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Background: The hazards due to sun exposure are well known. Many recent studies have emphasized the protection against the harmful effects of the sun by the use of sunscreens and, moreover, by staying in the shade and wearing long-sleeved shirts, hats and sunglasses. Switzerland has one of the highest rates of skin cancer induction in Europe and the incidence of melanoma in Switzerland is constantly increasing with an incidence of 10–12/100,000 inhabitants/year. Interestingly, some studies have evoked the possibility that sunscreen use can increase the risk of melanoma by increasing overall sun exposure. Objective and Methods: In this context, the aim of our study was to estimate the amount of sun exposure of children, and their parents, living in Switzerland and to give a description of how they protect themselves against sun irradiation. Questionnaires were provided to pediatricians in every state (canton) in Switzerland and were given to families coming for consultation. Results: A total of 328 forms including 1,285 individuals were returned from most of the cantons in Switzerland. The majority of the Swiss families had 2 children under 16 years of age with middle-aged parents (30–45 years) and a central European skin type (light skin of type II–III, brown or blue eyes, and brown to blond hair). An important sun exposure was noted even though the population seems to be conscious of the associated dangers. Sunscreens were the first-line defense against sun exposure with clothing and shielding oneself from the sun not being highly used. Moreover, sunscreens tended to be misused with most people applying them at the beach or swimming pool (instead of 15 min before exposure) and few applications throughout the day. Conclusions: Prevention should imperatively be emphasized for lower overall sun exposure as sunscreens are primarily used at the beach and not in routine daily exposure. In addition, it is agreed that prevention campaigns would be better directed towards children because up to 80% of detrimental sun exposure occurs during childhood.

As ferritin has been identified as an important factor in antioxidant defense in cultured human skin cells we evaluated the presence of ferritin in human skin in vivo and the modifications following irradiation with UVA I, UVA I + II, and solar simulating light by immunohistochemical analysis. We report that the putative protective protein ferritin is regularly present in the basal layer of unirradiated epidermis in vivo and that the induction of ferritin was dependent on wavelength and cell type. Following UVA I radiation, ferritin increased both in epidermal and in dermal tissue. The same response occurred, although to a lesser extent, with UVA I + II but did not occur following solar simulating radiation. Quantitative analysis for ferritin in cultured keratinocytes and fibroblasts from seven individuals following each UV spectra were also assessed by enzyme-linked immunosorbent assay. The induction of ferritin by UV was highly dependent on the waveband and cell type. UVA I and UVA I + II radiations induced ferritin expression in dermal fibroblasts up to 260% and 200% over basal levels, respectively. Solar simulating radiation produced only a small induction of ≈130% over basal ferritin levels in dermal fibroblasts. Ferritin increased in cultured fibroblasts as early as 3 h post-UVA with a peak at 6 h that remained until 48 h; there was no observable qualitative or quantitative increase seen in the undifferentiated cultured epidermal keratinocytes. Our findings indicate that the putative defense system of ferritin exists in human skin in vivo and its induction is dependent on UV spectra and cell type. The increased concentrations of this antioxidant in human skin following acute UV radiation could afford increased protection against subsequent oxidative stress. Key word: oxidative stress. J Invest Dermatol 111:159–163 1998

