Dysplastic Naevi Research Articles

Utility of the Wood's light: five cases from a pigmented lesion clinic

We demonstrate the utility of the Wood's light in a practice that specializes in the evaluation of pigmented lesions. The Wood's light assisted the physician in locating the site of a completely regressed primary cutaneous melanoma, determining the clinical borders of a lentigo maligna melanoma, differentiating between agminated naevi and a naevus spilus and detecting the recurrence of pigmentation after the excision of a dysplastic naevus, and also proved useful in monitoring a large segmental speckled atypical lentiginous naevus for change. Despite the availability of many 'high-tech' imaging and diagnostic devices designed to evaluate skin lesions, the relatively simple Wood's lamp continues to be of great value. We encourage physicians not to abandon the use of the Wood's light in their clinical practice.

Dermoscopy of skin lesions in two patients with xeroderma pigmentosum

Xeroderma pigmentosum (XP) is a rare disorder produced by a genetic defect in the repair of DNA damage caused by ultraviolet radiation. The early diagnosis of malignant skin tumours is crucial in the survival of patients with XP, but this is not easy even for experienced dermatologists due to the presence of a high number of actinic lesions. Dermoscopy is a new diagnostic method that increases the diagnostic accuracy for skin tumours. To describe the clinical and dermoscopic features of different benign and malignant lesions [focusing on malignant melanoma, basal cell carcinoma (BCC) and benign melanocytic naevi] in two patients with XP. Three dermatologists with experience in pigmented skin lesions and dermoscopy examined two siblings with XP over a period of 54 months. Diagnosis of skin tumours was obtained using clinical examination and dermoscopy with 10-fold magnification and digital images. All the tumours with criteria of malignancy were excised for further histopathological analyses. Multiple skin tumours showing some degree of pigmentation were detected in the patients. Clinical and dermoscopic examination allowed the discrimination of four melanomas (three of them in situ), 26 BCCs and five dysplastic naevi from other pigmented skin lesions. The features and parameters previously described for dermoscopy were shown to be appropriate for the recognition of tumours in our patients with XP. Generalized actinic lentigos were distinguished from BCCs by the presence of a delicate brown pigmented network. Fine vessels from poikiloderma were differentiated from the arborizing telangiectasia of BCC. The dermoscopic findings in the tumours were similar to those previously described in patients not affected by XP. Diagnosis by dermoscopic pattern analyses allowed a correct classification of malignant tumours in these cases.

Inheritance of malignant melanoma in the melim strain of miniature pigs

Selective breeding of miniature pigs bearing cutaneous tumours resulted in the establishment of the MeLiM strain with hereditary malignant melanoma. The inheritance of melanoma was tested in a two-generation kindred comprising 456 progeny from 78 litters. Melanomas were recognisable visually as black-pigmented lesions on the skin. Their size, shape, number, progression and metastatic spreading varied widely. All possible melanoma forms known in human melanoma, i.e. pigmented naevi, dysplastic naevi, superficial spreading melanoma and nodular malignant melanoma, were found in the MeLiM pigs. Because the occurrence of nodular malignant melanoma segregated in all recorded litters we have included only this form in the genetic analysis. The tumours were nodular with exophytic growth over the skin surface. All showed similar histopathological features, vertical growth to muscle fascia and high metastatic activity. We hypothesize, on the basis of segregation ratios obtained from various mating types, that the mode of inheritance of nodular melanoma in the MeLiM strain is probably controlled by three genes.

Cutaneous melanoma in childhood and adolescence: retrospective study of 32 patients

