Guidelines of care for nevi I (nevocellular nevi and seborrheic keratoses). Committee on Guidelines of Care. Task Force on Nevocellular Nevi.
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Humans↗
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[Dysplastic melanocytic nevi: quantitative ultrastructural investigation comparing intraepidermal melanocytes of dysplastic melanocytic nevi, superficial spreading melanoma, nevocellular nevi, and normal skin].
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Adult↗
Prevalence of common "acquired" nevocytic nevi and dysplastic nevi is not related to ultraviolet exposure.
The precise role of ultraviolet radiation in the induction of nevocytic nevi is unsettled. We studied mole counts in relation to the attitude toward ultraviolet exposure in 508 students 18 to 30 years of age. Moles were counted on the chest, back, and legs. Lesions measuring 2 mm or less in diameter and those measuring more than 2 mm were recorded separately. Dysplastic nevi were also recorded separately. The attitude toward sun worship was related to the average periods of sunbathing, the frequency of holidays in sunny climates, and the use of artificial ultraviolet sources. The frequency of pigmented nevi showed no correlation with sun behavior, irrespective of sex, mole size, or burning and tanning propensities. This lack of correlation between ultraviolet exposure and mole counts held true for all solar parameters: periods of sunbathing, sunny holidays, and sunlamp usage. Contrary to expectation, there was a clear, although not statistically significant, excess of dysplastic nevi in subjects with short periods of ultraviolet exposure during leisure. From these data insufficient evidence emerges to support the hypothesis of a correlation between the occurrence of common nevocytic nevi and dysplastic nevi and the degree of insolation by natural or artificial ultraviolet radiation.
Adolescent↗
The histological spectrum of acquired nevi. An analysis of the intraepidermal melanocytic proliferation in common and dysplastic nevi.
The histological intraepidermal characteristics considered to be specific to dysplastic nevi (radial extension, lentiginous and disordered nest proliferations, cytological atypia or dyskaryosis) were investigated in a series of 114 acquired nevi showing various clinical appearances in an attempt to establish whether dysplastic nevi can be considered a homogeneous class of lesions, clearly distinct from common nevi. On the basis of the distribution of investigated architectural features, found singly or variously associated, the examined lesions were divided into 5 groups, showing an increasing incidence of dyskaryosis. Results suggest that acquired nevi, rather than two distinct classes (common and dysplastic nevi), form a histological spectrum of lesions, within which the border between lesions implying and not implying an increased melanoma risk cannot be objectively fixed.
Cell Division↗
UV light from 290 to 325 nm, but not broad-band UVA or visible light, augments the formation of melanocytic nevi in a guinea-pig model for human nevi.
We have previously described a guinea-pig model where pigmented nevi similar to human nevi can be produced by application of low-dose topical 7,12-dimethylbenzanthracene (DMBA) followed by solar-simulated light. Five groups of guinea-pigs were used to test the effect of various spectral bands of solar-simulated light on low-dose DMBA-induced melanocytic nevi. Animals were irradiated with either UVB to near UVA2 (290-325 nm), UVA, visible light, full solar spectrum or no irradiation three times per wk for 12 mo to determine the broad-band effect of nevi-inducing irradiation. There was a significant increase in nevi/animal in the UVB-treated group (mean 1.53) compared with all groups (versus UVA 0.3, p<0.001; versus visible light 0.24, p<0.001; versus full spectrum (UVB+UVA+visible) 0.68, p=0.02; versus control (nil irradiation) 0.37, p=0.01). No differences in skin thickness were found between any group (p=0.11). In conclusion, we present a report of the active waveband of melanocytic nevi induction; where UVB to near UVA2 is the likely responsible waveband. Furthermore, because there was a significant decrease in nevi/animal receiving the full solar spectrum compared with the UVB group, it is possible that broad-band UVA and or visible light may be inhibitory wavebands for nevi induction.
