Genetic and Epidemiologic Evaluation of Dysplastic Nevi

Dysplastic Nevus Syndrome (DNS) has been defined as that trait characterized by the presence of at least one dysplastic melanocytic nevus. DNS was originally described in kindreds having multiple members with melanoma. Various types DNS have been described in other situations to include individuals with apparently sporadic cases, familial DNS without melanoma and individuals with apparently sporadic DNS with melanoma. These categories are based on historical information in general, and not on examination of family members. In all cases, the presence of dysplastic nevi appear to confer some increased risk of melanoma, which varies between the groups. Similarly cutaneous melanoma is thought to occur in several distinct populations-random individuals without DNS, individuals with sporadic DNS, and those with familial DNS. Genetic analysis of DNS has been largely confined to the classically ascertained kindreds associated with melanoma. These studies have usually used diagnostic criteria based on pathology of clinically selected material, and that evidence suggests that DNS is inherited as an autosomal dominant trait in these families. Surveys of the general population have detected rates of dysplastic nevi of 5% 20%. In our Utah-based studies, we have evaluated probands and family members from three groups. These included kindreds with multiple occurrences of melanoma, random individuals with at least one dysplastic nevus, and cases of melanoma with unknown family history. Controls were spouses of study subjects. We sought to determine the percentage of each group associated with dysplastic nevi and/or genetic DNS. The range of phenotype of patients with dysplastic nevi was large with some individuals having few nevi, none of which were clinically atypical, and others having greater than 100 nevi. The prevalence of dysplastic nevi in at least one of two biopsies in Utah population controls is presently Wtimated at 62%. Some probands with melanoma as well as some of their relatives had elevated numbers of nevi, suggesting that this predisposition to melanoma may be inherited.     

Black lesions of the skin

Benign melanocytic lesions include lentigo, ephelid (freckle), pigmented nevus, sacral spot, blue nevus, and combined nevus and blue nevus. Malignant melanocytic lesions are melanomas, which arise from melanocytes at the epidermodermal junction, or, rarely, from blue nevi. They usually originate in brown plaques known as lentigo maligna, in pigmented nevi, or in normal skin. Melanoma is diagnosed clinically in less than 50 per cent of instances. Biopsy is therefore of great importance, since practically all melanoma can be cured by adequate early resection.     

Dysplastic nevus--risk factor or disguise for melanoma

Dysplastic nevus is an acquired or hereditary nevus that clinically seems atypical and pathohistologically dysplastic. The term of dysplastic nevus has changed through history and even until now the dermatologists and pathologists have not found the same conclusion for name and definition of dysplastic nevus. Epidemiology of dysplastic nevus is different depending on geographic lattitude, being three times higher in Australia than in Great Britain. Genetic factors play a role in etiology of dysplastic nevus but are still not well defined. UV radiation is indisputable main etiological factor in developing dysplastic nevus. Many studies confirm that children who have been using sun protection creams with SPF have less dysplastic nevi than those who did not. Nevus with geographic shape and muddy borders, dominately macular, red to brown colored and has 5 mm or more in diameter is clinically dysplastic nevus. ABCDE rules count for dysplastic nevus as well as for melanoma but prefferable diagnostic criteria for dysplastic nevus would be "ugly duckling sign". Pathohistologic analysis is the key in confirming the diagnosis of dysplastic nevus. Great experience and knowledge in dermatopathology field is essential for pathologists to make a distinction between dysplastic nevus and melanoma in situ. Likewise great experience in dermatooncology field is essential in differentiating dysplastic nevus from other nevi. Surgical excision is the only therapy that should be done for dysplastic nevus. Regular follow up is highly recommended for patients with dysplastic nevus and syndroma naevi dysplastic. Education about sun protection measures and self-examination techniques is essential for all patients with dysplastic nevi and their family.     

Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features

Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC). A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001). The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001). Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC) compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.     

