color atlas of melanocytic lesions of the skin - h. soyer, et al., (springer, 2007)

as practicing dermatologists with back-grounds in dermoscopy and dermatopathology, we wanted to describe the many faces of benign and malignant pigmented skin lesions based on clinico-pa

Color Atlas of Melanocytic Lesions of the Skin

of the Skin

123

H Peter Soyer, MD, FACD

Robert H Johr, MD

Clinical Professor of Dermatology and PediatricsDirector, Pigmented Lesion Clinic

University of Miami, School of MedicineMiami, FL 33136

This book is dedicated to the memory of Paolo Carli

an outstanding scientist

and a special human being

H Peter Soyer and Giuseppe Argenziano

on behalf of all authors

Melanocytic tumors of the skin deserve special

attention because of the following important

facts

■ Melanoma is frequent and early detection

is critical

■ a correct interpretation is necessary

because the implications may be very

serious

■ it is a dynamically developing field where

major progress has been made over the

past decade

This atlas, written in a concise way, is a highly

useful presentation that focuses on the full

spec-trum of pigmented skin tumors The prominent

features include classical clinical as well as

his-topathological criteria for diagnosis,

illustra-tions of excellent quality, as well as new concepts

and practical aspects of management of special

interest are modern diagnostic techniques with

emphasis on dermatoscopy Case studies and

core messages indicating pathways of the

diag-nostic approach are at the end of each chapter

all these features characterize the book as an impressive contribution to the literature in the area of melanocytic tumors

My co-workers in Graz, Dr H Peter Soyer and Dr rainer Hofmann-Wellenhof, as well as

Dr Giuseppe argenziano from Naples and Dr robert Johr from Miami, together with many international contributors who are all experts in their respective disciplines, have produced a splendid piece of work which presents highly relevant information on a complex and chal-lenging subject This book will greatly assist physicians in providing optimal care for pa-tients with melanocytic skin lesions

Helmut Kerl

Professor & ChairmanDepartment of DermatologyMedical University of Grazaustria

at the beginning of many scientific endeavors

there is an idea shared by a small group of

en-thusiastic people This was the case with our

group, friends and colleagues from austria,

ita-ly, and the United States our idea was to write a

color atlas of melanocytic skin lesions, with

particular emphasis on the morphological

di-mension, using a systematic and logical

ap-proach as practicing dermatologists with

back-grounds in dermoscopy and dermatopathology,

we wanted to describe the many faces of benign

and malignant pigmented skin lesions based on

clinico-pathological and

dermoscopic−patho-logical correlations Together with a large group

of distinguished dermatologists from around

the world, we prepared this atlas

in 1894 Paul Gerson Unna published the

text-book Histopathology of Skin Diseases His

well-known saying on the relationship between matology and histopathology has been slightly modified by us and now reads as follows: “The dermatologist is fortunate in being able to study the clinical and dermoscopic picture with his/her histologically trained eye and the micro-scopic picture with his/her clinically and der-moscopically trained eye.” in this spirit we hope that you enjoy reading this atlas and that it will help you in your daily practice

der-H Peter Soyer Giuseppe Argenziano Rainer Hofmann-Wellenhof Robert Johr

I.1 The Morphologic Dimension

in the Diagnosis of Melanocytic

III.8 Congenital Melanocytic Nevi 106

Alon Scope, Cristiane Benvenuto-Andrade, Ashfaq A Marghoob

III.9 Melanocytic Nevi on the Genitalia

and Melanocytic Nevi

on other Special locations 119

III.10 Halo Nevus 124

Alessandro Di Stefani

and Sergio Chimenti

III.11 irritated Nevus

and Meyerson’s Nevus 129

Regina Fink-Puches,

Iris Zalaudek, Rainer Hofmann-Wellenhof

III.12 Melanocytic lesions

in Darker racial Ethnic Groups 135

XII Contents

III.14 Nevi with Particular Pigmentation:

Black, Pink, and White Nevus 142

III.17 Syndromes involving

Melanocytic lesions 164

Cheryl G Aber,

Elizabeth Alvarez Connelly, Lawrence A Schachner

III.18 Nail apparatus Nevus (Subungual

Nevus, Nail Matrix Nevus) 173

Michele Farber, Dina Gutkowicz-IV.5 False-Negative Melanomas 221

IV.8 Melanoma of the Trunk

and limbs including Superficial and Nodular Melanoma 237

V.3 lentigines including lentigo

Simplex, reticulated lentigo and actinic lentigo 290

Paolo Carli and Camilla Salvini

V.4 Squamous Cell Carcinoma

including actinic Keratosis, Bowens Disease, Keratoacanthoma, and its Pigmented Variants 295

Iris Zalaudek, Jason Giacomel,

Bernd Leinweber

V.5 Vascular lesions 303

V.6 Seborrheic Keratosis including

lichen Planus-like Keratosis 313

Subject Index 329

Miller School of Medicine

Cedars Medical Center

and Cutaneous Surgery

University of Miami, Miller School of Medicine

Cedars Medical Center

Second University of Naples

Nuovo Policlinico − Edificio 13

Photomedicine and Telemedicine laboratory

Federal University of rio Grande do Sul

R.P Braun

Department of DermatologyUniversity Hospital Zurich

8091 ZurichSwitzerlandE-mail: braun@melanoma.ch

H Cabo

Section of Dermatologyinstituto de investigaciones Médicas

† Deceased

L Cerroni

Department of DermatologyMedical University of Grazauenbruggerplatz 8

8036 GrazaustriaE-mail: lorenzo.cerroni@meduni-graz.at

S Chimenti

Department of Dermatology

University of rome “Tor Vergata”

PTV − Policlinico di Tor Vergata

University of rome “Tor Vergata”

PTV − Policlinico di Tor Vergata

Pathologic anatomy Service

Gaetano rummo General Hospital

E-mail: jasongiacomel@optusnet.com.au

C.M Giorgio

Department of DermatologySecond University of NaplesVia S Pansini 5

80131 Naplesitaly

E-mail: caterinagiorgio@libero.it

S González

Dermatology ServiceMemorial Sloan-Kettering Cancer CenterNew York, NY 10022

USaE-mail: gonzals6@mskcc.org

D Gutkowicz-Krusin

Electro-optical Sciences, inc

1 Bridge Streetirvington, NY 10533USa

E-mail: gutkowicz@eosciences.com

A Halpern

Dermatology ServiceMemorial Sloan-Kettering Cancer CenterNew York, NY 10022

USaE-mail: halperna@mskcc.org

E.R Heilman

Department of DermatologySUNY Health Science Center at BrooklynBrooklyn, N.Y

USaE-mail: eheilman@ameripath.com

550 First avenueNew York, NY 10016USa

E-mail: akopf@compuserve.com

J Kreusch

Dermatological PracticeSkin Cancer Diagnostic CenterMoislinger allee 95

23558 luebeckGermanyE-mail: juergen.kreusch @web.de

B Leinweber

Department of DermatologyMedical University of Graz, austriaauenbruggerplatz 8

8036 GrazaustriaE-mail: bernd.leinweber@meduni-graz.at

G.P Lozzi

Department of DermatologyUniversity of l’aquila, italyVia Vetoio − Coppito 2

67100 l’aquilaitaly

E-mail: gilozzi@inwind.it

J Malvehy

Melanoma UnitDepartment of DermatologyHospital Clinic

Villarroel 170

08036 BarcelonaSpain

E-mail: jmalvehy@clinic.ub.es

A.A Marghoob

Section of DermatologyMemorial Sloan-Kettering Cancer Center

160 East 53rd Street, 2nd floorNew York, NY 10022

USaE-mail: marghooa@mskcc.org

Sydney Melanoma Diagnostic Centre

2nd Floor, Gloucester House

royal Prince alfred Hospital

67100 l’aquilaitaly

E-mail: pizzichetta@cro.it

D Polsky

Department of DermatologyNew York University School of Medicine

550 First avenueNew York, NY 10016USa

E-mail: david.polsky@med.nyu.edu

H.S Rabinovitz

Skin and Cancer associates

201 N.W 82nd avenuePlantation, Fl 33324USa

E-mail: harold@admcorp.com

D.S Rigel

Department of DermatologyNew York University School of Medicineadjunct Clinical Professor

