cutaneous melanoma is a highly aggressive malignant tumor of melanocytic origin with increasing incidence in most countries of the world over the last few decades . in caucasian populations the incidence rates for cutaneous melanoma have risen faster than those for any other malignant entity over the last 30 years . v ) or mutations of tumor - suppressor genes ( e.g. , cdkn2a , encoding for cyclin - dependent kinase inhibitor 2a ) , which might be reflected by a positive family history of melanoma . when a patient s risk for melanoma needs to be assessed during daily clinical routine , the personal and family history of melanoma , number of common and atypical nevi , skin type , presence of freckles , eye color , hair color , and the presence of non - melanoma skin cancer lesions should be considered . the overall number of nevi induced by ultraviolet radiation in early infancy was shown to be an especially important predisposing risk factor for the development of melanoma . individuals with a high nevus count are endangered notably , whereby the risk of melanoma development increases almost linearly with rising numbers of melanocytic nevi on the whole body . although cutaneous melanoma is less common than other skin cancers , it causes the majority ( approximately 90 percent ) of deaths related to skin cancer . an advanced tumor thickness ( breslow s depth ) is strongly associated with an increased mortality . therefore , the early detection of melanoma at early and curable stages is critical for the patients survival . in contrast to many other tumor entities , cutaneous melanoma may already develop metastases at a low tumor volume . once distant metastases have occurred , the median survival is approximately nine months and the five - year survival rate is less than 10 percent . on the contrary , for thin melanomas with a tumor thickness of less than 0.76 mm , these rates markedly decrease to 48 percent for lesions with more than 3 mm tumor thickness . until today , the most common method for detecting melanoma is visual diagnosis . to make a correct diagnosis , the most frequent form of cutaneous melanoma is superficial spreading melanoma ( ssm , figure 1 ) . it grows slowly and initially in a horizontal plane and subsequently , in more advanced cases , it will reach a vertical growth phase . with naked eye examination , lesions are often sharply demarcated , polycyclic and multicolored . in contrast , nodular melanoma ( nm ) , a much more aggressive form , exhibits an early vertical growth phase . nm emerges primarily and is then often detected late , at an advanced tumor thickness , or it develops secondarily within a ssm ( figure 2 ) . the nodes often grow rapidly , are vulnerable with a tendency to ulceration and bleeding , or might appear non - pigmented . lentigo maligna melanoma ( lmm , figure 3 ) characteristically occurs at older age and is localized in areas of chronically sun - exposed skin , like the face or dorsa of the hands . similar to ssm , it appears polycyclic , sharp - bounded and often shows multiple brown spots . a rare growth variant of cutaneous melanoma , the acral - lentiginous melanoma ( alm , figure 4 ) is localized in palmoplantar skin but may also involve the nail unit . alm represents the most common growth variant in dark - skinned ( e.g. , asian ) populations . due to the architecture of palmoplantar skin with parallel ridges and furrows , the margins are often not clearly defined and the pigmentation is incoherent . moreover , special forms like mucosal and ocular malignant melanoma exist . in summary , the most effective approach to improve the prognosis of cutaneous melanoma the identification and the screening of high - risk patients is an important prerequisite to further enhance efforts to lower the mean tumor - thickness at the time of diagnosis . excisional biopsies of suspicious lesions with subsequent histopathologic examination of specimens will allow for a definite classification . the application of the clinical abcd rule ( table 1 ) devised by friedman et al in 1985 is a common method for the clinical diagnostics of cutaneous melanoma . the criteria asymmetry , irregular margin , multiple colors and a diameter over 6 mm , cutaneous melanoma has to be considered . however , the abcd rule is characterized by a low specificity as other benign skin lesions such as seborrheic keratosis may also fulfill the aforementioned criteria . moreover , it is not applicable for pigmented lesions on the palms , soles or face due to the particular skin anatomy at these sites . small melanomas with a diameter of 6  mm or less or rare non - pigmented subtypes of melanoma will also not be detected by the abcd rule . certain dynamic changes within melanocytic lesions are also suggestive of cutaneous melanoma , for instance , asymmetrical changes in size , shape or color , or itching and bleeding . in consequence , e  for evolving or evolution to the abcde rule . before examination of selected nevi in more detail , it is useful to get an overview of recurrent and predominant patterns of a patient s nevi . nevi in the same individual tend to resemble one another , so - called  signature lesions ,  indicating benign nevi on a regular basis . in contrast , melanomas often deviate from the individual s nevus pattern , so - called  ugly duckling sign  . recently , a high sensitivity for the early detection of melanoma with the help of the  ugly duckling sign  could be demonstrated . medical total body photography is often used in dermatology to support the clinical surveillance of high - risk patients . photographically assisted follow - up images help clinicians and patients to detect new and changing pigmented lesions with the unaided eye . in contrast to digital dermoscopy , which allows for