- Email: [email protected]
Dermoscopy of pigmented skin lesions – a valuable tool for early
Dermoscopy of pigmented skin lesions
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Dermoscopy of pigmented skin lesions – a valuable tool for early diagnosis of melanoma Giuseppe Argenziano and H Peter Soyer
The clinical use of dermoscopy has uncovered a new and fascinating morphological dimension of pigmented skin lesions. Dermoscopy is a noninvasive diagnostic technique that links clinical dermatology and dermatopathology by enabling the visualisation of morphological features not seen by the naked eye. Close examination of pigmented skin lesions in this way increases the effectiveness of clinical diagnostic tools by providing new morphological criteria for distinguishing melanoma from other melanocytic and non-melanocytic pigmented skin lesions. In the past, dermoscopy has been known by various names, including skin surface microscopy, epiluminescence microscopy, incident light microscopy, dermatoscopy, and videodermatoscopy. However, the term ‘dermoscopy’, first used by Friedman and colleagues in 1991,1 is the most widely used. Lancet Oncol 2001; 2: 443–49
Current practice in the diagnosis of melanoma During the past two decades, the frequency of melanoma has been increasing. Owing to the lack of adequate therapies for metastatic melanoma, the best treatment is still early diagnosis (Figure 1) and prompt surgical excision of the primary tumour. In the 1960s and 1970s, the clinical diagnosis of melanoma was based on observable symptoms such as bleeding, itching, and ulceration, and the presence all of these at the time of diagnosis was associated with poor prognosis. In the 1980s, the ABCD rule was introduced.2 This is based on the simple clinical morphological features of melanoma – asymmetry, border irregularity, colour variegation, and a diameter of more than 5 mm – and is now used worldwide, allowing early detection of many melanomas. Further improvement might be achieved by adding a fifth criterion, called E for evolution, to describe morphological changes of the lesion over time.3 There are two major problems with the current practice of clinical diagnosis of melanoma. First, clinical diagnosis based on the ABCD rule is only 65–80% sensitive,4 because it does not recognise that melanomas of less than 5 mm may occur. In addition, very early melanomas may have a regular shape and homogeneous colour; such lesions would be falsely classified as benign. Second, many unnecessary excisions may be carried out, since benign melanocytic THE LANCET Oncology Vol 2 July 2001
Figure 1. Clinical image. Early invasive melanoma.
naevi may mimic melanomas on clinical examination. Dermoscopy can help overcome these problems and is a useful addition to clinical diagnosis. Dermoscopy is a noninvasive diagnostic technique for the in vivo observation of pigmented skin lesions, enabling better visualisation of surface and subsurface structures and improvement in diagnostic accuracy.5,6 The skin lesion is covered with mineral oil, alcohol, or even water, and then a hand-held lens, a hand-held scope (also called a dermatoscope), a stereomicroscope, a camera, or a digital imaging system, is used to inspect it. The magnifications of these instruments range from six-fold to 40-fold and even up to 100-fold. The widely used dermatoscope has a ten-fold magnification, sufficient for routine assessment of pigmented skin lesions. The fluid placed on the lesion eliminates surface reflection and renders the cornified layer translucent, so that the pigmented structures within the epidermis, the dermoepidermal junction, and the superficial dermis can be seen more easily. Also, the size and shape of vessels of the superficial vascular plexus can be easily visualised by this procedure.
GA is at the Department of Dermatology, Second University of Naples, Naples, Italy. HPS is at the Department of Dermatology, University of Graz, Austria. Correspondence: Dr H Peter Soyer, MD, Department of Dermatology, University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria. Tel: +43 316 385 3235. Fax: +43 316 385 4957. Email: [email protected]
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Personal view Classical pattern analysis Dermoscopy has advanced from being an experimental method used in only a few highly specialised centres to become part of the normal practice for screening pigmented skin lesions in many outpatient clinics worldwide. This is mainly because of the simple diagnostic techniques involved. However, before dermoscopy can be more widely used in routine practice, it must become easier to do and more reliable. For this to happen, the diagnostic criteria must be standardised and simplified, and a more objective method of quantifying their diagnostic weighting must be developed. The recent history of dermoscopy began in 1987 when Pehamberger and colleagues published details of a new diagnostic approach, known as ‘pattern analysis’, which was dedicated to the dermoscopic diagnosis of pigmented skin lesions.7 Pattern analysis is the most well-known and reliable method for the dermoscopic diagnosis of pigmented skin lesions, but its practical application requires experience. Its complexity is due to the need for simultaneous and subjective assessment of many criteria and morphological patterns. Further difficulties are presented by the many variations in the morphological expression of each parameter. Because some of the criteria
Dermoscopy of pigmented skin lesions
are not properly defined, accurate assessment of some dermoscopic variables is difficult, and studies have shown that the reproducibility of a criterion is greater in its quantitative evaluation (presence or absence) than in its qualitative evaluation (regularity, distribution, size, shape, etc).8 Table 1 shows the associations between some dermoscopic criteria and their corresponding histopathological substrates, and Figure 2 shows a typical dermoscopic image.
