar
entities with aggressive pathological patterns that will be dis-
cussed together. These entities make up approximately 5 to 10%
of all BCCs. Morpheaform BCCs occur most commonly in areas
of intense UV exposure, such as head and neck. They present as
skin-colored, white, or, less commonly, pink atrophic plaques.
Lesions rarely ulcerate unlike most BCC. These tumors may clin-
ically appear as smooth and shiny plaques and feel indurated
when palpated. As such, they are commonly confused for scars
(Fig. 2.4). Pain and itching may accompany this subtype of
BCC, given there is a greater tendency for deep invasion into
subcutaneous fat and muscle as well as perineural invasion.
2.2 Squamous Cell Carcinoma
2.2.1 Introduction
SCC is the second most common skin malignancy worldwide.
SCC is a malignancy of the squamous keratinocyte epithelium.
Tumors are sporadic or may be part of genetic conditions such
as xeroderma pigmentosum (XP), oculocutaneous albinism
Fig. 2.2 Superficial basal cell carcinoma. Slowly expanding pink scaly
plaque with subtle roll to peripheral borders.
Fig. 2.3 (a) Pigmented variant of superficial basal cell carcinoma in a patient of middle-eastern descent. (b) Pigmented variant of nodular basal cell
carcinoma on the inferior orbital rim in a middle-aged Chinese male.
Clinical Detection of Skin Cancer
24

(OCA), and epidermodysplasia verruciformis (EV). SCCs are
linked to UV exposure, whether natural or occupational. Other
risk factors include human papillomavirus (HPV) infection,
chronic immune suppression, ionizing radiation, scarring,
chronic sinus tract formation, chronic ulcerations, and chemical
carcinogenic exposures. In general, patients who have sporadic
or UV-induced SCCs do much better than their counterparts
who develop the malignancy in chronic wounds, scars, or as a
result of immunosuppression. Invasive SCC, defined as tumor
that has invaded below the skin basement membrane, can arise
within an existing SCC in situ (SCCis) or arise de novo. Various
clinical presentations of SCC, including SCCis, will be discussed.
2.2.2 History and Physical Exam
SCCs are induced by both chronic UV exposure and chronic
inflammation in the setting of scars and nonhealing wounds.
Physicians should be vigilant with the patient with general
signs of chronic UV exposure, including numerous solar lenti-
gines, fine facial wrinkling, skin atrophy, telangiectasias, and
Favre–Racouchot changes. A subtype, the Marjolin’s ulcer, is an
ulcerating SCC in sites of past trauma such as burns. As with
BCC, a careful examination of areas exposed to UV radiation
including head and neck, dorsal hands, and arms should be con-
ducted. Again, a history should concentrate on possible sources
for immune suppression, as well as a history of personal or fam-
ily history of past SCC.
2.2.3 Squamous Cell Carcinoma In Situ
Actinic Keratoses
While some controversy exists over the exact characterization
of actinic keratoses (AKs) with regard to malignant potential,
AKs, also known as solar keratoses, are generally felt to be a
form of low-grade squamous dysplasia. Studies have shown
that AKs transform into invasive SCC on the order of 0.025 to
20% per year.2 It is estimated that a quarter of the population in
the northern hemisphere has at least one of these lesions.
Clinically, AKs present in a number of di erent forms. Generally,
they are ill-defined, pink to erythematous papules with overly-
ing scale. They are small, with the majority being less than 1 cm
in size (Fig. 2.5a). Variants of AKs are named based on clinical
appearance: pigmented, hyperkeratotic (or hyperplastic), and
verrucous. When exuberantly hyperkeratotic, an AK may be
referred to as a cutaneous horn (Fig. 2.5b). AKs have a rough,
scaly, or sandpaperlike texture when palpated. AKs are generally
diagnosed in the broader clinical context of more widespread
UV or actinic damage. Di erential diagnosis for AKs includes
inflammatory dermatoses of the head and neck, such as sebor-
rheic dermatitis and contact dermatitis. Neoplasms such as
Bowen’s disease, superficial BCC, and melanoma in situ may
mimic AK.
Actinic Cheilitis
Actinic cheilitis (AC) is a clinical variant of AK involving the lips.
The characteristic pink or red scaly plaques may simulate
chapped or dry lips (Fig. 2.6). The normally well-demarcated
vermilion border of the lip may be obscured or blurred. The
lower lips are more extensively involved due to increased UV
exposure. There is also increased risk for AC in patients who
smoke or chew tobacco products.
Bowen’s Disease
A distinct form of SCCis, Bowen’s disease has distinct clinical
and histopathologic presentation. Similar to AK, Bowen’s dis-
ease may present on sun-exposed skin and mucosa of the head
and neck. Bowen’s disease may also present in oral or anal
mucosa, as well as on the genitals. Clinical appearance is that of
a red, well-defined scaly papule or plaque with distinct borders.
Bowen’s disease lesions may slowly grow both in height and in
diameter over time. They may also take on a verrucous or fis-
sured appearance. Di erential diagnosis again includes inflam-
matory conditions, as well as neoplasms mentioned for AK.
Mucosal Bowen’s may mimic oral candidiasis or oral blistering
conditions such as pemphigus or pemphigoid. Bowen’s disease
on the vaginal mucosa may mimic uncomplicated vaginitis.
Fig. 2.4 Infiltrative basal cell carcinoma clinically resembling a scar.
Clinical Detection of Skin Cancer
25