monitoring of a few lesions only , full body photography permits monitoring of all lesions of a patient . dermoscopy ( also known as epiluminescence microscopy , dermatoscopy , or amplified surface microscopy ) allows for a significant improvement in the preoperative diagnostic accuracy of pigmented skin lesions . dermoscopy is a non - invasive technique for the in vivo examination of melanocytic and non - melanocytic skin lesions . the handheld dermoscope traditionally consists of a magnifier , a non - polarized light source and a transparent plate . a liquid medium , for instance , immersion oil or spray for skin disinfection , is needed between the instruments contact plate and the skin to reduce the reflection of light . with the help of dermoscopy further information about the architecture , e.g. , the pigmented network , the vascular pattern and the distribution of color of a single lesion is obtained . today , many different dermoscopes are commercially available ( e.g. , dermatoscope by heine optotechnik ; episcope by welch allyn ; dermogenius by rodenstock przisionsoptik ) . more recently dermoscopes that emit polarized light to eliminate skin surface reflection entered the market . these instruments do not require skin contact and a liquid medium can be omitted ( e.g. , dermlite 3 gen ) . this procedure for classification of pigmented skin lesions was agreed on at an international consensus meeting . in the first step it has to be determined whether a melanocytic or non - melanocytic , the differentiation between benign or malignant / suspicious lesions follows in a second step . for this most algorithms ( e.g. , the abcd rule of dermoscopy , the 7-point checklist of dermoscopy , or menzies scroring method ) use a number of criteria associated with the presence of melanoma as first described for the pattern analysis by pehamberger et al . especially , three algorithmic methods ( qualitative pattern analysis , the abcd rule of dermoscopy , and the 7-point checklist ) were shown to be valid and reliable in distinguishing benign and malignant melanocytic tumors . the pattern analysis is based on a detailed , qualitative assessment of numerous dermoscopic criteria , and a high rate of diagnostic accuracy could be obtained by experienced investigators after a significant degree of formal training ( 19 ) . the abcd - rule of dermoscopy uses a semiquantitative scoring system based on a complex evaluation of asymmetry , border , color , and different dermoscopic structures within the lesion . the 7-point checklist ( table 2 ) was developed as a quantitative scoring system with three major criteria ( score of 2 points ) and four minor criteria ( score of 1 point ) . the 7-point checklist can be learned and applied more easily and in comparative studies allowed the best sensitivity in the hands of non - experts . two unsuspicious melanocytic nevi are shown in figures 5 and 6 , while three superficial spreading melanomas with their typical criteria for malignancy are demonstrated in figures 79 . a systematic overview of medline publications between 1983 and 1997 showed that dermoscopy leads to a 1027% increase in sensitivity as compared to the clinical diagnosis with the unaided eye . dermoscopy not only allows for an earlier detection of melanoma but was also shown to avoid unnecessary excisions of benign nevi . depending on the individual experience of the clinician , a sensitivity of up to 92%and a specificity of up to 99% were documented for the detection of cutaneous melanoma by dermoscopy . among dermatologists , dermoscopy has become a routine examination technique in europe and is with gaining acceptance worldwide . when computer hardware became more and more available and affordable , digital dermoscopy devices were developed and rapidly integrated into the clinical setting . digital overview and dermoscopic images offer the advantage of computer storage and retrieval during later examinations of patients . some digital dermoscopy devices even offer a computer - assisted diagnosis [ 2426 ] . despite a higher impact on financial and personnel resources , the sequential digital dermoscopic examination offers a number of advantages for patients with a high number of atypical nevi and a personal and/or family history of melanoma . due to the multitude of atypical pigmented lesions in these high - risk patients , it is often difficult to detect melanoma at an early stage without excising hundreds of benign nevi ( figure 10 ) . by comparison of dermoscopic follow - up images with baseline images a range of studies have proven that digital dermoscopy follow - up of high - risk patients allows for the early detection of melanomas that have not yet acquired melanoma - typical dermoscopic features , thus increasing the sensitivity [ 2729 ] . with the help of sequential digital dermoscopy , incipient melanomas can be identified by detection of intralesional changes , for instance asymmetrically enlargement or architectural changes ( figure 11 a  c ) . this applies especially for melanomas without suspicious dermoscopic features , so - called  featureless melanoma . another strategy of sequential dermoscopic follow - up is the short - term follow - up ( three - month interval ) , which targets a restricted number of highly atypical nevi , which should be removed whenever dynamic changes become apparent . numerous systems for sequential digital dermoscopy imaging are commercially available ( e.g. , molemax , fotofinder , solarscan ) . the need for a further improved diagnostic accuracy for the assessment of skin tumors has led to the development and investigation of new imaging tools . an innovative technique is the in - vivo confocal laser scanning microscopy ( clsm ) , which represents a relatively novel imaging tool allowing