Other diagnostic methods There are three other approaches in addition to classical pattern analysis. The first attempt at simplifying the dermoscopic diagnosis of melanocytic skin lesions was a modification of the ABCD rule, which was introduced by Stolz and coworkers in 1994.9 This semiquantitative diagnostic method uses a scoring system to assess just four dermoscopic criteria. Nachbar and colleagues showed that this method was reproducible in a prospective study, and that it has specificity of 90% and sensitivity of 93% in the diagnosis of melanoma.10 A recent evaluation study on the ABCD rule confirmed the effectiveness of this modification, particularly in improving the diagnostic accuracy of inexperienced observers.11 Other studies,
Table 1. Dermoscopic criteria, their histopathological correlates and diagnostic significance* Criterion
Morphological definition
Associated histopathological changes
Diagnosis
Pigment network
Network of brownish lines over a diffuse tan background
Pigmented rete ridges
Melanocytic lesion
Typical network
Brown pigmented, regularly meshed and narrowly spaced network
Regular and elongated rete ridges
Benign melanocytic lesion
Atypical network
Black, brown, or grey network with irregular meshes and thick lines
Irregular and broadened rete ridges
Melanoma
Dots/globules
Black, brown, and/or grey round to oval, variously sized structures regularly or irregularly distributed within the lesion
Pigment aggregates within stratum corneum, epidermis, dermoepidermal lesion; junction, or papillary dermis
If regular, benign melanocytic if irregular, melanoma
Streaks
Irregular, linear structures not clearly combined with pigment network lines at the margins
Confluent junctional nests of melanocytes
Melanoma
Blue-whitish veil
Irregular, confluent, grey-blue to whitish-blue diffuse pigmentation
Acanthotic epidermis with focal hypergranulosis above sheets of heavily pigmented melanocytes in the dermis
Melanoma
Blotches
Black, brown, and/or grey pigmented areas with regular or irregular shape/distribution
Hyperpigmentation throughout the epidermis and/or upper dermis
If regular, benign melanocytic lesion; if irregular, melanoma
Regression structures
White (scar-like) areas, blue (pepper-like) areas, or combinations of both
Thickened papillary dermis with fibrosis and/or variable amounts of melanophages
Melanoma
Milia-like cysts
White-yellowish, roundish dots
Intraepidermal horn globules, also called horn pseudocysts
Seborrheic keratosis
Comedo-like openings
Brown-yellowish, round to oval or even irregularly shaped, sharply circumscribed structures
Keratin plugs situated within dilated follicular openings
Seborrheic keratosis
Leaf-like areas
Brown-gray to grey-black patches revealing a leaf-like configuration
Pigmented, solid aggregations of basaloid cells in the papillary dermis
Basal-cell carcinoma
Red-blue lacunas
Sharply demarcated, roundish to oval areas with a reddish, red-bluish, or red-black colouration
Dilated vascular spaces situated in the upper dermis
Vascular lesion
Vascular structures
Comma like vessels Arborising vessela Hairpin vessels Dotted or irregular vessels
Benign melanocytic lesion Basal-cell carcinoma Seborrheic keratosis Melanoma
* Adapted from references 14 and 40–43
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however, have shown that the ABCD method is less sensitive and less specific than pattern analysis for diagnosis of melanoma.12 In 1996, Menzies and colleagues proposed another diagnostic method.13 It is an algorithm based on the recognition of two negative dermoscopic features (not favouring melanoma diagnosis) and nine positive features (favouring melanoma diagnosis). When used by experts, the Menzies method had sensitivity of 92% and specificity of 71%.13 However, its reliability has not been investigated when used by less experienced dermoscopists. The seven-point checklist is another diagnostic approach, based on a simplified pattern analysis; it Figure 2. Dermoscopic image of early invasive melanoma. Note the irregular and thickened (atypical) uses seven standard criteria, most of pigment network in the centre and in the left part of the lesion. Blue areas (multiple, fairly which were reported in the guidelines aggregated blue-grey dots), corresponding histopathologically to melanophages, are also seen in several foci (original magnification x10). of the terminology consensus on 14 dermoscopy in 1990. The seven criteria are classified as specific experience in dermoscopy and thorough major or minor according to their diagnostic weighting. instruction are necessary. Nevertheless, all of the systems When at least two criteria (one major and one minor represent a substantial improvement of the dermoscopic criterion) are fulfilled, melanoma is diagnosed. In diagnostic method and, in terms of diagnostic sensitivity expert hands, this method allows correct classification of and specificity, are as effective as classic pattern analysis. 95% of melanomas and 75% of clinically atypical melanocytic naevi.15 We emphasise that, in general, the Integration of clinical and dermoscopic presence of a single criterion is not sufficient for diagnosis examinations The greatest advantage of dermoscopy lies in increasing the of melanoma. It is difficult to draw conclusions about the relative preoperative diagnosis of melanoma. Although clinical efficiency (in terms of diagnostic accuracy, simplicity of examination allows a correct diagnosis in 65–80% of use, and reproducibility) of the three methods described melanomas, depending on the examiner’s experience,4 the above, because of the absence or fragmentary nature of proportion of correct diagnoses based on dermoscopic comparative studies based on large-scale surveys. Each observation ranges from 70–95%.16–21 Nevertheless, method has intrinsic problems because interpretation of individually, neither method enables the correct diagnosis dermoscopic criteria is inevitably subjective; consequently, of all melanomas. Great progress has been made recently in integrating dermoscopic examinations into the overall clinical assessment of patients, with the aim of further improving the preoperative diagnosis of melanoma. For examples of clinical and dermoscopic images see Figures 3 and 4. In 1996, Menzies and colleagues had already described nine melanomas that had no diagnostic features, but were excised because of a history of morphological changes.13 Bearing in mind the clinical importance of the growth of a pigmented skin lesion, Kittler and colleagues developed a new diagnostic system, adding a fifth criterion to the ABCD rule (E), which represented the evolutionary history of the lesion.22 At the same specificity value, the ABCDE method is more sensitive than the Figure 3. Clinical image of early invasive melanoma. THE LANCET Oncology Vol 2 July 2001
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sheet, or can even be stored in a personalised smart card. In 1996, Stolz and colleagues showed that a digitised documentation system of dermoscopic images can highlight modifications of colour and dermoscopic structures, which are not visible during clinical examination.26 In a study of 150 pigmented skin lesions over a period of 2 years, Braun and colleagues described two different dermoscopic patterns of evolution.27 The first one concerned an increase in pigmentation that was probably a result of seasonal variation in exposure to the sun. The second was characterised by a pronounced variation of the dermoscopic architecture that was also associated with an increase in the diameter of the lesion. According to the researchers, the latter evolutionary pattern could indicate a higher tendency towards dysplasia, and lesions of this kind would need Figure 4. Dermoscopic image of early invasive melanoma. Regression structures, combinations of white areas and blue areas (blue-whitish areas) are seen on the leftfurther careful observation or even excision. hand side of the lesion. At the periphery, irregular dots/globules (bottom left and top The dermoscopic characteristics of growing right), atypical pigment network, and irregular streaks (top right) are further dermoscopic lesions were described in detail in a more recent criteria suggestive of melanoma (original magnification x10). study carried out by Kittler and colleagues on 1612 common melanocytic naevi.28 During a ABCD method, increasing the number of correctly follow-up period averaging nearly 1 year, a rim of brown diagnosed melanomas by 3–8%. globules, symmetrically distributed around the edge of the Benelli and colleagues reported a substantial increase in lesions, was detected in about half the enlarging naevi (5% diagnostic sensitivity with a combined clinical–dermoscopic of the total number of lesions). This phenomenon was more approach, resulting in the correct diagnosis of 93% of common in lesions on younger patients (less than 20 years examined lesions.23 By comparison, the diagnostic sensitivity old). Furthermore, histopathological examination of the of clinical examination alone was 67%, and the diagnostic enlarging lesions showed that the brown globules seen with sensitivity of dermoscopic observation alone was 80%. 