Common Nevi Research Articles

Expression of Ligands to NKp46 in Benign and Malignant Melanocytes

Human melanoma cell lines were shown to express ligands for the natural cytotoxicity receptor, NKp46, expressed by natural killer (NK) cells. We aimed to examine the expression of ligands for NKp46 by various primary human melanocytic cells and melanocytic lesions. Sections from primary nevi and melanomas were tested for expression of NKp46 ligands employing chimeric NKp46-Fc for staining. The melanocytes present in the reticular dermis were negative for NKp46 ligands in common nevi; in malignant melanocytic lesions, the deeper melanocytes were focally positive. In dermoepidermal junction of all melanocytic lesions, the melanocytes showed enhanced expression of NKp46 ligands. Melanophages in all lesions were consistently positive for NKp46 ligands. These observations establish the expression of NKp46 ligands by primary-transformed melanocytes. Normal melanocytes did not express ligands to NKp46. Therefore, the results show (i) a correlation between the malignant potential of the lesion and the expression of NKp46 ligands in the reticular dermis, and (ii) enhanced expression of NKp46 ligands in the active proliferation zone (dermoepidermal junction) of nevi and melanomas. Ligands to NKp46 were expressed on the membrane and within the cells. The physiological role of NKp46 ligands in the progression of malignancy within melanocytic lesions should be explored further.

Atypical Genital Nevi

Atypical genital nevi are rare melanocytic lesions that most commonly arise on the vulva of young women. They are currently regarded as nevi of special sites, in that despite histologically worrisome features, their clinical behavior is reportedly benign. However, only few studies with limited follow-up data are available. To better characterize the clinical presentation and behavior of these lesions and to further delineate their histologic features, we retrieved 56 atypical genital nevi arising in the lower female genital tract from our departmental and consultation files. The 56 lesions arose in 55 female patients with a median age of 26 years (range, 6 to 54 y). The dominant histologic feature was a lentiginous and nested junctional component composed of prominent round or fusiform nests, which often showed retraction artifact and/or cellular dyscohesion. Cytologic atypia was mild in 11 cases (20%), moderate in 34 (60%), and severe in 11 (20%). Ten cases (18%) showed focal pagetoid spread, with extension to the granular layer and stratum corneum in 1 case. The atypical junctional melanocytic proliferation was associated with a large common dermal nevus component that dominated the lesion in 26 cases (46%). Adnexal spread (46%) and nuclear atypia of melanocytes situated in the superficial dermis (39%) were relatively common, but dermal mitoses (7%) were uncommon and maturation was present in all cases. A broad zone of dense eosinophilic fibrosis within the superficial dermis was a frequent finding (41%). Clinical follow-up was available in 45 cases (80%) with a median follow-up period of 3.5 years (range, 1 to 16 y). Only 1 lesion recurred, 1.5 years after the initial excision. The original nevus in this patient had only mild cytologic atypia and was present at the margins of excision. The recurrent/persistent nevus was reexcised, and there was no further clinical recurrence in 11.5 additional years of follow-up. Our data support the hypothesis that atypical genital nevi have a benign clinical course despite their occasionally striking cytologic and architectural atypia. Awareness and recognition of this group of melanocytic lesions is important to avoid over diagnosis as melanoma with subsequent wide excision and possibly sentinel lymph node biopsy.

Consumption of the Epidermis: A Criterion in the Differential Diagnosis of Melanoma and Dysplastic Nevi That is Associated With Increasing Breslow Depth and Ulceration