9,10-Dimethyl-1,2-benzanthracene↗
The clinical appearance of clonal nevi (inverted type A nevi).
BACKGROUND: The term "clonal nevus" is used to describe a variant of melanocytic nevus that histologically exhibits a localized proliferation of pigmented epithelioid dermal melanocytes within an otherwise ordinary nevus (Ball NJ, Golitz LE. Melanocytic nevi with focal atypical epithelioid cell components: a review of seventy-three cases. J Am Acad Dermatol 1994; 30: 724-729). Reports to date have focused on the histologic appearance of these lesions. AIM: To characterize the clinical appearance of clonal nevi. METHODS: Clinical and histologic examinations were performed of a single clonal nevus from each of five patients (two men and three women; age range, 37-80 years). RESULTS: All nevi were round to oval in shape with smooth, well-defined borders. They were uniformly tan to light brown in color, except for a single blue-gray to blue-black focus of hyperpigmentation. The diameters of the nevi ranged from 2.5 to 10 mm. In individual nevi, the hyperpigmented focus was either centrally or eccentrically located and measured 1-2 mm in diameter. Histologically, these lesions showed banal melanocytes associated with a localized proliferation of melanocytes with abundant pigmented cytoplasm in the dermis, admixed with melanophages. CONCLUSIONS: The appearance of clonal nevi--tan with a focus of blue-gray to blue-black pigmentation--allows one to recognize the lesion clinically.
Adult↗
Common acquired melanocytic nevi, dysplastic melanocytic nevi and malignant melanomas: an image analysis cytometric study.
We used computerized image analysis cytometry to analyze 10 melanocytic lesions from each of the following categories: common acquired nevi, melanocytic nevi with architectural features of dysplasia, dysplastic melanocytic nevi (DMN) with slight atypia, DMN with moderate atypia, DMN with severe atypia, and superficial spreading melanomas. The nuclei of at least 50 consecutive nevomelanocytes in the most atypical zones were digitized at x 1000 under oil immersion, without knowledge of diagnosis by one observer. Grading of atypia was based on current practices as described in the literature. The results showed significant differences (p < 0.05) in nuclear area and standard deviation of nuclear area between melanoma and DMN with severe atypia, and between DMN with severe atypia and all other categories of nevi. There were no differences among any lesions with respect to nuclear shape. No differences in nuclear area were found among DMN with moderate, or slight atypia, nevi with features of dysplasia, and typical nevi. These results show for the first time objective distinction of low-grade (slight-moderate atypia), and high-grade or severe atypia in pre-malignant nevomelanocytic lesions of the skin.
Humans↗
Silhouette symmetry: an unsupportable histologic criterion for distinguishing Spitz nevi and compound nevi from malignant melanoma.
BACKGROUND: In 1989, Ackerman proposed that pattern analysis can be a more accurate method of evaluating neoplasms than assessment of nuclear morphology. He stated that malignant melanomas tend to be asymmetrical, and benign melanocytic neoplasms tend to be symmetrical. METHODS: We examined a series of typical Spitz nevi, compound nevi, and malignant melanomas with the loupe and with higher magnifications. We also considered pattern analysis from the standpoint of solid geometry. RESULTS: The ratio of symmetrical to asymmetrical lesions (visualized in histologic sections) in malignant melanomas approximated that of Spitz nevi and compound nevi. The configuration seen in sections does not necessarily reflect the three-dimensional configuration of a lesion. Lesions with three-dimensional reflective symmetry cannot be shown to have this property in sections unless cuts are made perpendicular to the plane of symmetry, which is an impossibility. CONCLUSIONS: The presence or absence of symmetry in sections of neoplasms must be considered coincidental or focal. Using symmetry as a criterion to distinguish malignant melanomas from Spitz nevi and compound nevi is without validity on both theoretical and empirical grounds.
Diagnosis, Differential↗
Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.
