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Diagnostic accuracy of dermoscopy - Dermatology

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Dermoscopy<br />

The <strong>accuracy</strong> <strong>of</strong> the clinical diagnosis <strong>of</strong> cutaneous<br />

melanoma with the unaided eye is only about 60%.<br />

Dermoscopy, a non-invasive, in vivo technique for the<br />

microscopic examination <strong>of</strong> pigmented skin lesions,<br />

has the potential to improve the diagnostic <strong>accuracy</strong>.<br />

Our objectives were to review previous publications,<br />

to compare the <strong>accuracy</strong> <strong>of</strong> melanoma diagnosis with<br />

and without <strong>dermoscopy</strong>, and to assess the influence<br />

<strong>of</strong> study characteristics on the diagnostic <strong>accuracy</strong>.<br />

We searched for publications between 1987 and 2000<br />

and identified 27 studies eligible for meta-analysis.<br />

The diagnostic <strong>accuracy</strong> for melanoma was<br />

significantly higher with <strong>dermoscopy</strong> than without<br />

this technique (log odds ratio 4.0 [95% CI 3.0 to 5.1]<br />

versus 2.7 [1.9 to 3.4]; an improvement <strong>of</strong> 49%, p =<br />

0.001). The diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong><br />

significantly depended on the degree <strong>of</strong> experience <strong>of</strong><br />

the examiners. Dermoscopy by untrained or less<br />

experienced examiners was no better than clinical<br />

inspection without <strong>dermoscopy</strong>. The diagnostic<br />

performance <strong>of</strong> <strong>dermoscopy</strong> improved when the<br />

diagnosis was made by a group <strong>of</strong> examiners in<br />

consensus and diminished as the prevalence <strong>of</strong><br />

melanoma increased. A comparison <strong>of</strong> various<br />

diagnostic algorithms for <strong>dermoscopy</strong> showed no<br />

significant differences in their diagnostic<br />

performance. A thorough appraisal <strong>of</strong> the study<br />

characteristics showed that most <strong>of</strong> the studies were<br />

potentially influenced by verification bias. In<br />

conclusion, <strong>dermoscopy</strong> improves the diagnostic<br />

<strong>accuracy</strong> for melanoma in comparison with<br />

inspection by the unaided eye, but only for<br />

experienced examiners.<br />

Lancet Oncol 2002; 3: 159–65<br />

Early diagnosis is thought to be very important for<br />

improving the prognosis <strong>of</strong> patients with cutaneous<br />

melanoma, but even in specialised centres the <strong>accuracy</strong> <strong>of</strong><br />

the clinical diagnosis for melanoma achieved with the<br />

unaided eye is only slightly better than 60%. 1 Dermoscopy<br />

(epiluminescence microscopy, dermatoscopy, skin-surface<br />

microscopy, incident light microscopy) is a non-invasive, in<br />

vivo examination with a microscope that uses incident light<br />

and oil immersion to make subsurface structures <strong>of</strong> the skin<br />

accessible to visual examination (Figure 1). Dermoscopy<br />

allows the observer to look not only onto but also into the<br />

superficial skin layers, and thus permits a more detailed<br />

inspection <strong>of</strong> pigmented skin lesions. 2 The results <strong>of</strong> several<br />

studies have suggested that <strong>dermoscopy</strong> improves the rate<br />

<strong>of</strong> detection <strong>of</strong> melanoma compared with inspection by the<br />

unaided eye. 3 However, the reported sensitivity and<br />

specificity vary significantly between studies, partly because<br />

the diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong> depends on the<br />

Review<br />

<strong>Diagnostic</strong> <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong><br />

H Kittler, H Pehamberger, K Wolff, and M Binder<br />

Figure 1. Superficial spreading melanoma viewed with <strong>dermoscopy</strong> (large<br />

panel) and with the unaided eye (inset panel). Compared with the unaided<br />

eye, <strong>dermoscopy</strong> reveals several additional structural features, which are<br />

typical <strong>of</strong> melanoma, including irregular dots and irregular extensions<br />