BLACK LESIONS OF THE SKIN

Benign melanocytic lesions include lentigo, ephelid (freckle), pigmented nevus, sacral spot, blue nevus, and combined nevus and blue nevus.Malignant melanocytic lesions are melanomas, which arise from melanocytes at the epidermodermal junction, or, rarely, from blue nevi. They usually originate in brown plaques known as lentigo maligna, in pigmented nevi, or in normal skin.Melanoma is diagnosed clinically in less than 50 per cent of instances. Biopsy is therefore of great importance, since practically all melanoma can be cured by adequate early resection.     

Comparison of image analysis with flow cytometry for DNA content analysis in pigmented lesions of the skin.

The DNA ploidy of 85 melanocytic skin lesions was determined by flow cytometry (FCM) and interactive image analysis (IA) using nuclear extracts of paraffin-embedded tissue. Of the 85 lesions analyzed, 43 were malignant melanomas in different stages of evolution, 15 were dysplastic nevi, 11 were Spitz nevi, and 16 were other types of nevi. Some of the last had features of congenital nevi. Within the melanoma category, there was 42% aneuploidy by FCM versus 56% by IA. Of those melanomas aneuploid by FCM, all but one were aneuploid by IA. All dysplastic nevi, 10/11 Spitz nevi and 15/16 other nevi were diploid by both methods. One of the 16 nevi from the "other types" category was tetraploid by IA but diploid by FCM. A single Spitz nevus was tetraploid by FCM but diploid by image analysis. While our results suggest that interactive IA is potentially a more sensitive method than FCM for detecting aneuploidy in cutaneous pigmented lesions, it remains to be shown whether this will translate into better prognostic assessment of the biologic behavior of melanocytic neoplasms than provided by flow cytometric ploidy analysis.     

Dermatoscopy and High Frequency Sonography: Two Useful Non-Invasive Methods to Increase Preoperative Diagnostic Accuracy in Pigmented Skin Lesions

Dermatoscopy and high frequency sonography have recently been combined to increase diagnostic preoperative accuracy in the treatment of pigmented skin lesions. In this monocentric study 80 patients with pigmented skin lesions were evaluated clinically, by dermatoscopy, and 20 MHz-sonography followed by dermatohistopathological evaluation; 39 malignant melanomas, 37 common nevi, 3 dysplastic nevi, and 1 nevus Spitz were diagnosed histologically. In 72 of the 80 cases (91.3%) dermatoscopical diagnoses were confirmed by histopathology, compared to only 79% correct clinical diagnoses. For the mere clinical diagnosis of melanoma sensitivity was 79%, specificity was 78% and diagnostic accuracy was 65%. All diagnostic values increased by dermatoscopy: sensitivity reached 90%, specificity was 93%, and diagnostic accuracy was 83%. In order to determine tumor thickness preoperatively tumor thickness was measured by 20 MHz sonography. The correlation of tumor thickness between histometric and sonographic results was determined for nevi (r = 0.93) and melanoma (r = 0.95); 74.3% of melanomas were diagnosed correctly within an 0.2 mm range. Regarding the clinical important limit of 1 mm tumor thickness, 87.2% were diagnosed in accordance with histometric evaluation. An increase of 18% in diagnostic accuracy by dermatoscopy and 87.2% of correctly diagnosed cases of tumor thickness of malignant melanoma by high frequency sonography clearly demonstrate that these methods should be considered standard procedures in the diagnosis of pigmented skin lesions and will facilitate the decision on necessary surgical treatment.     

Evaluation of human monoclonal antibody (2-139-1) in cutaneous melanocytic neoplasms in fixed tissue sections.

Despite the growing list of xenogeneic monoclonal antibodies (MAb) that recognize malignant melanoma-associated antigens (MAA) in formalin-fixed, paraffin-embedded tissue, none has been able to detect epitopes found in malignant melanomas and not in melanocytic nevi. A human MAb, 2-139-1, that showed promise in this regard was evaluated against 85 melanocytic neoplasms, including malignant melanoma and histological simulators, particularly Spitz's nevus. MAb 2-139-1 stained 18 (53%) of 34 melanomas, eight (57%) of 14 dysplastic nevi, six (38%) of 16 Spitz's nevi, and three (14%) of 21 banal nevi, which included three small congenital nevi. We observed a significant increasing trend in reactivity (% positive cells x intensity) associated with the potential for malignancy (p for linear trend = 0.002). We conclude that human MAb 2-139-1 is applicable to the study of melanocytic neoplasms in routinely processed tissue. Although the ability of this MAb to separate benign from malignant cells is not absolute, our results suggest that the expression of the 2-139-1 epitope may be an early event in melanocytic tumor progression.     