BACKGROUND: Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. METHODS: Ten specimens of each type of tumor were studied, using an in situ hybridization technique. RESULTS: All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. CONCLUSIONS: hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.
Diagnosis, Differential↗
Follow-up of melanocytic skin lesions with digital epiluminescence microscopy: patterns of modifications observed in early melanoma, atypical nevi, and common nevi.
BACKGROUND: Digital epiluminescence microscopy (DELM) has been reported to be a useful technique for the follow-up of melanocytic nevi. One of the promises of this technique is to identify modifications over time that indicate impending or incipient malignancy and to facilitate surveillance of melanocytic skin lesions, particularly in patients with multiple clinically atypical nevi. OBJECTIVE: Our purpose was to report on patterns of modifications over time observed in benign melanocytic skin lesions and melanoma. METHODS: A total of 1862 sequentially recorded DELM images of melanocytic lesions from 202 patients (mean age, 36.1 years; 54.0% female patients) with multiple clinically atypical nevi were included in the analysis. The median follow-up interval was 12. 6 months. Melanocytic lesions with substantial modifications over time (enlargement, changes in shape, regression, color changes or appearance of ELM structures known to be associated with melanoma) were excised and referred to histopathologic examination. RESULTS: A total of 75 melanocytic skin lesions (4.0%) from 52 patients (mean age, 33.3 years; 63.5% female patients) showed substantial modifications over time and were excised and referred to histopathologic examination. Eight changing lesions were histologically diagnosed as early melanomas. These lesions frequently showed focal enlargement associated with a change in shape as well as appearance of ELM structures that are known to be associated with melanoma. In contrast, the majority of benign changing lesions (common and atypical nevi) showed symmetric enlargement without substantial structural ELM changes. Six of the 8 patients in whom melanoma developed were unaware of the fact that the lesion had changed over time. CONCLUSION: We demonstrate that follow-up of melanocytic lesions with DELM helps to identify patterns of morphologic modifications typical for early melanoma. DELM may therefore serve as a useful tool to improve the surveillance of patients with multiple atypical nevi.
Adult↗
Frequency of congenital nevi, nevi spili and café-au-lait spots and their relation to nevus count and skin complexion in 939 children.
To determine the prevalence of congenital melanoevocytic nevi (CMN), of so-called congenital nevus-like nevi (CNLN), nevi spili (NS) and café-au-lait spots (CLS) in childhood, a series of 939 children aged 8-16 years had total skin examination. CMN/CNLN were observed in a frequency of 5.9%, NS in 2.1% and CLS even in 32.7%. Except CLS (which occurred more frequently in boys), all of these lesions were equally represented in both sexes. According to the classification of Kopf and coworkers, 44/55 CNM/CNLN were small and 11/55 medium-sized. CMN/CNLN affected preferentially trunk and upper limbs while head and neck were spared. Such nevi occurred more frequently in dark types of skin complexion and showed a tendency to be more frequent in groups of patients with increased average number of acquired melanonevocytic nevi. Remarkably, CLS were also found in 23/55 (41.7%) children with CMN/CNLN and in 12/20 (60%) children with NS (in a higher frequency than such combinations have to be expected). Compared with the data from other studies, both CMN/CNLN and CLS in our patients were observed in highest prevalence in the literature. Since the frequency of CLS in adults is much lower, it cannot be ruled out that some of the CLS disappear in adolescence.
Adolescent↗
Prevalence of congenital-nevus-like nevi, nevi spili, and café au lait spots.
To determine the clinical prevalence of medium-sized (1.5- to 19.9-cm-diameter) congenital-nevus-like nevi (CNLN), a consecutive series of 601 patients (mostly adults) had total cutaneous examinations. In this series, 15 (2.5%) were found to have such lesions. In addition, 14 (2.3%) had nevi spili and 83 (13.8%) had café au lait spots. All three types of lesions were equally represented in both sexes and tended to spare the head, neck, and upper extremities. Compared with CNLN, nevi spili were found to have significantly larger diameters and lower mean age, suggesting that these are different types of lesions. Some recommend the surgical removal of all congenital nevocytic nevi because of their malignant potential. Since it is not possible to clinically distinguish congenital nevocytic nevi and CNLN and since the observed prevalence of these lesions in adults is over four times that previously reported in newborns, such a recommendation becomes less feasible.
