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EVIDENCE-BASED DERMATOLOGY: ORIGINAL CONTRIBUTION

Is Dermoscopy (Epiluminescence Microscopy)


Useful for the Diagnosis of Melanoma?
Results of a Meta-analysis Using Techniques Adapted
to the Evaluation of Diagnostic Tests
Marie-Lise Bafounta, MD; Alain Beauchet, MD, PhD; Philippe Aegerter, MD, PhD; Philippe Saiag, MD

Objective: To assess, by means of meta-analysis tech- Data Synthesis: Selected studies represented 328 mela-
niques for diagnostic tests, the accuracy of dermoscopic nomas, mostly less than 0.76 mm thick, and 1865 mostly
(also known as dermatoscopy and epiluminescence mi- melanocytic benign pigmented skin lesions. For dermo-
croscopy) diagnosis of melanoma performed by experi- scopic diagnosis of melanoma, the sensitivity and speci-
enced observers vs naked-eye clinical examination. ficity ranges were 0.75 to 0.96 and 0.79 to 0.98, respec-
tively. Dermoscopy had significantly higher discriminating
Data Sources: MEDLINE, EMBASE, PASCAL-BIOMED, power than clinical examination, with respective esti-
and BIUM databases were screened through May 31, 2000, mated odds ratios of 76 (95% confidence interval, 25-
without any language restrictions. 223) and 16 (95% confidence interval, 9-31) (P=.008),
and respective estimated positive likelihood ratios of 9
Study Selection: Original studies were selected when (95% confidence interval, 5.6-19.0) and 3.7 (95% con-
the following criteria were met: spectrum of lesions well fidence interval, 2.8-5.3). The roles of the number of le-
described, histologic findings as standard criterion, and sions analyzed, the percentage of melanoma lesions, the
calculated or calculable sensitivity and specificity. Eight instrument used, and dermoscopic criteria used in each
of 672 retrieved references were retained. study could not be proved.

Data Extraction: Three investigators extracted data. In Conclusion: For experienced users, dermoscopy is more
case of disagreement, consensus was obtained. Sum- accurate than clinical examination for the diagnosis of
mary receiver operating characteristic curve analysis was melanoma in a pigmented skin lesion.
used to describe the central tendency of the studies, and
to compare dermoscopy and clinical examination. Arch Dermatol. 2001;137:1343-1350

M
ORBIDITY and mortal- ments have been used, ranging from widely
ity attributed to skin used, inexpensive, handheld instru-
melanoma have dra- ments (eg, Dermatoscope [Heine Ltd,
matically increased in Herrshing, Germany] and Episcope
recent years.1 As there [Welch Allyn Inc, Skaneateles Falls, NY])
is a strong inverse correlation between sur- that provide a fixed magnification of ⫻10,
vival rate and tumor thickness, and no ef- to binocular microscopes and, more re-
fective therapy exists for advanced mela- cently, to digital videomicroscopy,3 the
noma, early diagnosis and excision are last 2 options providing higher magnifi-
essential to reduce morbidity and im- cation.
prove patients’ survival. Dermoscopy (also
known as dermatoscopy, epilumines- For editorial comment
cence microscopy, incident light micros-
copy, and skin-surface microscopy) is a see page 1361
From the Service de noninvasive technique to examine pig-
Dermatologie mented anatomic structures of the epider- It has been claimed that dermos-
(Drs Bafounta and Saiag) and
mis, dermoepidermal junction, and su- copy improves sensitivity (up to 30%) and
Antenne d’Informatique
Médicale (Drs Beauchet and perficial papillary dermis that are not specificity of melanoma diagnosis com-
Aegerter), Hôpital Ambroise visible to the naked eye.2 The technique pared with clinical diagnosis4-11 and thus
Paré, Assistance uses in vivo microscopy with fluid ap- could lower the excision rate of histologi-
Publique-Hôpitaux de Paris, plied to the skin to render the stratum cor- cally benign but clinically doubtful nevi.
Boulogne, France. neum more translucent. Various instru- However, there is no consensus on this

