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Modern Pathology : An Official Journal... Jan 2020In daily clinical practice melanocytic nevi are commonly encountered. Traditionally, both benign and malignant melanocytic tumors have been sub-classified by their... (Review)
Review
In daily clinical practice melanocytic nevi are commonly encountered. Traditionally, both benign and malignant melanocytic tumors have been sub-classified by their histopathologic characteristics with differing criteria for malignancy applied to each group. Recently, many of the mutations that initiate nevus formation have been identified and specific sets of mutations are found in different subtypes of nevi. Whereas a single mutation appears sufficient to initiate a nevus, but is not enough to result in melanoma, specific combinations of mutations have been identified in some melanocytic tumors that are regarded to be of low biologic potential. The term "melanocytoma" has recently been proposed by the World Health Organization to describe those tumors that demonstrate genetic progression beyond the single mutations that are found in nevi but are not frankly malignant. Melanocytomas occupy intermediate genetic stages between nevus and melanoma and likely have an increased risk of malignant transformation as compared to nevi. This review provides an update on the broad spectrum of melanocytic nevi and melanocytomas and outlines their key histopathologic and genetic features.
Topics: Biomarkers, Tumor; Genetic Predisposition to Disease; Humans; Melanocytes; Mutation; Nevus, Pigmented; Phenotype; Skin Neoplasms
PubMed: 31659277
DOI: 10.1038/s41379-019-0390-x -
Oncogene Oct 2017Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result... (Review)
Review
Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAF-activating mutations, will never progress to melanoma. Herein, we synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. In particular, we focus on the mechanisms by which growth arrest is established after BRAF mutation. Means by which growth arrest can be overcome and how melanocytic nevi relate to melanoma are also considered. Finally, we present a new conceptual paradigm for understanding the growth arrest of melanocytic nevi in vivo termed stable clonal expansion. This review builds upon the canonical hypothesis of oncogene-induced senescence in growth arrest and tumor suppression in melanocytic nevi and melanoma.
Topics: Animals; Cell Proliferation; Epigenomics; Gene Expression Regulation, Neoplastic; Humans; Melanocytes; Melanoma; Mice; Models, Animal; Mutation; Nevus, Pigmented; Proto-Oncogene Proteins B-raf; Signal Transduction; Skin Neoplasms
PubMed: 28604751
DOI: 10.1038/onc.2017.189 -
International Journal of Molecular... Feb 2023One effort to combat the rising incidence of malignant melanoma is focused on early detection by the clinical and dermoscopic screening of melanocytic nevi. However, the... (Review)
Review
One effort to combat the rising incidence of malignant melanoma is focused on early detection by the clinical and dermoscopic screening of melanocytic nevi. However, the interaction between nevi, which are congenital or acquired benign melanocytic proliferations, and melanoma is still enigmatic. On the one hand, the majority of melanomas are thought to form de novo, as only a third of primary melanomas are associated with a histologically identifiable nevus precursor. On the other hand, an increased number of melanocytic nevi is a strong risk factor for developing melanoma, including melanomas that do not derive from nevi. The formation of nevi is modulated by diverse factors, including pigmentation, genetic risk factors, and environmental sun exposure. While the molecular alterations that occur during the progression of a nevus to melanoma have been well characterized, many unanswered questions remain surrounding the process of nevus to melanoma evolution. In this review, we discuss clinical, histological, molecular, and genetic factors that influence nevus formation and progression to melanoma.
Topics: Humans; Melanoma; Skin Neoplasms; Nevus; Nevus, Pigmented; Risk Factors; Nevus, Epithelioid and Spindle Cell
PubMed: 36834954
DOI: 10.3390/ijms24043541 -
Giornale Italiano Di Dermatologia E... Aug 2016Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic... (Review)
Review
Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups.
Topics: Dermoscopy; Humans; Melanocytes; Melanoma; Nevus; Nevus, Pigmented; Skin; Skin Neoplasms
PubMed: 27119653
DOI: No ID Found -
Bioscience Trends 2019We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different...
