how to diagnose nonpigmented skin tumors a review of vascular structures seen with dermoscopy part...

8/12/2019 How to Diagnose Nonpigmented Skin Tumors a Review of Vascular Structures Seen With Dermoscopy Part I. Melanocytic Skin Tumors 2010 Journal of the A

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CONTINUING MEDICAL EDUCATION

How to diagnose nonpigmented skin tumors: A reviewof vascular structures seen with dermoscopy

Part I. Melanocytic skin tumors

Iris Zalaudek, MD,a Jurgen Kreusch, MD, PhD,b Jason Giacomel, MBBS,c Gerardo Ferrara, MD,d

Caterina Catricala, MD,e and Giuseppe Argenziano, MD, PhDf

Graz, Austria; Lubeck, Germany; South Perth, Australia; and Benevento, Rome, and Naples, Italy

Dermoscopy is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumors. This isbecause dermoscopy permits the visualization of key vascular structures that are usually not visible to thenaked eye. Much work has concentrated on the identification of specific morphologic types of vessels thatallow a classification into melanocytic versus nonmelanocytic and benign versus malignant nonpigmentedskin tumors. Among a broad spectrum of different types of vascular patterns, six main morphologies can beidentified. These are comma-like, dotted, linear-irregular, hairpin, glomerular, and arborizing vessels. With

some exceptions, comma, dotted, and linear irregular vessels are associated with melanocytic tumors,while the latter three vascular types are generally indicative of keratinocytic tumors. Aside from vascularmorphology, the architectural arrangement of vessels within the tumor and the presence of additionaldermoscopic clues are equally important for the diagnosis. This article provides a general overview of thedermoscopic evaluation of nonpigmented skin tumors and is divided into two parts. Part I discussesthe dermoscopic vascular patterns of benign and malignant melanocytic skin tumors. Part II discusses thedermoscopic vascular patterns of benign and malignant nonmelanocytic nonpigmented skin tumors. Ineach part, additional special management guidelines for melanocytic and nonmelanocytic nonpigmentedskin tumors, respectively, will be discussed. ( J Am Acad Dermatol 2010;63:361-74.)

Learning objectives: After completing this learning activity, participants should be able to categorizedifferent vascular structures and the architectural arrangement of vessels within tumors and additionaldermoscopic clues of nonpigmented skin tumors, recognize the diagnostic significance of vesselsassociated with nevi and melanoma, and appropriately manage nonpigmented melanocytic skin tumors.

Key words:amelanotic melanoma; Clark nevus; dermal nevus; dermoscopy; hypomelanotic melanoma;Spitz nevus; Spitz tumor; vessels.

Dermoscopy is a noninvasive technique thathas gained great popularity for the diagno-sis of pigmented skin tumors (PSTs) be-

cause it improves diagnostic accuracy compared toexamination with the naked eye.1-3 Dermatoscopesare modified magnifying devices that permit the

visualization of pigmented structures or vessels inthe epidermis and superficial dermis. Because mostdermoscopic structures correspond to specific histo-pathologic correlates, dermoscopy can be regarded

as a link between clinical (macroscopic) andhistopathologic (microscopic) morphology.4

In contrast to the traditional liquid or gel-immersion (contact) dermatoscopes, newer genera-tions of handheld skin surface microscopes usecross-polarized light to visualize cutaneous struc-

tures.

5

Both systems are commercially available andgenerally operate at 10-fold magnification.6 Polarizedlight dermatoscopes have the advantage that directphysical contact between the glass plate and the skin

From the Division of Dermatology,a Medical University of Graz;

private practice,b Lubeck; Mends St Medical Centre,c South

Perth; the Pathologic-Anatomy Unit,d Gaetano Rummo Hospi-

tal, Benevento; Department of Dermatologic Oncology,e Santa

Maria and San Gallicano Dermatologic Institute, Rome; and the

Department of Dermatology,f Second University of Naples.

Dr Zalaudek is supported by the Elise Richter Program (V9-B05) of

the Austrian Science Fund (FWF).

Conflicts of interest: The authors, editors, planners, and peer

reviewers have no relevant financial relationships.

