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Hematology/oncology Clinics of North... Jun 2024Cutaneous melanoma is an aggressive form of skin cancer derived from skin melanocytes and is associated with significant morbidity and mortality. A significant fraction... (Review)
Review
Cutaneous melanoma is an aggressive form of skin cancer derived from skin melanocytes and is associated with significant morbidity and mortality. A significant fraction of melanomas are associated with precursor lesions, benign clonal proliferations of melanocytes called nevi. Nevi can be either congenital or acquired later in life. Identical oncogenic driver mutations are found in benign nevi and melanoma. While much progress has been made in our understanding of nevus formation and the molecular steps required for transformation of nevi into melanoma, the clinical diagnosis of benign versus malignant lesions remains challenging.
PubMed: 38880666
DOI: 10.1016/j.hoc.2024.05.005 -
Cancers May 2024Spitz and Spitzoid lesions represent one of the most challenging melanocytic neoplasms in dermatopathology. Nosologic classification has been more recently improved by...
Spitz and Spitzoid lesions represent one of the most challenging melanocytic neoplasms in dermatopathology. Nosologic classification has been more recently improved by the discovery of novel molecular drivers, particularly translocations. In the current study, we aimed to use an unbiased approach to explore the gene expression profile of a group of melanocytic Spitz and Spitzoid melanocytic lesions ranging from benign lesions to melanoma, including intermediate lesions such as SPARK nevi and atypical Spitz tumors/melanocytomas. Using unsupervised analysis of gene expression data, we found some distinct hierarchical clusters of lesions, including groups characterized by and translocations. Few non-ALK translocated tumors demonstrated increased ALK expression, confirmed by immunohistochemistry. Spitz tumors with overlapping features of dysplastic nevi, so-called SPARK nevi, appear to have a common gene expression profile by hierarchical clustering. Finally, weighted gene correlation network analysis identified gene modules variably regulated in subtypes of these cases. Thus, gene expression profiling of Spitz and Spitzoid lesions represents a viable instrument for the characterization of these lesions.
PubMed: 38791877
DOI: 10.3390/cancers16101798 -
Northern Clinics of Istanbul 2024Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study...
OBJECTIVE
Although the role of MMPs in the pathogenesis of melanoma is known, few studies have investigated their role in the development of nevi and dysplastic nevi. This study aims to search the expression differences of MMP-9, MMP-13, MMP-21, and TIMP-1 between malignant melanoma (MM), intradermal nevi (IDN), and dysplastic nevi (DN).
METHODS
MMP-9, MMP-13, MMP-21, and TIMP-1 antibodies were studied immunohistochemically for 60 cases in our pathology clinic archive between 2013 and 2014.
RESULTS
The MM group had the highest expression percentage and intensity for MMP-9 (p<0.001). There was no statistical significance between MMP-13 expression intensities of lesion cells and stromal cells and stromal expression intensities (p>0.05). MMP-21 lesion staining intensities in DN and MM compared to IDN were statistically significant (p=0.001, p=0.011, respectively). For TIMP-1, there was a significant difference between the IDN and the MM group regarding the staining proportion of lesion cells (p<0.01). There was a statistically significant difference in all groups according to lesion cells' expression intensity. (IDN-DN p<0.001, IDN-MM p=0.044, DN-MM p<0.001).
CONCLUSION
The following markers can be helpful when lesions cannot be differentiated; increased staining proportions and intensity of MMP-9 in both lesion and stromal cells favor MM in cases where MM and IDN cannot be differentiated. The increased MMP-13 staining proportion of lesion cells can favor DN in cases where the pathologist cannot differentiate DN and MM. Intense expression of MMP-21 by lesion cells can be a potential marker for evaluating the lesion in favor of DN in cases where DN and IDN cannot be differentiated. The high expression intensity of TIMP-1 in lesion cells can favor DN in cases where there is ambiguity between DN and MM. High expression proportion and intensity of stromal cells of TIMP-1 can be useable in favor of MM in cases where MM and DN cannot be differentiated.
PubMed: 38757103
DOI: 10.14744/nci.2023.69009 -
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 -
The Australasian Journal of Dermatology Jun 2024Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based...
BACKGROUND/OBJECTIVES
Although excision of melanocytic nevi with high-grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions.
