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Diagnostic Pathology May 2020Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with...
BACKGROUND/OBJECTIVE
Acral and cutaneous melanomas are usually difficult to accurately diagnose in the early stage, owing to the similarity in clinical manifestations and morphology with those of dysplastic nevus (DN). In this study, we aimed to evaluate the diagnostic value of four-color fluorescence in-situ hybridization (FISH) probes specific to the RREB1,CCND1,and MYB genes, and centromere of chromosome 6, in distinguishing DN and melanoma.
METHODS
Fifty one DN and 58 melanoma cases were collected and tested with four-color FISH. Histological features were reviewed and concordant morphologic diagnosis by three pathologists was considered the golden criterion.
RESULTS
Fifty DN and 59 melanoma cases, with 37 melanomas in situ and 22 melanomas in Clark level 2, were confirmed finally; among them, 42 (71.2%) cases were acral. A comparison of clinicopathological features between the two entities showed that several features were considerably more frequently observed in the melanoma group, including more mitotic figures, stratum corneum pigmentation, lymphocyte infiltration, cell atypia, successive or pagetoid melanocyte growth pattern in the epidermis, larger tumor size, and older age at diagnosis. FISH was positive in 3 (6.0%) DN and 56 (94.9%) melanoma cases according to Gerami's criteria. In distinguishing the two groups, the sensitivity of the four-color FISH was 94.9% and specificity was 94.0%.We found that CCND1 gain was the most sensitive, either in Gerami's or Gaiser's criteria. Further analysis showed that CCND1gain was more obvious in the acral group of melanoma.
CONCLUSIONS
We conclude that the four-color FISH test was highly sensitive and specific in distinguishing early-stage acral and cutaneous melanomas from dysplastic nevus in Chinese population, and the most sensitive criterion was the gain of CCND1.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Child, Preschool; Female; Humans; In Situ Hybridization, Fluorescence; Male; Melanoma; Middle Aged; Nevus, Pigmented; Skin Neoplasms; Young Adult
PubMed: 32393283
DOI: 10.1186/s13000-020-00937-9 -
The Journal of Investigative Dermatology Mar 1993Patterns in giant congenital nevi are classified as to extent of cellular involvement of the reticular dermis and by the quality of the fibrous matrix. In addition,... (Review)
Review
Patterns in giant congenital nevi are classified as to extent of cellular involvement of the reticular dermis and by the quality of the fibrous matrix. In addition, classifications are influenced by degrees of cellular atypia. Two general categories are defined. In one, the phenomena are relatively independent of those operative at the dermal-epidermal interface. The lesions are characterized as dermal congenital tumorous dysplasias-blastomas. They are subdivided into major, intermediate, and minor categories and into mature and immature variants. In these variants, disparate populations in the patterns of nodules and plaques (lumpy-bumpy variants) qualify as dermal variants of minimal deviation melanoma as seen in the setting of giant congenital nevi. The respective melanomas in this category are small-cell malignant neoplasms (melanoblastomas of infancy and childhood). In a second category in the clinical setting of giant congenital nevus, rare childhood and some adult melanomas of a more common histologic type evolve from lentiginous and junctional components in patterns that recapitulate those of the dysplastic nevus syndrome. The suspicious areas in all categories are evaluated by the same clinical criteria. In the dysplasia-blastoma category, enlarging nodules must be biopsied. The criteria for the evaluation of lesions in the dysplastic nevus syndrome and in the category of minimal deviation melanoma have application to the unstable regions in giant congenital nevi.
Topics: Humans; Nevus
PubMed: 8440910
DOI: 10.1111/1523-1747.ep12470191 -
BioRxiv : the Preprint Server For... Jul 2023TERT promoter mutations (TPMs) are frequently found in different cancer types, including approximately 70% of sun-exposed skin melanomas. In melanoma, TPMs are among the...