23 dermoscopy were probably the visible manifestation of Similar results were obtained in a study involving small heavily pigmented junctional nests of melanocytes at the melanomas (less than 7 mm diameter), in which Bono and peripheral rim of the lesion. Also, in the absence of other colleagues reported sensitivities of 50%, 72%, and 86%, with atypical features, the symmetrical growth of a melanocytic clinical, dermoscopic, and combined clinical–dermoscopic lesion did not, on its own, indicate that it was malignant. examinations, respectively.24 Nevertheless, growing lesions in adults, especially when accompanied by globular peripheral rims, must be treated with the utmost attention, since they may indicate Dermoscopic follow-up of pigmented skin melanoma. lesions There are two reasons why a patient must be examined over Digital follow-up examinations have been done to time. First, some patients run a high risk of developing study the effect of ultraviolet-irradiation on melanocytic melanoma (eg patients with a personal or family history of naevi. We carried out studies on the dermoscopic changes melanoma, a high number of naevi, or skin phototype I or of melanocytic naevi exposed to ultraviolet irradiation. II), so should be monitored periodically. Second, When exposed to UVB, melanocytic naevi displayed morphological changes eventually occur in melanocytic morphological variations that can be seen in follow-up naevi, and objective, long-term observation is necessary to dermoscopic examinations. In most naevi, these changes monitor those changes.25 This approach is even more were only transitory, and presumably associated with a important for monitoring patients who have many reversible activation of melanocytes.29 Similar results were clinically atypical naevi, which would be practically difficult reported by Stanganelli and colleagues, who showed how exposure to the sun also causes dermoscopic variations in to remove simultaneously. Many video-microscopes are now available that allow acquired melanocytic naevi, including increased easy digital, photographic documentation of pigmented pigmentation and the appearance of some melanomaskin lesions. By means of a simple image storage and specific criteria.30 This study also showed the transient retrieval system one can rapidly compare digitised nature of ultraviolet effects and emphasised the need to reimages over a period of time. Compared with traditional examine the melanocytic skin lesions at least 4–6 weeks methods of photographic documentation, this digital after exposure to the sun. Some patients have many atypical melanocytic naevi, approach is simple to use. Obviously, the digitised images have to be integrated with the electronic patient’s record also known as dysplastic naevus syndrome, or BK-mole 446
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Dermoscopy of pigmented skin lesions
syndrome.31 However, simultaneous excision of these lesions is not practicable. For these patients, dermoscopic follow-up examinations should be standard practice.
However, we believe that it is a promising area for further research and development.
Automatic diagnosis Teledermoscopy When family doctors in rural areas, without access to specialised equipment or knowledge, have doubts about diagnosing and treating certain pigmented skin lesions, they are obliged to refer their patients to consultants in larger specialist centres. This procedure is time-consuming and costly for both the patient and the health service involved. Recent advances in information technology have permitted the introduction of a revolutionary diagnostic system known as telemedicine, which enables general practioners and specialists to exchange digital image information over telecommunication networks. 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 also proven to be a valid diagnostic system in areas where dermatologists are not available.32 Teledermoscopy, the latest development of teledermatology, consists of a data-processing system that enables the clinical and dermoscopic images of pigmented skin lesions to be transmitted over telecommunication networks. In 1999, Piccolo and colleagues carried out a teledermoscopic study in which images of 66 pigmented skin lesions were sent from L’Aquila, Italy to Graz, Austria via the internet, by conventional email transmission.33 There was good agreement (91% concordance) between the face-to-face diagnosis and the remote diagnosis, based on the transmitted dermoscopic images. Furthermore, the study highlighted the fact that the accuracy of remote diagnosis appears to be influenced less by the image quality than by the degree of difficulty in diagnosing the lesions. These results were confirmed in a subsequent multicentre study in which Piccolo and colleagues transmitted dermoscopic images of 43 pigmented lesions via the internet to 11 doctors, dermatologists, and oncologists, with widely differing dermoscopic experience.34 The accuracy of the remote diagnosis was only comparable with diagnoses carried out face-to-face when experienced clinicians are involved. Until now, the validity of teledermoscopy of pigmented skin lesions has been shown by only a few studies.
Another exciting and fascinating approach in the diagnosis of pigmented skin lesions is the automatic analysis of dermoscopic images, which seeks to increase the reliability of melanoma diagnosis carried out by non-expert clinicians. These new developments initially concentrated on the study of the clinical features of melanoma and are now moving rapidly in the direction of the digital analysis of dermoscopic images. Table 2 summarises the diagnostic effectiveness of different automatic diagnostic systems based on dermoscopic features. A critical analysis of the studies listed in Table 2 clearly shows the difficulty of comparing the systems, in terms of methods and instruments used. For example, the lesions being examined should have similar average melanoma thickness and clinical atypia to the lesions in the control group. If the main research objective is the development of an automatic diagnostic system that can be used in daily clinical practice, the model needs to be tested on a wide range of both melanocytic and non-melanocytic pigmented skin tumours. In fact, systems based on the automatic analysis of symmetry and dermoscopic colours could be less specific in the diagnosis of purely benign lesions, such as seborrhoeic keratoses, many of which have an asymmetric silhouette, multiple colours, or both features. From a histopathological perspective, to obtain accurate results from automatic diagnostic systems is difficult because there is disagreement on the diagnostic criteria for many melanomas in situ or early invasive melanomas, moderately dysplastic naevi, and Spitz naevi in adults. Nearly all the research groups currently using computer-aided or computer-assisted diagnosis still consider the expertise of a well-trained and experienced clinician to be the ultimate standard. One may speculate, however, that the management of pigmented skin lesions will be strongly influenced by teledermoscopy, as well as by automatic diagnostic approaches, in the very near future.