Adhesion molecules are involved in leukocyte recruitment, lymphocyte recirculation, and in several aspects of tumour biology. Recent discoveries of surface proteins on tumour cells involved in tumour metastasis may explain the invasive behaviour, the migration involving reversible adhesive contacts, the release into the circulation and the extravasation of tumour cells. CD44 is a family of glycoproteins involved in cell-cell and cell-matrix interactions. The v6 (variant exon v6) form of CD44 confers a metastatic potential onto some carcinoma cells. In the present study, the expression of CD44v6 on skin biopsies of 10 inflammatory skin diseases, 30 cutaneous lymphomas (CL), 11 reactive lymph nodes, 10 primary nodal non-Hodgkin's lymphomas (NHL) and 5 secondary nodal NHL was investigated immunohistochemically. None of the 10 nodal NHL were CD44v6 positive for the neoplastic B- or T-cells, whereas 11/12 CL with systemic spread showed a distinct CD44v6 expression in the skin. CD44v6 was not expressed on the tumour cells of skin biopsies of patients without systemic spread (18 cases of CL). In conclusion, CD44v6 expression is connected to an aggressive behaviour of CL.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Background: Surgical excision is the gold standard for cutaneous squamous cell carcinoma (cSCC), however its application is limited in specific cases. Superficial radiotherapy (RTx) is an alternative treatment option, but long-term follow-up data are limited. Objective: To determine the outcome of superficial RTx of cSCC in correlation to histological differentiation grade and tumor localization. Methods: The outcome of 180 large cSCCs after superficial RTx between 1960 and 2004 was retrospectively reviewed. Results: Mean tumor size was 3.5 cm2 (SD 7.5) and mean follow-up period was 4.9 years (SD 4.7). Relapse-free survival was 95.8 and 80.4% after 1 and 10 years. Two-year relapse-free survival was 94.8% for good, 88.9% for moderate and 85.7% for poor differentiated tumors. Five-year relapse-free survival was highest in cSCCs located around the eyes (100%) and cheeks (90.9%). Conclusion: Superficial RTx is an effective alternative for cSCC if surgery is difficult due to localization or concomitant disease.

Wegener’s granulomatosis is a systemic disease characterized by necrotizing granulomas and vasculitis involving the upper and lower respiratory tract as well as the kidneys. Cutaneous manifestations consist mainly of papules or papulonecrotic lesions. c-ANCA are known to be a valuable adjunct for the diagnosis and follow-up of Wegener’s granulomatosis with systemic involvement. We report the case of a 49-year-old man with Wegener’s granulomatosis who developed two relapses of the disease with cutaneous manifestation and who presented with concomitant elevation of the c-ANCA and more precisely the subset PR3-ANCA during the acute phase of the disease.

BACKGROUND: Antitumour necrosis factor (anti-TNF) treatments may reactivate latent tuberculosis infection (LTBI). For detecting LTBI, the tuberculin skin test (TST) has low sensitivity and specificity. Interferon-gamma release assays (IGRA) have been shown to be more sensitive and specific than TST. OBJECTIVE: To compare the TST and the T-SPOT.TB IGRA for identifying LTBI in patients with psoriasis before anti-TNF treatment. METHODS: A retrospective study was carried out over a 4-year period on patients with psoriasis requiring anti-TNF treatment. All were subjected to the TST, T-SPOT.TB and chest X-ray. Risk factors for LTBI and history of bacillus Calmette-Guerin (BCG) vaccination were recorded. The association of T-SPOT.TB and TST results with risk factors for LTBI was tested through univariate logistic regression models. Agreement between tests was quantified using kappa statistics. Treatment for LTBI was started 1 month before anti-TNF therapy when indicated. RESULTS: Fifty patients were included; 90% had prior BCG vaccination. A positive T-SPOT.TB was strongly associated with a presumptive diagnosis of LTBI (odds ratio 7.43; 95% confidence interval 1.38-39.9), which was not the case for the TST. Agreement between the T-SPOT.TB and TST was poor, kappa = 0.33 (SD 0.13). LTBI was detected and treated in 20% of the patients. In 20% of the cases, LTBI was not retained in spite of a positive TST but a negative T-SPOT.TB. All patients received an anti-TNF agent for a median of 56 weeks (range 20-188); among patients with a positive TST/negative T-SPOT.TB, no tuberculosis was detected with a median follow-up of 64 weeks (44-188). One case of disseminated tuberculosis occurred after 28 weeks of adalimumab treatment in a patient with LTBI in spite of treatment with rifampicin. CONCLUSION: This study is the first to underline the frequency of LTBI in patients with psoriasis (20%), and to support the use of IGRA instead of the TST for its detection. Nevertheless, there is still a risk of tuberculosis under anti-TNF therapy, even if LTBI is correctly diagnosed and treated.

