ARTICLE
The diagnosis of early melanoma is a challenge that dermatologists face
every day. In fact this tumor can be completely cured with surgery if
discovered at an early stage, i.e. with a maximum thickness less
than 0.75 mm. According to some statistics, the clinical diagnosis of
melanoma has a mean sensitivity of 67%, (range 48 to 81% according both
to the physician's ability, dermatologists having better results than
general practitioners, and to the type of melanoma, the thinner the melanoma
the more difficult the diagnosis) [1].
Among the new techniques developed to ameliorate the clinical diagnosis,
dermoscopy or epiluminescence microscopy is one of the more promising.
Epiluminescence microscopy can be performed either with a simple or a
compound microscope. The simple microscope yields an image at a fixed
10x magnification, is small, handy and suitable to be used in an outpatient
practice for the screening of pigmented skin lesions. Stolz proposed in
1994 a diagnostic method for the dermoscopic diagnosis of pigmented skin
lesions with a simple microscope that he called the ABCD rule of Dermoscopy
[2-4]. In 1996 we developed a simplified diagnostic dermoscopic method
which evaluated the presence or the absence of only seven dermoscopic
features: we called the method Seven features for melanoma (7FFM) [5-8].
The dermoscopic diagnosis, as the clinical diagnosis of pigmented skin
lesions, is based on the analysis of a visual image and is a subjective
diagnosis. The reliability of a diagnostic test or method depends on the
reproducibility of the interpretation or result on a given specimen. Therefore,
the usefulness of a diagnostic dermoscopic method, in the screening of
pigmented skin lesions, is mainly dependent on the rate of concordance
among different observers in the interpretation of the dermoscopic features
present in the lesion under examination.
To inform people about our method and to evaluate its reproducibility
we held eight dermoscopy courses from October 1996 to April 1998 which
were attended by 207 dermatologists.
At the end of the course the participants had a self-examination test
where they evaluated a set of dermoscopic slides with our method.
This article presents an analysis of their evaluations.
Material
From October 4, 1996 to April 3, 1998 we held eight courses in dermoscopy
to present our dermoscopic diagnostic method. A total of 207 dermatologists
attended our courses. Each course lasted about six hours, from 9.30 a.m.
to 17.30 p.m. In the morning session we presented the principles of dermoscopy,
the correlation between dermoscopic features and histopathology, the dermoscopic
features of non melanocytic and melanocytic skin tumors.
In the afternoon session, the various diagnostic dermoscopic methods
were shown, including the one developed by us, and finally the participants
were asked to execute a self-examination test using our diagnostic test.
The self-examination test was formed of 25 dermoscopic slides of pigmented
skin lesions. Histologically the lesions proved to be: seborrhoeic keratoses
2, pigmented basal cell carcinoma 1, blue nevus 1, Spitz nevus 1, compound
nevi 9, melanomas 11.
The maximum diameter of the lesions was 1 cm, the maximum thickness
of melanomas was 0.63 mm. and the minimum thickness was 0.20 mm.
Each slide was projected for 45 seconds onto a screen of 2 x 2 m with
the observers at a distance of 3-5 m.
The courses were held in the following Italian cities, on the dates
indicated and were attended by the respective number of dermatologists:
Course held in Milan, 10/04/96 attended by 25 dermatologists.
Course held in Milan, 05/23/97 attended by 26 dermatologists.
Course held in Milan, 10/24/97 attended by 30 dermatologists.
Course held in Bergamo, 11/15/97 attended by 31 dermatologists.
Course held in Milan, 11/29/98 attended by 24 dermatologists.
Course held in Turin, 01/16/98 attended by 24 dermatologists.
Course held in Milan, 03/20/98 attended by 23 dermatologists.
Course held in Padova, 04/03/98 attended by 24 dermatologists.
Diagnostic method
Our method (7FFM) has two steps: in the first step one decides if the
lesion under examination is melanocytic in nature, following the dermoscopic
algorithm used to distinguish melanocytic from non-melanocytic lesions
[2-8].
