What dermoscopy tells us about nevogenesis ZALAUDEK, Iris; CATRICALÀ, Caterina; MOSCARELLA, Elvira ...
Journal of dermatology,
January 2011, Letnik:
38, Številka:
1
Journal Article
Recenzirano
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The evolution of nevi is a complex process involving several constitutional and environmental factors. Although histopathology is the gold standard for the diagnosis and classification of melanocytic ...nevi, the widespread use of in vivo diagnostic technologies such as dermoscopy and more recently of reflectance confocal microscopy, has enriched profoundly our knowledge regarding the morphological variability of nevi in different stages of their evolution. In addition, significant progress has been made in our understanding of genetic alterations and molecular pathways involved in the formation of melanocytic tumors. All this newly acquired knowledge increasingly questions whether morphologically different nevi are also histiogenetically different. In this article, we intend to extract some of the salient points from published clinical and molecular studies on melanocytic tumors and attempt to assimilate them into an integrative concept of nevogenesis.
Differential gene expression of cell lines derived from a malignant melanoma or its autologous lymph node metastasis using cDNA arrays indicated down-regulation of PRSS11, a gene encoding the serine ...protease HtrA1, a homolog of the Escherichia coli protease HtrA, in the metastatic line. Stable PRSS11 overexpression in the metastatic cell line strongly inhibited proliferation, chemoinvasion and Nm23-H1 protein expression in vitro, as well as cell growth in vivo in nu/nu mice. A polyclonal anti-HtrA1 serum demonstrated a significantly higher expression in primary melanomas when compared to unrelated metastatic lesions in a human melanoma tissue array, and down-modulation of HtrA1 expression in autologous lymph node melanoma metastases in seven out of 11 cases examined. These results suggest that down-regulation of PRSS11 and HtrA1 expression may represent an indicator of melanoma progression.
Asymptomatic solitary nodule of the forehead Carbone, Anna, MD; Ferrari, Angela, MD; Cota, Carlo, MD ...
Journal of the American Academy of Dermatology,
12/2016, Letnik:
75, Številka:
6
Journal Article
Dermoscopy is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumors. This is because dermoscopy permits the visualization of key vascular structures that are usually not ...visible to the naked eye. Much work has concentrated on the identification of specific morphologic types of vessels that allow a classification into melanocytic versus nonmelanocytic and benign versus malignant nonpigmented skin tumors. Among a broad spectrum of different types of vascular patterns, six main morphologies can be identified. These are comma-like, dotted, linear-irregular, hairpin, glomerular, and arborizing vessels. With some exceptions, comma, dotted, and linear irregular vessels are associated with melanocytic tumors, while the latter three vascular types are generally indicative of keratinocytic tumors. Aside from vascular morphology, the architectural arrangement of vessels within the tumor and the presence of additional dermoscopic clues are equally important for the diagnosis. This article provides a general overview of the dermoscopic evaluation of nonpigmented skin tumors and is divided into two parts. Part I discusses the dermoscopic vascular patterns of benign and malignant melanocytic skin tumors. Part II discusses the dermoscopic vascular patterns of benign and malignant nonmelanocytic nonpigmented skin tumors. In each part, additional special management guidelines for melanocytic and nonmelanocytic nonpigmented skin tumors, respectively, will be discussed.
Background Little is known about the dermoscopic features of keratinocyte skin cancer. Objective We sought to determine the dermoscopic features of facial actinic keratosis (AK), intraepidermal ...carcinoma (IEC), moderately to poorly differentiated invasive squamous cell carcinoma (SCC), and well-differentiated SCC of the keratoacanthoma type. Methods This was a retrospective analysis of dermoscopic images of histopathologically diagnosed keratinocyte skin cancer. Results A total of 243 (70 AK, 71 IEC, 78 SCC, and 24 keratoacanthomas) tumors of the face from 243 patients (mean age: 71.1 years; range: 44-94 years) were analyzed. The majority of patients had a fair skin type, history of melanoma or nonmelanoma skin cancer, and multiple AK. A red pseudonetwork was significantly associated with AK ( P < .001), whereas dotted/glomerular vessels, diffuse yellow opaque scales, and microerosions were significantly more prevalent among IEC ( P < .001). Hairpin vessels, linear-irregular vessels, targetoid hair follicles, white structureless areas, a central mass of keratin, and ulceration were significantly associated with invasive SCC ( P < .001 for all criteria). Similar patterns as in SCC were observed among keratoacanthomas. Limitations The retrospective design of our study and the lack of assessment of sensitivity and specificity of the dermoscopic criteria are limitations. Conclusions Based on our findings we propose a progression model of facial AK developing into IEC and invasive SCC.