This study was performed to analyse the behaviour, risk factors, prognosis and evolution of cutaneous melanoma in childhood and adolescence treated in a single institution. A retrospective study was performed between 1980 and 2000 of patients aged 18 years or younger followed at the Hospital do Cancer de Sao Paulo, Brazil. Data included demographic status, risk factors, clinical and histopathological characteristics of the primary and metastatic lesions, stage and follow-up. Seventeen female (53.1%) and 15 male (46.9%) patients were studied. Twelve patients (37.5%) were aged 12 years or younger. The trunk was the most common location (14 patients; 43.8%). Five patients (15.6%) had giant congenital melanocytic naevus, three (9.4%) had xeroderma pigmentosum and one (3%) had dysplastic melanocytic naevus. Nodular melanoma was the most frequent histological type and 43.8% had a thickness of more than 4 mm. Five of the 32 patients (15.6%) were lost to follow-up and 15 (46.9%) were alive at the last year's follow-up, 11 (34.4%) without disease and four (12.5%) with active disease. The 5-year overall survival was 64.34%. An overall survival of 11.71% was found in patients with visceral metastasis with or without cutaneous and/or lymph node involvement, whereas the corresponding value was 90.48% (P value=0.0002) in patients with only cutaneous and/or lymph node metastasis. Cutaneous melanomas are uncommon in the young and are seldom diagnosed in the early stages, perhaps due to a reluctance to accept this diagnosis in this age group. Prevention and early stage diagnosis depend upon the recognition that this disease is present in the young.

Melanocytic Lesions of the Face: Diagnostic Pitfalls

The pathologist often has a difficult task in evaluating melanocytic lesions. For lesions involving the face the consequences of misdiagnosis are compounded for both cosmetic and therapeutic reasons. In this article, the pathological features of common and uncommon benign and malignant melanocytic lesions are reviewed and pitfalls in their diagnosis are highlighted. Benign lesions resembling melanomas include regenerating naevus, “irritated” naevus, combined naevus, “ancient naevus”, Spitz naevus, dysplastic naevus, halo naevus, variants of blue naevi, balloon and clear cell naevi, neurotised naevus and desmoplastic naevus. Melanomas that can easily be missed on presentation include desmoplastic, naevoid, regressed, myxoid and metastatic types as well as so-called malignant blue naevi. Pathological clues to benign lesions include good symmetry, V-shaped silhouette, absent epidermal invasion, uniform cellularity, deep maturation, absent or rare dermal mitoses and clustered Kamino bodies. Features more commonly present in melanomas include asymmetry, peripheral epidermal invasion, heavy or “dusty” pigmentation, deep and abnormal dermal mitoses, HMB45 positivity in deep dermal melanocytes, vascular invasion, neurotropism and satellites. Familiarity with the spectrum of melanocytic lesions and knowledge of the important distinguishing features should assist in interpretation. Occasionally, the use of ancillary studies may also provide additional useful information. Application of standard criteria for diagnosing such lesions should enable the correct diagnosis to be established in most cases.

Common and uncommon variants of melanocytic naevi

Numerous variants of melanocytic naevi have been described. Their main pathological significance lies in their distinction from melanoma, as well as being precursors and risk markers for melanoma. Various degrees of atypia such as cytological atypia, architectural disorder and pagetoid spread (pagetoid melanocytosis) may be present in naevi and need to be recognised as appropriate for the subtype. As well as the distinction from melanoma, naevi must be differentiated from atypical lesions, such as atypical Spitz tumours, which do not fulfil all the criteria of melanoma, may be benign or malignant and have been called 'melanocytic tumours of unknown malignant potential'. The diagnostic grey area also includes a group of benign atypical naevi which are difficult to subclassify into specific entities. In this paper naevi are divided into: firstly, the common acquired group with a brief discussion of junctional, compound and intradermal naevi, minor variants such as halo and balloon naevi and the major variants that may cause problems -- dysplastic naevi, naevi of special sites, recurrent naevi and Spitz naevi; secondly, congenital naevi; thirdly, blue naevi and related lesions (dermal melanocytoses); and finally, combined naevi. The emphasis is on diagnostic pathological features and the differential diagnosis with melanoma.