METHODS
We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded.
RESULTS
Sixty-six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high-grade dysplastic nevi, and 50% (n: 33) were low-grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high-grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17-12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15-13.2), and total colour count (OR = 3.21, 95% CI, 1.2-8.5) were significant predictive factors for the lesions with high-grade dysplasia and melanomas.
CONCLUSIONS
To avoid the underdiagnosis of both melanomas and high-grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1-year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high-grade dysplasia.
Topics: Humans; Male; Skin Neoplasms; Female; Melanoma; Retrospective Studies; Adult; Middle Aged; Nevus, Pigmented; Dysplastic Nevus Syndrome; Dermoscopy; Young Adult; Aged; Adolescent; Neoplasm Grading; Age Factors
PubMed: 38572867
DOI: 10.1111/ajd.14261 -
Cureus Feb 2024Leser-Trélat sign (LTS) is characterized as an eruptive display of multiple seborrheic keratoses (SKs) in association with malignancy. This case highlights the variable...
Leser-Trélat sign (LTS) is characterized as an eruptive display of multiple seborrheic keratoses (SKs) in association with malignancy. This case highlights the variable presentation of LTS secondary to melanoma. To our knowledge, this LTS pattern is the first case where the sign manifests as a subtle pattern secondary to melanoma. This stands in contrast to the five documented cases in the literature of LTS-melanoma, which exhibited distinctive and eruptive patterns. A 64-year-old Caucasian female presented for a wellness examination. No personal history of skin cancer was noted. Patient displayed an onset proliferation of SKs with an irregular, sub-centimeter macular nevus over her right lateral mid back. A 6mm punch biopsy was significant for melanoma in situ, arising within a lentiginous compound dysplastic nevus, focally abutting one peripheral tissue edge. A re-excision with a minimum of 5mm margins was completed and the specimen was negative for residual in situ melanoma. Because of the rare occurrence of this delicate pattern at the site of the melanoma, this presentation adds to the knowledge surrounding this diagnosis. This case emphasizes the importance of maintaining vigilance regarding skin manifestations associated with disease and highlights the critical importance of observation and identification of subtle physical exam findings.
PubMed: 38449989
DOI: 10.7759/cureus.53639 -
PNAS Nexus Feb 2024Telomerase reverse transcriptase (TERT) promoter mutations (TPMs) are frequently found in different cancer types, including ∼70% of sun-exposed skin melanomas. In...
Telomerase reverse transcriptase (TERT) promoter mutations (TPMs) are frequently found in different cancer types, including ∼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 datasets, where melanomas with BRAF V600E mutations were more likely to have a 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: 38371417
DOI: 10.1093/pnasnexus/pgae041 -
Dermatology Practical & Conceptual Jan 2024The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the...
INTRODUCTION
The term "atypical melanocytic nevus" (AMN) is used as a synonym for dysplastic nevus (DN) in clinical practice. Although the criteria for diagnosis of AMN/DN by the Agency for Research on Cancer helps to differentiate AMN/DN from common acquired nevi, they do not have high degrees of specificity, as they are similar to those used for the diagnosis of melanoma.
OBJECTIVES
In this retrospective study we evaluated the correlation and diagnostic concordance of dermoscopy, confocal microscopy, and histological examination in 50 AMN.
METHODS
A graded scale was used to compare histological examination with dermoscopy and confocal microscopy. Low magnification histological images of only the central part of lesions were examined. This allowed histological diagnoses based almost exclusively on architectural criteria instead of simultaneously architectural and cytological, as in the global histological examination.
RESULTS
Our data demonstrate that the diagnostic accuracy of dermoscopy and confocal microscopy diagnosis of the clinical aspects of AMN/DN as nevi or melanomas tends to be equivalent, being fair for nevi and excellent for melanomas. The total percentage of AMN suggested that the accuracy of confocal microscopy in the diagnosis of melanoma (86.7%) is greater than that of dermoscopy (73.3%).
CONCLUSIONS
This study demonstrated that diagnostic assessments of AMN/DN by dermoscopy and confocal microscopy are accurate and often coincide with those of histological examination and that their combined use helps to better manage and monitor these patients by facilitating early detection of melanomas and reducing unnecessary excisions of benign melanocytic lesions.
