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The Journal of Investigative Dermatology Apr 2017A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are... (Comparative Study)
Comparative Study
A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42). Exome sequencing revealed that dysplastic nevi harbored a substantially lower mutational load than melanomas (21 protein-changing mutations versus >100). Known "driver" mutations in genes for melanoma, including CDKN2A, TP53, NF1, RAC1, and PTEN, were not found among any melanocytic nevi sequenced. Additionally, melanocytic nevi including dysplastic nevi showed a significantly lower frequency and a different UV-associated mutational signature. These results show that although melanocytic nevi and dysplastic nevi harbor stable genomes with relatively few alterations, progression into melanomas requires additional mutational processes affecting key tumor suppressors. This study identifies molecular parameters that could be useful for diagnostic platforms.
Topics: Adult; Cell Transformation, Neoplastic; DNA Mutational Analysis; Dysplastic Nevus Syndrome; Female; Genetic Predisposition to Disease; Genomics; Humans; Male; Melanoma; Precancerous Conditions; Prognosis; Risk Assessment; Sampling Studies; Skin Neoplasms
PubMed: 27890785
DOI: 10.1016/j.jid.2016.11.017 -
Acta Dermato-venereologica Nov 2022Malignant melanoma poses a clinical diagnostic problem, since a large number of benign lesions are excised to find a single melanoma. This study assessed the accuracy of...
Malignant melanoma poses a clinical diagnostic problem, since a large number of benign lesions are excised to find a single melanoma. This study assessed the accuracy of a novel non-invasive diagnostic technology, hyperspectral imaging, for melanoma detection. Lesions were imaged prior to excision and histopathological analysis. A deep neural network algorithm was trained twice to distinguish between histopathologically verified malignant and benign melanocytic lesions and to classify the separate subgroups. Furthermore, 2 different approaches were used: a majority vote classification and a pixel-wise classification. The study included 325 lesions from 285 patients. Of these, 74 were invasive melanoma, 88 melanoma in situ, 115 dysplastic naevi, and 48 non-dysplastic naevi. The study included a training set of 358,800 pixels and a validation set of 7,313 pixels, which was then tested with a training set of 24,375 pixels. The majority vote classification achieved high overall sensitivity of 95% and a specificity of 92% (95% confidence interval (95% CI) 0.024-0.029) in differentiating malignant from benign lesions. In the pixel-wise classification, the overall sensitivity and specificity were both 82% (95% CI 0.005-0.005). When divided into 4 subgroups, the diagnostic accuracy was lower. Hyperspectral imaging provides high sensitivity and specificity in distinguishing between naevi and melanoma. This novel method still needs further validation.
Topics: Humans; Hyperspectral Imaging; Melanoma; Skin Neoplasms; Nevus, Pigmented; Sensitivity and Specificity; Melanoma, Cutaneous Malignant
PubMed: 36281811
DOI: 10.2340/actadv.v102.2045 -
Epilepsia Sep 2011We report the case of a child who presented at 3 months of age with complex partial seizures, a linear facial nevus, and magnetic resonance imaging (MRI) showing delayed...
We report the case of a child who presented at 3 months of age with complex partial seizures, a linear facial nevus, and magnetic resonance imaging (MRI) showing delayed myelination and thickened cortex in the left temporal, parietal, and occipital regions. A repeat 3Tesla MRI scan with and without contrast at 6 months again showed cortical dysplasia of the left hemisphere. No other abnormalities were seen. A third scan at 3 years 6 months showed a 2.5 cm, round, hyperintense lesion on both T(2) and T(1) sequences. The lesion and surrounding dysplastic cortex were resected. Palmini grade IIA dysplasia and a ganglioglioma were diagnosed. These findings suggest that cellular components of cortical dysplasias have oncogenic potential.
Topics: Brain Neoplasms; Female; Ganglioglioma; Glial Fibrillary Acidic Protein; Humans; Infant; Magnetic Resonance Imaging; Malformations of Cortical Development; Phosphopyruvate Hydratase
PubMed: 21668439
DOI: 10.1111/j.1528-1167.2011.03124.x -
Cancer Biology & Therapy Nov 2008Studies of early neoplasia have revealed fundamental molecular pathways that drive tumorigenesis. Despite this progress, synthesis of principles of tumorigenesis that... (Review)
Review
Studies of early neoplasia have revealed fundamental molecular pathways that drive tumorigenesis. Despite this progress, synthesis of principles of tumorigenesis that span tissue types has lagged. Such forays into the 'comparative anatomy' of cancer can stimulate new models and refine key questions. We envision commonality of pathways important in formation of two early benign neoplasms that are found in different tissues and which are not generally thought to be similar: dysplastic nevi of the skin and intestinal aberrant crypt foci. We propose that these neoplasms result from an ongoing 'tug of war' between the tumor suppression barrier posed by cellular senescence and the tumor-promoting activity of Wnt-signaling. Whether or not such neoplasms progress to malignancy or persist in a benign state for many years might be largely determined by the outcome of this tug of war and its modulation by other genetic and epigenetic alterations, such as inactivation of p16(INK4a).
