Risk factors for limb melanomas compared with trunk melanomas in Queensland

The objective of this study was to investigate the risk factors for melanoma on the arms and legs in comparison with well-known risk factors for trunk melanoma. The study was a population-based case-control study of 77 individuals with limb (25 arm; 52 leg) and 86 with trunk melanoma, who were representative of all the individuals newly-diagnosed with primary limb melanomas in Queensland during 1979-1980 and 232 controls. A single physician interviewed and examined all individuals and assessed complexion type, sun exposure history and other potential risk factors and clinical features. After multivariate analysis, the strongest risk factor for both limb and trunk melanomas was the presence of more than 10 naevi on the arm (odds ratio limb melanoma=41.4, 95% confidence interval 10.4-164), though on histology, a preexisting naevus was more strongly associated with trunk than limb melanoma (P<0.004). Associations with blonde/light brown hair, propensity to freckle and sunburn were similar for melanoma on both sites. A lifetime history of painful sunburns significantly raised the risk of trunk but not limb melanoma, whereas solar keratoses on the arm or face were more strongly associated with limb than with trunk melanoma (marginally significant, P(homogeneity)=0.056). High ambient solar ultraviolet radiation in adolescence was also a stronger risk factor for limb than for trunk melanoma. In conclusion, this population-based investigation into specific differences in causes of limb versus melanomas of other sites suggests that the risk factor profile is intermediate between the profiles for head/neck melanoma (mostly cumulative sun damage) and for trunk melanomas (most strongly related to naevi).     

Abnormal sensitivity to UV-radiation in cultured skin ibroblasts from patients with hereditary cutaneous malignant melanoma and dysplastic nevus syndrome

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). Although environmental exposures, especially solar UV-irradiation, have been implicated as risk factors in sporadic melanoma, the role of such exposures in the pathogenesis of HCMM is unknown. We have studied the in vitro radiation responses of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. All six HCMM/DNS strains were found to show some degree of enhanced cell killing sensitivity, compared with normal controls, following 254 nm UV-irradiation. The abnormal survival responses appeared to relate to specific characteristics of HCMM/DNS cells since the six strains had essentially normal sensitivity to γ-radiation. The enhanced photosensitivity was not associated with abnormal patterns in either DNA repair synthesis or UV-induced inhibition and recovery of de novo DNA synthesis. The survival results are consistent with the hypothesis that the genetically determined predisposition to malignant melanoma may directly or indirectly be the consequence of increased susceptibility to UV-induced cellular damage.     

Effect of a novel somatostatin analogue combined with cytotoxic drugs on human tumour xenografts and metastasis of B16 melanoma

A novel somatostatin analogue, TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human melanoma and lymphoma xenografts as a single treatment or in combination with DTIC (dacarbazine) and etoposide. TT-232 inhibited the growth of HT-18 melanoma xenografts, a dose of 5 mg kg(-1) being the most effective. Combination of 1 mg kg(-1) TT-232 with 30 or 60 mg kg(-1) DTIC (administered daily) resulted in a stronger inhibitory effect compared to TT-232 or DTIC as a single modality. Antimetastatic effect of TT-232 treatment combined with DTIC was studied using the B16 mouse melanoma muscle - lung metastasis model. The number of lung metastases of B16 melanoma could be decreased by the daily administration of 1 mg kg(-1) TT-232 or 60 mg kg(-1), but not of 30 mg kg(-1) DTIC. TT-232, combined with 30 or 60 mg kg(-1) DTIC decreased the lung metastasis number significantly lower than the control. Nearly 50% growth inhibition of HT-58 lymphoma was achieved by daily treatment with 1 mg kg(-1) TT-232. 5 mg kg(-1) etoposide, administered daily, resulted in a similar effect. The combination of 1 mg kg(-1) TT-232 and 5 mg kg(-1) etoposide was significantly more effective than TT-232 or etoposide as a single treatment. The very strong tumour growth inhibitory effect of 10 mg kg(-1) etoposide could even be increased by combination with TT-232. These experimental data suggest that TT-232 may be an effective new tool in the combination chemotherapy of malignant tumours like melanoma and lymphoma.     

