Dermoscopy Author: Ignazio Stanganelli, MD, Director of Cutaneous Oncology, Niguarda Ca' Granda Hospital; Director, Skin Cancer Unit, Center for Cancer Prevention, Italy Coauthor(s): Maria Antonietta Pizzichetta, MD, Consulting Staff, Division of Preventive Oncology, Centro Di Riferimento Oncologico of Aviano, Italy Contributor Information and Disclosures Introduction The widely used acronym ABCDE (asymmetry, irregular borders, multiple colors, diameter >6 mm, enlarging lesion) contains the primary clinical criteria for diagnosing suspected cutaneous malignant melanoma (CMM). The early phase of malignant melanoma is difficult to identify because CMM can share many clinical features with an atypical nevus. Several studies have described diagnostic accuracy rates ranging from 50-75%, indicating a need for additional diagnostic tools. In the last 10 years, the introduction of dermoscopy, also termed epiluminescence microscopy (ELM), has opened a new dimension in the examination of pigmented skin lesions (PSLs) and, especially, in the identification of the early phase of CMM. Dermoscopy is a noninvasive method that allows the in vivo evaluation of colors and microstructures of the epidermis, the dermoepidermal junction, and the papillary dermis not visible to the naked eye. These structures are specifically correlated to histologic features. The identification of specific diagnostic patterns related to the distribution of colors and dermoscopy structures can better suggest a malignant or benign PSL. The use of this technique provides a valuable aid in diagnosing PSLs. Because of the complexity involved, this methodology is reserved for experienced clinicians. The equipment; technologic methods; diagnostic features; and primary aspects of melanoma, common nevi, atypical nevi, and other nonmelanocytic PSLs are discussed in this article. The Medscape Skin Cancer Resource Center may be of interest, as may the Medscape CME course Complete Skin Examination With or Without Dermoscopy Feasible for Skin Cancer Screening and the eMedicine article Malignant Melanoma. Technical Procedures and Equipment Dermoscopy involves an evaluation of the skin surface. During a dermoscopy assessment, the PSL is covered with a liquid (usually oil or alcohol) and examined under a specific optical system (see Media Files 1-4). Applying oil reduces the reflectivity of the skin and enhances the transparency of the stratum corneum. This allows visualization of specific structures related to the epidermis, the dermoepidermal junction, and the papillary dermis, and it also suggests the location and distribution of melanin. Dermatoscope The dermatoscope (see Media File 1) is the simplest and best-recognized piece of equipment used to perform a dermoscopy examination. It is similar to an otoscope, is user friendly, and is inexpensive. This optical system's features include monocular observation, magnification X10, and the use of an illumination system (3.5-V halogen lamp). Stereomicroscope Another optical instrument, the stereomicroscope (see Media File 1), allows an accurate binocular observation with different magnifications (X6-80). The illumination system includes a halogen lamp (12 V/50 W). The stereomicroscope is expensive, is large and bulky, and is only available in a few centers. From an empiric point of view, visualization is better than with the dermatoscope, but formal studies of the differences in diagnostic features and accuracy of the 2 instruments have never been published. Videodermatoscope Features of another optical system, the videodermatoscope (see Media File 2), include a video probe that transmits images of the PSL to a color monitor. The recent addition of a digital system to the stereomicroscope, also termed the digital epiluminescence microscope (see Media File 3), and/or to the videodermatoscope has opened a new area of development with the advantages of computerized technology. However, the technologic features (which are cost dependent) of the camera (single-chip video charge-coupled device, 3-chip charge-coupled device, or still digital; see Media File 4), optical system, monitor, digitized board, and software can influence the resolution and quality of the images. These features can strongly influence the evaluation of a PSL; a low-resolution instrument may prevent accurate diagnosis. Color Accurate evaluations of the color of a PSL, the degree of pigmentation, and the distribution of the colors within the lesion are the most important elements of a dermoscopy examination. The epidermis usually appears white, but acanthosis results in a grayish-brown or brownish-yellow color. Melanin is the most important pigment in determining different structural and chromatic patterns. The PSL can have a different degree and distribution of pigmentation depending on the location of melanin in different layers of the skin. Melanin location and lesion color Upper epidermis (stratum corneum, stratum spinosum) - Black Dermoepidermal junction - Light-to-dark brown Papillary dermis - Slate blue Reticular dermis - Steel blue Other possible colors include various shades of white and red. White shades are related to regression and may be seen with melanomas, benign melanocytic nevi (halo nevus), and nonmelanocytic lesions (lichenoid keratosis, scars). Red shades are related to increased vascularization in tumors, an increased number of capillary vessels, and