Topics: Animals; Cellular Senescence; Epithelial Cells; Gene Expression Regulation, Neoplastic; Humans; Models, Biological; Models, Genetic; Mutation; Neoplasms; Nevus; Oncogenes; Phosphorylation; Signal Transduction; Wnt Proteins
PubMed: 18836285
DOI: 10.4161/cbt.7.11.6943 -
Acta Dermato-venereologica Apr 2024Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed...
Nevus-associated lentigo maligna and lentigo maligna melanoma (NALMM) are rarely described in the literature and are considered an incidental finding. This study aimed to evaluate the frequency of NALMM and its clinicopathological features. A total of 201 histopathology reports were reviewed and among them 20% of the samples corresponded to NALMM, with females overrepresented in this group (p = 0.02). A significant association was also observed between NALMM with the presence of multiple nevi (p = 0.01), and dysplastic nevi (p = 0.04). Moreover, the risk of developing a second melanoma of nevus-associated type was 4.3 times higher in patients with NALMM. These results indicate that NALMM is more frequent than previously reported, suggesting that the associated nevus could interact or even act as a precursor for LM/LMM. Future studies with larger samples allied to techniques like confocal microscopy and molecular analysis are essential to determine this biological link between nevus and LM/LMM.
Topics: Female; Humans; Hutchinson's Melanotic Freckle; Melanoma; Nevus, Pigmented; Nevus; Skin Neoplasms
PubMed: 38629956
DOI: 10.2340/actadv.v104.18381 -
Skin Research and Technology : Official... Jun 2023Phacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an...
INTRODUCTION
Phacomatosis pigmentokeratotica (PPK), an epidermal nevus syndrome, is characterized by the coexistence of nevus spilus and nevus sebaceus. Within the nevus spilus, an extensive range of atypical nevi of different morphologies may manifest. Pigmented lesions may fulfill the ABCDE criteria for melanoma, which may prompt a physician to perform a full-thickness biopsy.
MOTIVATION
Excisions result in pain, mental distress, and physical disfigurement. For patients with a significant number of nevi with morphologic atypia, it may not be physically feasible to biopsy a large number of lesions. Optical coherence tomography (OCT) is a non-invasive imaging modality that may be used to visualize non-melanoma and melanoma skin cancers.
MATERIALS AND METHOD
In this study, we used OCT to image pigmented lesions with morphologic atypia in a patient with PPK and assessed their quantitative optical properties compared to OCT cases of melanoma. We implement a support vector machine learning algorithm with Gabor wavelet transformation algorithm during post-image processing to extract optical properties and calculate attenuation coefficients.
RESULTS
The algorithm was trained and tested to extract and classify textural data.
CONCLUSION
We conclude that implementing this post-imaging machine learning algorithm to OCT images of pigmented lesions in PPK has been able to successfully confirm benign optical properties. Additionally, we identified remarkable differences in attenuation coefficient values and tissue optical characteristics, further defining separating benign features of pigmented lesions in PPK from malignant features.
Topics: Humans; Tomography, Optical Coherence; Support Vector Machine; Skin Neoplasms; Nevus
PubMed: 37357662
DOI: 10.1111/srt.13377 -
Journal of Clinical Medicine Apr 2022The differential diagnosis of benign nevi (BN), dysplastic nevi (DN), and melanomas (MM) represents a considerable clinical problem. These lesions are similar in...
