ArticleLiterature Review

Sun and Malignant Melanoma

Authors:
Article

Sun and Malignant Melanoma

If you want to read the PDF, try requesting it from the authors.

Abstract

The incidence and mortality rates of malignant melanoma in Caucasians are increasing rapidly in many countries worldwide. Considerable circumstantial evidence suggests that exposure to solar radiation may play a role in this substantial rise in malignant melanoma. This evidence comes primarily from epidemiologic studies and from the identification of susceptible phenotypes. Despite the increasing data that implicate sunlight as an important factor in the development of certain types of malignant melanomas in humans, the role of solar electromagnetic radiation in the pathogenesis of human malignant melanomas is yet to be determined.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Well-recognized characteristics of children who have an increased risk for developing melanoma include fair skin, blue or green eyes, and sun sensitivity [8][9][10][11]. However, additional risks are associated with rare syndromes [9,12,13], immunosuppression [4,8,14,15], increased number of melanocytic nevi [3,10,[16][17][18], family history [8,11,14,15,[19][20][21][22][23], prior chemotherapy [15] and hereditary retinoblastoma [24]. ...
... Well-recognized characteristics of children who have an increased risk for developing melanoma include fair skin, blue or green eyes, and sun sensitivity [8][9][10][11]. However, additional risks are associated with rare syndromes [9,12,13], immunosuppression [4,8,14,15], increased number of melanocytic nevi [3,10,[16][17][18], family history [8,11,14,15,[19][20][21][22][23], prior chemotherapy [15] and hereditary retinoblastoma [24]. ...
Article
Full-text available
Melanoma accounts for 7% of all cancers in adolescents ages 15–19 years but is an unexpected malignancy in younger children. The prevalence of malignant melanoma is very rare in children ages 1–4 years, but certain non-modifiable risk factors such as xeroderma pigmentosum, congenital melanocytic nevus syndrome and other inherited traits increase the risk for its development in these young children. Recent genomic studies have identified characteristics of pediatric melanoma that differ from conventional melanoma seen in adults. In this review the authors inform on the types of melanoma seen in children and adolescents, discuss similarities and differences in melanoma between children and adults, and discuss the role of imaging in the care of these children.
... Various biological therapies such as cellular immunotherapy, cytokine, and monoclonal antibody therapies have been widely used in the treatment of SKCM, and in-depth research on the pathogenesis of SKCM and the discovery of new therapeutic targets is still the current focus (Wong et al., 2017). Numerous studies have confirmed that sunlight exposure is an important environmental factor in the pathogenesis of SKCM (Kopf et al., 1984;Elwood, 1996;Oliveria et al., 2006). Sunlight-driven alterations in DNA chemistry and DNA replication errors are potential mechanisms driving melanocyte mutations (Jin et al., 2021). ...
Article
Full-text available
Objectives: Sunlight exposure is an important environmental factor in the pathogenesis of skin cutaneous melanoma (SKCM). Ultraviolet (UV) from sunlight can cause excessive intracellular production of reactive oxygen species (ROS), resulting in damage from oxidative stress to cells. As a major iron-rich and ROS-producing organelle, mitochondria are considered as an important place for cell ferroptosis. Thus, the pathology and potential biological process of UV exposure-induced ferroptosis in the development of SKCM has aroused our strong interest. Methods: Gene expression profile datasets of melanoma cell line datasets (GSE31909) and UV-irradiated mitochondria dataset (GSE3632) were downloaded from the Gene Expression Omnibus (GEO) database, and ferroptosis-related genes were obtained from the FerrDb v2 database. After identifying the common differentially expressed genes (DEGs), comprehensive analyzes were performed, including functional annotation, protein-protein interaction (PPI) network construction, hub gene identification, and gene and tissue protein expression levels, survival analysis, and immune cell infiltration analysis. Results: A total of 14 common DEGs was identified for subsequent analyses. Seven DEGs, including PSMB4, CRELD2, CDKN2A, TIMP1, NDRG1, ATF3 and JUND, have consistent performance in mRNA and protein expression in normal skin and SKCM tissues can be regarded as a good biomarker with SKCM diagnostic effectiveness. Functional enrichment analysis results indicate that HIF-1 signaling pathway and angiogenesis involved in the pathogenesis and development of SKCM. Induction of ferroptosis in tumor cells by enhancing the function of CD8 ⁺ T cells is expected to be an effective intervention to promote tumor therapy. Conclusion: Our study reveals the pathogenesis and potential biological processes of UV exposure-induced ferroptosis in the development of SKCM, which may provide potential immunotherapy targets for SKCM treatment via tumor cell ferroptosis mechanisms.
... The most important environmental mutagen by far is the ultraviolet (UV) component of sunlight which has been rated as carcinogenic to humans by IARC (IARC Press, 1992). Exposure to UV is a dose-dependent risk factor (Kopf et al., 1984; Gallagher et al., 2005), which can cause skin cancers, mostly basal cell and squamous cell carcinoma. Radiation-induced cancers are a stochastic late effect of ionizing or non-ionizing radiation. ...
Article
Cancer is one of the most serious diseases that threaten human being today. Most cancer results from the interaction of genetic and the environment. Genetic factors by themselves are thought to explain only about 5%-10% of all cancers and the remainder can be attributed to environmental carcinogens. The involuntary or voluntary exposure to these carcinogens may account for the recent growing incidence of cancer. These agents include; microorganisms (viruses, bacteria and parasites), radiations (radioactivity, UV and pulsed electromagnetic fields), occupational exposures, tobacco smoke, sexual behavior, alcohol, dietary constituents, pollutants (in the workplace, air, water, and food supply), formaldehyde, volatile organic compounds such as benzene and 1,3 butadiene and many xenochemicals, carcinogenic metals and metalloids, pharmaceutical medicines, food additives, additive in cosmetics, etc. The industrial revolution over the second half of the last century and its consequences in domains such as energy, transport, agriculture, food and health led to synthesize, produce and introduce into the environment, millions of man-made chemicals or substances. Although environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans, variation in incidence and progression of cancers among individuals can be attributed to inter-individual variation in genetic makeup. The risk fraction attributable to environmental factors is still unclear. One of the hopeful messages from cancer research is that most of the cases of cancer are linked to environmental factors and, in principle, can be prevented by growing awareness about the modulating risks from environmental carcinogens.
... The primary etiology of melanoma is unknown but there is strong evidence that UVlight exposure plays a major role in the development of the cutaneous melanoma (28,29). The incidence of this disease has increased markedly during the last three decades in the Caucasian population all over the world (30,31). ...
... Sober and Kopf. [35][36][37][38] The early diagnosis of melanoma has allowed the US and Australia to improve their 5-year survival rates (currently >90%). 1 There remains much work to be done, because early detec-tion and screening methods have remained underused in many parts of the world, in particular in several Eastern European countries and Northern Ireland, in which 5-year survival rates are notably lower (53%-60%). 39 It is worth noting that Koh et al were the first to bring an evaluation component into our approach to melanoma screening. ...
... However, a number of surveys suggest that sunlight does influence the development of at least some of these malignancies. (28) Caucasians with melanomas statistically tend to have light eyes, light hair, fair complexions, and spend more time outdoors when compared to a control group of patients without melanomas. Surveys of the geographic distribution of this cancer, even in genetically similar populations, have demonstrated a much greater melanoma prevalence associated with high insolation (Le., exposure to sunlight), as compared to low insolation. ...
Chapter
The medical aspects of the science of photobiology are among the most important parts of this discipline, since they are concerned primarily with direct effects of nonionizing radiation on humans. Two organ systems are directly affected by sunlight: the eye and the skin. The eye is discussed in Chapter 9. Therefore, the present discussion will be concerned primarily with cutaneous reactions to the sun.(1–6)
... Non-ionizing radiations comprise ultraviolet (UV) rays, which have been rated as carcinogenic to humans by IARC (1992). Exposure to UV is a dose-dependent risk factor (Kopf et al., 1984;Gallagher et al., 2005), which can cause skin cancers, mostly basal cell and squamous cell carcinoma (Henriksen et al., 1990;Urbach, 1991;Feychting et al., 1995;Foliart et al., 2006) and can be also involved in carcinogenesis of melanoma (IARC, 1992) and consequently, in its current growing incidence. Increase in lifestyle-related natural or artificial (sun beds) exposure to UV has been incriminated to account for the growing incidence of melanoma. ...