Reprint requests: Iris Zalaudek, MD, Department of Dermatology,

Medical University of Graz, Auenbruggerplatz 8, 8036 Graz,

Austria. E-mail: [email protected].

0190-9622/$36.00

2010 by the American Academy of Dermatology, Inc.

doi:10.1016/j.jaad.2009.11.698

361
mailto:[email protected]:[email protected]


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is not required. Conversely, a disadvantage of non-polarized instruments is that contact of the opticalglass plate can exert pressure on the tumor surface,compressing surface capillaries and making themdifficult to visualize. While this is of limited diagnosticdisadvantage in the evaluation of PSTs, vessels maybe the only dermoscopic features observable innonpigmented skin tumors(NPSTs) and they are there-fore a valuable key fordiagnosis.

Given that NPSTs repre-sent a diagnostic challengefor the clinician, much workhas concentrated on theidentification of vascularpatterns that may aid theircorrect recognition. 7-12 An

overview of the dermoscopicvascular patterns is providedin this article, and key pointsand diagnostic clues for themanagement of the mostcommon NPSTs areprovided.

BASIC ASPECTS TOVIEW VESSELS BYDERMOSCOPY

The visualization of vas-

cular structures stronglydepends on the optical de-vice (contact or noncontactdermatoscope) and thetechnique of dermoscopicexamination.6,7 When usingcontact dermatoscopes, thecontact glass plate of these instruments must be setcarefully on the tumoral surface, applying minimaldownward pressure. Liquids of low viscosity, such asalcohol or immersion oil, are sometimes used ascontact media, but are best avoided in contact

dermoscopy. This is because they require excessivedownward pressure to be exerted by the instrumentonto the tumor in order to obtain complete opticalcontact. In most dermatology offices, translucentultrasound gel is an effective contact medium be-cause of its high viscosity. Moreover, a practical tipfor using contact dermoscopy in the examination ofNPSTs is to apply a sufficiently generous dollop ofultrasound gel onto the lesion, which allows theglass plate to be softly dipped into the gel.

Although noncontact dermoscopy does not re-quire a liquid interphase between the lens and the

skin, very dry or scaly lesions may cause significant

reflection, which can limit visualization of underly-ing vascular structures. In such cases, the applicationof liquids (water, alcohol, immersion oil, or ultra-sound gel) onto the lesion often helps to diminishthis surface reflection and improves the visualizationof vessels.

A THREE-STEPDIAGNOSTIC

ALGORITHM FOR THEDIAGNOSIS OFNONPIGMENTED SKIN

TUMORSKey pointsd Before beginning the

dermoscopic evaluationof a given nonpigmen-

ted skin lesion, it isnecessary to establishwhether the lesion is atumor or belongs to thespectrum of inflam-matory or infectiousskin diseases, becausethe vascular patternbetween these two cate-gories may overlap

d The dermoscopic ex-amination of a NPSTshould follow a stepwisealgorithm assessing themorphology of the vas-cular pattern, the architec-tural arrangement ofvessels in the tumor, andthe presence of additio-nal dermoscopic criteria

The accurate diagnosis of NPST is clinically diffi-cult given the wide spectrum of possible differentialdiagnoses, which vary from benign inflammatory tohighly aggressive malignant skin tumors, such as

amelanotic melanoma or Merkel cell carcinoma.Vascular patterns of NPSTs may overlap with

those of inflammatory skin disorders, so it is criticalto establish whether the lesion is a tumoror repre-sents an inflammatory or infectious process.12Whena nonpigmented skin lesion (NPSL) is clinicallyclassified as a tumor (taking into consideration lesionsize, number, distribution, clinical features, and his-tory), the dermoscopic examination should follow astepwise algorithm assessing first the morphology ofthe vascular pattern, second the architectural ar-rangement of vessels in the tumor and, third the

presence of additional dermoscopic criteria that

CAPSULE SUMMARY

d Dermoscopy improves the diagnosis of

nonpigmented skin tumors because it

allows the visualization of vascular

patterns and residual pigmentation that

are not visible to the naked eye.

d The dermoscopic diagnosis of a

nonpigmented skin tumor is based on a

three-step algorithm that considersvascular morphology, the architectural

arrangement of vessels, and additional

clues.

d The predominant vascular pattern of

amelanotic/hypomelanotic melanoma

strongly depends on the tumor

thickness.

d Comma, dotted, and linear irregular

vessels are suggestive of melanocytic

skin tumors.

d

Histopathologic diagnosis should alwaysbe obtained for lesions displaying

dotted, linear irregular, or polymorphous

vessels, milky red color or globules, or

those that have a nonspecific

dermoscopic appearance.