bleeding within the lesion. If bleeding persists and crust develops, the color ranges from red-black to blue-black. A good evaluation of colors and their relative distribution is essential for achieving the correct clinical diagnosis of a PSL. Guide Criteria ELM features can be divided into primary and secondary guide criteria, which show numerous different manifestations related to chromatic and geometric variables (eg, distribution, width, caliber); these are discussed in detail in the description of each ELM feature. Primary criteria Pigment network The most important ELM feature of melanocytic lesions is the pigment network (PN), which consists of pigmented network lines and hypopigmented holes. This feature is correlated histologically to the length of the rete ridges and to the distribution of melanin within the keratinocytes of the epidermal rete ridges. The network of hypopigmented holes corresponds to the suprapapillary plate, which is relatively thin and contains less melanin. The network lines correspond to the rete ridges, which are thicker and have a greater quantity of melanin. In melanocytic nevi, the PN is slightly pigmented. Light-brown network lines are thin and fade gradually at the periphery. Holes are regular and narrow (see Media Files 5-9). The distribution is symmetric and sometimes accentuated in the center of the lesion (see Media Files 10-13). In melanoma, the PN usually ends abruptly at the periphery and has irregular holes, thickened and darkened network lines, and treelike branching at the periphery (see Media File 14). In CMM, the PN features change between bordering regions. Some areas of malignant lesions manifest as a broad and prominent PN, while others have a discrete irregular PN. The PN also may be absent in some areas (see Media File 15). Atypical nevi (dysplastic nevi) are difficult to diagnose at times because they may show areas of irregular and discrete PN distributed asymmetrically (see Media File 16). Pseudopigmented network ELM features of homogeneous pigmentation of the face (interrupted by hypopigmented hair follicles and hypopigmented sweat gland openings) create a pseudopigmented network. In benign lesions, this pseudonetwork tends to be uniform and symmetric in color and pattern (see Media Files 17-18). In contrast, in lentigo maligna (see Media File 19) and lentigo maligna melanoma, the pseudonetwork becomes nonuniform and asymmetric in color and pattern because of the increased number of atypical melanocytes extending down hair follicles and adnexal structures. The meshes become broader, and the holes are larger. Radial streaming and pseudopods Radial streaming and pseudopods are different morphologic expressions of malignant melanoma, specifically melanoma in the radial growth phase. Radial streaming (see Media File 20) is a linear extension of pigment at the periphery of a lesion, often appearing in groups of nearly parallel, radially arranged linear structures. Depth determines the colors, which are brown, dark brown, blue-gray, and black. Pseudopods (see Media File 21) are curved fingerlike projections that are predominantly dark brown or black and are located at the periphery of a lesion. They occasionally have small knobs at their tips. Radial streaming and pseudopods histologically correspond to confluent junctional nests of atypical melanocytes. Pigmented globules Pigmented globules are round or oval, dark brown or black, and larger than 1 mm in diameter. They are uniform in PSLs but vary in size, color, and shape in atypical nevi and melanoma. When abundant, aggregated globules have a cobblestone pattern (see Media Files 22-23), which is typical of benign melanocytic lesions (see Media Files 22-25). In CMM, globules are dark or slate blue and are distributed irregularly (see Media File 26). Occasionally, isolated dark globules are seen at the margins of an achromic lesion; in this case, a diagnosis of melanoma is suggested. Pigmented globules correspond histologically to nests of pigmented melanocytes (nevus or melanoma) at the junction in the papillary dermis or, because of melanin storage, in melanophage clusters in the papillary dermis. Milky-red globules can be seen in CMM, representing melanoma cell nests with increased vascularization. Secondary criteria Pigmented dots Pigmented dots are small, round or irregularly shaped pinpoint structures that are black or dark brown. They correspond to focal accumulations of free melanin or an increased number of highly pigmented melanocytes in the cornified layers of the epidermis. The presence of melanophages and/or atypical melanocytes in the dermis correlates with bluegray or slate blue dots and is typically found in pigmented melanocytic and nonmelanocytic lesions undergoing regression. Vertical capillaries found on apical dermal papillae appear as red dots on the palms and soles; sweat gland openings appear as white dots. In benign melanocytic lesions, dots in the center of the lesion are homogeneous in color and are regular in size, shape, and distribution (see Media File 27). In CMM or in atypical lesions, dots may occur at the periphery of the lesion and are irregular in size, shape, and distribution (see Media File 28). Blue-white veil A blue-white veil is a ground-glass area of pigmentation that is blue-gray to blue-white in color. This ELM feature is present in homogeneously pigmented black or dark