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CME ARTICLE

 
 
Epiluminescence microscopy in the management of pigmented skin lesions

P.Carli, V. De Giorgi, H.P.Soyer*, M.Stante and B.Giannotti
Department of dermatology University of Florence, Italy and *Department of Dermatology, University of Graz, Graz, Austria.


ABSTRACT

Epiluminescence microscopy (ELM) is an in vivo, non-invasive technique that has disclosed a new dimension of the clinical morphologic features of pigmented skin lesions using incident light magnification systems with immersion oil at the skin-microscope interface. The features used in the "standard pattern analysis" and proposed at the Consensus Conference of Hamburg has undergone numerous modifications in relation to the individual experience of the various research groups performing epiluminescence microscopy in the clinical practice all over the world. Various authors proposed new diagnostic algorithms during the last years. These dermoscopic score system can be easily lerned and applied, even by less experienced ELM investigators, still giving a high rate of diagnostic accuracy. Therefore the new methods recently proposed can be considered as efficient alternatives to standard pattern analysis in the dermoscopic diagnosis of melanoma.

Melanoma thickness is used to establish the width of surgical margin for excision of melanoma as well as to select the patients for sentinel lymph node biopsy. Previous studies showed the poor reliability of melanoma palpability (clinical elevation of the lesion ) in predicting melanoma thickness. During melanoma progression, the occurrence of specific histopathologic patterns obviously modifies also the dermoscopic profile of a given lesion. In a previous study of our group dermoscopic criteria were elaborated that characterise the different phases of melanoma progression as well as the various tumor depths. Based on the combination of clinical criteria ( palpability and diameter > 1.5 cm ) and dermoscopic criteria ( pigment network, grey-blue areas and atypical vascular pattern ) the accuracy in the preoperative assessment of melanoma thickness could be enhanced compared to the separate application of these two criteria. Moreover, according to preliminary results of a study carried out by our group, also the ABCD-rule of dermoscopy was found to play a possible role in the preoperative evaluation of melanoma thickness.


INTRODUCTION

Epiluminescence microscopy (ELM), also known as in vivo cutaneous surface microscopy, incident light microscopy, magnified oil immersion diascopy, dermatoscopy and dermoscopy, is an in vivo, non invasive technique that has disclosed a new dimension of the clinical morphologic features of pigmented skin lesions using incident light magnification systems with immersion oil at the skin-microscope interface (1) .

The purpose of this method is to obtain the visualisation of numerous morphological features, not visible with the naked eye, that enhance the clinical diagnosis of nearly all pigmented skin lesions (2)(3).

These morphologic features seen by ELM examination have specific, rather well-defined histopathologic correlates (4). By knowing the histopathologic equivalent of such structures, the investigators are able to better understand the dermoscopic features and also to increase the in vivo diagnostic accuracy of benign versus malignant pigmented skin lesions.


HISTORY

The history of in vivo cutaneous microscopy dates back to Goldman who in 1951 started using systematically this technique as a diagnostic procedure to evaluate pigmented skin lesions (1).

20 years later, in 1971 MacKie revived skin microscopy, almost forgotten, for the diagnosis of pigmented skin 
lesions (5).

In 1980 Fritsch and Pechlaner (6) described for the first time in the international literature the pigment network which at the present time is still considered to be an important dermoscopic criterion for the diagnosis of pigmented skin lesions. These investigators used a stereomicroscope for ophthalmologic surgery with oil immersion for the differentiation of benign from malignant melanocytic lesions (6).

The term "epiluminescence microscopy" (ELM) was coined in 1987 by the austrian authors Pehamberger, Steiner and Wolff, when they used in vivo surface microscopy with oil immersion technique in a study of more than 3000 pigmented skin lesions (2) (7). Based on their own large experience in this field they performed a systematic analysis of the new morphologic features that become apparent with ELM examination and proposed the "pattern analysis" model for the diagnosis of pigmented cutaneous lesions (2) (7).

Two years later, in 1989, a standardized terminology of ELM patterns together with their variables was provided by a Consensus Meeting held by the Committee on Analytical Morphology of the Arbeitsgemeinschaft Dermatologische Forschung held in Hamburg, Germany in order to better communicate this method to clinical dermatologists (8).

However, in subsequent years the features used in the "standard pattern analysis" and proposed at the Consensus Conference of Hamburg have undergone numerous modifications in relation to the individual experience of the various research groups performing Epiluminescence microscopy in the clinical practice all over the world.

More recently, in 1994 Stolz and colleagues introduced the so called "ABCD rule of dermatoscopy" which is a new algorithm based on a semiquantitative score system for the diagnosis of melanocytic skin lesions (9-11).

In order to introduce simple but reliable and reproducible dermoscopic methods for the evaluation of pigmented cutaneous lesions into the daily clinical practice, during the last years several authors proposed some new diagnostic algorithms (12-15). These dermoscopic score systems can be easily learned and applied even by less experienced ELM investigators, still giving a high rate of diagnostic accuracy. Therefore the new methods recently proposed can be considered as efficient alternatives to the standard pattern analysis model in the dermoscopic diagnosis of melanoma.


TECHNIQUE

ELM is performed by a surface microscope using incident light delivered from an acute angle and oil immersion (3)(16). By covering the lesion with immersion oil together with a glass slide applied with a slight pressure, the surface reflection due to the different refractive index mismatch between air and skin is eliminated (3). This makes the stratum corneum translucent, enabling in vivo visualisation of pigmented anatomic structures of the epidermis and, even beyond that, of the dermo-epidermal junction and superficial papillary dermis invisible with the naked eye (4-6).