J AMACADDERMATOLSEPTEMBER2010

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provide further clues for the diagnosis. Finally adiagnosisor at least an appropriate managementplan based on several clues and rulescan beestablished.13

Step 1: Morphology of vascular patternsThe most important chromophore in NPST is

hemoglobin within the erythrocytes of the vascularlumen. Vessels located in the dermis generally ap-pear pink and blurred because of the dispersion oflight by dermal connective tissue fibers, whereasvessels located more superficially (immediately be-low the epidermis) appear bright red and focused.

Given that dermoscopy provides a horizontal view ofthe skin, vessels arranged parallel to the skin surfaceappear as lines, whereas vertically arranged vesselswill be seen as dots or loops. Importantly, theprevailing vascular patterns strongly depend ontumor progression and volume.7 For example, clin-ically flat, superficial amelanotic/hypomelanoticmelanoma (AHM) or basal cell carcinoma (BCC)show different vascular patterns compared to theirthick, nodular counterparts.

NPSTs are characterized by specific morphologictypes of vessels that allow a further classification into

melanocytic versus nonmelanocytic and benign ver-sus malignant skin tumors. Among a broad spectrumof different types of vascular patterns that have beendescribed in the literature, six main morphologiccategories of vascular patterns can be identified.These are comma-like, dotted, linear irregular, hair-pin, glomerular, and arborizing vessels (Fig 1,A-F).In addition, three specific global features can bedifferentiatednamely, crown vessels surroundinga white center, strawberry pattern, and milky redareas/globules (Fig 1,G-I).7,9,11,13With some excep-tions, comma, dotted, and linear irregular vessels are

associated with melanocytic lesions (dermal nevi,

Spitz nevi, and AHM, respectively). Hairpin, glomer-ular, and arborizing vessels are generally indicativeof the nonmelanocytic tumors seborrheic keratosis(SK) and squamous cell carcinoma (SCC), includingkeratoacanthoma (KA)-(hairpin), Bowen disease(BD) and intraepidermal carcinoma (IEC)-(glomer-ular), and basal cell carcinoma (BCC)-(arboriz-ing).7,9,11 Crown vessels surrounding a whitepolylobular center are diagnostic for sebaceoushyperplasia (SH), while the strawberry pattern andmilky red areas/globules are relatively specific fea-tures of facial actinic keratosis (AK) and thick AHM,respectively.

Atypical linear vessels either alone or in combi-nation with any other vascular pattern (ie, a poly-morphous vascular pattern) should always raise theindex of suspicion for malignant skin tumors.9,14

Kittler et al15 have proposed defining vessels

using purely morphologic descriptive terminologies.According to this proposal, vessels can be classifiedinto three main morphologic types: red dots (for-merly dotted vessels), clods (formerly milky redglobules), and linear vessels.

With regard to the morphology of linear vessels,they can be further subdivided into linear straight(formerly linear irregular vessels), linear looped(formerly hairpin vessels), linear curved (formerlycomma vessels), linear serpentine (formerly linearirregular, arborizing, crown, or short fine arborizingtelangiectasias), linear helical (formerly corkscrew

vessels), and linear coiled (formerly glomerularvessels).

However, some of the newly introduced termsdescribe only barely the arrangement of vessels ortheir relation to tumor thickness. For example, in SH,the peripheral arrangement of vessels embracingthe central tumoral area is included in the termcrown vessels, but cannot bededuced from linearstraight or linear serpentine.15

Whether this may decrease the diagnostic accur-acy for some types of vascular patterns remains to beclarified. Because no study to date has been per-

formed comparing the inter- and intraobserveragreement for the traditional and new vessel termi-nologies, we have provided for convenience boththe traditional and newly introduced (in parenthesis)terminologies of vascular patterns (Table I).

