Should dermatologists go public? A skin cancer screening campaign at recreation centers.
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Adolescent↗
Biomedical subjects
R Hofmann-Wellenhof
Publications and source records attributed to R Hofmann-Wellenhof.
Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha.
Exposing human skin to ultraviolet radiation causes DNA damage, sunburn, immune alterations, and eventually, skin cancer. We wished to determine whether liposomes containing a DNA repair enzyme could prevent any of the acute effects of irradiation when applied after ultraviolet exposure. Fifteen human patients with a prior history of skin cancer were exposed to two minimal erythema doses of ultraviolet radiation on their buttock skin. Liposomes containing T4 endonuclease V or heat-inactivated enzyme were applied immediately and at 2, 4, and 5 h after ultraviolet irradiation. Transmission electron microscopy after anti-T4 endonuclease V-staining and immunogold labeling on biopsies taken at 6 h after ultraviolet exposure revealed that the enzyme was present within cells in the skin. Immunohistochemical DNA damage studies suggested a trend toward improved DNA repair at the active T4 endonuclease V liposome-treated test sites. Although the active T4 endonuclease V liposomes did not significantly affect the ultraviolet-induced erythema response and microscopic sunburn cell formation, they nearly completely prevented ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha RNA message and of interleukin-10 protein. These studies demonstrate that liposomes can be used for topical intracellular delivery of small proteins to human skin and suggest that liposomes containing DNA repair enzymes may provide a new avenue for photoprotection against some forms of ultraviolet-induced skin damage.
Administration, Topical↗
Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.
We performed a multicentre study to evaluate the agreement between the direct clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions. Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11 melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines, two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11 colleagues (six dermatologists, two residents in dermatology, one oncologist, one specialist in internal medicine and one general practitioner) in 10 centres. These 11 colleagues had different degrees of experience in dermoscopy. With histopathology as the gold standard, an average of 85% of the telediagnoses were correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by an expert dermatologist was correct in 91% of cases. The kappa value for all participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy can be a reliable technique for the diagnosis of pigmented skin lesions but one that will depend on the expertise of the observer.
Adolescent↗
Face-to-face diagnosis vs telediagnosis of pigmented skin tumors: a teledermoscopic study.
BACKGROUND: Teledermoscopy uses telecommunication technologies to transfer images of pigmented skin lesions, including clinical and anamnestic data, via e-mail to specialized centers for teleconsultation. DESIGN: Sixty-six pigmented skin lesions examined on a face-to-face basis in a skin lesion clinic in L'Aquila, Italy, were sent via e-mail on a standard-resolution color monitor for consultation at a university dermatology department in Graz, Austria. INTERVENTION: Digital photographs of the clinical and dermoscopic images of all pigmented tumors were taken with a stereomicroscope connected to a high-resolution video camera in Truevision advanced graphic array (Targa) format file and converted successively into a Joint Photographic Expert Group (PEG) format file. All lesions were excised surgically and diagnosed histopathologically. MAIN OUTCOME MEASURE: Diagnostic concordance between face-to-face diagnosis and telediagnosis. RESULTS: The diagnostic concordance was 60 (91%) of 66 cases. The number of correct telediagnoses was lower, but the difference was not statistically significant (Wilcoxon test, P = .10). The accuracy of the telediagnoses was not related to the quality of the images, but highly depended on the level of diagnostic difficulty of a given pigmented skin tumor (Spearman correlation, P= .01). CONCLUSION: Teleconsultation of clinical and dermoscopic images of skin tumors via e-mail provides a similar degree of diagnostic accuracy as face-to-face diagnosis.
Adolescent↗
Ultraviolet radiation of melanocytic nevi: a dermoscopic study.