Future considerations Several problems in the diagnosis of pigmented skin lesions remain unresolved. The most urgent problem is the need for standardisation of diagnostic criteria and methods. A virtual Consensus Net Meeting which was held between July and October last year aimed to provide such a standard.
Table 2. Diagnostic performance of different automatic diagnostic systems based on dermoscopic features Reference
Method*
Number of melanomas (average thickness)
44
3-CCD video-camera
45
Digitised dermoscopic slides
46
Digitised dermoscopic slides
37 (0.72)
75 (42)
90
74
47
Digitised dermoscopic slides
75 (0.7)
95 (non-melanomas)†
93
67
176 (non-melanomas)†
57 (< 0.5 mm) 194 (unknown)
48
3-CCD video-camera
45 (0.62)
49
1-CCD video-camera
31 (0.73)
50
1-CCD video-camera
18 (< 0.75)
Number of naevi (Number of dysplastic naevi) 90 (42) 126 (none)
Sensitivity %
Specificity %
81
88
Correct classification rate = 78%
89
80
59 (unknown)
93
95
365 (unknown)
100
92
*Method used for acquiring dermoscopic images; †Non-melanomas, melanocytic and non-melanocytic pigmented skin lesions
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Personal view Search strategy and selection criteria Published data up to 2000 were available to us for this review. Publications were identified through PubMed and our own database of dermoscopy publications. Papers submitted on the same topic by the same group of investigators to several journals were reviewed to identify one that was representative of the results. Case reports and (in most cases) preliminary results were excluded, and larger studies were selected instead.
Dermoscopy of pigmented skin lesions
In conclusion, dermoscopy opens up a new dimension in the clinical morphology of pigmented skin lesions and enables the well-trained physician to improve the accuracy of diagnoses in general, and melanoma in particular. Digital follow-up examinations, teledermoscopy, and computer-aided or computer-assisted diagnosis of pigmented skin lesions are exciting new tools that will certainly change the management of pigmented skin tumours. Acknowledgments
We thank Barbara J Rutledge for editing assistance.
Participants in the meeting included experts in dermoscopy, who tested the reproducibility of the dermoscopic variables, together with the repeatability and reliability of various diagnostic algorithms. The Consensus Net Meeting also attempted to verify a new unifying concept for the dermoscopic diagnosis of pigmented skin lesions. This concept consists of two successive phases. The first of these involves the application of an algorithm to differentiate between melanocytic and non-melanocytic lesions. The second phase uses diagnostic systems (listed below) developed to distinguish between melanomas and other melanocytic benign lesions: the pattern analysis method (modified according to the most recent findings), the ABCD method, the seven-point checklist, and the Menzies diagnostic system. Thanks to the new communication possibilities that the latest technology offers, the entire consensus meeting took place via the internet. General information, conceptual arguments and all results of this Consensus Net Meeting on dermoscopy are available at http://www.dermoscopy.org
Conclusions Developments in dermoscopic diagnostic methods, the integration of dermoscopic and clinical examinations, the new possibilities offered by digital instruments for followup examination of pigmented lesions, teledermoscopy and the automatic diagnostic systems all reflect the direction in which dermoscopic research is heading. Over the past few years, several research groups have helped to perfect the diagnostic criteria for the application of dermoscopy, enabling the precise characterisation of melanoma and most other common pigmented skin lesions. For example, we now know the morphological differences of melanomas in relation to specific locations such as the face35 and the acral areas.36 We also know the differing expression of melanoma-specific criteria according to the tumour thickness (Breslow index) of a given melanoma37 and the most common diagnostic pitfalls, such as the difficult differentiation between Spitz naevi and melanomas, which have similar dermoscopic features.38 The technique of dermoscopy could be a useful addition to clinical diagnosis in other contexts, although at the moment the potential application of low-power microscopy to other accessible surface lesions has been shown only for colposcopy of the uterine cervix.39 To the best of our knowledge, the potential application to other accessible surface lesions on anatomical structures such as rectum, colon, and stomach has not yet been studied. 448
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recognition of lentigo maligna using dermatoscopy. J Am Acad Dermatol 2000; 42: 25–32. Saida T, Oguchi S, Ishihara Y. In vivo observation of magnified features of pigmented lesions on volar skin using video macroscope. Usefulness of epiluminescence techniques in clinical diagnosis. Arch Dermatol 1995; 131: 298–304. Argenziano G, Fabbrocini G, Carli P, et al. Clinical and dermatoscopic criteria for the preoperative evaluation of cutaneous melanoma thickness. J Am Acad Dermatol 1999; 40: 61–68. Argenziano G, Scalvenzi M, Staibano S, et al. Dermatoscopic pitfalls in differentiating pigmented Spitz naevi from cutaneous melanomas. Br J Dermatol 1999; 141: 788–93. Mitchell MF, Schottenfeld D, Tortolero-Luna G, et al. Colposcopy for the diagnosis of squamous intraepithelial lesions: a metaanalysis. Obstet Gynecol 1998; 91: 626–31. Soyer HP, Smolle J, Hodl S, et al. Surface microscopy. A new approach to the diagnosis of cutaneous pigmented tumors. Am J Dermatopathol 1989; 11: 1–10. Yadav S, Vossaert KA, Kopf AW, et al. Histopathologic correlates of structures seen on dermoscopy (epiluminescence microscopy). Am J Dermatopathol 1993; 15: 297–305. Soyer HP, Kenet RO, Wolf IH, et al. Clinicopathological correlation of pigmented skin lesions using dermoscopy. Eur J Dermatol 2000; 10: 22–28. Argenziano G, Soyer HP, De Giorgi V, et al. Interactive atlas of dermoscopy Milan: Edra Medical Publishing and New Media 2000. Andreassi L, Perotti R, Rubegni P, et al. Digital dermoscopy analysis for the differentiation of atypical nevi and early melanoma: a new quantitative semiology [see comments]. Arch Dermatol 1999; 135: 1459–65. Schindewolf T, Stolz W, Albert R, et al. Comparison of classification rates for conventional and dermatoscopic images of malignant and benign melanocytic lesions using computerised colour image analysis. Eur J Dermatol 1993; 3: 299–303. Binder M, Kittler H, Seeber A, et al. Epiluminescence microscopybased classification of pigmented skin lesions using computerized image analysis and an artificial neural network. Melanoma Res 1998; 8: 261–66. Menzies SW, Bischof L, Peden G. Automated instrumentation for the diagnosis of invasive melanoma: image analysis of oil epiluminescence microscopy. In: Altmeyer P, Hoffman K, Stucker M (Eds). Skin Cancer and UV Radiation. Berlin: Springer-Verlag 1997. Menzies SW, Crook B, McCarthy WH. Automated instrumentation for the diagnosis of invasive melanoma [abstract]. Skin Res Technol 1997; 3: 200. Seidenari S, Pellacani G, Pepe P. Digital videomicroscopy improves diagnostic accuracy for melanoma. J Am Acad Dermatol 1998; 39: 175–81. Seidenari S, Pellacani G, Giannetti A. Digital videomicroscopy and image analysis with automatic classification for detection of thin melanomas. Melanoma Res 1999; 9: 163–71.