Consumption of the epidermis (COE), defined as thinning of the epidermis with attenuation of basal and suprabasal layers and loss of rete ridges adjacent to collections of melanocytes, is a recently coined term encompassing changes of the epidermal architecture associated with melanoma. To evaluate this feature as an additional diagnostic criterion for melanoma, we examined COE in 453 melanocytic lesions, including 213 invasive melanomas from a population-based series and 240 suspicious pigmented lesions from a clinic-based series, excluding halo and Spitz nevi. In the population-based series, COE was identified in 92/213 (43%) invasive melanomas and became progressively more frequent with increasing Breslow depth (P < 0.0001) and Clark level (P = 0.0002). COE was more frequent when mitotic figures (P < 0.0001), ulceration (P = 0.005), or vertical growth phase (P = 0.009) were present, but it was not significantly associated with age, gender, site, regression, or tumor-infiltrating lymphocytes. In the clinic-based series of pigmented lesions, COE was present in 2/25 (8%) in situ melanomas, 1/29 (3%) lesions classified as melanoma in situ/high-grade dysplastic nevi, and 1/40 (2.5%) high-grade dysplastic nevi. COE was not identified in 146 low-grade dysplastic, congenital, or common nevi. In the combined datasets, 94/96 (98%) lesions exhibiting COE were classified as melanoma. This study demonstrates that COE is frequently present in invasive melanomas, is associated with more aggressive histopathologic features (including increased Breslow depth and ulceration) and may be a useful supplementary diagnostic criterion for melanoma. Furthermore, the process leading to COE may be the first step in a progression to ulceration.

Histologic Spectrum of Melanocytic Nevi Removed from Patients &gt; 60 Years of Age

The histology of melanocytic nevi removed from older patients often differs from that of nevi from younger adults. According to the literature, the most common nevus in older individuals is the intradermal nevus, and purely junctional nevi are rare and should alert the pathologist to a possible melanoma precursor. To evaluate the histologic features of melanocytic nevi removed from patients > 60 year of age. Biopsies of nevi (N=215) from 172 patients > 60 years (mean age 69+/-7 years) were examined retrospectively by three dermatopathologists, a consensus diagnosis was rendered, and the spectrum of histologic features was documented. Junctional melanocytic nevi were frequently diagnosed in older patients (21% of cases) and a lentiginous, often heavily pigmented growth pattern was common (12% of nevi). Severely atypical (dysplastic) changes were found in 6% of nevi removed from older patients. We conclude that benign junctional nevi are relatively common in older patients and that a lentiginous, heavily pigmented growth pattern, traditionally associated with younger individuals, is often seen in both junctional and compound nevi in this older age group. This pattern must be differentiated from dysplastic nevus and melanoma in situ, which they may clinically resemble.

Melanocytic nevi simulant of melanoma with medicolegal relevance

A group of melanocytic benign nevi are prone to be misdiagnosed as nodular or superficial spreading melanoma. This review illustrates the most frequent forms of these nevi in direct comparison with their malignant morphologic counterparts. The nevi are: hyper-cellular form of common nevus to be distinguished from nevoid melanoma, Spitz nevus (vs spitzoid melanoma), Reed nevus (vs melanoma with features of Reed nevus), cellular atypical blue nevus (vs melanoma on blue nevus), acral nevus (vs acral melanoma), Clark dysplastic nevus (vs superficial spreading melanoma), desmoplastic nevi (vs desmoplastic melanoma), benign proliferative nodules in congenital nevi (vs melanoma on congenital nevi), epithelioid blue nevus (vs animal type melanoma) and regressed nevus (vs regressed melanoma). For each single 'pair' of morphological look-alikes, a specific set of morphological, immunohistochemical and genetic criteria is provided.

Sequentially-accumulated genetic alterations at chromosome 9p21 play a role in melanoma progression

8522 Background: Cytogenetic and molecular studies indicated the chromosome 9p21 and its CDKN locus, with the p16/CDKN2A tumor suppressor genes, as the genomic regions involved into the pathogenesis of malignant melanoma (MM). To further elucidate the role of such regions in melanoma, we evaluated the 9p21-linked molecular alterations during the different phases of melanocytic tumorigenesis. Methods: Paraffin-embedded tissue sections from common nevi, dysplastic nevi, and melanomas, including primary and metastatic MM lesion, as well as melanoma cell lines were evaluated by both fluorescence in situ hybridization (FISH) using probes spanning the entire 9p21 region and immunohistochemistry (IHC) for p16/CDKN2A expression. Results: Allelic deletion at the CDKN locus and p16/CDKN2A gene silencing were both observed at increased rates moving from nevi to early or advanced primary melanomas and to correspondent metastases. Dysplastic nevi, primary and secondary melanomas were instead found to be heterozygously deleted at one or more loci within the 9p21 chromosome in a quite similar fraction (55–62%) of cases. Inactivation of the p16/CDKN2A gene was found at rates higher in melanoma cell lines (67%) than in vivo melanomas (62% secondary and 12.5% primary melanomas), with a normal p16/CDKN2A IHC staining in all analyzed nevi. Conclusions: Our findings indicate a model of sequential accumulation of genetic alterations from normal melanocytes to metastatic melanoma, with a) 9p21 allelic loss playing a role in melanocytic transformation and tumor initiation; b) deletions at CDKN locus and p16/ CDKN2A gene inactivation participating to tumor dissemination. Presence of such alterations could be further evaluated as markers of the different phases of melanoma progression. No significant financial relationships to disclose.