Article
Sonnenschutzfilter dienen der Prophylaxe von akuten und chronischen UV-Schäden. Der LSF trifft eine Aussage über die erythemprotektive Wirkung im Bereich der UV-B-Strahlung, gibt jedoch keine Auskunft über den UV-A-Schutz oder eine eventuell vorhandene oder fehlende immunprotektive Wirkung. Verschiedene Untersuchungen in vitro und in vivo im Tiermodell haben sich mit der Frage der immunprotektiven Eigenschaften von Sonnenschutzfiltern auseinandergesetzt, allerdings gibt es nur wenige Arbeiten, die sich mit den in vivo Bedingungen im humanen Modell auseinandersetzen. Es konnte belegt werden, dass steigende Dosen von UV-B-Strahlung (0-100 J/m²) in transformierten (KB Zellen) oder normalen humanen Keratinozyten (HNK), dosisabhängig die Zytokin-(IFN-g, TNFa)-induzierte ICAM-1-Expression inhibieren. Diese Eigenschaft wurde in dieser Arbeit zu nutze gemacht, um im humanen in vivo Testsystem, den Nachweis zu erbringen, dass Lichtschutzfilter in der Lage sind vor UV-B bedingter Immunsuppression zu schützen. Als biologischer Marker wurde hierfür die UV-B-induzierte Hemmung der zytokinabhängigen ICAM-1 Expression als Read-out-System genutzt. Es konnte nachgewiesen werden, dass eine 2%-ige Uvinul-Formulierung und eine 5%-ige Parsol-Formulierung in der Lage sind, nicht nur vor UV-B-Strahlung im Bereich des ausgewiesenen LSF zu schützen, sondern auch in erheblichem Maße vor UV-B bedingter Suppression der IFN-g-induzierter ICAM-1 Aufregulierung. Hiernach sind diese Lichtschutzfilter also in der Lage nicht nur vor UV-B bedingtem Erythem sondern auch vor UV-B bedingter Immunsuppression zu schützen.
Article
ABSTRACTUVB irradiation depletes all-trans-retinol (ROL) and all-trans-retinyl esters (RE) from the hairless mouse epidermis. Prevention of this may be of relevance in counteracting the long-term side effects of UVB exposure. We studied the effects of a topical treatment with natural retinoids before and after UVB exposure on three parameters involved in vitamin A metabolism: the amount of epidermal ROL and RE, the level of functional cellular retinol-binding protein I (CRBP-I), which is likely to protect ROL from UVB, as well as the cytosolic and microsomal enzyme activities which generate ROL and RE, i.e. all-trans-retinaldehyde (RAL) reductase, acylCoA:retinol acyltransferase (ARAT) and retinyl-ester hydrolase (REH). Topical pretreatment with retinoids promoted a dramatic increase of epidermal ROL, RE and CRBP-I levels, a transient increase of RAL reductase and ARAT activities as well as a decreased activity of REH, indicating a direction of epidermal vitamin A metabolism toward storage. In untreated mice UVB irradiation induced a depletion of epidermal ROL and RE in 10 min and a 50% decrease of CRBP-I after 24 h. In mice treated with topical retinoids, and then exposed to UVB, epidermal RE levels were higher than in vehicle-treated, nonirradiated mice. In contrast, ROL was as much depleted after UVB in pretreated as in untreated animals in spite of an induction of CRBP-I, indicating that CRBP-I does not actually protect ROL from UVB-induced depletion in this model. However, the reconstitution of both epidermal ROL and RE, after their depletion induced by UVB, was accelerated by previous topical treatment with RAL. Our results indicate that topical delivery of retinoids partly counteracts UVB-induced vitamin A depletion and promotes recovery.
Article
In the USA malignant neoplasms of the skin are the most common cancers of man. Annually, over 500,000 new cutaneous cancers are diagnosed. Of particular concern is the inexorable increase in the incidence and mortality rate of malignant melanoma (in 1978: 25,000 new cases; 5800 deaths). There are substantial data that (1) implicate sunlight as the probable cause of many cancers of the skin, and that, (2) indicate early diagnosis and prompt treatment results in cure in most instances. The time has come to create, implement, and evaluate a National Program on Education of the Medical Profession and the Public on Cancers of the Skin with emphasis on cutaneous malignant melanoma.
Article
Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, is an indispensable step in all primary prevention efforts. This paper aims to assess the prevalence of different pigmented lesions among schoolchildren and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. One to 10 common melanocytic naevi were found in 27% of the participants, and the naevus numbers were in the range of 10-100 in 67%; 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Statistically significant associations were found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, a history of severe painful sunburns and a family history of a large number of melanocytic naevi. Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of a large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.
Article
To evaluate the effectiveness of cellular telephone text messaging as a reminder tool for improving adherence to sunscreen application. We conducted a randomized, controlled trial of the effect of an electronic text-message reminder system on adherence to sunscreen application. Adherence to daily sunscreen use was evaluated using a novel electronic monitoring device. Participants were recruited from the general community. Seventy participants constituted a volunteer sample from the general community. The inclusion criteria required participants to be 18 years or older, to own a cellular telephone with text-message features, and to know how to retrieve text messages. Intervention Half of the participants received daily text-message reminders via cellular telephone for 6 weeks, and the other half did not receive reminders. The text-message reminders consisted of 2 components: a "hook" text detailing daily local weather information and a "prompt" text reminding users to apply sunscreen. Main Outcome Measure The primary end point of the study was adherence to sunscreen application measured by the number of days participants applied sunscreen during the 6-week study period. All 70 participants completed the 6-week study. There were no statistically significant differences in baseline characteristics between the 2 study groups. At the end of the study period, the 35 participants who did not receive reminders had a mean daily adherence rate of 30.0% (95% confidence interval, 23.1%-36.9%). In comparison, the 35 participants who received daily text-message reminders had a mean daily adherence rate of 56.1% (95% confidence interval, 48.1%-64.1%) (P < .001). Among the participants in the reminder group, 24 (69%) reported that they would keep using the text-message reminders after the study, and 31 (89%) reported that they would recommend the text-message reminder system to others. Subgroup analysis did not reveal any significant demographic factors that predicted adherence. Despite awareness of the benefits of sunscreen, adherence is low, even in this population, for whom adherence was knowingly monitored. Short-term data demonstrate that using existing cellular telephone text-message technology offers an innovative, low-cost, and effective method of improving adherence to sunscreen application. The use of ubiquitous communications technology, such as text messaging, may have implications for large-scale public health initiatives. Trial Registration clinicaltrials.gov Identifier: NCT00535769.
Article
L'épiderme humain contient des rétinoides endogènes et des caroténoïdes. Nous présentons une méthode d'évaluation de la pénétration et du métabolisme des rétinoïdes (acide rétinoïque, rétinaldéhyde, rétinol, palmitate-de-rétinyle) dans la peau humaine "ex-vivo" à partir de peau totale incubée dans des cellules de Franz. Les résultats montrent qu'il n'y a pas de métabolisme pour l'acide rétinoïque, forme active de la vitamine A qui lie les récepteurs nucléaires, alors qu'on observe un métabolisme d'oxydation et de réduction pour le rétinaldehyde, ainsi qu'une augmentation des rétinoïdes endogènes pour le rétinol et ses esters. Nous mettons en évidence pour la première fois que le β-carotène est un précurseur de la vitamine A dans l'épiderme humain. Nous montrons un effet filtre de la vitamine A (palmitate-de-rétinyle) "in vivo" chez l'homme qui contribue potentiellement à la protection de l'ADN contre les effets des UVB.
Article
Malignant melanoma is an increasing public health problem worldwide; accordingly, identification of the constitutional and environmental factors which contribute to the development of the disease, and hence identification of the individuals at high risk of melanoma, are indispensable steps in all primary prevention efforts. The objective of the present study was to assess the prevalence of different pigmented lesions among schoolchildren, and to investigate their relationship with phenotypic pigmentary characteristics, sun exposure and other factors. A cross-sectional study was performed in two secondary schools in Szeged, Hungary. A total of 1320 schoolchildren, aged 14 to 18 years, underwent a whole-body skin examination. A standardized questionnaire was used to collect data on phenotypic, sun exposure and other variables. Between 1-10 common melanocytic naevi were found in 27% of the participants, and naevi numbers were in the range between 10-100 in 67%. 5.4% of them had more than 100 common melanocytic naevi. The prevalence of clinically atypical naevi was 24.3%. Congenital naevi were detected in 6.2% of the schoolchildren. A statistically significant association was found between the number of pigmented lesions and gender, hair colour, eye colour, skin phototype, the history of severe painful sunburns, and the family history of a large number of melanocytic naevi. Our study population displayed a markedly high prevalence of clinically atypical melanocytic naevi. Moreover, a considerable proportion of the investigated individuals had multiple common melanocytic naevi. Since the presence of large number of melanocytic naevi is a strong predictor for future melanoma development, health educational programmes on melanoma prevention should be aimed at young age groups.
Article
Evaluated the impact of a large scale campaign to encourage increased protection from solar ultra violet radiation. Representative household interview surveys were conducted both before (252 men and 308 women, age 14 to 50+ yrs) and after (291 men and 314 women, age 14 to 50+ yrs) the campaign. The initial survey showed high levels of awareness of a skin protection message. The survey following the campaign showed large increases in awareness of the campaign slogan. There were high levels of reporting about taking extra precautions for sun protection and of encouraging other people, particularly children, to increase their sun protection. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
To optimize skin pigmentation in order to help body prevention against UV radiation, the mechanism of melanin pigment transfer from melanocytes to keratinocytes must be elucidated. Melanin transfer to keratinocytes requires specific recognition between keratinocytes and melanocytes or melanosomes. Cell surface sugar-specific receptor (membrane lectin) expression was studied in human C32 melanoma cells, an amelanotic melanoma, by flow cytometry analysis of neoglycoprotein binding as an approach to the molecular specificity. Sugar receptors on melanocytes are mainly specific for alpha-L-fucose. Their expression is enhanced upon treatment by the diacylglycerol analogue 1-oleoyl-2-acetylglycerol, which can induce melanin synthesis in amelanotic human melanoma cells in a dose-dependent manner. Flow cytometry analyses showed a small-sized population of vesicles distinguishable from large cells by their fluorescence properties upon neoglycoprotein binding. Sorting indicated that the small-sized subpopulation is composed of vesicles produced by melanocytic cells. Upon vesicle formation, a selective concentration of sugar receptors specific for 6-phospho-beta-D-galactosides appears in the resulting melanocytic vesicles. Vesicles are recognized and taken up by cultured keratinocytes and a partial inhibitory effect was obtained upon cell incubation in the presence of neoglycoproteins, indicating a possible participation of sugar receptors in this recognition. The validity for such a model to help in understanding the natural melanin transfer by melanosomes is confirmed by electron microscopy, which demonstrates the presence of melanin inside keratinocytic cells upon incubation with melanocytic vesicles.