Erythroplasia of Queyrat
Similar to Bowen’s disease, erythroplasia of queyrat represents
a raised red plaque of the penis, most commonly the glans
penis in uncircumcised men.
Oral Leukoplakia
A form of oral SCCis, oral leukoplakia clinically manifests as a
white patch or plaque in the mouth that cannot be scrubbed or
rubbed o . The most common area of occurrence is the buccal
mucosa along the lateral surfaces of the oral cavity, but can
involve any mucosal surface including the tongue ( Fig. 2.7).
Oral leukoplakia may take on a verrucous appearance, a har-
binger for greater propensity for progression to SCC. This entity
must be distinguished from benign mucosal conditions such as
oral candidiasis, syphilis, or morsicatio buccarum—maceration
and irritation of the buccal mucosa due to repeated chewing or
biting.
2.2.4 Squamous Cell Carcinoma
Squamous Cell Carcinoma Arising from
Squamous Cell Carcinoma In Situ
Most commonly, SCC is associated and contiguous with SCCis
that has progressed and invaded over time with lack of treat-
ment. Again, the most common areas a ected are those
exposed chronically to UV radiation over years, including head
and neck, dorsal forearms, and hands. In sunbathers and
females, anterior legs including shins are also commonly
a ected. Middle-aged to elderly men are the highest repre-
sented demographic group. Cutaneous SCC may take on a vari-
ety of clinical appearances; clinically distinct subtypes will be
discussed separately. In general, SCC manifests as a well-defined
plaque, larger in size than typical AK or SCCis. Plaques are
thicker and may have prominent erosions or ulcerations
(Fig. 2.8). There may be focal areas of increased scale or
hyperkeratosis, resulting in an exophytic appearance. The
Fig. 2.5 (a) Multiple actinic keratoses in a middle-aged female with remote history of arsenic exposure. (b) Cutaneous horn.
Fig. 2.6 Actinic cheilitis involving the lower lip in
a patient with remote history of tobacco use,
ultraviolet exposure, and use of a photosensitiz-
ing azole antifungal medication.
Clinical Detection of Skin Cancer
26