With no less than 15,000 estimated new cases diagnosed per year, non melanomatous carcinomas are the commonest cutaneous cancers in the Swiss population. About 1 in 3 new cancer case is a basal (BCC) or a squamous cell carcinoma (SCC). Incidence rates are steadily increasing, faster for BCC than SCC. Rates are higher for men than women and increase exponentially with age. Systematic population-based registration of non melanomatous skin cancers faces many challenges that few cancer registries can meet. Rates of these cancers in Switzerland are among the highest in Europe. Primary and secondary nationwide prevention campaigns have been carried out for nearly 20 years with a focus on the deadliest cutaneous cancer: melanoma. However, detection of non melanomatous skin cancers benefits from these campaigns since prevention messages and means of early detection are similar for melanomas and other skin cancers.

Posttransplant cutaneous T cell lymphomas are rare and have been reported to have a poor prognosis. We report the case of a follicular mycosis fungoides in a lung transplant recipient who was successfully treated with topical mechlorethamine, prior to subsequent renal transplantation.

We report the case of a 42-year-old man with symptomatic HIV infection (C3 CDC stage) who presented widespread hyperkeratotic skin lesions diagnosed as Norwegian scabies. The CD4 count was 87 cells/mm3. The patient has been the source of a nosocomial outbreak (20 individuals affected). He was treated successfully with combined topical treatment (permethrin 5% cream plus keratolytic agents) and oral ivermectin.

Background Multiple nodules of the scrotum are uncommonly reported. Their origin is controversial. Treatment is always surgical but the best procedure is still to be determined. Materials and methods Five new cases are reported with description of the histopathological findings and surgical procedure. Results Nodules of the scrotum were more frequent in patients with dark skin suggesting an ethnic susceptibility. No other predisposing factors were noted. Screening for disturbances of phosphate or calcium balance was negative. The following histopathological findings were observed: non-calcified epidermoid cysts (3 patients), calcified epidermoid cysts (1 patient) and nodular calcifications without epithelial or glandular structures (1 patient). Subtotal excisions of the scrotum wall using tumescent anaesthesia were performed in all patients without any significant complications. Cosmetic results were excellent. No new lesions were observed during the 1-year follow-up period. Conclusions Most cases of multiple nodules of the scrotum are due to non-calcified epidermoid cysts. The term scrotal calcinosis is therefore probably abusively used by many authors. Some cases of nodular calcifications may be due to dystrophic calcification of epidermoid cysts, but calcifications may also occur without any visible epithelial or glandular structure. Subtotal excision of the scrotum wall is a safe and effective surgical procedure to treat multiple nodules of the scrotum. Cosmetic results are excellent and recurrences are rare.

Imatinib is a specific and potent inhibitor of the BCR-ABL tyrosine kinase. Several clinical trials have demonstrated the efficacy of imatinib in chronic myeloid leukemia. Adverse cutaneous reactions induced by imatinib are frequent and may be dose related. We report a case of an unusual pustular eruption in a patient with chronic myeloid leukemia, who received high doses imatinib for blast crisis and later voriconazole for invasive pulmonary aspergillosis. At the time of his skin eruption, elevated plasma levels of imatinib were recorded. Imatinib is primarily metabolized by the cytochrome CYP3A4. Voriconazole is a cytochrome CYP3A4 inhibitor and can lead to high plasma levels of imatinib. This case suggests that severe drug reactions to imatinib may be related not only to imatinib doses, but also to elevated plasma drug levels resulting from pharmacokinetic interactions. The monitoring of imatinib plasma levels may be of help for identifying patients at risk for severe toxicity.

As part of the national skin cancer prevention programme coordinated by the Swiss League against Cancer, a mobile unit visited 29 Swiss towns to inform people on skin type, skin cancer risk and sun protection behaviour. In the summer of 2003, among 6725 visitors, 3662 took the offered possibility of having a cutaneous lesion checked free of charge by a dermatologist present in the mobile unit. The campaign satisfactorily covered, albeit to various degrees, its 3 fields of activity, i.e. (1) primary prevention, (2) secondary prevention and (3) clinical examination. Participants were predominantly females (60%), except for visits on work sites (firms and universities), half were aged 15-44 years, and 40% were considered at increased risk for skin cancer. Sociodemographic and regional differences in the profile of visitors were observed and could largely be attributed to variations in daily availability of the mobile unit. 108 malignant lesions were observed, including 21 cutaneous melanomas. Relative to the number of examinations performed, more cancers were detected in men, those aged 65 or over, and visitors who experienced a prior skin screening and severe sunburns during childhood. Limitations and prospects of this type of preventive campaigns are briefly discussed.