(pseudopods) in the periphery and a blue-whitish veil.<br />

amount <strong>of</strong> training <strong>of</strong> the dermatologist, the diagnostic<br />

difficulty <strong>of</strong> the lesions, and the type <strong>of</strong> algorithm used for<br />

assessment, 4–6 but also as a result <strong>of</strong> differences in the<br />

explicit or implicit threshold used to differentiate between<br />

melanoma and non-melanoma. We have used the metaanalytic<br />

method for diagnostic tests, which combines data<br />

from many studies, 7,8 takes into account differences in the<br />

test threshold, and provides a way to examine the<br />

association between test <strong>accuracy</strong> and study characteristics,<br />

to compare the diagnostic <strong>accuracy</strong> for melanoma with and<br />

without <strong>dermoscopy</strong>, to assess the influence <strong>of</strong> study<br />

characteristics on the diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong>,<br />

and to report summary estimates <strong>of</strong> the diagnostic <strong>accuracy</strong><br />

by combining data from many reports.<br />

Methods<br />

Eligible studies (see Search strategy and selection criteria)<br />

were classified, with no masking, by two readers in<br />

consensus on prospectively defined characteristics<br />

important for assessment <strong>of</strong> diagnostic tests. The following<br />

information was extracted from each report: authors’<br />

names; year <strong>of</strong> publication; description <strong>of</strong> pigmented skin<br />

lesions (melanoma prevalence, melanoma invasion<br />

thickness, frequency <strong>of</strong> non-melanocytic lesions);<br />

experience <strong>of</strong> examiners; independence <strong>of</strong> clinical and<br />

histological assessment; type <strong>of</strong> diagnostic algorithm; mode<br />

All the authors are at the Department <strong>of</strong> <strong>Dermatology</strong>, Division <strong>of</strong><br />

General <strong>Dermatology</strong>, University <strong>of</strong> Vienna Medical School, Vienna,<br />

Austria. HK is a Research Assistant, HP is a Pr<strong>of</strong>essor, KW is<br />

Pr<strong>of</strong>essor and Chairman, and MB is an Associate Pr<strong>of</strong>essor.<br />

Correspondence: Dr Harald Kittler, Department <strong>of</strong> <strong>Dermatology</strong>,<br />

University <strong>of</strong> Vienna Medical School, Waehringerguertel 18–20,<br />

A-1090 Vienna, Austria. Tel: +43 1 40400 7701.<br />

Fax: +43 1 4081928. E-mail: h.kittler@akh-wien.ac.at<br />

THE LANCET Oncology Vol 3 March 2002 http://oncology.thelancet.com 159<br />

For personal use. Only reproduce with permission from The Lancet Publishing Group.


<strong>of</strong> diagnosis, mode <strong>of</strong> presentation; and results (sensitivity<br />

and specificity). The independence <strong>of</strong> clinical and<br />

histological assessment was defined according to whether<br />

the clinical diagnosis was made without knowledge <strong>of</strong><br />

histology. The diagnostic algorithm refers to the type <strong>of</strong><br />

analysis that was used for the dermoscopic assessment <strong>of</strong><br />

pigmented lesions. We differentiated between pattern<br />

analysis as described by Pehamberger and colleagues, 9 the<br />

ABCD rule for <strong>dermoscopy</strong> reported by Stolz and coworkers,<br />

10,11 and algorithms that used a modified form <strong>of</strong><br />

pattern analysis in conjunction with a scoring system. The<br />

latter group included the 7-point checklist <strong>of</strong> Argenziano<br />

and colleagues, 12 Menzies and co-workers’ scoring<br />

system, 13,14 risk stratification as described by Kenet and<br />

Fitzpatrick, 15 and the seven features <strong>of</strong> melanoma as<br />

described by Benelli and others. 16–18<br />

160<br />

Review<br />

Table 1. Main characteristics <strong>of</strong> eligible studies<br />

Dermoscopy<br />

First author Ref Number <strong>of</strong> NML Dermoscopic Dermoscopic Mode <strong>of</strong> Assessment Mode <strong>of</strong><br />

lesions included experience <strong>of</strong> algorithm presentation independent diagnosis<br />

(% melanomas) examiners<br />

Argenziano 12 342 (34%) No Experts and Scoring system, Images Yes Consensus<br />

non-experts ABCD rule*, pattern<br />

analysis<br />

Bauer 19 279 (15%) No Experts Pattern analysis Patients Yes Consensus<br />

Benelli 17 401 (15%) Yes Experts Scoring system Patients Yes Not recorded<br />

Binder 20 100 (40%) No Experts Pattern analysis Images Yes Consensus<br />

Binder 6 240 (24%) Yes Experts and<br />

non-experts<br />

Pattern analysis Images Yes Individual<br />

Binder 5 100 (37%) Yes Non-experts before<br />

and after training<br />

Pattern analysis Images Yes Individual<br />

Binder 4 250 (16%) No Experts and ABCD rule*, Images Yes Individual<br />

non-experts pattern analysis<br />

Carli 21 15 (27%) No Experts Pattern analysis Images Yes Individual<br />

Crist<strong>of</strong>olini 22 220 (15%) Yes Experts Pattern analysis Patients Yes Consensus<br />