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Dermoscopy of pigmented skin lesions – a valuable tool for early diagnosis of melanoma Giuseppe Argenziano and H Peter Soyer
The clinical use of dermoscopy has uncovered a new and fascinating morphological dimension of pigmented skin lesions. Dermoscopy is a noninvasive diagnostic technique that links clinical dermatology and dermatopathology by enabling the visualisation of morphological features not seen by the naked eye. Close examination of pigmented skin lesions in this way increases the effectiveness of clinical diagnostic tools by providing new morphological criteria for distinguishing melanoma from other melanocytic and non-melanocytic pigmented skin lesions. In the past, dermoscopy has been known by various names, including skin surface microscopy, epiluminescence microscopy, incident light microscopy, dermatoscopy, and videodermatoscopy. However, the term ‘dermoscopy’, first used by Friedman and colleagues in 1991,1 is the most widely used. Lancet Oncol 2001; 2: 443–49
Current practice in the diagnosis of melanoma During the past two decades, the frequency of melanoma has been increasing. Owing to the lack of adequate therapies for metastatic melanoma, the best treatment is still early diagnosis (Figure 1) and prompt surgical excision of the primary tumour. In the 1960s and 1970s, the clinical diagnosis of melanoma was based on observable symptoms such as bleeding, itching, and ulceration, and the presence all of these at the time of diagnosis was associated with poor prognosis. In the 1980s, the ABCD rule was introduced.2 This is based on the simple clinical morphological features of melanoma – asymmetry, border irregularity, colour variegation, and a diameter of more than 5 mm – and is now used worldwide, allowing early detection of many melanomas. Further improvement might be achieved by adding a fifth criterion, called E for evolution, to describe morphological changes of the lesion over time.3 There are two major problems with the current practice of clinical diagnosis of melanoma. First, clinical diagnosis based on the ABCD rule is only 65–80% sensitive,4 because it does not recognise that melanomas of less than 5 mm may occur. In addition, very early melanomas may have a regular shape and homogeneous colour; such lesions would be falsely classified as benign. Second, many unnecessary excisions may be carried out, since benign melanocytic THE LANCET Oncology Vol 2 July 2001
Figure 1. Clinical image. Early invasive melanoma.
naevi may mimic melanomas on clinical examination. Dermoscopy can help overcome these problems and is a useful addition to clinical diagnosis. Dermoscopy is a noninvasive diagnostic technique for the in vivo observation of pigmented skin lesions, enabling better visualisation of surface and subsurface structures and improvement in diagnostic accuracy.5,6 The skin lesion is covered with mineral oil, alcohol, or even water, and then a hand-held lens, a hand-held scope (also called a dermatoscope), a stereomicroscope, a camera, or a digital imaging system, is used to inspect it. The magnifications of these instruments range from six-fold to 40-fold and even up to 100-fold. The widely used dermatoscope has a ten-fold magnification, sufficient for routine assessment of pigmented skin lesions. The fluid placed on the lesion eliminates surface reflection and renders the cornified layer translucent, so that the pigmented structures within the epidermis, the dermoepidermal junction, and the superficial dermis can be seen more easily. Also, the size and shape of vessels of the superficial vascular plexus can be easily visualised by this procedure.
GA is at the Department of Dermatology, Second University of Naples, Naples, Italy. HPS is at the Department of Dermatology, University of Graz, Austria. Correspondence: Dr H Peter Soyer, MD, Department of Dermatology, University of Graz, Auenbruggerplatz 8, A-8036 Graz, Austria. Tel: +43 316 385 3235. Fax: +43 316 385 4957. Email: [email protected]
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Personal view Classical pattern analysis Dermoscopy has advanced from being an experimental method used in only a few highly specialised centres to become part of the normal practice for screening pigmented skin lesions in many outpatient clinics worldwide. This is mainly because of the simple diagnostic techniques involved. However, before dermoscopy can be more widely used in routine practice, it must become easier to do and more reliable. For this to happen, the diagnostic criteria must be standardised and simplified, and a more objective method of quantifying their diagnostic weighting must be developed. The recent history of dermoscopy began in 1987 when Pehamberger and colleagues published details of a new diagnostic approach, known as ‘pattern analysis’, which was dedicated to the dermoscopic diagnosis of pigmented skin lesions.7 Pattern analysis is the most well-known and reliable method for the dermoscopic diagnosis of pigmented skin lesions, but its practical application requires experience. Its complexity is due to the need for simultaneous and subjective assessment of many criteria and morphological patterns. Further difficulties are presented by the many variations in the morphological expression of each parameter. Because some of the criteria
Dermoscopy of pigmented skin lesions
are not properly defined, accurate assessment of some dermoscopic variables is difficult, and studies have shown that the reproducibility of a criterion is greater in its quantitative evaluation (presence or absence) than in its qualitative evaluation (regularity, distribution, size, shape, etc).8 Table 1 shows the associations between some dermoscopic criteria and their corresponding histopathological substrates, and Figure 2 shows a typical dermoscopic image.