lesions may have exudate or be superficially impetiginized,
resulting in an adherent scale crust. SCC may take on unusual
or distinct clinical appearances due to the past treatments or
partial treatments, duration since onset, location of tumor, or
host immune system.
Keratoacanthoma
Keratoacanthoma (KA) is a clinically distinct entity, represent-
ing a histopathologically well-di erentiated form of SCC. KA
occurs most commonly in middle-aged to elderly fair-skinned
individuals on sites of heavy UV damage. These tumors have a
natural history characterized by approximately 1 month of
rapid growth from onset, a period of stability without growth
that can last 3 to 6 months, and lastly a period of spontaneous
involution that takes place over 1 to 2 subsequent months. KAs
clinically appear as dome-shaped red or pink papules, or nod-
ules with a central keratinaceous plug (Fig. 2.9). Patients often
report that the lesion suddenly appeared.
There are several distinct subtypes of KA based on clinical
appearance, location, or number of lesions. Subungual KAs
develop on nail beds and may cause significant pain due to
rapid growth. Mucosal KAs arise on any mucosal surface, and
Fig. 2.7 Oral leukoplakia involving the lateral tongue.
Fig. 2.8 Large ulcerated and bleeding squamous cell carcinoma of the
scalp.
Fig. 2.9 Pink papule on the scalp with central
keratin plug. Consistent pathologically with ker-
atoacanthoma.
Clinical Detection of Skin Cancer
27

may occur in syndromes with multiple KAs. Giant KAs are sim-
ilar in morphology, but larger in size than typical KA. Ranging
from 2 to more than 15 cm, these variants have a predilection
for the nose, eyelids, and face.3 While they may spontaneously
involute as typical KAs, they may be locally and permanently
disfiguring. Keratoacanthoma centrifugum marginatum (KCM)
are similarly large, growing sometimes greater than 15 or
20 cm, but have spontaneous central involution. Clinically, this
presents as an expanding erythematous rim with central clear-
ing. These variants are less likely to spontaneously resolve than
typical or giant KA.4
Generalized eruptive keratoacathomas of Grzybowski is a
rare syndrome characterized by abrupt occurrence of numerous
KAs over many body surface areas, including mucosal surfaces.
Hundreds to thousands of pruritic, variably sized lesions may
develop over a short period of time.5 Multiple KAs may present
as part of multiple self-healing squamous epithelioma (MSSE)
also known as Ferguson–Smith disease, an autosomal dominant
disorder involving the transforming growth factor beta receptor
1 (TGFBR1) gene.
Verrucous Squamous Cell Carcinoma
Verrucous SCC is considered a low-grade variant of SCC that
commonly a ects the oral mucosa, feet, and genitalia. These
tumors are very slow growing and have a characteristic papil-
lomatous or warty exterior. Though slow growing, these tumors
may be locally destructive and disfiguring ( Fig. 2.10a). HPV
and carcinogen exposure are thought to be driving forces
behind this m alignancy, rather than UV radiation. Depending
on the anatom ical locale at presentation, di erent terms can
be used to describe these tum ors. Verrucous SCC of the oral
cavity is also known as oral florid papillomatosis, while that
of the anogenital region is known as a Buschke–Lowenstein
tum or ( Fig. 2.10b). The later subtype m ay be associated
with verrucous SCC of the urethra or bladder. When pre-
Fig. 2.10 (a) Verrucal squamous cell carcinoma (SCC) of the subungual fingertip. (b) Photograph after complete resection via Mohs micrographic
surgery demonstrates the locally destructive nature of the lesion. (c) Verrucal SCC of the penis.
Clinical Detection of Skin Cancer
28