Article
Women with stage I malignant melanoma (MM) have a survival advantage over men as judged by univariate analysis. However, on multivariate analysis, gender was found to be an independent predictor of survival in only 8 of 14 published studies. This study attempts to explain the disparate findings for gender as a prognostic factor in different multivariate analyses. Univariate and multivariate analyses were performed on 832 patients with stage I MM in the New York University Melanoma Cooperative Group (NYU-MCG) data base. The results were compared with those of 14 similar studies. In the NYU-MCG data base, gender, age of the patient, and number of mitoses per square millimeter were not independent factors on multivariate analysis, whereas thickness, anatomic site, and presence of ulceration were. The statistically significant difference in survival by gender on univariate analysis, in the NYU-MCG data base, could be explained by the differences in thickness and anatomic site of the MMs in the sexes. Comparison of these results with the reviewed reports from the literature consistently shows thickness and ulceration to be independent prognosticators of survival. Likewise, most authors agree that age is not an independent predictor. However, there is no consensus with respect to gender and site, each of which was found to be an independent predictor of survival in only about half the studies reviewed. The disparate findings for gender in different multivariate analyses are explained by a gender-related difference in anatomic distribution of MM. Gender and site appear to have a similar influence in multivariate analysis and thus either one or the other is a dominant factor in different multivariate analyses.
Article
We analyze published data on cancer incidence as a function of age for (i) cutaneous melanoma for cohorts of males in Connecticut and (ii) hepatocellular cancer in Mozambique, China and Romania, on the basis of multi-hit models for carcinogenesis. The simple multi-hit model suggests an unlikely scenario in which, as the cohorts advance or the intensity of mutagenesis increases, fewer mutations are required to bring about the appearance of cancer. We present a new version of the multi-hit model in which two sets of mutatable loci are present, of differing sensitivities to mutagens. This provides a more acceptable description in which the number of rate-limiting steps for the appearance of cancer drops as the frequency of mutation rises, so that some of these steps are no longer rate-limiting.
Article
The mechanisms of UV-induced ageing and carcinogenesis of the skin have been elucidated in animals and humans, and both UVB and UVA radiation have been shown to have deleterious effects on the skin. Thus the use of solaria which deliver mostly UVA radiation is not safe. There is also an increased risk of ageing when using therapeutic UV sources. UV radiation is beneficial in many cases of skin disorders such as psoriasis, atopic eczema, acne and pruritus. Nevertheless by careful patient selection and follow-up the risks of UV can be minimised when treating patients with artificial UV radiation. During recent years there has been intensive research into the development of agents which prevent harmful effects of radiation. The retinoids are particularly interesting as they enhance skin repair after UV damage, have an anticarcinogenic effect and are effective for treating precancerous lesions such as solar keratosis and as adjuvant therapy for skin cancers. Topical retinoids are already used for the treatment of actinic skin damage, and systemic retinoids are also used in certain groups of patients who have an increased risk of contracting skin cancers such as xeroderma pigmentosum.
Article
There is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of sun exposure on the skin. Studies indicate that excessive sun exposure during the first 10-20 years of life greatly increases the risk of skin cancer. Nonmelanoma skin cancer (basal cell and squamous cell carcinoma) has been associated with cumulative sun exposure, whereas melanoma has been associated with short, intense sun exposure or blistering sunburn. Under normal circumstances, children receive three times the annual sun exposure of adults; most of one's lifetime sun exposure occurs in childhood. Depletion of the earth's protective ozone layer adds to the photodamage problem. It is clear that sun protection is most vital in the early years. Those with fair skin are at highest risk. Photoprotective measures including sunscreen, clothing, and sun avoidance in childhood may significantly reduce the occurrence of melanoma and other skin cancer in later life. Regular use of sunscreen with a sun protection factor of 15 during the first 18 years of life could reduce the lifetime incidence of nonmelanoma skin cancer by 78%. Pediatricians can play a major role in educating parents and children.
Article
This chapter compares the ability of multistage and clonal growth models for carcinogenesis to fit the cancer incidence/age profiles. It could well be, however, that the two models should not be so sharply distinguished. Indeed, the two may be unrealistic and unrealizable extremes of a continuum of mechanisms, all of which are really multistage and clonal growth processes. The two stages in carcinogenesis as the initiation and then the promotion of cancer, does not negate the possibility of further and clinically important progression of cancer. The chapter presents comparison figures in which two-stage, three-mutation models are fitted to the cancer incidence data and where these same data are fitted by the two-stage, two-mutation model that shows how difficult it will be to kinetically distinguish between these alternatives. Similarly, the multistage models in their pure form cannot be considered as realistic. It is far more realistic to assume that it is this cell and its descendants that are subject to the possibility of the fourth mutation. Indeed, it is necessary to assume this, since it is only during cell division that a thrice-mutated cell is at the risk of mutating once again. The arguments taken together should therefore be seen as supporting a multistage, clonal growth model rather than any extreme case on a continuum of such models.
Article
Despite the exciting new techniques being developed to help diagnose early malignant melanoma, the current standard of care remains periodic examination of the skin. The combination of routine physician examination coupled with self-examination of the skin provides an opportunity for the identification of early malignant melanoma. Removal of such thin lesions can significantly reduce the ever-increasing mortality rate from this potentially serious form of cutaneous cancer.
Article
Objectives To study in detail the characteristics of patients attending a screening campaign for detection of malignant melanoma. Background Malignant melanoma is the malignant tumour exhibiting the greatest increase in incidence in most countries. Design On September 15 and 16 1990 an “open house” for evaluation of skin tumours was performed mainly at dermatologic departments throughout Sweden. In the city of Malmö such patients were investigated by dermatologists and oncologists and documented in a more detailed manner than in the national campaign. Subjects 380 patients. Methods Ocular whole body examination for premalignant and malignant skin tumours. Registration of patient characteristics concerning sex, age, reason for attending. Registration of therapeutic action and possible differences between dermatologists and oncologists. Results The median age of attending persons was 67 years probably reflecting the higher prevalence of skin tumours among the elderly. Three quarters of patients sought advice for a specific skin change, in most cases verruca seborrhoica. Several premalignant and malignant non melanoma skin changes were found. Altogether two malignant melanoma were found, both of the thin type and. thus, potentially curable. Dermatologists referred 10.4% of specific skin changes to surgery compared to 30.8% for oncologists. Conclusions The great number of attending patients reveals a great concern about skin tumours among the public. This indicates the need for permanent, easily accessible skin tumour clinics, preferably run by dermatologists, where patients can be evaluated without delay.
Article
The effects of sunlight on skin are described. The principal types of sunscreens and their properties are discussed. The three types of skin tumors, their cure rates, and treatment methods are examined. (Author/MT)
Article
Models for monotone trends in hazard rates for grouped survival data in stratified populations are introduced, and simple closed form score statistics for testing the significance of these trends are presented. The test statistics for some of the models understudy are shown to be independent of the assumed form of the function which relates the hazard rates to the sets of monotone scores assigned to the time intervals. The procedure is applied to test monotone trends in the recovery rates of erythematous response among skin cancer patients and controls that have been irradiated with a ultraviolent challenge.
Chapter
Man unterscheidet zu Recht exogene und endogene Risikofaktoren, die bei der Entstehung maligner Melanome eine Rolle spielen oder spielen könnten. Als exogene Faktoren kommen Alter, Geschlecht und hormoneile Kontrazeption in Frage, aber auch die exogene Belastung durch UV-Bestrahlung und diejenige durch Umwelt-Karzinogene [8, 10]. Das Pigmentkleid (homogen oder inhomogen) und die Pigmentierungsmöglichkeiten spielen wichtige Rollen zum adaptiven Schutz vor Exzessen der exogenen UV-Belastung der Haut. Der exogenen Belastbarkeit und der Anfälligkeit der menschlichen Haut zur Entstehung maligner Melanome liegen zudem endogene Faktoren zugrunde, deren Erfassung, Messung und Beeinflussung wesentliche Voraussetzungen zur Prävention maligner Melanome darstellen.
Chapter
Das Melanom ist der maligne Tumor der Melanozyten (Pigmentzellen) der Haut und der körpernahen Schleimhäute, in Ausnahmefällen auch anderer Organe (Auge, Meningen, Lymphknoten, etc.)