Depending on the localisation of the melanin pigment within the skin, different colours can be observed with ELM (7). Melanin pigment localised in the horny layers of the epidermis appears black; pigmentation of lower epidermal layers appears light to dark brown depending on its concentration. Pigment localised in the papillary dermis appears grey, whereas pigmentation of the reticular dermis is steel blue (7)(17).

ELM can be performed with binocular stereomicroscopes, which provide a magnification range from 6X to 80 X. These instruments can be equipped with additional optical systems for simultaneous viewing by a second investigator and a camera mounted on a side arm for instant photography (3). The stereomicroscopes permit high and variable magnification, a three-dimensional appearance of the lesions and the simultaneous viewing by a second investigator; disadvantages are size, weight and costs of the instrument, space requirements and the long time needed for the examination (3).

ELM can also be performed with an hand-held microscope equipped with an achromatic lens that allows a fixed magnification of 10X; an incident light at an acute angle of 20° is delivered from a built-in light source powered by a battery in the shaft of the. This relatively inexpensive equipment is adequate for use in daily clinical practice (3)(18).

Modern advanced systems are presently based on advanced computer technology enabling image data to be processed (acquisition, storage and retrieval). These digital ELM camera systems are a powerful technology that can improve clinical visualisation and facilitate a more detailed study of the subtle epidermal and superficial dermal pathology of pigmented lesions (19-20).

Digital ELM camera systems are now available in order to acquire, process, print and review clinical and ELM images thus facilitating the follow-up of doubtful pigmented skin lesions (20).


ELM CRITERIA

The structures seen by ELM examination are very heterogeneous and can confuse an inexperienced investigator. Therefore, it has been necessary to define the terminology for these dermoscopic features – also called ELM criteria (2)(7). Moreover, the diagnostic significance of these ELM criteria has been elaborated.

ELM criteria are defined by purely descriptive terms and have been correlated with the underlying histopathologic substrates (4) (17). For each criterion, additional descriptors are used to specify the architectural distribution thus contributing to the final diagnosis (8). For example, pigmented network represents a subtle network of brownish lines over a diffuse backgound tan, whose anatomic basis is melanin pigment in the epidermal basal cells (Fig 1). The holes of the network correspond to the tips of the dermal papillae whereby the lines of the network result from the projection of the pigmented rete ridges to the skin surface. According to the size and configuation of the rete ridges – differently associated with the benign or malignant nature of the lesion - the pigment network can be regular or irregular (depending on the size and shape of the meshes of the network), narrow or wide (depending on the thickness of the lines), delicate or prominent (depending on the intensity of pigmentation), and it may be well or ill defined at the margin of the lesion (depending on the cutoff at the borderlines) (Fig 2) (4)(6-8) . In evaluating these descriptors as well as the ELM features described below, the observer is able to recognize the nature - benign or malignant - of the given lesion. Major ELM criteria together with their histopathologic correlates are summarised in Table I.

In spite of many efforts in this direction, it remains difficult to define precisely the dermoscopic terminology. In fact, still today investigators are using different names even for morphologically identical criteria (21).


DIAGNOSIS OF PIGMENTED SKIN LESIONS:
ELM PATTERN ANALISIS.

Austrian research groups introduced, in a study dating back in 1987, a systematic analysis of these new morphologic features that become apparent with ELM. They proposed a model of qualitative pattern analysis based on ELM criteria, in order to distinguish the different types of cutaneous pigmented lesions (2-3)(7)(22-24). So, the "Standard ELM pattern analysis" is based on the qualitative assessment of numerous individual ELM criteria recognised within a given pigmented skin lesion (7) (15)(25).

The features analysed in this diagnostic model include specific patterns, colors, and intensities of pigmentation, as well as the configuration, regularity and other characteristics of both the margin and the surface of pigmented skin lesions (7). According to this, a dermoscopic diagnosis of a pigmented skin lesion must be based always on a critical, simultaneous evaluation of all available criteria (8).

According to Pehamberger, the assessment of ELM criteria is based on the following rules (3):

  1. The presence of a criterion is more important than its absence. Because the frequency of each criterion in melanomas is far from 100%, it is inappropriate to reason that a given pigmented lesion is not considered to be a melanoma just because those criteria considered the most specific for melanoma diagnosis, i.e. pseudopods, radial streaming or grey-blue areas, are absent (Fig 3) (22).
  2. One single criterion usually is not suffice to make a diagnosis. Even if some criteria are more specific than others for diagnosis of melanoma (i.e. less frequently expressed in melanocytic nevi), actually a single criterion cannot be considered as stereotypical for malignancy.

    Also in benign lesions, only the simultaneus assessment of several criteria permits a definitive diagnosis, for example: horny pseudo-cysts are suggestive for seborrheic keratosis but only in the absence of so-called melanocytic parameters. Indeed, horny pseudo-cysts can be present in dermal nevi or even - though exceptionally - in malignant melanomas (26).

  3. Some criteria are more important than others. This derives from the evidence that the association between some criteria and diagnosis of melanoma is very close. The consequence is that the combination of particular criteria (i.e. irregular prominent pigment network and irregularly distributed pseudopods ) results more predictive (i.e. associated with a lower probablity of false-positive diagnosis) than others (i.e. irregular brown globules and presence of depigmentation )(Fig 4) (22)(27).
  4. The absence of defined criteria does not permit an ELM diagnosis.