senting on the palm s or soles, the term epitheliom a cunicu-
latum is used.
2.3 Melanoma
2.3.1 Melanoma In Situ
Almost all melanomas begin as melanoma in situ, with epider-
mal proliferation of malignant melanocytes that eventually
invade past the epidermal basement membrane into the der-
mis. Melanoma in situ can clinically present in a number of dif-
ferent ways and be clinically indistinguishable from banal nevi.
Lentigo Maligna
Lentigo maligna (LM) is a specific type of melanoma in situ that
commonly occurs on the head and neck of elderly Caucasian
individuals. LM clinically presents as a brown, tan, or multi-
colored pigmented macule or patch that grows slowly over time
(Fig. 2.11a). Clinical diagnosis is often di cult or impossible
to make in elderly individuals with years of sun damage and
numerous obscuring lentigines, seborrheic keratoses, and AKs.
Clues that a particular lesion may signify an LM include the
following: irregular borders, lesion asymmetry, and radial
growth over time. LM is notorious for having malignant exten-
sion beyond the visible borders of the tumor. In these circum-
stances, histologic “skip areas” are seen, further complicating
the clinical characterization of LM. A lesion may develop other
colors as part of its natural progression, and exhibit black, blue,
pink, red, or white hues. Lesions may keep their brown or tan
color, but exhibit uneven darkening through the lesion. LM is
flat without surface change, which helps to distinguish it from
an actinic or solar keratosis. However, a pigmented nodule
within a larger LM is typically a harbinger for progression to
lentigo maligna melanoma (LMM). Of note, LM is sometimes
associated with desmoplastic melanoma, which will be dis-
cussed later.
2.3.2 Lentigo Maligna Melanoma
LMM represents the invasive counterpart to the LM. Common
clinical features include a brown to black nodule that develops
within a broad tan or brown LM that has been slowing growing
for months to years as described earlier (Fig. 2.11b). There
may be ulceration or bleeding present.
2.3.3 Superficial Spreading Melanoma
Superficial spreading melanoma (SSM) is the most common
form of invasive melanoma, despite an increasing incidence of
LMM.6 This tumor subtype is found in adults of any age, with
median in the sixth decade of life—though incidence continues
to rise in younger age groups.7,8 These tumors are commonly
found on the trunk, back, and lower extremities. Classically, the
mnemonic device ABCDE (A-asymmetry, B-borders, C-colors, D-
diameter, and E-evolving/enlarging)—often used as a clinical
tool for detection of all melanoma—is especially e ective in
SMM. When compared to banal pigmented lesions, SMM show
marked asymmetry, scalloped or irregular borders, multiple
colors including red, blue, and black, and usually have size
greater than 5 mm (Fig. 2.12). These lesions evolve over time,
and may ultimately ulcerate, bleed, and become painful. There
is loss of normal skin marking or dermatoglyphics as the lesion
expands. The appearance of a scar incorporated into the lesion
Fig. 2.11 (a) Lentigo maligna involving the face of an elderly male. (b)
Lentigo maligna melanoma with exophytic red nodules.

Fig. 2.12 Superficial spreading melanoma.
Clinical Detection of Skin Cancer
29

is sometimes present and histologically represents tumor
regression.
2.3.4 Nodular Melanoma
Nodular melanoma makes up approximately 15 to 20% of mela-
noma diagnoses. Tumors arise on areas of increased UV radia-
tion exposure including head and neck and upper extremities.
Nodular melanomas are darkly or variably pigmented smooth
or papillomatous nodules that may demonstrate erosion, ulcer-
ation, or spontaneous bleeding at late stages (Fig. 2.13).
2.3.5 Acral Melanoma
Acral melanoma or acral lentiginous melanoma (ALM) is a sub-
type commonly encountered on acral site or within the nail
unit. ALM is the most common type of melanoma in patients
with skin of color such as those of Asian, African American, or
Caribbean decent. Men and women are equally a icted with
ALM, and patients commonly present in middle age. Clinically,
tumors may present as darkening of the skin under or sur-
rounding the nail. Hutchinson’s sign—which is a dark-brown or
black discoloration in the proximal nail fold at the end of a
linear black streak through the nail—may be an indicator of
melanoma in the nail matrix ( Fig. 2.14). As with all melano-
mas, these tumors may grow in size, change color, and ulti-
mately ulcerate and bleed. Di erential diagnosis for these
lesions includes pyogenic granuloma, glomus tumor, subungual
hematoma, talon noir, tinea nigra, and Kaposi’s sarcoma.
2.3.6 Mucosal Melanoma
Melanoma may present on any mucosal surface. Physicians
should consider mucosal melanoma for any pigmented lesion
on mucosal surface, especially when demonstrating exophytic
growth, ulceration, or bleeding.
2.3.7 Desmoplastic and Amelanotic
Melanoma
While di erent histologically, desmoplastic and amelanotic
melanoma are clinically similar entities. These lesions present
as flesh-toned, pink, or white papules. Desmoplastic melanoma
Fig. 2.13 (a, b) Nodular melanoma.
Fig. 2.14 (a, b) Acral melanoma.
Clinical Detection of Skin Cancer
30