The approach to the patient with a difficult melanocytic lesion

Although most histological diagnoses are made with relative ease and with great specificity and reproducibility, there is a subset of cases in which a specific and reproducible diagnosis is difficult or even impossible to render. In the melanocytic system, these cases can be divided into two broad categories. The first category, 'superficial atypical melanocytic proliferations of uncertain significance' (SAMPUS), includes predominantly junctional melanocytic proliferations, and melanocytic proliferations that are confined to the epidermis and papillary dermis, without evidence of tumorigenic proliferation or mitotic activity there. The prognosis for cure of these lesions is excellent if they are completely excised. Such lesions may include, for example, dysplastic naevi, Spitz naevi or pigmented spindle cell naevi with a few atypical melanocytes above the dermal-epidermal junction, or with greater than average cytological atypia, or with mitoses, where the differential diagnosis of melanoma in situ is difficult or impossible to rule out. The other category, 'melanocytic tumours of uncertain malignant potential' (MELTUMP), is comprised of melanocytic proliferations that form tumours in the dermis, and are therefore potentially capable of metastasis. Examples of such lesions may include atypical Spitz naevi, deep penetrating naevi, possible naevoid melanomas, or cellular blue naevi, where because of increased mitotic activity or cytologic atypia, a diagnosis of invasive or tumorigenic melanoma cannot be ruled out. In managing such lesions, we follow two main principles. The first is to manage each lesion with therapy designed to be adequate for management of the most significant consideration in the differential diagnosis. The second principle is to make clinicians and patients specifically aware of the diagnostic difficulty in their lesion, so that management can be undertaken on a true informed consent basis.

Ectopic expression of tyrosinase increases melanin synthesis and cell death following UVB irradiation in fibroblasts from familial atypical multiple mole and melanoma (FAMMM) patients.

Patients with familial atypical multiple mole and melanoma (FAMMM) [so-called familial dysplastic naevus syndrome (FDNS)] have a high risk for the development of malignant melanoma. The underlying gene defect has an autosomal dominant inheritance with variable expression and incomplete penetrance. Fibroblasts derived from FAMMM patients have high sensitivity to UVC and mutagens, e.g. 4-nitroquinoline-1-oxide. We were interested in identifying how the combination of inherent sensitivity to UV light and abnormal melanin synthesis interacts in the development of melanoma in FAMMM patients. Intermediates of melanin synthesis produce free radicals that are toxic to cells. Atypical moles (dysplastic naevi) are engaged in the biosynthesis of abnormal melanin pigments. This study examined whether there was any abnormal melanin pigmentation or cell damage after the ectopic expression of tyrosinase in fibroblasts from FAMMM patients when compared with fibroblasts from normal subjects. Fibroblasts from FAMMM patients (3012T and 3072T) were associated with a higher sensitivity than normal human fibroblasts to the toxicity of UVB. When cells were infected with tyrosinase-expressing adenovirus (Ad-HT) and irradiated with UVB, FAMMM fibroblasts showed higher tyrosinase activity, produced more melanin pigments and were degraded more significantly than normal human fibroblasts. Western blot analysis revealed that Ad-HT-infected 3072T produced a larger amount of tyrosinase protein than did Ad-HT-infected normal fibroblasts after UVB irradiation. Our findings suggest: (1) that FAMMM fibroblasts have an unknown machinery which enhances tyrosinase expression by UVB irradiation; and (2) that the resulting increase in melanin synthesis affects the cytotoxicity of UVB to FAMMM fibroblasts. All of these processes may be involved in the genomic instability and development of melanoma in FAMMM patients.

Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi

Dysplastic naevi (DN) are a known risk factor for malignant melanoma. Their occurrence is closely connected with the degree of skin pigmentation. People with a light complexion are more likely to develop DN than dark-skinned individuals. We examined the proposition that DN exhibit altered melanin formation, which may be involved in their malignant transformation. X-ray microanalysis was used to study the composition of melanosomes from DN and to compare the results with those obtained from melanomas, banal (dermal) naevi and normal cutaneous melanocytes. We analysed sulphur (an indicator of phaeomelanin) and two metals, iron and calcium, involved in oxidative stress. FACS analysis of dihydrorhodamine-123-labelled cells was employed to quantify differences in the production of radical oxygen species in DN cells and normal skin melanocytes. A significantly higher sulphur content was found in melanosomes from DN cells and melanoma cells when compared with normal melanocytes and naevus cells from banal naevi. In addition, melanosomes of DN cells and melanoma cells contained higher amounts of iron and calcium. In the case of calcium, this was associated with a significantly elevated cytoplasmic concentration. FACS analysis showed that DN cells exhibited higher concentrations of radical oxygen species than normal skin melanocytes from the same individuals. We propose that increased phaeomelanogenesis in DN cells is connected with oxidative imbalance, which is reflected by increased intracellular concentrations of reactive oxygen species and raised calcium and iron concentrations. We show that the metabolic alterations in DN cells resemble those found in melanoma cells. Our findings provide support for the idea that DN cells are true precursor lesions of melanoma.

