A simple scoring system for the diagnosis of palmo-plantar pigmented skin lesions by digital dermoscopy analysis.

BACKGROUND: Many research groups have recently developed equipments and statistical methods enabling pattern classification of pigmented skin lesions. To differentiate between benign and malignant ones, the mathematical extraction of digital patterns together with the use of appropriate statistical approaches is a challenging task. OBJECTIVE: To design a simple scoring model that provides accurate classification of benign and malignant palmo-plantar pigmented skin lesions, by evaluation of parameters obtained by digital dermoscopy analysis (DDA). PATIENTS AND METHODS: In the present study we used a digital dermoscopy analyser to evaluate a series of 445 palmo-plantar melanocytic skin lesion images (25 melanomas 420 nevi). Area under the receiver operator curve, sensitivity and specificity were calculated to evaluate the diagnostic performance of our scoring model for the differentiation of benign and malignant palmo-plantar melanocytic lesions. RESULTS: Model performance reached a very high value (0.983). The DDA parameters selected by the model that proved statistically significant were: area, peripheral dark regions, total imbalance of colours, entropy, dark area and red and blue multicomponent. When all seven model variables were used in a multivariate mode, setting sensitivity at 100% to avoid false negatives, we estimated a minimum specificity of about 80%. CONCLUSIONS: Simplicity of use and effectiveness of implementation are important requirements for the success of quantitative methods in routine clinical practice. Scoring systems meet these requirements. Their outcomes are accessible in real time without the use of any data processing system, thus allowing decisions to be made quickly and effectively.

Dermoscopy and digital dermoscopy analysis of palmoplantar 'equivocal' pigmented skin lesions in Caucasians.

BACKGROUND/AIM: The diagnosis of palmoplantar melanoma is often delayed and misdiagnosis is common, due to frequently unusual clinical presentation. We used a digital dermoscopy analyzer with a series of palmoplantar pigmented skin lesions (PP-PSL), and we compared sensitivity, specificity and diagnostic accuracy obtained with digital dermoscopy analysis (DDA) and classical dermoscopy. METHODS: Digital dermoscopy images of 107 PP-PSL were retrospectively obtained from the database of images of 3 Italian centers. The lesions (25 melanomas and 82 nevi) were all removed because of the presence of clinical and/or dermoscopic suspicious features. All digital images were analyzed using appropriate algorithms, and the diagnostic accuracy of the model was calculated. For comparison, dermoscopic images were clinically evaluated by two dermatologists and the Cohen ĸ concordance with DDA was calculated. RESULTS: The stepwise logistic regression analysis selected only 5 parameters out of 49. The logistic model achieved a sensitivity of 96% and a specificity of 87.8%. The Cohen ĸ concordance, evaluated by the Landis and Koch scale, supplied a substantial agreement between dermoscopy and DDA. CONCLUSIONS: DDA might be a useful diagnostic instrument in the evaluation of preselected PP-PSL. However, these findings should be confirmed in a formal clinical trial.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Dysplastic naevus vs. in situ melanoma: digital dermoscopy analysis.

BACKGROUND: To date, much confusion exists about the biological significance of dysplastic naevi and about the relationship between melanocytic dysplasia and clinical atypia. OBJECTIVES: To use a digital dermoscopy analyser with a series of 'borderline' pigmented skin lesions (i.e. dysplastic naevi and in situ melanomas) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. METHODS: The pigmented skin lesions (n = 174) were histologically examined by three experienced dermatopathologists and identified as in situ melanomas (n = 38) and dysplastic naevi (n = 136). The system evaluated 48 parameters as possible discriminant variables, grouped into four categories: geometry, colours, textures and islands of colour. Once the lesions were analysed (stepwise discriminant analysis), sensitivity, specificity and accuracy were calculated. RESULTS: At the end of the stepwise procedure the percentage of cases classified correctly was 71.8%. Of 136 dysplastic naevi only 98 were classified correctly, while 27 of 38 in situ melanomas were recognized correctly. CONCLUSIONS: We conclude that there are so far no digital dermoscopic criteria that can clearly distinguish dysplastic naevi from in situ melanomas.

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.

Digital dermoscopy analysis of atypical pigmented skin lesions: a stepwise logistic discriminant analysis approach.

BACKGROUND: Digital microscopy is a non-invasive diagnostic technique enabling determination of characteristics that cannot be appreciated by direct observation. If correctly applied, this technique can be useful for the diagnosis of pigmented skin lesions. PURPOSE: To evaluate the utility of digital microscopy for analysing atypical benign and malignant pigmented skin lesions exploiting digital numerical filtering and automatic measurements. METHODS: Forty-eight parameters were identified as possible discriminating variables, and were grouped in four categories: geometries, colours, textures, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. RESULTS: The high quality of the digital image made it possible to observe diagnostic signs in pigmented skin lesion images, acquired by the present technique, in great detail. Specially designed filtering enhanced certain diagnostic patterns. Stepwise discriminant analysis selected only 10 variables (the means of these variables were higher in melanomas than in nevi). CONCLUSIONS: The combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing atypical nevi and early melanoma.