Department of DermatologyMount Sinai School of MedicineNew York, NY

USaE-mail: dsrigel@prodigy.net

S Puig

Melanoma UnitDepartment of DermatologyHospital Clínic

Villarroel 170

08036 BarcelonaSpain

E-mail: spuig@clinic.ub.es

University Hospital Geneva

24 rue Micheli Du Crest

1211 Geneva 14

Switzerland

E-mail: jean.saurat@medecine.unige.ch

L.A Schachner

Division of Pediatric Dermatology

University of Miami, Miller School of Medicine

Department of Dermatology and Cutaneous

Memorial Sloan-Kettering Cancer Center

160 East 53rd Street, 2nd floor

8010 GrazaustriaE-mail: josef.smolle@meduni-graz.at

H.P Soyer

School of MedicineUniversity of Queensland

australia

W Stolz

abteilung für Dermatologie, allergologie und UmweltmedizinKrankenhaus München SchwabingKölner Platz 1

80804 MunichGermanyE-mail: wilhelm.stolz@kms.mhn.de

M Tanaka

Department of DermatologyTokyo Women’s Medical University Medical Center East

2-1-10 Nishi-ogu, arakawa-kuTokyo 116-8567

JapanE-mail: masarutanaka@1984.jukuin.keio.ac.jp

L Thomas

Department of DermatologyHotel Dieu

69288 lyon Cedex 02France

E-mail: luc.thomas@chu-lyon.fr

S.Q Wang

Department of DermatologyMayo Mail Code 98

420 Delaware Street S.E

Minneapolis, MN 55455USa

E-mail: sqwang01@yahoo.com

The Queensland institute of Dermatology

Brisbane, QlD 4102Princess alexandra Hospital

E-mail: p.soyer@ug.edu.au

allergologie und Umweltmedizin

Krankenhaus München Schwabing

8036 GrazaustriaE-mail: lissy.wurm@gmail.com

Y Yamazaki

Department of DermatologyShinshu University School of Medicine 3-1-1 asahi

Matsumoto 390-8621Japan

E-mail: y.yamazaki@sihp.jp

I Zalaudek

Department of DermatologyMedical University Grazauenbruggerplatz 8

8036 GrazaustriaE-mail: iris.zalaudek@meduni-graz.at

scopic features, relevant clinical differential agnosis, histopathology, as well as practical as-pects of management Core messages recapitulate the most pertinent facets of each entity

di-This introductory chapter, therefore, can be considered a plea for recognition of the signifi-cance, and the unchanging importance, of the human eye and the human neural network for achieving diagnosis in the protean field of mela-nocytic skin lesions We currently are on the edge of the development of new technologies, such as imaging technologies and molecular-biologic tests, for identifying individuals at risk and for refining the benign/malignant thresh-old These new technologies are challenging the currently well-accepted morphologic methods including histopathology However, the present

reality, even in high-tech countries, is that matologists are, and most probably will remain,

der-at the forefront of diagnosing and treder-ating skin cancers as well as managing melanocytic skin lesions

I.1.2 The Benign/Malignant Threshold

in Morphology

The boundary between benignity and nancy is not as sharp as our established catego-ries would like them to be Dermoscopic – but also histopathologic – diagnoses, not to men-tion clinical diagnosis, are subjective as well as objective in 1962 these facts were well depicted for the histopathologic diagnosis by rambo who stated that “pathologists are physicians and hu-man beings They […] traditionally have been regarded to be more scientific than many of their colleagues a mystic perversion of this as-sumption prevails among those clinicians who

malig-Chapter I.1

The Morphologic Dimension in the

Diagnosis of Melanocytic Skin Lesions

H Peter Soyer and Elisabeth M.T Wurm

I.1.1 A Color Atlas of Melanocytic

Lesions of the Skin

The book in your hands has been designed

basi-cally as an atlas entitled Color Atlas of

Melano-cytic Lesions of the Skin and focuses on the

mor-phologic dimension of melanocytic skin lesions

it encompasses all the classical methods of

mor-phology such as the clinical and dermoscopic

examination and dermatopathology, as well as

the most up-to-date diagnostic approaches such

as laser scanning in-vivo microscopy,

multi-spectral image analysis, automatic diagnosis,

and teledermatology With the exception of the

chapters on automatic diagnosis and on

multi-spectral analysis, all chapters focus on the

mor-phologic dimension, albeit in its various facets,

thus justifying the title of this book

The core of this book represents an atlas with

clinical, dermoscopic, and histopathologic

im-ages of the many faces of melanocytic nevi, the

various types of melanomas, as well as the

vari-able features of non-melanocytic pigmented

skin tumors Each of these well-illustrated

enti-ties are presented following the same ductus

characterized by definition, clinical and

dermo- H P Soyer, E M.T Wurm

I.1 believe that the pathologist, given only a piece of the patient’s tissue, has all the other ingredients

necessary to produce a statement of absolute

truth at the end of his report More dangerous to

the mankind is a pathologist with the same

con-cept…” [1] Even today it is not easy at all to find

references which indicate that expert

patholo-gists sometimes have great difficulties in

recog-nizing, for example, the threshold separating

carcinoma in situ or melanoma in situ from

atypia or dysplasia interestingly, many

dermos-copists reveal more insight with regard to their

diagnostic limitations in a recent issue of the

“archives of Dermatology” an article by Skvara

et al entitled “limitations of dermoscopy in the

recognition of melanoma” focuses on the

limi-tations of dermoscopy in the diagnosis of very

early, and mainly featureless, melanomas [2]

The authors report that baseline dermoscopic

patterns of 262 melanocytic nevi and 63

mela-nomas, which were followed by digital

dermos-copy and finally excised because of changes over

time, did not differ substantially from each

oth-er Suffice it to say that histopathology

repre-sented the gold standard in this study

I.1.3 A New Era of “Clinicoimaging”

Diagnosis in Dermatology

in 2005 June robinson, the editor of the

“ar-chives of Dermatology,” wrote in an editorial

titled “Biotechnology succeeds in

revolutioniz-ing medical sciences” the followrevolutioniz-ing statement:

“Given the unique visual learning patterns of

our discipline, it is not surprising that we

eager-ly adapt emerging bioimaging techniques [ ]

We are beginning to move away from

clinico-pathologic diagnosis into an era of

‘clinicoimag-ing’ diagnosis” [3] The introduction of these

new ‘clinicoimaging’ techniques in the near

fu-ture certainly will have a major impact on the

current dermatologic practice, although there

will be a need to define new quality standards in

order to integrate these techniques into the

dai-ly workflow We should not forget, however, that

all of these new “clinicoimaging” techniques

have, like every other purely morphologic

meth-od, limitations due to methodologic drawbacks, and sometimes even due to personal restraints

in addition, we are presently also on the edge of

a period of radical change in histopathology, as DNa and rNa can be analyzed by advanced technologies even from archival paraffin-em-bedded material, allowing us to make diagnos-tic leaps and bounds [4] This “new biology” will certainly also affect the benign/malignant threshold in pathology, and a more functional approach to establish the risk associated with sharply defined categories will substitute the fanciful separation of benign from malignant [4, 5]; thus, one can easily foresee that in the fu-ture the conventional morphologic methods will probably be substituted by these new “clini-coimaging” techniques and by novel microbio-logic methods Until then, a combined approach linking the most legitimate and effective mor-phologic methods, namely, clinical examina-tion, dermoscopy, and histopathology, will strengthen the validity of classical morphology [6, 7] in this spirit this introductory chapter, and this atlas, has been written

References

1 rambo oN The limitations of histologic diagnosis Progr radiat Ther 1962; 2: 215–224