Pattern analysis model based on criteria seen on dermatoscopy allows the investigators to better differentiate between melanocytic and non-melanocytic, and between benign and malignant melanocytic pigmented skin lesions (3)(27-28). It is worth noting that the dermoscopic diagnosis of melnaoma, in particular when performed in accordance with the pattern analysis procedure, needs a specific trained of observers. Formal studies carried out by Binder et al showed that diagnostic performance of dermoscopy gave better results than clinical examination only when carried out by experts. On the contrary, sensitivity of technique, i.e. the percentage of melanoma diagnosed over the total number of melanoma observed, resulted lower than that of the clinical examination for untrained dermatologists (29). An improvement of diagnostic performance was subsequenlty found with a formal training of 9 hours (30) .

Facing a pigmented skin lesion with dermoscopy, the diagnostic approach leading to diagnosis begins with the definition of melanocytic or non-melanocytic origin of the lesion. To achieve this goal pattern analysis remains, in our opinion, the basic methodological approach, because the so-called melanoma algorythms (see later) are useful only when facing clear-cut melanocytic lesions. As a consequence of their histopathologic correlates, ELM features suggestive for melanocitic proliferation are as follows : pigment network, brown globules, radial streaming and pseudopods (10). Lacking these ELM features, the observer must look for other dermoscopic parameter allowing a final diagnosis (e.g. horny pseudo-cysts and pseudo-follicular openings : seborrheic keratosis; maple-leaf-like areas : pigmented basal cell carcinoma; red-blue lagoons: angioma or angiokeratoma) (Table II). Only when a lesion is definitely classified as "melanocytic" the use of one of the reported dermoscopic algorithms for melanoma (see later) e.g. ABCD of dermoscopy, allows differentiation between benign from malignant melanocytic lesions as an alternative procedure of pattern analysis (10). Table II shows the main characteristics of melanocytic nevi and melanoma, respectively, as assessed by means of pattern analysis.

In a recent study on 342 clinically doubtful melanocytic skin lesions, the diagnostic performance of melanoma by means of pattern analysis carried out by experienced observers showed better results concerning sensitivity (91%), specificity (90%), diagnostic accuracy value (76%) and number of correct diagnosis (90%) when compared to those obtained with two dermoscopic algorithms (ABCD rule of dermoscopy and 7-point checklist) (15).


ELM OF PIGMENTED LESIONS AT PECULIAR SITES :

FACE
Due to the special architecture of the dermal-epidermal junction on the face a "pseudopigment network", instead of a regular honeycomb network, is usually observed. This peculiar dermoscopic feature can be explained by the numerous follicular openings of facial skin causing the regular broad holes of the "pseudopigment network". In this context the major challenge is the differentiation of a lentigo actinica or reticulated type of seborrheic keratosis from a lentigo maligna (LM) or a lentigo maligna melanoma (LMM). As a rule, the dermoscopic diagnosis of LM or LMM of the face is based on the accentuated pigmented rim of follicular openings which creates, because follicular openings are lying close together , a pseudopigment network characterized by thin meshes and thin holes (Fig 5) (10). The particular pigment network of facial melanoma is therefore different from that commonly observed in non-melanocytic lesions (broad meshes/holes).
Other dermoscopic criteria for the diagnosis of melanoma on sun-damaged skin of the face are brown streaks and a romboidal pattern due to confluence of the streaks.

GLABROUS SKIN
Concerning glabrous skin of palms and soles, benign melanocytic lesions show a particular dermoscopic feature characterised by a linear pigmentation regularly distributed in the sulci between the papillary tips ending abruptly at the periphery. Studies carried out in the Japanese population, frequently affeected by palmar and plantar nevi (about 10% of Japanese people) (31) suggested additional ELM patterns (at least four ) in acral skin , roughly associated with histopathologic subtipes (32). On the contrary, melanoma affecting palms and soles shows – at the first step of malignant progression - an irregular dermoscopic pattern due to the aggregation of pigmentation around acrosyringia (if they are not obliterated by a diffuse pigmentation or destroyed by white scarlike/grey-blue areas). Recently, Oguki and coworkers reported on a unique epiluminescence feature, the parallel ridge pattern, for the diagnosis of acral melanoma in situ. This parallel ridge pattern, in which the pigmentation follows the papillary tips has not been found in any benign lesion, thus exhibiting –at least in Japanese population - a specificity of 100% and a high sensitivity too (83%-94%)(33).

MELANOSIS OF MUCOSAL SITES
Concerning mucosal site, a frequently appearing lesion is labial and genital melanosis whose clinical aspect, despite its benign behaviour, can share some features with malignant melanoma (Fig 6) (34). In these cases, in particular when occurrs on genital mucosa, diagnosis by clinical criteria alone may be unreliable and biopsy with histological examination is necessary (35-36). Recently Carli and colleagues analysed ELM features of mucosal melanosis clinically mimicking malignant melanoma (34). The presence of a diffuse pigmentation, without any other dermoscopic features related to melanocyte proliferation – so called "structureless pattern" -, represents the distinctive dermoscopic pattern of such lesions (FOTO), thus allowing a non invasive diagnosis of mucosal melanosis (Fig 7) (34)(37).