Chapter
Das maligne Melanom ist der bösartige Tumor, der aus den Pigmentzellen (Melanozyten) der Haut hervorgeht. Das Melanom kann in normaler Haut entstehen oder in gutartigen Anreicherungen von Melanozyten, den sogenannten Pigmentnaevi oder Muttermalen. Das maligne Melanom ist ein ausgesprochen bösartiger Tumor mit früher und unberechenbarer Metastasierung. Eine vertiefte Information über maligne Melanome ist notwendig, hilfreich und von großer Bedeutung. Dazu kommen einige Besonderheiten: Die Häufigkeit der Melanome hat in den letzten 50 Jahren bei der weißhäutigen Bevölkerung um einen Faktor 20 zugenommen. Während die Inzidenz in der Jahrhundertmitte noch bei 0,5 neue Fälle pro Jahr pro 100.000 Menschen lag, ist sie jetzt in Mitteleuropa auf über 10 angestiegen. Dies ist nicht der Fall bei der dunkelhäutigen Bevölkerung und bei den Asiaten. Es besteht ein deutlicher Zusammenhang zwischen dem ultravioletten Licht der Sonne und der Melanom-Inzidenz. Melanome sind an lichtexpornierten Hautstellen häufiger, und sie sind um so häufiger, je stärker die Sonnenexposition der Menschen ist. Eine geographische Anreicherung der Melanome bei der weißhäutigen Rasse zum Äquator hin ist evident. Melanome sind dank ihrer braun-schwarzen Eigenfarbe sehr deutlich erkennbar, auch wenn sie noch sehr klein sind, und sie fallen auf. Verdächtige Stellen sollten einem Facharzt gezeigt werden, obschon sie keine subjektiven Symptome verursachen. Melanome sind bösartig, sie metastasieren ausgesprochen früh und unberechenbar. Metastasierende Melanome sind kaum noch heilbar. Nur die früh erkannten, noch nicht in die Tiefe eingedrungenen Melanome können durch eine vollständige dermatochirurgische Excision mit einem Sicherheitsabstand von 1–3 cm vollständig geheilt werden.
Chapter
Cumulative epidemiological evidence suggests that exposure to solar radiation plays an important role in the pathogenesis of cutaneous malignant melamona (CM) (Kopf et al. 1984). This evidence is derived primarily from the fact that CM is most frequent in fair-skinned, red-haired persons who tend to freckle, burn easily, and tan poorly following exposure to sunlight. Direct experimental evidence that CM is correlated with increased susceptibility to skin injury induced by ultraviolet radiation (UVR) is rather limited.
Chapter
Cells containing pigments are widely distributed in the various kingdoms: we find porphyrins, such as chlorophyll or hemoglobin, hemocyanin, hemerythrin, ascaracruorin which are important for such processes as the autotroph assimilation of green plants, or as respiratory pigments in the body fluids of animals. They may be concentrated in cells of plants and as hemoglobins in several animal species but also diluted in fluids as the hemoglobin of certain species of protostome animals. Guanine is contained in cells known as guanophores in the skin of cold-blooded vertebrates. The neoplasms of melanophores, known as melanomas, are very common whereas those of the guanophores (iridophores) and the guanophoromas (iridophoromas) are investigated by Matsumoto (453). The fish, Xiphophorus may be used as a model to study oncogenes (17). Proto-oncogenes seem to direct cellular transformation and/or maintenance of the neoplastic cellular condition. The relationship of genes to neoplasia is shown by insertional mutagenesis, gene amplification, structural alteration of a gene and the production of fusion genes (656).
Chapter
Die Inzidenz des malignen Melanoms (MM) variiert für weiße Bevölkerungen stark nach geographischen Regionen. Während in Nord- und Mitteleuropa 5–10 Neuerkrankungen pro 100 000 Einwohnern und Jahr auftraten, wurden in Regionen mit hoher Sonneneinstrahlung wie Australien und den Südstaaten der USA > 30 Neuerkrankungen registriert. In der Bundesrepublik Deutschland wurden in der Mitte der 80er Jahre im Saarland 6 MM pro 100 000 Einwohner und Jahr für beide Geschlechter und in Berlin (West) 8 MM für Frauen und 10 MM für Männer (altersstandardisiert für die europäische Standardbevölkerung) erhoben. Bevölkerungen mit stärkerer Pigmentierung wiesen erheblich niedrigere Inzidenzen auf: In derselben Wohnregion fanden sich für Afrikaner um einen Faktor 5–10 und für Asiaten um einen Faktor 10–100 geringere Inzidenzen als für Weiße. In den westlichen Industrieländern zeigte sich in den letzten Jahrzehnten eine starke Zunahme der Inzidenz und Mortalität. Die Inzidenz verdoppelte sich im Durchschnitt annähernd alle 15 Jahre und die Mortalität in etwa 30 Jahren. Das Risiko zur Entwicklung von MM variiert in weißen Bevölkerungen erheblich nach genetisch bedingten Dispositionen. Das größte Risiko wiesen Personen mit dysplastischen Naevuszellnaevi (NZN) und familiärem Vorkommen von MM auf, ihr relatives Risiko zur Entwicklung von MM ist mehr als lOOfach erhöht. Personen mit vielen erworbenen NZN zeigten ebenfalls ein stark erhöhtes relatives Risiko zur Entwicklung von MM, bei mehr als 60 NZN am gesamten Integument war es in einer deutschen Studie um den Faktor 16 erhöht. Ein um den Faktor 2–4 erhöhtes Risiko wiesen Personen mit geringer Pigmentierung, roten oder blonden Haaren und blauen Augen auf. Das individuelle Risiko für die Entwicklung von MM wird durch Sonnenexposition mit nachfolgenden Sonnenbränden allenfalls um einen Faktor 2–4 erhöht. Eine Zunahme der Sonnenexposition in ganzen Bevölkerungen scheint jedoch der wichtigste Faktor für die steigende Inzidenz des MM bei Weißen zu sein. Die Letalität an primären MM steigt nahezu linear mit zunehmender Tumordicke (nach Breslow), daher erscheint derzeit die frühe Diagnose und Behandlung als wichtigster Ansatzpunkt zur Senkung der Mortalität an MM.
Chapter
Omdat het een universeel fenomeen is, wordt veroudering gezien als een normaal fysiologisch proces. Hoewel het verouderingsproces de kans op ziekte doet toenemen, wordt veroudering op zichzelf niet beschouwd als iets pathologisch. Begripsmatig lijkt dit een duidelijk onderscheid, maar de haarfijne scheidslijn tussen veroudering en ziekte wordt vaak onduidelijk wanneer hij toegepast wordt op individuele gevallen. De biologische, fysiologische, anatomische en functionele belastbaarheid nemen af op hogere leeftijd (zie hoofdstuk 3). Ook is een zekere mate van atrofie aanwezig in alle lichaamsweefsels. Een groot aantal degeneratieve processen wordt ‘normale veroudering’ genoemd totdat ze zo ver voortgeschreden zijn dat ze duidelijke klinische beper-kingen veroorzaken.
Article
There is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of sun exposure on the skin. Studies indicate that excessive sun exposure during the first 10-20 years of life greatly increases the risk of skin cancer. Nonmelanoma skin cancer (basal cell and squamous cell carcinoma) has been associated with cumulative sun exposure, whereas melanoma has been associated with short, intense sun exposure or blistering sunburn. Under normal circumstances, children receive three times the annual sun exposure of adults; most of one's lifetime sun exposure occurs in childhood. Depletion of the earth's protective ozone layer adds to the photodamage problem. It is clear that sun protection is most vital in the early years. Those with fair skin are at highest risk. Photoprotective measures including sunscreen, clothing, and sun avoidance in childhood may significantly reduce the occurrence of melanoma and other skin cancer in later life. Regular use of sunscreen with a sun protection factor of 15 during the first 18 years of life could reduce the lifetime incidence of nonmelanoma skin cancer by 78%. Pediatricians can play a major role in educating parents and children.
Chapter
Natural light and UV radiation (UVR) from artificial sources has always been recognized for and endowed with health-giving powers as well as for its tonic value of generating a feeling that it is good for our psyche and contributes to the synthesis of vitamin D essential for maintaining calcium and phosphorus homeostasis and a healthy skeleton. It provides the healthy looking tan that enhances the photoprotective properties of our skin against skin cancer and photoaging.
Chapter
Die Epidemiologie des Hautkrebses ist in den letzten Dekaden eingehend untersucht worden. Ausschlaggebend dafür war die starke Zunahme der Inzidenz sowohl der epithelialen Hautkrebse als auch des malignen Melanoms. Für das maligne Melanom der Haut war mit der Zunahme der Inzidenz gleichzeitig eine Zunahme der Mortalität verbunden. Mit dieser Entwicklung traten das maligne Melanom der Haut und auch die epithelialen Hautkrebse aus dem Kreis der seltenen Entitäten in den Bereich derjenigen Neoplasien ein, die eine wichtige medizinische Bedeutung besitzen.
Article
A 32 years old man presented with well-defined lesion on the left sole 8 months back. Biopsy and FNAC from the lesion confirmed malignant melanoma left foot & the patient was advised excision. After 4 months patient gave h/o swelling on the medial aspect of the thigh. The patient was diagnosed to have fulminant metastatic malignant melanoma of the left foot with metastasis to femoral lymph node. This case report re-emphasizes the importance of the combined approach to ascertain diagnose early.