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 step, used to evaluate only the lesions considered as melanocytic,
is based on seven dermoscopic features that a statistical analysis on
a training set of 218 cutaneous pigmented lesions showed significant for
malignancy and were divided in to 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 [9] 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 lesions.
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 have proposed the concept of unhomogeneity
but in our opinion they did not define it in a way which is easy to understand
and to reproduce. Nilles et al. [16] considered an asymmetrical
pigment distribution (no relation with dermatoscopic features) with four
different grades of severity. Kenet et al. [14] described a multicompetent
pattern which consists of three or more discrete regions with different
ELM appearances, including a darkly pigmented region with a broadened
network. The multicompetent pattern as described 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 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 [10].
Following such selection we attributed a score 2 to the Major features
and a score 1 to the Minor features (Table I). The lesions where
the sum of the features gave a score of >= 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.
We called this method the Seven Features for Melanoma (7FFM) [5-8].
The method has been used to evaluate a test set of 713 pigmented skin
lesions: three different observers unaware of the clinical and personal
characteristics of patients recognized 159 out 168 melanomas and 466 out
of 545 benign lesions.
We obtained a sensitivity of 94.6%, a specificity of 85.5%, a predictive
value positive of 66.8%, a predictive value negative of 98.1% and an efficiency
of 87.6% [7]. In a prospective study of one year's length our method showed
a sensitivity of 80%, a specificity of 89.1%, a predictive value positive
of 54.4%, a predictive value negative of 96.2% and an efficiency of 87.7%
[8].
In the self-examination test of 25 slides proposed to the participants
of our courses the dermoscopic features were present as follows.
Unhomogeneity was present in 12 lesions, irregular pigment network in
11 lesions, gray-blue veil in 4 lesions, pseudopods in 3 lesions, regression-erythema
in 2 lesions, radial streaming in 1 lesion; no lesion showed a sharp margin.
Statistical analysis
The mean, the median, the minimum and the maximum number of correct
answers and the respective percentages of agreement were calculated.
To evaluate agreement between observers, i.e. inter-rater reliability,
a kappa statistic has been used.
Kappa statistic is the statistic most often used to measure agreement
between two observers on a binary variable. Kappa is defined as the agreement
beyond chance (i.e. observed agreement minus chance agreement),
divided by the amount of agreement possible beyond chance (i.e.
100% agreement minus chance agreement).
Kappa statistic is calculated as follows.
The correct answer has been considered as a judge 1, while each dermatologist
has been considered as a judge 2, therefore, for each dermatologist a
K value has been calculated.
The data observed have been displayed on a 2 x 2 table.
The observed agreement is O = (a + d)/n
The chance (expected) agreement is C = [(a + c)(a + b) + (b + d)(c +
d)]/n2
Kappa is k = (O C)/(1 C).
Kappa values may range between 1 and 1: negative results are
obtained when the agreement occurs less often than expected by chance,
K values 0-0.40 indicate poor agreement, 0.41-0.75 from fair to good agreement,
> 0.75 excellent agreement [11-12].
The mean, the median, the minimum, the maximum and the standard deviation
of the values obtained have been reported.
The mean percentages of agreement and kappa for each dermoscopic feature
with the respective median, minimum, maximum and standard deviation have
also been calculated.
The calculations have been performed with Microsoft Excel 4.0.
Results
A total of 201 tests out of 207 were suitable for statistical analysis.
An answer was considered correct when the score obtained gave a diagnosis
concordant with the one obtained by us and confirmed by the histological
examination (the test did not included false positives or false negatives).
The lesions with a score < 2 were considered non melanomas while the
lesions with a score >= 2 were considered melanomas. The mean value
of correct answers is 21.4, the median 22, the minimum 15, the maximum
25; the mean value of agreement is 85.7%, the median 88%, the minimum
60%, the maximum 100%.
The cumulative results of the dermoscopic courses are reported in the
histogram in Figure 1.
Kappa statistical analysis to evaluate inter-rater reliability gives
a mean K value of 0.699, median 0.684, minimum 0.219, maximum 1, standard
deviation 0.152.