DIAGNOSIS OF MELANOMA BY MEANS OF DERMOSCOPIC ALGORYTHMS

1. ABCD OF DERMOSCOPY
Several studies have shown that, with the ELM, an high rate of diagnostic accuracy of pigmented skin lesions can be obtained only if the technique is performed by dermatologists with a long experience in the field or, in alternative, formally trained for this technique (29-30)(38). Because of the great number of subtle features and special criteria that have to be assessed qualitatively when performing pattern analysis, the investigators must undergo a formal training developed especially for this technique (29-30). For novices, in fact, the correct interpretation of the images may be difficult to learn and apply. Therefore, a new diagnostic algorithm termed "ABCD rule of dermatoscopy" has been developed in order to increase the diagnostic accuracy also by non-experienced ELM investigators (9)(11). This method can be easily learned, easily applied, and has been proven to be reliable and reproducible (9-11)(39).
Stolz together with other researchers introduced this new diagnostic model based on multivariate analysis of only four dermoscopic criteria with a semiquantitative score system.

  1. Asimmetry
  2. abrupt cutoff of the pigment pattern at the Border
  3. Colour variegation
  4. Different dermatoscopic structures

Asimmetry is evaluated with respect to colour and structures along none (0 points), one (1 point) or both (2 points) of the two perpendicular axes located in such a way that the lowest asymmetry score possible is obtained (possible score 0-2).
For the calculation of border score, the lesions are divided into eight segments; each segment which includes an abrupt cutoff of pigment pattern gives a score of one point (possible score 0-8).
In assessing the colour score, the investigator counts the number of different colours seen with dermoscopy (possible colours are six: white, red, light and dark brown, blue-gray, black) (possible score 1-6).
For evaluating the different dermatoscopic structures score, five possible components are considered: network, homogeneous areas, dots, globules, streaks (score 1-5).
The individual scores obtained according to these rules are multiplied for different weight factors obtained by multivariate analysis of the four dermoscopic criteria, referring to the real diagnostic weight of each of them (10).
With this easy-to-perform scoring system (table III) the investigator is able to calculate the Total Dermoscopy Score (TDS) which can be used for grading the malignancy potential of melanocytic pigmented skin lesions (TDS<4.75 = benign lesion; TDS > 5.45 = malignant lesion; intermediate values = doubtful lesions) (Fig 8).
In earlier reports on the ABCD rule of dermatoscopy, this method gave 92.8% of sensitivity, 91.2% of specificity and 80% of diagnostic accuracy (11). This algorithm has proven, when applied to clinically equivocal melanocytic cutaneous lesions, to allow the dermatologist a more objective and reproducible diagnosis (11). Some new data from international literature underscore that the use of the ABCD-rule of dermatoscopy appreciably improves the diagnostic ability of less experienced investigators performing ELM (39).
This method, as well as standard pattern analysis, obviously doesn’t yield 100% diagnostic accuracy in detecting melanomas (2)(7)(15)(22) (24)(30)(34). Therefore further efforts must be made in order to enhance our ability in diagnosing malignant melanocytic skin lesions.
EXTENSION OF THE ABCD RULE FOR DERMOSCOPY.
Recently, Kittler et al performed a prospective study which demonstrates that the ABCD scoring system is appreciably enhanced if it includes informations about macroscopic morphologic changes of the lesion, observed and reported by the patient himself (40). The enhanced algorithm including the additional morphologic criterion is termed "ABCD-E score". The letter E added to the acronym stands for "Enlargement" and other macroscopic morphologic changes of pigmented skin lesions, that could be reported by the patient himself to the investigator. The enhanced ABCD-E score can be calculated by adding 1.2 to the standard ABCD score for changing lesions and subtracting 0.8 from the standard ABCD score for non-changing lesions. At a giving point of 60% specificity, the sensitivity of the method increase from 89.9% to 93.1% by including the E- score.

2. THE SEVEN FEATURES FOR MELANOMA (7FFM)
In order to introduce a diagnostic algorithm based on the evaluation of ELM criteria in the daily clinical practice, this must be simple, reliable and reproduceable. Following these main lines, Dal Pozzo and coworkers developed a new method based only on a few dermoscopic features showing an high malignancy predictive value (12-13).
All the seven selected criteria used to develope this scoring system show a histopathologic correlation with malignancy, even if this doesn’t mean that the features are specific for melanoma. There is a general accordance in literature, in fact, that none of the known dermoscopic criteria is 100% specific for melanoma (2)(22)(41)(42).
The Seven dermoscopic features useful for the diagnosis of melanoma were thus detected and considered to perform this algorithm termed "The seven features for melanoma (7FFM)"(13). Following a selection based on the specificity obtained for each criteria, the authors attributed a score of 2 to the major features (specificity >95%) and a score of 1 to the minor ones (specificity 95-80%) (Table IV) (13).
According to this score system, the pigmented skin lesions showing a total score = 2 or more are diagnosed as being malignant, those whose score is < 2 can be considered benign. Therefore foe the diagnosis of melanoma the presence of at least one of the maior criteria or the coexistence of two of the minor ones is regarded as sufficient (Fig 9)(12)(13).
This recently developed diagnostic dermoscopic method shows a sensitivity of 95%, a specificity of 86% and an efficiency of 88% (13).

3. The 11 SURFACE MICROSCOPIC FEATURES METHOD OF DIAGNOSIS OF INVASIVE MELANOMA
Menzies and colleagues have designed a method which is based on the identification of eleven ELM features, thus enabling even the less expert observer to use it easily (14).
The ELM criteria considered to design the model (14)(42-43) were selected for low sensitivity (negative features) and high specificity (positive features) (14).
According to this algorithm, a pigmented skin lesion showing none of the negative dermoscopic features and at least one of the positive ones, can be considered as a melanoma
(table V).
This method is easy to perform, riproducible and reliable, showing a sensitivity of 92% and a specificity of 71% in diagnosing cutaneous melanoma (14).

