Dermoscopy of pigmented lesions : a valuable tool in the diagnosis of melanoma

Although malignant melanoma is not the most frequent cancer, its incidence is increasing faster than any other. It is considered to be the most serious of skin cancers because it has a potential for metastasis which explains why melanoma is responsible for 90% of all skin cancer-related deaths. According to the national tumour registry there are approximately 1500 new cases of melanoma per year in Switzerland. Early diagnosis of melanoma is particularly important because if the diagnosis is made at an early stage, meaning that the tumour thickness is less than 1 mm, the prognosis is excellent and the 10-year survival rate is estimated to be between 90 and 97% [1, 2]. If the diagnosis is made at a more advanced stage the five-year survival rate drops to 10–15%. A further important point is that melanoma is a skin cancer that in almost 100% of cases is localized to the skin and is therefore detectable by simple examination. For these two reasons early diagnosis of melanoma is important. Although malignant melanoma is not the most frequent cancer, its incidence is increasing faster than any other. Early diagnosis of melanoma is particularly important because if the diagnosis is made at an early stage when the tumour thickness is less than 1 mm the prognosis is excellent. Dermoscopy is an in vivo method for the early diagnosis of melanoma and the differential diagnosis of pigmented lesions of the skin. It has been shown to increase diagnostic accuracy over clinical visual inspection in the hands of experienced physicians. This paper reviews the principles of dermoscopy, diagnostic strategies and recent technological developments.


Clinical diagnosis of malignant melanoma
In the 1960s and 1970s the clinical diagnosis of malignant melanoma was based on symptoms such as bleeding, itching or ulceration.The presence of these criteria at the time of diagnosis was associated with a poor prognosis as these symptoms only appear in advanced stages of disease.In the 1980s the clinical "ABCD rule" was introduced.This diagnostic rule was based on simple clinical morphological features of melanoma such as asymmetry, border irregularity, colour variegation and a diameter exceeding 5 mm.This clinical algorithm is now used worldwide allowing early detection of a large proportion of melanomas.Later a fifth criterion called evolution was added to describe morphologic changes in the lesion over time (ABCDE rule).
Figure 1 shows the clinical presentation of a malignant melanoma.It is an asymmetric lesion with an irregular border, a multitude of different colours and a diameter of 9 mm.
This clinical algorithm has a sensitivity of 65 to 80% but has been shown to have a tendency to fail in small melanomas of <5 mm in diameter.These small, early melanomas are frequently not diagnosed with the clinical ABCDE rule, because very early melanomas can be regular in shape and homogeneous in colour.Figure 2 shows a malignant melanoma that is perfectly symmetrical with a regular border and a homogenous brown pigmentation.Clinically this lesion looks like any of several hundred pigmented lesions in this patient.Clinical presentation of a malignant melanoma.

Differential diagnosis of pigmented lesions
To understand the difficulties related to the diagnosis of pigmented lesions it is important to know the differential diagnosis of a pigmented skin lesion.
This comprises all other skin cancers including malignant melanoma and pigmented basal cell carcinoma, the large group of pigmented melanocytic naevi (compound naevi, junctional naevi etc) and a group of benign lesions such as pigmented seborrhoeic keratoses and benign vascular lesions.
Clinical examination alone has been shown to have a rather low specificity and sensitivity.In practice this means that many benign lesions are over diagnosed as malignant lesions leading to unnecessary surgery.On the other hand some melanomas might remain undiagnosed or be diagnosed too late.
The diagnosis of melanoma can also be difficult as they can in certain instances resemble benign lesions or vice versa.
One possible approach would be to systematically remove all pigmented lesions, but since most patients have a large number of lesions, this is virtually impossible in practice and would be very expensive.This is why there is a need for a non-invasive method that is simple to use and allows the analysis of a large number of lesions with better sensitivity and specificity than simple clinical examination.Dermoscopy (also known as epiluminescence microscopy, dermatoscopy, or amplified surface microscopy) is an in vivo method that is a useful tool for the early recognition of malignant melanoma [3][4][5][6].
The term "dermatoscopy" was introduced in 1920 by the German dermatologist Johann Saphier who published a series of communications using a new diagnostic tool resembling a binocular microscope with a built in light source for the examination of the skin [7][8][9][10].He used this new tool in various indications and made some interesting morphological observations on anatomical structures of the skin, thus demonstrating the high performance of his equipment.He used this technique for the observation of lupus erythematoses and lichen planus but not for pigmented lesions.The technique was then forgotten until a renaissance in 1971 when Rona MacKie et al. clearly identified the advantages of surface microscopy in the preoperative diagnosis of pigmented skin lesions and the differential diagnosis of benign versus malignant pigmented skin lesions [11].Thereafter further investigations were continued mainly in Europe by several Austrian and German groups.
Table 1 Provides an overview of the most important dermoscopy criteria, their definition and their histopathological correlation according to Argenziano et al. [46].