2 Skvara H, Teban l, Fiebiger M, Binder M, Kittler

H limitations of dermoscopy in the recognition of melanoma arch Dermatol 2005; 141: 155–160

3 robinson JK, Callen JP Biotechnology succeeds olutionizing medical sciences arch Dermatol 2005; 141: 133–134

rev-4 Quirke P, Mapstone N The new biology: ogy lancet 1999; 354: Si26–Si31

histopathol-5 Foucar E Carcinoma-in-situ of the breast: Have thologists run amok? lancet 1996; 347: 707–708

pa-6 Soyer HP, Massone C, Ferrara G, argenziano G limitations of histopathologic analysis in the recog- nition of melanoma: a plea for a combined diagnostic approach of histopathologic and dermoscopic evalu- ation arch Dermatol 2005; 141: 209–211

7 Bauer J, leinweber B, Metzler G, Blum a, Wellenhof r, leitz N, Dietz K, Soyer HP, Garbe C Correlation with digital dermoscopic images can help dermatopathologists to diagnose equivocal skin tumours Br J Dermatol 2006;155: 546–551

Hofmann-ideally, the patient should lie in a horizontal position on the examining table The entire an-terior and posterior cutaneous surface of the patient is examined with the patient assuming a supine, then a prone, position intertriginous areas, including the axillae, groin, and interdig-ital webs of the hands and feet, plus the nail ap-paratus, are included in the complete cutaneous examination.

Finally, examination of the scalp is best complished by the use of a hair blower that parts the hair down to the skin of the scalp for view-ing

ac-I.2.2 ABCDE Criteria and Other Diagnostic Methods

The acronym aBCDE was created as a simple mnemonic to alert both the general community and health care workers of some of the key fea-tures of melanoma The acronym stands for:

a = asymmetry No matter where the lesion

is bisected, the one half will not match the other

in silhouette and/or lesion content

B = Border irregularity The perimeter of the

lesion is uneven, undulating, ragged, notched,

or blurred

C = Color Multiple shades of tan, brown,

black, red, white, and blue are admixed, ing a mottled appearance

produc-D = produc-Diameter >6 mm The largest diameters

of most melanomas will exceed 6 mm at a point

in their evolution that can be identified This is not an inviolate rule, and currently a significant portion of melanomas are diagnosed by experts when these cancers are 6 mm or less in diame-ter

Chapter I.2

Clinical Examination of Melanocytic

Neoplasms Including ABCDE Criteria

alfred W Kopf

I.2

Contents

I.2.1 Clinical recognition of Melanoma 3

I.2.2 aBCDE Criteria and other

Diagnostic Methods 3

I.2.1 Clinical Recognition of Melanoma

The clinical recognition of melanoma in its

ear-ly phases of progression is exceedingear-ly

impor-tant since the total surgical removal of such

lesions is almost invariably curative When the

clinical recognition is delayed, the opportunity

for distant metastases increases and the

progno-sis is guarded since treatment of such

metasta-ses is problematic

Since dysplastic nevi and melanomas can

occur on any area of the cutaneous surface, it is

mandatory that a complete cutaneous

examina-tion be performed on every patient regardless of

age all new patients should have a complete

cu-taneous examination either at the initial visit or

in the near future The frequency for an

estab-lished patient depends on their history Those

patients with a history of actinic keratosis,

dys-plastic nevi, non-melanoma skin cancer or

mel-anoma should be seen every 6 months for a

complete cutaneous examination

The examining room should have proper

illumination and the temperature should be

comfortable for the patient, who should be

completely undressed except – maybe – for the

examination gown, which should be provided

The examiner should have available a simple

magnifying lens, an instrument for

dermosco-py, and an ultraviolet lamp (“Woods light”) for

special examinations such as looking for areas

of hyper- or hypopigmentation on the skin

 A.W Kopf

I.2

E = Evolving While common melanocytic

nevi evolve slowly and reach a final stage of

growth usually within the first few decades of

life, melanomas usually undergo constant

change in size, shape, shades of color,

symme-try, symptoms (especially pruritus, scaliness,

oozing, bleeding), or surface alterations

[ero-sion, ulceration, papule, and/or nodule

forma-tion and the development of areas of

hypopig-mentation and depighypopig-mentation (a clinical

correlate of spontaneous regression)]

Another easy mnemonic are the three Cs of

melanoma standing for: color, contour, and

change

The diagnostic method of the Glasgow

7-point checklist for diagnosis of melanoma

in-cludes: (a) change in size; (b) irregular shape; (c)

irregular color (major criterion); (d) diameter at

least 7 mm; (e) inflammation; (f)

oozing/bleed-ing; and (g) change in sensation (minor

criteri-on)

The features described above are suggestive

of melanoma (especially superficial spreading

melanoma), but they also appear in benign

le-sions (such as atypical nevi), thus causing

diag-nostic difficulties Nodular melanomas, on the

other hand, often appear as small and

symmet-ric round nodules, smaller than 6 mm in

diam-eter, the only hint of malignancy being a clinical

history of evolution and change These

limita-tions to specificity and sensitivity of naked-eye

examination can be reduced by dermoscopy as a

useful aid in the in-vivo differentiation of such

lesions (see Chap I.3)

Furthermore, total cutaneous photography

can be performed for patients who have many

melanocytic nevi (especially when atypical)

Baseline total-cutaneous photographs (Fig I.2.1)

are very helpful in identifying significant

chang-es in pre-existing lchang-esions and identifying new

melanocytic neoplasms on subsequent

follow-up clinical examinations

Last but not least, patients should be

instruct-ed and encouraginstruct-ed to regularly perform

self-ex-amination of their skin (Fig I.2.2)

Fig I.2.1 Illustrations for different views taken of tal-body photographs Sites photographed are bound by

to-dashed lines or solid-line rectangles Top: On anterior and

posterior surfaces of body, all demarcated areas (shaded and unshaded) are photographed On lateral aspects of body, only shaded areas are photographed

Clinical Examination of Melanocytic Neoplasms Chapter I.2 

Fig. I.2.2. Self-examination of the skin (continuation see next page)

C Core Messages

■ It is mandatory that a complete

cutaneous examination be performed

on every patient regardless of her/his

age

■ The examination should include

examination of intertriginous areas

including axillae, groin, and

interdigi-tal webs of hands and feet, as well as

nail apparatus and scalp

■ Features of melanoma can be

memo-rized by the acronym ABCDE:

Asym-metry; Borders; Color; Diameter;

and Evolution

■ The diagnostic method of the Glasgow 7-point checklist for diagnosis of melanoma includes: (a) change in size;

(b) irregular shape; (c) irregular color (major criterion); (d) diameter at least

7 mm; (e) inflammation; (f) oozing/

bleeding; and (g) change in sensation (minor criterion)

■ Patients should be encouraged to regularly perform a self-examination

of their skin

 A.W Kopf

I.2

Fig. I.2.2. (continued)

