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Towards a computer-aided diagnosis system for pigmented skin lesions.

This paper presents a computer-aided diagnosis system for pigmented skin lesions, with solutions for the lesion boundary detection and for the quantification of the degree of symmetry. Lesion detection results were validated by expert dermatologists, who also provided hand-drawn boundaries of the lesions. These reference boundaries were not used as a gold standard, but were allowed to statistically determine the accuracy of the boundaries provided by computerized techniques. We could show that the dermatologists were not able to reproduce their results, and that the boundaries of any expert taken alone showed higher divergence from those of the set of remaining experts than the automatic techniques we developed. Feature extraction is restricted in this paper to the quantification of degree of symmetry, even though it is clear that many other features will be necessary for a complete diagnosis system. The symmetry quantification step provides a six-dimensional feature vector that can be used to classify pigmented skin lesions as being benign or malignant. We demonstrate that our scheme outperforms methods based on the principal component decomposition, which is widely used for this kind of application.

Algorithms↗

The 'common mole' from the point of view of digital dermoscopy analysis: subjective vs. objective evaluation of easy pigmented skin lesions.

BACKGROUND: The term 'common mole', often used to describe a subset of benign pigmented skin lesions, is traditionally defined on the basis of morpho-chromatic features. In recent years, certain research groups have developed equipment and methods, such as digital dermoscopy analysis, that enable objective evaluation of pigmented skin lesions. OBJECTIVE: In this study we use a digital dermoscopy analyser trained for the recognition of pigmented skin lesions to compare the subjective definition of 'common' and the mathematical concept of 'close to the mean of measurements'. METHODS: A subset (100) of digital images of flat pigmented lesions, obtained in daily practice, were classified by trained and non-expert clinicians as common moles (60) or clear-cut melanoma (40), and processed with a DB-Mips analyser. The resulting parameters, validated by a classifier, were used to evaluate Hotelling's T2 multivariate distances from the mean. RESULTS: 'Common' moles could not be clearly defined in terms of closeness to the means of objectively evaluated parameters. Their diagnosis indudes many other evaluations and clusters of variables. CONCLUSION: The clinical semantics of the term 'common' does not conform to any unambiguous mathematical definition.

Diagnosis, Computer-Assisted↗

Precision of automatic measurements of pigmented skin lesion parameters with a MelaFind(TM) multispectral digital dermoscope.

The purpose of this study was to assess the precision of automatic computerized measurement of parameters that may be useful in the differentiation of malignant melanoma from benign pigmented skin lesions, and also to determine the feasibility of quantitative monitoring of skin lesions over time. Ten independent sequences of images were acquired with a MelaFind multispectral digital dermoscope for each of 12 benign or malignant pigmented skin lesions. The sequences of images were processed automatically to provide 10 independent measurements of the various parameters for each lesion. Parameters included lesion area, greatest 'diameter', perimeter, reflectance and asymmetry. The precision of each parameter determination was computed from the mean and standard deviation of the 10 measurements of that parameter. The relative errors in determining the lesion area, 'diameter' and perimeter were found to be 6%, 3% and 4%, respectively. Other lesion parameters that are used in differentiating melanomas from benign skin lesions were also analysed as a function of wavelength. In the blue band (about 430 nm) the relative error was about 7% for the mean lesion reflectance and about 7% for the asymmetry parameter. These results demonstrate the feasibility of using MelaFind for objective quantitative monitoring of changes in pigmented skin lesions over time. As suggested by some studies, such information is useful in the early detection of malignant melanoma. The results show that parameters obtained automatically from MelaFind images are sufficiently precise to allow pertinent parameters to be used to classify pigmented skin lesions.

Databases, Factual↗

The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma.

In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients and 174 matched controls and in 168 CMM patients and 176 matched controls. Measurements were performed at the forehead, the upper chest, the upper back, the lateral and medial aspects of the upper arm, and the buttocks. Self-estimation of sun exposure in childhood, in youth and in adulthood was performed by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different between BCC patients and controls except that women patients had higher pigmentation at the lateral side of the upper arm. For CMM, men patients had higher pigmentation at the lateral side of the upper arm. Self-estimations of sun exposure did not show differences between patients and controls but indicated high exposure levels in childhood and youth and in adult leisure time. Sun exposure estimated by increase in facultative pigmentation above the constitutive level (the Sun Exposure Index) was not significantly different between BCC patients and controls, whereas CMM men patients had higher estimates for the lateral side of the upper arm, the chest and the back.