Adolescent↗
Congenital-nevus-like nevi, nevi spili, and café-au-lait spots in patients with malignant melanoma.
The prevalence of congenital-nevus-like nevi (CNLN) in a group of 105 adults who had malignant melanoma (MM) was compared with that in a control group of 601 adults not afflicted by MM. Total cutaneous examinations were performed on both groups. The control group presented with complaints other than pigmented lesions. In this series, 10 (9.5%) of the group with MM had clinically diagnosed CNLN 1.5 cm or larger in diameter. These CNLN were not in contiguity with the MM sites. The 9.5% prevalence of CNLN in the group with MM was significantly higher (p less than 0.005) than the 2.5% CNLN observed in the control population. None of the patients in either group had large congenital nevocytic nevi (greater than or equal to 20 cm). In addition, in the group with MM, 5 patients (4.8%) had nevi spili (NS) and 13 (12.4%) had café-au-lait spots (CLS). The prevalence rates for these two types of pigmented lesions were not significantly different from those observed in the nonmelanoma control group (2.3% for NS; 13.8% for CLS). The relative risk for developing MM is 4.1 in people with CNLN compared with those without CNLN, which indicates that these nevi may be markers for individuals prone to develop malignant melanoma.
Adult↗
Expression of Melan-A in Spitz, pigmented spindle cell nevi, and congenital nevi: comparative immunohistochemical study.
The expression of the antibody Melan-A in 27 benign melanocytic skin lesions (10 congenital nevi, 10 Spitz nevi, and 7 pigmented spindle cell nevi) was compared to that of S100 protein and HMB-45. To evaluate the role of Melan-A in differentiating melanocytic and nonmelanocytic lesions we assessed a number of benign nonmelanocytic skin lesions including neurofibromas, granular cell tumors, and dermatofibromas. Melan-A had an identical staining pattern to S100 protein in the melanocyte population of all lesions, but had the advantage of only staining cells of melanocytic lineage and no other cell types. HMB-45, although staining the junctional components of all lesions with a junctional component, showed varied intensity and distribution in the dermal components. Melan-A is much cleaner than S100 protein, having no background staining, and in skin appears to be specific for melanocytes. The nonmelanocytic lesions did not express Melan-A.
Antigens, Neoplasm↗
Melanocytic nevi, dysplastic nevi, and malignant melanoma in children from melanoma-prone families.
BACKGROUND: Melanocytic nevi, particularly dysplastic nevi (DN), are important markers of increased risk of malignant melanoma in adults, but little is known about their prevalence and relation to melanoma in children. OBJECTIVE: Our purpose was to define the prevalence of DN, number of nevi, and their relation to the risk of melanoma in children younger than 20 years of age from melanoma-prone families. METHODS: One hundred twenty-five persons younger than 20 years of age, from 23 melanoma-prone families, underwent clinical evaluation with nevus counts, photography, and biopsy of suspected melanocytic lesions and were observed for development of DN and melanoma. RESULTS: In melanoma-prone families, 37% of children had DN. The patients were divided into four categories: those with melanoma, DN (without melanoma), indeterminant (largely because of age at examination), and unaffected. The risk of melanoma was assessed by nevus number and presence of DN. High nevus number was strongly correlated with the presence of DN. The risk of the development of melanoma in children from melanoma-prone families appeared most related to the presence of DN (relative risk, 45; 95% confidence intervals, 2.6-786.4) and started at an early age. Of note, all children in whom melanoma developed had DN. CONCLUSION: Family history of melanoma and the presence of DN defines children with a high risk for melanoma developing at an early age.