brown lesions and is associated with thickening of the epidermis (see Media Files 28-29). It is correlated histologically with compact orthokeratosis and hypergranulosis, with confluent nests of heavily pigmented melanocytes in the dermis. A blue-white veil is often found in melanomas (see Media File 14, Media Files 20-21, Media File 28) and Spitz nevi (see Media File 29). Blue-gray areas Blue-gray areas are ELM features with coloration varying from gray-blue to deep gray. Blue-gray or bluish areas may be either isolated disseminated granules or peppering and ill-defined spots with bizarre margins (see Media File 30). They may be associated with melanoma regression. They are correlated histologically with the presence of melanin and/or hemosiderin within melanocytes and melanophages, and blue-gray areas may be free in the papillary and middle dermis. Steel blue areas Steel blue areas are structureless, gray-blue, and homogeneously diffuse. They are found in blue nevi (see Media File 31) and occasionally are associated with globules, dots, or both. A central steel blue area may be found in some combined blue nevi. Depigmentation Depigmentation depends on a lack or reduction of pigment in the PSL. With depigmentation, differentiation can occur in hypopigmented regions that correspond to pigmented areas lighter than other areas within the nevus (see Media File 32). Differentiation also can occur in white areas that correspond to well-defined white (see Media File 28) or milky red-white areas (see Media File 33). In contrast to hypopigmented areas, depigmented areas completely lack pigment. Histologically, they correspond to fibroplasia, telangiectasias, and loss of melanin. Nonspecific Guide Criteria Milialike cysts Milialike cysts are small, circular, whitish-yellow areas with sizes ranging from 0.1-1 mm (see Media File 34). They are important for the diagnosis of seborrheic keratosis but can also be found in papillary melanocytic nevi and melanoma, although in seborrheic keratosis, they are larger. Histologically, milialike cysts correspond to keratin-filled cysts. Comedolike openings Comedolike openings are another typical diagnostic feature of seborrheic keratosis. They are keratin-filled porelike openings that communicate with the surface of the lesion. They appear yellow-brown, with a circular or oval shape and a light round halo (see Media File 34-35). They are correlated histologically with keratin within the invaginations of the epidermis. Red-black lagoons Red-black lagoons are the pathognomonic diagnostic criteria of hemangioma and angiokeratomas. They are small, well-defined, oval or round areas that range from blue-red to blue-black (see Media File 36). Histologically, they correspond to large lagoons and thrombi within the vascular spaces of papillary dermis. Subungual hemorrhages can have blue-red and/or red-black homogeneous pigmentation without vascular lagoons (see Media File 37). Maple leaf–like pigmentations Maple leaf–like pigmentation, an important diagnostic criterion for basal cell carcinoma, is graybrown to gray-black with a shape similar to that of a maple leaf or to the fingers of a hand (see Media File 38). Histologically, they correspond to heavily pigmented basaloid cells within the nest of basal cell carcinoma. Vascular Patterns Vascular patterns are important markers for melanocytic and nonmelanocytic lesions. The vascular pattern can be evaluated more accurately using magnification of higher than 10X. Kreusch and Koch described the main vascular patterns as follows: Treelike vessels are described as thick, arborizing vessels; they are compatible with pigmented basal cell carcinoma of any type (see Media File 39). Corona vessels are thinner and less curved than treelike vessels. Generally, they surround a sebaceous gland hyperplasia (see Media File 39) Comma-shaped vessels are parallel to the skin surface and appear as short, strong, curved vascular structures often visible in the dermal nevi (see Media File 40). Point vessels are short capillary loops visible as pinpoint dots. They are commonly seen in all types of melanocytic tumors and superficial epithelial tumors (ie, actinic keratosis [see Media File 40]; Bowen disease). Hairpin vessels are long capillary loops of thicker tumors and are related to angiogenesis of thick melanomas (at the border) but also squamous cell carcinoma, keratoacanthoma, and seborrheic keratosis. A combined evaluation of linear and other types of vascular features is called linear irregular vessels and is often seen in melanoma (see Media File 41). Overview of Different Dermoscopic Diagnostic Procedures The different technical instruments and the guidelines for dermoscopy diagnosis for PSLs are described in Guide Criteria and Technical Procedures and Equipment, respectively. This section describes the different methods of classification and diagnosis using dermoscopy that have been developed in the last several years. In the world of dermatology, ELM recognition of suggestive melanomas is based on the observation of numerous parameters; not just one of these factors is specific for melanoma. The literature shows that many different methods of classification are used for dermoscopy. The most widely used ELM procedures are pattern analysis, the ABCD dermoscopy rule, the Menzies methods, the 7-point checklist, and the stratification of risk level. Pattern analysis