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METHODS described (with a spectrum of melanoma lesions and lesions
commonly confused with melanoma), blinded comparison
of diagnostic tests with histologic findings as the standard cri-
We followed the guidelines for meta-analyses evaluating terion, and calculated or calculable statistical values (sensi-
diagnostic tests.15,18 tivity, specificity, and positive and negative likelihood
ratios).18,19 A study was held to be of insufficient quality when
DATA SOURCES 1 criterion was absent. Studies of acceptable quality were fi-
nally selected when the diagnostic performance of dermos-
Four bibliographic databases were screened through May copy on melanoma was compared with that of naked-eye clini-
31, 2000: (1) the online MEDLINE (National Library of cal examination and when dermoscopy was performed by
Medicine, Bethesda, Md; http://www.ncbi.nlm.nih.gov/ experienced operators. Excluded from this research were re-
entrez/query.fcgi) from January 1968; (2) Elsevier Sci- views; editorials; original articles on the development of der-
ence online EMBASE (http://www.ovid.com/products/ moscopic criteria for diagnosing PSLs, terminology of der-
databases/database_info.cfm) from 1989; (3) moscopy, accuracy of diagnosis of a single type of PSL, and
PASCAL-BIOMED on CD-ROM (http://www.silverplatter accuracy of computer-assisted lesion analysis; and studies not
.com/catalog/pbma.htm), which also contains congres- comparing dermoscopy with naked-eye examination.
sional reports, from 1987; and (4) BIUM (Bibliothèque In-
ter Universitaire Médicale, Paris, France), which contains DATA EXTRACTION
all French doctoral theses in medicine from 1985.
No language restrictions were applied. The MEDLINE The following data were extracted from selected articles (af-
search was conducted by successively calling the follow- ter translation if not in English or French): setting, lesion-
ing keywords: dermatoscopy, dermoscopy, epilumines- selection criteria, total number and spectrum of lesions ana-
cence microscopy, diascopy, surface microscopy, incident lyzed, prevalence of melanoma, Breslow index of the tested
light microscopy, in combination with melanoma or melanomas, degree of observer blinding, study type (pro-
skin neoplasm (exploded mode), sensitivity, and specific- spective study or analysis of randomly selected lesions from
ity. Similar strategies were used to search EMBASE and a database), instrument used, criteria applied for clinical and
PASCAL-BIOMED. Other sources were the references of dermoscopic diagnoses, dermoscopy reproducibility, and per-
the retrieved articles and textbooks on the topic. All of the centage of lesions in which no dermoscopic diagnosis could
retrieved references were entered into the bibliography man- be made. The potential bias of these studies was ana-
agement software EndNote 3.01 (ISI Research Soft, Berke- lyzed.15,18 Dermoscopic criteria for melanoma were classi-
ley, Calif), to facilitate the search for duplicate references. fied as either pattern analysis20 (even when slightly differ-
ent pattern criteria were added to the original publication)
STUDY SELECTION or ABCD21 (asymmetry, border, color, and differential struc-
ture) or 7FFM22 (7 features for melanoma) criteria. Sensi-
Three investigators, 2 dermatologists (M.-L.B. and P.S.) and tivity, specificity, and positive and negative likelihood ra-
1 statistician (A.B.), independently reviewed the studies and tios were calculated according to standard formulas. When
filled in preestablished evaluation grids. In case of divergent possible, these values were recalculated from the data given
evaluations, consensus was obtained. We first selected origi- in the articles. When dermoscopy was performed by both
nal studies on dermoscopy by reading the titles and ab- nonexpert and expert observers, we selected only the re-
stracts. An initial review evaluated selected studies for the fol- sults recorded by skilled operators. When individual clini-
lowing quality criteria: spectrum of included patients well cal or dermoscopic evaluations from multiple observers were

claim,12 and studies on dermoscopy to detect malignant groups defined by the characteristics of the patients and
melanoma are heterogeneous in their design and the types tests; and (4) identify areas for future research. To as-
of dermoscopic criteria for melanoma applied.13 It has also sess the clinical value of dermoscopy in the evaluation
been reported that dermoscopy does not sufficiently of PSL, we focused our analysis on the comparison of der-
improve the accuracy of diagnosis to alter the clinical moscopic and naked-eye clinical examinations. As train-
management of most pigmented skin lesions (PSLs).13 ing in dermoscopy clearly improves diagnostic efficacy,
To objectively assess the diagnostic accuracy of der- we restricted our analysis to dermoscopy performed by
moscopy in detecting melanoma, we performed a meta- formally trained operators.17
analysis. This method is the critical review of the litera-
ture and mathematical combination of the results of
previous research, to obtain a quantified and reproduc- RESULTS
ible synthesis of data, and to diminish the bias of each
study.14 While it is mostly used to assess studies on thera- LITERATURE SEARCH
peutic efficacy, this method can also evaluate diagnostic
tests.15,16 Such meta-analyses can (1) provide an overall Five hundred sixty-four articles were identified from
summary of diagnostic accuracy; (2) determine whether MEDLINE, 223 from EMBASE (with 138 references found
estimates of diagnostic accuracy depend on the study de- in both databases), 117 from PASCAL-BIOMED (with 96
sign characteristics (study validity) of primary studies; references also found in MEDLINE or EMBASE), and 2
(3) determine whether diagnostic accuracy differs in sub- doctoral theses from the BIUM database. After elimina-