Article
Malignant melanoma is the leading cause of death as a result of skin disease in the United States. The incidence of melanoma has increased exponentially during the last two decades, and the disease is now the eighth most common cause of cancer in the United States, with an estimated annual incidence of approximately 13 per 100,000. Melanoma is curable if diagnosed and treated early in its course, but unfortunately, many patients are still diagnosed with invasive melanoma; the 5-year survival rate for those diagnosed with melanoma that has spread to. regional lymph nodes is 50%. Careful physical examination of pigmented lesions and attention to the clinical history guide the physician toward establishing a diagnosis. The early warning signs of melanoma are a change in the size, shape, or color of a lesion and symptoms associated with pigmented lesions, such as pruritus; ulceration and bleeding are generally late findings in primary melanoma. The ABCD guide for diagnosis of melanoma includes Asymmetry of the lesion, Border irregularity with notching, scalloping, or poorly defined margins, Color variegation, and Diameter greater than 6 mm. The diameter of a lesion should not be used to exclude otherwise suspicious lesions because small diameter melanomas are reported.
Article
Exposure to UV light contributes to the development of skin cancer. The importance of reactive oxygen species in UV-radiation carcinogenesis has been recognized for some time and several associated DNA base modifications have been identified. In particular, 8-hydroxydeoxyguanosine (8-OHdG) has been well studied as an indicator of oxidative damage to calf thymus DNA exposed to a variety of oxygen-generating systems, including UV light. However, to date, few studies of 8-OHdG have been conducted in cell or animal systems and those in vitro investigations that studied UV exposure have used UVC (<290 nm), not the UVB (290–320 nm) or UVA (320–400 nm) ranges to which organisms are exposed through sunlight. The objective of this study was to measure 8-OHdG formation in the DNA of cultured mouse keratinocytes exposed to UVB. Using HPLC with electrochemical detection, background levels of 8-OHdG were ∼6 fmol/μg DNA in DNA isolated and digested to the nucleoside level. UVB induced 8-OHdG up to 100% above that for mock-treated cells at a dose of 630 mJ/cm2 (dose—response range: 210–630 mJ/cm2). UVB exposure at 630 mJ/cm2 combined with 5 mM H2O2 elevated 8-OHdG formation up to 280% above that in control cells, whereas H2O2 alone had no effect. These results suggest that factors which increase the generation of reactive oxygen species by UV light may be potent cofactors of UV-radiation carcinogenesis.
Article
Summary Skin cancer is the most common human carcinoma. There has been a dramatic increase of the incidence over the last decades. This trend is very likely caused by the increased UV-light exposition of the population. Whereas basalioma and spinalioma as the most frequent types of skin cancer have a low mortality, the bad prognosis of malignant melanoma is the reason for the 100% increase of the mortality rate over the last ten years. Cancer prophylaxis means the early detection of precancerous or suspect lesions. Popular information on the risk and a more generous indication for excision are the best instruments to lower the mortality of skin cancer.
Article
An animal experiment is presented in which two groups of pigmented hairless mice were exposed daily to suberythemal doses of UVA to study tumourigenesis. The aim of the study was to estimate the carcinogenic risks of tanning by UVA. The pigmented hairless mice, Skh-hr2, were separated by selective breeding into two groups, the "browns" and the "blacks". Both groups were exposed daily to UVA from fluorescent UVA lamps (Philips TL40W/09) purified by rigorously filtering out the shorter wavelengths. No acute actinic damage was observed after any exposure. However, in most UVA exposed animals, especially in the blacks, a marked scratching preceded the development of tumours. Hyperkeratosis was also observed. All animals developed tumours. Histopathologically at least 60% of the tumours were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. It is beyond any doubt that UVA is carcinogenic in laboratory animals. The present state of knowledge justifies no preference for tanning with UVA over tanning with UVB.
Article
Full-text available
Both the incidence and mortality from malignant melanoma are rising rapidly in all countries in which they have been studied. Solar radiation has been incriminated as a possible cause for this trend and as a possible etiological factor in malignant melanoma. Israel is a subtropical country developed as a result of waves of immigration mainly in the last century from Europe, Asia, and Africa. To evaluate the role of solar radiation on the pathogenesis of malignant melanoma, 966 cases of malignant melanoma, diagnosed in the last 10 years, were evaluated. The incidence of malignant melanoma was found to be higher (34/million) among European‐born Jews than among Jews who came from Africa (2.7/million) or Asia (4.4/million). Among European‐born Jews of the same age and ethnic background, there was a definite higher incidence of the disease in those who stayed in Israel 20–30 years prior to diagnosis (58/million) as compared to those who stayed in Israel only two to five years prior to diagnosis (17/million). A higher incidence of malignant melanoma was found among agricultural workers in the Kibbutz settlements (54/million) than in the city (17/million) and among the residents of the coastal region (35/million) than in the mountains (20/million). The disease tends to manifest itself on the lower extremity in females (50%) and the trunk in males (30%). The preponderance of the disease to the lower extremity in females is higher in the 50–79 year age group (55%) than in the 0–19 year age group (41%), and is higher in females who stayed 20–30 years in Israel (61%) as compared to females of the same age and ethnic group who stayed in Israel only two to five years prior to diagnosis (49%).
Article
Chronic UV irradiation has a profound effect on the immune response to skin tumors induced by UV light. Although many of these highly antigenic tumors are immunologically rejected by normal syngeneic mice, they grow progressively in UV-irradiated hosts. The mechanism by which UV light interferes with immunologic rejection is not completely understood, but several points have been elucidated. Some type of intermediate induces a population of suppressor lymphoid cells which prevents the induction of an immune response against the spectrum of tumor-specific transplantation Ags on UV-transformed cells. The primary skin tumors induced by UV radiation can then grow unchecked in these altered hosts. This tumor system has a number of unusual features in addition to the high degree of antigenicity of the UV-induced tumors. The specificity of the alteration in UV-irradiated mice is not truly 'tumor-specific' because each UV-induced tumor has different tumor-specific transplantation Ags. It is, however, tumor-related, since it includes all UV-induced tumor Ags, but does not necessarily extend to tumors of other etiology. Thus, the immunologic specificity of this UV-induced induced alteration is quite unusual. This is also the only case in carcinogenesis where the carcinogen has been shown to act as a highly selective immunosuppressive agent which prevents the development of immunity against the tumors that it induces. It is possible that this situation exists in chemical carcinogenesis as well, but this has not been thoroughly explored. The finding that the growth of some non-UV-induced tumors is enhanced in UV-irradiated recipients raises an important issue. That is, UV light might act as a potentiating agent for the growth of certain tumors of diverse etiology. The enhanced development of the B16 melanoma is especially intriguing because of the evidence that human melanoma is associated with UV exposure, but in an indirect way. This issue should provide a fruitful area for future investigation.
Article
• This study demonstrated an increasing incidence of malignant melanoma during the past ten years and a very high incidence of this tumor in southern Arizona. During the ten-year period, 533 melanomas were removed from white patients. Of these, 52% were male and 48% were female. The number of melanomas increased yearly, from 20 in 1969 to 120 in 1978, a crude rate incidence of 6.49 to 28.57 (27.20 standardized) per 100,000, respectively. This reflects an average annual increase of 34% to 37% and a 340% increase for the period. The highest incidence of tumor was in the 50 to 59 year and 60 to 69 year age groups. The most common site of occurrence was the back, with twice as many tumors arising there in males. The legs were involved in 13% of patients, with an occurrence rate eight times higher in females. The extremely high incidence of melanomas in southern Arizona is probably due to meteorologic and geographic factors allowing large amounts of ultraviolet light to reach the earth's surface. (Arch Dermatol 117:6-11, 1981)
Article
Six established lines of malignant melanoma cells produced particles having a buoyant density of 1.14 to 1.18 g/ml and containing RNA with a component of approximately 70S. Fractions containing these particles showed RNase-sensitive DNA polymerase activity, and in simultaneous assays the DNA product was found to be associated with 70S RNA. Similar results were obtained in control studies with two known oncornaviruses (Rauscher and WM1-B mouse leukaemia viruses), but not with particles from three normal human fibroblast strains. Filtration studies showed that the uridine-labelled particles from four melanoma cell lines, as well as the materials from two melanoma lines active in the simultaneous assay, were largely retained by filters with an average pore diameter of 100–650 nm. In negative-stained preparations of 1.14 to 1.18g/ml fractions from four melanoma lines, a small number of virus-like particles about 125 nm in diameter were detected, as well as smaller amorphous material and minute ring-like structures about 12–14 nm in diameter. The evidence strongly suggests the production by these cultured malignant melanoma cells of particles with properties closely resembling those of oncornaviruses. Although evidence was found of similar virus-like particles in a malignant melanoma biopsy, their role in the aetiology of malignant melanoma remains unknown.
Article
The spectral transmission of ultraviolet radiation in the wavelength range 290–320 nm has been measured in various samples of common clothing fabrics. The transmission data have been combined with estimates of the spectral irradiance of sunlight and the erythema action spectrum in order to derive a‘protection factor’for each material. The results show that the structure, or weave, of a material is the most important factor in determining the protective nature of the material, and that colour and thickness are a poor guide to actinic protection.