Dysplastic melanocytic nevi contain high levels of pheomelanin: quantitative comparison of pheomelanin/eumelanin levels between normal skin, common nevi, and dysplastic nevi.

The degree and type of melanogenesis, i.e., either eumelanin of pheomelanin, has been shown to be a reliable marker for the differentiation of the melanocyte. If exposed to UV light, these two melanins were reported to behave differently; eumelanin was photoprotective whereas pheomelanin was phototoxic to cultured tumor cells. Our previous study indicated that dysplastic melanocytic nevus (DMN) undergoes altered melanogenesis, forming pheomelanosome-like granules. The present study examined chemically the type and degree of melanin synthesized in 31 melanocytic nevi excised from 27 patients as compared with that occurring in the surrounding normal skin. The tissue content of eumelanin and pheomelanin was expressed by the amounts of pyrrole-2,3,5-tricarboxylic acid (PTCA) and aminohydroxyphenylalanine (AHP), respectively. We found that DMN lesions contain significantly higher amounts of pheomelanin than either common melanocytic nevus (CMN) or normal skin. Differences in pheomelanin content between DMN and CMN could not be accounted for by inherently higher levels of pheomelanin within the skin in general from DMN patients. Our present finding substantiates our previous claim that epidermal melanocytes in DMN undergo deranged melanogenesis.     

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient's age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.     

Dysplastic Melanocytic Nevi Contain High Levels of Pheomelanin: Quantitative Comparison of Pheomelanin/Eumelanin Levels Between Normal Skin,Common Nevi,and Dysplastic Nevi

The degree and type of melanogenesis, i.e., either eumelanin of pheomelanin, has been shown to be a reliable marker for the differentiation of the melanocyte. If exposed to UV light, these two melanins were reported to behave differently; eumelanin was photoprotective whereas pheomelanin was phototoxic to cultured tumor cells. Our previous study indicated that dysplastic melanocytic nevus (DMN) undergoes altered melanogenesis, forming pheomelanosome-like granules. The present study examined chemically the type and degree of melanin synthesized in 31 melanocytic nevi excised from 27 patients as compared with that occurring in the surrounding normal skin. The tissue content of eumelanin and pheomelanin was expressed by the amounts of pyrrole-2,3,5-tricarboxylic acid (PTCA) and aminohydroxyphenylalanine (AHP), respectively. We found that DMN lesions contain significantly higher amounts of pheomelanin than either common melanocytic nevus (CMN) or normal skin. Differences in pheomelanin content between DMN and CMN could not be accounted for by inherently higher levels of pheomelanin within the skin in general from DMN patients. Our present finding substantiates our previous claim that epidermal melanocytes in DMN undergo deranged melanogenesis.     

Immunohistochemical study of pepsinogen C expression in cutaneous malignant melanoma: association with clinicopathological parameters

BACKGROUND: The aim of this study was to evaluate the pepsinogen C expression in malignant cutaneous melanomas and analyze its possible relationship to clinical and pathological parameters. Pepsinogen C is an aspartyl proteinase primarily involved in the digestion of proteins in the stomach and represents one of the main androgen-inducible proteins in breast cancer cells. METHOD: Tumoral pepsinogen C expression was retrospectively analyzed in 35 paraffin-embedded tissues from patients with primary malignant cutaneous melanoma and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi and 2 dysplastic melanocytic nevi), using immunohistochemical methods. RESULTS: The benign lesions were consistently negative for pepsinogen C, whereas 20 of the 35 malignant melanomas (57%) showed positive immunostaining for pepsinogen C. The percentage of pepsinogen C-positive tumors was significantly higher in men than in women (p=0.01) and in epithelioid melanomas than in fusocellular or mixed type melanomas (p=0.003). In addition, the percentage of pepsinogen-C positive tumors was positively and significantly correlated with lesion thickness (p=0.003), Clark's level of invasion (p=0.028) and tumor stage (p<0.001). CONCLUSION: Pepsinogen C could be a new prognosticator of unfavorable outcome in cutaneous malignant melanoma.     