Described by Pehamberger et al1 and recently redefined by the Consensus Net Meeting on Dermoscopy (CNMD), pattern analysis is the procedure most used by dermatologists. Its efficiency is correlated to the experience of the observer. Pattern analysis uses a process of diagnostic framing that keeps control of the known analytic data of all the dermatoscopic parameters of PSLs and of the prevalence of single variables. That is, it helps determine if the PN is present or absent, and, if the PN is present, if it is regular or irregular and delicate or prominent, among other variables discussed earlier. The various types of PSLs, and specifically differentiation between benign and malignant melanocytic lesions, can be determined through pattern analysis of specific dermatoscopic features. The 2 steps in the new process of pattern analysis are (1) deciding whether the lesion is melanocytic or nonmelanocytic and (2) identifying the melanocytic lesion, making a diagnosis, and planning relative management. Pattern analysis has been deemed superior to the other algorithms (ie, ABCD dermoscopy rule, Menzies method, 7-point checklist) for diagnostic efficiency by experts all over the world in the 2000 CNMD. Pattern analysis - Step 1 The first step to identifying a melanocytic lesion is to look for the presence of aggregated globules (see Media Files 22-23), PN (see Media Files 5-8 and Media File 16), or branched streaks (ie, fragmented irregular PN) (see Media Files 14-15). If the above patterns are absent, other characteristics should be sought (substeps). First, note that a typical marker for blue nevus is the presence of homogeneous steel blue areas (see Media File 31). Second, the lesion should be evaluated for the presence of moth-eaten borders, fingerprinting, comedolike openings, and milialike cysts. In this case, the lesion is suggestive of either a solar lentigo (see Media File 18) or a seborrheic keratosis (see Media File 34). Third, if red or red-blue to black lagoons are present, the lesion should be considered a hemangioma (see Media File 36) or an angiokeratoma. Finally, the lesion should be evaluated for maple leaf–like structures, arborizing telangiectasias, spoke-wheel–like areas, and gray-blue ovoid nests. This lesion is compatible with a basal cell carcinoma (see MediaFile 38). All lesions should be reevaluated to determine if they have a melanocytic structure, even if they do not have the structures described above. Pattern analysis - Step 2 The main goal for step 2 is to make an accurate differential diagnosis between benign melanocytic lesions and melanomas. The important features in distinguishing these 2 groups are the overall general appearance of color, architectural order, symmetry of pattern, and homogeneity, known by the acronym CASH. Melanocytic nevi have few colors, a regular design, and symmetrical patterns (see Media File 5, Media File 10, Media File 12, Media Files 16-17, Media File 22, Media File 24, and Media File 31). In contrast, malignant melanoma often has several colors, architectural disorder, asymmetrical patterns, and heterogeneity (see Media Files 14-15, Media File 21, and Media File 46). For the asymmetry evaluation, the lesions are bisected by two 90° axes positioned to produce the lowest possible asymmetry score. Importantly, also incorporate color and structural asymmetry into this ELM parameter because most equivocal lesions have a symmetrical contour (see Media File 50). Thus, asymmetry must be calculated according to the distribution of colors and structures on either side of each axis, and not solely based on contour, as in the clinical ABCD rule (ie, by naked eye). Borders (B): The emphasis is borders that brusquely interrupt at the periphery (see Media File 46). The lesion is visually divided into 8 pie-shaped segments, or eighths, and then the number of segments is counted in which an abrupt cut off is present at the margins of the pigment pattern. The score can range from 0-8 (see Media File 50). Colors (C): The emphasis is the different colors in the lesion (see Media File 47). They include red, white, light and dark brown, blue-gray, and black. White should be counted only if it is lighter than the surrounding skin (white areas) and should not be confused with the hypopigmentation commonly seen in all types of melanocytic lesions. Each color is assigned 1 point, and the total score ranges from 1-6 (see Media File 50). Different structural components (D): The emphasis is different structural components (see Media File 47). These components include the PN, branched streaks (thickened and branched PN anywhere in the lesion, not only at the borders), structureless or homogeneous areas (color, but no structures such as PN, branched streaks, dots, or globules), dots, and globules (see Media File 50). In order to be counted, structureless or homogeneous areas must be larger than 10% of the lesion. Menzies scoring method Menzies scoring method is another effort to simplify the pattern analysis ELM system. This classification identifies 2 negative aspects and 9 positive aspects commonly used in the semeiotics of dermoscopy. To make a diagnosis of melanoma, 2 negative aspects (negative features) must be absent from the lesion and 1 or 2 positive aspects (from 1 of the 9 positive features) must be present. Negative features (see Media Files 51-52) o The symmetry of the pattern is related to