Ultraviolet B but not ultraviolet A radiation initiates melanoma

Cutaneous malignant melanoma is one of the fastest increasing cancers with an incidence that has more than doubled in the last 25 years. Sunlight exposure is strongly implicated in the etiology of cutaneous malignant melanoma and the UV portion of the sunlight spectrum is considered responsible. Data are, however, conflicting on the roles of ultraviolet B [UVB; 280-320 nanometers (nm)] and ultraviolet A (UVA; 320-400 nm), which differ in their ability to initiate DNA damage, cell signaling pathways and immune alterations. To address this issue, we have used specialized optical sources, emitting isolated or combined UVB or UVA wavebands or solar simulating radiation, together with our hepatocyte growth factor/scatter factor-transgenic mouse model of UV-induced melanoma that uniquely recapitulates human disease. Only UVB-containing sources initiated melanoma. These were the isolated UVB waveband (>96% 280-320 nm), the unfiltered F40 sunlamp (250-800 nm) and the solar simulator (290-800 nm). Kaplan-Meier survival analysis indicated that the isolated UVB waveband was more effective in initiating melanoma than either the F40 sunlamp or the solar simulator (modified log rank P < 0.02). The latter two sources showed similar melanoma effectiveness (P = 0.38). In contrast, transgenic mice irradiated with either the isolated UVA waveband (>99.9% 320-400 nm, 150 kJ/m2), or an F40 sunlamp filtered to remove > 96% of the UVB, responded like unirradiated control animals. We conclude that, within the constraints of this animal model, UVB is responsible for the induction of mammalian cutaneous malignant melanoma whereas UVA is ineffective even at doses considered physiologically relevant. This finding may have major implications with respect both to risk assessment from exposure to solar and artificial UVB, and to development of effective protection strategies against melanoma induction by UVB. Moreover, these differences in wavelength effectiveness can now be exploited to identify UV pathways relevant to melanomagenesis.     

Pigmentary traits, modalities of sun reaction, history of sunburns, and melanocytic nevi as risk factors for cutaneous malignant melanoma in the Italian population: results of a collaborative case-control study

BACKGROUND: To the authors' knowledge, limited data are available from Mediterranean populations concerning risk factors for malignant melanoma. A few Italian case-control studies have produced conflicting results regarding the association between malignant melanoma and pigmentary traits, sunburns, and melanocytic nevi. METHODS: A case-control study was conducted within the framework of the Italian Group for Epidemiologic Research in Dermatology (GISED). Twenty-seven centers in the north and south of Italy participated. A total of 542 cases and 538 controls were entered onto the study. A standardized questionnaire was administered to cases and controls. Cases and controls also were examined by trained dermatologists who were required to count the number of melanocytic nevi (those measuring > or = 2 mm and > 6 mm in greatest dimension, separately) and to make judgments regarding pigmentary traits. RESULTS: In the multivariate analysis, eye and skin color, propensity to sunburn, history of sunburns before age 15 years, and solar lentigines all were associated with malignant melanoma. In addition, the risk of melanoma increased with the number of melanocytic nevi > or = 2 mm. Nevi > 6 mm in greatest dimension had effects on risk that appeared to be independent from the effects of smaller nevi (2-6 mm). CONCLUSIONS: The results of the current study largely are similar to those obtained in northern European countries, the U.S., and Australia and provide further evidence of the importance of selected pigmentary traits, sun exposure, and the number of melanocytic nevi in the risk of cutaneous malignant melanoma.     