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given in a study, we retained only the responses most fre- values [FPR, 1−specificity]) defines the receiver operating
quently given by the investigators. When melanoma had characteristic (ROC) space, and the points within this space
been clinically diagnosed according to the ABCDE (asym- are the combinations of the different values. The ROC curve
metry, border, color, diameter, and evolution) criteria, we joins the different points and enables assessment of the varia-
required the presence of at least 2 criteria; this gives the tion of sensitivity as a function of varying specificity. The
best sensitivity with acceptable specificity.23 closer the curve comes to the upper left-hand corner of the
graph, the better the test.
STATISTICS While the ROC curve illustrates data for a diagnostic
test coming from a single study, an sROC curve fits data
Sensitivity and specificity, commonly used in diagnostic from different studies into the same curve. The method used
tests, rely on a single threshold whose modification to in- in this study, proposed by Moses et al,24 follows these steps:
crease sensitivity decreases specificity, and vice versa. When 1. Convert each FPR and TPR into its logistic trans-
studies use different criteria to define positive and nega- formation (logit):
tive test results, the thresholds differ. Even when studies U=logit(FPR)=Ln[FPR/(1−FPR)]
apply the same criteria, the thresholds may not be the same, V=logit(TPR)=Ln[TPR/(1−TPR)]
since interpretation of the test depends on subjective judg- 2. For each study, calculate:
ment. To take different thresholds into account across stud-
ies, we used summary receiver operating characteristic D=V−U=Ln(odds ratio),
(sROC) curve analysis, proposed by Moses et al,24 to de- where the odds ratio equals [TPR/(1−TPR)]/[FPR/(1−FPR)]
scribe the central tendency of the studies, and also to com- and D measures how well the test discriminates between sub-
pare the discriminatory powers of naked-eye clinical ex- jects with and without the disease.
amination and dermoscopy. The significance of differences S=V+U,
was statistically analyzed by applying a Wilcoxon paired- where S is a measurement of the threshold for classifying
sample test to the parameter Ln(odds ratio), where Ln in- a test as positive.
dicates the neperian logarithm. A P value less than .05 was 3. Plot each study’s point (Si,Di) in an (S,D) space and
considered significant. Estimated positive and negative like- fit an unweighted least-squares regression line. The linear
lihood ratios were calculated from the point of intersec- regression model is:
tion of the sROC curve with the line (1−specificity)+ sen- D=␣+␤S.
sitivity=1, which slopes from the upper left to the lower
right corners.24 At that intersection, sensitivity equals speci- The regression coefficient ␤ provides an estimate of the ex-
ficity. That point is a global measurement of test efficacy. tent to which the Ln(odds ratio) is dependent on the thresh-
Statistical analysis was performed with the SAS 6.12 soft- old used. If it is near 0, the common odds ratio is given by
ware package (SAS Institute Inc, Cary, NC). exp␣.
4. Reverse-transform (TPR) and plot the sROC curve
CONSTRUCTION OF sROC CURVES onto the FPR-vs-TPR graph.
TPR={1+exp-␣/(1-␤) [(1−FPR)/FPR](1+␤)/(1-␤)}-1
A diagnostic test within a single study may have several com- 5. Compare the 2 diagnostic tests. All the points are
binations of sensitivity and specificity values, depending plotted for both tests in the (S,D) space, and the regres-
on the threshold value. The graph reporting these values sion line is fitted. If ␤ is nonstatistically different from 0, a
(where the y-axis represents true-positive rate values [TPR, Wilcoxon paired-samples test is applied to compare the Ln
sensitivity] and the x-axis represents false-positive rate (odds ratio) for clinical examination and dermoscopy.

tion of duplicates, we obtained 672 studies. Screening of istry, and the entire series of patients with benign clinical
the reference lists of retrieved articles and textbooks dis- or dermoscopic diagnosis and no referral for excision were
closed no additional studies. cross-checked with this registry a median of 31 months
after dermoscopic examination. This registry has good
STUDY SELECTION indicators of satisfactory levels of registration complete-
ness,25 and we ascertained that it contains the expected
Forty-nine studies were subjected to further selection pro- number of patients with melanoma,26 as compared with
cedures after we read their titles and abstracts. Thirty- the most recent figures of disease incidence in Italy.27 Only
four references fulfilled the required quality criteria. Eight 2 additional patients with melanoma have been found.
studies, all referenced in the MEDLINE database, met all Thus, only a few patients with melanoma seem to have
of our selection criteria.7-12,22,25 been missed in that study. As our standard criterion was
The study by Stanganelli et al25 was included de- histologic findings, only verified lesions were consid-
spite the absence of histologic findings for 92% of the 3372 ered for the analyses presented in Table 1 (see below),
PSLs assessed, for the following reasons: (1) all lesions including those found through the cancer registry.
clinically or dermoscopically suspected of being mela- The exclusion of certain studies needs further ex-
noma had been subjected to histologic examination, thus planation. In one article, the standard criterion did not
allowing the calculation of true- and false-positive evalu- allow clear discrimination between melanoma and atypi-
ations, and (2) all of the included patients were inhab- cal nevus.28 Although Ascierto et al29 tested 15719 PSLs,
itants of the region covered by the Romagna Cancer Reg- the results of clinical and dermoscopic examinations were

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Table 1. Design of the Selected Studies*

Method of Clinical Method of Dermoscopic


Lesion Selection Diagnosis of Dermoscopy Criteria for
Source Setting/Study Type Criteria Observers Melanoma (Magnification) Melanoma
Benelli et al22 Dermatologic surgery All consecutive PSLs 2 Dermatologists, ABCDE Not given 7FFM (score ⱖ2)
department/ excised during 1 y not involved in (ⱖ2 criteria)
prospective in vivo (No. of patients decision whether
evaluation not given) to excise lesions
Carli et al11 Dermatology Not given 15 Dermatologists, Not given Dermaphot† (slides Pattern analysis
department/ all skilled taken at ⫻10
retrospective magnification)
evaluation of
photographs
Cristofolini et al10 Dermatology All consecutive PSLs 4 Dermatologists, ABCDE criteria Handheld Pattern analysis
department/ excised during 9 with consensus (ⱖ2 criteria) dermoscope (⫻10)
prospective in vivo mo (700 patients evaluation
evaluation during a seen), all nevi with
campaign for the ABCDE criteria ⱖ1
early detection of excised
melanoma
Dummer et al9 Dermatology All consecutive 3 Dermatologists, ABCDE criteria Videomicroscopy Pattern analysis
department/ difficult-to- not involved in (threshold not (⫻25 to ⫻400)
prospective in vivo diagnose PSLs decision whether given)
evaluation seen during 1 y to excise lesions,
(No. of patients not involved in
not given) clinical diagnosis
Krähn et al8 Dermatology Not given Not given Not given Not given Not given
department/
prospective in vivo
evaluation
Lorentzen et al7 Dermatology All clinical and 4 Expert Not given Dermaphot (slides Pattern analysis
department/ dermatoscopic dermatologists taken at ⫻10)
retrospective photographs of (5 novices
evaluation on PSLs taken during discarded)
photographs a 4-y period
Soyer et al12 PSL clinic/prospective Not given, but 3 Expert Not given Handheld Pattern analysis
in vivo evaluation among clinically dermatologists dermoscope
difficult-to- (⫻10) and
diagnose PSLs stereomicroscope
referred by (⫻6 to ⫻40)
general
practitioners or
dermatologists
Stanganelli et al25 Skin cancer All patients with 1 Expert ABCDE (threshold Stereomicroscope Pattern analysis,
clinic/prospective PSLs recorded in dermatologist not given) (⫻ 6 to ⫻16) and with digital
in vivo evaluation database (see digital contrast and
“Results” section) videomicroscopy enhancement
(⫻6 to ⫻40) procedures