the symmetry of the melanocytic lesion. o A symmetry of color (a single color) is observed. Positive features (see Media Files 51-52) o A blue-white veil appears as irregular, confluent, structureless, blue pigmentation with an overlying ground-glass or hazy appearance. o Multiple brown dots appear as focal collections of multiple, dark brown dots, not to be confused with the dark brown globules that are larger and are commonly found in benign nevi. o Peripheral black dots and globules appear as black dots and/or globules found at or near the periphery of a lesion. o Radial streaming is observed. o Pseudopods can be considered variations of the fourth criterion. They are radially oriented or bulbous, fingerlike extensions of the PN at the periphery of a lesion. They should not be scored if they are seen regularly or symmetrically around the lesion. o Scarlike depigmentation (white scarlike area) appears white or milky-white and represents true scarring. o Multiple (5-6) colors are observed, including black, gray, blue, red, dark brown, and tan. White is not counted as a color. o Multiple blue or gray dots appear as foci of multiple "pepperlike" small, blue or gray dots. They are irregular in size and shape (not globules) in the regression areas. o A broadened network shows a localized, thickened, and irregular PN. The 7-point checklist Developed by Argenziano et al2 in 1998, the 7-point checklist is another variation of the qualitative pattern analysis system, but with a point system. This method uses 7 criteria specific for melanoma. It includes 3 major criteria, to each of which is attributed 2 points, and 4 minor criteria, to each of which is attributed 1 point (see Media Files 53-54). This method has fewer criteria to identify and analyze compared with the pattern analysis method. A score of 3 or greater has a high sensitivity of being melanoma. Major criteria o Atypical PN: Black, brown, or gray thickened and irregular line segments are observed anywhere in a lesion. o Blue-whitish veil: Irregular, confluent, gray-blue to whitish-blue diffuse pigmentation is observed that can be associated with PN alterations, dots/globules, or streaks. This differs from the Menzies definition, in which the blue color should be featureless. o Atypical vascular pattern: Linear-irregular and/or dotted red vessels are not seen in regression areas. Minor criteria o Irregular streaks: Pseudopods or radial streaming are irregularly arranged at the periphery of the lesion. o Irregular pigmentation: Black, brown, or gray featureless areas with an irregular shape and/or distribution are observed. o Irregular dots/globules: Black, brown, or gray; round to oval; variously sized structures are irregularly distributed in the lesion. o Regression structures: White scarlike areas and/or blue pepperlike areas are observed. Stratification of risk level Described by Kenet and Fitzpatrick3 in 1994 and recently revised by the Melanoma Cooperative Group, this methodology seems to provide very simple and standardized management of both the diagnosis and therapy of early melanomas and suggestive melanocytic lesions. The stratification of risk level is the basis for the management of melanocytic pigmented lesions. This classification system is based on a wide database of 61,000 examined cutaneous lesions, with 478 diagnosed as cutaneous melanomas (62% stage I, per the American Joint Committee on Cancer). It has 5 risk levels essentially correlated to the history (as described by the patient) and clinical course of the lesion, the presence or absence of a PN, the different variables of the PN associated with the lesion, and other ELM structures (see Media Files 55-56). The stratification risk level includes the following 3 integrated steps: 1. 2. 3. History and clinical evaluation: Genetic factors, including melanoma susceptibility, and a suggestive clinical history (ie, lesion recently changed shape or dimension) should alert the clinician. After a full body evaluation of the skin, PSLs are first classified by the clinical ABCDE rules (ie, asymmetry, irregular border, different colors, diameter >6 mm, evolution) as visible by the naked eye. After this first step, all PSLs showing at least 2 ABCDE criteria and a suggestive family or clinical history should be evaluated using dermoscopy. Dermoscopy evaluation, first analysis: A preliminary ELM evaluation should be performed to classify PSLs as either nonmelanocytic lesions or melanocytic lesions, using the same criteria according to previous guidelines. Melanocytic lesions must be further subclassified in order to plan the best diagnostic strategy. ELM evaluation, second level evaluation for risk-related classification of melanocytic lesions: Melanocytic lesions are classified as very-low, low, medium, high, and very-high risk lesions on the basis of accurate assessment of structural and morphological parameters (see Media Files 55-56). The characteristics and classification of individual lesions is based on the presence or absence of dermoscopy melanocytic features. o o o Type 1 is considered very high risk. These lesions are suspected of being melanoma because they demonstrate dermoscopy features typical for melanoma (see Media File 56). Type 2 is considered high risk. These are atypical nevi or borderline lesions that manifest an irregular network and other features, such as pseudopods or radial streaming, that, in