The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: A systematic review

Exposure to solar ultraviolet (UV) radiation is a known cause of skin cancer. Sunbed use represents an increasingly frequent source of artificial UV exposure in light-skinned populations. To assess the available evidence of the association between sunbed use and cutaneous malignant melanoma (melanoma) and other skin cancers, a systematic review of the literature till March 2006 on epidemiological and biological studies on sunbed use was performed in Pubmed, ISI Web of Science, Embase, Pascal, Cochrane library, Lilacs and Medcarib. Search for keywords in the title and in the abstract was done systematically and supplemented by manual searches. Only case-control, cohort or cross-sectional studies were selected. Data were abstracted by means of a standardized data-collection protocol. Based on 19 informative studies, ever-use of sunbeds was positively associated with melanoma (summary relative risk, 1.15; 95% CI, 1.00-1.31), although there was no consistent evidence of a dose-response relationship. First exposure to sunbeds before 35 years of age significantly increased the risk of melanoma, based on 7 informative studies (summary relative risk, 1.75; 95% CI, 1.35-2.26). The summary relative risk of 3 studies of squamous cell carcinoma showed an increased risk. For basal cell carcinoma, the studies did not support an association. The evidence does not support a protective effect of the use of sunbeds against damage to the skin from subsequent sun exposure. Young adults should be discouraged from using indoor tanning equipment and restricted access to sunbeds by minors should be strongly considered.     

Sunburn and malignant melanoma

We investigated the relationship between cutaneous malignant melanoma and multiple sunburns in the Queensland population. Interview data were gathered from 236 case-control pairs concerning their lifetime experience of severe sunburns, their occupational and recreational sun exposure, and their skin type. Excluding the lentigo maligna melanoma subtype, an association between multiple sunburns and melanoma was evident. After controlling for other major risk factors there was a significant dose-response relationship (P less than 0.05): the estimated relative risk associated with 2-5 sunburns in life was 1.5, and with 6 or more was 2.4. This observation extends the hitherto circumstantial evidence of a causal relationship between exposure to solar ultraviolet radiation and melanoma, and suggests that precautionary measures could prevent the development of this disease in a proportion of cases in fair-skinned populations.     

Incidence of cutaneous malignant melanoma in Denmark 1978-1982. Anatomic site distribution, histologic types, and comparison with non-melanoma skin cancer.

The variations by sex, age and anatomic site of 2,376 cutaneous malignant melanomas, 10,846 basal cell carcinomas, and 2,005 squamous cell carcinomas were analyzed using incident cases from the Danish Cancer Registry for the period 1978-1982. Melanoma have a flat age-incidence curve, whereas for other skin cancers, the increase is exponential with age. Sex- and age-patterns differ for various anatomic locations of the body. In a population based case series of 551 patients with malignant melanoma of the skin diagnosed in the period 1982 to 1985 collected as part of a population-based case-control study, the specific anatomic site of the primary lesion was recorded, and the lesions were classified as to histologic subtype. The estimated incidence rates per unit surface area were highest for melanoma of the back, followed by the face, scalp and neck, and the chest in males. In females highest incidence was recorded for the leg, followed by the face, scalp and neck, and the back. Superficial spreading and nodular melanoma did not differ in their age-pattern. This was markedly different from that of lentigo maligna melanoma undoubtedly due to a strong cohort phenomenon of the former.     

Etiologic and other factors predicting nevus-associated cutaneous malignant melanoma.

Cutaneous malignant melanomas with histologic evidence of an associated nevus (N+) may have a different risk factor profile from that of melanomas without it (N-). To address this question, a case-only analysis of 932 people with cutaneous malignant melanoma was done to identify etiologic and other factors associated with N+ melanoma. Evidence of an associated nevus was found in 36% of melanomas. N+ melanomas were thinner (Ptrend=0.0009) and more likely to be of the superficial spreading type than other types of melanoma. Subjects with N+ melanomas were younger (Ptrend<0.0001) and reported a higher nevus density on their skin than subjects with N- melanomas [odds ratio (OR), 3.1; 95% confidence interval (CI), 1.6-6.0, for high nevus density versus no nevi]. Indicators of high accumulated sun exposure were less prevalent among subjects with N+ melanomas (OR, 0.3; 95% CI, 0.2-0.4, for melanoma location on the head and neck versus location on trunk; OR, 0.2; 95% CI, 0.1-0.4, for severe solar elastosis adjacent to the melanoma versus no elastosis; OR, 0.2; 95% CI, 0.1-0.4, for lentigo maligna melanoma subtype versus superficial spreading subtype). With the exception of solar elastosis and age, all of the aforementioned variables remained significantly associated with N+ melanomas in multivariate analyses. No associations with self-reported measures of sun exposure, sunburn, or pigmentation phenotype were apparent. Our findings provide some support for the hypothesis of etiologically separate pathways for melanoma, with N+ melanomas appearing less likely to develop in the presence of characteristics suggesting high accumulated sun exposure than N- melanomas. However, it is possible that high UV exposure causes involution of nevi, thus reducing the density of nevi in exposed skin and thereby the probability of N+ melanoma.     