Dal Pozzo 18 713 (22%) Yes Experts Scoring system Images Yes Consensus<br />

Dummer 23 824 (3%) Yes Experts Pattern analysis Patients Yes Not recorded<br />

Feldmann 24 500 (6%) No Experts ABCD rule* Patients Yes Individual<br />

Kittler 25 50 (46%) No Experts Pattern analysis Images Yes Individual<br />

Kittler 26 356 (21%) Yes Experts ABCD rule* Images Yes Individual<br />

Krähn 27 80 (49%) No Experts Not recorded Patients Yes Not recorded<br />

Lorentzen 28 232 (21%) Yes Experts and<br />

non-experts<br />

Pattern analysis Images Not recorded Individual<br />

Lorentzen 29 258 (25%) Yes Experts and Scoring system, Images Not recorded Individual<br />

non-experts ABCD rule<br />

Menzies 13 385 (28%) Yes Experts Scoring system Images Yes Not recorded<br />

Nachbar 11 172 (40%) No Experts ABCD rule* Patients Yes Not recorded<br />

Nilles 30 209 (20%) No Experts Scoring system Not recorded Not recorded Not recorded<br />

Seidenari 31 90 (34%) No Experts and<br />

non-experts<br />

Pattern analysis Images Not recorded Individual<br />

Soyer 32 159 (41%) Yes Experts Pattern analysis Patients Yes Individual<br />

Stanganelli 33 20 (50%) No Experts Pattern analysis Images Yes Individual<br />

Stanganelli 34 3329 (2%) No Experts Pattern analysis Patients Yes Individual<br />

Steiner 35 318 (23%) Yes Experts Pattern analysis Patients Yes Consensus<br />

Stolz 10 79 (61%) No Experts ABCD rule* Images Not recorded Consensus<br />

Westerh<strong>of</strong>f 36 100 (50%) Yes Non-experts before<br />

and after training<br />

Scoring system Images Yes Individual<br />

NML, non-melanocytic skin lesions. *The ABCD rule aids clinical diagnosis <strong>of</strong> melanoma on the basis <strong>of</strong> observable morphological features – asymmetry, border irregularity, colour<br />

variegation, and dermoscopic structure.<br />

For mode <strong>of</strong> diagnosis, we noted whether or not<br />

the diagnosis was established in consensus by a group<br />

<strong>of</strong> examiners, and for mode <strong>of</strong> presentation, we<br />

differentiated between studies that used presentation <strong>of</strong><br />

colour prints, photographs, slides, or digital images and<br />

studies that investigated the <strong>accuracy</strong> <strong>of</strong> face-to-face<br />

diagnosis. Studies were further examined according to<br />

whether their results were potentially influenced by<br />

verification bias. Verification bias is likely when the<br />

decision to proceed with the reference test<br />

(histopathology) partly depends on the results <strong>of</strong> the<br />

clinical diagnosis. The influence <strong>of</strong> verification bias<br />

on the diagnostic <strong>accuracy</strong> was not analysed<br />

statistically because only one study looked at the<br />

outcome <strong>of</strong> benign lesions that were not selected for<br />

excision.<br />

THE LANCET Oncology Vol 3 March 2002 http://oncology.thelancet.com<br />

For personal use. Only reproduce with permission from The Lancet Publishing Group.


Dermoscopy<br />

Statistical analysis<br />

Sensitivity and specificity were calculated according to<br />

standard formulae. When individual assessments from<br />

several observers were given in a study, the median values <strong>of</strong><br />

the sensitivity and specificity were used in our analysis.<br />

Least-squares linear regression was used to estimate<br />

parameters for summary receiver-operating-characteristic<br />

(SROC) models. Estimates <strong>of</strong> sensitivity and specificity<br />

were obtained from each study and used to calculate their<br />

log odds ratio (logit), which measures how well the test<br />

discriminates between melanoma and non-melanoma. The<br />

SROC model was obtained by regression <strong>of</strong> the difference,<br />

D, <strong>of</strong> the logits, logit (sensitivity) minus logit (1 minus<br />

specificity), on the sum, S, <strong>of</strong> the logits, logit (sensitivity)<br />

plus logit (1 minus specificity), to test whether the log odds<br />

ratio is associated with the test threshold. 7,8 An inverse<br />

transformation was then used to transform the data back to<br />

the ROC space and to express sensitivity as a function <strong>of</strong> 1<br />

minus specificity. SROC curves were constructed for each<br />

diagnostic method, and differences between them were<br />

compared by use <strong>of</strong> linear regression analysis. To adjust for<br />