BACKGROUND: UV radiation can lead to clinical, histological, and ultrastructural changes in melanocytic nevi. In this study, we investigated whether exposure to 2 minimal erythema doses of UV radiation induces changes in the dermoscopic image of acquired melanocytic nevi. OBSERVATIONS: Fifteen melanocytic nevi were exposed to 2 minimal erythema doses of UV radiation. Differences in dermoscopic parameters (asymmetry, border, erythema, and telangiectasias in the nevus; pigmentation; hypopigmented areas; presence, regularity, and sharpness of pigment network; and brown-black globules) in digital dermoscopic images taken before and 3, 7, 14, and 28 days after UV irradiation were scored. Three days after UV irradiation, the borders of nevi were more faded (P<.02), the nevi were darker brown (P<.02), the hypopigmented areas were smaller (P<.02), and the pigment network structures were more faded (P<.007) and less prominent (P<.02) than before UV irradiation. Seven days after UV irradiation, pigmented globules have also grown (P<.05). After 28 days, all parameters, except hypopigmented areas, were essentially the same as before UV irradiation. CONCLUSION: UV irradiation of melanocytic nevi with 2 minimal erythema doses induces transient changes in their dermoscopic appearance that are sometimes suggestive of malignant melanoma.
Adult↗
Automated measurement of melanoma cross-sectional area.
The object of this study was to evaluate the prognostic impact of a cross-sectional area measured in routinely stained slides of cutaneous melanoma using fully automated image analysis. Hematoxylin-eosin stained slides of 238 specimens of primary cutaneous melanoma with Clark levels III to V were evaluated by digital image analysis using color video images, a scanning stage, and autofocus equipment. The cross-sectional area was significantly related to metastasis-free survival. Lesions with a cross-sectional area < or = 12 mm2 showed a 2-year metastasis-free survival rate of 92+/-2% compared with 41+/-8% in lesions with a cross-sectional area > 12 mm2 (log rank test: z = 71, p < 0.0001). The same was true for overall survival (98+/-1% compared with 82+/-6%; z = 42.12, p < 0.0001). In multivariate analysis, the cross-sectional area seems to provide prognostic information in addition to that provided by Breslow's index. In cases with regression and in small melanomas with vertical growth, however, metastatic spread may occur in lesions with a small cross-sectional area. It was concluded that automated measurement of the cross-sectional area may be helpful in assessing prognosis in cutaneous melanoma.
Adolescent↗
Autocrine growth stimulation as a potential source of asymmetry in melanocytic skin tumors.
The presence of asymmetry is a major diagnostic criterion for the differentiation of melanoma from benign melanocytic proliferations. It is helpful in both clinical and histological evaluation. The underlying biological features that determine asymmetry have not yet been evaluated. Using computer simulation of the growth of neoplasms, we demonstrate that a functionally homogeneous cell population can give rise to asymmetric lesions when the cells respond to autocrine growth signals. In contrast, neoplastic cells that depend on paracrine stimuli tend to form symmetric lesions. Since the progression of melanocytic neoplasms has been demonstrated to be accompanied by increasing independence of paracrine growth signals and the development of autocrine loops, autocrine growth stimulation has to be considered as a potential source of asymmetry in melanoma.
Autocrine Communication↗
Expression of two morphologic parameters concerning tumor-stroma interaction in benign and malignant melanocytic skin lesions.
The importance of tumor-stroma interaction in many solid tumors of the skin has been demonstrated in recent years. Invasion and metastasis require multiple interactions of the tumor cells with the surrounding stroma. In malignant melanoma most studies concerning tumor-stroma interaction focus on the peritumoral infiltrate, whereas other aspects of tumor-stroma interactions have not been considered. We investigated two morphologic criteria of tumor-stroma interaction in melanocytic skin tumors. Simple infiltration into the surrounding dermis or subcutis without evident stromal reaction (DERMSIMPLE) and the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk (PRECOLL) were examined in 373 benign common nevi, 239 dysplastic nevi, 322 Spitz nevi, 368 primary malignant melanomas, and 344 melanoma lesions metastatic to the skin. Our results showed that there is a highly significant difference in the expression of DERMSIMPLE and PRECOLL between benign and malignant melanocytic skin tumors. Concerning DERMSIMPLE, 13.3% of benign skin lesions compared with 28.2% of malignant lesions were positive for this feature; PRECOLL was found in 13.8% benign and 37.1% malignant lesions (chi-squared test; p = 0.0001 for both features). Furthermore, it could be demonstrated that simple infiltration into the surrounding stroma as well as the existence of morphologically intact collagen bundles of the reticular dermis within the tumor bulk increases with tumor progression; between primary malignant melanoma and melanoma metastatic to the skin, for example, there was a highly significant difference for DERMSIMPLE, as well as for PRECOLL (chi-squared test; p = 0.00001). These data indicate that morphologic aspects of tumor-stroma interactions in different benign and malignant melanocytic skin lesions may reflect biological behavior of tumor cells. The analysis of further aspects of tumor-stroma interaction and the relation to the patient's outcome may lead to the development of further prognostic parameters in malignant melanoma.