TERT promoter mutations (TPMs) are frequently found in different cancer types, including approximately 70% of sun-exposed skin melanomas. In melanoma, TPMs are among the earliest mutations and can be present during the transition from nevus to melanoma. However, the specific factors that contribute to the selection of TPMs in certain nevi subsets are not well understood. To investigate this, we analyzed a group of dysplastic nevi (DN) by sequencing genes commonly mutated in melanocytic neoplasms. We examined the relationship between the identified mutations, patient age, telomere length, histological features, and the expression of p16. Our findings reveal that TPMs are more prevalent in DN from older patients and are associated with shorter telomeres. Importantly, these TPMs were not found in nevi with BRAF V600E mutations. Conversely, DN with BRAF V600E mutations were observed in younger patients, had longer telomeres, and a higher proportion of p16-positive cells. This suggests that these nevi arrest growth independently of telomere shortening through a mechanism known as oncogene-induced senescence (OIS). These characteristics extend to melanoma sequencing data sets, where melanomas with BRAF V600E mutations were more likely to have inactivation, overriding OIS. In contrast, melanomas without BRAF V600E mutations showed a higher frequency of TPMs. Our data imply that TPMs are selected to bypass replicative senescence (RS) in cells that were not arrested by OIS. Overall, our results indicate that a subset of melanocytic neoplasms face constraints from RS, while others encounter OIS and RS. The order in which these barriers are overcome during progression to melanoma depends on the mutational context.
PubMed: 37503286
DOI: 10.1101/2023.07.14.548818 -
Dermatopathology (Basel, Switzerland) 2017
PubMed: 29457000
DOI: 10.1159/000485181 -
Annals of Diagnostic Pathology Dec 2023Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a...
BACKGROUND
Pathologists face ongoing challenges distinguishing between benign and malignant melanocytic tumors. PRAME (PReferentially expressed Antigen in Melanoma) has a demonstrated value distinguishing between these types of lesions. However, the sensitivity of single immunohistochemistry is variable. HMB-45 is another valuable marker, but on its own, has a limited ability in setting of primary melanocytic tumors. This study sought to evaluate the diagnostic potential of a dual panel combining PRAME and HMB-45 in the assessment of primary melanocytic tumors.
METHODS
259 tumors, of which 141 were benign nevi, 31 dysplastic nevi (either low- or high grade dysplasia), and further 87 malignant melanomas, were retrieved from the department's archives and assessed by two experienced dermatopathologists. New sections were stained with PRAME and HMB-45, respectively. For PRAME, a nuclear, and for HMB-45, a cytoplasmic staining, was considered positive and scored as described in the literature on a scale from 0 to 4+. Only dermal component was assessed on HMB-45 stain.
RESULTS
PRAME was diffusely expressed in only 1 benign nevus, with focal expression in further 28 compared to 22 diffusely and 103 focally HMB-45-positive benign nevi. 5 high-grade dysplastic nevi showed diffuse PRAME expression in epidermal component, with varying degree of positivity in adjacent dermal compartment, and further 8 dysplastic nevi showed only focal expression. HMB-45 was diffusely expressed in only 2, with focal expression in 23, and no apparent positivity in remaining 6 dysplastic nevi. In invasive melanoma group, PRAME stained >75 % cells in 64/87 tumors, however, 10/87 melanomas were completely negative. HMB-45 was captured diffusely in 49/87 melanomas, 32 showed patchy expression, and 6 tumors were blank negative. Diffuse 4+ PRAME positivity showed superior sensitivity and specificity of 73,6 % and 96,5 %, respectively, compared to HMB-45, 56,3 % and 86,0 %, respectively. No nevi showed double 4+ positivity, however, the sensitivity for double positivity was only 49,4 %.
CONCLUSION
Our results confirm the superiority of PRAME over HMB-45 in the differential diagnosis of melanocytic tumors. However, combined staining can significantly increase specificity, rendering a benign diagnosis more unlikely in a double 4+ diffuse positivity setting.