*PSL indicates pigmented skin lesion. ABCDE are clinical criteria for the diagnosis of melanoma23; 7FFM, dermoscopic criteria for the diagnosis of melanoma.22
†Heine Ltd, Herrshing, Germany.

not clearly reported. The possibility of performing “in- were not reported, although figures were given for diag-
formal” dermoscopy to support the clinical evaluation, nostic accuracy and index of suspicion.
as explained by Nachbar et al,5 could have biased the clini-
cal diagnosis. In both studies, the choice of lesions to be INTERNAL AND EXTERNAL VALIDITY
assessed by the standard criterion (ie, histologic find- OF THE SELECTED STUDIES
ings) was also dictated by the result of dermoscopy (veri-
fication bias). The well-done study by Steiner et al6 was The main characteristics of the 8 retained studies are given
eliminated because of the unavailability of data to cal- in Table 1. All came from dermatology departments, were
culate dichotomous outcomes of melanoma or nonmela- published between 1993 and 2000, and were set in der-
noma for dermoscopy, although such data were given for matology clinics or even in specialized PSL clinics. Two
the clinical evaluations. Two studies17,30 were excluded studies were performed on images originating from a da-
because dermoscopy was compared with pictures taken tabase, and 6 prospectively recorded dermoscopy re-
without oil at magnifications of ⫻16 and ⫻10, respec- sults in vivo. As required by our selection criteria, all stud-
tively, and not with naked-eye examination. The study ies used histologic findings as a standard criterion, but
by Pazzini et al31 was rejected because the data needed only 4 had histologic findings verified by an external re-
to calculate sensitivity, specificity, and likelihood ratios view or derived from a consensus among at least 2 ob-