Article
In certain fish hybrids, malignant transformation of pigment cells is due to the presence of a tumor gene (Tu), the action of which is controlled by several regulatory elements. Absence of these controlling genes causes rapid proliferation of the Tu-transformed cells and ultimately results in melanoma formation. One of these genes has been identified as a differentiation gene (Diff), since it seems to control the differentiation of the transformed pigment cells. Light and electron microscopy of Tu-transformed cells of fish differing in the dosage of Diff, and the determination of tyrosinase activity in homogenates of the respective tissues revealed that the degree of cellular differentiation depends on the dosage of Diff present in the genome. It is concluded that the gene Diff promotes the differentiation of malignant melanoma cells into benign melanophores.
Article
A high-molecular-weight RNA encapsulated with an RNA-instructed DNA polymerase in particles possessing the density characteristic of the RNA tumor viruses has been detected in 13 out of 14 human malignant melanomas. The [3H]DNA synthesized by these particles in an endogenous reaction hybridizes to RNA extracted from the human melanoma particulate structures, but not to RNA from normal skin. Similar particles containing RNA and enzyme have been found in basal cell and squamous cell carcinomas of the skin. The RNA of the melanoma particles is easily distinguishable by hybridization from the RNAs found in the particles of the basal and squamous cell carcinomas.
Article
Ultraviolet (UV)-irradiated mice were compared with unirradiated mice for their susceptibility to primary and transplanted tumors etiologically unrelated to UV radiation. Although UV-irradiated mice are unable to reject transplants of highly antigenic syngeneic tumors induced by UV light, the growth of syngeneic, non-UV-induced tumors generally was not accelerated in these animals. Furthermore, UV-irradiated mice were no more susceptible to the induction of primary leukemias, mammary tumors, or sarcomas than were unirradiated animals. Tests of immune responses to weak transplantation antigens showed that UV-irradiated mice rejected H-Y-incompatible skin grafts as vigorously as did normal animals, and that the primary in vitro cytotoxic responses of spleen cells from UV-irradiated mice to trinitrophenyl (TNP)-modified syngeneic cells and to Hh antigens were unaffected. We conclude that the susceptibility of UV-irradiated mice to challenge with UV-induced tumors represents a selective unresponsiveness, and that it is not attributable to a generalized deficiency in the immune response to tumor-specific antigens or to weak transplantation antigens.
Article
Interest in the etiology of human malignant melanoma has increased considerably in recent years. The basis for this heightened concern can be attributed to two seemingly unrelated issues. The first is that the incidence of malignant melanoma is increasing at an alarming rate. At the present time, both the incidence of melanoma and the mortality rate are doubling every 10 to 17 years. Thus identification of causal factors in the development of melanoma is an urgent necessity if this upward trend is to be curbed. The second issue that has directed attention to the identification of etiologic factors in malignant melanoma is ozone depletion. The layer of ozone surrounding the earth shields it from solar uv radiation. Anticipated decreases in stratospheric ozone, resulting from high-altitude aircraft, nuclear explosions, and the release into the atmosphere of chlorofluoromethanes from refrigerants and aerosol sprays, raised concerns about the effects of an increased exposure of all life forms to uv light. One anticipated effect of increased exposure of humans to uv light is a corresponding increase in some types of skin cancer in humans. If malignant melanoma is included among the types of skin cancer at risk of increasing, then the impact of ozone depletion on humans is serious indeed. In the prognosis for melanoma is less favorable, particularly in cases in which the tumor is already invasive at the time of diagnosis. Thus the threat of an increased level of exposure to light has stimulated a careful reevaluation of the role of radiation in the induction of melanoma.
Article
A case-control study including 78 patients with malignant melanoma of the skin and 131 controls with the diagnoses of malignant lymphoma, testicular cancer or bone and soft-tissue sarcoma, was performed at the Norwegian Radium Hospital 1974-1975. The questionnaire contained questions for evaluating the comparability between cases and controls, and questions bearing on the relation between sun exposure and malignant melanoma. No essential difference between cases and controls was found as regards hair and eye colour, time spent outdoors during leisure, and degree of solar exposure. The melanoma patients liked sunbathing less than controls, worked more outdoors, more often went to Southern Europe for sunbathing and more often used sun lotions. These differences, however, were not clearly statistically significant. Highly significant differences were demonstrated as regards the tolerance of sun exposure and propensity to freckling. The melanoma patients tolerated sun exposure less well and freckled more easily than the controls. Although attempts were made to eliminate bias, there are still limitations and loop-holes in the study, and the relative risks demonstrated are not large enough to be of great immediate practical or scientific value. It seems justified, however, to advise persons with a low sun exposure tolerance to be cautious in following the sun-tan-demanding fashions. The study may also provide certain clues for the planning of future epidemiological and clinical studies regarding the etiology of malignant melanoma.
A selected series of primary malignant melanoma of the skin, clinical stage I, was originally classified according to Clark's system. The consistency of this classification was tested by two Brisbane pathologists who indicated that we had misinterpreted some cases of superficial spreading malignant melanoma as lentigo maligna melanoma. We have therefore reclassified the original group of 86 lentigo maligna melanomas. This resulted in a total series of 37 (5.5%) lentigo maligna melanomas, 301 (45%) superficial spreading malignant melanomas, 194 (29%) nodular malignant melanomas (unchanged) and 137 (20.5%) unclassifiable malignant melanomas. The diagnosis of lentigo maligna melanoma was not made unless the epidermis was atrophic and dermal solar elastosis was present. The new group of lentigo maligna melanomas is dominated by cases on the head among patients over 50 years of age (especially women). This is in better agreement with other studies than our previous findings. The relationship with tumour cell type, pigmentation, mitotic count, atypia, transsectional profile, level of invasion, ulceration, vascular invasion, lymphocyte infiltration and prognosis shown by the new groups of lentigo maligna melanoma and superficial spreading malignant melanoma indicates that the cases by which the diagnosis has been changed are relatively benign. Our previous conclusions are still valid. The lentigo maligna melanoma is still the most benign type and nodular malignant melanoma still the most malignant type of melanoma. The superficial spreading malignant melanoma still represents an intermediate tumour type, although it has deviated in the benign direction.
Article
The incidences of malignant melanoma recorded by 59 population-based cancer registries were investigated to determine the effects of racial and skin-colour differences. White populations exhibited a wide range of melanoma incidences and females commonly, though not invariably, had a higher incidence than males. Non-white populations experienced in general a much lower incidence of melanoma although there was some overlap of white and non-white rates. No predominant sex difference emerged among non-whites. Populations of African descent were found to have a higher incidence than those of Asiatic origin, but it was concluded that this was due largely to the high frequency of tumours among Africans on the sole of the foot. A clear negative correlation between degree of skin pigmentation and melanoma incidence emerged for the exposed body sites. These data provide strong support for the hypotheses that UV radiation is a major cause of malignant melanoma and that melanin pigmentation protects against it. Further research is required to elucidate the aetiology of melanoma of the sole of the foot.
Article
The photoprotective role of melanin was evaluated by comparing the transmission of ultraviolet (UV) radiation through skin samples of blacks and Caucasians, using both biologic and spectroscopic techniques. UVA transmission was measured using fluoranthene, which causes a phototoxic response to UVA wavelength. UVB was measured by monitoring erythema produced by either a 150-watt xenon arc or FS-20 sunlamps. It was found that on the average, five times as much ultraviolet light (UVB and UVA) reaches the upper dermis of Caucasians as reaches that of blacks. Differences in transmission between the stratum corneum of blacks and of Caucasians were far less striking. The main site of UV filtration in Caucasians is the stratum corneum, whereas in blacks it is the malpighian layers. Melanin acts as a neutral density filter, reducing all wavelengths of light equally. The superior photoprotection of black epidermis is due not only to increased melanin content but also to other factors related to packaging and distribution of melanosomes. Not only are these data consistent with epidemiologic evidence, but they also may indicate why blacks are less disposed to phototoxic drug responses as well as less susceptible to acute and chronic actinic damage.
Article
In most of England and Wales the incidence of malignant melanoma of the skin has risen rapidly in recent years, especially in women. Mean incidences in the 14 English health regions and Wales correlated negatively with latitude and positively with hours of sunshine, suggesting that exposure to sunshine was an important causal factor. Male and female incidences within a region tended to show similar yearly fluctuations, implying a common factor affecting the incidence in both men and women with a short latent period of action. This factor may be exposure to sunshine, which may cause melanoma after an induction period of about two years; for women the incidence of melanoma in the regions of England and Wales correlated positively with hours of sunshine two years earlier.
A selected series of primary malignant melanoma of the skin, clinical stage I, was studied. The series includes 37 lentigo maligna melanomas, 301 superficial spreading malignant melanomas, 194 nodular malignant melanomas and 137 unclassifiable malignant melanomas. Dermal solar elastosis was graded. The most common finding was lack of solar elastosis which together with slight elastosis was mostly found on the trunks of young men and on the legs of young women in cases of superficial spreading malignant melanoma. Marked and moderate elastosis was found almost exclusively on the head, especially in old women with lentigo maligna melanoma. Nodular malignant melanoma was related neither to any special grade of solar elastosis, nor to localization, but showed some relation to the male sex after 50 years of age. The present study does not permit any conclusions to be made about a possible causal relationship between the three types of malignant melanoma and previous sun-exposure, because of lack of clinical information and a control series concerning solar elastosis in the normal population. Level of invasion and prognosis of the patient did not show any covariation with grade of solar elastosis.