covariates we used multiple linear regression analysis.<br />

For the comparison <strong>of</strong> more than two groups, the log<br />

odds ratios were compared by ANOVA, and adjustment for<br />

covariates was done by ANCOVA. The Scheffe test was used<br />

to account for multiple comparisons.<br />

For paired observations, the log odds ratios were<br />

compared by use <strong>of</strong> the paired t test. If studies that were<br />

included in the paired analysis reported the results for<br />

experts and non-experts, only the experts’ readings were<br />

included in the model. The mean difference between the log<br />

odds ratios observed in the paired analysis was used to<br />

calculate the relative improvement achieved with<br />

<strong>dermoscopy</strong>.<br />

Univariate and multivariate regression analyses were<br />

done to assess the variation in diagnostic <strong>accuracy</strong> due to<br />

study characteristics. The regression coefficients give a<br />

measure <strong>of</strong> the difference in diagnostic performance, with<br />

positive coefficients indicating better discriminatory power<br />

and negative coefficients corresponding to lower<br />

discriminatory ability. For multivariate analysis we used a<br />

Review<br />

forward stepwise linear regression analysis. Variables were<br />

entered in the stepwise model if the probability obtained<br />

from the F test was below 0.05 and removed if p was greater<br />

than 0.1.<br />

Statistical analyses used SPSS (version 10.0). All p values<br />

are two-tailed.<br />

Results<br />

Study characteristics<br />

The main characteristics <strong>of</strong> each <strong>of</strong> the 27 eligible<br />

studies 4–6,10–13,17–36 are presented in Table 1. The pooled<br />

sample was 9821 pigmented skin lesions (median per study<br />

232). The prevalence <strong>of</strong> melanoma ranged from 1.6% to<br />

60.8% (mean 28.3%). The mean or median Breslow<br />

thickness was reported in 15 studies and ranged from 0.40<br />

mm to 1.11 mm (median 0.70 mm).<br />

In most <strong>of</strong> the available studies, all lesions were selected<br />

for disease verification. Only one study looked at the<br />

outcome <strong>of</strong> benign lesions that were not selected for<br />

excision. 34<br />

Several studies compared different diagnostic methods<br />

for the diagnosis <strong>of</strong> melanoma. In fourteen studies (52%),<br />

the diagnostic <strong>accuracy</strong> for melanoma with and without<br />

<strong>dermoscopy</strong> was directly compared and in three (11%) two<br />

or more diagnostic algorithms for <strong>dermoscopy</strong> were<br />

compared. Pattern analysis was used in 16 studies (59%),<br />

the ABCD rule in seven (26%), and modified pattern<br />

analysis in conjunction with a scoring system in seven<br />

(26%). Five studies (19%) compared the performance <strong>of</strong><br />

experts and non-experts, and two (7%) assessed the<br />

influence <strong>of</strong> training on the performance <strong>of</strong> non-experts.<br />

All but one study investigated dermatologists; Westerh<strong>of</strong>f<br />

and colleagues studied the effect <strong>of</strong> <strong>dermoscopy</strong> on the<br />

diagnostic performance <strong>of</strong> primary-care physicians. 36<br />

The first model was a paired analysis and included only<br />

those studies that directly compared the diagnostic<br />

<strong>accuracy</strong> for melanoma with and without <strong>dermoscopy</strong><br />

(Table 2). One <strong>of</strong> these 14 studies presented the results in<br />

such a way that the sensitivity and specificity <strong>of</strong> <strong>dermoscopy</strong><br />

could not be calculated, and it was therefore excluded from<br />

the paired analysis. The mean log odds ratio achieved with<br />

Table 2. Main results <strong>of</strong> studies that directly compared the diagnostic <strong>accuracy</strong> for melanoma with and without <strong>dermoscopy</strong><br />

First author Ref Sample size Sensitivity Specificity Log odds ratio<br />

Unaided eye Dermoscopy Unaided eye Dermoscopy Unaided eye Dermoscopy<br />

Benelli 17 401 0.67 0.80 0.79 0.89 2.04 3.49<br />

Binder 6 240 0.58 0.68 0.91 0.91 2.64 3.07<br />

Binder 5 100 0.73 0.73 0.70 0.78 1.84 2.26<br />

Carli 21 15 0.42 0.75 0.78 0.89 0.93 3.17<br />

Crist<strong>of</strong>olini 22 220 0.85 0.88 0.75 0.79 2.83 3.32<br />

Dummer 23 824 0.65 0.96 0.93 0.98 3.21 7.07<br />

Krähn 27 80 0.79 0.90 0.78 0.93 2.59 4.78<br />

Lorentzen 28 232 0.77 0.82 0.89 0.94 3.30 4.27<br />

Nachbar 11 172 0.84 0.93 0.84 0.91 3.29 4.89<br />

Soyer 32 159 0.94 0.94 0.82 0.82 4.27 4.27<br />

Stanganelli 33 20 0.55 0.73 0.79 0.73 1.52 1.94<br />

Stanganelli 34 3329 0.67 0.93 0.99 1.00 5.82 8.25<br />

Westerh<strong>of</strong>f 35 100 0.63 0.76 0.54 0.58 0.66 1.46<br />

THE LANCET Oncology Vol 3 March 2002 http://oncology.thelancet.com 161<br />

For personal use. Only reproduce with permission from The Lancet Publishing Group.