Characterization of digital medical images utilizing support vector machines.

BackgroundIn this paper we discuss an efficient methodology for the image analysis and characterization of digital images containing skin lesions using Support Vector Machines and present the results of a preliminary study.MethodsThe methodology is based on the support vector machines algorithm for data classification and it has been applied to the problem of the recognition of malignant melanoma versus dysplastic naevus. Border and colour based features were extracted from digital images of skin lesions acquired under reproducible conditions, using basic image processing techniques. Two alternative classification methods, the statistical discriminant analysis and the application of neural networks were also applied to the same problem and the results are compared.ResultsThe SVM (Support Vector Machines) algorithm performed quite well achieving 94.1% correct classification, which is better than the performance of the other two classification methodologies. The method of discriminant analysis classified correctly 88% of cases (71% of Malignant Melanoma and 100% of Dysplastic Naevi), while the neural networks performed approximately the same.ConclusionThe use of a computer-based system, like the one described in this paper, is intended to avoid human subjectivity and to perform specific tasks according to a number of criteria. However the presence of an expert dermatologist is considered necessary for the overall visual assessment of the skin lesion and the final diagnosis.

XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk.

We recently reported an association between low DNA repair capacity, measured through the host-cell reactivation assay, and melanoma risk in subjects with dysplastic naevi or low tanning ability. We investigated the genetic basis for these findings by analysing the Asp312Asn and Lys751Gln polymorphisms of the XPD (ERCC2) DNA repair gene in the same subjects. Similar to our previous report, no significant association between XPD polymorphisms and melanoma risk was found in 176 melanoma cases and 177 controls (odds ratio (OR)=1.5, 95% confidence interval (CI)=0.9–2.5 for 312Asn; OR=1.3, 95% CI=0.8–2.1 for 751Gln, adjusted for age, gender, dysplastic naevi and pigmentation characteristics). However, XPD variants were associated with increased risk in older (>50 years) subjects (OR=3.4, 95% CI=1.6–7.3 for 312Asn; OR=2.3, 95% CI=1.1–4.9 for 751Gln). The 751Gln allele was associated with elevated melanoma risk among subjects without dysplastic naevi (OR=2.6, 95% CI=1.1–6.4). Subjects with low tanning ability and XPD variants exhibited a nonsignificant increase of melanoma risk (OR=2.3, 95% CI=0.7–7.0 for 312Asn; OR=3.0, 95% CI=1.0–8.8 for 751Gln). DNA repair capacity was slightly decreased in subjects carrying 751Gln alleles. XPD variants may modify melanoma risk in subjects with specific host characteristics, such as older age, lack of dysplastic naevi or low tanning ability.

Histopathological characteristics of small diameter melanocytic naevi

Background/Aims: The clinical definition of an atypical naevus (“dysplastic naevus” or “naevus with architectural disorder and cytological atypia of melanocytes”) stresses size larger than 5 mm in diameter as a...

Assessment of genetic instability in melanocytic skin lesions through microsatellite analysis of benign naevi, dysplastic naevi, and primary melanomas and their metastases.