The mean percentages of agreement for each dermoscopic feature are:
unhomogeneity 81.6%, irregular pigment network 79.2%, sharp margin 95.2%,
pseudopods 90.4%, radial streaming 88.7%, regression-erythema 95.1% and
gray-blue veil 89.2%.
The mean Kappa for each dermoscopic feature are: unhomogeneity 0.636,
irregular pigment network 0.587, pseudopods 0.513, radial streaming 0.34,
regression-erythema 0.602 and gray-blue veil 0.636. Sharp margin has no
K value because of its absence in all of the 25 lesions of the test.
The mean, the median, the minimum, the maximum and the standard deviation
of both percentages of agreement and kappa for each dermoscopic feature
are shown in Table 1.
Discussion
The first diagnostic method developed for epiluminescence microscopy
(ELM) was pattern analysis [13-15]. This method uses all ELM criteria
and is suited for stereomicroscopes (i.e. compound microscopes).
These instruments are used only by research centers, are cumbersome, expensive,
and therefore they cannot be used extensively for the screening of pigmented
skin lesions.
Stoltz in 1994 developed a diagnostic dermoscopic method for the dermatoscope
(i.e. simple microscope): he called the method the ABCD rule of
dermoscopy [2-4]. The method has a two step procedure: first it must be
determined whether a melanocytic or nonmelanocytic skin lesion is present.
If a melanocytic lesion is diagnosed the second step is to determine whether
this lesion is malignant, benign or suspicious.
The features considered in the second step were quite different from
those proposed in the consensus conference held in Hamburg in 1989 [9].
The ABCD rule of dermoscopy, used by the authors, showed good values of
both sensitivity (97.9%) and specificity (90.3%) for the diagnosis of
melanoma. In 1996 we proposed our method (7FFM) which presents a first
step identical to that of the ABCD rule of dermoscopy and a second step
with seven features more similar to those proposed in the consensus conference
[5-8]. Our method, the methods proposed by Nilles et al. in 1994
[16], by Menzies et al. in 1996 [17-19] and the more recent seven
point checklist based on pattern analysis [20] have both values of sensitivity
(94.6, 90, 92 and 95% respectively) and specificity (85.5, 85, 70 and
75% respectively) not significantly different from those obtained by Stoltz
et al.
These data should have smoothed the way for the extensive use of dermoscopy
in the screening of pigmented skin lesions, but the difficulty of learning
dermoscopy and the scarce data on reproducibility or diagnostic agreement
have clipped this technique's wings.
In fact Binder et al. [21] showed that ELM pattern analysis has
a low kappa value for ELM nonexperts, median K = 0.36, while ELM experts
presented a higher value median K = 0.56.
These authors underlined the fact that ELM criteria are often confusing
for non-experienced observers, reported that almost all studies about
the value of ELM are based on data derived from ELM experts and concluded
that a formal broad-based training in ELM should be offered to the dermatological
community.
In a subsequent paper [22] they evaluated the effect of short formal
ELM training on the diagnostic performance of 11 previously untrained
dermatologists, obtaining a significant improvement of their diagnostic
performance.
Some studies have been published about the reproducibility of dermoscopic
features among different observers. Stanganelli et al. [23], in
a study between two observers, concluded that the best K value (median
K = 0.77) was obtained in the evaluation of the presence or the absence
of ELM features. Lower values were obtained for distribution, for width,
thickness and size, and for pigmentation, of ELM features (median K 0.47,
0.39 and 0.21 respectively). In a study involving 12 dermatologists of
the reproducibility of ELM features and ELM diagnosis Stanganelli et
al. [24] found better values for ELM diagnosis (mean K = 0.65) than
for ELM features (mean K range = 0.14-0.49). Carli et al. [25]
found good K values for ELM criteria among 9 ELM experts (K range = 0.607-0.827
except pigment network K = 0.009).
In 1996, after having developed our method (7FFM), we decided to hold
some dermoscopic courses to offer a formal broad based training in dermoscopy
to our dermatological community.