Step 2: Architectural arrangement of vesselsAfter the assessment of morphology, the recogni-

tion of the architectural arrangement of vascularstructures is a critical step in the diagnosis of NPSTs.This is because different skin tumors may revealsimilar types of vessels, but these can differ in their

architectural arrangement.Figure 2summarizes the

Abbreviations used:

AHM: amelanotic/hypomelanotic melanomaAK: actinic keratosisBCC: basal cell carcinomaBD: Bowen diseaseCCA: clear cell acanthomaCMN: congenital melanocytic nevusDM: desmoplastic melanomaIEC: intraepidermal carcinomaKA: keratoacanthomaNPSL: nonpigmented skin lesionNPST: nonpigmented skin tumorPPV: positive predictive valuePST: pigmented skin tumorSCC: squamous cell carcinomaSH: sebaceous hyperplasiaSK: seborrheic keratosis

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vessels and intersectto form a white network struc-ture (Fig 4, B).13,18 Less frequently, chrysalis-likestructures can also be seen.19 The latter structure is anewly described morphologic criterion that is onlyvisible when using polarized dermoscopy and con-sists of short, shiny white orthogonal lines, whichprobably correspond to altered papillary dermalcollagen.20 In hypopigmented Spitz nevi, a residual

starburst or globular pattern may facilitate the diag-nosis.18 In our experience, nodular and atypicalSpitz nevi differ from flat Spitz nevi in their vascu-lature as they often exhibit atypical vascular struc-tures indistinguishable from those of thick AHM,including linear irregular vessels (linear straight),glomerular vessels (linear coiled), or milky redglobules (red clods; Fig 4, Cand D).9 Importantly,no single dermoscopic criterion has yet been de-scribed that allows for an accurate differentiation offlat, atypical, and nodular Spitz nevi from AHM.Therefore, excisionof all Spitzoid lesions is gener-

ally recommended.

21

Dotted vessels (red dots) and comma vessels(linear curved) in red Clark neviKey pointd It is important to evaluate all lesions in fair

skinned individuals who have multiple redClark nevi in order to verify similar vascularpatterns and colors of these nevi

Another type of melanocytic tumor frequentlyshowing dotted vessels (red dots) is the red Clarknevus,as seen in fair skinned individuals (skin type Ior II).22 In contrast to the dense arrangement ofdotted vessels in Spitz nevi, vessels in red Clarknevi are more loosely arranged throughout the lesionand are often associated with a few comma-like(linear curved) vessels (Fig 5). The background colormay provide a further criterion helpful in distinguish-ing red Clark nevi from Spitz nevi. The formercommonly show a tan colored background, whileSpitz nevi usually reveal a striking pink (milky red)color.

Fig 2. Schematic drawing of vascular arrangements. A, Regular, (B) in a string, (C) clustered,(D) radial, (E) irregularly branched, and (F) irregular.


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Hypopigmented Clark nevi in fair skin individ-uals often reveal dotted (red dots) or comma-likevessels (linear curved) within an elevated hypopig-mented center that is surrounded by a flat periph-eral light brown reticular or homogenouspigmentation.23

In fair skinned individuals with multiple red Clarknevi, it is critical to evaluate all lesions in order to

detect deviation from the signature vascular patterns

and colors. This is particularly helpful for the diag-nosis of nevi located on the legs of individualssuffering from chronic venous insufficiency, acrocy-anosis, and livedo reticularis (cutis marmorata),which frequently display dotted vessels.12 In suchcases, comparison with neighboring nevi enables therecognition of similar vascular structures, whichhelps to reduce the suspicion of hypomelanotic

melanoma.