is commonly found on head and neck, and has been described
in close proximity to LM. Amelanotic melanoma is the most
common subtype found in patients with albinism (Fig. 2.15).
2.4 Merkel Cell Carcinoma
Merkel cell carcinoma (MCC) is a rare form of skin cancer
thought to be derived from dermal or epidermal Merkel cells.
MCCs occur most commonly in elderly fair-skinned individuals
with median age of onset 65 years with a slight male predomi-
nance. Many cases are caused by Merkel cell polyomavirus
(MCV). They have a predilection for UV-exposed areas on the
head and neck, face, and upper extremities. Clinically, these
tumors appear as shiny, firm dark-red to violaceous dermal
nodules ( Fig. 2.16). MCCs are usually asymptomatic. Tumors
are generally symmetric and dome-shaped. To aid in diagnosis,
the acronym “AEIOU” has been o ered to identify key clinical
features: asymptomatic, expanding rapidly, immune suppres-
sion, older than 50 years of age, and UV damaged.9 MCC is an
aggressive form of skin cancer that has tendency to locally recur
and/or metastasize. MCC occurs in greater frequency in older
patients, with median age of onset 65 years.
2.5 Dermatofibrosarcoma
Protuberans
Derm atofibrosarcom a protuberans (DFSP) is the malignant
counterpart to benign derm atofibrom a. These rare cutaneous
m alignancies present mainly on the trunk and proxim al
extremities as elevated, firm , skin-toned to red nodules or
plaques ( Fig. 2.17). They tend to grow slowly with time
and m ay ulcerate or bleed. These tum ors tend to become
painful in their later stages due to tum or invasion into nerve
fibers.
2.6 Types of Biopsy Techniques,
Rational, Pitfalls
2.6.1 General Principles
Skin biopsies of suspected neoplasm s are conducted for sev-
eral reasons. First and forem ost, a skin biopsy is obtained to
provide histologic diagnostic evidence regarding a neoplasm
of uncertain significance. Skin biopsies can provide impor-
tant prognostic evidence as well. For example, punch biop-
sies help determ ine the depth of an invasive m elanom a for
staging purposes. Biopsies m ight also be conducted w ith a
therapeutic or curative intent if su cient tissue is taken
and m argins are rendered negative by a pathologist. Specific
m ethodologies for biopsy will be discussed individually,
and should be tailored to conditions such as lesion type,
location on body, concern for cosm esis, and type of skin
involved.
Before a biopsy is performed, it is important to conduct a
thorough history and physical exam ination. A discussion of
risks and benefits should also be conducted, and consent
obtained. Skin should be cleansed w ith isopropyl alcohol,
chlorhexidine, or povidone iodine. Skin should then be anes-
thetized w ith an injectable local anesthetic, such as lido-
caine 1%.
Fig. 2.15 (a) Desmoplastic melanoma. (b) Firm shiny plaque consistent with desmoplastic melanoma extending from lentigo maligna.
Fig. 2.16 Merkel cell carcinoma of the forehead.
Clinical Detection of Skin Cancer
31

2.6.2 Shave Biopsy
A shave biopsy is conducted with a Dermablade, No. 10 or
15 blade. Anesthetic is injected subcutaneously, such that it cre-
ates a wheal in the dermis. While stretching the skin, the blade
is used to saw through the lesion ( Fig. 2.18). Forceps may be
used to aid retrieval of the specimen. A hemostatic agent such
as aluminum chloride 20% should be applied along with gentle
pressure after the procedure. Shave biopsy is preferred for exo-
phytic growths such as SCC, BCC, and KA. For LM, a broad shave
or several small “scouting” shaves are preferred to other biopsy
techniques. This technique is minimally invasive, requires no
sutures, and can be performed quickly in the o ce. Cosmesis is
generally acceptable. Common side e ects of this procedure
include oval to round scar at site of procedure, postprocedure
hyperpigmentation, and possibly cutaneous depression.
2.6.3 Scoop Shave
A “scoop shave” is utilized for lesions that may extend deeper
into the dermis or subcutis. A Dermablade may be preferred
due to the innate pliability of the instrument. One or more
sutures for hemostasis may need to be placed based on depth of
the shave.
2.6.4 Punch Biopsy
The punch biopsy technique allows for histologic visualization
of all levels of skin from epidermis to subcutaneous fat. As such,
punch biopsy is the preferred technique for inflammatory der-
matoses. The punch biopsy technique for neoplasms is typically
utilized when the depth of tumor invasion is required for diag-
nostic or prognostic purposes. Punch or excisional biopsy is the
Fig. 2.17 (a) Dermatofibrosarcoma protuberans (DFSP) involving the groin fold. (b) Another DFSP.
Fig. 2.18 Demonstration of shave biopsy.
Clinical Detection of Skin Cancer
32