DNA ploidy and nuclear morphometry for the classification of dysplastic nevi

OBJECTIVE: To examine the diagnostic value of DNA ploidy and nuclear morphometric features in sporadic dysplastic nevi as compared to those in compound nevi and melanoma. STUDY DESIGN: DNA ploidy profiles plus seven direct and three derived nuclear features were obtained in a series of 120 melanocytic skin neoplasms (30 dysplastic nevi [DN], 30 melanomas [MM], 60 compound nevi [CN]) and the results compared. RESULTS: DNA ploidy separated melanomas from benign melanocytic skin neoplasms with 96.5% accuracy in classifying the grouped cases. The derived nuclear shape factor Form PE and nuclear axis ratio were the most successful discriminants separating DN from MM but allowed only 73.3% correct classification of cases. Separation of DN from CN was best achieved using Form PE and mean nuclear area (74.4% correctly classified). Results from compound nevi in subjects < 25 years of age fell between those for DN and MM. CONCLUSION: Quantitative nuclear cytologic characteristics in sporadic dysplastic nevi span a range seen in common nevi through to those in thin melanomas. Cytologic changes in sporadic dysplastic nevi overlap those seen in other melanocytic skin neoplasms. Therefore, other reproducible morphometric features need to be assessed in order to further refine the histopathologic diagnosis of this entity.     

The dysplastic nevus: recognition and management

The recognition of atypical or dysplastic nevomelanocytic nevi potentially provides clinicians with another means of identifying individuals at increased risk for cutaneous malignant melanoma. However, a great deal of controversy still surrounds these lesions, their significance, and the clinical and histologic criteria needed for their diagnosis at present. In general, dysplastic nevi tend to be asymmetrical and larger (greater than 5 mm) than ordinary acquired nevi, have a macular component, irregular and ill-defined borders, and haphazard (variegate) coloration. A clinical diagnosis of dysplastic nevi must be confirmed by histopathology, since not all clinically atypical nevi are dysplastic. While precise histopathologic criteria for dysplastic nevi are lacking, most authorities agree that an abnormal nevomelanocytic proliferative pattern as manifested by increased numbers of basilar melanocytes and/or abnormal junctional nevomelanocytic nesting in the setting of lentiginous epidermal hyperplasia, variable degrees of nevomelanocytic nuclear atypia, and a lymphocytic host response are consistent with a histologic diagnosis of dysplastic nevi. Current data for individuals with dysplastic nevi and a family history of cutaneous malignant melanoma (at least two family members with cutaneous malignant melanoma) indicate a relative risk for cutaneous malignant melanoma about 148 times that of the general population. In comparison, cutaneous malignant melanoma risk seems lower for individuals with familial dysplastic nevi (but without familial cutaneous malignant melanoma) and "sporadic" dysplastic nevi. With respect to progression to melanoma, probably the vast majority of dysplastic nevi remain stable or possibly regress. Management of individuals with histologically confirmed dysplastic nevi involves periodic skin examinations. Regional overview and life-size photography are helpful in following these patients. Patients should also be instructed in the examination of their own skin. While a definite relationship between sun exposure and dysplastic nevi remains unproved, the use of sunscreens and avoidance of unnecessary sun exposure are advised. Examination of family members for atypical melanocytic lesions is also recommended.     