Microsatellite instability (MSI) is caused by replication errors due to deficient DNA mismatch repair and has been associated with tumour progression in various types of cancer. Controversial results have been reported concerning the frequency and significance of MSI in malignant melanoma. In this study, the time of onset and relative incidence of MSI were determined during the progression of melanocytic tumours, starting with benign melanocytic naevi. MSI was studied at 13 loci containing single, di- or trinucleotide repeat sequences and mapping to five different chromosomal locations. Tumours were classified as being low frequency MSI (L-MSI+) or high frequency MSI (H-MSI+) when either one or at least two marker loci, respectively, displayed mutant alleles in tumour DNA compared with the corresponding normal tissue DNA. None of the eight melanocytic naevi studied showed MSI, whereas a moderate frequency of H-MSI was detected in dysplastic naevi (one out of 11; 9%) and primary melanomas (six out of 56; 11%). The incidence of H-MSI was increased in melanoma metastases from the same patients (nine out of 42; 21%). In contrast to previously reported data showing higher rates of MSI in melanoma, genetic instability seems to be present in a minority of malignant melanoma lesions. However, our findings are consistent with the hypothesis that MSI may be sequentially induced during malignant evolution, contributing to the progression of a subset of melanocytic tumours.

Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis.

12-Lipoxygenase (12-LOX), through its metabolite 12( )-hydroxyeicosatetraenoic acid [12( )-HETE], has been demonstrated to play a pivotal role in experimental melanoma invasion and metastasis, and 12-LOX expression may be important in early human melanoma carcinogenesis. We have studied the differences in 12-LOX protein expression during the progression of melanoma from human melanocytic cells to benign and dysplastic naevi to malignant metastatic disease. 12-LOX expression was determined in normal human skin melanocytes and in melanocytes found in compound naevi, dysplastic naevi and melanomas using a platelet-type 12-LOX antibody with a diaminobenzidine immunoperoxidase system detection system and was quantified using the analysis software NIH Image 1.62. Mean cellular pixel densities for 12-LOX staining ( = 50 cells/histological type) were unchanged in compound naevi ( = 0.14) and were increased in dysplastic naevi and melanomas compared with normal skin melanocytes ( = 0.03 and = 0.01, respectively). Similarly, melanomas had higher levels of expression compared with dysplastic naevi ( = 0.03). 12-LOX expression was significantly different between compound naevus and dysplastic naevus melanocytes ( = 0.01). These data suggest that 12-LOX may be an important novel marker for cancer progression within the melanoma system, and therefore could be a useful biomarker and therapeutic target for melanoma chemoprevention.

Spitz naevi may express components of the plasminogen activation system.

The plasminogen activation (PA) system is involved in the process of invasion and metastasis. Its major components are urokinase (uPA) and tissue-type plasminogen activator (tPA), plasminogen activation inhibitor type 1 and 2 (PAI-1 and PAI-2) and a receptor for urokinase (uPAR). In this study, the expression of plasminogen activation components in Spitz naevi was compared with that in common and dysplastic naevi on the one hand and primary cutaneous melanomas on the other. Spitz naevi had melanocytic positivity for uPA in 0% (0/36), tPA in 30% (6/20), PAI-1 in 10% (3/35), PAI-2 in 40% (8/21) and uPAR in 60% (13/21) of cases. This far exceeded the expression found in common (n = 25) and dysplastic (n = 15) naevi, which only showed melanocytic positivity for PAI-2 (20% and 15% respectively) and in one dysplastic naevus also for uPAR. This was much (for most components significantly) less than the proportion of primary melanomas with tumour cell positivity, which was 30% (11/38) for uPA, 80% (19/24) for tPA, 75% (28/38) for PAI-1, 80% (19/24) for PAI-2 and 80% (19/24) for uPAR. The main findings of this study are that Spitz naevi, firstly, may express plasminogen activator (tPA), inhibitors and the receptor of the PA system, but in a much smaller proportion than cutaneous melanomas; and secondly, do not express urokinase, whereas some of the melanomas do. uPA positivity may therefore be suggestive of melanoma. However, overlapping staining results imply that the PA system has limited value in the differential diagnosis between Spitz naevus and primary melanoma. As serine protease components are expressed, Spitz naevi may use this proteolytic machinery to accomplish matrix degradation, although in a more restricted, possibly transient manner than melanomas.

White dysplastic melanocytic naevi

We describe three cases of a new variant of dysplastic melanocytic naevi (DMN), which is characterised by complete lack of pigmentation. Clinically, white DMN were non-pigmented white to pale-red macules with accentuated skin markings, and had a silvery, shiny appearance under tangential light. Histology showed characteristic features of DMN--ie, non-typical melanocytes arranged as solitary units and nests at the dermoepidermal junction and in the papillary dermis, and mild stromal changes. Association with malignant melanoma in all three patients emphasises the importance of this morphological type of DMN as a possible precursor to, or marker of, malignant melanoma.