Cell cycle and apoptosis regulators in Spitz nevi: Comparison with melanomas and common nevi

Deregulated cell cycle control is one of the hallmarks of tumor development. The expression of different cell cycle regulators has been used in various neoplasms as an adjunct to diagnosis. We sough to determine the expression of cell cycle and apoptosis regulators in Spitz nevi and to appraise its value as a diagnostic adjunct in the differential diagnosis from melanomas and common nevi. Ki-67, p-27, p-16, p-53, p-21, Rb, cyclin D1, cyclin A, cyclin B1, bcl-2, and bax expression was assessed by immunohistochemistry in 10 Spitz nevi and was compared with 16 melanomas and 20 common nevi immunohistochemical expression. P-27 (60% +/- 20.13), p-16 (62.00% +/- 10.85), and bcl-2 (46.00% +/- 42.47) were highly expressed in Spitz nevi, whereas Ki-67 (2.80% +/- 2.55), Rb (3.75% +/- 4.55), p-53 (2.30% +/- 0.10), cyclin A (0.70% +/- 1.56), B1 (0.20% +/- 0.34), and bax (2.65% +/- 6.37) demonstrated a limited expression. Cyclin D1 (8.60% +/- 7.30) and p-21 (6.40% +/- 5.37) showed a moderate expression. The expression of bax (P = .001), Ki-67 (P < .0001), Rb (P < .0001), p-16 (P < .0001), cyclin A (P < .0001), and cyclin B1 (P < .0001) was significantly higher in melanomas in comparison with Spitz nevi, whereas p-27 expression was significantly higher in Spitz nevi (P < .0001). A trend for significant difference in favor of melanomas was also observed for p-53 (P = .002). On the other hand, no difference was detected for bcl-2 (P = .275), p-21 (P = .055), or cyclin D1 (P = .077). Spitz nevi demonstrated a trend for a higher expression for p-21 (P = .008) and cyclin D1 (P = .006), whereas they exhibited lower p-16 (P = .004) in comparison with common nevi. The number of Spitz nevi was relatively small. Spitz nevi differ from melanomas in their immunohistochemical pattern of expression of cell cycle and apoptosis regulators and more closely resemble common benign nevi.

Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression

The biological significance of the almost constant presence of macrophages in the tumoral microenvironment is an issue debated by several authors. The major difficulty in understanding the role played by tumor-associated macrophages (TAMs) in tumor progression is due to the contrasting effects of TAMs found in different studies. In addition, there is a limited information on which of the many biological activities expressed by TAMs are critical in inducing stimulatory or inhibitory effect on tumor growth. The aim of our study was: (a) to explore to what extent cyclo-oxygenase-2 (COX-2) in TAMs associated with human melanoma is expressed at different stages of tumor progression; and (b) to explore whether COX-2 expression in TAMs is stimulated by melanoma cells. In order to answer this question, we determined COX-2 positive TAMs associated with cutaneous melanocytic nevi, in situ, invasive and metastatic melanoma. In addition, we investigated whether COX-2 is expressed in peritoneal thioglycollate-elicited macrophages after co-cultivation with murine B16 melanoma cells. We found that COX-2-positive TAMs, as revealed by immunohistochemical analysis, were rare in common nevi and “dysplastic nevi”, but present in a high percentage in in situ and thin melanoma. COX-2-positive TAMs were also found in more advanced tumors and metastatic melanoma, although at a significantly lower percentage in these latter. The in vitro protocol revealed that COX-2 was expressed in peritoneal macrophages upon contact with B16 murine melanoma cells, but not with normal murine fibroblasts. On the whole, the results of in vivo and in vitro studies suggest that COX-2 expressed in TAMs appears to act as an effective biomarker of melanoma progression, and melanoma cells themselves might stimulate COX-2 in macrophages.