Adolescent↗

Dermatoscopy and high frequency sonography: two useful non-invasive methods to increase preoperative diagnostic accuracy in pigmented skin lesions.

Dermatoscopy and high frequency sonography have recently been combined to increase diagnostic preoperative accuracy in the treatment of pigmented skin lesions. In this monocentric study 80 patients with pigmented skin lesions were evaluated clinically, by dermatoscopy, and 20 MHz-sonography followed by dermatohistopathological evaluation; 39 malignant melanomas, 37 common nevi, 3 dysplastic nevi, and 1 nevus Spitz were diagnosed histologically. In 72 of the 80 cases (91.3%) dermatoscopical diagnoses were confirmed by histopathology, compared to only 79% correct clinical diagnoses. For the mere clinical diagnosis of melanoma sensitivity was 79%, specificity was 78% and diagnostic accuracy was 65%. All diagnostic values increased by dermatoscopy: sensitivity reached 90%, specificity was 93%, and diagnostic accuracy was 83%. In order to determine tumor thickness preoperatively tumor thickness was measured by 20 MHz sonography. The correlation of tumor thickness between histometric and sonographic results was determined for nevi (r = 0.93) and melanoma (r = 0.95); 74.3% of melanomas were diagnosed correctly within an 0.2 mm range. Regarding the clinical important limit of 1 mm tumor thickness, 87.2% were diagnosed in accordance with histometric evaluation. An increase of 18% in diagnostic accuracy by dermatoscopy and 87.2% of correctly diagnosed cases of tumor thickness of malignant melanoma by high frequency sonography clearly demonstrate that these methods should be considered standard procedures in the diagnosis of pigmented skin lesions and will facilitate the decision on necessary surgical treatment.

Humans↗

Pre-operative diagnosis of pigmented skin lesions: in vivo dermoscopy performs better than dermoscopy on photographic images.

BACKGROUND: Epiluminescence microscopy (ELM) (dermoscopy, dermatoscopy) is a technique for non-invasive diagnosis of pigmented skin lesions that improves the diagnostic performance of dermatologists. Little is known about the possible influence of associated clinical features on the reliability of dermoscopic diagnosis during in vivo examination. OBJECTIVE: To compare diagnostic performance of in vivo dermoscopy (combined clinical and dermoscopic examination) with that of dermoscopy performed on photographic slides (pure dermoscopy). DESIGN: This case series comprised 256 pigmented skin lesions consecutively identified as suspicious or equivocal during examination in a general dermatological clinic. Clinical examination and in vivo dermoscopy were performed before excision by two trained dermatologists. The same observers carried out dermoscopy on photographic slides at a later time, and these three diagnostic classifications were reviewed together with the histological findings for the individual lesions. This was carried out in a university hospital. RESULTS: In vivo dermoscopy performed better than dermoscopy on photographic slides for classification of pigmented skin lesions compared with histological diagnosis, and both performed better than general clinical diagnosis. In vivo dermoscopic diagnosis of melanoma showed 98.1% sensitivity, 95.5% specificity and 96.1% diagnostic accuracy while dermoscopic diagnosis of melanoma on photographic slides was less reliable with 81.5% sensitivity, 86.7% specificity and 85.2% diagnostic accuracy. In particular, diagnosis of melanoma based on photographic slides led to nine false negative cases (three in situ, six invasive; thickness ranges 0.2-1.5 mm). CONCLUSIONS: In vivo dermoscopy, i.e. combined clinical and dermoscopic examination, is more reliable than dermoscopy on photographic slides. In clinical practice, therefore, in vivo dermoscopy cannot be considered independent from associated clinical characteristics of the lesions, which help the trained observer to reach a more precise classification. This may have implications on the reliability of ELM diagnosis made by an observer not fully trained in the clinical diagnosis of pigmented skin lesions or by a remote observer during digital ELM teleconsultation.