Technique
Light is reflected, dispersed or absorbed by the stratum corneum due to its refraction index and its optical density, which is different from air [12].Thus, deeper underlying structures cannot be ad-equately visualised.However, when various immersion liquids are used to render the skin surface translucent and reduce the reflection, underlying structures are readily visible.The application of a glass plate flattens the skin surface and provides an even surface.Optical magnification is used for examination.Taken together, these optical means allow the visualisation of many new structures, which were named by morphologists more then 15 years ago.These dermoscopy criteria are referred to as pigment network, globules, points, dots, streaks, branched streaks, leaf-like areas, pseudopods, radial streaming, blue white veil, pseudo horns cysts, milia like cysts or structureless areas.
Figure 3 shows the dermoscopy image of the melanoma seen in figure 1.We see an asymmetric lesion with a peripheral hyperpigmentation showing an irregular pigment network and multiple irregular dots and globules.In the periphery one can also find some pseudopods and in the centre of the hyperpigmentation a blue white veil.
Figure 4 shows the dermoscopy image of the melanoma of figure 2. The lesion is clinically symmetric and homogenous in colour, shape and structure.Dermoscopically one can perceive an irregular pigment network and multiple irregular dots and globules.In the periphery a rim of peripheral irregular globules can be seen which indicate the horizontal growth of this melanoma.
Colours also play an important role in dermoscopy because it tells us which chromophore we are dealing with and where it is localized in the skin.As an example, melanin, which is the most important chromophore in the skin, appears to be black in the stratum corneum and in the upper epi- Dermoscopy image of the melanoma seen in figure 1.

Figure 4
Dermoscopy image of the melanoma of figure 2.
dermis, light brown to dark brown in the lower epidermis, grey to grey blue in the papular dermis and steel blue in the reticular dermis.It appears to be blue when it is localized within the deeper parts of the skin because visible light with shorter wavelengths (blue) is better dispersed than light with a longer wavelength (red), therefore less blue light is absorbed and more is reflected.

Correlation with histopathology
The next step after the identification of these criteria is their correlation with the histopathology.This turned out to be rather difficult because of some methodological limitations.Dermoscopy provides a horizontal overview of the whole lesion whereas the pathologist only has a focal vertical view of different sections of the lesion.In order to improve the correlation we recently described a micro punch technique [13] that allows the direct correlation of a precise area of a dermoscopical image with the histopathological slide.Following surgery a superficial incision using a 1 mm punch (as used for hair transplantation) is made.Contrary to the standard punch biopsy the punched tissue is left in place and the sections are chosen in a manner so as to pass through the site of the punch biopsy.The incisions can thus be easily visualised in the histopathological slide and a direct visual correlation with the dermoscopical image is possible.