I.3.1 Introduction

Dermoscopy (also known as epiluminescence microscopy, dermatoscopy, amplified surface microscopy) is an in-vivo method that has been reported to be a useful tool for the early recogni-tion of melanoma and the differential diagnosis

of pigmented lesions of the skin [1, 2] its use creases diagnostic accuracy between 5 and 30% over clinical visual inspection, depending on the type of skin lesion and the experience of the physician This was confirmed by two recent evidence-based publications from a meta-analy-sis of the literature [3]

in-I.3.2 Physical Aspects

light is either reflected, dispersed, or absorbed

by the stratum corneum due to its refraction dex and its optical density, which is different from air; thus, deeper underlying structures cannot be adequately visualized The use of immersion liquids renders the skin surface translucent and reduces reflections, so that un-derlying structures will become visible The ap-plication of a glass plate flattens the skin surface and provides an even surface optical magnifi-cation is used for examination Taken together, these optical means allow the visualization of certain epidermal, dermo-epidermal, and der-mal structures as immersion liquid we recom-mend the use of 60° alcohol (ethanol) which can

in-Chapter I.3

Dermoscopic Examination

ralph P Braun, Harold S rabinovitz, Margaret oliviero,

Contents

I.3.1 introduction 7

I.3.2 Physical aspects 7

I.3.3 Equipment for Dermoscopy 8

I.3.4 Dermoscopic Criteria 9

I.3.4.1 Colors 9

I.3.4.2 Blood Vessels 9

I.3.5 Dermoscopic Structures 11

I.3.5.1 Pigment Network 11

I.3.5.9 Blue-White Veil 13

I.3.5.10 Milia-like Cysts 13

I.3.5.11 Comedo-like openings

(Crypts, Pseudofollicular openings) 13

I.3.5.12 Fingerprint-like Structures 14

I.3.5.13 Moth-Eaten Border 14

I.3.5.14 Fissures and ridges

(“Brain-like” appearance) 14

I.3.5.15 leaf-like areas 14

I.3.5.16 Spoke-Wheel-like Structures 14

I.3.5.17 large Blue-Gray ovoid Nests 14

I.3.5.18 Multiple Blue-Gray Globules 14

I.3.6 Differential Diagnosis

of Pigmented lesions of the Skin 15

I.3.7 aBCD rule of Dermatoscopy [11, 12] 19

I.3.7.1 asymmetry 19

I.3.7.2 Border .19

I.3.7.3 Colors 19

I.3.7.3 Dermoscopic Structures 19

I.3.7.3.1 Seven-Point Checklist 20

I.3.7.3.2 Menzies Method 20 I.3.7.3.3 Three-Point Checklist 21

references 21

 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

be applied directly on the skin using an eye

dropper bottle [4] The advantages are that

eth-anol results in the best image quality and the

least air inclusions it evaporates immediately,

does not have to be wiped off, and does not stain

the patient’s clothing or underwear in areas

close to the eyes or to the mucosa, as well as for

the examination of the nail apparatus, we

rec-ommend instead the use of a gel (ultrasound gel,

cosmetic gel, etc.) a cosmetic gel does not burn

the eyes and, most importantly, it fills out very

nicely the gap between the convex nail surface

and the handheld device as an alternative to the

immersion technique, some devices use

polar-ized light in order to reduce the surface

reflec-tions This technique allows a faster

examina-tion of the patient, but if the patient has dry skin

the use of immersion liquid is still required

I.3.3 Equipment for Dermoscopy

as mentioned, dermoscopy requires optical

magnification and liquid immersion Specially

designed handheld devices with 10–20 times

magnification are commercially available

(Der-matoscope Delta 20, Heine, Herrsching,

Ger-many; DermoGenius Basic, Biocam,

regens-burg, Germany; Dermlite (3Gen, San Juan

Capistrano, Calif.); see Fig i.3.1) all devices

mentioned above are devices of the second

gen-eration which have improved optics and

illumi-nation (lED) compared with the older devices [1] The optic is designed in such a way that a le-sion can be examined at distance from the skin This is an advantage, because the examination is much faster and it is more comfortable for both, the physician and the patient, if the lesion is, for example, on the face or the genital area

Photographic documentation can be formed in different ways [1]: The digital camera

per-is directly attached to a handheld dermatoscope (coupling adapters are available for most hand-held devices) in this case, the camera uses the optics and the illumination of the handheld der-matoscope Since the optics of the handheld de-vices are not designed to fit a camera, the der-moscopic image is always a bit blurred towards the periphery, but this is the most inexpensive way of taking dermoscopy images

Dermoscopy attachments (lenses) are

direct-ly attached to digital cameras Their optics and illumination are designed to fit digital cameras and they provide the best image quality These lenses can only be used with digital cameras and not for the examination of patients There are many different attachments available, but

we mainly use the Dermlite Foto attachment (3GEN; Fig i.3.1) or a Dermaphot lens (Heine, aG) which can be attached to digital Slr cam-eras The attachments can be used with differ-ent cameras and the resolution depends on the digital camera used This solution enables con-veniently taking images of excellent quality

Fig I.3.1 a choiceof held dermatoscopes of the latest generation (from left to right): DermoGenius Basic (Biocam); Delta 20 (Heine); Dermlite ii pro Hr (3GEN); and Dermlite Foto (3GEN)

hand-on a Coolpix 4500 (Nikhand-on)

Dermoscopic Examination Chapter I.3 

Storage and retrieval remain tricky for both

ways of photo documentation mentioned above,

and by the end of the day one finds himself with

a camera full of images which have to be

attrib-uted to patients and stored in a way that they

can be easily retrieved

Systems for digital dermoscopy consist of a

video camera which is linked directly to a

com-puter The lesion can be examined “live” on the

computer screen These systems offer physicians

many more features than the previous solutions,

such as the possibility of easy storage and

re-trieval of lesions, which is important for

follow-up examinations of suspect lesions This is a big

advantage, because when the patient leaves the

office, all images (lesions) are correctly stored

and there is no additional work to be done Some

systems offer even the possibility of

computer-assisted diagnosis and/or teledermoscopy Since

these systems use a video camera, the resolution

is not as good as with a digital consumer camera

and a dermoscopy attachment, but the image

quality is very good on the computer screen

Systems for digital dermoscopy offer many more

features and can make life much easier, but their

disadvantages are their high cost and their lack

of portability

I.3.4 Dermoscopic Criteria

The use of dermoscopy allows the identification

of many different structures, colors, and blood

vessels not seen by naked-eye examination

I.3.4.1 Colors

Colors play an important role in dermoscopy

Common colors are light brown, dark brown,

black, blue, blue-gray, red, yellow, and white

The most important chromophore of the skin,

especially in melanocytic neoplasms, is

mela-nin The color of melanin as seen with

dermos-copy depends on its localization in the skin For

example, melanin appears black in the stratum corneum and the upper epidermis, light to dark brown in the epidermis, gray to blue-gray in the papillary dermis, and steel blue in the reticular dermis Melanin appears to be blue when it is localized within the deeper parts of the skin, be-cause the portions of the visible light with lon-ger wavelengths (red end of visible spectrum) are more dispersed than the portions with shorter wavelengths (blue-violet end of the spec-trum) The color red is associated with either an increased number or dilatation of blood vessels, trauma, or neo-vascularization (see vascular pattern) The color white is often due to regres-sion and/or scaring (see regression)

I.3.4.2 Blood Vessels

in recent publications, blood vessels have gained much more importance and their morphologi-cal aspect enables the clinician in many cases to make the diagnosis, especially in non-pigment-

ed lesions and lesions of non-melanocytic gin

ori-The following types of blood vessels have been described: red lagoons; hairpin vessels; dotted vessels; “comma”-like vessels; glomeru-lar vessels; string of pearls; crown vessels; cork-screw vessels; and arborizing vessels (Table i.3.1) [5] an atypical vascular pattern, also called ir-regular (polymorphous) vessels, may include linear, dotted, or globular red vessels, irregu-larly distributed within the lesion Some of the vascular patterns may be due to neo-vascular-ization For the evaluation of blood vessels, there has to be as little pressure as possible on the le-sion during the examination, because otherwise the vessels are simply compressed and will not

be visible The use of ultrasound gel for sion helps to reduce the pressure an excellent alternative is the use of non-contact polarized light examination as used in some handheld dermatoscopes

immer-10 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

Table I.3.1 Vascular architecture of pigmented skin lesions (From [5])

Morphological aspect Correlation

structures, red, violaceous, brownish, bluish, or black

Hemangiomas

or angiokeratomas

or keratinizing tumor irregular and thick melanoma

or Spitz nevus

observed also in psoriasis and squamous cell carcinoma

Comma-like

Clusters of glomerular

and stasis dermatitis

vessels at the periphery of the tumor; white-yellow globules

in the center of the tumor

Sebaceous gland hyperplasia

irregular

dotted irregular lines, screw, glomerular, and others

cork-Melanoma

Dermoscopic Examination Chapter I.3 11

I.3.5 Dermoscopic Structures

in this chapter we use the nomenclature as

pro-posed by the Consensus Netmeeting on

Der-moscopy with some revisions [6]