4. THE NEW 7-POINT CHECKLIST BASED ON PATTERN ANALYSIS
Epiluminescence microscopic images of 342 melanocytic skin lesions were studied during a research carried out by Argenziano and coworker in order to evaluate the frequency of seven ELM criteria (and eleven variables of them) (15). These dermoscopic features were selected for their frequent association with melanoma (44) and for their particular histopathologic correlates (17)(45) to develope a new diagnostic method based on simplified ELM pattern analysis.
Most of the features considered to perform the new algorithm belong to the terminology that has been standardised during the Consensus Meeting held in Hamburg (8). (Table VI).
In addition the followings ELM features were included in order to design a diagnostic model termed "ELM 7-point checklist": irregular diffuse pigmentation (blotches)(3),"Peppering" (multiple gray-blue dots)(46) and atypical vascular pattern (Fig 10)(10)(45)(47).
Using an arbitrary cut-off of odds ratios calculated by a multivariate analysis, the authors divided the selected dermoscopic features into 2 main groups: "major criteria" (odds ratios> 5) and "minor criteria" (odds ratios <5). A score of 2 is given to the 3 major features and a score of 1 to the 4 minor criteria considered. By adding all the individual scores found whithin the melanocytic skin lesion examined by means of ELM, a total score ³ 3 allows the diagnosis of melanoma. For a melanoma to be diagnosed, the identification of at least 1 major and 1 minor dermoscopic criterion (or 3 minor criteria) is needed, thus confirming the basic rule of epiluminescence microscopy that one single criterion is never enough to make a diagnosis and the absence of a criterion doesn’t rule out the diagnosis (3).
The 7-point checklist gave a sensitivity of 95%, a specificity of 75% and a diagnostic accuracy of 64% in the diagnosis of melanoma (15).


DIAGNOSTIC PERFORMANCE: CLINICAL EXAMINATION VS. ELM

There is a general agreement in the international literature that the most effective management of malignant melanoma consists in early recognition and subsequent surgical excision of thin lesions (48). The strong inverse correlation of 5-years survival rate with tumor thickness measured according to Breslow (49), and the lack of effective therapies for metastatic melanomas still today gives early detection of equivocal melanocytic proliferation of the skin the highest priority in order to increase the cure rate of melanoma (50).
Epiluminescence microscopy is not really required for the diagnosis of advanced and clinically typical forms of melanomas or benign pigmented skin lesions where purely clinical criteria usually suffice a correct diagnosis . On the other hand, even in specialized centers the diagnostic accuracy of clinical examination alone is not higher than 64% (51) dealing with small pigmented lesions that have may not yet developed enough the standard clinical features of malignancy (51-52).
Dermatoscopy has the ability to move these diagnostic limitations to a higher level, because this method allows the investigators to recognize in vivo malignant melanomas much earlier than by clinical examination alone (34)(41).
The percentage of correct diagnoses increased from 73% to 83% for junctional naevi, from 56% to 93% for pigmented spitz naevi, from 50% to 83% for in situ SSM, from 54% to 91% for invasive SSM and from 46% to 62% for nodular melanomas (3). A remarkable improvement was found especially for pigmented, non-melanocytic lesions, namely, seborrhoeic keratosis (from 62% to 77%) (Fig 11), basal cell carcinomas (from 58% to 84%) and angiomas-angiokeratomas (Fig 12) (from 83% to 100%) (3).
According to a formal study designed to compare the reliability of dermoscopy to that of clinical diagnosis in a series of doubtful melanocytic skin lesions, clinical diagnosis was correct in 40% of cases whereas the dermoscopic diagnosis was correct in 55% (34). From these data, the average gain in the percentage of correct diagnoses by dermoscopy was 15.6%. Concerning the diagnosis of melanoma the sensitivity increased from 42% to 75% and the specificity from 78% to 89% by means of dermoscopy (34).
It is important to emphasize, however, that the ELM analysis doesn’t completely eliminate diagnostic errors (22) and cannot replace histopathologic diagnosis (3). ELM does not provide 100% diagnostic accuracy, therefore it cannot be used as the only indicator for excision (14). To achieve this purpose an integration between clinical and dermoscopic features should be obtained (34).


ELM DIAGNOSIS: INTRA- AND INTER- OBSERVER REPRODUCIBILITY

In determinating the level of standardization for dermoscopic diagnostic criteria there is no alternative to agreement studies. Intraobserver variability researches have been performed in several branches of pathology and have played an important role in developing standardised classification .
The aim of a study carried out by Stanganelli and colleagues was to evaluate intraobserver agreement on ELM criteria by means of kappa (k) statistics (53). High levels of agreement were found for the following descriptors: presence/absence of pigment network, diffuse pigmentation, pseudopods, radial straming, gray-blue areas, brown globules and depigmentation . However, most descriptors other than presence/absence (Distribution, width, thickness, size, pigmentation ) showed lower levels of agreement for all the criteria considered with the only two exceptions of black dots and whitish veil.
The most plausible explanation for the low levels of intra-observer agreement for some types of criteria is the lack of standardised definitions (53).
Concerning the inter-observer agreement of dermoscopy in the diagnosis of melanocytic skin lesions Binder and co-workers (29) showed an increase of interobserver agreement by using dermoscopy compared to clinical examination for ELM trained examiners (average gain 7%). Another study did not confirm this finding showing that inter-observer reproducibility of dermoscopy compared to clinical examination, also for experienced obserevers, remains substantially unchanged (k value of 0.52 and 0.54, respectively) (34). The level of inter-observer agreement in the detection of specific dermoscopic paramters, intended as presence/absence of the parameter, was found to be good for all of them, with the highest value for pseudopods . The lowest value of agreement among the examiners was shown for pigment network probably due to the morphological variability of network structures particularly in malignant lesions (34).