The Y152X MC1R gene mutation: occurrence in ethnically diverse Jewish malignant melanoma patients

MC1R sequence variants are associated with malignant melanoma risk, and most commonly are missense mutations. Few (n=9) truncating mutations have been described in this gene as predisposing to malignant melanoma. In this study, three Jewish individuals were found to harbor an identical truncating MC1R mutation--Y152X: an Ashkenazi patient with two malignant melanomas, a non-Ashkenazi malignant melanoma patient with familial malignant melanoma and her asymptomatic mother. Both malignant melanoma patients carried additional, seemingly pathogenic MC1R variants. Haplotype analysis revealed that all three mutation carriers shared the same haplotype. This sequence variant was previously described in ethnically diverse, non-Jewish individuals and in all likelihood represents an error-prone domain that, in conjunction with other genetic and environmental factors, increases malignant melanoma risk.     

Shedding light on melanocyte pathobiology in vivo

Cutaneous malignant melanoma is rapidly increasing in the developed world and continues to be a challenge in the clinic. Although extensive epidemiologic evidence points to solar UV as the major risk factor for melanoma, there is a significant gap in our knowledge about how this most ubiquitous environmental carcinogen interacts with the largest organ of the mammalian body (skin) at the microenvironmental and molecular level. We review some recent advances that have started to close this gap.     

Elevated pretreatment serum levels of soluble vascular cell adhesion molecule 1 and lactate dehydrogenase as predictors of survival in cutaneous metastatic malignant melanoma.

Very rapid progression of disease with a median survival of 6-9 months is a common feature of metastatic cutaneous malignant melanoma. Nevertheless, substantial variability of survival suggests that metastatic cutaneous malignant melanoma can be divided into several biological subgroups. Pretreatment serum levels of soluble adhesion molecules and various clinical parameters in cutaneous metastatic malignant melanoma were evaluated to determine their prognostic value. In this study pretreatment serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular cell adhesion molecule 1 (sICAM-1), soluble endothelial leukocyte adhesion molecule 1 (sE-selectin) and multiple clinical factors were assessed in relation to overall survival of 97 consecutive patients with metastatic cutaneous malignant melanoma seen at our institution between May 1990 and April 1996. For statistical analysis, both univariate and multivariate Cox proportional-hazards models were used. Elevated pretreatment serum levels of sVCAM-1 (P < 0.005) and of lactate dehydrogenase (P < 0.002) were rendered statistically independent and were significantly associated with unfavourable outcome. Patients were assigned to one of three risk categories (low, intermediate and high) according to a cumulative risk score defined as the function of the sum of these two variables. There were significant differences in overall survival (P < 0.0001) between low- (n = 53, 5-year survival probability of 23.3%), intermediate- (n = 29, 5-year survival probability of 9.9%) and high-risk (n = 15) patients. Elevated pretreatment serum levels of sVCAM-1 and of lactate dehydrogenase correlate with poor outcome in metastatic cutaneous malignant melanoma. These data support risk stratification for future therapeutic trials and identify factors that need to be validated in prospective studies and may potentially influence decision-making in palliative management of patients with disseminated cutaneous malignant melanoma.     