Collagen↗
Incorporation of pre-existing collagen bundles in primary cutaneous melanoma.
In a previous qualitative study it has been shown that the incorporation of pre-existing collagen bundles from the reticular dermis into the bulk of melanoma lesions metastatic to the skin indicates rapid systemic spread. In the present study the amount of pre-existing dermal collagen in the bulk of the melanoma lesions in 267 cases of primary melanoma of the skin with a Clark level of at least III was quantitatively assessed using automated image analysis based on RGB (red, green and blue) colour images of sections stained with haematoxylin and eosin. There was a weak correlation between the amount of pre-existing collagen and the Clark level and the Breslow index. With regard to prognosis, a large amount of pre-existing collagen (> 0.13 mm2 per index slide) was significantly associated with a particularly poor outcome (24-month survival rate: 71 +/- 17% compared with 96 +/- 2%; log rank test: P < 0.001). It is clear that a large amount of pre-existing collagen bundles occurring as a particular feature of tumour-stroma interaction indicates high metastatic capacity in primary malignant melanoma.
Adolescent↗
CD44 and variants in melanocytic skin neoplasms.
Expression of cell surface molecules that mediate cell-matrix and cell-cell interactions largely contributes to the ability of melanoma cells to migrate and spread beyond the primary site of the tumor. CD44, the principal cell-surface receptor for hyaluronate, and its numerous splice variants have been reported to play a crucial role in invasion and the metastatic process of different human neoplasms, including primary malignant melanoma (PMM). The aim of this study was to clarify which isoforms of CD44 (standard CD44 and CD44 variants) are distributed in PMM with a vertical tumor thickness of >1.4 mm. Staining of CD44 standard (CD44s) and splice variants was further examined for diagnostic and prognostic relevance in a panel of melanocytic skin lesions. Ten cases of PMM with Breslow >1.4 mm were analysed by immunohistochemistry using monoclonal antibodies specific for CD44s and the splice variants v3, v5, v6, v7, v7-8, and v10. In addition, using anti-CD44s, v5, and v6 antibodies, 55 melanocytic lesions, including dermal nevi (n=12), Clark nevi (dysplastic nevi) (CN; n=11), melanoma in situ (Mis; n=8), PMM (n=18), and cutaneous metastasis of malignant melanoma (cMMM; n=6) were assessed. Staining intensities were scored visually and evaluated by means of a staining index. In ten cases of PMM with a Breslow index >1.4 mm positive staining was ascertained for CD44s, v5 and for v6 in three cases. No staining was found for v3, v7, v7-8, and v10. Examination of CD44s, v5, and v6 in 55 melanocytic skin lesions revealed a high index for CD44s in all specimens and a weak staining of v5 in Mis; dermal nevi and CN did not stain for v5. However, in PMM and cMMM we found v5 to be strongly positive. The isoform v6 showed a variable index only in PMM, but without connection to established prognostic criteria. We conclude that CD44s and splice variants can not be regarded as indicators for tumor progression in malignant melanomas. However, v5 may potentially serve as a diagnostic marker for melanocytic skin lesions.