I.3.5.1 Pigment Network

The pigment network is a honeycomb-like

net-work that consists of pigmented “lines” and

hypopigmented “holes.” The reticulation

(net-work) represents the rete ridge pattern of the

epidermis its histopathological correlation is

either melanin pigment in keratinocytes, or in

melanocytes along the dermo-epidermal

junc-tion The hypopigmented holes in the network

correspond to tips of the dermal papillae and

the overlying supra-papillary plates of the

epi-dermis

The pigment network can be classified as

typical or atypical a typical network is

relative-ly uniform, regularrelative-ly meshed, homogeneous in

color, and usually thinning out at the periphery

(Fig i.3.2) an atypical network is non-uniform,

with darker and/or broadened lines and “holes”

that are heterogeneous in diameter and shape

The lines are often hyperpigmented and may

end abruptly at the periphery

I.3.5.2 Dots

Dots are small, round structures of less than

0.1 mm in diameter which may be black, brown,

gray, or blue-gray Black dots are due to pigment

accumulation in the stratum corneum and the

upper part of the epidermis (see colors) Brown

dots represent focal melanin accumulations at

the dermo-epidermal junction Gray-blue

gran-ules are due to tiny melanin structures in the

papillary dermis Gray-blue or blue granules are

due to loose melanin, fine melanin particles, or

melanin “dust” in melanophages, or exist freely

in the deep papillary or reticular dermis

I.3.5.3 Globules

Globules are round to oval, well-demarcated structures that may be brown, black, or gray They have a diameter larger than 0.1 mm and correspond to nests of pigmented melanocytes, clumps of melanin, and/or melanophages situ-ated usually in the lower epidermis, at the der-mo-epidermal junction, or in the papillary der-mis

Both dots and globules may occur in benign

as well as in malignant melanocytic tions in benign lesions, they are regular in size and shape and evenly distributed (frequently in the center of a lesion; Fig i.3.2) in melanomas, they tend to vary in size, color, and shape and are frequently found in the periphery of lesions

prolifera-Fig I.3.2 Clinical picture of a benign compound nevus Dermoscopy shows a regular pigment network (reticular architecture) at the periphery and regular globules (glob- ular architecture) in the center of the lesion.

1 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

I.3.5.4 Branched Streaks

Branched streaks are an expression of an

al-tered, perturbed pigment network in which the

network becomes broken up (see aBCD rule of

Dermoscopy; Figs i.3.3, i.3.4) Their

pathologi-cal correlations are remnants of pigmented rete

ridges and bridging nests of melanocytic cells

within the epidermis and papillary dermis This

term is exclusively used in the aBCD rule of

dermoscopy and should not be confounded with

the term “streaks,” which is used in the 7-point

checklist of dermoscopy

Fig I.3.3 Clinical image of a lesion which has criteria

for melanoma on clinical examination Dermoscopy

shows an irregular pigment network but no other

crite-ria for melanoma Using the 7-point checklist this lesion

would have a score of 2 and would be classified as

non-melanoma

I.3.5.5 Streaks

Both radial streaming and pseudopods spond histopathologically to intraepidermal or junctional confluent radial nests of melano-cytes This is why some authors prefer using the term “streaks” interchangeably with radial streaming or pseudopods

corre-Streaks can be irregular (unevenly

distribut-ed in melanoma) or regular (symmetrical radial arrangement over the entire lesion); the latter is found particularly in the pigmented spindle cell nevi (reed’s nevi)

Radial Streaming

radial streaming appears as radially and metrically arranged, parallel linear extensions

asym-at the periphery of a lesion (Fig i.3.4)

Fig I.3.4 Clinical image of a melanoma Dermoscopy shows atypical pigment network, irregular dots in the periphery, regression areas, irregular pigmentation, and irregular streaks (radial streaming)

Dermoscopic Examination Chapter I.3 13

Pseudopods

Pseudopods represent finger-like projections of

dark pigment (brown to black) at the periphery

of the lesion They may have small knobs at their

tips, and are either connected to the pigment

network or directly to the tumor body

I.3.5.6 Structureless Areas

Structureless areas represent areas devoid of any

discernible structures (globules, network, etc.)

They tend to be hypopigmented, which is due to

the absence of pigment or diminution of

pig-ment intensity within a pigpig-mented skin lesion

a structureless or hypopigmented area cannot

be lighter than the surrounding skin and does

not have signs of granularity (peppering) in its

periphery

I.3.5.7 Blotches

a blotch (black lamella) is a diffuse

pigmen-tation of black to dark brown color which

ob-scures underlying structures it is due to a large

concentration of melanin pigment localized

throughout the epidermis and/or dermis

visu-ally a blotch can be regular, often in the center

of a lesion (junctional nevus), or irregular

(mel-anoma)

I.3.5.8 Regression

regression appears as white scar-like

depig-mentation (lighter than the surrounding skin)

or “peppering” (speckled multiple blue gray

granules within a hypopigmented area; see

Fig i.3.4) Histopathologically, regression shows

fibrosis, loss of pigmentation, epidermal

thin-ning, effacement of the rete ridges, and melanin

granules free in the dermis or in melanophages

scattered in the papillary dermis

I.3.5.9 Blue-White Veil

Blue-white veil is an irregular, indistinct, fluent blue pigmentation with an overlying white ground-glass haze The pigmentation cannot occupy the entire lesion and is found mainly in the papular part of the lesion Histo-pathologically this corresponds to an aggrega-tion of heavily pigmented cells or melanin in the dermis (blue color) in combination with a com-pact orthokeratosis Blue-white veil should not

con-be confused with confluent peppering larity) in regression areas of melanomas; the latter is the dermoscopy aspect of (histopatho-logical) melanosis Both entities might have a similar dermoscopy aspect but do not have the same histopathological correlation The blue-white veil is, together with pigment-network structures, a highly specific criterion for the di-agnosis of melanoma

(granu-I.3.5.10 Milia-like Cysts

Milia-like cysts are round whitish or yellowish structures which are seen mainly in seborrheic keratosis They correspond to intraepidermal keratin-filled cysts and may also be seen in con-genital nevi as well as in some papillomatous melanocytic nevi (Fig i.3.5)

I.3.5.11 Comedo-like Openings

(Crypts, Pseudofollicular Openings)

Comedo-like openings (pseudocomedos) are seen mainly in seborrheic keratosis (Fig i.3.5)

or in some rare cases in papillomatous cytic nevi Histopathologically they correspond

melano-to keratin-filled invaginations of the epidermis

1 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

I.3.5.12 Fingerprint-like Structures

Some flat seborrheic keratoses (also known as

solar lentigines) can show tiny ridges running

in parallel and producing a pattern which

re-sembles fingerprints

I.3.5.13 Moth-Eaten Border

Some flat seborrheic keratoses (mainly on the

face) have a concave border so that the pigment

ends with a curved structure This has been

compared to a moth-eaten garment

I.3.5.14 Fissures and Ridges

(“Brain-like” Appearance)

Fissures are irregularly, linear keratin-filled

de-pressions, commonly seen in seborrheic

kerato-sis (Fig i.3.5) They may also be seen in

melano-cytic nevi with congenital patterns and in some

dermal melanocytic nevi Multiple fissures

might give a “brain-like” appearance to the

lesion This pattern has also been named “gyri

and sulci” by some authors

I.3.5.15 Leaf-like Areas

leaf-like areas (maple-leaf-like areas) are seen

as brown to gray-blue discrete bulbous blobs,

sometimes forming a leaf-like pattern Their

distribution reminds one of the shape of finger

pads in the absence of a pigment network, they

are suggestive of pigmented basal cell

carcino-mas

I.3.5.16 Spoke-Wheel-like Structures

Spoke-wheel-like structures are

well-circum-scribed brown to gray-blue-brown radial

pro-jections meeting at a darker brown central hub

in absence of a pigment network, they are

high-ly suggestive of basal cell carcinoma

Fig I.3.5 Clinical image of a pigmented seborrheic keratosis Dermoscopy shows multiple milia-like cysts, pseudocomedos, some crypts (fissures), regular hairpin blood vessels, as well as a sharp demarcation