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servers.7-9,25 Although clearly stated only for the 2 stud- RESULTS OF SELECTED STUDIES
ies with image databases, clinical and dermoscopic
examinations seem to have been conducted in all stud- Results of the 8 studies are summarized in Table 2. The
ies independent of the standard criterion because of evi- respective sensitivity, specificity, and positive and nega-
dent temporal relationship. The choice of patients to be tive likelihood ratio ranges were as follows: 0.50 to 0.94,
assessed by the standard criterion was not entirely inde- 0.55 to 0.89, 1.91 to 10.66, and 0.61 to 0.08 for the clini-
pendent of the test results, as, in all studies, lesions were cal diagnosis of melanoma; and 0.75 to 0.96, 0.79 to
excised mainly because of a clinically presumed risk of 0.98, 4.21 to 76.62, and 0.28 to 0.04 for the dermoscopic
malignancy or, possibly, patient request. Only Stangan- diagnosis of melanoma. Variations of sensitivity, specific-
elli et al25 collected information aimed at calculating the ity, and positive and negative likelihood ratios for the di-
true false-negative rate (see above). Lesion-selection cri- agnoses of melanoma after dermoscopy were as follows:
teria were absent or almost absent from 2 articles. It was −0.05 to +0.30, 0.00 to +0.33, 0.00 to +65.96, and −0.34 to
stated in only 4 reports that all consecutive PSLs ex- 0.00, respectively.
cised4,9 or recorded7,25 within a determined period had According to the results of 5 studies, dermoscopy had
been included. higher sensitivity than nondermoscopic diagnosis,7-9,11,25
To assess the validity of the comparison between but only 2 of them demonstrated statistical signifi-
clinical and dermoscopic evaluations, we investigated cance.7,25 Because individual data were not detailed in the
their independence. Only 111 of the 2 retrospective 3 remaining reports, we were unable to perform post hoc
studies clearly stated that the dermoscopic evaluations statistical tests. In the only study that addressed that is-
had been made without knowing the results of the sue, the improvement of sensitivity was more pro-
clinical ones, and both claimed that dermoscopy did nounced for melanomas less than 0.76 mm thick, as com-
not influence clinical judgment.7,11 For the 6 in vivo pared with thicker ones.25 In all of these studies, specificity
dermoscopic evaluations, it is highly probable that der- and positive and negative likelihood ratios were also bet-
moscopy had been performed after the lesions were ter. Four of these studies used high-magnification der-
examined with the naked eye. Clinical evaluations were moscopy, with either Dermaphot or videomicroscopy. The
clearly recorded before dermoscopy was done in all but remaining one provided no information on the instru-
2 of these studies.12,25 ment used.
Criteria for the clinical diagnosis of melanoma were For 2 studies, in which the clinical evaluation al-
specified in 4 reports, with a threshold value clearly given ready had achieved high sensitivity and specificity, no
in only 2. The number of clinically atypical nevi was not difference was found between clinical and dermoscopic
clearly stated in most studies. The instruments used dif- assessments.10,12 For another study, in which the clini-
fered among the studies. Transparencies taken with a Der- cal evaluation had high sensitivity but low specificity, der-
maphot (Heine Ltd) at original ⫻10 magnification were moscopy had comparable sensitivity but better specific-
analyzed in 2 studies.7,11 One study used a handheld mon- ity and positive and negative likelihood ratios.22
ocular dermoscope with ⫻10 magnification,10 and an-
other used a digital videomicroscope with magnifica- STATISTICS
tions up to ⫻400.9 One study used both a handheld
dermoscope (⫻10) and a binocular stereomicroscope (⫻6 The sROC curves of clinical and dermoscopic evalua-
to ⫻40),12 and another one, both a stereomicroscope (⫻6 tions of melanoma (Figure) indicate that dermoscopy
to ⫻16) and digital videomicroscopy (⫻6 to ⫻40)25 with has significantly higher discriminatory power, with es-
digital contrast and enhancement procedures, but none timated odds ratios of 76 (95% confidence interval [CI],
clearly distinguished their results. One study indepen- 25-223) vs 16 (95% CI, 9-31) for naked-eye examina-
dently assessed dermoscopy (with an unspecified instru- tion (P =.008). The weighted least squares, the robust-
ment) and high-frequency sonography.8 No authors stated resistant line, and other methods proposed by Moses et
that a skin lesion could not be diagnosed by dermos- al24 gave similar values. For dermoscopy and naked-eye
copy, and only one group7 stated that 4% of the photo- examination, respectively, the estimated positive likeli-
graphs were not suitable for evaluation. Various dermo- hood ratios were 9 (95% CI, 5.6-19.0) and 3.7 (95% CI,
scopic criteria have been used to diagnose melanoma: 2.8-5.3), and the estimated negative likelihood ratios, 0.11
pattern analysis for 6 studies and 7FFM criteria for 1 (95% CI, 0.05-0.18) and 0.27 (95% CI, 0.19-0.36). Ex-
study.4 Interobserver agreement for dermoscopy was as- ploratory analyses were performed to investigate whether
sessed simultaneously in only 1 study.11 diagnostic accuracy differed in subgroups defined by the
The spectrum of lesions examined is given in characteristics of the patients and diagnostic tests. No re-
Table 2. There were 2193 lesions, with 328 melano- lationship could be established between dermoscopic di-
mas. Sample size varied from 15 to 824 lesions. Mela- agnostic sensitivity and the number of lesions analyzed,
noma lesions represented 3% to 49% of the excised le- the percentage of melanoma lesions, or the dermoscope
sions. Most melanomas were thin (⬍0.76 mm) in the 4 or dermoscopic criteria used.
studies that provided such information. Nonmelanoma
lesions represented 1865 lesions. Their histologic find- COMMENT
ings were detailed in all but 1 study25; they were mainly
melanocytic lesions (67%-100% of all nonmelanoma Our results showed that, for dermatologists working
PSLs). No study gave demographic information on in- within specialized clinics and experienced in dermos-
cluded patients. copy, this technique has higher discriminatory power than

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Table 2. Main Results of the Selected Studies

No. of No. of
No. of Melanomas Nonmelanoma Sensitivity Specificity
No. of Melanomas ⬍0.76-mm Thick Lesions
Source Lesions (% of Lesions) (% of Melanomas) (% Melanocytic) Clinical Dermoscopy Clinical Dermoscopy
Benelli et al22 401 60 (15) 48 (80) 341 (99) 0.85 0.80* 0.55 0.89†
Carli et al11 15 4 (27) Not given 11 (100) 0.50 0.75‡ 0.82 0.91‡
Cristofolini et al10 220 33 (15) Not given 187 (97) 0.85 0.88* 0.75 0.79*
Dummer et al9 824 23 (3) Not given 801 (89) 0.65 0.96‡ 0.93 0.98‡
Krähn et al8 80 39 (49) 29 (74) 41 (100) 0.79 0.90‡ 0.78 0.93‡
Lorentzen et al7 232 49 (21) Not given 183 (78) 0.78 0.82§ 0.89 0.94§
Soyer et al12 159 65 (41) 38 (58) 94 (67) 0.94 0.94* 0.82 0.82*
Stanganelli et al25 262 55 (21) 24 (46) 207 (Not given) 0.67 0.93§ 0.84 0.94§

*Not significant (P ⱖ.05).


†P⬍.01.
‡Not done.
§P⬍.05.

1.0 mate of diagnostic accuracy of a test among primary studies


12-12 Dermoscopy
4 26
Clinical Examination
is not simply the calculation of the mean sensitivity and
0.9 10
8
9
25 10
25
the mean specificity of this test. Such an approach would
0.8 8 9
be inappropriate, because it is likely that different studies
11
0.7 4 26 used different explicit or implicit thresholds, so that a pri-
0.6 mary study with high sensitivity may have low specific-
Sensitivity