Topics: Humans; Dysplastic Nevus Syndrome; Coloring Agents; Melanoma; Skin Neoplasms; Antibodies, Monoclonal; Nevus; Antigens, Neoplasm; Staining and Labeling; Diagnosis, Differential
PubMed: 37717457
DOI: 10.1016/j.anndiagpath.2023.152211 -
Cell Cycle (Georgetown, Tex.) Jul 2008Although melanoma ultimately progresses to a highly aggressive and metastatic disease that is typically resistant to currently available therapy, it often begins as a... (Review)
Review
Although melanoma ultimately progresses to a highly aggressive and metastatic disease that is typically resistant to currently available therapy, it often begins as a benign nevus consisting of a clonal population of hyperplastic melanocytes that cannot progress because they are locked in a state of cellular senescence. Once senescence is overcome, the nevus can exhibit dysplastic features and readily progress to more lethal stages. Recent advances have convincingly demonstrated that senescence represents a true barrier to the progression of many types of cancer, including melanoma. Thus, understanding the mechanism(s) by which melanoma evades senescence has become a priority in the melanoma research community. Senescence in most cells is regulated through some combination of activities within the RB and p53 pathways. However, differences discovered among various tumor types, some subtle and others quite profound, have revealed that senescence frequently operates in a context-dependent manner. Here we review what is known about melanocyte senescence, and how such knowledge may provide a much-needed edge in our struggles to contain or perhaps vanquish this often-fatal malignancy.
Topics: ADP-Ribosylation Factors; Animals; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Humans; Melanocytes; Melanoma; Proto-Oncogene Proteins c-mdm2; Retinoblastoma Protein; Skin Neoplasms; Telomerase; Telomere; Tumor Suppressor Protein p53
PubMed: 18604170
DOI: 10.4161/cc.7.13.6230 -
Skin Research and Technology : Official... Jan 2022Melanoma screening includes the assessment of changes in melanocytic lesions using images. However, previous studies of normal nevus temporal changes showed variable...
BACKGROUND
Melanoma screening includes the assessment of changes in melanocytic lesions using images. However, previous studies of normal nevus temporal changes showed variable results and the optimal method for evaluating these changes remains unclear. Our aim was to evaluate the reproducibility of (a) nevus count done at a single time point (method I) versus two time points (method II); and (b) manual and automated nevus diameter measurements.
MATERIALS AND METHODS
In a first experiment, participants used either a single time point or a two time point annotation method to evaluate the total number and size of nevi on the back of an atypical mole syndrome patient. A Monte Carlo simulation was used to calculate the variance observed. In a second experiment, manual measurements of nevi on 2D images were compared to an automated measurement on 3D images. Percent difference in the paired manual and automated measurements was calculated.
RESULTS
Mean nevus count was 137 in method I and 115.5 in method II. The standard deviation was greater in method I (38.80) than in method II (4.65) (p = 0.0025). Manual diameter measurements had intraclass correlation coefficient of 0.88. The observed mean percent difference between manual and automated diameter measurements was 1.5%. Lightly pigmented and laterally located nevi had a higher percent difference.
CONCLUSIONS
Comparison of nevi from two different time points is more consistent than nevus count performed separately at each time point. In addition, except for selected cases, automated measurements of nevus diameter on 3D images can be used as a time-saving reproducible substitute for manual measurement on 2D images.
Topics: Dysplastic Nevus Syndrome; Humans; Nevus; Nevus, Pigmented; Reproducibility of Results; Skin Neoplasms
PubMed: 34455638
DOI: 10.1111/srt.13092 -
The Turkish Journal of Gastroenterology... Dec 2011A case of gallbladder malignant melanoma in a 62-year-old woman is reported. The gallbladder, resected for tumor mass seen on ultrasound examination, revealed neoplastic... (Review)
Review
A case of gallbladder malignant melanoma in a 62-year-old woman is reported. The gallbladder, resected for tumor mass seen on ultrasound examination, revealed neoplastic epithelioid cells with dark granules in the cytoplasm. These cells with pigment were positive immunohistochemically for S-100, HMB45 and vimentin. The patient, affected by dysplastic nevus syndrome, had a history of a melanoma in situ in her left upper arm that was excised 11 years ago. This is only the second case reported to date of primary malignant melanoma in dysplastic nevus syndrome.
