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Journal of Cutaneous Pathology Jul 2020Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations... (Comparative Study)
Comparative Study Review
Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations are responsible for the majority of hereditary melanoma, but many other susceptibility genes have been discovered in recent years, including CDK4, TERT, ACD, TERF2IP, POT1, MITF, MC1R, and BAP1. Additionally, melanoma risk is increased in mixed cancer syndromes caused by mutations in PTEN, BRCA2, BRCA1, RB1, and TP53. While early onset, multiple tumors, and family cancer history remain the most valuable clinical clues for hereditary melanoma, characteristic epithelioid cytology of melanocytic tumors may suggest an underlying BAP1 mutation. Herein, we review the clinical and histopathologic characteristics of melanocytic tumors associated with these germline mutations and discuss the role of genetic counseling.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase Inhibitor p16; Genes, p16; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Melanoma; Microphthalmia-Associated Transcription Factor; Middle Aged; Nevus, Pigmented; Phenotype; Receptor, Melanocortin, Type 1; Shelterin Complex; Telomerase; Telomere-Binding Proteins; Tumor Suppressor Proteins; Ubiquitin Thiolesterase; Young Adult
PubMed: 32249949
DOI: 10.1111/cup.13689 -
The American Journal of Surgical... Nov 2018PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen that was isolated by autologous T cells in a melanoma patient. While frequent PRAME... (Comparative Study)
Comparative Study
PRAME (PReferentially expressed Antigen in MElanoma) is a melanoma-associated antigen that was isolated by autologous T cells in a melanoma patient. While frequent PRAME mRNA expression is well documented in cutaneous and ocular melanomas, little is known about PRAME protein expression in melanocytic tumors. In this study we examined the immunohistochemical expression of PRAME in 400 melanocytic tumors, including 155 primary and 100 metastatic melanomas, and 145 melanocytic nevi. Diffuse nuclear immunoreactivity for PRAME was found in 87% of metastatic and 83.2% of primary melanomas. Among melanoma subtypes, PRAME was diffusely expressed in 94.4% of acral melanomas, 92.5% of superficial spreading melanomas, 90% of nodular melanomas, 88.6% of lentigo maligna melanomas, and 35% of desmoplastic melanomas. When in situ and nondesmoplastic invasive melanoma components were present, PRAME expression was seen in both. Of the 140 cutaneous melanocytic nevi, 86.4% were completely negative for PRAME. Immunoreactivity for PRAME was seen, albeit usually only in a minor subpopulation of lesional melanocytes, in 13.6% of cutaneous nevi, including dysplastic nevi, common acquired nevi, traumatized/recurrent nevi, and Spitz nevi. Rare isolated junctional melanocytes with immunoreactivity for PRAME were also seen in solar lentigines and benign nonlesional skin. Our results suggest that immunohistochemical analysis for PRAME expression may be useful for diagnostic purposes to support a suspected diagnosis of melanoma. It may also be valuable for margin assessment of a known PRAME-positive melanoma, but its expression in nevi, solar lentigines, and benign nonlesional skin can represent a pitfall and merits further investigations to better assess the potential clinical utility of this marker.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Child; Female; Humans; Hutchinson's Melanotic Freckle; Immunohistochemistry; Male; Melanocytes; Melanoma; Middle Aged; Nevus, Pigmented; Reproducibility of Results; Skin Neoplasms; Young Adult
PubMed: 30045064
DOI: 10.1097/PAS.0000000000001134 -
Cell Jun 2022Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to...
Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.
Topics: Animals; Heterografts; Humans; Melanoma; Mice; Neoplasm Transplantation; Nevus, Pigmented; Skin Neoplasms
PubMed: 35561684
DOI: 10.1016/j.cell.2022.04.025 -
Pigment Cell & Melanoma Research Nov 2015Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this... (Review)
Review
Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial 'driver' mutations are thought to trigger the establishment of benign nevi. After this initial phase of the cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene-induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy.
Topics: Carcinogenesis; Genetic Predisposition to Disease; Humans; Nevus, Pigmented; Skin Neoplasms
PubMed: 26300491
DOI: 10.1111/pcmr.12412 -
Ugeskrift For Laeger Jul 2022Benign skin tumours are commonly seen by general practitioners. They are important to differentiate from skin malignancies. Most benign skin lesions are diagnosed based...
Benign skin tumours are commonly seen by general practitioners. They are important to differentiate from skin malignancies. Most benign skin lesions are diagnosed based on the history and clinical features. However, if the clinical diagnosis is uncertain, a skin biopsy, e.g. excisional or punch for histopathological examination is necessary to rule out malignancy. Seborrheic keratoses are the most common benign skin tumours with an increasing incidence with age. Other common benign skin lesions include melanocytic naevi, acrochordons and dermatofibromas, which may resemble malignant neoplasms.