Adolescent↗
Teledermascopy: a preliminary study.
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Journal Article↗
Influence of UVB therapy on dermoscopic features of acquired melanocytic nevi.
BACKGROUND: Exposure to UV radiation can lead to clinical, histologic, and ultrastructural changes in acquired melanocytic nevi. OBJECTIVE: We investigated whether UVB therapy can induce changes in melanocytic nevi detectable by dermoscopy. METHODS: Eighty acquired melanocytic nevi of 13 patients (10 females, 3 males; mean age, 28 years; range, 13 to 62 years) undergoing UVB therapy were documented under standardized conditions by means of a Dermaphot apparatus before and at the end of suberythemal UVB therapy. The mean duration of therapy was 8 weeks (range, 2 to 17 weeks) and the mean total UVB dose was 1120 mJ/cm2 (range, 247 to 2771 mJ/cm2). During UV irradiation, 40 nevi were left unprotected and 40 nevi were protected from UV exposure in a randomized manner. Color dermoscopic images of nevi before and after UVB therapy were projected side by side and examined blindly by five investigators. Fifteen different features were evaluated in the nevi. RESULTS: Unprotected nevi became more irregular (p < or = 0.01) and darker brown (p < or = 0.03) by the end of the therapy, whereas the protected nevi showed no significant changes. CONCLUSION: Suberythemal UVB therapy can lead to changes in the dermoscopic image of acquired melanocytic nevi, presumably by activating melanocytes.
Adolescent↗
Cytoplasmic microtubules in two different mouse melanoma cell lines: a qualitative and quantitative analysis using confocal laser scanning microscopy and computer-assisted image analysis.
The microtubular system as one part of the cellular cytoskeleton is not only necessary for mitotic activity of malignant cells but also for invading neighboring tissues and for the formation of distant metastases. In the present study, the amount and distribution of tubulin in two murine melanoma cell lines (K1735-M2: high metastatic clone; K1735-c116: low metastatic clone) were determined quantitatively using an indirect immunofluorescence technique, confocal laser scanning microscopy (CLSM) and computer-assisted image analysis. Additionally, qualitative and quantitative changes after application of the microtubule-inhibitor nocodazole were investigated. Quantitative analysis showed a significant difference between the high and low metastatic cell line for the parameter TEXTURE, indicating a finer structured network within the high metastatic cells. After treatment with nocodazole the parameters TEXTURE and DENSITY were reduced, suggesting a decrease of assembled tubulin and a less delicate structure of the remaining microtubules. Our study shows that CLSM combined with computer-assisted image analysis provides a new method to examine quantitative variations of the cytoskeleton possibly related to cell function.
Animals↗
Interrelation of motility, cytoskeletal organization and gap junctional communication with invasiveness of melanocytic cells in vitro.
Intercellular communication and the active movement of malignant cells into and through host tissue barriers play a critical role during the complex process of tumor invasion. Motile activity, cytoskeletal actin and vinculin organization as well as gap junctional communication of in vivo benign and malignant melanocytes were compared and related to in vitro invasiveness. Normal melanocytes, Melan-a, showed significantly less motile activity, a higher organization of the actin cytoskeleton and more vinculin-containing cell-substratum adhesion plaques than highly metastatic melanoma cells, K1735-M2. There was no pronounced difference in gap junctional communication under comparable culture conditions. However, cultivation of Melan-a cells in a conventional melanocyte growth medium containing the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) enhanced intercellular communication. Melanocytes were less invasive than melanoma cells both in the embryonic chick heart model and in the Matrigel invasion assay. The least invasive activity was determined for melanocytes cultivated in TPA-deficient medium indicating that the medium supplement TPA stimulates invasion. The comparison of certain in vitro properties of both melanocytic cell lines revealed a positive correlation of motility with in vitro invasion, whereas an inverse correlation was found for the degree of actin filament organization as well as for the number of vinculin plaques. Gap junctional communication was not directly related to in vitro invasiveness.
Actins↗
Pathological findings suggestive of interclonal stabilization in a case of cutaneous melanoma.