Congenital nevocellular nevus: a review of the treatment controversy and a report of 46 cases

Because congenital nevocellular nevi can be distinguished clinically and histologically from acquired nevi, and because of their apparent increased potential for malignant degeneration, we favor complete one-stage excision of these nevi, regardless of the size of the lesion or the age of the patient, at the earliest opportunity, whenever such surgery is feasible and practical. If there is a question about the clinical diagnosis, a cutaneous punch biopsy can help determine the true nature of the lesion. Significantly, Walton et al. and Rhodes and coworkers found discrepancies in the literature concerning the level of nevus cells in neonates. They concluded that until these differences are reconciled, nevus cells in the deep reticular dermal collagen may be a sufficient, but not a necessary criterion for the diagnosis of congenital melanocytic nevus. We currently favor complete one-stage excision of congenital nevocellular nevi and feel that treatment by tangential excision or dermabrasion require further study. Finally, we present this paper as "advice" not only to the three authors who, in a recent issue of the British Journal of Plastic Surgery, requested it, but also to all clinicians. Hopefully, with time and further study, better criteria will be determined and a more definitive approach to this problem will be established.     

NRAS and BRAF Mutations in Melanoma-Associated Nevi and Uninvolved Nevi

According to the prevailing multistep model of melanoma development, oncogenic BRAF or NRAS mutations are crucial initial events in melanoma development. It is not known whether melanocytic nevi that are found in association with a melanoma are more likely to carry BRAF or NRAS mutations than uninvolved nevi. By laser microdissection we were able to selectively dissect and genotype cells either from the nevus or from the melanoma part of 46 melanomas that developed in association with a nevus. In 25 cases we also genotyped a control nevus of the same patients. Available tissue was also immunostained using the BRAF^V600E-mutation specific antibody VE1. The BRAF^V600E mutation was found in 63.0% of melanomas, 65.2% of associated nevi and 50.0% of control nevi. No significant differences in the distribution of BRAF or NRAS mutations could be found between melanoma and associated nevi or between melanoma associated nevi and control nevi. In concordant cases immunohistochemistry showed a higher expression (intensity of immunohistochemistry) of the mutated BRAF^V600E-protein in melanomas compared to their associated nevi. In this series the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation. Our findings do not support the current traditional model of stepwise tumor progression.     

Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma

The Clark model for melanoma progression emphasizes a series of histopathological changes beginning from benign melanocytic nevus to melanoma via dysplastic nevus. Several models of the genetic basis of melanoma development and progression are based on this Clark’s multi-step model, and predict that the acquisition of a BRAF mutation can be a founder event in melanocytic neoplasia. However, our recent investigations have challenged this view, showing the polyclonality of BRAF mutations in melanocytic nevi. Furthermore, it is suggested that many melanomas, including acral and mucosal melanomas, arise de novo, not from melanocytic nevus. While mutations of the BRAF gene are frequent in melanomas on non-chronic sun damaged skin which are prevalent in Caucasians, acral and mucosal melanomas harbor mutations of the KIT gene as well as the amplifications of cyclin D1 or cyclin-dependent kinase 4 gene. Amplifications of the cyclin D1 gene are detected in normal-looking ‘field melanocytes’, which represent a latent progression phase of acral melanoma that precedes the stage of atypical melanocyte proliferation in the epidermis. Based on these observations, we propose an alternative genetic progression model for melanoma.     

Risk of melanoma arising in large congenital melanocytic nevi: a systematic review