Diagnostic approaches
Pattern recognition has historically been used by clinicians and histopathologists to differentiate benign lesions from malignant neoplasms.A similar process has been found to be useful in dermoscopy and is termed "pattern analysis".In 1987 the Austrian group of Pehamberger, Steiner and Wolff published a landmark article on pattern analysis in the Journal of the American Academy of Dermatology [14].On the basis of 3000-pigmented lesions, the Viennese group demonstrated that pattern analysis of specific dermoscopic features permitted a distinction between the various types of pigmented skin lesions, specifically between benign and malignant melanocytic lesions.Since then, the concept of classic pattern analysis has been confirmed and redefined continuously by experts all over the world.
There are two steps in the process of pattern analysis.The first step is to decide whether the lesion is melanocytic or non-melanocytic.A special algorithm is used for this first step and the presence of aggregated globules, a pigment network, or branched streaks is determined.If present, the lesion should be considered a melanocytic lesion.If not, one should evaluate the lesion for the presence of homogeneous steel-blue areas.If so, the lesion should be considered a blue naevus (unusual exceptions are a pigmented basal cell carcinoma or a metastatic melanoma).The lesion should then be evaluated for the presence of moth-eaten borders, fingerprinting, comedolike openings, milialike cysts, and fissures.If present, the lesion is suggestive of either a solar lentigo or a seborrhoeic keratosis.One then looks for red or red-blue to black lagoons and if these structures are present, the lesion should be considered a haemangioma or an angiokeratoma.
Finally, the lesion is evaluated for leaf-likestructures, arborizing telangiectasias, spoke-wheel-like areas, and blue-blue ovoid nests.If present, the lesion is likely to be a basal cell carcinoma.If all the preceding questions were answered with "no", the lesion should be considered a melanocytic lesion.
Step 2 of the pattern analysis process is the differentiation of benign melanocytic lesions from melanomas.The overall general appearance of Colour, Architectural order, Symmetry of pattern, and Homogeneity (CASH) are important components in distinguishing these two groups.Benign melanocytic lesions tend to have few colours, an architectural order, symmetry of pattern and are homogeneous.Malignant melanoma often has many colours, architectural disorder, asymmetry of pattern and is heterogeneous.
The reticular pattern, globular pattern, cobblestone pattern, homogeneous pattern, starburst pattern and parallel pattern are the patterns commonly found in benign pigmented lesions.
The combination of three or more distinctive dermoscopic structures (i.e.network, dots and globules as well as diffuse areas of hyper-and hypo-pigmentation) 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 naevi and congenital naevi.The term lesions with indeterminate patterns is retained for a non-specific pattern that can be seen in both benign and malignant pigmented lesions.Clinically and dermoscopically, one cannot distinguish between melanomas and atypical naevi.
Besides the global features mentioned above, there are important local features such as the pigment network, dots and globules, streaks, bluewhitish veil, blotch, regression structures and the vascular architecture or vascular structures, that can be used to evaluate melanocytic lesions.

Integration of clinical and dermoscopic examinations
Dermoscopy has been shown to increase diagnostic accuracy for pigmented skin lesions, especially melanoma.The efficiency of dermoscopy has been investigated by many authors.Its use increases diagnostic accuracy by 5-30% compared to clinical visual inspection, depending on the type of skin lesion and the experience of the physician [15][16][17][18][19].This was confirmed by recent evidence based publications and a meta-analysis of the literature [20,21].
Nevertheless, none of the methods enables the correct diagnosis of melanoma in all cases.

Digital dermoscopy
Digital dermoscopy uses digital or digitised dermoscopy images.Since computer hardware has become user-friendly and more affordable, digital dermoscopy has become more integrated into the clinical setting.The currently available systems for digital dermoscopy have an acceptable picture quality that comes close to that of a photograph [22].Digital images offer the possibility of computer storage and retrieval of dermoscopic images and patient data for follow up examination [23][24][25][26][27].In addition some systems offer the possibility of "computer-assisted diagnosis" [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] or teledermoscopy.Since diagnostic accuracy with dermoscopy has been shown do depend on the experience of the physician, such objective systems might help less-experienced physicians in the future.