Topics: Dysplastic Nevus Syndrome; Female; Gallbladder Neoplasms; Humans; Melanoma; Middle Aged
PubMed: 22287410
DOI: 10.4318/tjg.2011.0278 -
Journal of Medicine and Life 2017Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts...
Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period. Melanocytic nevi present a strict cellular architecture and an increased malignant transforming capacity. We investigated reelin presence in 32 melanocytic nevi (5 junctional, 27 compound or 14 dysplastic nevi and 18 non dysplastic nevi). The assessment of reelin presence was performed by histological semiquantitative criteria. Results showed the presence of reelin in 29 cases (29/ 32). The presence of reelin was elevated in junctional areas as in dysplastic nevi. VLDLR presented positive values in 16 cases (16/ 32) and ApoER2 was weak positive in 7 cases. Reelin or its receptors was peritumorally absent. Our study showed the presence of reelin in nevus cells from cutaneous melanocytic nevi and, in these cells, only the VLDLR receptor was present in half of the cases. The significance of the reelin presence in cutaneous nevus cells may be hypothetically considered correlated with the position maintenance of the nevus cells or migration of these cells in malignant transforming situation. ApoER2 = apolipoprotein receptor 2, VLDLR = very low density lipoprotein receptor, DAB-1 = DIABLO protein, HMB45 = gene HMB45.
Topics: Adolescent; Adult; Animals; Cell Adhesion Molecules, Neuronal; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; LDL-Receptor Related Proteins; Male; Middle Aged; Nerve Tissue Proteins; Nevus, Pigmented; Receptors, LDL; Reelin Protein; Serine Endopeptidases; Young Adult
PubMed: 28255385
DOI: No ID Found -
Cancer Feb 2021Patients with primary cutaneous melanoma are at increased risk for subsequent new primary melanomas. Indoor tanning is a recognized risk factor for melanoma. This study...
BACKGROUND
Patients with primary cutaneous melanoma are at increased risk for subsequent new primary melanomas. Indoor tanning is a recognized risk factor for melanoma. This study was aimed at determining the association between indoor tanning and the occurrence of multiple primary melanoma.
METHODS
This was a retrospective case-control study of cases with multiple primary melanoma and sex-matched controls with single primary melanoma retrieved at a 1:2 ratio from the Biological Sample and Nevus Bank of the Melanoma Center of the University of Pittsburgh Cancer Institute. Logistic regression models were used to examine the association between multiple primary melanoma and risk factors.
RESULTS
In total, 330 patients (39.1% men) with a median age of 51 years were enrolled. Compared with patients who had a single primary melanoma, patients with multiple melanomas were younger at the diagnosis of their first primary melanoma and were more likely to be discovered at stage 0 or I and to have had indoor tanning exposure, a family history of melanoma, atypical moles, dysplastic nevi, and a Breslow thickness less than 1 mm. Compared with patients' first melanomas, subsequent melanomas were more likely to be thinner or in situ. The estimated probability of the locus for the second primary being the same as that for the first primary melanoma was 34%. In a multivariate analysis after adjustments for age, a family history of melanoma, the presence of atypical and dysplastic nevi, and recreational sun exposure, indoor tanning remained significantly associated with the occurrence of multiple primary melanoma (odds ratio, 2.75; 95% confidence interval, 1.07-7.08; P = .0356).
CONCLUSIONS
Indoor tanning is associated with an increased risk of second primary melanoma. Subsequent melanomas are more likely to be thin or in situ and to occur in different anatomic locations.
Topics: Adult; Case-Control Studies; Female; Humans; Logistic Models; Male; Melanoma; Middle Aged; Neoplasms, Multiple Primary; Neoplasms, Radiation-Induced; Nevus, Pigmented; Risk Factors; Skin; Skin Neoplasms; Sunbathing; Tanning; Melanoma, Cutaneous Malignant
PubMed: 33170961
DOI: 10.1002/cncr.33307