Other diagnostic methods There are three other approaches in addition to classical pattern analysis. The first attempt at simplifying the dermoscopic diagnosis of melanocytic skin lesions was a modification of the ABCD rule, which was introduced by Stolz and coworkers in 1994.9 This semiquantitative diagnostic method uses a scoring system to assess just four dermoscopic criteria. Nachbar and colleagues showed that this method was reproducible in a prospective study, and that it has specificity of 90% and sensitivity of 93% in the diagnosis of melanoma.10 A recent evaluation study on the ABCD rule confirmed the effectiveness of this modification, particularly in improving the diagnostic accuracy of inexperienced observers.11 Other studies,
Table 1. Dermoscopic criteria, their histopathological correlates and diagnostic significance* Criterion
Morphological definition
Associated histopathological changes
Diagnosis
Pigment network
Network of brownish lines over a diffuse tan background
Pigmented rete ridges
Melanocytic lesion
Typical network
Brown pigmented, regularly meshed and narrowly spaced network
Regular and elongated rete ridges
Benign melanocytic lesion
Atypical network
Black, brown, or grey network with irregular meshes and thick lines
Irregular and broadened rete ridges
Melanoma
Dots/globules
Black, brown, and/or grey round to oval, variously sized structures regularly or irregularly distributed within the lesion
Pigment aggregates within stratum corneum, epidermis, dermoepidermal lesion; junction, or papillary dermis
If regular, benign melanocytic if irregular, melanoma
Streaks
Irregular, linear structures not clearly combined with pigment network lines at the margins
Confluent junctional nests of melanocytes
Melanoma
Blue-whitish veil
Irregular, confluent, grey-blue to whitish-blue diffuse pigmentation
Acanthotic epidermis with focal hypergranulosis above sheets of heavily pigmented melanocytes in the dermis
Melanoma
Blotches
Black, brown, and/or grey pigmented areas with regular or irregular shape/distribution
Hyperpigmentation throughout the epidermis and/or upper dermis
If regular, benign melanocytic lesion; if irregular, melanoma
Regression structures
White (scar-like) areas, blue (pepper-like) areas, or combinations of both
Thickened papillary dermis with fibrosis and/or variable amounts of melanophages
Melanoma
Milia-like cysts
White-yellowish, roundish dots
Intraepidermal horn globules, also called horn pseudocysts
Seborrheic keratosis
Comedo-like openings
Brown-yellowish, round to oval or even irregularly shaped, sharply circumscribed structures
Keratin plugs situated within dilated follicular openings
Seborrheic keratosis
Leaf-like areas
Brown-gray to grey-black patches revealing a leaf-like configuration
Pigmented, solid aggregations of basaloid cells in the papillary dermis
Basal-cell carcinoma
Red-blue lacunas
Sharply demarcated, roundish to oval areas with a reddish, red-bluish, or red-black colouration
Dilated vascular spaces situated in the upper dermis
Vascular lesion
Vascular structures
Comma like vessels Arborising vessela Hairpin vessels Dotted or irregular vessels
Benign melanocytic lesion Basal-cell carcinoma Seborrheic keratosis Melanoma
* Adapted from references 14 and 40–43
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however, have shown that the ABCD method is less sensitive and less specific than pattern analysis for diagnosis of melanoma.12 In 1996, Menzies and colleagues proposed another diagnostic method.13 It is an algorithm based on the recognition of two negative dermoscopic features (not favouring melanoma diagnosis) and nine positive features (favouring melanoma diagnosis). When used by experts, the Menzies method had sensitivity of 92% and specificity of 71%.13 However, its reliability has not been investigated when used by less experienced dermoscopists. The seven-point checklist is another diagnostic approach, based on a simplified pattern analysis; it Figure 2. Dermoscopic image of early invasive melanoma. Note the irregular and thickened (atypical) uses seven standard criteria, most of pigment network in the centre and in the left part of the lesion. Blue areas (multiple, fairly which were reported in the guidelines aggregated blue-grey dots), corresponding histopathologically to melanophages, are also seen in several foci (original magnification x10). of the terminology consensus on 14 dermoscopy in 1990. The seven criteria are classified as specific experience in dermoscopy and thorough major or minor according to their diagnostic weighting. instruction are necessary. Nevertheless, all of the systems When at least two criteria (one major and one minor represent a substantial improvement of the dermoscopic criterion) are fulfilled, melanoma is diagnosed. In diagnostic method and, in terms of diagnostic sensitivity expert hands, this method allows correct classification of and specificity, are as effective as classic pattern analysis. 95% of melanomas and 75% of clinically atypical melanocytic naevi.15 We emphasise that, in general, the Integration of clinical and dermoscopic presence of a single criterion is not sufficient for diagnosis examinations The greatest advantage of dermoscopy lies in increasing the of melanoma. It is difficult to draw conclusions about the relative preoperative diagnosis of melanoma. Although clinical efficiency (in terms of diagnostic accuracy, simplicity of examination allows a correct diagnosis in 65–80% of use, and reproducibility) of the three methods described melanomas, depending on the examiner’s experience,4 the above, because of the absence or fragmentary nature of proportion of correct diagnoses based on dermoscopic comparative studies based on large-scale surveys. Each observation ranges from 70–95%.16–21 Nevertheless, method has intrinsic problems because interpretation of individually, neither method enables the correct diagnosis dermoscopic criteria is inevitably subjective; consequently, of all melanomas. Great progress has been made recently in integrating dermoscopic examinations into the overall clinical assessment of patients, with the aim of further improving the preoperative diagnosis of melanoma. For examples of clinical and dermoscopic images see Figures 3 and 4. In 1996, Menzies and colleagues had already described nine melanomas that had no diagnostic features, but were excised because of a history of morphological changes.13 Bearing in mind the clinical importance of the growth of a pigmented skin lesion, Kittler and colleagues developed a new diagnostic system, adding a fifth criterion to the ABCD rule (E), which represented the evolutionary history of the lesion.22 At the same specificity value, the ABCDE method is more sensitive than the Figure 3. Clinical image of early invasive melanoma. THE LANCET Oncology Vol 2 July 2001
