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Notes: Background  A multicentre, centrally randomized, open-labelled study with temozolomide and interferon (IFN)-α2b was carried out to study the therapeutic effect in patients with metastatic melanoma stage IV.Objectives  The response rate, efficacy, side-effects, reasons for discontinuation of therapy and survival rate of 47 patients treated with temozolomide in combination with two different dosing regimens of IFN-α2b were documented.Patients/methods  Twenty-nine male and 18 female patients (mean age 57·6 years, range 34–74) were centrally randomized to two different arms: 20 patients received a treatment schedule with temozolomide 150 mg m−2 on days 1–5 orally every 28 days in combination with IFN-α2b 10 MIU m−2 every other day and 27 patients received temozolomide 150 mg m−2 on days 1–5 every 28 days in combination with IFN-α2b in a fixed dose of 10 MIU every other day.Results  We observed an overall response rate of 27·6% comprising five complete remissions (10·6%: one patient group A, four patients group B), in two of these five patients at the last follow-up in the study (4·3%, both in group B); and eight partial remissions (17%: six patients in group A, two patients in group B), in three of these eight patients at the last follow-up in the study (6·4%, two patients in group A, one patient in group B). Three patients showed stable disease (6·4%: one patient in group A, two patients in group B). Mean survival was 14·5 months [95% confidence interval (CI) 10–19] with no significant differences between treatment groups. However, there was a significant correlation with response after three cycles (log rank test, P 〈 0·03). Within the 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response showed a significantly better mean survival of 30·6 months (95% CI 19·1–42) compared with 25 patients who did not respond (13·7 months 95% CI 9·2–18·3). In total, patients with at least one complete remission showed the longest survival (37·1 months 95% CI 26·3–47·9), followed by patients with at least one partial response (17·4 95% CI 10·9–23·9). Major side-effects of the treatment were nausea, vomiting, headache, leucopenia, thrombopenia, elevation of liver function parameters and neurological symptoms. In five patients, the side-effects led to a discontinuation of treatment: neurological symptoms (two patients), sepsis (one patient), brain haemorrhage (one patient) and exanthema (one patient). There were no treatment-related deaths.Conclusions  The combination of temozolomide and IFN-α2b can easily be administered and shows tolerable toxicity. When an objective response occurs after three cycles, it indicates a significant survival advantage.

Notes: Background  Dermoscopy improves the diagnostic accuracy in pigmented skin lesions, but it is also useful in the evaluation of nonpigmented skin tumours as it allows the recognition of vascular structures that are not visible to the naked eye. Bowen's disease (BD) or squamous cell carcinoma in situ is usually nonpigmented, but may also rarely be pigmented.Objective  To describe the dermoscopic features in a series of pigmented and nonpigmented BD.Methods  Dermoscopic images of 21 histopathologically proven BD were evaluated for the presence of various dermoscopic features. Each lesion was photographed using the Dermaphot (Heine Optotechnik, Herrsching, Germany), at 10-fold magnification, and the colour slides were scanned to digital format using a Kodak Photo CD system.Results  The majority of cases of BD revealed a peculiar dermoscopic pattern characterized by glomerular vessels (90%) and a scaly surface (90%). In addition, in pigmented BD small brown globules regularly packed in a patchy distribution (90%), and structureless grey to brown pigmentation (80%) were observed.Conclusions  Dermoscopy can be helpful for diagnosing BD because of the presence of repetitive morphological findings such as glomerular vessels and a scaly surface. In pigmented BD, small brown globules and/or homogeneous pigmentation can be seen as well.