Adult↗

Long-term actinic damage in sun-exposed vitiligo and normally pigmented skin.

Vitiligo provides a model system for studying chronic actinic damage in skin devoid of melanin pigments and thereby permits assessment of their photoprotective function. Our study comprised 23 patients with a mean age of 67 years having stable, long-lasting vitiligo on light-exposed body regions. The vitiliginous and normally pigmented, light-exposed skin was examined clinically for manifestations of chronic actinic damage. In 11 patients skin biopsies were obtained from vitiliginous and adjacent pigmented skin for qualitative and quantitative histological comparison. Our study did not reveal evidence for a significant increase of chronic actinic damage in skin devoid of melanin pigments. These results are in agreement with the rareness of reported skin cancer in vitiligo.

Aged↗

Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms.

Melanin synthesized by epidermal melanocytes protects the skin against UVR-induced DNA damage and skin cancer. Exposure to UVR increases the synthesis of the photoprotective eumelanin on activation of MC1R, a melanoma susceptibility gene. We studied the expression of MC1R under UVR and alpha-MSH stimulation in skin of different ethnic origins and in melanocytes of various pigmentary levels. This study identifies and characterizes a novel MC1R isoform (MC1R350) generated by alternative splicing of the classically known MC1R (MC1R317). We demonstrate that the melanin content of melanocytes shows a significant positive correlation with MC1R317 levels but correlates inversely with the amount of MC1R350, suggesting that this latter isoform could act as a negative regulator of melanin synthesis. We confirmed that hypothesis by showing that while MC1R317 signaling significantly increases the expression of MITF and tyrosinase, two key factors in the melanin synthesis pathway, MC1R350 dramatically hampers their expression. In the skin, we show that UVR does not increase MC1R350 expression but does significantly increase MC1R317. Taken together, our results strongly suggest that MC1R350 acts as a negative regulator of skin pigmentation and demonstrate for the first time that MC1R isoform-specific expression is closely related to skin pigmentation and photoprotection.

Alternative Splicing↗

Automated diagnosis of pigmented skin lesions.

Since advanced melanoma remains practically incurable, early detection is an important step toward a reduction in mortality. High expectations are entertained for a technique known as dermoscopy or epiluminescence light microscopy; however, evaluation of pigmented skin lesions by this method is often extremely complex and subjective. To obviate the problem of qualitative interpretation, methods based on mathematical analysis of pigmented skin lesions, such as digital dermoscopy analysis, have been developed. In the present study, we used a digital dermoscopy analyzer (DBDermo-Mips system) to evaluate a series of 588 excised, clinically atypical, flat pigmented skin lesions (371 benign, 217 malignant). The analyzer evaluated 48 parameters grouped into 4 categories (geometries, colors, textures and islands of color), which were used to train an artificial neural network. To evaluate the diagnostic performance of the neural network and to check it during the training process, we used the error area over the receiver operating characteristic curve. The discriminating power of the digital dermoscopy analyzer plus artificial neural network was compared with histologic diagnosis. A feature selection procedure indicated that as few as 13 of the variables were sufficient to discriminate the 2 groups of lesions, and this also ensured high generalization power. The artificial neural network designed with these variables enabled a diagnostic accuracy of about 94%. In conclusion, the good diagnostic performance and high speed in reading and analyzing lesions (real time) of our method constitute an important step in the direction of automated diagnosis of pigmented skin lesions.

Automation↗

Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions.

