The dermoscopic (7FFM) versus the clinical (ABCDE) diagnosis of small diameter melanoma

ARTICLE

The incidence of cutaneous melanoma is rising all over the world. The best way to reduce the mortality due to this cancer is its early diagnosis. Most authors consider that an early diagnosis of melanoma has been achieved when the maximum thickness of the tumor excised is < 0.76 mm. In fact the 10 years survival of melanoma affected patients ranges from 99% to 95% if the thickness of the tumor is < 0.76 mm at the time of the excision. Nonetheless, the thickness of the melanoma can be assessed only histopathologically and can be evaluated only after the tumor has been excised: for this reason this criterion can not be used to identify early melanoma. Data from the literature show that the maximum diameter of the melanoma is probably the best clinical criterion to identify early melanoma. In fact, as shown by Kamino et al. [1], and by Shaw et al. [2], small melanomas, i.e. melanomas with a maximum diameter ¾ 6 mm, affect patients whose mean age is approximately 7 to 10 years less than the mean age of presentation reported for larger melanomas. This indicates that small melanomas are present up to a decade before being recognized by the conventional size criterion of the clinical ABCDE rule (criterion D is considered altered if the maximum diameter of the lesion under examination is larger than 6 mm). For this reason we think that small melanomas should be considered early melanomas, and that a method for the clinical differential diagnosis of pigmented skin tumor should be tested in the evaluation of small melanomas and not of thin melanomas (melanomas < 0.76 mm in thickness). Studies about the sensitivity in the clinical diagnosis of melanoma report a mean rate of 67%, the various rates ranging from 48 to 81% [3]; the variability in the results is probably due to both the features of melanomas evaluated and the experience of the examining physicians. The main method utilized to evaluate clinically pigmented skin lesions is the ABCD rule as developed by Rigel et al. [4], a simple checklist of the signs of early melanoma based on four clinical criterion: A, asymmetry in shape; B, border irregularity; C, variation in color; D, diameter > 6mm. Afterwards a new criterion E, for evolution, was added to improve the sensitivity in diagnosis: evolution is an anamnestic criterion based on patient's description, including in this term elevation, enlargement or change in the color of the lesion [5].

Nonetheless the mean value of sensitivity in the clinical diagnosis of melanoma is far from being satisfactory and dermatologists are experimenting new techniques to improve the clinical diagnosis of melanoma. Dermatoscopy, dermoscopy 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 stereo microscopes are expensive and cumbersome, therefore they can not be used for the analysis of pigmented skin lesions in daily office practice. On the contrary simple microscopes are handy, cheap, suited for daily use. Five diagnostic methods for the simple microscope or dermatoscope have been reported in literature: the ABCD rule of Dermoscopy [6-8], the methods developed by Nilles et al. [9], Menzies et al. [10-12], the seven features for melanoma (7FFM) developed by us [13-16], and the more recent 7 point Checklist based on pattern analysis [17]. These diagnostic dermoscopic methods, utilized by their own authors, have both values of sensitivity (97.9, 90, 92, 94.6 and 95% respectively) and specificity (90.3, 85, 70, 85.5 and 75% respectively) not significantly different one from another.

In all these studies the methods were used to evaluate melanomas of various thickness and diameter. No one study has evaluated the sensitivity of a diagnostic dermoscopic method in the diagnosis of small diameter melanomas, and the improvement given by this method to the clinical ABCDE rule in the diagnosis of small diameter melanomas. These data would be crucial to assess the utility of a diagnostic dermoscopic method in the early diagnosis of melanoma because, as previously described, small melanomas should be considered as early melanomas.

For these reasons we decided to evaluate the sensitivity and the specificity of the clinical ABCDE rule and of our diagnostic dermoscopic method (7FFM) in the diagnosis of small diameter melanomas. This article presents an analysis of the results.

Material and methods

This retrospective study concerns all small melanomas observed and excised at the Dermatologic surgery department of the Dermatologic Sciences Institute, IRCCS, University of Milan, from January 1 1993 to December 31 1998. In this period 468 melanomas were excised. All small melanocytic nevi excised from 1 September 1997 to 30 September 1999 were considered to evaluate the specificity of the two methods. Each lesion was photographed both clinically and dermoscopically at the time of the excision. The dermoscopic picture was obtained by means of a Dermaphot Heine at 10X, using a Kodak Ektachrome 64 ASA film. The lesions were then excised and submitted to histopathological examination.

The clinical and the dermoscopic evaluation of the lesions have been made on the basis of the photographic slides by three different observers according to the criteria or features below.

The clinical evaluation was made on the five ABCDE criteria. Criterion A has been defined as geometrical asymmetry on the two axes of the tumor, criterion B as irregular (ragged or indented) border, criterion C as the presence of at least two different colors within the lesion (except the usual symmetrical darkening of the lesion in its center typical of junctional nevi), criterion D as a maximum diameter > 6 mm.

Criterion E as evolution is an anamnestic criterion based on patient's description, including in this term elevation, enlargement or change in the color of the lesion.