Common Melanocytic Nevi in 7-Year-Old Schoolchildren Residing at Different Latitudes in Sweden

Current epidemiologic research shows consistently that increased number of acquired common melanocytic nevi (CMN) is an important risk factor for cutaneous malignant melanoma. The purpose of this study was to investigate the number of CMN in relation to tanning habits and complexion among 7-year-old children residing at different latitudes in Sweden. Two municipalities were chosen at latitude 65 degrees N to 68 degrees N in the north of Sweden and two at latitude 57 degrees N in the south. Children born in 1994 and registered in the municipalities were to be included (N = 1,676). A questionnaire was sent to their parents asking about the child's tanning habits. A body examination of CMN of size >or=2 mm was done by the same trained nurse in 1,380 (82.3%) of the children. CMN was significantly less prevalent among children living in the north with a prevalence of 5.6 [95% confidence interval (95% CI), 4.8-6.5] inland and 6.2 (95% CI, 5.3-7.2) coastal compared with the south with a prevalence of 9.5 (95% CI, 8.2-11.0) inland and 10.4 (95% CI, 8.9-12.0) coastal. In addition, blond hair, blue/gray/green eyes, holidays at seaside resorts abroad, more frequent sunburns, and parents fancying tanning were significant predictors of higher prevalence of CMN. These findings support previous evidence that the development of CMN is related to the level of sun exposure in childhood expressed as latitude of residence, holidays at seaside resort abroad, and number of sunburns. To reduce the incidence of cutaneous malignant melanoma, a change in attitude and behavior must start with young children and their parents.

Is melanocytic nevus with focal atypical epithelioid components (clonal nevus) a superficial variant of deep penetrating nevus?

We compare features of two similar nevi which may be confused with melanoma: deep penetrating nevus (DPN), and nevus with focal atypical epithelioid component (NFAEC). Clinical/demographic and histologic information regarding 146 DPN and 81 NFAEC were compared. Patient outcomes were ascertained via a questionnaire solicited to the referring physicians. Clinical features were similar for each type of nevus. Histologically, all lesions demonstrated identical aggregates of epithelioid melanocytes. DPN more often extended into the deep dermis or subcutaneous tissue, while NFAEC was typically confined to the superficial dermis. NFAEC more often demonstrated a junctional component (P < .001) and coexistent common nevus with congenital features (P = .035). DPN more often demonstrated adnexal spread (P < .001). A subgroup with overlapping features was identified. With an average of 6.4 years follow-up, there were just two recurrences, and no metastases. This retrospective study utilized tissue specimens from a single reference laboratory; ergo, some inherent selection bias exists. Specimens were randomly selected for P53 immunostaining, leading also to potential sampling error. DPN and NFAEC show considerable similarity, differing mainly in the depth of extent for the lesion. It is possible that NFAEC represents a more superficial variant of DPN. A subgroup with overlapping features, but intermediate depth, supports such a relationship.

Naevus nævocellulaires avec hyperplasie des fibres élastiques

In common intradermal or compound nevi, nevocytes may be associated with other kinds of cells, tissues or lesions. In rare cases, they are associated with notable hyperplasia of the elastic fibers. CASE-REPORTS AND RESULTS: In 11 nevi (10 intradermal or compound nevi and 1 blue nevus), we observed striking hyperplasia of the elastic fibers strictly limited to the nevi, with normal aspect of the elastic fibers in the surrounding reticular dermis. These fibers were thicker than normal elastic fibers and showed tight connexions with nevus cells. This hyperplasia was not clinically relevant. It was correlated neither with the age and sex of patients nor with the site of the excised nevi. It was seen in 0.1% of excised nevi.Hyperplasia of elastic fibers in some common nevi is a curiosity which may be classified together with other vascular, nervous, epithelial or connective twin lesions occasionally associated with the nevocytic nevi. It has to be added to the list of so-called "twin nevi".