The differential diagnosis of benign nevi (BN), dysplastic nevi (DN), and melanomas (MM) represents a considerable clinical problem. These lesions are similar in clinical examination but have different prognoses and therapeutic management techniques. A texture analysis (TA) is a mathematical and statistical analysis of pixel patterns of a digital image. This study aims to demonstrate the relationship between the TA of digital images of pigmented lesions under polarized and non-polarized light and their histopathological diagnosis. Ninety pigmented lesions of 76 patients were included in this study. We obtained 166 regions of interest (ROI) images for MM, 166 for DN, and 166 for BN. The pictures were taken under polarized and non-polarized light. Selected image texture features (entropy and difference entropy and long-run emphasis) of ROIs were calculated. Those three equations were used to construct the texture index (TI) and bone index (BI). All of the presented features distinguish melanomas, benign and dysplastic lesions under polarized light very well. In non-polarized images, only the long-run emphasis moment and both indices effectively differentiated nevi from melanomas. TA is an objective method of assessing pigmented lesions and can be used in automatic diagnostic systems.
PubMed: 35566634
DOI: 10.3390/jcm11092505 -
The Western Journal of Medicine Apr 1994Despite important advances in the treatment of melanoma, the prognosis for advanced disease remains discouraging. This fact, in combination with a worldwide epidemic of... (Review)
Review
Despite important advances in the treatment of melanoma, the prognosis for advanced disease remains discouraging. This fact, in combination with a worldwide epidemic of melanoma among persons of white skin type, has focused attention on identifying melanoma in its early, surgically curable stages. Attention has also been directed toward pinpointing which persons are at increased risk for melanoma to reduce risk where possible and to aid early diagnosis. Essentially all epidemiologic studies have identified an increased number of melanocytic nevi as an important risk factor in the development of melanoma, but controversy has arisen concerning the risk associated with certain types of nevi, particularly "dysplastic" nevi. We review melanoma risk factors and examine the relationship between melanocytic nevi and melanoma to clarify for primary care physicians what is "known" (non-controversial) and what is "unknown" (controversial). We propose a working definition of an atypical mole phenotype and outline an approach to managing high-risk patients.
Topics: Female; Humans; Male; Melanoma; Nevus; Referral and Consultation; Risk Factors; Skin Neoplasms
PubMed: 8023484
DOI: No ID Found -
Life (Basel, Switzerland) Jul 2022Clinical diagnosis of pigmented lesions can be a challenge in everyday practice. Benign and dysplastic nevi and melanomas may have similar clinical presentations, but...
Clinical diagnosis of pigmented lesions can be a challenge in everyday practice. Benign and dysplastic nevi and melanomas may have similar clinical presentations, but completely different prognoses. Fractal dimensions of shape and texture can describe the complexity of the pigmented lesion structure. This study aims to apply fractal dimension analysis to differentiate melanomas, dysplastic nevi, and benign nevi in polarized and non-polarized light. A total of 87 Eighty-four patients with 97 lesions were included in this study. All examined lesions were photographed under polarized and non-polarized light, surgically removed, and examined by a histopathologist to establish the correct diagnosis. The obtained images were then processed and analyzed. Area, perimeter, and fractal dimensions of shape and texture were calculated for all the lesions under polarized and non-polarized light. The fractal dimension of shape in polarized light enables differentiating melanomas, dysplastic nevi, and benign nevi. It also makes it possible to distinguish melanomas from benign and dysplastic nevi under non-polarized light. The fractal dimension of texture allows distinguishing melanomas from benign and dysplastic nevi under polarized light. All examined parameters of shape and texture can be used for developing an automatic computer-aided diagnosis system. Polarized light is superior to non-polarized light for imaging texture details.
PubMed: 35888097
DOI: 10.3390/life12071008 -
Medicina (Kaunas, Lithuania) Nov 2021Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic...
Molecular Proof of a Clinical Concept: Expression of Estrogen Alpha-, Beta-Receptors and G Protein-Coupled Estrogen Receptor 1 (GPER) in Histologically Assessed Common Nevi, Dysplastic Nevi and Melanomas.
Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERβ), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. ERβ expression was higher in dysplastic nevi margin melanocytes compared to common nevi ( = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes ( = 0.021). ERβ expression was significantly higher in margin melanocytes compared to melanoma melanocytes ( = 0.009). No difference in ERβ expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi ( = 0.02 and = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi ( = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes ( = 0.016 nuclear, = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Further large-scale studies are warranted to investigate the potential role of ERβ and GPER in the pathogenesis of melanocytic lesions.
Topics: Cross-Sectional Studies; Dysplastic Nevus Syndrome; Estrogen Receptor alpha; Estrogen Receptor beta; Humans; Melanoma; Receptors, Estrogen; Receptors, G-Protein-Coupled; Skin Neoplasms
PubMed: 34833446
DOI: 10.3390/medicina57111228