Article
The influence of selective breeding on the incidence of cutaneous melanomas was studied in the Sinclair miniature swine melanoma model. Evaluation of the results of a large breeding study that produced 349 live progeny indicated that the incidence of melanomas (54%) was highest in newborn progeny derived from melanoma female × melanoma male (MF × MM) matings. Newborn progeny from normal female × melanoma male (NF × MM) and melanoma female × normal male (MF × NM) matings had incidences of 22% and 21% respectively; normal female × normal male (NF × NM) progeny had an incidence of 2%. Although most of the progeny were black, melanomas were observed in swine of various colors. Tumors occurred at differing cutaneous sites and did not demonstrate a predilection for any particular area of the body. During the first year of life, additional melanomas developed in some animals from all groups of progeny. At 1 year of age, the incidence of melanomas (85%) remained highest in MF × MM progeny. The incidence had increased to 57% and 50% in progeny from NF × MM and MF × NM matings while NF × NM progeny had an incidence of 4%. Although tumors were observed in newborn swine, most of the tumors (75.5%) developed after birth either from flat melanocytic lesions (19.3%) or from skin free of detectable melanocytic lesions (80.7%). An age effect was observed in tumor development; tumor development decreased as the age of the animals increased. These results demonstrate that selective breeding influences the incidence of melanomas in Sinclair swine and provide basic information required for further studies of tumor development, growth and regression in this unique spontaneous tumor system.
Article
The age-adjusted death rates from malignant melanoma of the skin have increased from 1951 to 1975 by about 3% per year in the populations of England and Wales, Canada, and the white population of the US. This is due to large increases in risk of successively later born cohorts. Any effects of earlier diagnosis of improved treatment within the period 1951--1975 have been sufficiently steady to fail to alter these trends. The slope of the log rates with log age is about 3.5. Projections of rates for at least the next decade can be made with some confidence, and provide a basis for evaluating control measures.
Article
The numbers of clinically diagnosed, elevated nevocytic nevi (at least 2 mm in diameter) within 50 sq cm areas on the lateral and medial aspects of the arms of 1,000 subjects (age range 2 to 87 years) were compared. A total of 349 nevi was found on the lateral aspects and only 116 on the medial aspects of arms. Nevi were found on the lateral aspects of the arms in 23.4% (234) of the subjects and on the medial aspects in but 10.9% (109) of the subjects. These differences are highly significant in both men and women. Nevi were found in 30.2% (281) of the 930 whites but in only 9.1% (5) of the 55 blacks included in the study. Also, blacks did not show greater prevalence of nevi on the lateral as compared to the medial aspects of their arms. One explanation for the greater prevalence of nevi on the lateral over that on the medial aspects of the arms is that sunlight plays a role in the induction of acquired nevocytic nevi.
Article
The series of cutaneous melanoma compiled by the Finnish Cancer Registry, a total of 2501 cases covering all tumors diagnosed in Finland in 1953–1973, was analysed. The age adjusted incidence was equal in both sexes (about 3.5/105 in the 1970s). The risk more than doubled during the study period. The most common locations of melanoma in males were the trunk (48%) and lower limbs (17%), and in females the lower limbs (36%) and the trunk (28%).The age adjusted incidence rates were higher in urban areas than in rural districts and higher in southern parts of the country than in northern areas. However, after adjusting the rates for urban/rural residence of the population, the north south differences almost disappeared. In conclusion, the north south gradient was attributable to the degree of urbanization and not necessarily to the effect of latitude itself. Melanomas on the trunk in both sexes and those on the lower limbs in females had two features in common—the incidence of tumors on these locations increased markedly with time, and the age specific incidence rates increased sharply in middle age and levelled off thereafter. On the other hand, melanomas on the head and neck in both sexes and those on the lower limbs in males did not increase with time, and the risk was rather low in middle age and increased throughout life. The increase with time in the risk of melanoma could be accounted for by a cohort effect. These findings are not totally in accordance with the hypothesis of the association between sunlight and risk of melanoma, and it is concluded that recognition of sunlight as the only important risk factor of cutaneous melanoma may be an oversimplification of a complex problem.
A selected series of 669 primary malignant melanomas of the skin, stage I, has been classified according to Clark's system into lentigo maligna melanoma (86), superficial spreading malignant melanoma (259), nodular malignant melanoma (194) and unclassifiable malignant melanoma (130). It was often difficult to distinguish between lentigo maligna melanoma and superficial spreading malignant melanoma, and sometimes also between this last type and nodular melanoma. There seem to be borderline cases between the respective types. The 10-year specific cumulative survival rate (approximately the cure rate) was 98.3% for the lentigo maligna melanomas, 78.6% for nodular malignant melanomas and 76.7% for the unclassifiable group of melanomas. The 5-year observed prognosis ofthe 3 main types is satisfactory compared with other investigations. As the prognosis of the 3 types of cutaneous malignant melanoma differs considerably the use of this classification is recommended. The number of unclassifiable cases is likely to be reduced in the routine work when several sections of each tumour are studied.
The relationship between tumour incidence rate and habitation patterns was investigated in 3289 patients registered between 1959 and 1968 as cutaneous malignant melanoma in the Swedish Cancer Registry. A linear correlation analysis between latitude and melanoma incidence rate in various regions showed a coefficient, r, was -0.74, which implies a decreasing incidence with increasing latitude. This result supports the hypothesis that ultraviolet irradiation is the predominant cause of melanoma. However, considerable deviations from the regression line were seen in some regions. Moreover, a comparison between town and country indicated melanoma incidence increased with population density, an increase not explained by overdiagnosis and thus not in agreement with the working hypothesis of UV-irradiation as the predominant cause of melanoma. Increase of foreign travel, as estimated by passport issue, may explain the overrepresentation of melanoma in some regions namely city and county of Stockholm, city of Malmö and Göteborg county. As foreign travel in Sweden generally means sunshine trips, this town versus country paradox may also be explained on the basis of increased irradiation, as may the anomalies observed in some counties. A regression analysis of the epidemiological index for UV-irradiation and melanoma incidence, adjusted for foreign travel, demonstrated a close agreement with the results of the latitude gradient analysis.
Article
Seventy albino guinea pigs were used in the experiment to investigate the influence of 9,10-dimethyl-1,2-benzanthracene on amelanotic melanocytes. A field 5 sq cm was marked on the flank of each animal. Hairs from these fields were clipped twice a week and painted for 20 consecutive weeks with 0.3 ml of 1% 9,10-dimethyl-1,2-benzanthracene in acetone. During the 1-year observation period, pigmented sports appeared in 40 animals. Biopsies were taken under local anesthesia, and sections were prepared for light and electron microscopic observations. Melanin formation of unknown mechanism took place in the epidermal melanocytes and in the melanocytes from the outer root sheath. These melanocytes also formed junctional and compound nevi; serial sections revealed various stages of pigmented nevi development. Schwann cells did not participate in the formation of nevi. Evidence is presented that 9,10-dimethyl-1,2-benzanthracene can convert amelanotic melanocytes into melanin-producing cells in the albino guinea pig skin. In addition, this system produces an animal model for the development of junctional and compound nevi.
Article
Malignant melanoma has been induced in the Weiser-Maple guinea pig by prolonged application of 7,12-dimethylbenz(a)anthracene. The tumor shows a biphasic growth pattern analogous to the radial and vertical growth phase of human cutaneous malignant melanoma. It evolves through a predictable series of cellular events classified as intraepidermal melanocytic hyperplasia, dermal melanocytosis, dermal melanocytoma, malignant melanoma without intralesional transformation, and, finally, malignant melanoma with intralesional transformation, which is characterized by the appearance of "new kinds of cells" and is associated with widespread metastases and massive lymph node involvement. Clinically, the lesions evolve from diffuse hyper-pigmentation to brown-black macules, to nodules of increasing size, to overt malignant melanoma associated with metastases, wasting, and death. Examples of intralesional transformation analogous to that in guinea pigs are found not only in human malignant melanomas, but in other human neoplastic systems, and such analogous cellular events are discussed in this paper.
Article
Fifty xeroderma pigmentosum patients in Japan were examined for clinical characteristics and DNA repair of their cells, Skin cancers developed in 22 patients. Most of the patients without skin cancers were children, except for 5 older patients who had intermediate or nearly normal levels of DNA repair in their cells. All patients younger than 10 years old had no or very low activity of unscheduled DNA synthesis after ultraviolet light irradiation. Three genetic complementation groups, A, D, and E, and variants were found. Many Group A patients and no Group C patients characterized Japanese patients, compared with those in Europe and the United States, where Group C patients were most frequent. The high frequency of patients with low DNA repair capacities in their cells may account for the apparent high frequency of xeroderma pigmentosum patients in Japan. Age distribution of the cancer-bearing patients and their DNA repair characteristics suggest that almost all xeroderma pigmentosum patients will develop skin cancers unless their cells have nearly normal levels of DNA repair.
Article
That sunlight leads to skin cancer has been generally accepted for nearly a century. Physical data are, for the first time, available which support this hypothesis. The authors have found that a simple power relationship can be used to describe the data and that the form of this power function suggests that the risk of nonmelanoma skin cancer is related to cumulative lifetime ultraviolet (UV) exposure and that the risk of melanoma skin cancer is related to annual UV exposure. The authors emphasize that skin cancer risk also depends on location-specific demographic variables other than ultraviolet radiation.