Atypical lentiginous junctional naevi of the elderly and melanoma

The diagnosis of atypical lentiginous melanocytic naevi in chronic sun-damaged skin is a clinical and pathological challenge. Mottled skin in the elderly is a result of extensive freckling, guttate hypomelanosis, solar lentigines, seborrhoeic keratoses and small dark lentigines. In addition, atypical lentiginous junctional naevi may be seen as isolated lesions and may merge with lesions that are indistinguishable from lentigo maligna. The predominant site distribution of such lesions on the trunk and limbs and the presence of a nested naevoid pattern on biopsy differs from classical lentigo maligna, which develops mainly on the head and neck. Based on case studies combining dermatoscopy with clinical and pathological features, we have found that atypical lentiginous junctional naevi of the elderly may evolve to lentigo maligna and in some cases to small cell (naevoid) melanomas. Such lesions have been previously classified as dysplastic naevi, atypical melanocytic hyperplasia, atypical melanocytic proliferation, atypical lentiginous melanocytic proliferation or premalignant melanosis (McGovern). The current definition of lentigo maligna appears too narrow and the pathway to lentigo maligna in the elderly skin may include a naevoid subset.

Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions.

When a biopsy is taken of a suspicious pigmented skin lesion, histological examination is expected to establish the definitive diagnosis. This study evaluated the inter-observer variation of 20 pathologists in the histological diagnosis of a randomly selected set of suspicious pigmented skin lesions (PSLs), by comparing their diagnoses to a reference diagnosis. Overall sensitivity for melanoma was 87%, ranging from 55% to 100% between the observers. Sensitivity was significantly lower for thin (Breslow thickness <1 mm) than for thick melanomas (83% versus 97%, p=0.005). Overall melanoma specificity was 94%, ranging from 83% to 100% between observers. Dysplastic naevus was the most important source of false-positive diagnoses, mainly in situ melanomas. Positive and negative predictive values in the given test set were 75% and 97%, respectively. In the case of melanoma, there was quite some variation in measured Breslow thickness. This would have led to a different therapeutic approach in 12% of the readings. Some of the variation seemed to be due to a different interpretation of the presence of a co-existent naevus. In 9% (3/35) of the readings, participants did not agree on the presence of ulceration. These results reflect a tendency to overdiagnose mainly thin melanomas in general histopathological practice. They also demonstrate variation in the assessment of major prognostic factors of melanoma.

Rarity of CDK4 germline mutations in familial melanoma.

To date, two genes have been implicated in melanoma pathogenesis. The first, CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second, CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons of CDK4 and screened additional members of two previously reported families with the Arg24Cys germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4 mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, although CDK4 is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.

In vitro transformation of human congenital naevus to malignant melanoma.

The incidence of melanoma is estimated to be growing at the second fastest rate among all cancers in the United States. The progression of the melanocyte to a malignant melanoma involves various sequential steps: development of benign naevocellular naevus, preneoplastic dysplastic naevus, primary melanoma, and metastatic melanoma. Despite these clearly defined stages, very little is known about the molecular events leading to melanoma progression. We established a human congenital naevus cell line (UISO-CMN-1). UISO-CMN-1 cells were confirmed to have melanocytic origin by S100 immunoreactivity and the presence of melanin granules and melanosomes. UISO-CMN-1 cells, even though they showed structural and numerical abnormalities in karyotype, were non-tumorigenic when transplanted into athymic mice. However, following frequent exposure to ultraviolet C radiation, UISO-CMN-1 cells acquired tumorigenic potential. Transformation of UISO-CMN-1 cells into tumorigenic cells was accompanied by induction of ganglioside-2 expression without any significant changes in cellular ganglioside-3. These transformed and non-transformed UISO-CMN-1 cell lines can serve as excellent research tools for studying the molecular changes associated with melanoma development and progression, and for identifying agents that might prevent development of malignant melanoma.