PubMed: 38364391
DOI: 10.5826/dpc.1401a36 -
Italian Journal of Dermatology and... Feb 2024While the average lifetime risk of melanoma worldwide is approximately 3%, those with inherited high-penetrance mutations face an increased lifetime risk of 52-84%. In...
While the average lifetime risk of melanoma worldwide is approximately 3%, those with inherited high-penetrance mutations face an increased lifetime risk of 52-84%. In countries of low melanoma incidence, such as in Southern Europe, familial melanoma genetic testing may be warranted when there are two first degree relatives with a melanoma diagnosis. Testing criteria for high incidence countries such as USA, or with very-high incidence, such as Australia and New Zealand, would require a threshold of 3 to 4 affected family members. A mutation in the most common gene associated with familial melanoma, CDKN2A, is identified in approximately 10-40% of those meeting testing criteria. However, the use of multi-gene panels covering additional less common risk genes can significantly increase the diagnostic yield. Currently, genetic testing for familial melanoma is typically conducted by qualified genetic counsellors, however with increasing demand on testing services and high incidence rate in certain countries, a mainstream model should be considered. With appropriate training, dermatologists are well placed to identify high risk individuals and offer melanoma genetic test in dermatology clinics. Genetic testing should be given in conjunction with pre- and post-test consultation. Informed patient consent should cover possible results, the limitations and implications of testing including inconclusive results, and potential for genetic discrimination. Previous studies reporting on participant outcomes of genetic testing for familial melanoma have found significant improvements in both sun protective behavior and screening frequency in mutation carriers.
Topics: Humans; Melanoma; Melanoma, Cutaneous Malignant; Genetic Predisposition to Disease; Cyclin-Dependent Kinase Inhibitor p16; Skin Neoplasms; Genetic Testing; Dysplastic Nevus Syndrome
PubMed: 38287743
DOI: 10.23736/S2784-8671.23.07761-7 -
Medicina (Kaunas, Lithuania) Jan 2024: Melanoma, a malignant tumor arising from uncontrolled melanocytic proliferation, commonly found in the skin but capable of affecting extracutaneous sites, ranks fifth... (Review)
Review
: Melanoma, a malignant tumor arising from uncontrolled melanocytic proliferation, commonly found in the skin but capable of affecting extracutaneous sites, ranks fifth among diagnosed oncological entities and is a significant cause of cancer deaths, constituting over 80% of skin cancer mortality. Genetic factors and ultraviolet radiation (UVR) exposure, from both natural and artificial sources, are the primary risk factors. : We reported the case of a 25-year-old female with numerous pigmented nevi and notable changes attributed to extensive indoor tanning sessions. Dermatological examinations and dermoscopic evaluations revealed atypical features in two pigmented nevi, leading to surgical excision. Histopathological and immunohistochemical analyses confirmed a compound nevus in one lesion and superficial spreading melanoma in the other, emphasizing the importance of vigilant follow-up and the correct use of immunohistochemistry. : Indoor tanning significantly elevates the cutaneous melanoma risk, with initiation before age 35 amplifying the risk by up to 75%, especially in young women. The risk escalates with cumulative sessions, particularly exceeding 480, and individuals undergoing over 30 sessions face a 32% higher risk. UVR induces DNA damage, genetic mutations, and immunosuppression, contributing to oncogenesis. Genetic factors, like the PTCHD2 gene, may influence the tanning dependency. Legislation targeting minors has been enacted globally but only with partial efficacy. Tanning accelerators, though associated with minor side effects, correlate with high-risk behaviors. The case underscores the urgency of addressing indoor tanning risks, emphasizing targeted awareness efforts and legislative improvements. : In conclusion, the reported case highlights the increased risk of cutaneous melanoma linked to indoor tanning, particularly among young women and specific sociodemographic groups. Despite legislative measures, challenges persist, suggesting the potential efficacy of online campaigns involving relatable influencers to raise awareness and discourage artificial tanning.
Topics: Female; Humans; Adult; Melanoma; Skin Neoplasms; Ultraviolet Rays; Skin; Nevus, Pigmented
PubMed: 38276066
DOI: 10.3390/medicina60010187