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The initial presentation and diagnosis of an aviator with a pigmented skin lesion. The epidemiology of the skin cancer epidemic, including melanoma is discussed. Prognostic implications of melanoma and the U.S. Air Force experience with melanoma in aircrew are also depicted.
The poor prognosis of thick malignant melanomas emphasizes the importance of their early detection. Skin microscopy using a stereomicroscope has been shown to increase the accuracy of clinical diagnosis significantly in pigmented skin lesions. Owing to the development of the Heine Delta 10 dermatoscope, skin microscopy has become less difficult and more rapid. Therefore, this technique can now be applied routinely in daily office practice.
This paper describes three girls with an incomplete form of the McCune-Albright syndrome. Polyostotic fibrous dysplasia and precocious puberty were present but the typical abnormal skin pigmentation was absent.
A 66-year-old man suffering from atrial flutter developed cutaneous blue-gray pigmentation while receiving 600 mg of amiodarone daily for 15 months. With reduction of the dose to 100 mg, skin discoloration disappeared within 16 months, to reappear within 7 months after increasing the dose to 400 mg. Finally, the discoloration disappeared within 13 months with a dose reduction to 200 mg daily. It seems that a tissue threshold level for amiodarone exists in this patient, above which skin discoloration appears and below which it fades. Dose, duration, metabolism, macrophage transfer, and spillover saturation-excretion may be relevant in amiodarone-induced skin pigmentation.
The authors describe a patient with changes in oculocutaneous pigmentation that cleared after chlorpromazine was discontinued. They suggest that loxapine may be a suitable alternative to phenothiazines when skin pigmentation and ocular involvement occur, although the patient must be carefully monitored for ocular problems.
BACKGROUND: Given the increasing demographic diversity in the United States, clarifying relationships between race, color, ethnicity, and disease processes is critical. OBJECTIVES: We sought to examine the correlation between objective measures of skin pigmentation, racial identification, and physician-diagnosed and self-reported skin phototypes. METHODS: A total of 558 participants (76 nonwhite) were evaluated. A subset underwent spectrometric readings and digital photography of the upper aspect of the inner arm. Self-identified race was compared with 7 measures of pigmentation. RESULTS: Race correlates best with physician-diagnosed skin phototype (r = 0.55, P < .01), whereas self-reported skin phototype, spectrometry, and colorimetry correlate poorly with race (r = 0.28, < 0.40, and r > -0.31, respectively, P < .01). Associations between race and subjective measures strengthen among patients with darker skin. CONCLUSION: Objective measures of pigmentation fail to correlate well with race, whereas race correlates moderately with physician-diagnosed skin phototype. Including objective methods of analyzing skin color may reduce subjective influences of race in assessing photosensitivity and potential risk for skin cancer.
Exposure to ultraviolet (UV) radiation may induce erythema, DNA damage and suppression of immune responses. Melanin pigmentation offers protection against the first two of these effects, but immunosuppression seems to occur irrespective of the subject's pigmentation. Cis-urocanic acid (cis-UCA), produced by isomerization of trans-UCA in the stratum corneum on UV exposure, initiates some of the immunomodulatory effects of UV radiation. In the present study the relationship between skin pigmentation and UCA isomerization has been examined in 28 healthy individuals of skin types I-IV. Pigmentation is measured in five areas of not recently exposed back skin before irradiation with 0, 0.45, 0.9, 1.8 and 3.6 standard erythema dose (SED) of filtered broadband UV-B (1 SED = 10 mJ cm-2 at 298 nm). The concentration of UCA isomers is measured immediately after the irradiation. With 3.6 SED, the relative production of cis-UCA is close to the maximum obtainable, irrespective of skin type. A significant negative correlation is found between pigmentation and relative production of cis-UCA at 0.45 and 1.8 SED, and between pigmentation and absolute production of cis-UCA at 0.45 SED. At doses of 0.45 and 0.9 SED the relative and absolute production of cis-UCA are higher in the group with skin types I and II when compared with the group with skin types III and IV. The higher isomerization in the lightly pigmented subjects than in the more pigmented ones may indicate that people with fair skin are at a relatively higher risk of immunosuppression when exposed to low doses of UV radiation.
An accurate answer to the clinical question of whether a pigmented skin lesion has become a malignant melanoma or not is difficult because of the clinical variability of this lesion. Because of the low incidence of 2400 new melanoma cases each year in The Netherlands, a general practitioner only sees one new case every 3-4 years. The best way to distinguish between a benign lesion and a malignant melanoma is the combined use of several criteria, such as in the ABCD-formula: asymmetry, border irregularity, colour variation and a diameter > 6 mm. Dermatoscopical examination, provided that the technique is used by well-trained and experienced physicians, is a valuable adjunct to clinical examination. A pigmented lesion should always be excised if there is not enough convincing evidence to exclude its malignant nature. Histological classification of pigmented lesions may prove difficult because of morphological overlap between benign and malignant melanocytic tumours.