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sheet, or can even be stored in a personalised smart card. In 1996, Stolz and colleagues showed that a digitised documentation system of dermoscopic images can highlight modifications of colour and dermoscopic structures, which are not visible during clinical examination.26 In a study of 150 pigmented skin lesions over a period of 2 years, Braun and colleagues described two different dermoscopic patterns of evolution.27 The first one concerned an increase in pigmentation that was probably a result of seasonal variation in exposure to the sun. The second was characterised by a pronounced variation of the dermoscopic architecture that was also associated with an increase in the diameter of the lesion. According to the researchers, the latter evolutionary pattern could indicate a higher tendency towards dysplasia, and lesions of this kind would need Figure 4. Dermoscopic image of early invasive melanoma. Regression structures, combinations of white areas and blue areas (blue-whitish areas) are seen on the leftfurther careful observation or even excision. hand side of the lesion. At the periphery, irregular dots/globules (bottom left and top The dermoscopic characteristics of growing right), atypical pigment network, and irregular streaks (top right) are further dermoscopic lesions were described in detail in a more recent criteria suggestive of melanoma (original magnification x10). study carried out by Kittler and colleagues on 1612 common melanocytic naevi.28 During a ABCD method, increasing the number of correctly follow-up period averaging nearly 1 year, a rim of brown diagnosed melanomas by 3–8%. globules, symmetrically distributed around the edge of the Benelli and colleagues reported a substantial increase in lesions, was detected in about half the enlarging naevi (5% diagnostic sensitivity with a combined clinical–dermoscopic of the total number of lesions). This phenomenon was more approach, resulting in the correct diagnosis of 93% of common in lesions on younger patients (less than 20 years examined lesions.23 By comparison, the diagnostic sensitivity old). Furthermore, histopathological examination of the of clinical examination alone was 67%, and the diagnostic enlarging lesions showed that the brown globules seen with sensitivity of dermoscopic observation alone was 80%. 23 dermoscopy were probably the visible manifestation of Similar results were obtained in a study involving small heavily pigmented junctional nests of melanocytes at the melanomas (less than 7 mm diameter), in which Bono and peripheral rim of the lesion. Also, in the absence of other colleagues reported sensitivities of 50%, 72%, and 86%, with atypical features, the symmetrical growth of a melanocytic clinical, dermoscopic, and combined clinical–dermoscopic lesion did not, on its own, indicate that it was malignant. examinations, respectively.24 Nevertheless, growing lesions in adults, especially when accompanied by globular peripheral rims, must be treated with the utmost attention, since they may indicate Dermoscopic follow-up of pigmented skin melanoma. lesions There are two reasons why a patient must be examined over Digital follow-up examinations have been done to time. First, some patients run a high risk of developing study the effect of ultraviolet-irradiation on melanocytic melanoma (eg patients with a personal or family history of naevi. We carried out studies on the dermoscopic changes melanoma, a high number of naevi, or skin phototype I or of melanocytic naevi exposed to ultraviolet irradiation. II), so should be monitored periodically. Second, When exposed to UVB, melanocytic naevi displayed morphological changes eventually occur in melanocytic morphological variations that can be seen in follow-up naevi, and objective, long-term observation is necessary to dermoscopic examinations. In most naevi, these changes monitor those changes.25 This approach is even more were only transitory, and presumably associated with a important for monitoring patients who have many reversible activation of melanocytes.29 Similar results were clinically atypical naevi, which would be practically difficult reported by Stanganelli and colleagues, who showed how exposure to the sun also causes dermoscopic variations in to remove simultaneously. Many video-microscopes are now available that allow acquired melanocytic naevi, including increased easy digital, photographic documentation of pigmented pigmentation and the appearance of some melanomaskin lesions. By means of a simple image storage and specific criteria.30 This study also showed the transient retrieval system one can rapidly compare digitised nature of ultraviolet effects and emphasised the need to reimages over a period of time. Compared with traditional examine the melanocytic skin lesions at least 4–6 weeks methods of photographic documentation, this digital after exposure to the sun. Some patients have many atypical melanocytic naevi, approach is simple to use. Obviously, the digitised images have to be integrated with the electronic patient’s record also known as dysplastic naevus syndrome, or BK-mole 446
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Dermoscopy of pigmented skin lesions
syndrome.31 However, simultaneous excision of these lesions is not practicable. For these patients, dermoscopic follow-up examinations should be standard practice.
However, we believe that it is a promising area for further research and development.
Automatic diagnosis Teledermoscopy When family doctors in rural areas, without access to specialised equipment or knowledge, have doubts about diagnosing and treating certain pigmented skin lesions, they are obliged to refer their patients to consultants in larger specialist centres. This procedure is time-consuming and costly for both the patient and the health service involved. Recent advances in information technology have permitted the introduction of a revolutionary diagnostic system known as telemedicine, which enables general practioners and specialists to exchange digital image information over telecommunication networks. 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 also proven to be a valid diagnostic system in areas where dermatologists are not available.32 Teledermoscopy, the latest development of teledermatology, consists of a data-processing system that enables the clinical and dermoscopic images of pigmented skin lesions to be transmitted over telecommunication networks. In 1999, Piccolo and colleagues carried out a teledermoscopic study in which images of 66 pigmented skin lesions were sent from L’Aquila, Italy to Graz, Austria via the internet, by conventional email transmission.33 There was good agreement (91% concordance) between the face-to-face diagnosis and the remote diagnosis, based on the transmitted dermoscopic images. Furthermore, the study highlighted the fact that the accuracy of remote diagnosis appears to be influenced less by the image quality than by the degree of difficulty in diagnosing the lesions. These results were confirmed in a subsequent multicentre study in which Piccolo and colleagues transmitted dermoscopic images of 43 pigmented lesions via the internet to 11 doctors, dermatologists, and oncologists, with widely differing dermoscopic experience.34 The accuracy of the remote diagnosis was only comparable with diagnoses carried out face-to-face when experienced clinicians are involved. Until now, the validity of teledermoscopy of pigmented skin lesions has been shown by only a few studies.