Deregulations or mutations of WNT/β-catenin signaling have been associated to both tumour formation and progression. However, contradictory results concerning the role of β-catenin in human melanoma ...address an open question on its oncogenic nature and prognostic value in this tumour. Changes in WNT signaling pathways have been linked to phenotype switching of melanoma cells between a highly proliferative/non-invasive and a slow proliferative/metastatic condition. We used a novel panel of cell lines isolated from melanoma specimens, at initial passages, to investigate phenotype differences related to the levels and activity of WNT/β-catenin signaling pathway. This in vitro cell system revealed a marked heterogeneity that comprises, in some cases, two distinct tumour-derived subpopulations of cells presenting a different activation level and cellular distribution of β-catenin. In cells derived from the same tumor, we demonstrated that the prevalence of LEF1 (high β-catenin expressing cells) or TCF4 (low β-catenin expressing cells) as β-catenin partner for DNA binding, is associated to the expression of two distinct profiles of WNT-responsive genes. Interestingly, melanoma cells expressing relative low level of β-catenin and an invasive markers signature were associated to the TNF-α-induced pro-inflammatory pathway and to the chemotherapy resistance, suggesting that the co-existence of melanoma subpopulations with distinct biological properties could influence the impact of chemo- and immunotherapy.
Lichenoid keratosis-like melanomas Moscarella, Elvira, MD; Zalaudek, Iris, MD; Pellacani, Giovanni, MD ...
Journal of the American Academy of Dermatology
65, Številka:
3
Journal Article
Summary
Wnt/β‐catenin signaling plays important roles in many developmental processes including neural crest‐derived melanocyte development and migration. However, the effective contribution of ...Wnt/β‐catenin pathway in melanogenesis in adult human melanocytes has not been fully elucidated. Here, we report that in melanoma cells and in normal human melanocytes, melanogenesis stimulation by α‐melanocyte‐stimulating hormone (α‐MSH) induces phosphorylation of β‐catenin‐Ser675 and stabilization of β‐catenin protein. Activation of protein kinase A by α‐MSH attenuates glycogen synthase kinase‐3β, which regulates ubiquitin‐dependent degradation of β‐catenin, suggesting a coordinated mechanism of β‐catenin activity stimulation. Consistent with increased nuclear β‐catenin, cyclic adenosine monophosphate (cAMP) elevation facilitates β‐catenin‐dependent transactivation of many Wnt target genes. Moreover, chromatin immunoprecipitation assays demonstrated an increased association of β‐catenin with the proximal promoter of microphthalmia‐associated transcription factor, the master regulator of pigmentation. These results demonstrate the existence of cross talk between the cAMP and Wnt pathways in melanocytes, suggesting that β‐catenin could play a key role in the physiological regulation of epidermal melanogenesis.
Background CDKN2A and CDK4 are high risk susceptibility genes for cutaneous malignant melanoma. Melanoma families with CDKN2A germline mutations have been extensively characterised, whereas CDK4 ...families are rare and lack a systematic investigation of their phenotype. Methods All known families with CDK4 germline mutations (n=17) were recruited for the study by contacting the authors of published papers or by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic data related to primary melanoma and pigmentation characteristics were collected. The CDK4 exon 2 and the complete coding region of the MC1R gene were sequenced. Results Eleven families carried the CDK4 R24H mutation whereas six families had the R24C mutation. The total number of subjects with verified melanoma was 103, with a median age at first melanoma diagnosis of 39 years. Forty-three (41.7%) subjects had developed multiple primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62 melanoma cases) of 209 tested subjects. CDK4 positive family members (both melanoma cases and unaffected subjects) were more likely to have clinically atypical nevi than CDK4 negative family members (p<0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010). Conclusion Our study shows that families with CDK4 germline mutations cannot be distinguished phenotypically from CDKN2A melanoma families, which are characterised by early onset of disease, increased occurrence of clinically atypical nevi, and development of MPM. In a clinical setting, the CDK4 gene should therefore always be examined when a melanoma family tests negative for CDKN2A mutation.
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