Notes: Background  Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so-called blue–white structures (BWS).Objectives  To evaluate diagnostic significance and histopathological correlates of BWS seen by dermoscopy in a series of clinically equivocal melanocytic skin lesions that were excised.Methods  Patients were recruited from six specialized pigmented lesion clinics in Austria, Italy and Spain over a period of 9 months. All consecutive patients showing one or more melanocytic lesions with BWS, but not classified as melanoma dermoscopically, were included. Each lesion was photographed clinically and dermoscopically. All images were reviewed by one of us and the degree, type and location of BWS evaluated for each lesion. A panel of four experienced dermatopathologists independently reviewed all specimens for diagnosis and one of them evaluated presence and degree of melanosis and/or fibrosis. The main outcome measures were the percentage and histopathological correlates of lesions with different degree, type and location of BWS.Results  All included lesions with BWS (n = 158) showed partial or focal regression histopathologically. One hundred and thirty-five (85·4%) lesions were diagnosed as melanocytic naevi (complete histopathological interobserver agreement), whereas 23 (14·6%) were defined as equivocal because at least one of four pathologists diagnosed the given lesion as melanoma. Only one lesion was diagnosed as melanoma by all four pathologists. The majority of naevi exhibited blue areas (84·4%) with a central distribution (57%) and involving 〈 50% of the lesion surface (89·6%). By contrast, 78·3% of equivocal lesions revealed a combination of white and blue areas with an irregular distribution (60·9%) and involving 〉 50% of the lesion surface (47·8%).Conclusions  Using degree and type of BWS, an algorithm was constructed that can be applied for the management of lesions exhibiting dermoscopic features of regression.

Notes: Background  The dermoscopic classification is a useful tool for handling patients with atypical naevi (Clark naevi).Objectives  To investigate if the dermoscopic classification of atypical naevi is of any value to discriminate benign from malignant melanocytic lesions.Methods  Consecutive patients (n = 205) were included with 254 suspicious melanocytic lesions, confirmed by histopathology at the Pigmented Lesions Clinic of the Department of Dermatology, University Medical Center, University of Tuebingen, Germany. In this retrospective study, dermoscopic images of benign and malignant melanocytic lesions were classified according to the dermoscopic classification of atypical naevi (reticular, globular, homogeneous or combinations of two of these) and pigmentation (uniform, central hyper- or hypopigmentation, eccentric peripheral hyper- or hypopigmentation, or multifocal hyper- or hypopigmentation). The three-structure type (reticular, globular and homogeneous) was additionally defined.Results  Reticular, homogeneous and reticular–homogeneous types were significantly more frequent in naevi than in melanomas, whereas the three-structure type was significantly more frequent in melanomas (P 〈 0·001). A sensitivity of 86·7%, specificity of 87·7% and diagnostic accuracy of 87·4% was obtained. Uniformly pigmented and centrally hyperpigmented types were significantly more frequent in naevi than in melanomas, whereas eccentric peripheral hyperpigmented and multifocal hyper- or hypopigmented types were significantly more frequent in melanomas (P 〈 0·001).Conclusions  The dermoscopic classification of atypical naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions. The three-structure type and eccentric peripheral hyperpigmentation were significantly more frequently found in malignant than in benign melanocytic lesions. The knowledge of these two dermoscopic types should be helpful for the management of patients presenting with multiple melanocytic lesions.

Notes: Background  The clinical history of a given pigmented lesion could influence the therapeutic decision. Teledermatology and automated image analysis also hold great potential for revolutionizing dermatology services.Aim  The aim of this retrospective study was to evaluate the diagnostic accuracy of users with different experiences in dermoscopy with and without information about patients and their history compared with classification by an automated analysing system.Setting  One hundred and fifty-seven dermoscopic images of pigmented lesions, taken and proved by histopathology at the Pigmented Lesions Clinic of the Department of Dermatology of the University Tuebingen, Germany, were included.Methods  All images were viewed by three investigators with different experience: excellent (A), average (B) and beginner (C). In the first dermoscopic classification, no information was available. After 3 months the same images were once more classified by the three investigators, now with the information about the patients and their history. The melanocytic lesions were tested by the Tuebinger Mole Analyser.Results  For user A the sensitivity, specificity and diagnostic accuracy revealed no improvement on including the history (81.3% to 84.4%, 94.6% to 92.3% and 92.0% to 90.7%), whereas user B clearly improved his results (75.0% to 87.5%, 76.9% to 88.5% and 76.5% to 88.3%). No change in the sensitivity was seen by user C (84.4%), but there was a clear improvement in the specificity (69.2% to 87.7%) and diagnostic accuracy (72.2% to 87.0%). Using the computer algorithm, a sensitivity of 100%, a specificity of 76.9% and a diagnostic accuracy of 81.9% were achieved.Conclusions  The study revealed results relevant to the use of dermoscopy: (1) continuing dermoscopic education influences the diagnostic accuracy; (2) the history is helpful for averaged users and beginners in dermoscopy; (3) digital image analysis has the highest sensitivity, but a lower specificity compared to the clinicians; and (4) digital dermoscopy could be used for store-and-forward systems in teledermoscopy.