DERMOSCOPIC CRITERIA OF CUTANEOUS MELANOMA PROGRESSION.

Cutaneous melanoma develops through a series of evolutionary phases that are traceable in specific histologic patterns (54). During melanoma progression, the occurrence of specific histologic patterns obviously modifies also the dermoscopic profile of a given lesion.
In a previous study of our group dermoscopic criteria were elaborated that characterise the different phases of melanoma progression as well as the various tumor depths (45). A significant association was found between the presence of pigment network within the lesions and melanomas < 0.76 mm thickness (thin MM), and between the presence of gray-blue areas, vascular pattern and melanomas >0.75 mm thickness (thick MM) . Pigment network variations associated to radial streaming were the most significant association of dermoscopic criteria in thin lesions, whereas the association of gray-blue areas and vascular pattern is the most relevant finding in thick melanomas (45).


ELM CRITERIA FOR THE PREOPERATIVE ASSESSMENT OF CUTANEOUS MELANOMA THICKNESS.

Melanoma thickness is used to estabilish the width of surgical margins for excision of melanoma (55-56) as well as to select the patients for sentinel lymph node biopsy (57-58). In order to ensure a correct surgical approach reliable preoperative parameters on melanoma thickness are warranted.
Previous studies showed the poor reliability of melanoma palpability (clinical elevation of the lesion) in predicting melanoma thickness (59-60).
Recently, it has been demonstrated by Argenziano and co-workers that there exists a good correlation between the frequency of appearence of certain dermoscopic criteria and the thickness of the lesion (45). Based on the combination of clinical criteria (palpability and diameter > 1.5 cm) and dermoscopic criteria (pigment network, gray-blue areas, and atypical vascular pattern) the accuracy in the preoperative assessment of melanoma thickness could be enhanced compared to separate application of these two criteria (60).
According to preliminary results of a study carried out by our group, also the ABCD rule of dermoscopy was found to play a possible role in the preoperative evaluation of melanoma thickness. In facts, we found that Total Dermoscopic Score (TDS) attributed to melanomas according to the ABCD rule of dermatoscopy correlates with the the thickness of the lesion (62).


DIGITAL EPILUMINESCENCE MICROSCOPY (D-ELM).

Digital ELM (D-ELM) is a new technology that can improve clinical visualisation and facilitate a more detailed study of the subtle epidermal and superficial dermal anatomy of pigmented lesions (19)(25)(63). By enabling high-quality visualisation, documentation and measurement of subtle ELM diagnostic features, the development of standards for ELM differential diagnosis and management of pigmented skin lesions can be facilitated.
Therefore, there is a current push toward the possibility of introducing objective, computer-based, image analysis (machine vision) into the daily clinical practice of specialized medical centers dedicated to the diagnosis of pigmenetd skin lesions.
Digitisation of dermoscopic images has been driven by the requirements of several applications: digital image processing to assist the naked eye (19)(25)(64); developement of expert systems for automatic classification of melanocytic lesions (65-66) ; automatic machine vision, a fully automatic digital processing that employs images at wavelengths invisible by naked eye (UV, IR) (66-67); electronic transmission of images for remote diagnosis (telemedicine) (68-69); and image storage and retrieveval (70) .
To date, dermatologists are using for diagnosis of pigmented skin lesions only a very small fraction of the informations located into ELM images. Thus one of the main challenge of the research in digital acquisition and processing of dermoscopic images is to disclose a new dimension of informations residing in such images (63).
The new technologies, actually, enables high quality digital ELM images to be sent with the support of network systems such as Internet and ISDN by using common telephon lines and satellite communication (teledermatology) (68)(71). Analysis of image data shows that "informativeness" (72) of selected dermoscopic structures of lesions employed for naked-eye diagnosis of pigmented skin lesions is preserved despite their remote location (69). So, we can conclude that the future of early diagnosis of melanoma by means of digital epiluminescence microscopy depends directly on further investigations in the fields of communication technology.

 

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Table I. ELM criteria and histologic correlates for pigmented skin lesions (8)(41)

ELM CRITERION DEFINITION HISTOLOGIC CORRELATES
Pigment network Network of brownish lines over a background tan Pigmented rete ridges
Diffuse pigmentation (blotches) Pigmentation that preclude recognition of other criteria Melanin at all levels of the epidermis and/or the dermis
Brown globules Round, oval or sferical bodies Nests of pigmented melanocytes at the dermal-epidermal junction and/or in the papillary dermis; or clusters of melanophages in the papillary dermis
Black dots Small, punctate and black structures Focal collections of melanin in the stratum corneum
Radial streaming Linear, brown to black streaks radiating from the border of the lesions Radially arranged pigmented nests
Pseudopods Bulbous, often kinked projections, directly connected to the body of the lesion or to the pigmented network Radially arranged pigmented nests
Whitish veil Whitish film overlying a more darkly pigmented area Compact orthokeratosis and hypergranulosis
Gray-blue areas Circumscribed zones that have a gray and/or blue hue Fibrosis and pigmented melanophages or melanocytes in a thickened papillary or reticular dermis
White areas Depigmented areas that appear as dead white or light pink patches Lack of melanin and fibroplasia
Hypopigmented areas Areas of relatively lighter pigmentation Reduced amount of melanin
Vascular pattern Linear, dotted, or globular red structures Neovascularization or vascularized nests of amelanocytic cells
Horny pseudocystis Circular whitish-yellow areas Intraepidermal horn globules underneath the surface
Pseudofollicular openings Comedo-like openings Intraepidermal horn globules reaching the surface
Red-blue areas Red-blue, sharply demarcated areas Dilated vascular spaces in the papillary dermis
Maple leaf-like areas Maple leaf-like, light to dark brown areas with branching or bud-like arrangement Pigmented epithelial nodules
Pseudopigment network A grid of large, roundish, brown meshes Melanotic pigment arranged around sebaceous follicles, quite numerous on the face

 

 

Table II. Pattern analysis suggestive for benign nevi and melanoma.