Table II. Criteria and management recommendations for nonpigmented skin tumors

Step 1: Vessel

morphology

Step 2: Vessel

arrangement Step 3: Additional criteria Diagnosis Management

Level of

evidence

Comma Regular Residual brown

globules, hairs

CMN or dermal

nevus

No action IIA*

Dotted pluscomma Regular Brownishpigmentation Red clark Nevus If similar other nevi,follow-up; if single

lesion: excision

IIA*

Dotted Regular Reticular

depigmentation;

chrysalis structures;

remnants of

pigmentation

Spitz nevus or

thin AHM

Excision IIA*

Dotted String-like White halo CCA No action IIIy

Dotted plus

glomerular

Clustered White halo, surface

scales

BD or IEC Excision IIA*

Hairpin Regular White halo; milia-like

cysts; comedo-like

openings

SK No action IIBz

Radial or irregular White halo; centralkeratin crust

SCC or KA Excision IIBz

Arborizing Large stem vessels;

branching over

lesion

Blue-gray ovoid

nests/globules/

dots/blotches

Nodular cystic BCC Excision IIA*

Fine

microarborizing

vessels scattered

throughout lesion

Multiple erosions;

brown-gray, leaf-

like, or wheel spoke

areas

Superficial BCC Excision IIBz

Linear irregular Central or irregular Red homogeneous

pigmentation

PG or nodular AHM Excision IV

Linear irregular

and dotted

Central or irregular Chrysalis structures;

remnants of white-

pink-brown-graypigmentation

Thin or intermediate

thick AHM

Excision IIBz

Linear irregular

and hairpin or

corkscrew or

arborizing

Central or irregular Multiple colors;

milky red

globules/areas

Thick AHM or

melanoma

metastases

Excision IIA*

Crown Radial White polylobular

center

SH No action IIIy

AHM, amelanotic/hypomelanotic melanoma; BCC, basal cell carcinoma; BD, Bowen disease; CCA, clear cell acanthoma; CMN, congenital

melanocytic nevus; IEC, intraepidermal carcinoma; KA, keratoacanthoma; PG, pyogenic granuloma; SCC, squamous cell carcinoma; SH,

sebaceous hyperplasia; SK, seborrheic keratosis.

*Level IIAEvidence from at least one controlled study without randomization.zLevel IIBEvidence from at least one other type of experimental study.

yLevel IIIEvidence from nonexperimental descriptive studies, such as comparative studies, correlation studies, and case control studies.Level IVEvidence from expert committee reports or opinions or clinical experience of respected authorities, or both.


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VASCULAR PATTERNS OF AMELANOTICAND HYPOMELANOTIC MELANOMA

The predominant vascular patterns of AHM andtheir arrangement strongly depend on the thick-

ness of the tumor. The observed vascular patternsundergo time-related changes according to mela-noma progression and should therefore always becorrelated with the clinical palpability of a givenlesion (ie, flat, elevated, or nodular). Generally, inearly (flat) AHM, dotted vessels are seen, whichappear homogeneous in shape and are arrangedregularly. In contrast, vessels in advanced (raised)tumors are more irregularly distributed andappear longer, coarser, and more variable inshape.

Hypopigmentation in melanoma requires a more

precise definition. Tumors lacking any trace of mel-anin, even if viewed under the dermatoscope, aretrue amelanotic melanomas.17 Hypomelanotic tu-mors have some remnants of melanin pigmentationbut are lighter overall than conventional pigmentedmelanoma. One subtype has faint brownish melaninpigment that may occupy the entire lesion area(light colored melanoma). Another has larger orsmaller pigmented sections occupying less than 25%of the lesion, with the remaining part being amela-notic (partially pigmented melanoma).17 Finally,melanomas in advanced stages of regression are

poorly pigmented or focally depigmented.

24,25

Dotted vessels (red dots) in thin amelanoticmelanoma (


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polymorphous vascular pattern). The latter vesselsare often kinked and can be difficult to discern (PPVfor melanoma = 67.6%; Fig 6).7,17,14,17,26,29-35

Although the vessels in melanoma tend to be moreirregularly distributed than in Spitz nevi, it is unde-niable that a proportion of AHMs are indistinguish-able dermoscopically from Spitz nevi (Fig 7). In

addition, a milky red color (shades of pink and

white), reticular depigmentation, or chrysalis-like

structures can occur in both tumors, giving rise tothe general rule that one should excise all lesionswith a Spitzoid appearance under dermoscopy.