technique of choice for lesions suspected to be melanoma. As
depth at diagnosis is key to tumor staging and prognosis, these
factors cannot be ascertained from a previously shave-biopsied
lesion. This technique may also be used with curative intent, if a
su cient size of punch is used to provide curative margins
around the lesion of interest. This is known as punch excision.
Punch instruments come in a number of sizes. Smaller punches
of 1- to 3-mm diameter can be used without the use of sutures.
Generally speaking, punch biopsies of 4-mm or greater diame-
ter should be closed with one or more interrupted sutures for
adequate hemostasis and cosmesis.
After selecting an appropriately sized instrument, the skin
should be made taut by stretching in a direction perpendicular
to relaxed skin tension lines. When done properly, an oval-
shaped skin defect will form after the procedure, allowing for
easy closure. Using a twisting motion between index finger and
thumb, the punch is drilled perpendicularly into the skin. For-
ceps and scissors are used to cut the specimen from attached
underlying subcutaneous fat.
Pitfalls of the punch biopsy technique include insu cient epi-
dermal sampling from a small biopsy (2 or 3 mm), and creation
of histologic artifact if the skin is crushed with forceps during
transfer. To avoid insu cient sampling, several “scouting
punches” are often conducted in a larger lesion (i.e., melanoma)
to properly sample the neoplasm for both diagnosis and determi-
nation of the accurate depth of lesion. Patients should be warned
that a small linear scar will likely result from the procedure.
2.6.5 Excisional Biopsy
Excisional biopsies may be utilized to remove a suspected skin
cancer in toto. For lesions with strong clinical suspicion for
malignancy, or for those lesions too large to remove via punch
biopsy, an excisional technique may be useful. Standard mar-
gins for excisional biopsy of pigmented lesions are 1 to 3 mm
for lesions less than 2 cm. These margins are favored in order to
minimally disrupt local skin lymphatic networks in the event
that a sentinel lymph node biopsy procedure is needed for
those lesions ultimately diagnosed as melanoma.
2.7 Role of Dermoscopy
Dermoscopy or amplified surface microscopy—the microscopic
examination of cutaneous neoplasms in vivo—can increase
diagnostic sensitivity and specificity in the hands of trained
clinicians. A handheld, lightweight dermatoscope illuminates
and magnifies skin surface 10 to 20 times the naked eye. When
combined with immersion fluids, the upper layer of the skin
can be rendered translucent, allowing for better visualization of
targeted lesions from epidermis to upper dermis. Newer der-
matoscopes equipped with polarized light accomplish the same
visualization without immersion fluids. Dermoscopy has been
used to more closely describe a broad range of cutaneous neo-
plasms. We will focus on the technique’s utility for classifying
pigmented lesions and briefly describe criteria for other com-
mon cutaneous malignancy such as BCC. When used in the
proper clinical context, dermoscopy improves accuracy and
sensitivity for diagnosis of melanoma and BCC over the naked-
eye examinations, decreasing needless biopsies.10 Dermoscopy