As a result of our improved understanding of the biologic importance of the various forms of pigmented skin lesions, we now have the ability to distinguish troublesome spots from those having no medical importance. These circumstances parallel an astronomical rise in the incidence of malignant melanoma. When evaluating the skin, attention to the concepts presented here will allow a high degree of accuracy in classifying moles in the benign or malignant category. For the most part, consideration of the lesion's border, shape, color, and size provides sufficient information with which to decide when a biopsy is warranted. Moles should never be destroyed by burning or freezing. If they are important enough to be removed, histologic verification of their nature must be obtained.
Prompted by the development of the lightweight, inexpensive and simple to use dermatoscopy, skin surface microscopy can now be applied in daily practice. The case reports presented here document the diagnostic improvement achieved with dermatoscopy in pigment skin lesions of children.
In this review, an attempt is made to provide a status on the current knowledge concerning the connection between skin pigmentation, naevi, sunshine and development of cutaneous malignant melanoma. Our knowledge is based partly on descriptive epidemiological reports, and partly on information obtained from case control investigations. The descriptive investigations have revealed characteristic geographical and ethnic differences in the distribution of the disease. Cancerregistry data have revealed a rapid increase in the incidence among white populations during the past 30-40 years with particularly pronounced increase for the areas of the body normally covered with clothes. Lacking consistency between indicators for cumulative exposure to sunlight and descriptive epidemiological studies have led to the hypothesis that intermittent exposure to sunlight is particularly harmful. Case control investigations have provided further support to this hypothesis and have demonstrated that sunbathing is associated with an increased risk for development of melanoma, particularly during childhood and particularly if it leads to sunburning. In addition, the risk of development of melanoma is increased in persons with a tendency to freckle and/or with many naevi. On this background, certain risk groups may be informed about prophylactic measures with subsequent possibility of reducing the number of new cases of cutaneous melanoma in the future. Finally, it is emphasized that the disease is multifactorial in origin and that the pathogenesis is not fully elucidated.
In this review, an attempt is made to provide a status on the current knowledge concerning the connection between skin pigmentation, naevi, sunshine and development of cutaneous malignant melanoma. Our knowledge is based partly on descriptive epidemiological reports, and partly on information obtained from case control investigations. The descriptive investigations have revealed characteristic geographical and ethnic differences in the distribution of the disease. Cancer registry data have revealed a rapid increase in the incidence among white populations during the past 30-40 years with particularly pronounced increase for the areas of the body normally covered with clothes. Lacking consistency between indicators for cumulative exposure to sunlight and descriptive epidemiological studies have led to the hypothesis that intermittent exposure to sunlight is particularly harmful. Case control investigations have provided further support to this hypothesis and have demonstrated that sunbathing is associated with an increased risk for development of melanoma, particularly during childhood and particularly if it leads to sunburn. In addition, the risk of development of melanoma is increased in persons with a tendency to freckle and/or with many naevi. On this background, certain risk groups may be informed about prophylactic measures with subsequent possibility of reducing the number of new cases of cutaneous melanoma in the future. Finally, it is emphasized that the disease is multifactorial in origin and that the pathogenesis is not fully elucidated.
BACKGROUND: It is mandatory that a new diagnostic method be validated by comparison with a well-established reference procedure before being introduced for use in clinical practice. In the field of pigmented skin lesions (PSL), clinical examination should be considered the reference procedure for new diagnostic methods, such as dermoscopy. However, it has not yet been established which is the best photographic procedure for obtaining the most informative clinical images to be used in a formal diagnostic setting. METHODS: In this study we investigated the diagnostic information provided by the two most popular methods currently used for clinical photographing of PSL: "contact" images obtained with a Dermaphot (Heine Ltd) at original x 10 magnification without oil application and "distant" images obtained with a macro objective from a distance of 10 cm. RESULTS: Two experienced dermatologists observed clinical images of a series of 57 PSL (11 melanomas, 31 melanocytic nevi, 10 pigmented basal cell carcinomas, and four other diagnoses). The degree of concordance between the diagnoses based on "contact" and "distant" images (melanoma/non-melanoma) was very good (k = 0.819). Regarding histology, the degree of concordance was better when the diagnosis was based on "contact" images (k = 0.54) than "distant" images (k = 0.47). In particular, "contact" images were superior to "distant" images for diagnosis of non-melanoma lesions (specificity of melanoma diagnosis 87.7% vs. 83.6%), but we found no difference in melanoma detection (73% of sensitivity for both methods). CONCLUSIONS: Although the two photographic procedures appear to provide similar levels of diagnostic information, the "contact" method seems to provide a higher specificity for melanoma diagnosis.