<strong>dermoscopy</strong> was significantly higher than that achieved<br />

without <strong>dermoscopy</strong> (4.0 [95% CI 3.0 to 5.1] versus 2.7 [1.9<br />

to 3.4]), resulting in a mean difference <strong>of</strong> 1.3 (0.7 to 2.0), or<br />

an improvement <strong>of</strong> 49% (p = 0.001).<br />

The second model included the results <strong>of</strong> all 27 eligible<br />

studies and yielded similar results. The mean log odds ratio<br />

achieved with <strong>dermoscopy</strong> was again significantly higher<br />

than that achieved without <strong>dermoscopy</strong> (3.4 [2.9 to 3.9]<br />

versus 2.5 [1.9 to 3.1], p = 0.03). Inclusion <strong>of</strong> information<br />

on the experience <strong>of</strong> the examiners showed that the<br />

diagnostic performance <strong>of</strong> <strong>dermoscopy</strong> was significantly<br />

better for experts than for non-experts (mean log odds ratio<br />

3.8 [3.3 to 4.3] versus 2.0 [1.4 to 2.6]; mean difference 1.8<br />

[0.8 to 2.7], p = 0.001). To account for this finding, we<br />

generated a model that compared the performance <strong>of</strong> the<br />

clinical diagnosis without <strong>dermoscopy</strong>, <strong>dermoscopy</strong> by<br />

non-experts, and <strong>dermoscopy</strong> by experts. For each <strong>of</strong> the<br />

methods, SROC curves were constructed (Figure 2). The<br />

clinical diagnosis without <strong>dermoscopy</strong> showed similar<br />

diagnostic <strong>accuracy</strong> to <strong>dermoscopy</strong> by non-experts (mean<br />

log odds ratio 2.5 versus 2.0; mean difference 0.5 [95% CI<br />

for difference -0.4 to 1.4], p = 0.65). For both approaches<br />

the diagnostic <strong>accuracy</strong> was significantly lower than that<br />

achieved with <strong>dermoscopy</strong> by experts (mean log odds ratio<br />

3.8, p = 0.003 and p = 0.001).<br />

The influence <strong>of</strong> study characteristics on the diagnostic<br />

performance <strong>of</strong> <strong>dermoscopy</strong> was investigated by univariate<br />

and multivariate regression analysis including the results <strong>of</strong><br />

all eligible studies. As in the analysis above, the diagnostic<br />

performance <strong>of</strong> <strong>dermoscopy</strong> increased for experts<br />

(regression coefficient 1.8 [95% CI 0.8 to 2.8], p < 0.001).<br />

The diagnostic performance also increased when the<br />

Sensitivity<br />

162<br />

Review<br />

1.0<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0.1<br />

0.0<br />

Without <strong>dermoscopy</strong><br />

Dermoscopy when performed by experts<br />

Dermoscopy when performed by non-experts<br />

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0<br />

1Specificity<br />

Figure 2. SROC curves for the performance <strong>of</strong> the clinical diagnosis<br />

without <strong>dermoscopy</strong> (red line), <strong>dermoscopy</strong> by experts (black line), and<br />

<strong>dermoscopy</strong> by non-experts (blue line).<br />

Dermoscopy<br />

diagnosis was made by a group <strong>of</strong> two or more examiners in<br />

consensus (regression coefficient 1.1 [0.2 to 2.1], p = 0.02).<br />

Although consensus increased the discriminatory power <strong>of</strong><br />

<strong>dermoscopy</strong>, the procedure performed by experts achieved<br />

higher <strong>accuracy</strong> than inspection with the unaided eye<br />

whether or not the dermoscopic diagnosis was made in<br />

consensus. The <strong>accuracy</strong> <strong>of</strong> the (clinically more relevant)<br />

non-consensus diagnosis achieved with <strong>dermoscopy</strong> was<br />

significantly higher than that achieved without <strong>dermoscopy</strong><br />