most cases, indicate the presence of atypia. Type 3 is considered medium risk. These are lesions with a PN showing the subtle perturbations that may be present in atypical nevi and lesions with melanocytic hyperplasia. The detection of slight alterations can make diagnosis more difficult, lead to overestimation of the seriousness of a lesion, and result in unnecessary surgery. Clinical history and evaluation findings are important aids to avoiding such overdiagnosis. o o Type 4 is considered low risk. These are PSLs with benign-appearing networks (see Media File 56). Type 5 is considered very low risk. These include lesions with a benign-appearing network and with a globular or other benign ELM pattern. The Melanoma Cooperative Group emphasizes that anamnesis, clinical observation, and other additional parameters be integrated into dermoscopy evaluations for the stratification of risk level in order to standardize the management of melanocytic lesions. Practical approach to the management of a PSL The different dermoscopy classifications have their own worthy internal coherence; however, the use of the different diagnostic scores can be affected by interobserver and intraobserver variability when only a single guideline is used for evaluation (ie, limited qualitative and quantitative agreement). Furthermore, all of these classifications can prove to be very sensitive but not very specific; thus, they do not allow 100% accuracy. Although very useful to detect intraepidermal lesions, dermoscopy is limited in regard to nodular lesions or clearly dermal lesions, lesions without pigmentation, very dark lesions in which the amount of pigment does not allow the observation of ELM signs, and faintly pigmented seborrhoic warts. The efficiency of dermoscopy is closely related to an integrated diagnostic synopsis for trained clinicians. The user must think in global diagnostic terms when considering the accuracy of dermoscopy findings, independent of the methods used; a broader aim is to include case histories and clinical assessment. In fact, the first steps to be integrated by dermatoscopic evaluation are as follows: Anamnesis (personal and family background) Photo-type Previous sunburn history Complete analysis of the entire skin surface (with the intent of finding the so-called "ugly duckling sign") Careful evaluation of the timing of first appearance (and eventual widening) of the lesion being examined and/or modifications of previously existing lesions: A magnifying glass is to be used to carefully observe and evaluate the shape, color, and dimensions of the lesion. Such a combination of the traditional clinical diagnostic procedures and dermoscopy allows better classification of suggestive melanocytic lesions. Hot Topics in Dermoscopy Amelanotic melanoma Amelanotic malignant melanoma is a subtype of cutaneous melanoma with little or no pigment at visual inspection. A review of the literature indicates that amelanotic melanomas represent 2-8% of all malignant melanomas; the precise incidence is difficult to calculate because the term amelanotic is often used to indicate melanomas only partially devoid of pigment. Truly amelanotic melanomas are rare; often some pigmentation is present at the periphery of the lesion, and they may mimic benign and malignant variants of both melanocytic and non-melanocytic lesions. According to the extent of the hypopigmentation, amelanotic melanoma can be classified as follows (1) truly amelanotic melanoma, lacking any trace of melanin even if viewed under dermoscopy; (2) partially pigmented melanoma, with larger or smaller pigmented sections covering up to 30% of its total surface; (3) hypomelanotic melanoma, showing a faint brownish tan with little variation of its intensity, which can occupy more than 30% of its total surface and may cover the entire area. Amelanotic malignant melanoma tends to occur in sun-exposed skin, especially in elderly persons with photodamage, and may appear as erythematous, sometimes scaly, macules or plaques with irregular borders, simulating benign inflammatory plaques, superficial basal cell carcinoma, actinic keratosis, Paget disease, or Bowen disease. It may also manifest as translucent papules, thereby resembling basal cell carcinoma, or it may clinically resemble keratoacanthoma or Merkel cell carcinoma. Alternatively, it may manifest as an exophytic nodule, often eroded, simulating a pyogenic granuloma or hemangioma, or as a skincolored dermal plaque/nodule known as desmoplastic malignant melanoma. From a dermoscopic point of view, amelanotic melanoma lacks most of the dermoscopic criteria reflecting pigmentation, and the vascular structures are frequently the only clue for its diagnosis. The vascular patterns associated to amelanotic melanoma include milky-red globules/areas of dotted or linear irregular or polymorphous vessels (ie, a combination of dotted and linear irregular vessels; see Media Files 40-41). In addition, irregular hairpinlike or glomerular vessels can also be found in amelanotic melanoma, albeit less frequently. Because dermoscopy uses criteria reflecting pigmentation and vascular patterns, it is a useful technique for pigmented melanoma and for amelanotic melanoma. However, the vascular patterns can suggest a diagnosis of melanoma when associated with other criteria found in melanocytic lesions, such as pigment network, irregular