11
ity, and vice versa. That is why it is recommended, for each
0.5
primary study, to plot a scattergram of the true-positive
0.4 rate (sensitivity) against the false-positive rate (1−speci-
0.3 ficity), which are also the axes used for an sROC curve.15
0.2 The odds ratio of each primary study can be combined,
allowing the 95% CI to be calculated and statistical com-
0.1
parisons between different diagnostic tests to be made. Fur-
0.0
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
thermore, it is possible to calculate estimated positive and
1–Specificity negative likelihood ratios for dermoscopy for the detec-
tion of melanoma, which are more useful for clinicians than
Summary receiver operating characteristic curves showing the
discriminatory powers of both naked-eye examination (triangles,
odds ratios. As dermoscopy achieved likelihood ratios far
discontinuous curve) and dermoscopy (circles, continuous curve) for from 1, this technique seemed an accurate diagnostic test.
melanoma diagnosis. The closer the curve comes to the upper left-hand It should be noted that values greater than 10 or less than
corner of the graph, the better the test. The curves suggest the superiority 0.1 are considered to generate large and often conclusive
of dermoscopy over naked-eye examination. Numbers next to triangles or
circles correspond to the reference citations of the studies analyzed. See changes from pretest to posttest probability, and values
“Methods” section for details. of 5 to 10 and 0.1 to 0.2, moderate but substantial shifts
of these probabilities.34 Thus, this technique gives pre-
cise information on the confidence clinicians may have in
does naked-eye examination to detect melanoma in a PSL. a test to detect or exclude a disease, ie, with dermoscopy
As other studies have shown that dermoscopy increased of a PSL to exclude melanoma and to decide not to excise
the diagnostic ability only when performed by formally a clinically doubtful lesion. However, this technique is com-
trained operators,17,32,33 dermatologists should make ev- plex, particularly when subgroup analysis or modeling is
ery efforts to master this useful tool. done. Therefore, someone with methodologic expertise
These conclusions are more favorable for dermos- should be included in the research team,18 as in our study.
copy than those of Mayer’s systematic review.13 One ex- As for all meta-analyses, one important limitation is
planation is that she selected only 2 studies on this is- publication bias, with small studies on dermoscopy or with
sue, whereas we retained 5 additional studies published negative results not having been submitted or accepted for
later and another study published in German. publication. We tried to limit this handicap by conduct-
Moreover, we were able to obtain a quantitative sum- ing a comprehensive search in 4 different databases, in-
mary of the diagnostic efficacy of dermoscopy by apply- cluding 2 databases potentially covering studies unpub-
ing meta-analysis methods adapted for the evaluation of lished in the peer-reviewed medical literature. This strategy
diagnostic tests.15,16,18,24 To the best of our knowledge, we proved useful, because overlaps between these databases
have used this approach for the first time in dermatology, were small. The selection of relevant studies followed
as a MEDLINE search (data not shown) did not find any strictly established guidelines,15,18 with extensive evalua-
meta-analysis for diagnosis of skin diseases. Indeed, meta- tion of the design and validity of selected studies. How-
analyses are more commonly conducted to examine treat- ever, because we retained only studies that met predeter-
ments or prognosis. In fact, obtaining a summary esti- mined quality criteria, numerous others were rejected.

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moscopy by missing some false-negative cases. Notably,
the clinical threshold for considering a lesion sufficiently
suspect to be excised seemed to have been set low (at least
2 ABCDE criteria) in the 2 studies that gave this informa-
Positive Likelihood Ratio Negative Likelihood Ratio tion. Fourth, data concerning intraobserver and interob-
Clinical Dermoscopy Clinical Dermoscopy server variability were absent or sparse in most selected
1.91 7.18 0.27 0.23
studies. However, satisfactory reproducibility of the der-
2.75 8.25 0.61 0.28 moscopy results was shown in most studies specifically
3.45 4.21 0.20 0.15 addressing that issue.11,17,22
10.66 76.62 0.37 0.04 Nevertheless, several points enhance the value of der-
3.62 7.18 0.26 0.23 moscopy in detecting melanoma. First, its superiority to
7.10 13.58 0.25 0.20 clinical examination was demonstrated despite the high
5.19 5.19 0.08 0.08
4.22 16.00 0.39 0.08
sensitivity and specificity of the clinical diagnosis of mela-
noma reported in most selected studies, as compared with