Notes: Numerous attempts have been made to apply image analysis in dermatopathology. The technics used comprise measurement of nuclear size, shape, chromatin content, and texture, evaluation of immunohistological slides, assessment of proliferation, pattern analysis, and tumor volume estimation. For commonly accepted routine use, however, image analysis research has to be extended to large numbers of cases, using straightforward and reproducible measuring procedures, and to the development of ready-to-use equipment for specific tasks. In this way, image analysis in dermatopathology might supply useful diagnostic tools in addition to conventional microscopy, and may increase our understanding of morphology as a whole.

Notes: Patients with melanoma metastatic to the skin show variable prognosis. Though some may survive for quite a long time, some die of disseminated disease within 1 year of removal of cutaneous metastases. The aim of this study was to find out whether there are any histological criteria indicating particular poor outcome. Clinical and histological features of 344 melanoma lesions metastatic to the skin were assessed and their prognostic relevance was investigated. H&E stained histological slides were scanned for the presence of morphological criteria expressing certain tumor cell - stroma interactions: capsule formation (CAPSULE), formation of intratumoral septa (NEWSEPTA), simple invasion between collagen of reticular dermis (DERM-SIMPLE), or subcutis (SCSIMPLE), preservation of preexistent collagen (PRECOLL) or fatty tissue (PREFAT) and, finally, histological site of metastasis. Additionally, anatomical location of the metastases, time between removal of primary tumor and metastases, age and sex of patients were recorded. The metastases were divided into two groups: lesions of patients who died within 1 year after resection (n=59) and lesions from patients with a longer survival (n=285).Metastases which were associated with death within one year were significantly more often found in male patients (54.2% versus 34.7%), in younger patients (mean age 51.1±14.1 years versus 58.8 ± 15.3 years), had developed earlier after the primary tumor (mean time of 21.7±19.9 months versus 43.3±27.4 months) and were more often found at distant sites than in localregional sites (45.7% versus 30.5%), and were more often involved in the subcutis (74.5% versus 56.1%). From a histological point of view, DERMSIMPLE (80% versus 46%; p〈0.001) and PRECOLL (82.8% versus 57.6; p〈0.01) were more frequent in metastases of poor outcome. The same was true for SCSIMPLE (50% versus 25.6%; p〈0.01) and PREFAT (68.1% versus 46.8%; p〈0.05) in lesion with subcutaneous growth, whereas CAPSULE (54.5% versus 75%) was less frequently seen.In conclusion, melanoma deposits metastatic to the skin with particular poor outcome differ clinically and histologically from other cutaneous melanoma metastases. This should be taken into account in the design of therapeutic clinical trials.

Notes: Confocal laser scanning microscopy (CLSM) is a new optical microscopic technique, which offers significant advantages over conventional microscopy. CLSM is microscopy of optical sections. Light, which is emitted from regions other than the focal plane, is cut off by introducing a diaphragm in the beam path. The result is an optical “slice”, which shows more details because the blurring from out of focus haze disappears. It has been repeatedly used in experimental, but also in diagnostic dermatopathology. The “in vivo” confocal microscopy, applied directly to the intact skin provides details of living cells in the superficial layers comparable to that of fixed and stained tissue. While the extent of its future applications is hard to predict, its potential for applications in dermatology appears enormous, particularly for studies of fixed or living tissues, where it is desirable to obtain clear images many micrometers below the surface of the tissue under examination.