Is the birthdate a risk factor for congenital hypothyroidism? A statistical answer based on personal experience.

BACKGROUND: To verify statistically the hypothesis that birthdate represents a risk factor for Congenital Hypothyroidism, as proposed by some European Authors. Moreover, to verify the existence of seasonal cyclic trends in TSH levels. METHODS: For the verification of birthdate as a risk factor, we considered retrospectively a data set of all consecutives newborns of Marche Region (Italy) affected by Congenital Hypothyroidism, in the period 1981-1996 (n = 92). For the evaluation of seasonal cyclic trends in TSH, we considered the level of the hormone in all newborns of Marche Region screened in the period 1989-1996. Data were collected from Neonatal Screening Register of Marche Region. All the statistical analyses are based on circular statistics techniques (Rayleigh test, Roger test, estimation of density by kernel method, Mardia test for circular-linear correlation, Maximization of Mean Vector Length). RESULTS: No cyclic trend was pointed out with regard to Congenital Hypothyroidism; neither seasonal rhythms nor other cyclic patterns of TSH levels were evidenced. CONCLUSIONS: Neither the hypothesis of birthdate as a risk factor for Congenital Hypothyroi-dism, nor the existence of seasonal variations in TSH hormone releasing were confirmed.

Differentiation between pigmented Spitz naevus and melanoma by digital dermoscopy and stepwise logistic discriminant analysis.

Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.

Digital epiluminescence microscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions. A statistical comparison between visual and computer inspection.

Epiluminescence light microscopy (ELM) has been confirmed to be a useful tool for the diagnosis of pigmented skin lesions. The application of digital systems to epiluminescence represents the latest attempt to improve the diagnosis of cutaneous melanoma. The aim of this study was to compare the diagnostic accuracy of one of these systems, the DB-Dermo MIPS, with the accuracy of well-trained dermatologists using the ELM technique in order to establish the real usefulness of this instrument and to verify how much it can help the clinician make a diagnosis in a clinical setting. During a campaign for the early diagnosis of cutaneous melanoma, 311 patients with non-melanocytic lesions, common naevi, dysplastic naevi and melanomas underwent clinical diagnosis using ELM, computerized evaluation with DB-Dermo MIPS and skin biopsy. Sensitivity, specificity, true and negative predictive value were evaluated for epiluminescence and digital epiluminescence. Our study revealed that the inspection of pigmented skin lesions by digital epiluminescence has a better diagnostic accuracy than that of a trained dermatologist using the epiluminescence technique only. In our experience, this computerized system can play an essential role in the detection of early melanomas.

Digital dermoscopy analysis for the differentiation of atypical nevi and early melanoma: a new quantitative semiology.

OBJECTIVES: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. DESIGN: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color. SETTING: University medical department. PATIENTS: A sample of patients with excised pigmentary skin lesions (nevi and melanomas). MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions. RESULTS: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function. CONCLUSION: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.

Face-to-face diagnosis vs telediagnosis of pigmented skin tumors: a teledermoscopic study.

BACKGROUND: Teledermoscopy uses telecommunication technologies to transfer images of pigmented skin lesions, including clinical and anamnestic data, via e-mail to specialized centers for teleconsultation. DESIGN: Sixty-six pigmented skin lesions examined on a face-to-face basis in a skin lesion clinic in L'Aquila, Italy, were sent via e-mail on a standard-resolution color monitor for consultation at a university dermatology department in Graz, Austria. INTERVENTION: Digital photographs of the clinical and dermoscopic images of all pigmented tumors were taken with a stereomicroscope connected to a high-resolution video camera in Truevision advanced graphic array (Targa) format file and converted successively into a Joint Photographic Expert Group (PEG) format file. All lesions were excised surgically and diagnosed histopathologically. MAIN OUTCOME MEASURE: Diagnostic concordance between face-to-face diagnosis and telediagnosis. RESULTS: The diagnostic concordance was 60 (91%) of 66 cases. The number of correct telediagnoses was lower, but the difference was not statistically significant (Wilcoxon test, P = .10). The accuracy of the telediagnoses was not related to the quality of the images, but highly depended on the level of diagnostic difficulty of a given pigmented skin tumor (Spearman correlation, P= .01). CONCLUSION: Teleconsultation of clinical and dermoscopic images of skin tumors via e-mail provides a similar degree of diagnostic accuracy as face-to-face diagnosis.