(mean log odds ratio 3.7 versus 2.5; mean difference 1.2<br />

[95% CI for difference 0.3 to 2.2], p = 0.01).<br />

The diagnostic ability <strong>of</strong> <strong>dermoscopy</strong> was inversely<br />

correlated with the prevalence <strong>of</strong> melanoma in the sample<br />

(regression coefficient -0.04 [95% CI -0.06 to -0.01],<br />

p = 0.006) and lower for experimental studies that used<br />

presentation <strong>of</strong> slides, colour prints, or digital images than<br />

for clinical studies in which the diagnosis was made face to<br />

face (regression coefficient -1.3 [-2.1 to -0.5], p = 0.001).<br />

Other study characteristics did not significantly influence<br />

the diagnostic performance <strong>of</strong> <strong>dermoscopy</strong>.<br />

For multivariate analysis we used a forward stepwise<br />

regression analysis. The final model included three<br />

variables: the experience <strong>of</strong> examiners (regression<br />

coefficient 1.2 [0.3 to 2.1], p = 0.01), the prevalence <strong>of</strong><br />

melanoma (regression coefficient -0.04 [-0.06 to -0.01],<br />

p = 0.01), and whether the diagnosis was made in consensus<br />

(regression coefficient 1.0 [0.04 to 1.9], p = 0.04). Other<br />

variables were not independently associated with the<br />

diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong>. Since the<br />

dermatologists’ experience was the strongest predictive<br />

variable for the diagnostic performance <strong>of</strong> <strong>dermoscopy</strong>, we<br />

built a SROC model for the pooled diagnostic performance<br />

<strong>of</strong> <strong>dermoscopy</strong> adjusted for three settings with different<br />

degrees <strong>of</strong> experience (Figure 3).<br />

Univariate analysis <strong>of</strong> the individual results <strong>of</strong> all<br />

eligible studies showed that the diagnostic <strong>accuracy</strong> <strong>of</strong><br />

<strong>dermoscopy</strong> was similar for the different diagnostic<br />

algorithms. The log odds ratios achieved with pattern<br />

analysis (3.6 [95% CI 2.8 to 4.4]), the ABCD rule (3.2 [2.4<br />

to 3.9]), and scoring systems (3.1 [2.1 to 4.0]) did not differ<br />

significantly (p = 0.64). We analysed the influence <strong>of</strong> the<br />

experience <strong>of</strong> the examiners on the performance <strong>of</strong> the<br />

diagnostic algorithms. The degree <strong>of</strong> experience had a<br />

significant effect on the diagnostic <strong>accuracy</strong> <strong>of</strong> pattern<br />

analysis (regression coefficient 2.0 [95% CI 0.4 to 3.6],<br />

p = 0.02) and scoring systems (regression coefficient 2.3<br />

[0.5 to 4.1], p = 0.02). By contrast, the degree <strong>of</strong> experience<br />

had no significant effect on the diagnostic <strong>accuracy</strong><br />

achieved with the ABCD rule (regression coefficient 0.8<br />

[-1.1 to 2.7], p = 0.35).<br />

Discussion<br />

This meta-analysis <strong>of</strong> 27 studies provides evidence that<br />

<strong>dermoscopy</strong> gives better diagnostic <strong>accuracy</strong> for melanoma<br />

than clinical inspection without dermatoscopy (ie with the<br />

unaided eye). This conclusion accords with that <strong>of</strong> a<br />

previous review, which included six studies, 37 and another<br />

meta-analysis, which included eight studies. 38 The review<br />

did not provide a quantitative analysis and the other metaanalysis<br />

was restricted to studies that directly compared the<br />

THE LANCET Oncology Vol 3 March 2002 http://oncology.thelancet.com<br />

For personal use. Only reproduce with permission from The Lancet Publishing Group.


Sensitivity<br />

Dermoscopy<br />

1.0<br />

0.9<br />

0.8<br />

0.7<br />

0.6<br />

0.5<br />

0.4<br />

0.3<br />

0.2<br />

0.1<br />

0<br />

Best case<br />

Base case<br />

Worst case<br />

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0<br />

1Specificity<br />

Figure 3. SROC curves for the pooled diagnostic performance <strong>of</strong><br />

<strong>dermoscopy</strong>. The base case (black line) is adjusted to a setting at which<br />

half <strong>of</strong> the examiners are experienced in <strong>dermoscopy</strong> (experts). The best<br />

case (red line) is adjusted to a setting at which all examiners are experts in<br />

<strong>dermoscopy</strong>. The worst case (blue line) is adjusted to a setting at which<br />

all examiners are untrained or less experienced (non-experts).<br />

diagnostic performance with and without <strong>dermoscopy</strong>.<br />

Neither study addressed the influence <strong>of</strong> study<br />

characteristics on the diagnostic performance <strong>of</strong><br />

<strong>dermoscopy</strong>.<br />

According to our analysis, the diagnostic <strong>accuracy</strong> <strong>of</strong><br />