I.3.5.17 Large Blue-Gray Ovoid Nests

ovoid nests are large, well-circumscribed, fluent, or near-confluent pigmented ovoid ar-eas, larger than globules, and not intimately connected to a pigmented tumor body (Fig i.3.6) When a network is absent, ovoid nests are highly suggestive of basal cell carcino-

con-ma

I.3.5.18 Multiple Blue-Gray Globules

Multiple blue-gray globules are round cumscribed structures which are, in the absence

well-cir-of a pigment network, highly suggestive well-cir-of a basal cell carcinoma (Fig i.3.6) They have to be

Dermoscopic Examination Chapter I.3 1

differentiated from multiple blue-gray dots

(which correspond to melanophages and

mela-nin dust)

I.3.6 Differential Diagnosis

of Pigmented Lesions of the Skin

The Board of the Consensus Netmeeting agreed

on a two-step procedure for the classification of

pigmented lesions of the skin (see Fig i.3.7) [6]

The first step is the differentiation between a

melanocytic and a non-melanocytic lesion

once a lesion has been identified to be of

mela-nocytic origin, it has to be determined in a

sec-ond step whether the lesion is benign,

suspi-cious, or malignant This can be done with the

help of different algorithms, which are discussed

later

For the first decision (melanocytic vs melanocytic) the following algorithm is used (Fig i.3.8):

non-Steps 1-2: are pigment network, aggregated

globules, branched streaks, homogenous blue pigmentation, or a parallel pattern (palms, soles, and mucosa) visualized? if this is the case, the lesion should be considered as a melanocytic le-sion (Figs i.3.2, i.3.3, i.3.4)

Step 3: if this is not the case, the lesion should

be evaluated for the presence of comedo-like plugs, multiple milia-like cysts, and comedo-like openings, irregular crypts, light-brown fin-gerprint-like structures, or “fissures and ridges” (brain-like appearance) pattern; if so, the lesion

is suggestive of a seborrheic keratosis (Fig i.3.5) [7]

Step 4: if such is not the case, the lesion has to

be evaluated for the presence of arborizing blood

Fig I.3.6 a Clinical image of a partially pigmented basal

cell carcinoma b Dermoscopy shows arborized

telangi-ectasia as well as an ovoid nest and multiple blue-gray

dots and globules c Clinical image of a pigmented basal

cell carcinoma d Dermoscopy shows a spoke-wheel area,

a blue-gray ovoid nest, a small area of ulceration, and multiple blue-gray dots and globules

a

c

b

d

1 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

vessels (telangiectasias), leaf-like areas, large

blue-gray ovoid nests, multiple blue-gray

glob-ules, spoke-wheel areas, or ulceration if

pres-ent, the lesion is suggestive of basal cell

carci-noma (Fig i.3.6) [8]

Step 5: if such is not the case, one has to look

for red or red-blue (to black) lagoons if these

structures are present, the lesion should be

con-sidered as hemangioma or an angiokeratoma

(Fig i.3.9)

Step 6: if all the preceding questions were

an-swered with “no,” the lesion should still be sidered as melanocytic in order not to miss a melanoma

con-once the lesion is identified to be of cytic origin, the decision has to be made as to whether the melanocytic lesion is benign, sus-pect, or malignant To accomplish this, the fol-lowing algorithms are most common:

melano-Fig I.3.7 Two-step cedure for the classification

pro-of pigmented skin lesions (modified)

Fig I.3.8 algorithm for the decision of melanocytic vs non-melanocytic lesion ac- cording to the proposition of the Board of the Consensus Netmeeting (modified)

Dermoscopic Examination Chapter I.3 17

1 Pattern analysis [9]

Pattern recognition has historically been used

by clinicians and histopathologists to

differenti-ate benign lesions from malignant neoplasms

a similar process has been found to be useful

with dermoscopy, and has been termed “pattern

analysis.” it allows distinction between benign

and malignant growth features it was described

by Pehamberger and colleagues based on the

analysis of more than 7000 pigmented skin

le-sions [9] Table i.3.2 shows the typical patterns

of some common, pigmented skin lesions using

pattern analysis

2 Revised pattern analysis

The revised pattern analysis distinguishes

be-tween global patterns and local features [10]

The general appearance of Color, Architectural

order, Symmetry of pattern, and Homogeneity

(CaSH) are important components in benign

sions from melanoma Benign melanocytic sions tend to have few colors, architectural order, symmetry of pattern, and homogeneity Melano-

le-ma often has le-many colors, architectural disorder, asymmetry of pattern, and heterogeneity

The reticular pattern or network pattern is

the most common feature in melanocytic sions This pattern represents the junctional component of a melanocytic nevus

le-another pattern is the so-called globular tern it is characterized by the presence of nu-

pat-merous “aggregated globules.” This pattern is commonly seen in a congenital nevus, superfi-cial type

The cobblestone pattern is very similar to the

globular pattern but is composed of closer gregated globules, which are somehow angulat-

ag-ed, resembling cobblestones

The homogeneous pattern appears as diffuse

pigmentation, which might be brown, gray-blue, gray black, or reddish black No pigment net-work or any other distinctive dermoscopy struc-tures are found an example is the homogenous steel-blue color seen in blue nevi

The so-called starburst pattern is

character-ized by the presence of streaks in a radial rangement, which is visible at the periphery of the lesion This pattern is commonly seen in reed nevi or Spitz’s nevi

ar-The parallel pattern is exclusively found on

the palms and soles due to the particular

anato-my of these areas

The combination of three or more distinctive dermoscopic structures (i.e., network, dots, and globules, as well diffuse areas of hyper- and hy-popigmentation) within a given lesion is called

multicomponent pattern This pattern is highly

suggestive of melanoma but might be observed

in some cases in acquired melanocytic nevi and congenital nevi

The term “lesions with indeterminate terns” are dermoscopic patterns that can be seen

pat-in both benign and malignant pigmented sions Clinically and dermoscopically one can-not distinguish whether they are melanomas or atypical nevi

le-in addition to the global features mentioned above, the local features (dermoscopic struc-tures such as the pigment network, dots, and globules, etc.) are important to evaluate mela-nocytic lesions (Table i.3.3)

Fig I.3.9 Clinical picture of a cherry angioma

Dermos-copy shows multiple red lagoons

1 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

Table I.3.2 Pattern analysis (Modified after [9])

Lentigo simplex Junctional nevus Compound nevus Dermal nevus Blue nevus

regular pigment

network without

interruptions

regular pigment network without interruptions

regular pigment network without interruptions

regular border, thins

periphery

No pigment network No pigment

network Black dots over the

grids of the pigment

network

Heterogeneous holes of the pigment network

Heterogenous holes of the pigment network

all criteria for melanocytic lesion possible

“Comma”-shaped blood vessels Color heterogeneity

possible

Heterogeneous

(colors and

struc-tures)

irregular pigment network with interruptions

No features of

melano-cytic lesion asymmetry (colors

pigmen-tation irregular pigment

(globules, saccules)

irregular border with

abrupt peripheral

margin

Heterogeneity

comedo-like openings (plugs)

Tree-like blood vessels

brown to gray-black colors

Dermoscopic Examination Chapter I.3 1

I.3.7 ABCD Rule of Dermatoscopy

[11, 12]

The aBCD rule of dermatoscopy, described by

Stolz et al in 1994 [11], was based on an analysis

of 157 pigmented skin lesions it is based on a

scoring system for melanocytic neoplasms

that differentiates them into benign, suspicious,

and malignant categories This is accomplished

by calculating a total dermoscopy score

(Ta-ble i.3.4)