figures usually published.38 This finding may be ex-
plained by the expertise in PSLs of most investigators,
rather than by the high percentage of melanomas among
the lesions examined. Second, mostly highly equivocal
(ie, mainly or exclusively melanocytic) benign lesions and
This approach explains, at least partially, why we were thin, early melanomas, presumably difficult to diagnose
unable to explore with adequate statistical power an- but highly curable by complete excision, were exam-
other objective of such a meta-analysis, the effect of vari- ined. In this situation, sensitivity and specificity of the
ability of study design (eg, instrument or dermoscopic di- technique are expected to decrease. However, although
agnostic criteria used, percentage of melanomas among the dermoscopy seems to have all the qualities required for
lesions, types of nonmelanoma lesions, total number of a good diagnostic test—accuracy, absence of adverse effect,
lesions examined, or setting) on accuracy estimates. In- target disorder dangerous if left undiagnosed, and effec-
deed, before attempting to extrapolate our findings, it must tive treatment of the disease when diagnosed early34—
be recalled that the diagnostic efficacy of the handheld, its usefulness, which means providing information be-
low-magnification, inexpensive dermoscope was not shown yond that otherwise available and inciting a change of
to be significantly superior to clinical examination in the patient treatment, remains to be proved.
only study to test that instrument.10 All other studies in- To provide better evidence of the usefulness of der-
vestigated instruments with higher magnification rates, moscopy, future research should address the following
such as stereomicroscope, videomicroscope, or the less ex- issues. Studies should be undertaken to analyze, in the
pensive Dermaphot, which dramatically increases the mag- standard dermatology practice, a more representative mix-
nification of the lesion by the projection on a screen, but ture of melanoma and benign PSLs, as well as studies
is not suitable to give immediate information. Concern- aimed to lower the number of unknown false-negative
ing the dermoscopic criteria for melanoma used, only one results. The value of the handheld low-magnification der-
study22 used structured explicit criteria such as 7FFM35 matoscope needs to be assessed. However, the most im-
or ABCD,21 which have been reported to have increased portant issue would be to prove in a large patient popu-
sensitivity and specificity for detecting melanoma.5,36 Most lation that, with dermoscopy, it is possible to reduce the
studies examined a distorted spectrum of PSLs, with far number of excision biopsies performed for nonmela-
too many melanoma and too few nonmelanocytic PSLs, noma PSLs while increasing the number of thin mela-
such as seborrheic keratoses, as compared with their fre- nomas excised or, at least, without increasing the num-
quency in usual dermatology consultant practices. As der- ber of melanomas missed.
moscopy is a subjective interpretation of images, a high
number of melanomas in the sample may modify the Accepted for publication April 30, 2001.
threshold of the observer to conclude that melanoma is The authors received no outside support for this study.
present. Finally, as all selected studies were conducted in We thank Janet Jacobson for editing our English and
clinics with expertise on PSLs, the place of dermoscopy Marie-Dominique Allen for her help in searching comput-
in general dermatology practice remains unknown. erized databases.
Some limitations of the selected studies are, never- Corresponding author: Philippe Saiag, MD, Service de
theless, obvious. First, although pathologists may vary in Dermatologie, Hôpital Ambroise Paré, 9, av Charles-de-
classifying PSLs,37 only a few studies commented on how Gaulle, 92104 Boulogne CEDEX, France (e-mail:
the standard criterion was reached. Second, in some se- dermato.dermato@apr.ap-hop-paris.fr).
lected studies, naked-eye examination and dermoscopy
were not performed totally independently, and dermos- REFERENCES
copy could have “improved” the accuracy of the clinical
diagnosis proposed. Third, the impact of the verification
bias (mainly clinically equivocal lesions were excised) pre- 1. Hall HI, Miller DR, Rogers JD, Bewerse B. Update on the incidence and mortality
from melanoma in the United States. J Am Acad Dermatol. 1999;40:35-42.
sent in most studies must be considered. Although Stan- 2. Menzies SW, Ingvar C, Crotty KA, McCarthy WH. Frequency and morphologic
ganelli et al25 gave reassuring indirect information on that characteristics of invasive melanomas lacking specific surface microscopic fea-
issue, such studies may overestimate the sensitivity of der- tures. Arch Dermatol. 1996;132:1178-1182.