We conducted a study to try to plot the lesions of melanocytic nevus and malignant melanoma on the palm and fingers, and compared them to identify the different distribution pattern of both lesions. Data on 8 patients with melanomas (4 male and 4 female) and 26 patients with melanocytic nevus (6 male and 20 female) of palm and finger pulp who visited Wakayama Medical University Hospital between 1986 and 2018 was retrospectively collected. We found that all of the 8 lesions of melanoma were located on the finger pulps and distal to the 'distal transverse crease' of the palm, and that melanomas were not present proximal to the transverse crease. On the other hand, melanocytic nevus was present in the proximal area to the distal transverse crease of the palm more frequently than melanomas (50.0% vs. 0%), and there was statistically significant difference (p = 0.011 by Fisher's exact probability test). From these observations, our findings may reveal the contribution of mechanical stress to the cause of palmar melanoma, and may facilitate clinical differentiation between malignant melanoma and melanocytic nevus by the localization. Further studies with increased number of patients are needed to validate the finding.
Topics: Female; Hand; Humans; Male; Melanoma; Nevus, Pigmented; Retrospective Studies; Skin; Skin Neoplasms; Stress, Mechanical
PubMed: 31527333
DOI: 10.5582/bst.2019.01221 -
Pathology, Research and Practice Jul 2024BAP1-inactivated melanocytoma (BIM) is a novel subgroup of melanocytic neoplasm listed in the 5th edition of WHO classification of skin tumor. BIM is characterized by... (Review)
Review
BAP1-inactivated melanocytoma (BIM) is a novel subgroup of melanocytic neoplasm listed in the 5th edition of WHO classification of skin tumor. BIM is characterized by two molecular alterations, including a mitogenic driver mutation (usually BRAF gene) and the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, which encodes for BRCA1-associated protein (BAP1). The latter represents a nuclear-localized deubiquitinase involved in several cellular processes including cell cycle regulation, chromatin remodeling, DNA damage response, differentiation, senescence and cell death. BIMs are histologically characterized by a population of large epithelioid melanocytes with well-demarcated cytoplasmic borders and copious eosinophilic cytoplasm, demonstrating loss of BAP1 nuclear expression by immunohistochemistry. Recently, we have published a series of 50 cases, extending the morphological spectrum of the neoplasm and highlighting some new microscopic features. In the current article, we focus on some new histological features, attempting to explain and link them to certain mechanisms of tumor development, including senescence, endoreplication, endocycling, asymmetric cytokinesis, entosis and others. In light of the morphological and molecular findings observed in BIM, we postulated that this entity unmasks a fine mechanism of tumor in which both clonal/stochastic and hierarchical model can be unified.
Topics: Ubiquitin Thiolesterase; Humans; Tumor Suppressor Proteins; Melanoma; Skin Neoplasms; Nevus, Pigmented; Melanocytes; Biomarkers, Tumor; Mutation
PubMed: 38326181
DOI: 10.1016/j.prp.2024.155162 -
Dermatology Online Journal Feb 2014The melanocytic nevus is a benign and focal proliferation of nevus cells that can be congenital or acquired. Intraoral lesions are uncommon, and the etiology and...
The melanocytic nevus is a benign and focal proliferation of nevus cells that can be congenital or acquired. Intraoral lesions are uncommon, and the etiology and pathogenesis are poorly understood. The occurrence rate of oral compound nevus is about 5.9% to 16.5% of all oral melanocytic nevi. A 22-year-old male patient presented with a dark brown macule on the buccal mucosa of the maxilla in the region of tooth 26. The lesion was elliptical, 0.7 x 0.5 cm, well circumscribed, asymptomatic, and the evolution time was unknown. An excisional biopsy was performed and microscopic analysis revealed nests of nevus cells in the epithelium and underlying connective tissue that were compatible with melanocytic compound nevus. Owing to the clinical similarity between oral melanocytic nevus and oral melanoma, a histopathological analysis is mandatory for definitive diagnosis.