ELM CRITERION melanocytic nevus melanoma
Pigment network regular, delicate, faint at the periphery irregular, prominent, with abrupt end at the periphery
Diffuse pigmentation (blotches) absent or homogeneously present at the centre of the lesion, gradually thins at periphery irregularly distributed, inhomogeneous, abruptly ends at periphery
Brown globules absent (junctional nevus) or regularly distributed, mainly at the centre of the lesion, with homogeneous characteristics varied in size and shape, irregularly distributed
Black dots uniform in size and shape, regulalry distributed, mainly present at the centre of the lesion. irregularly distributed, with inhomogeneous features
Radial streaming usually absent frequently present (in about 25% of cases )(22)
Pseudopods absent (regularly distributed pseudopods can be found in pigmented Spitz’s nevi) (73) Irregularly distributed, present in about 31% of cases (22)
Whitish veil absent often present (51% of cases, depending on the thickness: higher frequency in thicker lesions) (21)(45)
Gray-blue areas absent (diffuse homogeneous greay-blue pigmentation without other ELM features : blue nevus); a small area of gray-blue pigmentation at the centre of the lesion can be seldom found in nevi with histologic atypia) present, irregulalry distributed (the frequency depend on the thickness of the lesion, higher in thicker lesions )(45)
White scarlike areas usually absent present, irregular
reticular depigmentation regularly present (centre of the lesion) in pigmetned Spitz’s nevi (negative pigment network) seldom present, but with irregular meshes and holes
Hypopigmented areas frequently present at the centre of the lesion, with homogeneous distribution when present, it is irregularly distributed
Vascular pattern homogeneous, "hair-pin like" in dermal nevi atypical (linear and dotted, presence of "milky red" glodules, ie. globules of melanocytes with erythema due to neovascularisation phenomena)
Horny pseudocystis seldom present in papillary dermal nevus (always present in seborrheic keratosis, without "melanocytic" ELM features) usually absent (a case-report of melanoma showing horny pseudocytic has been reported in the literature)(26)
Pseudofollicular openings absent (always present in seborrheic keratosis) absent
Red-blue areas absent (red blue areas are diagnostic for angioma when melanocytic ELM features are lacking) absent
Maple leaf-like areas absent (they are diagnostic for pigmented basal cell carcinoma when melanocytic ELM featrues are absent absent
Pseudopigment network peculiar of the lesions on the face; regularly distributed irregular

 

 

Tab III Calculation of ABCD score for dermatoscopy (9-10).

Criterion Possible points Weight factor Score (min/max)
Asimmetry 0-2 x 1.3 0.0/2.6
Border 0-8 x 0.1 0.0/0.8
Colors 1-6 x 0.5 0.5/3.0
Dermoscopic

structures

 

1-5

 

x 0.5

 

0.5/2.5

 

TDS

 

1.0/8.9

 

 

Tab IV Dermoscopic description and score of the seven ELM features used for the 7FFM (13).

Dermoscopic feature Description Score
Regression-erythema White-pinkish depigmented area 2
Radial streaming Thin, closely spaced, parallel pigmented streaming irradiating from the rim of the lesion 2
Gray blue veil Blue or gray-faded blue area with ill-defined margins, asymmetrically located inside the lesion.

No clearly dermoscopic features are observed.

2
Irregularly distributed pseudopods Finger-like extensions present at the periphery of the lesions, varyng in colour from brown to black 2
Unhomogeneity Asymmetrical or irregular distribution within the lesion of at least two dermoscopic features. 1
Irregular pigment network Coarse, strongly pigmented, irregular pigment network 1
Sharp margin Abrupt cessation, of the dermoscopic features at the periphery of the lesion not < ¼ of the margin 1
  • The criterion regression-erythema corresponds to regression together with vasodilatation and neoangiogenesis (74-76).
  • Unhomogeneity corresponds to an histopathological architectural disorder of the lesion (13).

 

 

Tab V Method of diagnosis of melanoma according to Menzies (14).

Positive features (at least one found) Negative features (can’t be found)
  1. Blue-white veil
  2. Multiple brown dots
  3. Pseudopods
  4. Radial streamings
  5. Scarlike depigmentation
  6. Peripheral black dots/globules
  7. Multiple (5-6) colors
  8. Multiple blue/gray dots
  9. Broadened network
  1. Point and axial symmetry of pigmentation
  2. Presence of a single colour

 

 

Tab VI ELM 7-point checklist: definitions, histological correlates and scores of dermoscopic criteria (15).