Polymorphous vessels in thick amelanoticmelanoma (>2 mm thickness)Key pointd Thick melanoma exhibits irregularly distrib-

uted, elongated, and variably sized linearvessels including twisted and splinteredhairpin vessels, corkscrew or arborizingvessels, and/or milky red globules

In contrast to the often subtle appearance ofvessels in thin AHM, thick AHM exhibit irregularlydistributed, elongated, and variably sized atypicallinear vessels, including twisted and splinteredhairpin loops (linear looped) and corkscrew vessels(linear helical).17,26,35-37 Of note, melanoma ofmore than approximately 3 mm thickness developsa different structure of vascular supply. Becausevertical growth apparently cannot be maintainedby further elongation of the capillary loops, vesselsarising from the adjacent dermal plexus appear

on the tumoral surface. These vessels resemble

Fig 4. Dermoscopic images of nonpigmented Spitz nevi.A, Regularly distributed small dottedvessels (red dots) over a milky red background are the most common finding in flat Spitz nevi.B, Example of a slightly pigmented Spitz nevus showing regularly distributed dotted vessels(red dots) and a reticular depigmentation appearing as white reticular lines.C, Nodular Spitznevus showing vascular polymorphism composed of dotted (red dots) and glomerular (linearcoiled) vessels along with reticular depigmentation. D, Atypical Spitz nevus showingpredominantly milky red globules (red clods), in addition to a single linear telangiectasia(arrow) and remnants of brown pigmentation.

Fig 5. Dermoscopy of a red Clark nevus revealing looselydistributed dotted (red dots) and comma-like (linearcurved) vessels on a light brownish background.


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arborizing vessels of BCC; however, their winding

and branching is less bizarre and irregular as com-

pared to BCC. At this stage, dotted vessels (red dots)

are rarely observed and, if present, are seen in a flat

portion of the tumor. Less commonly seen, but quite

suggestive of AHM (PPV = 77.8%) are milky red

globules (red clods).9 These are large ovoid or

polygonal structures of pink-white color that often

show a central atypical linear vessel (Fig 8).

Individual globules are usually separated from each

other by blurred whitish lines.

Dermoscopic features of hypomelanoticmelanomaKey pointd Dermoscopy improves the diagnosis of hy-

pomelanotic melanoma because it permits,besides vascular structures, the recognitionof brown-gray-blue pigmentation patternsnot discernible to the naked eye

While true AHMs lacking any pigmentation stillremain a diagnostic challenge, dermoscopy im-

proves the diagnostic sensitivity (96%) and

Fig 6. Clinical and dermoscopic images of true amelanotic melanoma (tumor thickness, 1.7mm). Dermoscopy reveals a striking pink (milky red) color and predominant linear irregular(linear straight) vessels.

Fig 7. Side-by-side comparison of a partially pigmented spitzoid melanoma with a tumorthickness of 1.5 mm (A) and a Spitz nevus (B). Both tumors exhibit a striking asymmetry ofcolors and structures, a combination of peripheral dotted (red dots) and central linear irregular

vessels (linear straight) and reticular depigmentation, making an accurate differentiationbetween the melanoma and nevus virtually impossible.


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specificity (88%) of hypopigmented melanoma com-pared with clinical examination alone (89% and 65%,respectively).17,26 This is because dermoscopy per-mits the visualization of vascular structures and therecognition of pigmentation patterns not discernibleto the naked eye. The latter includes structurelessbrown, gray, or bluish blotches, features of regres-

sion, irregular globules, streaks, and residual areas ofatypical pigment network (Figs 8 and 9).

Recently, Menzies et al17 conducted a study inves-tigating the predictive dermoscopic patterns of AHMin a series of benign and malignant, melanocytic, andNMSTs lacking significant pigmentation. In this study,comma-like (linear curved) vessels were a significantnegative predictor for AHM, while the presence ofremnants of pigment (including blue-white veil,scar-like depigmentation, multiple blue gray dots,irregular depigmentation, and irregular brown dots/globules), multiple colors, and predominant central

vessels were significantly associated with AHM.Based on their findings, a simple model for thediagnosis of nonmelanoma versus AHM was pro-posed. However, the latter model achieved only 70%sensitivity and 56% specificity in a test set. For thisreason, the authors formulated an alternative modelto distinguish between all malignant (including AHM,BCC, SCC, KA, and BD) and nonmalignant lesionslacking significant pigment. In an independent test,the diagnostic sensitivity for malignant lesions in thelatter model increased to 96%. However, the rise insensitivity of this model was attained at the expense

of a very low specificity (37%).