An embryo-specific expressing TGF-β family protein,growth-differentiation factor 3 (GDF3), augments progression of B16 melanoma

Malignant tumor cells often express embryonic antigens which share the expression with embryonic stem (ES) cells. The embryonic antigens are usually encoded by ES cell-specific genes, a number of which are associated with tumorigenesis and/or tumor progression. We examined the expression of ES cell-specific genes in the mouse B16 melanoma cell line to identify the factors promoting tumorigenesis. We found that endogenous growth-differentiation factor 3 (GDF3) expression was induced in implant B16 tumor during tumor progression in syngenic C57BL/6 mice. B16 F10, a subline with a high metastatic potential, continuously expressed GDF3 while low metastatic B16 F1 expressed comparatively decreased levels of GDF3. Overexpression of GDF3 promoted growth of implanted melanoma B16 F1 and F10 in syngenic mice. Ectopic expression of GDF3 was accompanied by an increased level of production of CD24/CD44. Such a profile was reported to be characteristic of melanoma stem cell-like cells. GDF3 expression was observed in embryonal carcinomas, primary testicular germ cell tumors, seminomas and breast carcinomas. However, the role of GDF3 in these cancers remains undetermined. Overexpression of GDF3 did not affect the growth of mouse hepatoma high or low metastatic sublines G5 or G1, both of which do not express GDF3. Since GDF3-driven CD24 acts as a receptor for endogenous innate immune ligands that modulate cell proliferation, CD24 is an effective determinant of tumorigenesis in malignant cell transformation. Finally, our results support the view that GDF3 has the ability to induce progression of CD24-inducible melanoma in mice.     

Cancer, soleil et UV. Quelle protection ?

Skin cancer is the most frequently occurring malignancy. It is influenced by an individual’s susceptibility factors (phototype and pigmentary traits) and exposure to solar ultraviolet radiation, although the type of exposure (high intensity and short duration vs. chronic) and pattern of exposure (continuous vs. intermittent) may differ among the three main types of skin cancer. Squamous cell carcinoma is influenced by chronic exposure, while basal cell carcinoma and melanoma are influenced by intermittent exposure, especially during childhood. Artificial UV tanning increases the risk of melanoma and squamous cell carcinomas. The prevention of skin cancer is based on reducing exposure to the sun (seeking shadow and using clothing). There is limited evidence suggesting that the use of sunscreen can prevent squamous cell carcinoma, but its role in preventing basal cell carcinoma and cutaneous melanoma remains uncertain. The use of sunscreen can lead to longer periods of sun exposure. Exposure to solar ultraviolet radiation has been shown to reduce the incidence and lethality of some cancers (breast, colon, prostate and lymphomas). A mechanism involving vitamin D has been hypothesised and is currently under investigation.     

Effect of GSTM1 polymorphism on risks of basal cell carcinoma and squamous cell carcinoma: a meta-analysis

Glutathione S-transferases are important enzymes in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. Glutathione S-transferase M1 (GSTM1) null genotype may be a candidate genetic polymorphism with a role in susceptibility to skin cancer such as basal and squamous cell carcinomas. We conducted a systematic review and meta-analysis to define the effect of GSTM1 null polymorphism on skin cancer risk. We searched the PubMed, Embase, and Web of Science databases to identify published case–control studies investigating the association between GSTM1 null genotype and skin cancer risk. Between-study heterogeneity was assessed using the I ² statistic. Odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI) from individual studies were pooled using fixed and random effects models. Nineteen case–control studies (4,275 cases and 4,255 controls) were considered eligible and included in the meta-analysis, and 11 of which were on basal cell carcinoma; ten, on melanoma, and seven, on squamous cell carcinoma. Overall, the GSTT1 null genotype was not associated with the risk of skin cancer (OR, 1.01; 95 % CI 0.93–1.11; P?=?0.76). Subgroup analysis by histological types showed that GSTT1 null genotype was not associated with risks of basal cell carcinoma (OR, 1.06; 95 % CI 0.92–1.21; P?=?0.42), squamous cell carcinoma (OR, 0.97; 95 % CI 0.76–1.24; P?=?0.80), and cutaneous malignant melanoma (OR, 1.00; 95 % CI 0.88–1.14; P?=?0.60). Therefore, this meta-analysis suggests that GSTM1 null polymorphism is not associated with risks of basal and squamous cell carcinomas.     

