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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
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-
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
*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-
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§
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.