Topics: Biopsy; Humans; Male; Mouth Mucosa; Mouth Neoplasms; Nevus, Pigmented; Young Adult
PubMed: 24612575
DOI: No ID Found -
Journal Der Deutschen Dermatologischen... Apr 2022The magnitude of the topic of melanocytic nevi (MN) is directly related to its relevance in everyday clinical work. The different MN have different prognostic... (Review)
Review
The magnitude of the topic of melanocytic nevi (MN) is directly related to its relevance in everyday clinical work. The different MN have different prognostic significance in regard to comorbidity and possible risk of transformation. In addition to the criteria of the ABCDE rule, relevant criteria in the assessment of an MN are the time of occurrence, the growth tendency, the distribution and the comparison with other MN of the respective individual. The present CME article provides an overview of the knowledge that has been gained with regard to the development and genetic background of MN and any risk of degeneration that may exist. In addition, certain clinical and/or dermatoscopic features may provide the clinician with a decision-making aid in the management of different MNs.
Topics: Humans; Melanoma; Nevus, Pigmented; Prognosis; Skin Neoplasms
PubMed: 35446494
DOI: 10.1111/ddg.14776 -
Hereditas Sep 2022Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are...
BACKGROUND
Giant congenital melanocytic nevus (GCMN) is the benign nevomelanocytic proliferation. Mutations in NRAS have been previously detected in GCMN, but mutations in BRAF are generally lacking in the Chinese population. Mutated genes in this disease can estimate the risk of malignant transformation in GCMN. Therefore, it is worth investigating the genetic information of GCMN.
METHODS
Here, we presented two cases of GCMN of the upper extremities. The clinical and histological data were analyzed. The whole exome sequencing (WES) was performed to investigate the mutational profile of peripheral venous blood (PB), normal skin (NS), small melanocytic nevus (SMN), deep penetrating and non-penetrating GCMN (dPGCMN and nPGCMN).
RESULTS
We showed a reduction in the circumference of involved upper extremities in both patients. The clinical and histopathological data indicated the reduction of adipose tissue associated with the invasion of GCMN. The WES data revealed that MUC16, MAP3K15 and ABCA1 were novel potential candidate genes for the disease as well as biomarkers for predicting malignant transformation.
CONCLUSION
The MUC16, MAP3K15 and ABCA1 may serve as novel biomarkers for predicting malignant transformation and targets for the diagnoses and therapy for the GCMN.
Topics: ATP Binding Cassette Transporter 1; CA-125 Antigen; Humans; Membrane Proteins; Mutation; Nevus, Pigmented; Skin Neoplasms; Exome Sequencing
PubMed: 36085074
DOI: 10.1186/s41065-022-00247-8 -
Romanian Journal of Morphology and... 2014Melanocytic nevi are frequently accompanied by inflammatory cells of different types, in varied amounts and distributed in different patterns. In the current report, we... (Review)
Review
Melanocytic nevi are frequently accompanied by inflammatory cells of different types, in varied amounts and distributed in different patterns. In the current report, we review the knowledge on inflammation seen in different types of melanocytic nevi. As an additional contribution, we studied the lymphocytic inflammatory component of Duperrat nevus, as well as the cytotoxic component of Sutton nevus, two contributions that we have not found in the literature. We conclude that: (a) Duperrat nevus has a mixed inflammatory reaction that includes histiocytes, foreign-body multinucleated giant cells, polymorphonuclears, lymphocytes (predominantly CD4+) and plasma cells (commonly abundant); (b) common melanocytic nevi with reactive inflammatory infiltrate usually show a CD4+ predominant population; (c) Meyerson nevus commonly shows an inflammatory infiltrate mainly made up of CD4+ T-cells; (d) Sutton nevus with halo phenomenon is accompanied by a dense inflammatory infiltrate with lymphocytes in a CD4:CD8 ratio varying from 1:1 to 1:3 and in which most of the CD8+ T-cells do not express cytotoxic markers; (e) Wiesner nevus commonly shows a spare lymphocytic infiltrate but the nature of the infiltrate has not yet been investigated.
Topics: CD8-Positive T-Lymphocytes; Humans; Inflammation; Nevus, Pigmented; Plasma Cells; Remission Induction; Skin Neoplasms
PubMed: 25611257
DOI: No ID Found