We present a 34-year-old patient with digital necrosis due to thromboangiitis obliterans. He was successfully treated with iloprost, a prostaglandin analogue. Duplex ultrasonography was performed during the perfusion of iloprost to optimize the doses and the treatment duration. A complete revascularization was observed after 10 days. Iloprost perfusions were stopped, and a slow regression of the necroses was observed in the subsequent days. With the use of duplex ultrasonography, unnecessary high doses of iloprost and long periods of treatment can be avoided reducing side effects and treatment costs.

We describe a 77-year-old patient with a giant acquired fibrokeratoma on the heel. The size and the localization of the tumor was unusual. Simple shave excision was curative.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is commonly regarded an angioproliferative process characterized by the presence of prominent, bizarrely shaped blood vessels. These vessels are accompanied by an inflammatory infiltrate that is thought to be a reactive component. Both the cell of origin and the pathogenesis of ALHE remain controversial. To define the histogenesis of this disorder, we analyzed the phenotypic and genotypic profile of the inflammatory infiltrate in ALHE by immunohistochemistry and T-cell receptor gene rearrangement by polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis, as well as automated high-resolution PCR fragment analysis. Five of 7 ALHE patients displayed a clonal T-cell population and proliferative T-cell activity in lesional tissue. Most of these cases followed a protracted and therapy-reluctant course with recurrences. These data suggest that ALHE or a subset of ALHE cases harboring a clonal T-cell population may represent a T-cell lymphoproliferative disorder of a benign or low-grade malignant nature.

SummaryBackground Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are the most common melanocytic neoplasms on sun-exposed skin of elderly patients. Objectives To perform a retrospective study of 150 patients with LM and LMM treated with radiotherapy using Grenz or soft X-rays. Methods The information recorded and analysed included gender, age, diagnosis, size of the lesion, localization, X-ray treatment, recurrence rate, other skin malignancies and non-dermatological neoplasms. Results The 150 patients comprised 78 women and 72 men (mean age 70 years). Ninety-three patients had LM, 54 had LMM and three had both neoplasms. Ninety per cent of lesions were located on the face. Treatment was with Grenz rays in 96 patients with LM and 11 with LMM (70%) and with soft X-rays in 46 patients with LMM (30%). Three patients were treated using both modalities. One hundred and one patients were followed up for at least 2 years after radiotherapy (mean 8 years). The mean time to recurrence was 45·6 months, and the recurrence rate was 7% (seven of 101). Other skin malignancies were observed in 65 of 150 patients, including basal cell carcinoma in 23 (35%) and actinic keratosis in 20 (31%). Four patients developed internal cancers. Conclusions The study showed that radiotherapy of LM and LMM was curative. In particular, radiotherapy proved to be an excellent treatment for elderly patients. Owing to the high incidence of other skin cancers, LM patients need careful follow-up.

Cutaneous plasmacytosis is a recently described skin disorder consisting of brown to red papules and nodules containing polyclonal plasmacytes. In this particular case, leg ulcers developed but also a diffuse patchy hyperpigmentation coexisting with a primary hypothyrodisim. The last two signs have only been described to date in POEMS syndrome, which is linked to monoclonal plasmacytic proliferation, and might suggest an overlap between these two entities.