Adolescent↗
Comprehensive analysis of 112 melanocytic skin lesions demonstrates microsatellite instability in melanomas and dysplastic nevi, but not in benign nevi.
INTRODUCTION: the length of DNA repetitive sequences (microsatellite instability (MSI)) represent distinct tumorigenic pathways associated with several familial and sporadic tumors. MATERIAL AND METHODS: To investigate the prevalence and frequency of MSI in melanocytic lesions, the polymerase chain reaction (PCR)-based microsatellite assay was used to examine formalin-fixed, paraffin-embedded tissues of 30 benign melanocytic nevi, 60 melanocytic dysplastic nevi (MDN), and 22 primary vertical growth phase cutaneous malignant melanomas (CMM). Twenty-four microsatellite markers at the 1p, 2p, 3p, 4q and 9p chromosomal regions were used. RESULTS: MSI was found at 1p and 9p in MDN and CMM but not in benign melanocytic nevi. The overall prevalence of MSI was 17/60 (28%) in MDN and 7/22 (31%) in CMM. The frequency of MSI ranged from 2/24 (9%) to 4/24 (17%) and was most commonly found at D9S162. There was a statistically significant correlation between degree of atypia and frequency of MSI (p<0.001) in MDN. There were two MSI banding patterns: band shifts and additional bands. CONCLUSIONS: The data presented revealed the presence of low-frequency MSI (MSI-L) at the 1p and 9p regions in both MDN and CMM. Whether the MSI-L pattern reflects a defect in mismatch repair genes is still to be determined.
Chromosome Mapping↗
C-fos protein expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.
The expression of c-fos protein was studied in formalin-fixed, paraffin-embedded sections of 11 compound Spitz nevi (SNs), 16 ordinary compound melanocytic nevi (MNs), and 17 malignant melanomas (MMs) using monoclonal antibody MAB1283 and an immunoperoxidase technique. Eleven (100%) SNs, 15 (94%) MNs, and 16 (94%) MMs showed positive reactions in some of the tumor cells (p = nonsignificant). In the majority of the tumors the staining was located in nuclei and graded as moderate to strong in intensity. The percentages of positively stained cells did not differentiate the three types of tumor, although they were higher in the melanocytic nevi. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Positive staining for c-fos was also frequently found in the normal skin constituents within and adjacent to the melanocytic tumors. In conclusion, the pattern of expression of c-fos in routinely processed specimens does not differentiate between SNs, MNs, and MMs.
Cell Nucleus↗
UV induction of cyclobutane thymine dimers in the DNA of cultured melanocytes from foreskin, common melanocytic nevi and dysplastic nevi.
We compared the induction of cyclobutane thymine dimers after exposure to 302 nm UV in foreskin-derived melanocytes and melanocytes from nevocellular nevi, as well as in melanocytes cultured from dysplastic nevi, precursor lesions of melanoma, derived from four, three and four individuals, respectively. Cyclobutane thymine dimers were quantified in situ by means of an immunofluorescence assay with a specific monoclonal antibody. A method was developed to compare separately performed experiments in a standardized manner. For melanocytes from each source, we demonstrated a linear relationship between UV dose and immunofluorescence. In nevocellular and dysplastic nevi, two subpopulations could be detected, distinguished by their nuclear size. Large nucleated nevocellular nevus cells were most susceptible to the induction of thymine dimers (49% higher induction compared to induction in foreskin melanocytes), while in normal-sized nuclei of these nevus cells the same induction of thymine dimers was found as in nuclei from foreskin melanocytes. In contrast, large nucleated dysplastic nevus melanocytes did not differ from the foreskin melanocytes, while normal-sized nuclei of dysplastic nevus cells showed a lower induction (32% lower induction than in foreskin melanocytes).
Cells, Cultured↗