pigmentation, streaks, irregular dots/globules, regression structures, and a blue-whitish veil. In truly amelanotic melanoma, vascular patterns alone may not be sufficient to diagnose melanoma because hairpin vessels, dotted areas, and even milky-red areas have also been found in seborrheic keratosis and common nevi, respectively, and in melanomas. A combined approach of dermoscopic evaluation and clinical examination including clinical information such as age, sex, history of melanoma and/or of excessive sun exposure, number and sites of lesions, time of onset, and descriptions of any changes of the lesion over time must play an important role in the diagnosis of truly amelanotic melanoma and for the so-called "featureless" melanomas that lack specific surface microscopic features. Difficult melanomas The primary goal of melanoma detection is early tumor recognition and subsequent surgical treatment. The ABCD method for detecting cutaneous melanoma has been a useful tool in distinguishing benign lesions from melanoma. However, the clinical diagnosis of cutaneous melanoma may be difficult because some melanomas lack all or most of the features of the “ABCD” rule. In fact, some authors have identified a subset of melanomas of unusual appearance, clinically indistinguishable from other pigmented and nonpigmented cutaneous lesions, that escape clinical recognition. The most common clinical diagnoses of these histopathologically confirmed melanomas were nevus, basal cell carcinoma, seborrheic keratosis, and lentigo, while the less common diagnoses included Bowen disease, verruca vulgaris, dermatofibroma, pyogenic granuloma, and hemangioma. Dermoscopic diagnosis for melanoma also may be difficult because some cases lack specific features for melanoma. Some authors have demonstrated the limitations of dermoscopy in the detection of early melanomas that present with an uncharacteristic dermoscopic appearance. Some melanomas, the so-called "featureless melanomas," may lack specific dermoscopic features for melanoma diagnosis and dermoscopically may even appear as benign melanocytic lesions (nevuslike melanomas) or as atypical nevi, so that the diagnosis is impossible to make on dermoscopic grounds alone.4,5 In fact, difficult melanomas present dermoscopic patterns indistinguishable from those of atypical nevi and common nevi. According some authors, melanomas that failed dermoscopic detection belong to the 3 following categories: melanomas showing criteria of melanocytic nevi, melanomas exhibiting criteria of nonmelanocytic lesions, and melanomas lacking specific criteria of a melanocytic or nonmelanocytic lesion (hypomelanotic/amelanotic melanoma).6 In addition, dermatoscopy does not solve the dilemma of discriminating early, featureless melanoma from dysplastic nevi. Only a meticulous comparative and interactive process based on an assessment of all the individual’s other nevi (ugly ducking sign) and a knowledge about recent changes can lead to the recognition of melanomas that are difficult to diagnose. Multimedia Media file 1: Hand-held dermatoscope and stereomicroscope. (Enlarge Image) Media file 2: Videodermatoscope. Courtesy of DS Medica, Milan, Italy. (Enlarge Image) Media file 3: Digital epiluminescence microscopy equipment, Skin Cancer Unit, Centro Prevenzione Oncologica, Ravenna, Italy. (Enlarge Image) Media file 4: Digital camera with implemented EPI30 zoom lens. Courtesy of Alpha Strumenti, Milan, Italy. (Enlarge Image) Media file 5: Brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 6: Brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 7: Light-brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 8: Brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 9: Brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 10: Dark-brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 11: Dark-brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 12: Dark-brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 13: Dark-brown pigment network in a melanocytic nevus. (Enlarge Image) Media file 14: In situ melanoma with asymmetric color distribution, irregular pigment network, and a whitish veil (*). (Enlarge Image) Media file 15: In situ melanoma with asymmetric color distribution, irregular pigment network, and pigment dots with varied size (*). (Enlarge Image) Media file 16: Dysplastic nevus with irregular pigment network and a whitish veil (*). (Enlarge Image) Media file 17: Pseudopigment network of a nevus located on the face. (Enlarge Image) Media file 18: Solar lentigo. (Enlarge Image) Media file 19: Malignant melanoma in situ on face or lentigo maligna. (Enlarge Image) Media file 20: Melanoma in situ with radial streamings at periphery and a whitish veil (*). (Enlarge Image) Media file 21: Microinvasive melanoma with pseudopods at the periphery and a whitish veil (*). (Enlarge Image) Media file 22: Melanocytic nevus with globular pattern. (Enlarge Image) Media file 23: Melanocytic nevus with globular pattern. (Enlarge Image) Media file 24: Melanocytic nevus with regular distribution of globules at periphery. (Enlarge Image) Media file 25: Melanocytic nevus with regular distribution of globules at periphery. (Enlarge Image) Media file 26: Peripheral irregular globules with varied colors in an invasive melanoma. (Enlarge Image) Media file 27: Pigmented dots (*) in a melanocytic nevus. (Enlarge Image) Media file 