I.3.7.1 Asymmetry

The lesion is bisected by two lines that are placed

90° to each other The first line attempts to

bi-sect the lesion at the division of most symmetry

and the other one is placed 90° to it Symmetry

takes into account the contour, colors, and

structures within the lesion lesions that are

symmetric in both axes are given zero points

Points for asymmetry are multiplied with a

weighting factor of 1.3 to calculate the

dermos-copy score

I.3.7.2 Border

First the lesion is divided into eight equal shaped pieces Next, one counts the number of segments that have an abrupt perimeter cut-off; thus, the points range from 0 to 8, which have to

pie-be multiplied with a weighting factor of 0.1

I.3.7.3 Colors

Number the following colors present: light brown; dark brown; black; red; white; and blue-gray The points will range from 1 to 6, which have to be multiplied with a weighting factor

of 0.5

I.3.7.3 Dermoscopic Structures

Number the following five structures: dots; globules; structureless areas; network; and branched streaks The points range from 1 to 6, which have to be multiplied with a weighting factor of 0.5

Table I.3.3 Patterns of benign and malignant melanocytic lesions

Benign melanocytic lesions Malignant melanocytic lesions

symmetrically located at the periphery,

centrally located, or uniform throughout

the lesion as in a cobblestone pattern

Globules which are unevenly distributed and when reddish in color are highly suggestive

of melanoma

or diffuse almost over the entire lesion

hyperpigmented area that extends almost

to the periphery of the lesion

asymmetrically located or there are often multiple asymmetrical blotches

to-dark uniform pigmented lines and

hypopigmented holes

atypical network which may be form with black/brown or gray thickened lines and holes of different sizes and shapes Network

0 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

Table I.3.4 The aBCD rule of dermoscopy (Modified after [11])

Points Weight factor Sub-score range

light brown; dark brown; black; blue gray

Differential

globules; branched streaks

The individual points are multiplied with

weighting factor which is specific for each

crite-rion The different sub-scores are then added

together in order to obtain the total dermoscopy

score (TDS) a lesion with a TDS <4.75 can be

considered to be benign a lesion with a TDS

>5.45 should be considered to be malignant and

should be removed lesions with a TDS between

4.75 and 5.45 should be considered to be

suspi-cious and should be either removed or

moni-tored

I.3.7.3.1  Seven-Point Checklist

in 1998 argenziano and colleagues described a

7-point checklist based on the analysis of 342

pigmented skin lesions [13] They distinguished

three major criteria (atypical pigment network,

blue-whitish veil, atypical vascular pattern) and

four minor criteria (irregular streaks, irregular

pigmentation, irregular dots/globules,

regres-sion structures; Table i.3.5) Each major

criteri-on has a score of 2 points and each minor

crite-rion has a score of 1 point a minimum total

score of 3 is required for the diagnosis of

mela-noma The 7-point checklist was the first

algo-rithm which compromised the vascular

Table I.3.5 The 7-point checklist (according to [6])

Dermoscopic Examination Chapter I.3 1

in addition, at least one or more of the

posi-tive features that are described in Table i.3.6 has

to be found

I.3.7.3.3  Three-Point Checklist

The three-point checklist [15] is based on a

sim-plified pattern analysis and is intended for use

by non-experts as a screening technique The

three-point checklist does not differentiate

be-tween melanocytic and non-melanocytic

le-sions its aim is to identify all potentially

malig-nant lesions, including basal cell carcinoma and

melanoma, with a high degree of sensitivity

re-markably, the sensitivity for detecting

malig-nancy by non-experts using the three-point

checklist has reached 96.3%; however, as is true

for all screening techniques, the specificity

achieved by non-experts was much lower (32.8%)

than that achieved by experts (94.2%)

The three-point checklist requires the

exam-iner to assess the lesion for only three

der-moscopic criteria: (a) asymmetry; (b) atypical

network; and (c) blue-white structures The

presence of two or three features suggests that

the lesion under investigation is suspect for

1 Colors (brown, black, blue, blue-gray, red, yellow, and white)

2 Blood vessel types (red lagoons, string of pearls, hairpin, dotted,

“comma”-like, glomerular, crown, corkscrew, arborizing, or irregular vessels)

3 architectural criteria (pigment network, dots, globules, branched streaks, streaks, structureless areas, blotches, regression, blue-white veil, milia-like cysts, comedo-like openings, fingerprint-like struc-tures, moth-eaten borders, fissures and ridges, leaf-like areas)

■ Potentially malignant lesions tend to show two of the following three features: asymmetry; atypical network;

and blue-white structures (3-step checklist)

Diag-4 Gewirtzman aJ, Saurat JH, Braun rP an evaluation

of dermoscopy fluids and application techniques Br

J Dermatol 2003; 149(1):59-63

5 Malvehy J, Puig S, Braun rP, Marghoob aa, Kopf

aW Handbook of dermoscopy First ed london and New York: Taylor and Francis; 2006

6 argenziano G, Soyer HP, Chimenti S, Talamini r, Corona r, Sera F, et al Dermoscopy of pigmented skin lesions: results of a consensus meeting via the internet J am acad Dermatol 2003; 48(5 Pt 1):679– 693

Table I.3.6 The Menzies method (according to [8])

Negative features

Point and axial symmetry of pigmentation

Presence of a single color

Peripheral black dots−globules

Multiple colors (five or six)

Multiple blue/gray dots

Broadened network

 R P Braun, H S Rabinovitz, M Oliviero et al.

I.3

7 Braun rP, rabinovitz H, Krischer J, Kreusch J,

oliviero M, Naldi l, et al Dermoscopy of

pig-mented seborrheic keratosis arch Dermatol 2002;

138:1556–1560

8 Menzies SW, Westerhoff K, rabinovitz H, Kopf aW,

McCarthy WH, Katz B Surface microscopy of

pig-mented basal cell carcinoma arch Dermatol 2000;

136(8):1012–1016

9 Pehamberger H, Steiner a, Wolff K in vivo

epilu-minescence microscopy of pigmented skin lesions

i Pattern analysis of pigmented skin lesions J am

acad Dermatol 1987; 17(4):571–583

10 argenziano G, Soyer HP, Giorgio V de, Piccolo D,

Carli P, Delfino M, et al Dermoscopy a tutorial

First ed Milan: EDra; 2000

11 Stolz W, riemann a, Cognetta aB, Pillet l,

abmayr W, Hölzel D, et al aBCD rule of

derma-toscopy: a new practical method for early

recogni-tion of malignant melanoma Eur J Dermatol 1994;

4:521–527

12 Stolz W, Braun-Falco o, Bilek P, landthaler M, Burgdorf WHC, Cognetta aB Color atlas of der- matoscopy, 2nd ed Berlin: Blackwell Wissenschafts- Verlag; 2002

13 argenziano G, Fabbrocini G, Carli P, Giorgio V de, Sammarco E, Delfino M Epiluminescence micros- copy for the diagnosis of doubtful melanocytic skin lesions Comparison of the aBCD rule of dermatos- copy and a new 7-point checklist based on pattern analysis arch Dermatol 1998; 134(12):1563–1570

14 Menzies SW, Crotty Ka, ingvar C, McCarthy WH

an atlas of surface microscopy of pigmented skin lesions: Dermoscopy, 2nd edn roseville: McGraw- Hill; 2003

15 Soyer HP, argenziano G, Zalaudek i, Corona r, Sera F, Talamini r, et al Three-point checklist of dermoscopy a new screening method for early de- tection of melanoma Dermatology 2004; 208(1):27– 31

I.4.1 Introduction

The histopathological diagnosis of melanocytic tumors, including malignant melanoma (hence referred to as melanoma) and benign melano-cytic nevi, has been the subject of countless studies published in the literature although precise histopathological criteria for distinction

of benign from malignant melanocytic erations have been established, in some instanc-

prolif-es a precise diagnosis is not possible, a problem that is reflected by the use of various terms coined during the years, including “melanocytic tumors of uncertain malignant potential (MElTUMP)” or “superficial atypical melano-cytic proliferation of uncertain significance (SaMPUS)” among others Despite uncertainty

in given cases, however, histological tion of a tissue specimen is still the gold stan-dard in diagnosis of melanocytic tumors, and the most important prognostic criteria for pri-mary melanoma (tumor thickness, ulceration) are established by the observation of the histo-pathological specimens as well Sharing unusual

examina-or controversial cases in consultation with matopathologists with special expertise in me-lanocytic tumors is helpful in minimizing the risk of misdiagnoses that may be potentially fatal for the patients

