ARTICLE
Dermoscopy, dermatoscopy or epiluminescence microscopy is a technique
for the in vivo diagnosis of pigmented skin lesions. It implies
the use of a microscope, simple or compound: the compound microscopes
or stereomicroscopes are expensive and cumbersome, therefore they cannot
be used for the screening of pigmented skin lesions in daily office practice.
On the contrary simple microscopes are handy, cheap and suitable for daily
use. Various diagnostic methods for the simple microscope or dermatoscope
have been developed: the ABCD rule of Dermatoscopy [1, 3], the methods
developed by Nilles et al. [4], Menzies et al. [5-7], the
Seven features for melanoma (7FFM) developed by us [8-11], the method
developed by Argenziano et al. [12].
All these methods have been developed (training set) and tested (test
set) on dermoscopic slides and have all achieved good values of both sensitivity
or specificity.
However, the standard conditions used to observe dermoscopic slides
are quite different from those present in a dermatology clinic: it is
quite difficult to observe a lesion with a dermatoscope for more than
30 seconds, while when observing a slide more time can easily be taken.
Besides, due to the fact that all these studies are retrospective, a possible
bias from a known histological diagnosis of the slide under examination
can not be excluded.
The sensitivity and the specificity of dermoscopic methods are usually
compared with the sensitivity and specificity of the clinical diagnosis
for melanoma reported in literature, i.e. historical controls have
been used, and the method utilized for obtaining a clinical diagnosis
are usually unreported. Even in the few works where the clinical and the
dermoscopic diagnosis of the same lesions are compared [13-14] the clinical
methods utilized are not clearly described.
For these reasons we decided to start a prospective study, one year
long, where the clinical and the dermoscopic diagnosis of pigmented skin
lesions were expressed only on the basis of the clinical and dermoscopic
view of the lesions under examination, before the lesions were excised.
This article presents an analysis of the results.
Material and methods
This study concerns all the pigmented skin lesions observed and excised
at the Dermatologic Surgery Department of the Dermatologic Sciences Institute,
IRCCS, University of Milan, from September 1 1997 to September 30 1998.
The real time scale of the study is twelve months because in August our
Department is closed. The decision to excise the lesions was taken by
three dermatologists (V.D.P., G.G., S.C.) separate from those (C.B., E.R.)
who subsequently clinically and dermoscopically evaluated the lesions,
before excision, on the day of the surgical operation, i.e. the
evaluation did not change the decision to excise the lesions.
The clinical evaluation was made on the five ABCDE criteria: criterion
A was defined as geometrical asymmetry on the two axes of the tumor, criterion
B as irregular (ragged or indented) border, criterion C as presence of
at least two different colors within the lesion (except the usual symmetrical
darkening of the lesion in its center, typical of juctional nevi), criterion
D as a maximum diameter > 6 mm, criterion E, an anamnestic criterion
based on the patient's description of the evolution including in this
term elevation, enlargement or change in the color of the lesion [15].
Dermoscopically the lesions were evaluated with the method we have developed
(7FFM).
Our method has two stages: in the first stage one decides if the lesion
under examination is melanocytic in nature, following the dermoscopic
algorithm used to distinguish melanocytic from non-melanocytic lesions
[1-3, 8-11].
The algorithm is as follows: the lesions showing network or globules
are regarded as melanocytic. The presence of horny pseudocysts and comedo-like
openings, without a network or globules, suggests seborrheic keratosis.
Maple leaf-like areas at the periphery suggest basal cell carcinoma, a
homogeneous blue coloring points to blue nevus, while red-blue areas are
typical of angioma and angiokeratoma. If none of these features is present
the lesion is regarded and evaluated as melanocytic.
The second stage, used to evaluate only the lesions considered as melanocytic,
is based on the seven dermoscopic features that a statistical analysis
on a training set of 218 cutaneous pigmented lesions showed significant
for malignancy. They were divided into major and minor features according
to statistical significance, sensitivity and specificity. The major features
were pseudopods, radial streaming, regression-erythema and gray-blue
veil; the minor features were unhomogeneity, irregular pigment
network and sharp margin.
These features are regarded as present or absent in the lesion under
examination. The different features of the pigment network, defined by
the Consensus Conference held in Hamburg in 1989 [16], were grouped as
regular and irregular networks.