Another exciting and fascinating approach in the diagnosis of pigmented skin lesions is the automatic analysis of dermoscopic images, which seeks to increase the reliability of melanoma diagnosis carried out by non-expert clinicians. These new developments initially concentrated on the study of the clinical features of melanoma and are now moving rapidly in the direction of the digital analysis of dermoscopic images. Table 2 summarises the diagnostic effectiveness of different automatic diagnostic systems based on dermoscopic features. A critical analysis of the studies listed in Table 2 clearly shows the difficulty of comparing the systems, in terms of methods and instruments used. For example, the lesions being examined should have similar average melanoma thickness and clinical atypia to the lesions in the control group. If the main research objective is the development of an automatic diagnostic system that can be used in daily clinical practice, the model needs to be tested on a wide range of both melanocytic and non-melanocytic pigmented skin tumours. In fact, systems based on the automatic analysis of symmetry and dermoscopic colours could be less specific in the diagnosis of purely benign lesions, such as seborrhoeic keratoses, many of which have an asymmetric silhouette, multiple colours, or both features. From a histopathological perspective, to obtain accurate results from automatic diagnostic systems is difficult because there is disagreement on the diagnostic criteria for many melanomas in situ or early invasive melanomas, moderately dysplastic naevi, and Spitz naevi in adults. Nearly all the research groups currently using computer-aided or computer-assisted diagnosis still consider the expertise of a well-trained and experienced clinician to be the ultimate standard. One may speculate, however, that the management of pigmented skin lesions will be strongly influenced by teledermoscopy, as well as by automatic diagnostic approaches, in the very near future.
Future considerations Several problems in the diagnosis of pigmented skin lesions remain unresolved. The most urgent problem is the need for standardisation of diagnostic criteria and methods. A virtual Consensus Net Meeting which was held between July and October last year aimed to provide such a standard.
Table 2. Diagnostic performance of different automatic diagnostic systems based on dermoscopic features Reference
Method*
Number of melanomas (average thickness)
44
3-CCD video-camera
45
Digitised dermoscopic slides
46
Digitised dermoscopic slides
37 (0.72)
75 (42)
90
74
47
Digitised dermoscopic slides
75 (0.7)
95 (non-melanomas)†
93
67
176 (non-melanomas)†
57 (< 0.5 mm) 194 (unknown)
48
3-CCD video-camera
45 (0.62)
49
1-CCD video-camera
31 (0.73)
50
1-CCD video-camera
18 (< 0.75)
Number of naevi (Number of dysplastic naevi) 90 (42) 126 (none)
Sensitivity %
Specificity %
81
88
Correct classification rate = 78%
89
80
59 (unknown)
93
95
365 (unknown)
100
92
*Method used for acquiring dermoscopic images; †Non-melanomas, melanocytic and non-melanocytic pigmented skin lesions
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Personal view Search strategy and selection criteria Published data up to 2000 were available to us for this review. Publications were identified through PubMed and our own database of dermoscopy publications. Papers submitted on the same topic by the same group of investigators to several journals were reviewed to identify one that was representative of the results. Case reports and (in most cases) preliminary results were excluded, and larger studies were selected instead.
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In conclusion, dermoscopy opens up a new dimension in the clinical morphology of pigmented skin lesions and enables the well-trained physician to improve the accuracy of diagnoses in general, and melanoma in particular. Digital follow-up examinations, teledermoscopy, and computer-aided or computer-assisted diagnosis of pigmented skin lesions are exciting new tools that will certainly change the management of pigmented skin tumours. Acknowledgments
We thank Barbara J Rutledge for editing assistance.
Participants in the meeting included experts in dermoscopy, who tested the reproducibility of the dermoscopic variables, together with the repeatability and reliability of various diagnostic algorithms. The Consensus Net Meeting also attempted to verify a new unifying concept for the dermoscopic diagnosis of pigmented skin lesions. This concept consists of two successive phases. The first of these involves the application of an algorithm to differentiate between melanocytic and non-melanocytic lesions. The second phase uses diagnostic systems (listed below) developed to distinguish between melanomas and other melanocytic benign lesions: the pattern analysis method (modified according to the most recent findings), the ABCD method, the seven-point checklist, and the Menzies diagnostic system. Thanks to the new communication possibilities that the latest technology offers, the entire consensus meeting took place via the internet. General information, conceptual arguments and all results of this Consensus Net Meeting on dermoscopy are available at http://www.dermoscopy.org
Conclusions Developments in dermoscopic diagnostic methods, the integration of dermoscopic and clinical examinations, the new possibilities offered by digital instruments for followup examination of pigmented lesions, teledermoscopy and the automatic diagnostic systems all reflect the direction in which dermoscopic research is heading. Over the past few years, several research groups have helped to perfect the diagnostic criteria for the application of dermoscopy, enabling the precise characterisation of melanoma and most other common pigmented skin lesions. For example, we now know the morphological differences of melanomas in relation to specific locations such as the face35 and the acral areas.36 We also know the differing expression of melanoma-specific criteria according to the tumour thickness (Breslow index) of a given melanoma37 and the most common diagnostic pitfalls, such as the difficult differentiation between Spitz naevi and melanomas, which have similar dermoscopic features.38 The technique of dermoscopy could be a useful addition to clinical diagnosis in other contexts, although at the moment the potential application of low-power microscopy to other accessible surface lesions has been shown only for colposcopy of the uterine cervix.39 To the best of our knowledge, the potential application to other accessible surface lesions on anatomical structures such as rectum, colon, and stomach has not yet been studied. 448
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