is often combined with whole-body digital photography or one
of a number of advanced diagnostic machines for high-risk
patients, a technique that has been demonstrated to increase
the detection of melanoma.11
2.7.1 Pigmented Neoplasms
Pigmented lesions can microscopically demonstrate a range of
unique features such as pigment networks and pseudonet-
works, globules, streaks, and parallel pattern. Standardization
of the evaluation of pigmented lesions using dermoscopy was
accomplished at the Consensus Net Meeting on Dermoscopy,
held in 2001 in Rome (for detailed information, see
moscopy.org).12 This meeting established a consensus two-step
algorithm for classification of clinically pigmented lesions using
dermoscopy. The first step di erentiates lesions between mela-
nocytic and nonmelanocytic pigmented lesions. The following
structures were identified as belonging to melanocytic lesions:
pigment network or pseudonetwork, aggregated globules,
streaks, homogeneous blue pigmentation, or parallel pattern on
palms and soles. If none of these features are identified, the
lesions should be evaluated for a number of features corre-
sponding to a diagnosis of nonmelanocytic confounder such as
seborrheic keratosis, vascular lesion, or pigmented BCC.
After determining that a lesion is likely melanocytic, the con-
sensus classification method guides the clinician to grade the
lesion as benign or malignant. Of the many algorithms for grad-
ing pigmented lesions, the four most commonly used methods
described are pattern analysis described by Pehamberger et al,
ABCD rule of dermatoscopy described by Stolz et al, the 7-point
checklist by Argenziano et al, and Menzie’s method, of course
each with modifications and exceptions.13,14 We will detail the
most basic method, pattern analysis.
Pattern analysis relies on the use of discrete elements to
formulate a diagnosis (Table 2.1). Elements analyzed include
pigment network, di use pigmentation, depigmentation,
brown globules, black dots, radial streaming, pseudopods, gray-
blue veil, and negative pigment network. Melanoma is charac-
terized by irregular networked or di use pigment, irregular
areas of depigmentation, brown globules, and black dots that
are varied in size and irregularly distributed (Fig. 2.19). Mela-
noma shows radial streaming, pseudopods, and blue-gray veil
(Fig. 2.20, Fig. 2.21, Fig. 2.22).15
2.7.2 Basal Cell Carcinoma
Characteristics of BCC include arborizing vessels, leaflike areas,
pigmented (blue-gray, brown-gray) ovoid nests, blue-gray glob-
ules, ulceration, and spoke wheel–like areas (Fig. 2.23). Ovoid
nests and globules of pigment without definable pigment net-
work are common for BCCs (Fig. 2.24). Spoke wheel–like areas
are areas of pigment radiating from a central hub.16
2.7.3 Confounders
Confounders such as seborrheic keratoses show milialike cysts
and comedolike openings, hairpin blood vessels, sharp demar-
cation of border, networklike structures, and fingerprintlike
structures ( Fig. 2.25). Angiomata demonstrate red, blue, or
black uniform lacunae (Fig. 2.26). Banal nevi and solar lenti-
gines display regular pigment networks, regular borders, black
Clinical Detection of Skin Cancer
33

