Negative Pigment Network Identifies a Peculiar Melanoma Subtype and Represents a Clue to Melanoma Diagnosis: A Dermoscopic Study of 401 Melanomas

The dermoscopic descriptor "negative pigment network" (NPN) has been reported in several types of melanocytic and non-melanocytic lesions, although it has a higher frequency of association with melanoma and Spitz naevus. In a study of 401 consecutive melanomas, excluding facial, acral and mucosal locations, the frequency and variability of NPN were investigated, and the results of NPN correlated with clinical and histopathological data. NPN of any extension was found in 27% of melanomas, most frequently invasive and arising from a naevus on the trunk of young subjects. Seven percent of melanomas in the study population showed presence of NPN in more than half of the lesion area; most of these did not show typical dermoscopic melanoma features. The authors propose a new melanoma subtype, in which extensive NPN should be considered as a diagnostic indicator

Are the neck malignant melanomas different from the ones affecting the head? Clinicopathologic, dermoscopic and prognostic findings

Background: Malignant melanomas of the head and neck are usually considered as a unique entity in comparison to other body sites. However, no characterization of neck melanoma has been performed so far, despite the clear anatomic and histological differences. Aim: We investigated clinical, demographic, histological and dermoscopic differences between face, scalp and neck melanoma. Materials and methods: A retrospective analysis of medical and histologic records from 116 melanomas of the head and neck area collected between January 2003 and January 2008 was performed. Body site, gender, age, number of lesions, age at first melanoma diagnosis, size, Clark level, association with nevi, presence or absence of mitoses and/or ulceration, presence of synchronous and/or metachronous melanoma were recorded. Moreover, digital dermoscopy images of 92 melanomas of the head and neck area were analyzed for main dermoscopic patterns and lesion diameter. Results: Significant differences in Breslow thickness, ex-naevo origin and tumor size among neck and face-scalp melanomas were observed. Neck MM patients were younger than those with MM of face and scalp. In contrast to scalp and face, no patient died from neck melanoma. Dermoscopic patterns were similar to those of trunk-limbs MM, and no lesion showed a lentigo maligna pattern which was observed in most lesions of the face. Conclusion: Melanomas of the neck must be distinguished from face and scalp melanomas because of younger age, different dermoscopic patterns and ex-naevo origin and better prognosis. These data should be taken into account both from an epidemiological and clinical point of view

Reconstruction of nasal skin cancer defects with local flaps.

Reconstruction of nasal defects must preserve the integrity of complex facial functions and expressions, as well as facial symmetry and a pleasing aesthetic outcome. The reconstructive modality of choice will depend largely on the location, size, and depth of the surgical defect. Individualized therapy is the best course, and numerous flaps have been designed to provide coverage of a variety of nasal-specific defects. We describe our experience in the aesthetic reconstruction of nasal skin defects following oncological surgery. The use of different local flaps for nasal skin cancer defects is reported in 286 patients. Complications in this series were one partial flap dehiscence that healed by secondary intention, two forehead flaps, and one bilobed flap with minimal rim necrosis that resulted in an irregular scar requiring revision. Aesthetic results were deemed satisfactory by all patients and the operating surgeons. The color and texture matches were aesthetically good, and the nasal contour was distinct in all patients. All scars were inconspicuous and symmetrical. No patient had tenting or a flat nose

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose. This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations. This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity; • be informed about the levels of natural radioactivity caused by different sources; • have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor; • and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.JRC.G.10-Knowledge for Nuclear Security and Safet

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose.This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations.This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity;• be informed about the levels of natural radioactivity caused by different sources;• have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor;• and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.Additional information at: https://remon.jrc.ec.europa.eu/About/Atlas-of-Natural-Radiatio

Thickness and echogenicity of the skin in children as assessed by 20-MHz ultrasound