The regular network has thin lines, a close mesh net and is uniform
throughout the lesion. The irregular network is thick, has a wide mesh
net and shows varying features in the same lesion.
To the classical dermoscopic features we added two new ones, detected
during our experience, namely Regression-Erythema and Unhomogeneity. The
term Regression-Erythema defines the disappearance of dermoscopic features
in a given area of the lesion, while diffuse erythema, possibly with a
few angiectases, is observed.
Unhomogeneity is an asymmetrical or irregular distribution in the lesion
of at least two dermoscopic features not necessarily predictive of malignancy.
Other authors in previous studies proposed dermoscopic features similar
to unhomogeneity.
Nilles et al. [4] considered an asymmetrical pigment distribution
(no relation with dermoscopic features) with four different grades of
severity. Kenet et al. [17] described a multicompetent pattern
which consists of three or more discrete regions with different ELM appearances,
including a darkly pigmented region with broadened network. As it is described,
the multicompetent pattern appears very different from unhomogeneity and
a higher magnification than that obtained with a dermatoscope is probably
necessary to detect it.
The Sharp Margin is regarded as such when an area of diffuse pigmentation
with an abrupt ending is present on at least one fourth of the margin
of the lesion.
The pigment network and the other dermoscopic features of the method
are not evaluated for sharp margin.
Pseudopods are considered predictive of malignancy when they display
an irregular distribution: in fact, epithelioid and/or spindle cell nevi
usually present pseudopods regularly distributed [18].
Following such selection we attributed a score 2 to the major features
and a score 1 to the minor features. The lesions where the sum of the
features gave a score of > or = 2 were diagnosed as being malignant,
therefore to make a diagnosis of melanoma, the presence of one major feature
or the concurrent presence of two minor features was regarded as sufficient.
The clinical and dermoscopic pre-operating evaluation of each lesion
by two dermatologists (C.B. and E.R.) was recorded in a register, the
lesion was measured and clinical and dermoscopic photographs were taken.
All the lesions were excised and histologically examined.
At the subsequent histopathological examination the lesions were classified
as follows:
Junctional melanocytic nevi: 45
Mainly junctional compound melanocytic nevi: 28
Compound melanocytic nevi: 123
Congenital compound melanocytic nevi: 34
Mainly dermal compound nevi: 7
Blue nevi: 5
Melanocytic nevi showing regression and inflammatory infiltrate: 68
Combined melanocytic nevi: 6
Epithelioid and/or spindle cell nevi: 18
Lentigo simplex: 5
Seborrheic keratoses: 1
Basal cell carcinoma: 1
Melanomas: 60 of which: 6 in situ, 42 < 0.75 mm thick, 8 0.76-1.5
mm thick, 4 1.5-4 mm thick (mean 0.60 mm, median 0.55 mm, max 1.9 mm,
min 0.10 mm, SD 0.45).
Statistical analysis
The clinical criteria and the dermoscopic features were evaluated as
present or absent.
A present clinical criterion was rated as 1 and an absent criterion
as 0. The sensitivity and the specificity in the diagnosis of melanoma
for each clinical criterion has been reported.
The sensitivity of a clinical criterion is the proportion of all cases
of histologically proved melanomas that show the criterion. The specificity
of a clinical criterion is the proportion of all cases histologically
proved not to be melanomas that do not show the criterion (Table
I).
The score of each lesion is the sum of the clinical criteria present
in the lesion, therefore the clinical score may range from 0 to 5. In
relation to the number of criteria, i.e. the score, whose presence
is considered necessary to classify as malignant a lesion, various diagnostic
methods can be obtained. The sensitivity, specificity, predictive value
positive, predictive value negative, efficiency and accuracy for each
score have been calculated.
The sensitivity of the diagnostic method is the proportion of all cases
of histologically proved melanomas that were clinically diagnosed as melanomas.
The specificity of the diagnostic method is the proportion of all cases
histologically proved not to be melanomas that were clinically diagnosed
as not melanomas. The predictive value positive is the proportion
of all cases clinically diagnosed as melanomas that were histologically
proved to be melanomas The predictive value negative is the proportion
of all the cases clinically diagnosed not to be melanomas that were histologically
proved not to be melanomas. The efficiency of the diagnostic method is
the proportion of all cases (melanomas and non melanomas) clinically and
histologically correctly diagnosed. The accuracy of the diagnostic method
is the proportion of cases in which the clinical diagnosis of melanoma
was correct (Table I).