ELM criterion Definition Histological correlates (NIH cons conf 92)(Stolz et al 94 color atlas) 7-point score
Maior criteria
Atypical pigment network Prominent (hyperpigmented or broad) and irregular network Hyperpigmented or broadened rete ridges with irregular shape or distribution 2
Gray-blue areas Irregular, confluent, gray-blue to whitish blue diffuse pigmentation not associated with red-blue lacunes or maple leaf pigmentation Pigmented melanophages or melanocytes of midreticular dermis location 2
Atypical vascular pattern Linear, dotted, or globular red structures irregularly distributes outside areas of regression and associated with other melanocytic pigment patterns Neovascularization or vascularized nests of amelanotic cells 2
Minor criteria
Radial streaming (streaks) Radially and asymmetrically arranged linear or bulbous extensions at the edge of the lesion Confluent radial junctional nests of melanocytes (42) 1
Irregular diffuse pigmentation (Blotches) Brown, gray and black areas of diffuse pigmentation with irregular shape or distribution and abrupt end Hyperpigmentation throughout all levels of epidermis or upper dermis (in melanocytes or melanophages) 1
Irregular dots and globules Black, brown or blue round structures irregularlydistributed within the lesion Aggregates of pigment of stratum corneum, junctional or dermis location 1
Regression pattern White scarlike depigmentation or "peppering" (speckled multiple blue-gray dots within a hypodepigmented area) irregularly distributed within the lesion (45) Areas of loss of pigmentation and fibroplasia, with scattered dermal melanophages 1

 

 

Appendix A. CME questions

  1. Covering the lesion with immersion oil together with a glass slide appplied with a slight pressure during ELM is aimed to:
  1. spread the surface of the lesion
  2. render the horny layer translucent
  3. eliminate the surface reflection
  4. eliminate the different refractive index mismacht between air and skin

True: b,c,d,; False: a,

 

  1. The anatomic basis of pigment network is
  1. amount of melanin in the whole epidermis
  2. nests of pigmented cell in the upper dermis
  3. melanin pigment in the epidermal basal cells

True: c, ; False a, b

 

3. The anatomic basis of brown globules is

  1. melanin pigment in the horny layer
  2. nests of pigmented cells at the dermo-epidermal junction
  3. thrombosed vessels in angiomatous lesions

True: a ; False a, c

 

4. Dermoscopic parameters suggestive of a melanocytic differentiation are :

  1. brown globules and pseudopods
  2. radial streaming
  3. horny pseudocysts
  4. pigment network
  5. grey-blue areas

True: a, b, d ; False : c, e

 

5. ELM diagnosis based on pattern analysis is:

  1. the simultaneous assessment of all dermoscopic features present within a lesion
  2. the use of dermoscopic features more strongly associated with malignancy
  3. a diagnostic procedure valid for both melanocytic and non-melanocytic pigmented lesions
  4. a diagnostic procedure valid for melanocytic pigmented lesions only

True: a, c ; False b, d

 

6. In the pattern analysis procedure:

  1. one single criterion is sufficient to make a diagnosis
  2. the absence of a criterion is more important than its presence
  3. the presence of a criterion is more important than its absence
  4. all criteria have the same importance
  5. some criteria are more important than others

True: c, e: False a, b, d

 

7. The diagnostic performance of ELM is influenced by

  1. the machinery used
  2. the age of the patient
  3. the level of experience of the examiners

True: c; False a, b

 

8. A diagnosis of melanoma should be suspected by means of pattern analysis when a lesion shows:

  1. delicate pigment network and numerous black dots at the centre of the lesion
  2. pigment network which faints at the periphery and brown globules homogenesouly distributed both at the centre and periphery
  3. pseudofollicular openings together with horny pseudocists
  4. irregular pigment network associated with grey-blue area

True: d; False: a, b, c

 

9. Radial streaming are most frequently observed in:

  1. cutaneous melanomas
  2. melanocytic naevi
  3. pigmented basal cell carcinomas
  4. vascular lesions

True: a; False: b,c,d

 

  1. A pigmented skin lesion shows under dermatoscopy the following ELM features: brownish-black pigmentation, black dots, horny pseudocysts. What is your diagnosis?
  1. dermal melanocytic naevus
  2. pigmented basal cell carcinoma
  3. in situ melanoma
  4. pigmented seborrheic keratosis

True: d; False: a,b,c

 

  1. Following the ABCD algorithm , a diagnosis of melanoma should be made when the total dermoscopic score (TDS) is:
  1. lower than 5.45
  2. higher than 4.75
  3. higher than 5.45

True: c ; False a, b

 

  1. Following the 7FFM algorithm, a diagnosis of melanoma should be made when the lesion shows:
  1. regression-erythema or grey-blue veil
  2. irregularly distributed pseudopods
  3. sharp margin and irregular pigment network
  4. only irregular pigment network

True: a, b, c ; False: d

 

  1. Following the seven -point check list algorithm the presence of at least one major parameter is sufficient for the diagnosis of melanoma
  1. true
  2. false

True: b; False : a,

 

  1. During melanoma progression thick lesions (> 0.75 mm in depth) more frequenlty reveal the following ELM features compared to thin lesions (< 0.75 mm in depth):
  1. irregular pigment network
  2. irregular black dots
  3. grey-blue areas and atypical vascular pattern

True : c; False: a, b,

 

  1. Mucosal melanosis can be classified by dermoscopy on base of the following features:
  1. presence of numerous globules and dots
  2. lack of diffuse pigmentation
  3. presence of diffuse pigmentation as only dermoscopic parameter
  4. regularly distributed pseudopods

True: c; False: a, b, d

 

Address for correspondence:

P.Carli
Department of Dermatology, University of Florence, Italy.