Background: Skin anatomy and physiology undergo modifications throughout the whole lifespan. in children the skin appears with structural characteristics, as evaluated by histology, which differ from those of adults, especially in the first years of life. Objective: The aim of our study was to evaluate skin thickness and echogenicity at different sites in children by 20-MHz ultrasound. Methods: Eight skin sites of 42 children and 30 young adults were studied with a 20-MHz B scanner. Skin thickness and mean echogenicity were evaluated. The echographic images were processed and segmented by a dedicated program: the 0-30 amplitude interval, which marks the hypoechogenic parts of the tissue, and the 201-255 range, highlighting the hyperreflecting areas, have been selected. Results and Conclusion: Whereas skin thickness shows a gradual increase from birth to adulthood, maturation of the skin leads to variations in the intensity of its echogenicity, depending on the different skin areas. Whereas on the face and the trunk it appears lower in adults with respect to children, a gradual increase can be observed on the limbs with growing age. The distribution of skin reflectivity also greatly varies in different phases of life. Copyright (C) 2000 S. Karger AG, Basel

Induzione dell'attività degli enzimi di fase I e II nei cheratinociti umani normali.

La cute può essere considerata come un effettivo distretto di biotrasformazione di composti chimici. Lo scopo di questo lavoro è stato analizzare l'espressione dei sistemi enzimatici per il metabolismo di fase I e fase II nei cheratinociti umani in proliferazione dopo irradiazione con raggi UVB e dopo esposizione a tre classici induttori: beta-naphthoflavone (BNF), 3-methylcholantrene (MC), phenobarbital (PB). Cheratinociti umani normali sono stati coltivati con fibroblasti 3T3 mitomicinati in Dulbecco's modified Eagle's medium/Ham's F12. A subconfluenza le cellule sono state incubate con gli induttori o irradiate a differenti dosi di UVB. La fase I è stata analizzata con attività 7-ethoxyresorufin O-deethylase (EROD) e 7-pentoxyresorufin O-depenthylase (PROD). la frazione microsomiale è stata studiata mediante analisi western blot. L'attività EROD indotta dall'MC era più alta di 4 volte rispetto al BNF. L'esposizione a raggi UVB risultava dose dipendente (50-75 mJ) e tempo dipendente (6-24h). L'attività della glutatione-S-transferasi(GST), enzima di fase II determinato con cinetica enzimatica, veniva significativamente espressa con UVB e PB. Questi risultati dimostrano il ruolo della cute nel metabolismo esogeno e la possibilità di utilizzare colture di cellule epidermiche per studi farmacotossicologici di agenti topici usati in dermatologia

Induction of cytochrome P450 enzyme activity by UVB and xenobiotics in normal human keratinocytes and melanocytes

Cytochrome P450 (CYP450) play a major role in the bioactivation of procarcinogenesis in target tissue and the expression of this enzyme i san important determinant of human susceptibility to cancer. Relatively little is known about the overall role of CYP450 in the metabolism of xenobiotics or endogenous cellular compounds in the skin. The aim of this study was to analyse the expression of cytochrome enzymes in proliferanting human keratinocytes and melanocytes after exposure to UVB radiation and to three classical cytochrome inducers such as: β-naphthoflavone (BNF), 3-methylcholanthrene (MC), phenobarbital (PB). We investigated 7-ethoxyresorufìn O-deethylase (EROD) (which is CYP450 1A1 dependent) and 7-pentoxyresorufìn O-depenthylase activities (PROD) (CYP450 2B1 dependent)activities. Normal human keratinocytes were cultured with mitomycin-treated 3T3 cells in Dulbecco’s modified Eagle’s medium/Ham’s F12 or with KGM serum-free medium. Melanocytes were grown in medium 154. At confluency cells were incubated with inducers or irradiated with different doses of UVB. At different times after treatments, cells were harvested for in vitro measurement of CYP450 induction. The microsomal fraction was studied by western-blot analysis. Low, but measurable levels of CYP activity were detected in both basal and differentianting keratinocytes. The MC-induced EROD activity was up to 4 fold higher when compared with BNF induced activity. UVB exposure resulted in a dose-dependent (10-75 mJ) and time dependent (4-24 h) induction of CYP450 1A1 for keratinocytes and CYP450 2B1 for melanocytes. Immunoblotting assay showed expression for CYP450 1B1 for both keratinocytes and melanocytes. Proadifen, an inhibitor of CYP450-monooxygenase, led to a significant decrease in EROD activity. The results of the present study clearly show that irradiation with UVB is capable of modifying the activity of CYP450 isoenzymes not only in keratinocytes but also in melanocytes.These experimental findings stress the value of epidermal cell culture for pharmaco-toxicological studies of topical agents used in dermatology