(REPRINTED) ARCH DERMATOL / VOL 137, OCT 2001 WWW.ARCHDERMATOL.COM


1349

©2001 American Medical Association. All rights reserved.


Downloaded From: http://archderm.jamanetwork.com/ by a University of North Dakota User on 05/28/2015
3. Seidenari S, Pellacani G, Pepe P. Digital videomicroscopy improves diagnostic 22. Benelli C, Roscetti E, Dal Pozzo V. Reproducibility of a dermoscopic method (7FFM)
accuracy for melanoma. J Am Acad Dermatol. 1998;39:175-181. for the diagnosis of malignant melanoma. Eur J Dermatol. 2000;10:110-114.
4. Benelli C, Roscetti E, Pozzo VD, Gasparini G, Cavicchini S. The dermoscopic ver- 23. Thomas L, Tranchand P, Berard F, Secchi T, Colin C, Moulin G. Semiological value
sus the clinical diagnosis of melanoma. Eur J Dermatol. 1999;9:470-476. of ABCDE criteria in the diagnosis of cutaneous pigmented tumors. Dermatol-
5. Nachbar F, Stolz W, Merkle T, et al. The ABCD rule of dermatoscopy: high pro- ogy. 1998;197:11-17.
spective value in the diagnosis of doubtful melanocytic skin lesions. J Am Acad 24. Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diag-
Dermatol. 1994;30:551-559. nostic test into a summary ROC curve: data-analytic approaches and some ad-
6. Steiner A, Pehamberger H, Wolff K. In vivo epiluminescence microscopy of pig- ditional considerations. Stat Med. 1993;12:1293-1316.
mented skin lesions, II: diagnosis of small pigmented skin lesions and early de- 25. Stanganelli I, Serafini M, Bucchi L. A cancer-registry–assisted evaluation of the
tection of malignant melanoma. J Am Acad Dermatol. 1987;17:584-591. accuracy of digital epiluminescence microscopy associated with clinical exami-
7. Lorentzen H, Weismann K, Petersen CS, Larsen FG, Secher L, Skodt V. Clinical nation of pigmented skin lesions. Dermatology. 2000;200:11-16.
and dermatoscopic diagnosis of malignant melanoma: assessed by expert and 26. Stanganelli I, Raccagni AA, Baldassari L, Calista D, Serafini M, Bucchi L. Analy-
non-expert groups. Acta Derm Venereol. 1999;79:301-304. sis of Breslow tumor thickness distribution of skin melanoma in the Italian re-
8. Krähn G, Gottlober P, Sander C, Peter RU. Dermatoscopy and high frequency gion of Romagna, 1986-1991. Tumori. 1994;80:416-421.
sonography: two useful non-invasive methods to increase preoperative diag- 27. EUCAN [database online]. Cancer incidence, mortality, and prevalence in the Eu-
nostic accuracy in pigmented skin lesions. Pigment Cell Res. 1998;11:151-154. ropean Union. 1996 estimates. Available at: http://www-dep.iarc.fr/eucan/
9. Dummer W, Doehnel KA, Remy W. Videomicroscopy in differential diagnosis of eucan.htm. Accessed September 6, 2000.
skin tumors and secondary prevention of malignant melanoma [in German]. Hau- 28. Carli P, De Giorgi V, Donati E, Pestelli E, Giannotti B. Epiluminescence micros-
tarzt. 1993;44:772-776. copy reduces the risk of removing clinically atypical, but histologically com-
10. Cristofolini M, Zumiani G, Bauer P, Cristofolini P, Boi S, Micciolo R. Dermatos- mon, melanocytic lesions. G Ital Dermatol Venereol. 1994;129:599-605.
copy: usefulness in the differential diagnosis of cutaneous pigmentary lesions. 29. Ascierto PA, Palmieri G, Celentano E, et al, for the Melanoma Cooperative Study.
Melanoma Res. 1994;4:391-394. Sensitivity and specificity of epiluminescence microscopy: evaluation on a sample
11. Carli P, De Giorgi V, Naldi L, Dosi G. Reliability and inter-observer agreement of of 2731 excised cutaneous pigmented lesions. Br J Dermatol. 2000;142:893-
dermoscopic diagnosis of melanoma and melanocytic naevi. Eur J Cancer Prev. 898.
1998;7:397-402. 30. Rao BK, Marghoob AA, Stolz W, et al. Can early malignant melanoma be differ-
12. Soyer HP, Smolle J, Leitinger G, Rieger E, Keri H. Diagnostic reliability of der- entiated from atypical melanocytic nevi by in vivo techniques? I: clinical and der-
moscopic criteria for detecting malignant melanoma. Dermatology. 1995;190: moscopic characteristics. Skin Res Technol. 1997;3:8-14.
25-30. 31. Pazzini C, Pozzi M, Betti R, Vergani R, Crosti C. Improvement of diagnostic ac-
13. Mayer J. Systematic review of the diagnostic accuracy of dermatoscopy in de- curacy in the clinical diagnosis of pigmented skin lesions by epiluminescence
tecting malignant melanoma. Med J Aust. 1997;167:206-210. microscopy. Skin Cancer. 1996;11:159-161.
14. D’Agostino RB, Weintraub M. Meta-analysis: a method for synthesizing re- 32. Stanganelli I, Bucchi L. Epiluminescence microscopy versus clinical evaluation
search. Clin Pharmacol Ther. 1995;58:605-616. of pigmented skin lesions: effects of operator’s training on reproducibility and
15. Irwig L, Tosteson AN, Gatsonis C, et al. Guidelines for meta-analyses evaluating accuracy. Dermatology. 1998;196:199-203.
diagnostic tests. Ann Intern Med. 1994;120:667-676. 33. Binder M, Puespoeck-Schwarz M, Steiner A, et al. Epiluminescence microscopy
16. Irwig L, Macaskill P, Glasziou P, Fahey M. Meta-analytic methods for diagnostic of small pigmented skin lesions: short-term formal training improves the diag-
test accuracy. J Clin Epidemiol. 1995;48:119-132. nostic performance of dermatologists. J Am Acad Dermatol. 1997;36:197-202.
17. Binder M, Schwarz M, Winkler A, et al. Epiluminescence microscopy: a useful 34. Jaeschke R, Guyatt GH, Sackett DL. User’s guide to the medical literature, III:
tool for the diagnosis of pigmented skin lesions for formally trained dermatolo- how to use an article about a diagnostic test: what are the results and will they
gists. Arch Dermatol. 1995;131:286-291. help me in caring for my patients? JAMA. 1994;271:703-707.
18. Cochrane Methods Working Group on Systematic Review of Screening and Di- 35. Dal Pozzo V, Benelli C, Roscetti E. The seven features for melanoma: a new der-
agnostic Tests. Recommended methods, updated June 6, 1996. Available at: http:// moscopic algorithm for the diagnosis of malignant melanoma. Eur J Dermatol.
www.cochrane.org/cochrane/sadt.htm. Accessed September 2, 2000. 1999;9:303-308.
19. Jaeschke R, Guyatt GH, Sackett DL. User’s guide to the medical literature, II: how 36. Binder M, Kittler H, Steiner A, Dawid M, Pehamberger H, Wolff K. Reevaluation
to use an article about a diagnostic test: are the results of the study valid? JAMA. of the ABCD rule for epiluminescence microscopy. J Am Acad Dermatol. 1999;
1994;271:389-391. 40:171-176.
20. Pehamberger H, Steiner A, Wolff K. In vivo epiluminescence microscopy of pig- 37. Krieger N, Hiatt RA, Sagebiel RW, Clark WH Jr, Mihm MC Jr. Inter-observer vari-
mented skin lesions, I: pattern analysis of pigmented skin lesions. J Am Acad ability among pathologists’ evaluation of malignant melanoma: effects upon an
Dermatol. 1987;17:571-583. analytic study. J Clin Epidemiol. 1994;47:897-902.
21. Stolz W, Riemann A, Cognetta AB, et al. ABCD rule of dermatoscopy: a new prac- 38. Miller M, Ackerman AB. How accurate are dermatologists in the diagnosis of mela-
tical method for early recognition of malignant melanoma. Eur J Dermatol. 1994; noma? degree of accuracy and implications. Arch Dermatol. 1992;128:559-
4:521-527. 560.

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