dots over grids of pigment network, brown-black globules at
center, and homogeneous colors (Fig. 2.27).
2.8 Use of Artificial Intelligence
Machines
Artificial intelligence (AI) machines are emerging as clinical
tools to aid in the detection of skin cancer, primarily melanoma.
The current consensus gold standard for diagnosis of melanoma
is examination of skin lesion(s) by a trained dermatologist fol-
lowed by pathological examination of a biopsy of the skin speci-
men.17 Most skin examinations are conducted using the naked
eye. Clinicians are tasked with finding aberrant pigmented
lesions among a plethora of banal nevi. The goal of new AI
machines is to improve biopsy decision-making and ultimately
find more cutaneous malignancies.
Table 2.1 Pattern analysis of pigmented lesions
Compound nevus
(benign)
Junctional nevus
(benign)
Superficial spreading
melanoma
Lentigo maligna mel-
anoma
Nodular melanoma
General appearance

Orderly

Orderly, uniform

Polymorphous

Polymorphous

Polymorphous or
uniform
Surface

Smooth;
hyperkeratotic
Skin surface preserved
or smooth, no scale
Skin surface not
preserved; may be
elevated; irregular
Preserved surface; flat Not preserved,
nodular, smooth, or
hyperkeratotic
Pigment pattern

Regular pigment
network, blurred; even
and regular brown
globules; central in
tense uniform
pigmentation; black
dots at center of lesion
may occur
Regular pigment
network at periphery;
uniform and regularly
spaced brown
globules; central
uniform pigmentation;
black dots in center of
lesion may occur
Irregular, prominent
pigment network;
brown and black
globules of uneven
size; intensely colored
patches; black dots at
periphery; areas of
uniform pigment
blue-gray to brown in
color
Highly irregular;
prominent pigment
network; loss of
pigment network in
nodular areas
Usually uniform
pigment; at periphery
a thin rim of
prominent and
irregular pigment;
uniform black dots at
periphery gray, blue,
brown, or black in
color
Border

Regular, simple
outline; network thins
at periphery
Regular, pigment
network thins at
periphery
Pigment network
irregular; stops
abruptly at edge;
pseudopods and radial
streaming present
Pigment network stops
abruptly at edge;
pseudopods and radial
streaming present
Pigment network
irregular, stops
abruptly; pseudopods
either blue or black;
radial streaming
present
Depigmentation or
hypopigmentation
Regular; well defined
Usually absent

Bizarre and irregular
with pink or white
areas
White and pink areas
of depigmentation
with irregular outline
White and pink areas
with irregular outline;
often speckled with
black and blue dots
Source: Adapted from Pehamberger et al.13
Fig. 2.19 Melanoma in situ (Mis) demonstrating
irregular pigment network, areas of diffuse
pigmentation, and irregular areas of depigmen-
tation. (Dermatoscopic images are courtesy of
Dr. Jeffrey Meffert.)
Clinical Detection of Skin Cancer
34

Fig. 2.20 Invasive melanoma arising in a nevus.
Arrows demonstrate areas of radial streaming.
Also note prominent blue-gray veil through the
more heavily pigmented portion of the lesion.
Fig. 2.21 Invasive melanoma demonstrating
prominent blue-gray veil. Arrows demonstrate
pseudopods at periphery.
Fig. 2.22 (a) Large, ulcerated nodular melanoma. (b) Dermatoscopic image demonstrating blue-gray veil, diffuse pigmentation, and irregular central
depigmentation. Arrows demonstrate radial streaming.
Clinical Detection of Skin Cancer
35

2.8.1 MelaFind
MelaFind (MELA Sciences, Inc., Irvington, NY) is a user-friendly
handheld imaging device designed to aid in the diagnosis of
melanoma among atypical melanocytic lesions, that is, those
that have one or more clinical or historical characteristics of
melanoma. The device received premarket approval by the Food
and Drug Administration in November 2011, as a pigmented le-
sion biopsy tool. It is available for physicians trained in the clin-
ical diagnosis of skin cancer who have completed the MelaFind
training program. MelaFind utilizes 10 spectral bands of light,
from 430 to 950 nm (blue to near-infrared) to analyze pig-
mented lesions in vivo. Images captured with the handheld
device are analyzed by software for lesion symmetry, color var-
iation, perimeter changes, texture changes, and wavelet max-
ima. MelaFind software algorithms are proprietary, having been
developed with use of clinical and histopathological data from
nearly 9,000 biopsied lesions from 7,000 test patients. MelaFind
di ers from other novel AI diagnostic tools in that it ultimately
provides a “lesions score” and makes a recommendation for or
against biopsy for the operator.
Not all lesions are considered suitable for MelaFind, and sev-
eral restrictions are described. It can be used for lesions
between 2 and 22 mm that are accessible to the handheld com-
ponent of the machine and at least 1 cm away from the eye. Tar-
get lesions must be pigmented; MelaFind is not suitable for
evaluation of amelanotic or skin-toned nevi. Skin must be intact
without ulceration, bleeding, scale crust, ink markings, or for-
eign matter. Lastly, several anatomic sites are o -limits, includ-
ing palmar, plantar, mucosal, and subungual regions. Lesions
should always be evaluated with MelaFind in the context of a
full-body skin examination.
Fig. 2.23 Pigmented nodular basal cell carcino-
ma. The lesion demonstrates arborizing telan-
giectasia and large blue ovoid nests.
Fig. 2.24 Pigmented nodular basal cell carcino-
ma. Arrows point to multiple blue-gray globules,
arrowhead to large blue-gray ovoid nest, asterisks
to arborizing telangiectasias.
Clinical Detection of Skin Cancer
36