The melanocortin-1 receptor (MC1R) and P gene product are two important components of the human pigmentary system that have been shown to be associated with red hair/fair skin and cause type II oculocutaneous albinism, respectively. However, their contribution to inter-individual variation at the population level is not well defined. To this end, we genotyped 3 single nucleotide polymorphisms (SNPs) in the MC1R gene (Arg67Gln, Gln163Arg, Val92Met) and 2 SNPs in the P gene (IVS 13-15 and Gly780Gly) in 184 randomly ascertained Tibetan subjects, whose skin color was measured as a quantitative trait by reflective spectroscopy. Single locus analyses failed to demonstrate an association between any of the 5 SNPs and skin pigmentation. However, when an epistatic model was applied to the data, a significant gene-gene interaction was identified between Val92Met in MCIR and IVS13-15 in the P gene (F=2.43; P=0.0105). We also discuss the possible mechanisms of how gene interactions arise in signal transduction pathways.
The background for this study was reports in the literature of stronger fluorescence observed visually for melanomas compared with benign naevi in formalin-fixed paraffin-embedded sections. Our objective was to carry out a quantitative study of the phenomenon and to investigate if such an approach could be used in the detection of melanomas. Microscopic digital imaging was used to measure quantitatively the fluorescence intensity in specimens from 50 malignant melanomas, four basal cell carcinomas and 58 benign lesions. The mean fluorescence intensity of the melanomas was considerably higher than of the other lesions. For melanomas, the intensity depended both on the distance from the skin surface and the distance from the centre of the lesion. A simple algorithm based on the intensity threshold correctly classified the melanomas with a sensitivity of 74% and a specificity of 59%. Quantitative measurements of the fluorescence of the pigmented skin lesions fixed with formalin and embedded in paraffin can be a useful auxiliary tool for differentiating melanoma from other pigmented lesions histopathologically.
Epiluminescence microscopy (ELM) is a non-invasive technique for in vivo examination which can provide additional criteria for the clinical diagnosis of pigmented skin lesions (PSLs). In the present study we attempt to determine whether PSLs can be automatically diagnosed by an integrated computerized system. This system should recognize the PSL, automatically extract features and use these features in training an artificial neural network, which should--if sufficiently trained--be capable of recognizing and classifying a new PSL without human aid. One hundred and twenty images of randomly selected histologically proven PSLs (33 common naevi, 48 dysplastic naevi and 39 malignant melanomas) were used in this study. The images were digitally obtained and the morphological features of the PSLs were extracted electronically without human assistance. The numerical data were then divided into learning and testing cases and linked to an artificial neural network for training and for further classification of lesions that the system had not been trained on. Our results show that the computerized system was able to automatically identify 95% of the PSLs presented. The sensitivity and specificity of the computerized system were 90% and 74% respectively. In contrast, when differentiating between individual types of lesions, the system performed at true positive rates of only 38% for malignant melanoma, 62% for dysplastic naevi and 33% for common naevi. Our data indicate that (1) ELM images of PSLs provide an excellent source for digital image analysis; (2) the vast majority of PSLs can be correctly identified by a relatively simple (and thus not "intelligent") application of digital image analysis; (3) automatic feature extraction based mainly on ABCD rules provides reliable data on the distinction between benign and malignant PSLs; and (4) there is evidence that artificial neural networks can be trained to adequately discriminate between benign and malignant PSLs.
We found an increased amount of immunoreactive tyrosinase in human melanocytes after 6-d culturing with vitamin D3 (cholecalciferol). Most of these melanocytes became more dendritic and swollen in a fashion similar to that noted in the skin after ultraviolet irradiation. However, 7-dehydrocholesterol (pro-vitamin D3) or 1 alpha,25-dihydroxy-vitamin D3 (activated vitamin D3) were found to have little effect on the same system. Because vitamin D3 is known to be photochemically converted from pro-vitamin D3 in the skin by ultraviolet irradiation, the mechanism of human skin pigmentation after ultraviolet irradiation, thus far unknown, may be at least partly explained by this stimulating effect of vitamin D3 on melanocytes.
We present a conceptual framework for applying techniques of SNP genotyping as a molecular biological approach and remote sensing as an ecological approach to elucidation of the contribution of polygene and environmental factors to inter-individual variation in skin pigmentation phenotype. Additionally, we discuss the obstacles that frustrate our efforts to identify how the human genome encodes the complex phenotype and suggest the use of computational methods designed for knowledge discovery within hereditary database.