Large congenital melanocytic nevi are cutaneous lesions regarded by many as premalignant; estimates of malignancy incidence range from 0 to 42 percent. Given the often complex and extensive nature of large congenital melanocytic nevi resection and reconstruction, the risk of malignant transformation is a crucial factor that surgeons and families must weigh when deciding whether or not to excise the lesion. The authors conducted a systematic analysis of data from the existing literature to critically evaluate the published studies and to establish a crude incidence rate for the risk of malignant melanoma transformation in large congenital melanocytic nevi. After a comprehensive literature search, they analyzed data from eight studies (containing a total of 432 large congenital melanocytic nevi patients) of sufficient scientific quality. Twelve patients (2.8 percent) in this sample developed cutaneous malignant melanoma during the reported follow-up periods. Using a subset of this data and comparing the incidence rates to those of the Surveillance, Epidemiology, and End Results population-based database using a standardized morbidity ratio, the authors found that the large congenital melanocytic nevi patients had an increased risk of melanoma (standardized morbidity ratio, 2599; 95 percent confidence interval, 844 to 6064) compared with the general population. Regarding treatment before developing melanoma in the 12 patients, 50 percent were observed before diagnosis, 17 percent had partial excision, 8.3 percent had dermabrasion, 8.3 percent had a chemical peel, and 17 percent did not have any treatment information. These combined data are clinically useful when consulting with the parents of children with large congenital melanocytic nevi and in the management of older patients with existing lesions. This study shows that there is a significantly increased risk of melanoma in large congenital melanocytic nevi patients. The data also reveal the need for a standardized definition of large congenital melanocytic nevi and a long-term, prospective outcomes study to determine the true lifetime risk of melanoma in patients with and without surgical excision.     

Real-time expression of hTERT in primary melanoma biopsies

Skin melanoma is by far the most lethal skin cancer, it is unpredictable by nature and presents a severe diagnostic problem. One of the major issues in melanoma diagnostics is to differentiate it with confidence from a dysplastic nevus. Thus, the aim of this study was to evaluate hTERT expression on a spectrum of dermal lesions (from normal skin toprimary melanoma) in order to examine its possible role as a diagnostic marker in melanoma diagnostics. In this study we analyzed the expression of hTERT by real-time PCR on 58 freshly obtained biopsy samples (4 samples of normal skin, 12 dermal nevi, 23 dysplastic nevi, 19 primary melanomas). Our results showed slightly greater hTERT expression in dysplastic nevi than melanomas with major data overlap. Considering the given results, hTERT does not seem to be a reliable diagnostic marker for melanoma.     

Giant congenital melanocytic nevi: the significance of neurocutaneous melanosis in neurologically asymptomatic children

Patients with a giant congenital melanocytic nevus can develop melanotic tumors characterized by central nervous system involvement, termed leptomeningeal melanocytosis or neurocutaneous melanosis. Although symptomatic neurocutaneous melanosis is rare, we previously reported distinct magnetic resonance (MR) findings of T1 shortening, strongly suggestive of neurocutaneous melanosis, in 30 percent (6 of 20) of children with giant congenital melanocytic nevi who presented initially without neurological symptoms. The purpose of this study was to determine the incidence of neurocutaneous melanosis in high-risk patients and its long-term clinical significance.Magnetic resonance imaging was recommended for all 46 patients with "at-risk" giant congenital melanocytic nevi involving the skin overlying the dorsal spine or scalp. The clinical histories and follow-up of these patients were evaluated by retrospective chart review. Forty-two underwent MR imaging of the brain and 11 underwent additional MR scanning of the spinal cord. Abnormalities were identified in 14 of 43 MR studies, and 23 percent (n = 10) had T1 shortening indicative of melanotic rests within the brain or meninges. None had associated masses or leptomeningeal thickening. The most common areas of involvement in these 10 included the amygdala (n = 8), cerebellum (n = 5), and pons (n = 3). In the group of 11 patients with spinal MR scans, a tethered spinal cord was demonstrated in one. Additional abnormalities were detected by MR scanning, including a middle cranial fossa arachnoid cyst, a Chiari type I malformation, and a crescentic enhancement that subsequently resolved. Clinical follow-up averaging 5 years (range, 2 to 8 years) revealed that only one of the 46 patients evaluated developed neurological symptoms, manifested as developmental delay, hypotonia, and questionable seizures but no other signs of neurocutaneous melanosis. No patient has developed a cutaneous or central nervous system melanoma. Magnetic resonance findings of neurocutaneous melanosis are relatively common, even in asymptomatic children with giant congenital melanocytic nevi. Although these findings suggest an increased lifetime risk of central nervous system melanoma, they do not signify the eventual development of symptomatic neurocutaneous melanosis during childhood.