Intraobserver agreement in interpretation of digital epiluminescence microscopy.

BACKGROUND: Although a major problem with the classification of epiluminescence microscopy (ELM) findings is the lack of standard definitions, reproducibility of the criteria proposed has never been investigated. OBJECTIVES: Our purposes were (1) to perform a review of four major published classifications to obtain a set of apparently well-defined ELM variables and descriptors and (2) to evaluate the ability of one of us to report consistently ELM findings in melanocytic lesions according to these criteria. METHODS: Intraobserver agreement (with a set of 44 selected descriptors) between two readings of 150 digital ELM images was evaluated with the kappa (kappa) statistic. Subgroups of descriptors were compared for kappa value distribution. RESULTS: The median kappa value for the whole series of descriptors was 0.66. Median kappa did not vary significantly among the four classification systems (kappa = 0.61 to 0.67). Agreement was significantly better as to the presence or absence of ELM findings (kappa range, 0.39 to 1.00; median kappa, 0.77) compared with agreement as to their distribution (kappa range, 0.10 to 0.79; median kappa, 0.47; p = 0.0007) and their width, thickness, and size (kappa range, 0.06 to 0.83; median kappa, 0.39; p = 0.0075). CONCLUSION: Although nothing can be inferred from a single study, descriptors associated with low intraobserver agreement are likely to be inadequately defined.

Characterization of phenylketonuria alleles in the Italian population.

In order to identify the molecular basis of phenylketonuria (PKU) in Italy, we screened the entire coding sequence of the phenylalanine hydroxylase gene in 20 Italian PKU patients, whose origins are scattered throughout Italy. The frequency of each identified mutation and of 5 other European mutations was determined within a panel of 92 Italian PKU patients. This approach allowed us to identify 20 different PKU mutations and characterize 64% of the Italian PKU chromosomes. Eleven mutations (IVS10nt546, L48S, R158Q, R261Q, P281L, R261X, R252W, delta T55, IVS7nt1, IVS12nt1, Y414C) represent 55.4% of the Italian PKU alleles, the most common mutations being IVS10nt546 (12.4%) and L48S (9%). All the other mutations are very rare. These data confirm the great heterogeneity expected from previous RFLP haplotype studies. Genotype/phenotype correlation allowed for assessment of the clinical impact of the 20 identified mutations.

Computerized evaluation of pigmented skin lesion images recorded by a videomicroscope: comparison between polarizing mode observation and oil/slide mode observation.

BACKGROUND/AIMS: It has now been established that ELM significantly improves the clinical diagnosis of pigmented skin lesions, particularly when associated with image analysis on digital pictures. Besides surface microscopes, so called "videomicroscopes" are nowadays commercially available. Thanks to their practicality and to their reasonable price and small volume, they could be usefully employed by general practitioners or peripheral dermatologists in their practice. The aim of our study was to evaluate the usefulness and the handiness of a videomicroscope provided with polarized light, and to compare images recorded in the polarizing mode to those of the same lesions recorded after application of oil and a glass slide. METHODS: 114 images of benign pigmented skin lesions were recorded both in polarizing mode and in oil/slide mode observation. Digital images were then analyzed by means of a dedicated software, evaluating 34 different parameters. RESULTS: The instrument is easy to handle and the acquisition of images is simple and quick. Polarizing mode observation enables the recognition of subsurface structures, like pigment network and capillaries. Red and blue components in the images tend to be more pronounced, when images are acquired by the polarizing system, whereas green components are prominent in oil images. Values referring to dark areas are also higher for oil images. However, the 2 observation modes provide digital images, whose values, in most cases, do not differ statistically. CONCLUSION: Videomicroscopes are cheap, space saving, and enable a quick examination of skin areas to be imaged. The possibility of a rapid switch from surface to subsurface polarizing mode observation, makes the examination procedure even faster. Our data demonstrate that polarizing mode observation and recording can be employed as a basis for clinical and computerized epiluminescence, particularly in situations, where a rapid screening of numerous patients and lesions is necessary.

Breathing disorders in males with acquired encephalopathy.

Six boys affected by acquired encephalopathy with an abnormal breathing pattern in wakefulness were studied. Polygraphic recordings showed two different patterns in our population. In two brothers a periodic breathing pattern was recorded in the awake and sleep states. In the others, central apneas with or without tachypnea and O2 desaturation were observed only during wakefulness. The analogy of these patterns with those of genetic syndromes such as familial encephalopathy and the Rett syndrome led us to postulate the aspecificity of this finding and the importance of further studies to elucidate the role of impaired behavioural and automatic breathing system control.