A new culture model was developed to study the role of proliferation and apoptosis in the etiology of keloids. Fibroblasts were isolated from the superficial, central, and basal regions of six different keloid lesions by using Dulbecco's Modified Eagle Medium containing 10% fetal calf serum as a culture medium. The growth behavior of each fibroblast fraction was examined in short-term and long-term cultures, and the percentage of apoptotic cells was assessed by in situ end labeling of fragmented DNA. The fibroblasts obtained from the superficial and basal regions of keloid tissue showed population doubling times and saturation densities that were similar to those of age-matched normal fibroblasts. In contrast, the fibroblasts from the center of the keloid lesions showed significantly reduced doubling times (25.9 +/- 6.3 hours versus 43.5 +/- 6.3 hours for normal fibroblasts) and reached higher cell densities. In long-term culture, central keloid fibroblasts formed a stratified three-dimensional structure, contracted the self-produced extracellular matrix, and gave rise to nodular cell aggregates, mimicking the formation of keloid tissue. Apoptotic cells were detected in both normal and keloid-derived fibroblasts, but their numbers were twofold higher in normal cells compared with all keloid fibroblasts. To examine whether apoptosis mediates the therapeutic effect of ionizing radiation on keloids, the cells were exposed to gamma rays at a dose of 8 Gy. Under these conditions, a twofold increase in the population of apoptotic cells was detected. These results indicate that the balance between proliferation and apoptosis is impaired in keloid fibroblasts, which could be responsible for the formation of keloid tumors. The results also suggest that keloids contain at least two different fibroblast fractions that vary in growth behavior and extracellular matrix metabolism.

Bullosis diabeticorum (BD), although a rare manifestation, is characteristic of diabetes mellitus. The exact origin of BD is unknown. We report another case of a 54-year-old man who developed a blistering lesion on his left leg. Histopathological examination revealed a microangiopathy with hyalinosis of the blood vessel walls.

We describe a case of intensively pruritic and partially bullous disseminated superficial actinic prorokeratosis, with acute flare-ups. Histopathological examination showed the characteristic cornoid lamella and subepidermal blister formation in one biopsy. Grenz ray treatment resulted in a marked regression of the skin lesions and pruritus.

Background: Monitoring of psoralen concen- tration and time-course in PUVA patients is vital for efficient PUVA therapy. Blood sampling is invasive and labour-intensive and thus unsuited for routine use and repeat measurements over the course of therapy. Objective: Psoralen pharmacokinetics in saliva were investigated and validated as a noninvasive, simple and biologically relevant alternative to measurements in blood. Methods: The time-course of psoralen concen- tration was measured in saliva and serum of volun- teers and patients receiving PUVA or extracorporeal photopheresis therapy. The samples were analysed by high-performance liquid chromatography. Three com- monly used oral psoralen preparations were tested: Psoraderm5 (5-methoxypsoralen; 5-MOP), Meladi- nine and Oxsoralen (both 8-methoxypsoralen; 8-MOP). Results: The pharmacokinetic parameter Cmax in saliva averaged 10% (range 6-20%) of the serum values for 8-MOP, and † 4% for 5-MOP. These concentrations correspond to the therapeutically relevant, non-albu- min-bound fraction of psoralen in serum that is avail- able to diffuse into the tissues. The parameter t max in saliva and serum coincided, indicating that psoralens diffuse rapidly between the two compartments. Con- clusion: Monitoring of psoralens in saliva is a valuable, noninvasive alternative to measurements in serum, suit- able for routine use. A series of five or six saliva sam- ples is sufficient to determine t max in a patient begin- ning photochemotherapy. To determine Cmax, three in- dependent saliva measurements at t = tmax are recom- mended.

Advances in the molecular definition of surface proteins (adhesion molecules) involved in tumor metastasis may help to explain the invasive behavior of malignant tumors, that is, the migration of tumor cells involving reversible adhesive contacts, their release in the circulation, and their extravasation into distant sites. Intercellular adhesion molecule-3 (ICAM-3), the third receptor for the lymphocyte function-associated antigen molecule-1 (LFA-1) was recently characterized. We investigated fresh frozen skin biopsies from 10 patients with mycosis fungoides, four with pleomorphic T-cell lymphoma, six with Sézary syndrome, 10 with primary cutaneous B-cell lymphoma, and 10 with eczematous lesions as controls. The biopsies were compared with lymph node biopsies of five patients with known cutaneous T-cell lymphoma (CTCL), 10 with primary nodal B-cell lymphoma, and 11 with lymph-node specimens showing dermatopathic lymphadenopathy as controls. The specimens were stained with ICAM-3 antibody (Bender Medical Science) using the alkaline phosphatase antialkaline phosphatase method. Using cytomorphologic criteria, neoplastic lymphocytes could be differentiated from smaller reactive cells. Staining intensities were classified semiquantitatively as follows: 4, strong expression in 75 to 100% of the tumor cells; 3, 50 to 75%; 2, 25 to 50%; 1, 5 to 25%; and 0 fewer than 5% of the tumor cells. The endothelial cells in skin biopsies of seven of 30 primary cutaneous lymphomas expressed ICAM-3. In contrast, no expression of ICAM-3 could be demonstrated on endothelial cells in lymph nodes infiltrated with tumor cells of CTCL. Finally, endothelial cells of lymph nodes infiltrated with primary nodal B-cell lymphomas showed expression of ICAM-3 in three of 10 patients. The endothelial cells in the 11 control patients presenting with both eczematous lesions and dermatopathic lymphadenopathy showed no staining for ICAM-3. Every patient who expressed ICAM-3 on endothelial cells showed systemic spread of this disease. The findings suggest that ICAM-3 expression may be induced on endothelial cells in late-stage cutaneous lymphomas, probably by a cytokine-mediated mechanism.