The data on the agreement of the seven dermoscopic features of our method
among a large number of dermatologists show that they have a fair reproducibility
except for radial streaming (K range of dermoscopic features 0.636-0.513,
radial streaming K = 0.34).
Of interest, the agreement for the diagnosis of pigmented skin lesions
of our diagnostic method presented a better reproducibility than that
of the single dermoscopic features (mean K = 0.699), as obtained by Stanganelli
et al. [24].
Unhomogeneity and irregular pigment network are frequently mistaken
for each other and this explains the lower mean percentages of agreement
(81.6 and 79.2%) among the features of our method. These two features
may seem over-represented in our test but this is due to the fact that
all the melanomas of our test were thin melanomas (maximum thickness 0.63
mm) and, as shown by Argenziano et al. [26], unhomogeneity and
irregular pigment network are often present in thin melanomas.
The results of the self-examination tests point to a good reproducibility
of our method among dermatologists of our community. We were interested
in a global evaluation of the reproducibility of our method from dermatologists
of our community and for this reason we did not evaluate their level of
knowledge in dermoscopy with a pre-test.
We understand that the design of this study does not exactly reproduce
a real clinical situation, but it is the only practical way to inform
people about our method and to evaluate its reproducibility.
The number of cases tested was not high but this number should be a
compromise between the requirements of the study and compliance of the
participants to the test.
Besides, the cases selected were not representative of daily routine.
Also, all the melanomas evaluated were thin melanomas and the results
obtained indicate that our method is easy to learn.
As shown before, the sensitivity of our method is similar to that of
the dermoscopic diagnostic methods developed by other authors and we have
no reason to believe that these methods work worse than ours.
So far, they have not presented data about the reproducibility of their
methods.
Article accepted on 14/10/99
CONCLUSION
Acknowledgements
The Dermoscopic courses were held with grants from:
Course held in Milan, 10/04/96, Roerig Pharmaceutical Industry.
Course held in Milan, 05/23/97, Schering Pharmaceutical Industry.
Course held in Milan, 10/24/97, Schering Pharmaceutical Industry.
Course held in Bergamo, 11/15/97, Schering Pharmaceutical Industry and
EDRA Publishing House.
Course held in Milan, 11/29/98, Schering Pharmaceutical Industry and EDRA
Publishing House.
Course held in Turin, 01/16/98, Restiva Pharmaceutical Industry.
Course held in Milan, 03/20/98, Restiva Pharmaceutical Industry.
Course held in Padova, 04/03/98, Restiva Pharmaceutical Industry.
REFERENCES
1. Piepkorn M, Odland PB. Quality of care in the diagnosis of
melanoma and related melanocytic lesions. Arch Dermatol 1997; 133:
1393-6.
2. Stolz W, Braun-Falco O, Bilek P, Landthaler M, Cognetta AB.
Color Atlas of Dermatoscopy. Blackwell Science Ltd, 1994.
3. Stolz W, Riemann A, Cognetta AB, Pillet L, Abmayr W, Holzel
D, Bilek P, Nachbar F, Landthaler M, Braun-Falco O. ABCD rule of dermatoscopy:
a new practical method for early recognition of malignant melanoma. Eur
J Dermatol 1994; 4: 521-7.
4. Nachbar F, Stolz W, Merkle T. The ABCD rule of dermatoscopy:
high prospective value in the diagnosis of doubtful melanocytic skin lesions.
J Am Acad Dermatol 1994; 30: 551-9.
5. Dal Pozzo V, Benelli C. Atlante di Dermoscopia. Edra Publishing
House, Milan, 1996.
6. Dal Pozzo V, Benelli C. Atlas of Dermoscopy. Edra Publishing
House, Milan, 1997.
7. Dal Pozzo V, Roscetti E, Benelli C. The seven features for
melanoma (7FFM) a new dermoscopic algorithm for the diagnosis of melanoma.
Eur J Dermatol 1999; 9: 303-8.