When a biopsy is taken of a suspicious pigmented skin lesion, histological examination is expected to establish the definitive diagnosis. This study evaluated the inter-observer variation of 20 pathologists in the histological diagnosis of a randomly selected set of suspicious pigmented skin lesions (PSLs), by comparing their diagnoses to a reference diagnosis. Overall sensitivity for melanoma was 87%, ranging from 55% to 100% between the observers. Sensitivity was significantly lower for thin (Breslow thickness <1 mm) than for thick melanomas (83% versus 97%, p=0.005). Overall melanoma specificity was 94%, ranging from 83% to 100% between observers. Dysplastic naevus was the most important source of false-positive diagnoses, mainly in situ melanomas. Positive and negative predictive values in the given test set were 75% and 97%, respectively. In the case of melanoma, there was quite some variation in measured Breslow thickness. This would have led to a different therapeutic approach in 12% of the readings. Some of the variation seemed to be due to a different interpretation of the presence of a co-existent naevus. In 9% (3/35) of the readings, participants did not agree on the presence of ulceration. These results reflect a tendency to overdiagnose mainly thin melanomas in general histopathological practice. They also demonstrate variation in the assessment of major prognostic factors of melanoma.

Biopsy↗

Assessment of pigmented skin lesions in terms of blood perfusion estimates.

BACKGROUND/AIMS: Cutaneous malignant melanoma is a disease of increasing clinical and economical importance. The prognosis is good with early diagnosis. The chief differential diagnosis is benign melanocytic naevus, a common lesion in Caucasians. Attempts have been made to use bioengineering techniques to aid in the initial diagnosis. The present study proposes a method of extracting possibly discriminative blood perfusion properties in pigmented skin lesions by combining information on the lesions' blood perfusion with optical or visual information of their spatial extent. METHODS: A total of 46 blood perfusion measurements were performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three histologically proven malignant melanomas, four histologically proven benign naevi and fifteen naevi assessed by two specialist dermatologists as being benign. Laser Doppler perfusion imaging gave two different types of two-dimensional data sets (64x64 pixels), one representing the total backscattered light intensity at each measurement point (TLI image) and the second corresponding to perfusion values. The boundaries of each examined lesion were derived from the TLI image employing greyscale thresholding, thus resulting in an estimated region of interest (ROI) approximating the optical extent of the lesion. The ROI was superimposed on the perfusion image and extraction of perfusion features was then performed. RESULTS: The processing of the TLI images was successful in delineating the lesions' boundaries. The first hypothesis that the mean perfusion quotients in MM and benign naevi are equal could not be rejected at the chosen 5% level of significance. The second hypothesis that the mean percent-age of elevated perfusion values (image pixels) within the ROI shows no difference between MM and benign naevi could be rejected at a 5% level of significance. CONCLUSIONS: This study has presented a method of extracting blood perfusion parameters of pigmented skin lesions by combining blood perfusion information with information on the lesion's optical extent. The proposed method of presenting data could prove to be a useful discriminative adjunct in the assessment of pigmented skin lesions.

Adult↗

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Asian People↗

Colorimetric assessment of the effects of azelaic acid on light-induced skin pigmentation.

A 20% azelaic acid (AZA) cream is currently used as a therapeutic agent in the treatment of acne vulgaris. Therefore, this product is intended to be applied on frequently or continuously sun-exposed skin. In certain disorders of hyperpigmentation, AZA has been reported to have a depigmenting effect as well, while showing no significant activity on normal skin. It has been suggested that AZA selectively inhibits hyperactive or malignant melanocytes. Knowing that light-stimulated melanocytes are in a state of hyperactivity, it seemed worthwhile to investigate AZA activity on light-induced skin pigmentation. This study aimed to assess the activity of 20% AZA cream on light-induced skin pigmentation in 10 subjects. There were 5 test zones, all located on the middle of the back: 2 were treated with AZA cream, 2 others with the vehicle and 1 was left untreated. Each product was applied twice daily, 5 days a week, for 4 weeks on one zone, and for 5 weeks on the other. In the middle of the fourth week, the tested zones were exposed to ultraviolet B (UVB) + UVA + visible light, with a total of 3 times the minimal erythema dose distributed progressively over 3 consecutive days. Seven and 10 days after the last irradiation, the induced photopigmentation was assessed by colorimetric and visual means. Compared with its vehicle, the AZA cream had neither a depigmenting effect nor a preventive effect on the light-acquired skin pigmentation. Moreover, interrupting or continuing the AZA treatment after skin irradiation had no influence on the resulting pigmentation.