The Danish case-control study of cutaneous malignant melanoma. II. Importance of UV-light exposure

A population-based case-control study of 474 patients with cutaneous malignant melanoma and 926 population controls, conducted in East Denmark over a 3-year period, included an evaluation of the relationship of UV-light exposure to cutaneous melanoma risk. Patients with lentigo maligna melanoma were not included. Significantly increased risk was associated with severe sunburn before age 15 (RR = 2.7 for 5 + vs. never), sunbathing (RR = 1.6), boating (RR = 1.4) and vacations spent in the sun (RR = 1.4 for very sunny vs. never). A significant decrease in risk was associated with occupational exposure during the summer in males (RR = 0.7), and no association with cutaneous microtopography was seen. These findings were independent of the effects of constitutional risk factors (naevi, freckles and light hair colour). No association was found between the risk of cutaneous melanoma and exposure to artificial UV-light (fluorescent light, sun lamps, or sun beds). No significant difference was found between superficial spreading melanoma and nodular melanoma with regard to any of the sun exposure variables. Our data indicate that exposure to intermittent intense sunlight is an important risk factor for cutaneous malignant melanoma, while long-term continuous exposure does not appear to be risk factor.     

Transplantation of human tumors in nude mice.

Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.     

Desmoplastic malignant melanoma: A light and electron microscopic study of two cases.

This light and electron microscopic study of two recent cases of desmoplastic malignant melanoma (DMM) attempts to resolve the conflict in views regarding the nature of the cells responsible for the desmoplasia associated with this clinicopathologic entity. On the basis of evidence presented, it is concluded that the cells are dedifferentiated tumor cells with fibroblastic features and probably functions, rather than host engendered fibroblasts in response to invasive melanoma. The evidence includes: observation of macular desmosomes between tumor cells, an unheralded feature previously noted in amelanotic and melanotic melanomas; electron microscopic observation of fibroblast-like cells by others in spindle cell squamous carcinomas; and light microscopic features of malignancy including vascular invasion in one of the two cases. A reproducible light microscopic pattern diagnosis of this variant of malignant melanoma is reaffirmed in both cases.     

Clinico-pathologic studies on 143 cases of tonsillar malignancies with special reference to lymphomas]

143 cases of tonsillar malignancies consulted or treated in our hospital during the past 33 years (1958-1991) were studied morphologically and histochemically. There were 126 non-Hodgkin's lymphomas (NHL), 14 squamous cell carcinomas and one each of mucoepidermoid carcinoma, malignant melanoma and histiocytic lymphoma. The results showed that: 1. The ratio of peripheral T-cell and B-cell lymphoma was high (2.08:1), of which the reason is unexplained, 2. Many tonsillar NHLs had been misdiagnosed as undifferentiated carcinomas, poorly differentiated carcinomas or reticular cell sarcomas in the past, and 3. Most of the B-cell lymphomas belong to the high grade malignant large cell lymphomas, like the large non-cleaved and immunoblastic type. These findings are different from what is generally believed and known.     

Sensitivity and specificity of confocal laser-scanning microscopy for in vivo diagnosis of malignant skin tumors

BACKGROUND: Melanoma and nonmelanoma skin cancer are the most frequent malignant tumors by far among whites. Currently, early diagnosis is the most efficient method for preventing a fatal outcome. In vivo confocal laser-scanning microscopy (CLSM) is a recently developed potential diagnostic tool. METHODS: One hundred seventeen melanocytic skin lesions and 45 nonmelanocytic skin lesions (90 benign nevi, 27 malignant melanomas, 15 basal cell carcinomas, and 30 seborrheic keratoses) were sampled consecutively and were examined using proprietary CLSM equipment. Stored images were rated by 4 independent observers. RESULTS: Differentiation between melanoma and all other lesions based solely on CLSM examination was achieved with a positive predictive value of 94.22%. Malignant lesions (melanoma and basal cell carcinoma) as a group were diagnosed with a positive predictive value of 96.34%. Assessment of distinct CLSM features showed a strong interobserver correlation (kappa >0.80 for 11 of 13 criteria). Classification and regression tree analysis yielded a 3-step algorithm based on only 3 criteria, facilitating a correct classification in 96.30% of melanomas, 98.89% of benign nevi, and 100% of basal cell carcinomas and seborrheic keratoses. CONCLUSIONS: In vivo CLSM examination appeared to be a promising method for the noninvasive assessment of melanoma and nonmelanoma skin tumors.