Article
The incidence of malignant melanoma of the skin has increased rapidly among white people during the last decades. Excellent possibilities for detailed epidemiological analysis of malignant melanoma are provided in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), where the five national cancer registries were established during the period 1942–1958. Their materials are based on reports from hospitals and histopathological laboratories and death certificates. The organization of the registries is largely similar, and efforts have been made to bring the materials into conformity. More than 14,000 cases are included in the analysis, which covers the period 1953–1972 in Denmark, Finland and Norway, 1955–1974 in Iceland and 1959–1971 in Sweden. The tumors have been grouped by anatomical site as follows: face, neck/trunk, upper limb, lower limb, and other and unspecified sites. The incidence of malignant melanoma is similar in Denmark, Norway and Sweden. Lower incidence rates are observed in Finland and Iceland. Time trends in incidence are remarkable and clearly statistically significant, except for Iceland where the number of cases was very small. The period for doubling the incidence rate ranged from 10 to 17 years. Striking contrasts by sex are observed when the material is grouped according to primary site. There is a male preponderance for incidence on the neck/trunk and the reverse is found for the lower limbs. There is only a slight increase in incidence of malignant melanoma of the face, whereas for the neck/trunk, particularly among males, and for the lower limbs, particularly among females, there is a consistent upward trend. A difference between the face, on the one hand, and the neck/trunk and lower limbs on the other, is also disclosed in the curves showing the age-specific incidence rates.
Article
A large number of melanocytic nevi characterize the Sinclair swine at their present stage of breeding. These tumors often dramatically regress, associated with generalized depigmentation, and occasionally evolve into diverse and metastasizing lesions. The melanocytes of these lesions and the clinical behavior of the tumors resemble the entire range of human melanocyte disorders from benign to malignant. Ultrastructural features of these tumors closely resemble human counterparts, varying only in amount of melanin. Malignant tumors show a close parallel to human superficial spreading melanoma and Klug's type A melanoma. Research into the etiology, progression, metastasis, and involution or therapy of melanocytic growth is now possible because of the close analogies demonstrated between this animal model and its human counterparts.
Article
A new animal model for the study of melanocytic tumors is presented. A strain of miniature swine, bred for small size, has genetically determined tumors similar to many types of human pigment tumors, from benign junctional nevi to bizarre metastatic melanomas. Some tumors regress spontaneously and this regression may be accompanied by a generalized depigmentation of the animal with a predilection for many of the same anatomic areas involved in human vitiligo. These animals are ideal for study of the interrelationships of senescence, actinic exposure, and other factors in malignant degeneration, as well as the role of immunity and growth control factors in regression and regulation of tumor growth.
Article
Melanotic lesions of skin and viscera are common in Sinclair miniature swine. Large exophytic melanomas of the skin invariably regress, and regression may be responsible for melanosis of local and regional lymph nodes and some visceral organs. Malignant transformation and metastasis of cutaneous melanomas are uncommon and primary visceral melanomas were heretofore unrecorded. Described are clinical and light microscopic characteristics of melanomas in 3 miniature pigs: one pig with a massive, possibly primary, melanoma of the mediastinum, one that died with widespread lymphatic and focal pulmonary metastasis of congenital melanomas of the skin, and one in which both a large congenital cutaneous melanoma and associated metastatic melanomas in regional lymph nodes regressed completely.
Article
A group of 79 patients with histologically proven malignant melanoma was compared with an agesex matched, cancer-free, control group for certain phenotypic characteristics, environmental influence (outdoor exposure) and genetic cancerproneness. Statistical analysis of the data shows that there is a tendency for patients with malignant melanoma to have light complexions, light eyes, blond or red hair, and to spend a greater amount of time outdoors, when compared with the control group. There is close correlation of findings in these respects with our previously reported study of patients with basal-cell epithelioma.
Article
The effects of chronic low-dose mid-ultraviolet (UVL) exposures on benign blue nevi were examined in pigmented hairless mice. The benign growths were produced by a single application of 7,12-dimethylbenz[a]anthracene (DMBA). In this study, large invasive melano-cytic tumors were produced by the UVL in 5 of 18 animals. Apparent seeding of regional lymph nodes with tumor cells was a consistent feature of the melanomas. No distant metastasis was noted. No similar growths occurred spontaneously or in control groups receiving DMBA or UVL alone. Histologic, electron microscopic, and autoradiographic studies established that the tumor was composed of functioning neoplastic melanocytic cells. It was suggested that the system could serve as a model for evaluation of factors influencing melanoma formation.
Article
In a study of 274 women with malignant melanoma, aged 18--54 years, and 549 matched controls in New South Wales, Australia, reported exposure to fluorescent light at work was associated with a doubling of melanoma risk (relative risk [RR] = 2.1; 95% confidence limits 1.32--3.32). The risk grew with increasing duration of exposure to fluorescent light and was higher in women who had worked mainly in offices (RR = 2.6) than in women whose main place of work was indoors but not in offices (RR = 1.8). The findings could not be explained by the differences in histories of sunlight exposure, in skin or hair colour, or in any other factor. There was a relative excess of lesions on the trunk in the group exposed to fluorescent light at work. 27 men with melanoma and 35 similarly aged controls were studied, and a significant increase in risk was also found: the RB in those exposed for greater than or equal to 10 years compared with those exposed for less than 10 years was 4.4 (95% confidence limits 1.1--17.5). Such an association has not been reported before, but it is plausible and could explain many of the paradoxical features of the epidemiology of melanoma. Until more data accumulate it must, however, be viewed cautiously.
Article
A randomized double-blind clinical trial involving twenty-two volunteers was conducted in two locations (Orlando, FL, and St. Paul, MN) to test the efficacy of the newly designed ultraviolet monitor badges (Sun Timers), described in another paper by us in this issue of the Journal, 1 and to establish the relationship between spectral band exposure dose and the biologic responses of erythema and pigmentation. Individuals with skin types II, III, and IV, exhibiting differences in reactivity to solar radiation, were exposed to varying doses of full-spectrum sunlight through templates mounted on the lower portion of the back. Simultaneously, on the upper portion of the back, the same volunteers were exposed through two different types of polyester filters that transmitted ultraviolet A (UVA) and visible radiation. Using templates with windows, exposures to full-spectrum sunlight, UVA, and visible radiation were carried out to 1, 2, 3, 6, and 9 sunburn units (approximately 30-270 millijoules/cm2 between 10:30 A.M. and 3:30 P.M. daylight time in mid summer), measured with the aid of a Robertson-Berger meter and an IL700 International Light radiometer. Erythema and pigmentation resulting from these exposures were graded (double-blind) immediately after exposure, at 24 hours, and after 5 days. Numerical skin response ratings at each exposure dose for different spectral bands were then averaged and plotted. It was found that the UVB monitor response was predictive of a 24-hour erythema response and 5-day pigmentation response within 30% of the biologic average for skin types II, III, and IV. UVA radiation stimulated melanogenesis. The minimal melanogenic dose (MMD) for skin type II was the same as the minimal erythemogenic dose (MED). The MMD for individuals of skin types III and IV was distinctly less than their MED. Thus, melanogenesis can be stimulated with a suberythemal dose of UVB or UVA radiation. The sun protection factor values of melanin for melanized skin have been estimated to vary from 1.0 (skin type II) to 4.3 (skin types V and VI).
Article
This review provides a comprehensive coverage of hereditary malignant melanoma with emphasis upon its heterogeneity as well as newly developed biomarker investigations. The recently described familial atypical multiple mole melanoma (FAMMM) syndrome is featured. Particular attention has been given to findings of increased hyperdiploidy observed as an in vitro phenomenon in cultured skin fibroblasts from high-risk and FAMMM-affected subjects. The FAMMM genotype is complex in that it predisposes a patient not only to melanoma (cutaneous and intraocular malignant melanoma) but also to other histologic varieties of cancer, including cancer of the lung, pancreas, and breast. Attention is given to cancer surveillance and management programs for patients at increased risk for the several forms of hereditary malignant melanoma. This approach capitalizes advantageously upon employment of a knowledge of genetics and hereditary cancer syndrome identification, with particular attention to tumor associations.
Article
Eleven PUVA-induced pigmented macules (PM) obtained from seven psoriatic adults 4 to 6 years after starting PUVA therapy were compared to eight sun-induced pigmented macules (SM) and five specimens of light-protected skin (LPS) from twelve nonpsoriatic control subjects who had not received ultraviolet radiation therapy. Unlike SM, many PM were darkly or irregularly pigmented. In a blind histologic assessment using routine and L-dihydroxyphenylalanine (dopa)-incubated tissue sections, both PM and SM were lentigines. Three of eleven PM had slight melanocytic atypism, compared to none of eight SM. When compared to SM and LPS, PM had a significantly increased proportion of hypertrophic melanocytes. These observations demonstrate that chronic PUVA induces pigmented macules characterized by a lentiginous proliferation of large melanocytes which, in some cases, may be slightly atypical. PUVA-treated individuals require continual monitoring for atypical melanocytic lesions.
Article
Report of a malignant melanoma occurring in a woman with severe pustular psoriasis treated for 5.5 years with photochemotherapy.Copyright © 1989 S. Karger AG, Basel