Criteria A, B and C have been evaluated on the basis of the photographic clinical slide, criterion D has been evaluated both on the basis of the maximum diameter of the lesion recorded on the date of the excision and of the maximum diameter of the lesion evaluated in the dermoscopic slide. A dermoscopic slide taken with a Dermaphot Heine has a field of vision of 11 x 8 mm, this permits us to assess the diameter of the lesion photographed. Criterion E has been evaluated on the basis of the anamnesis of the patient reported in the case file.

Dermoscopically the lesions were evaluated with the method we have developed (7FFM).

Our method 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 [6-8, 14-16].

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 pigment 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 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 [18], 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 a 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. [9] considered an asymmetrical pigment distribution (no relation with dermoscopic features) with four different grades of severity. Kenet et al. [19] 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 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 [20].

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 >= 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 criteria and the dermoscopic features were evaluated as present or absent. In the case of disagreement among the three observers, the majority view prevailed.

Statistical analysis

The 468 melanomas excised from January 1 1993 to December 31 1998 were classified in three subgroups according to their maximum diameter: melanomas ¾ 6 mm, melanomas ¾ 10 mm and melanomas > 10 mm. The mean, the median, the minimum, the maximum and the standard deviation of the age of all melanoma affected patients, and of the three subgroups of patients, were calculated. The mean, the median, the minimum, the maximum and the standard deviation of the thickness of all melanomas and of the three subgroups of melanomas were calculated. The 95% CI of the means were also calculated.

The clinical and the dermoscopic slides of melanomas having a maximum diameter ¾ 6 mm were evaluated with the clinical ABCDE rule and with our diagnostic dermoscopic method (7FFM). In the same way the clinical and the dermoscopic slides of 524 melanocytic nevi excised from 1 September 1997 to 30 September 1999, having a maximum diameter ¾ 6 mm, were evaluated.

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 score of each lesion is the sum of the clinical criteria present in the lesion, therefore the clinical score may range from 0 to 4 (all these melanomas were negative for criterion D). In relation to the number of criteria, i.e. the score, whose presence is considered necessary to classify a lesion as malignant, various clinical diagnostic methods can be obtained. As suggested by Thomas et al. [21], we considered as malignant the lesions that presented at least two clinical criteria (i.e. score 2).

Dermoscopically we evaluated as malignant the lesions that presented a score >= 2 with our dermoscopic diagnostic method (7FFM) obtained as previously reported. The sensitivity and the specificity of the ABCDE score and of our dermoscopic diagnostic method (7FFM) have been calculated.

The sensitivity of a diagnostic method is the proportion of all cases of histologically proved melanomas that were diagnosed as melanomas.

The specificity of a diagnostic method is the proportion of all cases of histologically proved non-melanomas that were diagnosed as non-melanomas.

To evaluate the difference of diagnostic power (i.e. the difference of sensitivity and specificity), between the clinical score 2 and the dermoscopic method (7FFM), a chi square test has been calculated.

A p value less than 0.05 has been considered statistically significant.

Results

According to the maximum diameter the 468 melanomas were classified as follows: 76 ¾ 6 mm (16.2%), 164 ¾ 10 mm (35%) and 229 > 10 mm (48.8%). The mean age of all patients was 53 years (95% CI 51.5-54.5), while the mean ages of the three subgroups were: 44 years for melanomas ¾ 6 mm (95% CI 40.8-47.1), 52 years for melanomas ¾ 10 mm (95% CI 49.5-54.4) and 56 years for melanomas > 10 mm (95% CI 53.9-58). The mean, the median, the minimum, the maximum and the standard deviation of the age of all patients and of the three subgroups are reported in Table I. The mean histopathological thickness of all melanomas was 1.09 mm (95% CI 0.94-1.15). The mean histopathological thickness of the three subgroups was 0.54 mm for melanomas ¾ 6 mm (95% CI 0.43-0.64), 0.73 mm for melanomas ¾ 10 mm (95% CI 0.61-0.84) and 1.53 mm for melanomas >10 mm (95% CI 1.33-1.72). Thirty-four melanomas were in situ: 14 in the subgroup ¾ 6 mm, 20 in the subgroup ¾ 10 mm. The mean, the median, the minimum, the maximum and the standard deviation of the thickness of all melanomas and of the three subgroups are reported in Table II.

The 524 small nevi consecutively excised from September 1 1997 to September 30 1999 were classified histopathologically as: 79 epithelioid and/or spindle cell nevi, 53 junctional melanocytic nevi, 175 compound melanocytic nevi, 54 dermal melanocytic nevi, 163 melanocytic nevi with inflammatory infiltrate and/or undergoing regression.

The 76 small melanomas (melanomas ¾ 6 mm) and the 524 small nevi were retrospectively evaluated with ABCDE and with 7FFM.