Lack of Association between BRAF Mutation and MAPK ERK Activation in Melanocytic Nevi

The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase signaling pathway can be activated through mutations of V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) oncogene, frequently found in melanoma (60%), common nevi (CN) (73-82%), and atypical nevi (AN) (52-80%). MAPK activation has been reported between 0 and 22% in nevi, and 86% of primary melanoma, without any knowledge of BRAF mutational status. We studied the correlation of MAPK activation status, BRAF mutation, and B-Raf expression in CN, AN, and melanoma. Using immunohistochemistry, phosphorylated (active) MAPK and B-Raf expression was studied in 24 CN, 21 AN, and 26 primary cutaneous melanomas (PM). BRAF mutations at codon 600 were assessed by PCR-RFLP. Active MAPK was detected in 29% of CN, 48% of AN, and 85% of PM. BRAF mutation was found in 67% of CN, 62% of AN, and 58% of PM. In all, 23% of CN, 54% of AN, and 93% of PM with BRAF mutation have activated MAPK. All lesions expressed B-Raf. BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi, and it is suggested that other events are needed to induce MAPK activation, that is, B-Raf overexpression, inhibition of MAPK phosphatases, or suppression of RAF kinase inhibitors.

Clinical and Dermoscopic Changes in Common Melanocytic Nevi in School Children: The Framingham School Nevus Study

Background: Nevi are potential precursors of malignant melanoma and are important risk factors for the development of the disease. Childhood may be a critical time for the formation and evolution of nevi. Objectives: To document the development of new nevi and to document the clinical and dermoscopic changes in index nevi in school children during a 1-year follow-up. Methods: Digital photographs and dermoscopic images of the back of subjects were compared at baseline and 1-year follow-up to assess changes in nevi counts and in clinical and dermoscopic features of index nevi. Results: Overall participation rate was 81% (42/52). 56.4% of study participants were found to have an increased number of nevi at 1-year follow-up. All nevi were small and clinically insignificant. Fifty percent of study participants were found to have dermoscopic changes in their index nevi at 1-year follow-up. Eighty-five percent of these changes were classified as subtle and 15.0% as obvious. Conclusions: A significant portion of students developed new nevi over the course of 1 year. Most index nevi remained stable in pattern and structure. Benign dermoscopic changes occurred in 50.0% of index nevi. However, none of the dermoscopically changed nevi revealed any major changes and the overall nevus pattern remained unchanged. The relevance of these changes is uncertain and further follow-up may elucidate their significance.

Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas

In malignant melanomas, the loss of cell cycle control is thought to be due to a lack of retinoblastoma protein (pRb)-activity. Members of the previously described family of retinoblastoma-binding proteins (RBPs) are supposed to act as pRb-modulating factors. Based on RNA-fingerprinting of normal human melanocytes, we previously described a new family member with high sequence homology to the retinoblastoma-binding protein-2 (RBP-2), termed RBP2-Homolog 1 (RBP2-H1). Based on its UVB responsiveness, it was hypothesized that this gene may also play a role in melanocytic tumors. In the present study, we can confirm by real-time RT-PCR (six common melanocytic nevi, five advanced nodular melanomas and seven melanoma metastases) and immunohistochemistry (tissue microarrays: 52 melanocytic nevi, 60 melanomas, 60 metastases; and conventional sections: five common nevi, four advanced nodular melanomas, five melanoma metastases) that RBP2-H1 expression is progressively downregulated in advanced and metastatic melanomas in vivo with a certain intratumoral heterogeneity. Whereas benign melanocytic nevi are RBP2-H1 positive in about 70% of the cases, a lack of RBP2-H1 expression was found in 90% of the primary malignant melanomas and 70% of the melanoma metastases, respectively. Interestingly, a similar deficiency can be found in glioblastomas, but not epithelial cancers. In accordance to the in vivo data, established melanoma cell lines exhibit low but heterogeneous levels of RBP2-H1 expression. By co-immunoprecipitation, we provide the first evidence that a subfraction of total RBP2-H1 can bind to pRb, which makes this protein a true pRb-interacting factor. We conclude that loss of RBP2-H1 is a common finding in the progression of malignant melanomas. Since a direct interaction of RBP2-H1 and pRb seems possible, the loss of RBP2-H1 may possibly contribute to uncontrolled growth in malignant melanomas.

Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma

Protease-activated receptors (PARs) are members of the G protein-coupled receptor superfamily that are activated by the proteolytic cleavage of their amino terminal domain. PAR-1 activation by thrombin results in several biologic effects, including platelet adhesion to other cells or extracellular matrix, fibroblast, and endothelial cell growth, whereas PAR-2, activated by trypsin, has mainly a proinflammmatory and angiogenetic role. PAR-1 and PAR-2 modulate cell proliferation in physiopathologic cell invasion processes, suggesting that they may play a role in the setting of cancer growth and metastasis. Here, we have investigated the expression of PAR-1 and PAR-2 proteins by immunohistochemistry in a series of benign and malignant melanocytic lesions: 20 melanocytic lesions (10 common melanocytic nevi and 10 atypical or "dysplastic" melanocytic nevi) and 50 melanomas (10 in situ melanomas, 10 melanomas T1, 10 melanomas T2, 10 melanomas T3 to T4, and 10 metastatic melanomas). PAR-1 was significantly overexpressed in atypical nevi and melanomas in comparison with common melanocytic nevi. PAR-2 was strongly and diffusely expressed by immunohistochemistry in all melanocytic lesions, with no statistically significant differences between nevi and melanomas. Because we found a differential expression in PAR-1 protein, but not in PAR-2, we next investigated the expression of PAR-1 messenger RNA (mRNA) by ribonuclease protection assay in paraffin-embedded tissues using a paraffin block RNA isolation procedure. Similarly to immunohistochemical results, PAR-1 mRNA expression was significantly higher in atypical nevi and melanomas in comparison with common nevi and controls. Overexpression of PAR-1 in atypical nevi and melanomas supports a role for PAR-1 in the initial phases of melanoma development as well as in tumor progression and metastasis. Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research.

Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays

Melanoma is one of the most aggressive types of cancer and resection of the tumour prior to dissemination of tumour cells is still the most effective treatment. Therefore, early diagnosis of melanocytic lesions is important and identification of novel (molecular) markers would be helpful to improve diagnosis. Moreover, better understanding of molecular targets involved in melanocytic tumorigenesis could possibly lead to development of novel interventions. In this study, we used a custom made oligonucleotide array containing 298 genes that were previously found to be differentially expressed in human melanoma cell lines 1F6 (rarely metastasising) and Mel57 (frequently metastasising). We determined differential gene expression in human common nevocellular nevus and melanoma metastasis lesions. By performing nine dye-swap array experiments, using individual as well as pooled melanocytic lesions, a constant differential expression could be detected for 25 genes in eight out of nine or nine out of nine array analyses. For at least nine of these genes, namely THBD, FABP7, H2AFJ, RRAGD, MYADM, HR, CKS2, NCK2 and GDF15, the differential expression found by array analyses could be verified by semiquantitative and/or real-time quantitative RT–PCR. The genes that we identified to be differentially expressed during melanoma progression could be potent targets for diagnostic, prognostic and/or therapeutic interventions.