RARE MELANOMA VARIANTSKey pointsd Nodular melanoma may lack significant

vascular patternsd Eczema-like melanoma should be considered

in the differential diagnosis of solitary, scaly,eczematous patches or plaques that do notrespond to topical treatment

d Dermoscopy may be helpful in the recogni-tion of fully regressed melanoma or desmo-plastic melanoma

d Cutaneous melanoma metastases reveal dot-ted or corkscrew vessels

Nodular melanoma commonly lacks any discern-ible vascular patterns. In such cases, polychromatism(shades of pink, white, red, blue, brown, or gray)may be the only clue for the correct diagnosis(Fig 10).17,26,35-39

Eczema-like melanoma is a rare variant of mela-noma (to our knowledge, only six cases have been

published to date) that can be extremely difficult todiagnose because of its similarity to a range ofinflammatory or infective processes, including num-mular eczema, psoriasis, verrucous lichen planus,and tinea corporis. The clinical presentation is re-markable in that it typically presents as a solitary,scaly patch or plaque typically located on the ex-tremities and is resistant to various topical treat-ments. However, dermoscopy may suggest thediagnosis by revealing vascular polymorphism in-cluding dotted (red dots), glomerular (linear coiled)or atypical linear (linear straight) vessels in associa-

tion with residual brown to gray pigmentation.

29,34,40

Fig 8. Clinical and dermoscopic images of hypomelanoticmelanoma (tumor thickness, 2 mm). The central nodularpart lacks any pigmentation and reveals milky red globules

with linear irregular vessels (linear straight; arrows). Inaddition, chrysalis-like structures can be seen (square).

The diagnosis of melanoma in this case is facilitated by thepresence of melanoma-specific patterns in the flat area,such as an atypical network, residual homogeneousbrown pigmentation, and large areas of white scar-likeregression.

Fig 9. Clinical (insert) and dermoscopic images of hypo-pigmented melanoma (tumor thickness, 1.5 mm). Dermo-scopy reveals predominantly dotted vessels (red dots) anda few linear irregular (linear straight) vessels, as well asstructureless brown to bluish pigmentation. Although the

lesion lacks pigmented patterns, such as a pigmentnetwork, globules, or streaks, the brown-blue pigmenta-tion is suggestive for a melanocytic tumor.


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Dermoscopy has been also shown to aid theclinical detection of fully regressed melanomas.25

In a recent study, seven specific changes wereassociated with melanomas that underwent com-plete regression, including scar-like depigmentation,background pink coloration, linear irregular vessels,dotted vessels, remnants of pigmentation (structure-less or pepper-like), and whitish transverse bands.The last feature was only observed with polarized

light dermoscopy devices. Similar changes have alsobeen recently described by Stante et al.41

Desmoplastic melanoma (DM) is a rare variant ofcutaneous melanoma that is typically located on thechronically sun exposed areas of the head and neck.The diagnosis of DM is often delayed, because DMmay mimic a variety of other less sinister skin lesions.In a recent study investigating the dermoscopicpatterns of six cases of DM, the authors found criteriaof a melanocytic tumor (ie, globules, network orstreaks) in only half of the cases, whereas theremaining lesions lacked any specific criteria of

either melanocytic or nonmelanocytic tumors.42

However, regression features were seen in all sixcases, including white scar-like areas (6/6), graypeppering (3/6), multiple ([4) colors (5/6), andmelanoma-related vascular patterns (5/6), such aslinear irregular (linear straight) vessels (4/6) andmilky red areas (2/6).