A new role of phase I and phase II enzyme in keratinocytes UVB induced apoptosis.

A new role of Phase I and Phase II enzymes in keratinocytes UVB induced apoptosis.UVB is the major cause for cutaneous malignancies in the human population. The skin is able to activate anti-oxidants and enzymatic detoxification reactions to neutralize reactive photochemical products. Apoptosis, removing irreversibly DNA-damaged and potentially neoplastic cells, represents a major defence mechanism towards malignant transformation. Very little is known about the role of cutaneous cytochrome P450 (CYP450) isoenzymes and glutathione S-transferase (GST) in UVB response. Although not yet fully investigated, it has been studied a possible relationship between CYP450 inductors and UVB initiated apoptosis in rat hepatocytes. Altered high levels of GST has been directly correlated to resistance to chemotherapeutic drugs suggesting that GST plays a role in prevention of apoptosis. Our study is focused on phase I and phase II enzyme activities in normal human keratinocytes. In the first part of the study we demonstrated that CYP450 (1A1 and 2B1) and GST are induced not only by classical inducers such as \u3b2-naphthoflavone, 3-methylcholanthrene, phenobarbital but also by UVB radiations (50 mJ/cm2). Differentiated keratinocytes were employed for all the experiments as confirmed by immunoblotting with Cytokeratin 10, a specific marker of the basal spinous transition. In the second part we evaluated a possible involvement of these enzyme in UVB mediated apoptosis process. Western blot analysis of Bcl2 expression and PARP cleavage showed that inhibition of CYP450 by Proadifen prevented UVB induced apoptotic cell death. In contrast, the diuretic drug, ethacrinic acid, a GST inhibitor, was able to improve UVB induced apoptosis. In order to confirm the anti-apoptotic activity displayed by GST, when GST activity was increased by Phenobarbital, UVB apoptosis was prevented.These results suggest that UVB radiations may play a critical role as tumour promoters even through the regulation of CYP450 and GST metabolising enzymes

Thickness and echogenicity of the skin in children as assessed by 20-MHz ultrasound

Background: Skin anatomy and physiology undergo modifications throughout the whole lifespan. in children the skin appears with structural characteristics, as evaluated by histology, which differ from those of adults, especially in the first years of life. Objective: The aim of our study was to evaluate skin thickness and echogenicity at different sites in children by 20-MHz ultrasound. Methods: Eight skin sites of 42 children and 30 young adults were studied with a 20-MHz B scanner. Skin thickness and mean echogenicity were evaluated. The echographic images were processed and segmented by a dedicated program: the 0-30 amplitude interval, which marks the hypoechogenic parts of the tissue, and the 201-255 range, highlighting the hyperreflecting areas, have been selected. Results and Conclusion: Whereas skin thickness shows a gradual increase from birth to adulthood, maturation of the skin leads to variations in the intensity of its echogenicity, depending on the different skin areas. Whereas on the face and the trunk it appears lower in adults with respect to children, a gradual increase can be observed on the limbs with growing age. The distribution of skin reflectivity also greatly varies in different phases of life. Copyright (C) 2000 S. Karger AG, Basel