The analysis of the clinical slides showed that criterion A was present in 38 melanomas and in 199 nevi, criterion B in 8 melanomas and in 96 nevi, criterion C in 43 melanomas and in 193 nevi, criterion E in 13 melanomas and in 137 nevi. Seventeen melanomas and 87 nevi did not present any clinical criterion, 23 melanomas and 205 nevi presented 1 criterion, 30 melanomas and 172 nevi presented 2 criteria, 5 melanomas and 57 nevi presented 3 criteria and 1 melanoma and 3 nevi presented 4 criteria. Thirty-six melanomas and 232 nevi presented two or more clinical criteria, therefore, the sensitivity and the specificity of the clinical diagnosis with score 2 are 47.3% and 56%.

The evaluation of the dermoscopic slides showed that unhomogeneity was present in 47 melanomas and in 64 nevi, irregular pigment network in 19 melanomas and in 52 nevi, sharp margin in 8 melanomas and in 11 nevi, radial streaming in 8 melanomas and in 7 nevi, pseudopods in 13 melanomas and in 20 nevi, gray-blue veil in 23 melanomas and in 21 nevi, regression-erythema in 4 melanomas and in 4 nevi. Our method 7FFM classified as malignant 52 melanomas and 70 nevi: the sensitivity and the specificity of our method are 68.8% and 86%. The difference of diagnostic power between the two methods calculated with chi-square test is statistically significant withkhi² = 6.9, P < 0.01 for sensitivity and khi² = 9.6, P < 0.01 for specificity. Ten melanomas and 27 nevi were correctly diagnosed clinically but not dermoscopically. The two methods together correctly diagnosed 62 melanomas (sensitivity 81.5%) and 265 nevi (specificity 50.5%). The 14 melanomas false negatives to both methods presented a maximum thickness of 0.50 mm. Some examples of the melanomas evaluated are given in Figures 1-3.

Discussion

In our series of 468 melanomas, 76 melanomas presented a maximum diameter ¾ 6 mm (16.2%), an intermediate result compared to those reported by Carli et al. (2.6%) [5], Gonzalez et al. (4.4%) [22] and Shaw et al. (31.3%) [2].

The clinical characteristics of our patients confirm that the mean age of patients with small melanomas is approximately 7 to 10 years earlier than the mean age of presentation reported for larger melanomas. In fact the mean age of our small melanomas affected patients is 44 years while the mean age of all our melanomas affected patients is 53 years. Our data are similar to those obtained by Kamino et al. [1], Shaw et al. [2], mean age of small melanomas 39 years, and by Gonzalez et al. [22], mean age of small melanomas 42.2 years. In our series the mean age of patients affected by melanomas whose maximum diameter ranged from 7 to 10 mm was 52 years, similar to the mean age of all melanoma affected patients of 53 years. The mean thickness of small melanomas is less than the mean thickness of all melanomas of our series and this confirms data from Shaw et al. [2] and Carli et al. [5]. On the contrary, Gonzalez et al. [22] found no significant difference of thickness between small melanomas and the total of melanomas of their series.

The diagnosis of small melanomas is particularly difficult.

Shaw et al. [2] in their analysis of 1,150 Australian melanomas found 358 small melanomas as 31.1% but, in the authors' opinion, this does not imply that Australian physicians are more adept at diagnosing early melanoma than physicians elsewhere because this result is achieved at a cost of a considerable number of unnecessary excisions.

Carli et al. [5] in their analysis of 90 melanomas with a maximum diameter ¾ 10 mm, of which 20 ¾ 6 mm, showed that the ABCD rule correctly diagnosed only 26.6% of melanomas and for this reason they suggested adding E as evolution to this rule.

Gonzalez et al. [22] in their study of 16 small melanomas considered that only 4 melanomas (25%) had been correctly diagnosed.

In this study we have shown that the adjunct of evolution to the ABCD rule can improve the diagnosis of small melanomas obtaining a sensitivity of 47.3% and a specificity of 56% with score 2. However this result is far from being satisfactory because more than half of our small melanomas are not correctly diagnosed. The evolution can be used to improve dermoscopy: in fact, in a recent paper, Kittler et al. [23] showed that the sensitivity of the ABCD rule of dermoscopy, first proposed by Stoltz et al. [23], can be improved with the adjunct of criterion E. Our diagnostic dermoscopic method 7FFM improves the diagnosis of small melanomas bringing the sensitivity to 68.8% and the specificity to 86%. As expected, these values are lower than those obtained in a previous prospective study of all the lesions excised from September 1 1997 to September 30 1998. In this study we obtained 80% for sensitivity and 89.1% for specificity [24]. Our data show that dermoscopy improves the sensitivity in the diagnosis of small melanomas. As the other diagnostic dermoscopic methods published in the literature show values of sensitivity and specificity similar to our method we have no reason to believe that these methods work worse than ours. Interestingly, the ABCDE clinical rule and our method 7FFM together improve the diagnosis of small diameter melanomas, obtaining a sensitivity of 81.5% and a specificity of 50%, indicating that dermoscopy and the clinical evaluation can be used together. For this reason we think that dermatologists should be encouraged to use a dermatoscope in the diagnosis of pigmented skin lesions and that a formal training in dermoscopy should be offered to dermatologists. In fact data about the reproducibility of our method (7FFM), obtained in various dermoscopic courses, point to a good concordance among different observers about the dermoscopic features of our method [25].

Article accepted on 6/1/00

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