Metastatic spread is a complex process based on manyfold interactions of the tumor cells with each other and with the surrounding stroma. In experimental systems tumor cell heterogeneity and presence of various subpopulations which interact with one another to stabilize their relative proportions within the population has been shown. Here we report a patient with melanoma, showing morphological evidence of two distinct tumor cell populations in the primary tumor and in all subcutaneous metastases. By image analysis, both populations were clearly characterized by minimal nuclear diameter and by nuclear form factor and were demonstrable in each specimen. The fact that these peculiar cell populations were present in all melanoma lesions removed from the patient might indicate that the populations require the presence of each other and that none of them is metastatically competent on its own.
Cell Division↗
Differential effects of synthetic sphingosine derivatives on melanoma cell motility, growth, adhesion and invasion in vitro.
Cancer cell surface glycosphingolipids are considered to play a critical role in tumor growth and metastasis. However, the implications of glycoconjugates in the control of cell motility, which is considered to be involved in tumor invasion, are not fully understood. In this study, the effects of a series of synthetic sphingosine derivatives, obtained by the chemical transformation of azidosphingosines, on directional migration of K1735-M2 melanoma cells grown on type I collagen-coated surfaces were investigated. Following the application of 60 microM (2R, 3S, 4E)-2, 3-epimino-4-octadecen-3-ol (S4) the migration rate was 94 +/- 10 microns/day, compared with 377 +/- 22 microns/day in the control experiment. Six other analogues were not as potent. S4 also considerably down-modulated melanoma single cell motility. Inhibition of motile activity was associated with changes in the actin filament organization as well as with changes in the number and distribution of vinculin plaques. Moreover, the compound reduced the attachment abilities of melanoma cells to basement membrane Matrigel. Tumor cell invasion, however, was less affected and proliferation remained unimpaired after treatment with S4. These data suggest at least one intracellular mode of action of this particular synthetic sphingosine derivative by modulation of cytoskeletal organization. Melanoma cell motility and growth may be controlled independently via glycosphingolipids.
Actins↗
Melanoma and stroma: an interaction of biological and prognostic importance.
Stromal relationships are crucial to metastatic spread of solid malignancies. Some aspects of this stroma interaction are obviously associated with particular morphological features, which may carry prognostic significance. In cutaneous melanoma, level of invasion, arrangement of cells (horizontal or vertical growth phase), neovascularization, vessel invasion, architecture of the border, and inflammatory infiltrate have been examined. Expression of adhesion molecules, signalling factors, cytoskeletal components, extracellular matrix molecules and matrix-degrading enzymes have been assessed by immunohistology and in situ hybridization. Besides providing prognostic information, a thorough evaluation of stromal relationships may help to increase our knowledge about factors mediating the growth and metastatic spread of malignancies.
Disease Progression↗
Quantitative morphology of collagen fibers in cutaneous malignant melanoma and melanocytic nevus.
Since tumor growth and metastastatic spread are considered to depend on tumor-stroma interaction, the present study describes the architecture of collagen fibers in 12 cases each of primary melanoma (vertical tumor thickness > 1 mm) and common melanocytic nevi in azan-stained sections by using automated image analysis. In each case, at least 100 high-power fields were consecutively sampled from the tumor center, the tumor periphery, and the surrounding normal-appearing reticular dermis. In both diagnostic groups, collagen density (amount of collagen per tissue volume) and mean collagen fiber bundle diameter was significantly lower in the tumor periphery than in the surrounding stroma and again lower in the tumor center than in the tumor periphery. When melanomas and nevi were compared with each other, melanomas had fewer, but thicker, collagen bundles than did nevi, particularly at the tumor periphery. Taking the mean values of each case as classifiers in multivariate logistic regression analysis, 21 of 24 cases were correctly classified (chi-squared test, p < 0.0001), indicating that the parameters of collagen architecture at least in part reflect biological differences between benign and malignant melanocytic skin lesions.
Adult↗