<strong>dermoscopy</strong> significantly depends on the experience <strong>of</strong> the<br />

examiners. Moreover, the diagnostic <strong>accuracy</strong> achieved is<br />

no better with <strong>dermoscopy</strong> applied by non-experts than<br />

with the unaided eye. This finding underlines the<br />

importance <strong>of</strong> training for the application <strong>of</strong> <strong>dermoscopy</strong>. 5,6<br />

The study by Westerh<strong>of</strong>f and colleagues, investigating the<br />

value <strong>of</strong> <strong>dermoscopy</strong> on the diagnostic performance <strong>of</strong><br />

primary-care physicians, deserves further attention. 36 It was<br />

the only study <strong>of</strong> non-dermatologists. Primary-care<br />

physicians were trained to use a simplified diagnostic<br />

scoring system for <strong>dermoscopy</strong>. Their diagnostic<br />

performance before training was only slightly better than<br />

chance. After training, there was a significant improvement<br />

in the diagnosis <strong>of</strong> melanoma by <strong>dermoscopy</strong> versus<br />

inspection with the unaided eye. However, the reported<br />

diagnostic <strong>accuracy</strong> after training was much lower than in<br />

comparable studies involving dermatologists.<br />

We also found that the diagnostic performance <strong>of</strong><br />

<strong>dermoscopy</strong> was improved when the diagnosis was made by<br />

a group <strong>of</strong> examiners in consensus. A consensus diagnosis<br />

might not be practicable in most clinical settings, but it may<br />

be important for telemedical applications. By electronic<br />

transmission <strong>of</strong> digital dermoscopic images,<br />

tele<strong>dermoscopy</strong> potentially involves two or more experts at<br />

Review<br />

geographically distant facilities. However, how a consensus<br />

can be reached for a group <strong>of</strong> examiners working at<br />

geographically distant facilities is unclear. Two studies that<br />

compared face-to-face diagnosis with remote diagnosis<br />

found no differences in the diagnostic performances,<br />

indicating that electronically transmitted dermoscopic<br />

images convey the information necessary for differentiation<br />

between melanoma and non-melanoma. 39,40 Future work<br />

should assess the value <strong>of</strong> a consensus diagnosis for<br />

electronically transmitted dermoscopic images.<br />

The prevalence <strong>of</strong> melanoma was inversely correlated<br />

with the diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong>. A possible<br />

interpretation <strong>of</strong> this finding is that if more melanomas are<br />

included in a sample, the overall diagnostic difficulty <strong>of</strong> the<br />

sample is increased. Another explanation could be<br />

differences in the criteria applied to select the lesions<br />

between the studies.<br />

Since the original reports by Pehamberger, Steiner, and<br />

colleagues, 3,9,35 describing the use <strong>of</strong> pattern analysis for the<br />

dermoscopic assessment <strong>of</strong> pigmented skin lesions, several<br />

diagnostic algorithms have been developed. Pattern analysis<br />

relies on the description <strong>of</strong> several dermoscopic features,<br />

which can be difficult for non-experts to recognise. Scoring<br />

systems are simplified versions <strong>of</strong> pattern analysis with a<br />

limited number <strong>of</strong> dermoscopic features. The ABCD rule is<br />

somewhat different from the other algorithms because the<br />

exact description <strong>of</strong> the dermoscopic features is not so<br />

important. Pattern analysis requires a sufficient amount <strong>of</strong><br />

training, 6 whereas the other, simpler, diagnostic algorithms<br />

might be more suitable for less experienced examiners. 4,12 In<br />

our analysis, all algorithms did equally well. Pattern analysis<br />

showed slightly better diagnostic <strong>accuracy</strong> than the other<br />

algorithms but the differences were not statistically<br />

significant. As expected, the diagnostic performance <strong>of</strong><br />

pattern analysis was strongly influenced by the experience<br />

<strong>of</strong> the examiners. Surprisingly, this was also true for scoring<br />

systems. One explanation might be that, as for pattern<br />

analysis, the recognition <strong>of</strong> dermoscopic features is crucial<br />

for the diagnostic procedure. Compared with pattern<br />

analysis and scoring systems, the degree <strong>of</strong> experience had<br />

less influence on the diagnostic ability <strong>of</strong> the ABCD rule for<br />