I.4.2 General remarks 25

I.4.2.1 Morphological observations 25

I.4.2.2 ancillary Techniques 25

I.4.2.3 Particular Morphological Types

of Melanoma 25

I.4.3 Special Settings 26

I.4.3.1 Melanocytic Tumors Biopsied

in Newborns or Shortly after Birth 26

I.4.3.2 Proliferations of Melanocytes

Within Chronic Sun-Damaged Skin 27

I.4.3.3 Proliferations of Melanocytes Biopsied

Shortly after Sun Exposure 28

I.4.3.4 Proliferations of Melanocytes

Within Mucosal Epithelium

(Genital and oral Mucosa) 28

I.4.3.5 Melanocytic Proliferations

at other Special Skin Sites 29

I.4.3.6 Proliferations of Melanocytes at Sites

of inflammatory Skin Disorders 30

I.4.4 Particular Histopathological Problems 30

I.4.4.1 Melanocytic Nevi with Several Cell

Populations (“Combined” Nevi) 30

I.4.4.2 Nodular Proliferations of Melanocytes

Within Congenital Nevi 30

I.4.4.3 Superficial Proliferations of Melanocytes

with Prominent Pigmentation 31

I.4.4.4 Proliferations of Melanocytes associated

with Prominent inflammatory response

and/or regression 31

I.4.4.5 recurrence (Persistence)

of Melanocytic lesions at the Site

of a Previous incomplete Excision

(recurrent Nevi, recurrent Melanoma) 32

I.4.4.6 atypical Melanocytic Nevi

with Degenerative Changes

(“ancient” Melanocytic Nevi) 32

I.4.4.7 Melanocytic Proliferations

with “Spitzoid” Morphology 33

I.4.5 Conclusion 34

references 35

 L Cerroni

I.4

it is crucial to remember that under the

mi-croscope each single melanocytic lesion should

first be analyzed at scanning magnification in

order to evaluate properly overall symmetry

and lateral circumscription it is also important

to emphasize that a proper biopsy is a

pre-requi-site for a specific diagnosis This is true in

der-matopathology in general, and even more so in

the evaluation of melanocytic lesions

incom-plete biopsies (e.g., punch biopsies, shave

biop-sies) often do not allow a precise classification of

the cases in a similar manner, biopsies with

surgical artifacts (crush artifacts) often cannot

be interpreted properly Finally, optimal

prepa-ration of the specimens in the

dermatopatho-logical laboratory is crucial as well all too often

we receive specimens in consultation that are

either badly cut, or badly stained, or both a

precise diagnosis in these cases is often

impos-sible

a good practice in the histopathological

evaluation of melanocytic tumors is to study

more than a single section of tissue Step

sec-tions should be prepared routinely, particularly

in cases that are controversial

histopathologi-cally, or that showed atypical features clinically

in this context, communication between

clini-cians and dermatopathologists is crucial in

ad-dition, photographic documentation of each

le-sion deemed to be suspicious clinically should

be attached to the referral sheet, in order to

avoid mistakes in the grossing of the specimens

in fact, in melanomas arising within

melano-cytic nevi the specific histopathological changes

may be found only focally, and a clinical picture

with remarks by the clinicians allows precise

identification of the suspicious areas before

grossing The occurrence of melanoma within

pre-existing melanocytic nevi is probably

un-derestimated [46]

The histopathological criteria for the

diagno-sis of melanoma are listed in Table i.4.1 They

include general architectural criteria, features of

the intraepidermal and dermal components,

and cytomorphological features of the

melano-cytes (Fig i.4.1) [1, 2] No single criterion is

spe-cific for benign or malignant proliferations of

melanocytes, and exceptions to any of these

cri-teria exist; thus, only integration of all cricri-teria

can be helpful in establishing the correct

diag-Table I.4.1 Histopathological features of melanoma

asymmetry of the lesion overall asymmetry asymmetry of pigment distribution asymmetry of inflammatory infiltrate Unsharp lateral circumscription Presence of ulceration

“Consumption” of the epidermis (thinning of the epidermis with attenuation

of the basal and suprabasal layers and loss of the rete ridges adjacent to collections of melanocytes) Solitary melanocytes predominate over melanocytes

in nests within the epidermis Pagetoid spread of melanocytes within the epidermis (melanocytes distributed in all layers

of the epidermis) incohesive melanocytes within nests Sheets of melanocytes within the dermis

“Pushing” lower margin of dermal complexes

of melanocytes obliteration and/or destruction of adnexal structures

Presence of intravascular complexes of melanocytes Perineural growth and/or neurotropism

Presence of atypical melanocytes Presence of several mitoses, especially at the base

of the lesion

Fig I.4.1 Melanoma shows scatter of melanocytes in small nests and as solitary units at all level of the epi- dermis

Melanoma: the Morphological Dimension Chapter I. 

nosis in this context, it is important to

under-stand that in most cases application of the

histo-pathological criteria listed in Table i.4.1 allows a

precise diagnosis of melanoma, and that

excep-tions are relatively rare; however, excepexcep-tions do

exist, and their recognition and precise

classifi-cation is crucial in order to manage patients

ad-equately We discuss herein the general aspects

of the histopathological diagnosis of melanoma

and nevi, as well as some of the

histopathologi-cal problems that may be encountered in the

microscopic evaluation of pigmented lesions of

the skin

I.4.2 General Remarks

I.4.2.1 Morphological Observations

in recent years, many different studies have

ad-dressed specific aspects of melanoma diagnosis

and prognosis, and many different suggestions

have been proposed as to what information a

histopathological report should include

Exam-ples are, among others, presence/absence of

tu-mor-infiltrating lymphocytes, vertical or

hori-zontal growth phase, number of mitoses per

unit area, presence of regression, presence of

neo-angiogenesis, and details on

histopatho-logical classification according to the categories

of superficial spreading melanoma, nodular

melanoma, lentigo maligna melanoma, or acral

melanoma [17, 19, 27, 28, 34, 43, 60, 73] This last

classification, in our opinion, is obsolete, and

does not convey any meaningful information to

physicians and/or patients in addition, the

prognostic value of most of the

histopathologi-cal features listed above have yet to be validated

in large studies, and at present the only accepted

prognostic features for TNM classification of

the tumors are the maximal thickness and the

presence of ulceration [6, 7] The Clark level

needs to be mentioned only in the rare cases of

thin melanoma (<1 mm) of levels iV or V For a

precise TNM classification of each case it is

cru-cial that prognostic criteria be evaluated

prop-erly (Fig i.4.2)

I.4.2.2 Ancillary Techniques

The diagnosis of melanoma rests upon careful examination of sections of tissue stained with hematoxylin and eosin although many studies addressed the value of immunohistochemical stainings in the diagnosis and classification of melanocytic tumors, there are no compelling data showing that any immunohistochemical marker provides informations that go beyond those already provided by routine histological examination of the specimen Genetic studies may provide in the near future additional valu-able informations, especially in controversial le-sions at present, however, careful examination

of routine histopathological sections and rate clinicopathological correlation are the gold standard in the histopathological diagnosis of benign and malignant melanocytic tumors, and

accu-in the assessment of prognostic parameters accu-in primary melanoma [38, 55, 93]

I.4.2.3 Particular Morphological Types

of Melanoma

in some cases, melanoma deviates from the conventional histopathological features listed in Table i.4.1, and is characterized by peculiar as-pects that may render the diagnosis difficult it

is important to be familiar with the different morphological presentations of melanoma in

Fig I.4.2 Melanoma growing along a hair follicle within the dermis is shown Breslow tumor thickness should not be measured in the proximity of adnexal structures (adventitial dermis)