for non - invasive examination of skin morphology in real time and at a near - histopathologic resolution . multiple studies have evaluated the use of reflectance mode clsm for the diagnosis of melanoma in the past decade . in this regard , two different algorithms for melanoma diagnosis have been developed by two independent groups from modena and barcelona , showing similar sensitivity and specificity values for several clsm criteria . the relative simple two - step method developed by segura et al   uses protective , as well as risk factors , whereby the presence of two risk factors results in a sensitivity of 86.1% and a specificity of 95.3% for the diagnosis of melanoma . pellacani et al identified six criteria , two major and four minor criteria , as independently correlated with a melanoma diagnosis . the two major criteria corresponded to the presence of atypical melanocytic cells within the epidermal basal layer and the papillary dermis or within the basal layer of non - edged papillae . the four minor criteria were represented by the presence of roundish cells in superficial layers spreading upward in a pagetoid fashion , pagetoid cells widespread throughout the lesion , cerebriform clusters within the papillary dermis and bright nucleated cells in the upper dermis . the presence of at least two features , one major and one minor criterion , was essential for melanoma diagnosis . on the other hand , regular dermo - epidermal architecture and absence of pagetoid infiltration and atypical cells were indicative of benign lesions . the evaluation of skin lesions by clsm is based on illumination of the tissue by a point laser light source and reflectance of individual skin structures , of which melanin is providing the strongest contrast [ 3537 ] . specific morphological pattern can be observed by clsm in nevi and melanoma allowing for differentiation of benign and malignant , but also for differentiating melanocytic from non - melanocytic lesions such as pigmented basal cell carcinoma ( figure 12 ) . due to scanning mode of clsm an area of up to 8  8 mm may be evaluated on horizontal sections and on different skin levels ( e.g. , stratum corneum , stratum spinosum , dermo - epidermal junction , dermis ) . thereby , the great advantage of clsm lies in the immediate diagnosis that may guide the clinician s decision for further management of a lesion . furthermore , clsm provides the clinician and the researcher with the possibility of monitoring of pigmented lesions over time and may change the way we evaluate melanocytic lesions in the future . to implement the clsm in the clinical setting , the multispectral digital dermoscopy , a new development of conventional dermoscopy , has recently entered the european market ( melafind ) and offers a fully automated differentiation of melanoma from atypical melanocytic nevi . light of different wavelengths is transmitted and the degree of reflection or absorption by the different components of human skin ( e.g. , collagen , melanocytes , and blood vessels ) is analyzed by a computer algorithm . a diagnosis is made by the assessment of the distribution of melanin , collagen and hemoglobin in a given lesion . a prospective multicenter trial , which led to the approval by the european agencies , showed a high sensitivity of 98.4% , but a low specificity of approximately 10% . however , as reported in the study by monheit et al , the specificity was superior to that of clinicians formally trained in the use of dermoscopy . another novel non - invasive optical biomedical imaging technique is the optical coherence tomography ( oct ) . the basic principle relies on low - coherence interferometry enabling high resolution , two- or three - dimensional , cross - sectional imaging of microstructural morphology in biological tissue . using conventional oct , the stratum corneum , the epidermis , and upper dermis and blood vessels can be visualized . however , with most of the present devices , it is not possible to investigate skin tissue on the cellular level , whereas the architecture of a pigmented lesion and the distribution of blood vessels can be assessed . cutaneous melanomas often show marked architectural disarray , the dermo - epidermal border is blurred and exhibits finger - shaped elongated rete ridges . more precise data concerning sensitivity and specificity of oct for the diagnosis of cutaneous melanoma are missing . of note , for the diagnosis of intraocular tumors , optical coherence tomography was shown to provide valuable information . early detection of cutaneous melanoma is one of the most effective ways of reducing mortality rates from this disease . in addition to the clinical assessment with the unaided eye , dermoscopy has become a standard examination technique throughout most european countries , as it was shown to significantly improve the diagnostic accuracy of the clinical examination . total body photography notably facilitates the detection of newly developed pigmented lesions in patients with a high nevi count . with the help of sequential digital dermoscopy imaging , even subtle dynamic changes are detectable , which is shown to improve the differentiation of atypical nevi and early melanomas in high - risk patients . a novel imaging tool is the confocal laser scanning microscopy , allowing examination of skin tumor morphology on a cellular level in real time . in the near future the recently approved melafind device will probably be applied for difficult - to - diagnose melanocytic lesions in selected centers . above all , it has to be emphasized that none of the aforementioned examination techniques are currently able to provide a definite and final diagnosis or to replace excisional biopsy of suspicious lesions followed by histological analysis .