<strong>dermoscopy</strong>, which suggests that this algorithm is especially<br />

suitable for beginners in <strong>dermoscopy</strong>.<br />

As shown by the SROC curves in Figure 3, the<br />

diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong> does not reach 100%<br />

even under the assumption <strong>of</strong> optimum conditions,<br />

indicating that <strong>dermoscopy</strong> cannot replace histopathology.<br />

However, <strong>dermoscopy</strong> may provide useful additional<br />

information for the histopathologist in difficult cases. Soyer<br />

and colleagues showed that clinicopathological correlation<br />

<strong>of</strong> pigmented skin lesions by <strong>dermoscopy</strong> is useful for<br />

dermatopathologists when reporting on melanocytic skin<br />

lesions. 41 Dermoscopy and histopathology should be<br />

regarded as concurrent examinations <strong>of</strong> a joint diagnostic<br />

procedure with additive information.<br />

The summary estimates <strong>of</strong> the diagnostic <strong>accuracy</strong> <strong>of</strong><br />

<strong>dermoscopy</strong> provided by this meta-analysis have to be<br />

interpreted with caution because the results <strong>of</strong> most studies<br />

were potentially influenced by verification bias, which is<br />

likely to occur when the decision to proceed with the<br />

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164<br />

Review<br />

Search strategy and selection criteria<br />

Relevant studies were identified and retrieved by a search<br />

<strong>of</strong> MEDLINE for the period January 1987 to December<br />

2000, by manual searches <strong>of</strong> the reference lists <strong>of</strong> retrieved<br />

articles, and by direct communication with experts on this<br />

topic. The terms “epiluminescence”, “<strong>dermoscopy</strong>”,<br />

“dermatoscopy”, and “incident light microscopy” were<br />

linked with a Boolean OR operator and the search yielded<br />

157 articles. 116 articles were excluded at this stage: those<br />

that were not relevant to the topic, did not address the<br />

diagnostic <strong>accuracy</strong> for melanoma, or were published in<br />

languages other than English or German, review articles,<br />

letters, and reports without original data. Additional<br />

articles were identified by manual searches <strong>of</strong> the<br />

reference lists <strong>of</strong> retrieved articles and by direct<br />

communication with experts. Articles that did not include<br />

original data on the diagnostic <strong>accuracy</strong> for melanoma<br />

and those that did not report sufficient data for the<br />

sensitivity and specificity to be estimated were excluded.<br />

Estimates <strong>of</strong> the diagnostic <strong>accuracy</strong> for melanoma<br />

involving computerised image analysis were also excluded<br />

from further analysis. The final sample included 27<br />

studies, <strong>of</strong> which 20 were identified by the MEDLINE<br />

search, three by manual searches <strong>of</strong> the reference lists <strong>of</strong><br />

retrieved articles, and four by communication with<br />

experts.<br />

reference test (histopathology) partly depends on the<br />

results <strong>of</strong> the clinical diagnosis. Suspect clinical findings<br />

are more likely to be investigated by histopathology, so the<br />

chance <strong>of</strong> detecting a true positive is higher than that for a<br />

false negative and the chance for detecting a false positive is<br />

higher than that for a true negative. In this case, sensitivity<br />

seems to be falsely increased and specificity falsely<br />

decreased. Since most <strong>of</strong> the studies included in our meta<br />

analysis were potentially influenced by verification bias, in<br />

general the sensitivity is probably overestimated and the<br />

specificity underestimated.<br />

Another important issue that may have influenced our<br />

results is publication bias. This bias refers to the systematic<br />

error induced in a statistical analysis by the requirement<br />

for studies to be published. The influence <strong>of</strong> publication<br />

bias is difficult to assess. The most important question is<br />

whether our results can be explained solely by its presence.<br />

We think that this is unlikely, because generally<br />

publication bias arises because studies with statistically<br />

significant results are more likely to be published<br />

than those with non-significant results, but only a few<br />

studies included in our analysis provided a direct statistical<br />

comparison <strong>of</strong> the diagnostic <strong>accuracy</strong> with and without<br />

<strong>dermoscopy</strong>. However, publication bias cannot be ruled<br />

out completely and may have influenced the results <strong>of</strong> our<br />

analysis towards an overoptimistic estimate <strong>of</strong> the<br />

diagnostic <strong>accuracy</strong> <strong>of</strong> <strong>dermoscopy</strong>.<br />

Conclusion<br />

Dermoscopy improves the diagnostic <strong>accuracy</strong> for<br />

melanoma in comparison with inspection by the unaided<br />

Dermoscopy<br />

eye. However, <strong>dermoscopy</strong> requires sufficient training and<br />

cannot be recommended for untrained users. A consensus<br />

diagnosis involving two or more experts is recommended to<br />

yield the highest possible diagnostic <strong>accuracy</strong>.<br />

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