The sensitivity, specificity, predictive value positive, predictive
value negative, efficiency and accuracy of the dermoscopic diagnostic
method (7FFM) have been calculated. To evaluate the difference of diagnostic
power, between the various clinical scores and the dermoscopic method
(7FFM), for both sensitivity and specificity, chi squared tests have been
calculated. The Fischer's exact test was also applied for the scores showing
an expected value < 6 in the 2 x 2 tables.
A P value less than 0.05 has been considered statistically significant.
Finally values of sensitivity, specificity, predictive value positive,
predictive value negative, efficiency and accuracy of the dermoscopic
diagnostic method plus each clinical criterion and plus the various clinical
scores have been reported.
Results
On the basis of the analysis by the two dermatologists (C.B., E.R.)
who, pre-operating, evaluated the lesions, the clinical criteria were
rated as follows: asymmetry was present in 40 melanomas and in 133 nevi,
irregular border in 11 melanomas and 52 nevi, irregular colour in 41 melanomas
and in 155 nevi, diameter was > 6 mm in 46 melanomas (mean diameter
of melanomas 11 mm, median 9 mm, minimum 3 mm, maximum 40 mm, SD 8 mm)
and in 141 nevi (mean diameter of nevi 7 mm, median 6 mm, minimum 3 mm,
maximum 20 mm, SD 3 mm), evolution in 29 melanomas and in 92 nevi.
The specificity and sensitivity of the clinical criteria for the diagnosis
of melanoma are reported in Table
II.
Sensitivity, specificity, predictive value positive, predictive value
negative, efficiency and accuracy for the various clinical score ranging
from 1 to 5 (on the basis of the presence of at least 1 clinical criterion
to all 5 clinical criteria) and for the dermoscopic method 7FFM are reported
in Table III.
As shown, 7FFM presents well-balanced values of both sensitivity and
specificity (80% and 89.1%) while the clinical scores are all pretty unbalanced.
The twelve melanomas which resulted false negatives with 7FFM presented
a mean thickness of 0.39 mm, median 0.34 mm, minimum 0.1 mm, maximum 1
mm, three melanomas were in situ.
The lesions which resulted false positives with 7FFM were histologically
classified as: 18 compound nevi, 11 nevi with regression and/or inflammatory
infiltrate, 3 juctional nevi, 2 compound mainly juctional nevi, 2 combined
nevi, 1 compound mainly dermal nevus, 1 Spitz nevus.
According to the surgical register the three dermatology surgeons correctly
diagnosed pre-operating 42 melanomas out of 60. The maximum thickness
of the melanomas misdiagnosed by dermatology surgeons was 1 mm, the maximum
diameter was 10 mm. The dermoscopic method correctly diagnosed 7 of these
18 melanomas. Some examples of the lesions evaluated are given in Figs.
1-4.
P values obtained with chi squared test (with Fisher's exact test for
sensitivity of score 1 and 5 versus 7FFM, and for specificity of
score 5 versus 7FFM) for the different diagnostic power between
7FFM and each clinical score are: for sensitivity p < 0.05 for score
1, p not significant for score 2, p < 0.05 for score 3, p < 0.001
for scores 4 and 5; for specificity, p < 0.001 for scores 1, 2 and
3, p < 0.01 for score 4, p < 0.001 for score 5.
Finally we decided to evaluate if the sensitivity and the specificity
of our dermoscopic method 7FFM can be improved with the adjunct of one
of the clinical criterion or one of the clinical scores. 7FFM + asymmetry
means that are regarded as malignant all the lesions that show asymmetry
or that are diagnosed as malignant with 7FFM; 7FFM + score 3 (at least
3 clinical criteria) means that are regarded as malignant all the lesions
that show 3 clinical criteria or that are diagnosed as malignant with
7FFM.
Sensitivity, specificity, predictive value positive, predictive value
negative, efficiency and accuracy for each clinical criterion plus dermoscopic
method are shown in Table IV.
Sensitivity, specificity, predictive value positive, predictive value
negative, efficiency and accuracy for the various clinical scores plus
the dermoscopic method (i.e. at least 1 clinical criterion plus
dermoscopic method, at least 2 clinical criteria plus dermoscopic method,
and so on) are reported in Table
V.