Adult↗

Optical devices used for image analysis of pigmented skin lesions: a proposal for quality assurance protocol using tissue-like phantoms.

Different technological tools have been developed to aid in the diagnosis of pigmented skin lesions, including cameras working with conventional RGB colour systems, epiluminescence microscopy and spectrophotometric methods using visible and near infrared wavelengths. All the different procedures should provide in an objective and reproducible fashion quantitative measurements of the colour and shape features of a given skin mole. At present, many devices have been introduced in experimental stages for clinical diagnosis, mainly used to provide to the clinicians an objective, computer-assisted second opinion. As for any diagnostic instruments, optical devices should also be subjected to a dedicated quality assurance protocol in order to evaluate the response repeatability of each device (intra-instrument agreement) and to check the accordance among the responses of different devices (inter-instrument agreement). The aim of this study was to design a quality assurance protocol for optical devices dedicated to image analysis of pigmented skin lesions and, in case, to detect cutaneous melanoma by using suitable tissue-like phantoms as standard references that enable testing of both hardware and software components. As an example, we report the results of intra-instrument and inter-instrument agreement when the protocol was applied on a series of 30 SpectroShade instruments, a novel optical device based on multi-spectral image analysis of colour and shape features of pigmented skin lesion.

Biophysical Phenomena↗

Spectrophotometric assessment of pigmented skin lesions: methods and feature selection for evaluation of diagnostic performance.

This study documents the optical reflectance characteristics of pigmented skin lesions and evaluates their potential for improving the differential diagnosis of malignant melanoma from benign pigmented skin lesions. Optical reflectance spectra in the wavelength range 320-1100 nm were obtained from 121 lesions already selected by expert dermatologists as suspicious of malignancy. Characteristic differences in spectra from benign and malignant lesions were studied. Feature extraction showed significant differences between lesion groups classified by histology. Seven of the most relevant features were used in the discriminant analysis of reflectance spectra from 15 melanoma and 32 compound naevi which resulted in a sensitivity of 100% and specificity of 84.4% when compared with histology. This simple objective technique appears to perform as well as the expert dermatologist and may improve the diagnostic accuracy of non-specialists such as trainees and GPs. Further prospective clinical study of reflectance spectrophotometry in a larger patient group is now required.

Adolescent↗

Reliability of near-infrared spectroscopy in people with dark skin pigmentation.

OBJECTIVE: Near-infrared spectroscopy (NIRS) is a promising non-invasive technique for the continuous monitoring of tissue oxygen delivery. NIRS detects light absorbance of haemoglobin chromophores to determine tissue oxygen saturation (StO2). As skin colour is also determined by the presence of chromophores, it is plausible that NIRS signal quality may be affected by dark skin pigmentation. METHODS: Tissue saturation in the anterior compartment of the lower leg during isometric contraction was measured using NIRS in 17 volunteers with dark skin pigmentation. Measurements were continued until StO2 was zero percent or until the signal disappeared. RESULTS: The NIRS device failed to register tissue saturation values at some point in nine of seventeen volunteers. This occurred more often in individuals with darker skin. CONCLUSIONS: In patients with a dark pigmented skin, NIRS StO2 measurements should be interpreted with caution, as melanin clearly interferes with the quality of the reflected NIRS signal.

Black People↗

Dermoscopy of pigmented skin lesions.

This paper describes the basic concepts of dermoscopy, the various dermoscopic equipments and the standard criteria for diagnosing pigmented skin lesions. In assessing dermoscopic images, both global and local features can be recognized. These features will be systematically described and illustrated in Part I of this article. First, we will focus on 8 morphologically rather distinctive global features that allow a quick, preliminary categorization of a given pigmented skin lesion. Second, we will describe various local features representing the letters of the dermoscopic alphabet. The local features permit a more detailed assessment of pigmented skin lesions.

Algorithms↗

Instrument capsules: laser hair removal in pigmented skin.

A 50-year old African-American woman presented to her physician's office seeking treatment of excess hair and secondary hyperpigmentation of her chin. On exam, her skin was noted to be Fitzpatrick Type V and her hair was course and dark.

Folliculitis↗