Statins are among the most widely prescribed drugs. An increasing number of lupus-like syndrome has recently been reported with these lipid-lowering agents. We describe a new case associated with simvastatin therapy. The presence of anti-dsDNA antibodies in the serum is for the first time reported confirming that statins may also induce a systemic autoimmune reaction. Statin-induced lupus-like syndrome is characterized by the long delay between the beginning of therapy and the skin eruption. Antinuclear antibodies may persist for many months after drug discontinuation. The causal relationship may be therefore difficult to establish, and probably many cases are unrecognized. Early diagnosis may avoid unnecessary immunosuppressive therapy.

Several case-control studies identified common and atypical melanocytic nevi as major risk indicators for the development of cutaneous melanoma. The present investigation was planned to detect factors associated with the prevalence of these melanoma risk markers. Whole-body examination findings and interview data of 513 melanoma patients and 498 age- and sex-matched control subjects were analyzed. Existence of more than 50 common melanocytic nevi and the presence of atypical melanocytic nevi were significantly related to age and gender, with significantly elevated relative risk for their prevalence before the age of 60 and in males. Additionally, sunburns before the age of 20 were significantly associated with both more than 50 common melanocytic nevi (relative risk = 1.7) and the presence of atypical melanocytic nevi (relative risk = 1.5). Actinic lentigines were found more frequently with increasing age, and the presence of actinic lentigines was significantly related to a tendency of freckling in adolescence (relative risk = 2.0) and to two or more sunburns after the age of 20 (relative risk = 1.6). In conclusion, sunburns before the age of 20 contribute to the development of multiple melanocytic nevi and atypical melanocytic nevi. In adulthood, this type of sun exposure is associated with the development of actinic lentigines. The relative risk of developing cutaneous melanoma increases in association with the development of these benign melanocytic lesions.

Different pigmentary characteristics as well as different parameters of sun exposure have previously been identified as risk factors for developing cutaneous melanoma. The aim of the present study was to identify significant risk factors, de- termine the related magnitude of their estimated relative risks, and define criteria for the detection of persons at risk. Five hundred thirteen melanoma patients and 498 controls matched for age and sex underwent a whole-body examination for the number and type of melanocytic lesions and were interviewed on ultraviolet exposure and other potential risk factors. The total number of common melanocytic nevi on all body sites represented the most important risk factor in multiple logistic regression analysis with a relative risk of 7.6 for subjects with more than 100 versus no more than 10 melanocytic nevi. Other significant independent risk factors were the number of atypical melanocytic nevi (relative risk, 6.1 for at least 5 melanocytic nevi versus none), the number of actinic lentigines (relative risk, 3.5 for many versus none), hair color, skin type, and reported melanocytic nevus growth. No single parameter of sun exposure was significantly related to melanoma risk in the multivariate analysis. Groups with an estimated relative risk between 1 and 121.0 were distinguished by considering common and atypical melanocytic nevi as well as actinic lentigines as the decisive criteria. In conclusion, even without any information on the case history, whole-body examination and diagnosis of pigmented lesions was found to be an effective strategy for identifying persons at risk of developing melanoma. Furthermore, clinical recognition of at least 5 atypical melanocytic nevi without histologic examination is a key for identifying subjects at high risk.