Similar to primary melanoma, the prevailing vas-cular pattern in melanoma metastases depends onthe vertical dimension of the lesion. As such, dottedvessels (red dots) prevail in thinner lesions, whilecorkscrew vessels (linear helical) or a saccular pat-

tern is more commonly encountered in thicker

tumors. The latter is characterized by poorly defined,largeovoid structures of homogeneous red-browncolor.43

CLUES AND RULES FOR DIFFERENTIALDIAGNOSIS AND MANAGEMENTREGARDING AMELANOTIC ORHYPOMELANOTIC MELANOMAFour main points to avoid missing amelanoticmelanoma

First, a fair proportion of AHMs are nodular.36,37 Inmany instances, AHM presents as a clinically ele-vated tumor that is firm on palpation and may havebeen noted by the patient to have grown in recentweeks or months. These three characteristics aresummarized in the clinical EFG rule, which can beused as a guide when dealing with melanomaslacking the classical ABCD clinical criteria.44-47

Second, the true prevalence of AHM is quite low.In most cases, melanomas lacking significant pig-mentation are of the hypomelanotic type. By usingdermoscopy, residual pigmentation can be bettervisualized as small areas of blue, white-blue, or gray,involving a subsection of the tumor. Sometimes aresidual pigment network and/or brown, gray, orblack dots/globules may also be seen as a residualepidermal component at the periphery of an amel-anotic proliferating nodule.17,26

Third, within the amelanotic area, vessels areeasily visualized by dermoscopy. In many instances,

melanoma is typified by atypical, polymorphic ves-sels (defined as having 2 or more vessel morphologictypes). Dotted vessels may be seen in combinationwith linear irregular and/or hairpin vessels and arenot surrounded by a whitish halo.9,14,17,26,31-35

Lastly, a fair proportion of AHMs show a typicalpinkish background color, the so-called milky redcolor.9,10,17,26 This particular dermoscopic feature isnot 100% specific for melanoma, because it may alsobe seen in BCC and pyogenic granuloma.47

However, milky red areas are very rare in benigntumors, such as intradermal nevi or seborrheic

keratoses.

Intradermal nevus versus thickamelanotic/hypomelanotic melanoma

Thick AHM may be a great masquerader, mimick-ing the most banal lesions such as intradermal nevus.The diagnosis in such cases is facilitated by thecorrect recognition of vascular patterns associatedwith these tumors. In our experience, comma-like(linear curved) vessels often cause diagnostic diffi-culties for beginners in dermoscopy, because of theirstriking variability in both size and caliber. It is

therefore advisable for novice dermoscopists to

Fig 10. Clinically this nodular melanoma (tumor thick-ness, 4 mm) lacks asymmetry and border irregularity, buthas subtle variegation in color. Dermoscopy highlights thepolychromatism of the lesion, which is an important cluefor the diagnosis of such challenging nodular melanoma

(which often lack one or more criteria of the ABCDalgorithm).


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practice observing banal dermal nevi so as to betterrecognize their repetitive morphology. This willassist in the recognition of lesions showing deviantvascular patterns. Apart from vascular morphology, apink (milky red) background color provides a furtherimportant criterion in recognizing AHM, which con-trasts to the tan background color of dermal nevi.

Nonpigmented Spitz nevus or atypical Spitztumor versus amelanotic/hypomelanoticmelanoma

Specific vascular criteria that differentiate non-pigmented or atypical Spitz tumors from AHM havenot been identified; therefore, excision is recom-mended for all lesions with a Spitzoid appearance(Fig 7).

Red Clark nevus versus nonpigmented Spitznevus

A helpful clue for differentiating Spitz nevus fromred Clark nevi in fair skinned individuals is that thedotted (red dots) vessels in the former are usuallydensely arranged, while they are more scantilydistributed in red Clark nevi. Furthermore, the diag-nosis of Clark nevi is suggested if assessment of allneighboring lesions reveals similar dermoscopicpatterns.

SUMMARYDermal nevi exhibit specific vascular patterns that

facilitate their diagnosis and assist in the differenti-ation from melanoma. In contrast, no reliable criteriahave yet been identified that allow the differentiationof Spitzoid neoplasms from AHM. Accordingly,lesions exhibiting dotted, linear irregular, and/orpolymorphous vessels should always be excised inorder to avoid missing AHM.

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