28: Invasive melanoma with white and gray areas (**), different expressions of pigmented dots (*), and globules (O). (Enlarge Image) Media file 29: Whitish blue veil in a pigmented Spitz nevus. (Enlarge Image) Media file 30: Whitish blue veil and gray-blue areas in invasive melanoma. (Enlarge Image) Media file 31: Homogeneous steel blue areas in a blue nevus. (Enlarge Image) Media file 32: Hypopigmented areas in a melanocytic nevus. (Enlarge Image) Media file 33: White areas in invasive melanoma. (Enlarge Image) Media file 34: Milialike cysts (*) and comedolike openings (O) in seborrheic keratosis. (Enlarge Image) Media file 35: Comedolike openings (*) in seborrheic keratosis. (Enlarge Image) Media file 36: Red vascular lagoons. (Enlarge Image) Media file 37: Subungual hemorrhage. (Enlarge Image) Media file 38: Maple leaf–like pigmentation (*), treelike vascular pattern, and grayblue ovoid nests in a basal cell carcinoma. (Enlarge Image) Media file 39: On the left, treelike vessels in a basal cell carcinoma, and, on the right, corona vessels that are thin and curved and are surrounding a sebaceous gland hyperplasia. (Enlarge Image) Media file 40: On the left, comma-shaped vessels parallel to the skin surface in a dermal nevi. On the right, point vessels in an actinic keratosis. (Enlarge Image) Media file 41: Linear irregular vessels and pinpoint dots in a malignant melanoma. (Enlarge Image) Media file 42: Global and local patterns such as additional features in the pattern analysis classification system. (Enlarge Image) ראה מוגדל למטה Media file 43: A typical globular pattern in a Clark nevus and the multifaceted colors and structures visible in a microinvasive malignant melanoma according to the pattern analysis classification. CNMD is Consensus Net Meeting on Dermoscopy. (Enlarge Image) Media file 44: Typical starburst pattern characterized by the presence of pseudopods (streaks) visible at the periphery of the lesion radially distributed in a Reed nevus. (Enlarge Image) Media file 45: The main patterns in acral lesions: parallel furrow pattern, latticelike pattern, fibrillar pattern, and parallel ridge pattern. (Enlarge Image) Media file 46: ABCD rule of dermoscopy. Asymmetry and border with relative weight and score. (Enlarge Image) ראה מוגדל למטה Media file 47: ABCD rule of dermoscopy. Color and different structures with relative weight and score. (Enlarge Image) ראה מוגדל למטה Media file 48: The scoring system developed using the ABDC rule of dermoscopy. (Enlarge Image) ראה מוגדל למטה Media file 49: Grading of melanocytic lesions using total dermoscopy score of the ABCD rule of dermoscopy. (Enlarge Image) ראה מוגדל למטה Media file 50: Application of ABCD rule of dermoscopy in melanocytic lesions. (Enlarge Image) Media file 51: Menzies method. Classification system used to make a diagnosis of suspected melanoma. (Enlarge Image) ראה מוגדל למטה Media file 52: Application of Menzies method to evaluate the different spectra of melanocytic lesions. (Enlarge Image) Media file 53: Seven-point checklist uses 7 melanoma-specific criteria: 3 major criteria (score 2 points each) and 4 minor criteria (score 1 point each). (Enlarge Image) ראה מוגדל למטה Media file 54: A typical benign melanocytic lesion and a malignant melanoma classified using the 7-point checklist parameters and the relative score. (Enlarge Image) Media file 55: Stratification of risk levels correlated to the different spectra of melanocytic lesions and relative management. (Enlarge Image) ראה מוגדל למטה Media file 56: A low-risk melanocytic lesion with a typical pigment network (Clark nevus) and a very high-risk melanocytic lesion (melanoma) classified using the level of risk stratification method. (Enlarge Image) Keywords epiluminescence microscopy, digital epiluminescence microscopy, videodermatoscope, video dermatoscope, video-dermatoscope, cutaneous malignant melanoma, pigmented skin lesions, malignant melanoma, skin cancer, skin cancer diagnosis, CMM, PSL, ELM, dermatologic color evaluation, skin lesion color evaluation Global and local patterns such as additional features in the pattern analysis classification system. ABCD rule of dermoscopy. Asymmetry and border with relative weight and score. ABCD rule of dermoscopy. Color and different structures with relative weight and score. The scoring system developed using the ABDC rule of dermoscopy. Grading of melanocytic lesions using total dermoscopy score of the ABCD rule of dermoscopy. Menzies method. Classification system used to make a diagnosis of suspected melanoma. Seven-point checklist uses 7 melanoma-specific criteria: 3 major criteria (score 2 points each) and 4 minor criteria (score 1 point each). Stratification of risk levels correlated to the different spectra of melanocytic lesions and relative management. References 1. Pehamberger H, Binder M, Steiner A, Wolff K. In vivo epiluminescence microscopy: improvement of early diagnosis of melanoma. J Invest Dermatol. Mar 1993;100(3):356S362S. [Medline]. 2. Argenziano G, Fabbrocini G, Carli P, De Giorgi V, Sammarco E, Delfino M. Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions. Comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis. Arch Dermatol. Dec 1998;134(12):1563-70. [Medline]. 3. Kenet RO, Fitzpatrick TB. Reducing mortality and morbidity of cutaneous melanoma: a six year plan. B). 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