Oral Nevi-A Clinicopathological Study of 29 Cases

Oral nevi are uncommon oral mucosal lesions. Twenty-nine cases of oral nevi including 21 intramucosal, 2 compound, and 6 common blue nevi were analyzed in this study. These 29 nevi were excised from 8 male and 19 female patients. Two patients each had 2 nevi. The mean age of patients at the time of diagnosis was 33 (range, 7~56) years. The more-common sites for oral nevi were the hard palate (12 cases) and vermilion border (9 cases). All 6 common blue nevi were located on the hard palate. The greatest dimension of the lesion was ≧1 cm in 3 cases and ＜1 cm in 24 cases. Excisional biopsy was the treatment of choice in 27 cases and wide excision in 2 cases. No recurrence of these lesions was found after surgical excision. Type A, type B, type C, and multinucleated giant nevus cells were found in 23 (100%), 19 (83%), 14 (61%), and 12 (52%) of 23 cases of intramucosal and compound nevi. The mean percentages of type A, type B, and type C nevus cells in total nevus cells were 73%±25%, 17%±15%, and 11%±18% in 23 cases of intramucosal and compound nevi, respectively. All 23 cases of intramucosal and compound nevi more or less contained nevus cells with pigmentation which varied from 1% to 91% (mean, 20%±26%). We concluded that the most-common type of oral nevi is an intramucosal nevus. Intramucosal and compound nevi were composed of approximately 3/4 of type A and 1/4 of type B and type C nevus cells. Oral nevi in this study occurred more often in female patients and in the third and fourth decades of life. The more-commonly affected sites were the hard palate and vermilion border. About 90% of these oral nevi were smaller than 1 cm.

BRAF V599E Mutation is Not Age Dependent: It is Present in Common Melanocytic Nevi in Both Children and Adults

BRAF encodes a serine‐threonine kinase, which acts in the RAS/RAF/MAPK pathway transducing regulatory signals from RAS to MEK1/2. Somatic mutations in BRAF have been identified in 53–80% of primary melanomas and 70–90% of common melanocytic nevi. More than 90% of these mutations consist of a valine to glutamate substitution at codon 599 (V599E) of exon 15. While a high prevalence of BRAF mutations in common melanocytic nevi has been reported in adults, nevi in children have not been studied. Of interest, we have previously shown that Spitz nevi in children do not harbor mutations in BRAF. To investigate the association of BRAF mutations with patient age, we studied common melanocytic nevi in children for the V599E activating mutation. Tumor cells were microdissected from 6 common melanocytic nevi in children 10 years of age or younger, and analyzed for the V599E mutation in BRAF by allele‐specific PCR and gel electrophoresis. In 6 of 6 (100%) nevi, the V599E mutant allele was observed. Our data suggest that similar genetic pathways are involved in the development of common melanocytic nevi in children and adults. The absence of BRAF mutations in Spitz nevi in children is therefore associated with tumor type, not patient age.

Toward the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy

We describe a study of the discrimination of early melanoma from common and dysplastic nevus using fiber optic diffuse reflectance spectroscopy. Diffuse reflectance spectra in the wavelength range 550 to 1000 nm are obtained using 400-microm core multimode fibers arranged in a six-illumination-around-one-collection geometry with a single fiber-fiber spacing of 470 microm. Spectra are collected at specific locations on 120 pigmented lesions selected by clinicians as possible melanoma, including 64 histopathologically diagnosed as melanoma. These locations are carried through to the histopathological diagnosis, permitting a spatially localized comparison with the corresponding spectrum. The variations in spectra between groups of lesions with different diagnoses are examined and reduced to features suitable for discriminant analysis. A classifier distinguishing between benign and malignant lesions performs with sensitivity/specificity of between 6469% and 7278%. Classifiers between pairs of the group common nevus, dysplastic nevus, in situ melanoma, and invasive melanoma show better or similar performance than the benign/malignant classifier, and analysis provides evidence that different spectral features are needed for each pair of groups. This indicates that multiple discriminant systems are likely to be required to distinguish between melanoma and similar lesions.

Mucinous Nevus

A 15-year-old boy first noticed multiple firm papules on his right upper chest two years before presenting to our clinic. These papules were densely distributed and showed epidermal nevus-like linear arrangement at some sites. The number, size, and distribution of these papules remained unchanged for one year of our observation. The papules flattened leaving scars and did not recur within a year after one shaving abrasion using a scalpel. Histopathologically, epidermis of the papule displayed acanthosis with elongated rete ridges. Accumulation of mucin was apparent in the papillary and subpapillary dermis. In mucinous nevus, the origin of cells with nevoid proliferation is obscure. In contrast with common collagenous connective tissue nevus, it is hard to define the localized persistent mucin accumulation as a nevoid manifestation. The present case of mucinous nevus might be caused by significantly stimulated glycosaminoglycan synthesis in a kind of epidermal nevus without extreme hyperkeratosis.