8. Benelli C, Roscetti E, Dal Pozzo V, Gasparini G, Cavicchini
S. The dermoscopic (7FFM) versus the clinical (ABCDE) diagnosis
of melanoma. Eur J Dermatol 1999; 9: 470-7.
9. Bahmer FA, Fritsch P, Kreusch J, Pehamberger H, Rohrer C,
Schindera I. Terminology in surface microscopy. J Am Acad Dermatol
1990; 23: 1159-62.
10. Steiner A, Pahemberger H, Binder M, Wolff K. Pigmented Spitz
nevi: improvement of the diagnostic accuracy by epiluminescence microscopy.
J Am Acad Dermatol 1992; 27: 697-701.
11. Armitage P, Berry G. Statistical methods in medical research.
Blackwell scientific publication Ltd Oxford, 1994.
12. Dawson-Saunders B, Trapp RG. Basic & Clinical Biostatistics.
Appleton & Lange, 1994.
13. Steiner A, Binder M, Schemper M, Wolff K, Pahemberger H.
Statistical evaluation of epiluminescence microscopy criteria for melanocytic
pigmented skin lesions. J Am Acad Dermatol 1993; 29: 581-8.
14. Kenet RO, Kang S, Kenet BJ, Fitzpatrick TB, Sober AJ, Barnhill
RL. Clinical diagnosis of pigmented lesions using digital epiluminescence
microscopy. Arch Dermatol 1993; 129: 157-74.
15. Soyer HP, Smolle J, Leitinger G, Rieger E, Kerl H. Diagnostic
reliability of dermatoscopic criteria for detecting malignant melanoma.
Dermatology 1995; 190: 25-30.
16. Nilles M, Boedeker RH, Schill WB. Surface microscopy of naevi
and melanomas-clues to melanoma. Br J Dermatol 1994; 130: 349-55.
17. Menzies SW, Crotty KA, Ingvar C, et al. An atlas of
surface microscopy of pigmented skin lesions. Sidney, Australia, McGraw-Hill,
1996.
18. Menzies SW, Ingvar C, McCarty WH. A sensitivity and specificity
analysis of the surface microscopy features of invasive melanoma. Melanoma
Res 1996, 6: 55-62.
19. Menzies SW, Ingvar C, Crotty KA, et al. Frequency
and morphologic characteristics of invasive Melanomas lacking specific
surface microscopic features. Arch Dermatol 1996; 132: 1178-82.
20. Argenziano G, Fabbroncini G, Carli P, De Giorgi V, Sammarco
E, Delfino M. Epiluminescence microscopy for the diagnosis of doubtful
melanocytic skin lesions. Arch Dermatol 1998; 134: 1563-70.
21. Binder M, Schwarz M, Winkler A, Steiner A, Kaider A, Wolff
K, Pehamberger H. Epiluminescence microscopy. Arch Dermatol 1995;
131: 286-91.
22. Binder M, Puespoeck-Schwarz M, Steiner A, Kittlewr H, Muellner
M, Wolff K, Pehamberger H. Epiluminescence microscopy of small pigmented
skin lesions: short-term formal training improves the diagnostic performance
of dermatologists. J Am Acad Dermatol 1997; 36: 197-202.
23. Stanganelli I, Burroni M, Rafanelli S, Bucchi L. Intraobserver
agreement in interpretation of digital epiluminescence microscopy. J
Am Acad Dermatol 1995; 33: 584-9.
24. Stanganelli I, Bucchi L. Epiluminescence microscopy versus
clinical evaluation of pigmented skin lesions: effects of operator's training
on reproducibility and accuracy. Dermatology 1998; 196: 199-203.
25. Carli P, De Giorgi V, Naldi L, Dosi G on behalf of the Dermatoscopy
Panel. Reliability and inter-observer agreement of dermatoscopic diagnosis
of melanoma and melanocytic naevi. Eur J Cancer Prev 1998; 7: 397-402.
26. Argenziano G, Fabbroncini G, Carli P, De Giorgi V, Delfino
M. Epiluminescence microscopy: criteria of cutaneous melanoma progression.
J Am Acad Dermatol 1997; 37: 68-74.
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