As shown, the improvement in sensitivity always brings about a loss
in specificity. Best values for sensitivity and predictive value negative
are obtained with diameter plus 7FFM (91.6% and 97.3%) and with score
2 plus 7FFM (93.3% and 97.3%). The five melanomas false negative with
D + 7FFM have a thickness of 1, 0.49, 0.4, 0.1 mm; the four melanomas
false negative with score 2 + 7FFM have a thickness of 1, 0.74, 0.49,
0.37 mm.
Discussion
Studies about the sensitivity in the clinical diagnosis of melanoma
report a mean rate of 67%, the various rates ranging from 48 to 81% [19]
the variability in the results is probably due to both the thickness of
melanomas evaluated and the experience of the examining physicians. The
sensitivity in the clinical diagnosis of the dermatologists (V.D.P., G.G.,
S.C.), who decided on the excision of the lesions of this study, was 70%,
a little above the mean rate reported in literature. The ABCDE rule for
the clinical diagnosis of melanoma is the most widely used clinical method
for the screening of pigmented skin lesions. However 10% or so of melanomas
flagrantly disregard this rule and many nevi also display one or more
ABCDE criteria. In a recent paper Thomas et al. [20] evaluated
the semiological value of the ABCDE rule obtaining results similar to
ours for criteria A, C, and D but a better sensitivity for B and E (57%
and 84% versus 18.3% and 48.3%). Also the scores in function of
the number of ABCDE criteria present obtained similar results except for
sensitivity with score 5 (43% versus 6.6%) and specificity for
scores 1 and 2 ( 36% and 65.3% versus 12.9% and 44.5%) This may
be due to the fact that the nevi used by Thomas et al. [20] were
not all lesions excised during the same lapse of time in which melanomas
were excised, but the frame of time for the control group was shorter
than that of the melanoma group. Besides that, the non melanoma group
of Thomas et al. encompassed more non melanocytic pigmented skin
lesions (40 lesions) than in the panel of our study (2 lesions) and this
may be another reason for the different results.
In this clinical trial with our dermoscopic method 7FFM we have obtained
a decrease in sensitivity (80% versus 94.6%) and an increase in
specificity (89.1% versus 85.5%) compared with our previous results
[11]. A part from the different conditions of the test (clinical versus
slide observation) this may be due to the difference of thickness of the
melanomas evaluated in the two studies (mean thickness of melanomas in
the previous study 0.92 mm versus 0.6 mm) [11].
Our method 7FFM compared with the clinical scores displays a better
balanced value of sensitivity and specificity and a better value of predictive
value negative. Of interest, score 3 displays a sensitivity value identical
to the clinical mean rate of sensitivity reported in literature [18] pointing
to the fact that the clinical diagnosis of melanoma is more frequently
made when at least 3 ABCDE criteria are present. Our method 7FFM has both
sensitivity and specificity better than score 3 and the difference of
diagnostic power is statistically significant (p < 0.05 for sensitivity
and p < 0.001 for specificity).
To evaluate if the sensitivity of our dermoscopic method may be improved
with the addition of a clinical criterion or a clinical score we evaluated
values of 7FFM plus each ABCDE criterion and of 7FFM plus each score.
For clinical criterion plus 7FFM best values are obtained with diameter
> 6 mm with a sensitivity of 91.6%, a specificity of 52.8% and a predictive
value negative of 97.3%.
The score plus 7FFM that yields better results is score 2 with a sensitivity
of 93.3%, a specificity of 42.2% and a predictive value negative of 97.3%.
This is in accordance with Thomas et al. [20] who on the basis
of their data suggested score 2 as the clinical score giving the best
values of sensitivity.
In conclusion in this prospective clinical trial our diagnostic dermoscopic
method 7FFM confirms good values of both sensitivity and specificity;
the sensitivity can be improved with the adjunct of the clinical evaluation,
particularly with score 2.
We think that our method plus the clinical evaluation can be used for
the screening of pigmented skin lesions in daily office practice.
CONCLUSION
Acknowledgements
This study has been supported with grants from Fondazione Polizzotto
via S. Pietro all'Orto, 9 Milan, Italy.
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