Dermoscopic follow-up of pigmented skin lesions
There are two reasons necessitating regular examination of patients over time.Firstly, patients with a high risk of developing melanoma (e.g.patients with a personal or family history of melanoma, a large number of naevi or fair skin) should be monitored periodically.Secondly, morphological changes can occur in melanocytic naevi, and objective, long-term observation is necessary to monitor these modifications.This approach is even more important when monitoring patients who have many clinically atypical naevi that are difficult to remove simultaneously.
Compared with traditional methods of photographic documentation this digital approach is simple to use.

Teledermoscopy
At the beginning of the digital dermoscopic era, teledermoscopy was used between experts to exchange difficult or interesting images.The development of new electronic media and the evolution of the internet will have an important impact as the infrastructure is becoming universally available and exchange of information is now easy to perform.Telemedicine is already a well-integrated part of everyday medical practice, particularly in specialties such as radiology and pathology, where digital images are important diagnostic and therapeutic tools.
More recently, teledermatology was shown to be a valid diagnostic system in geographic areas where dermatologists are not available.Teledermoscopy is a development of teledermatology using digital or digitised images that are transmitted via new electronic media.This can be done as a "store and forward system" where the images of the lesions are simply sent via e-mail (secured access and encrypted transmission) and visualised by the expert when it is convenient.Another possi-bility is the online consultation which is much more interactive but requires the presence of both participants at the same time.In our experience this may be quiet difficult.
One of the first articles on teledermoscopy was published by Provost et al.The authors transmitted compressed digital dermoscopy images over telephone lines and concluded that diagnosis at distance based on these images is feasible [37].More recently, Kittler et al investigated the impact of compression of digital images compared to standard photographs and concluded that compressed digital dermoscopy images (medium compression) were as informative as conventional photographs [38].This was an important finding because the authors defined for the first time the resolution and quality (compression) requirements for digital images used for teledermoscopy.
Piccolo et al. published a paper on the evaluation of face to face diagnosis versus tele-diagnosis based on the analysis of 66 pigmented skin lesions [44].The digital images were compressed and send to the pigmented skin lesion clinic of the Department of Dermatology of Graz (Austria) where the remote diagnosis was made.They found a concordance in 60 cases (91%) and concluded that teledermoscopy provides a similar degree of diagnostic accuracy as face to face diagnosis.The authors postulated that this accuracy was not related to the quality of the images (which had been the main concern of early publications) but rather to the "level of diagnostic difficulty of a given pigmented skin lesion".In a second study the same authors evaluated the diagnostic accuracy (based on 43 pigmented skin lesions) in a multicentre study involving 10 centres [45].Here the participants had greatly differing degrees of experience in dermoscopy, and diagnostic accuracy varied from 77% to 95% with a mean of 85%.The authors concluded that the diagnostic accuracy of teledermoscopy largely depends on the experience of the consultant.
Taken together it has been shown that teledermoscopy consultations are technically feasible and that the diagnostic performance depends on the "level of diagnostic difficulty" and the experience of the consultant who interprets the images.However, this remains a promising field for future research and development.

Figure 2
Figure 2Perfectly symmetrical malignant melanoma with a regular border and a homogenous brown pigmentation.

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W I S S M E D W K LY 2 0 0 4 ; 1 3 4 : 8 3 -9 0 • w w w. s m w. c h 89ConclusionDermoscopy is a useful addition to clinical examination that opens a new dimension in the clinical analysis of pigmented skin lesions and enables physicians to improve their diagnosis of malignant melanoma.Digital follow up examinations, teledermoscopy and computer-aided or computerassisted diagnosis of pigmented skin lesions are exciting new tools that will certainly change the management of pigmented skin lesions.Correspondence: R. P. Braun Department of Dermatology University Hospital Geneva 24, rue Micheli-du-Crest CH-1211 Geneva 14 Switzerland E-Mail: braun@melanoma.chSwiss Medical Weekly: Call for papers Swiss Medical Weekly The many reasons why you should choose SMW to publish your research Official journal of the Swiss Society of Infectious disease the Swiss Society of Internal Medicine the Swiss Respiratory Society Med Wochenschr (1871-2000) Swiss Med Wkly (continues Schweiz Med Wochenschr from 2001) Editores Medicorum Helveticorum