Topics: Biopsy; Humans; Nevus, Pigmented; Skin; Skin Diseases; Skin Neoplasms
PubMed: 35959819
DOI: No ID Found -
Singapore Medical Journal Nov 2018Although spongiotic (eczematous), psoriatic and cutaneous skin infections are among the most common in dermatology consultations, melanocytic lesions - including the... (Review)
Review
Although spongiotic (eczematous), psoriatic and cutaneous skin infections are among the most common in dermatology consultations, melanocytic lesions - including the different types of nevi and melanomas - are among those that cause a great deal of concern and stress to patients and their clinicians. A diagnosis of benign melanocytic nevus carries a very good prognosis. However, a diagnosis of melanoma might indicate more aggressive treatment, lifelong surveillance and a worse prognosis. Differentiating between these conditions is not always a straightforward process for clinicians and pathologists. Therefore, knowledge of melanoma mimickers is very important for clinicians in general, and dermatologists and pathologists in particular. In this review, we called attention to some of the more frequent benign but unusual melanocytic lesions that are of diagnostic concern for clinicians evaluating these cutaneous proliferations.
Topics: Cell Proliferation; Diagnosis, Differential; Humans; Incidence; Melanoma; Nevus, Pigmented; Prognosis; Risk; Skin; Skin Neoplasms; United States; Melanoma, Cutaneous Malignant
PubMed: 29774360
DOI: 10.11622/smedj.2018041 -
Anais Brasileiros de Dermatologia 2013Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is... (Review)
Review
Giant congenital melanocytic nevus is usually defined as a melanocytic lesion present at birth that will reach a diameter ≥ 20 cm in adulthood. Its incidence is estimated in <1:20,000 newborns. Despite its rarity, this lesion is important because it may associate with severe complications such as malignant melanoma, affect the central nervous system (neurocutaneous melanosis), and have major psychosocial impact on the patient and his family due to its unsightly appearance. Giant congenital melanocytic nevus generally presents as a brown lesion, with flat or mammilated surface, well-demarcated borders and hypertrichosis. Congenital melanocytic nevus is primarily a clinical diagnosis. However, congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin and by their more varied architecture and morphology. Although giant congenital melanocytic nevus is recognized as a risk factor for the development of melanoma, the precise magnitude of this risk is still controversial. The estimated lifetime risk of developing melanoma varies from 5 to 10%. On account of these uncertainties and the size of the lesions, the management of giant congenital melanocytic nevus needs individualization. Treatment may include surgical and non-surgical procedures, psychological intervention and/or clinical follow-up, with special attention to changes in color, texture or on the surface of the lesion. The only absolute indication for surgery in giant congenital melanocytic nevus is the development of a malignant neoplasm on the lesion.
Topics: Age Factors; Disease Progression; Female; Humans; Male; Melanoma; Nevus, Pigmented; Risk Factors; Skin Neoplasms
PubMed: 24474093
DOI: 10.1590/abd1806-4841.20132233 -
Head and Neck Pathology Mar 2019Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority... (Review)
Review
Black and brown-colored mucocutaneous lesions present a differential diagnostic challenge, with malignant melanoma being the primary clinical concern. The vast majority of pigmented lesions in the head and neck region are the result of benign, reactive factors such as post-inflammatory melanosis. However, it is not uncommon to discover a range of muco-cutaneous black and brown neoplasms in the oro-facial area. The majority of black/brown pigmented neoplasms are melanocytic in origin; these are neoplasms of neural crest derivation. Melanocytic nevi are a diverse group of benign neoplasms that are the result of specific oncogenic mutations. They are common on cutaneous surfaces but can manifest in mucosal sites. Currently, nevi are classified based on clinical and histological criteria. The most common cutaneous and oral mucosal nevus is the acquired melanocytic nevus; nevi do not pose an increased risk for the development of malignant melanoma. Emerging information on specific genetic differences supports the notion of biologically distinct nevi. This article will review the classic clinical and microscopic features of nevi commonly found in the head and neck region, and discuss emerging concepts in nevus pathogenesis and taxonomy. Melanoma is a malignant melanocytic neoplasm and is a result of cumulative genetic deregulation. The etiology of malignant melanoma (MM) is multifactorial and includes underlying genetic susceptibility, UV radiation, skin-type, and race. The majority of MM occurs on cutaneous surfaces and less commonly on mucosal and extra-cutaneous visceral organs. Regardless of location, MM exhibits clinical-pathological features that relate to horizontal or vertical tumor spread. Cutaneous and mucosal MM typically present as asymmetrical, irregularly bordered, large (> 0.5 cm), heterogeneous brown-black lesions with foci of erythema, atrophy or ulceration. As with melanocytic nevi, advances in melanomagenesis research have revealed primary oncogenic BRAF and NRAS mutations associated with cutaneous MM. Unlike their cutaneous counterparts, mucosal melanomas exhibit primary oncogenic alterations in c-KIT and other genes. This article will discuss the role of specific primary oncogenic and secondary/tertiary genetic defects in differential clinical presentation, anatomic distribution, future classification changes, and targeted therapy of melanoma. The clinical and microscopic features of mucosal melanomas and a summary of management guidelines will be discussed. Additionally, this article will cover the salient features of melanocytic neuroectodermal tumor of infancy, a neoplastic entity that can involve the oro-facial region, and the clinical-pathological features of selected, commonly occurring pigmented ectodermally-derived neoplasms that are often part of the clinical differential diagnosis of black-brown pigmented lesions.
Topics: Head and Neck Neoplasms; Humans; Melanoma; Mouth Mucosa; Mouth Neoplasms; Nevus, Pigmented; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30693458
DOI: 10.1007/s12105-019-01008-2 -
The Pan African Medical Journal 2021Congenital melanocytic nevus (CMN) is a proliferation of melanocytes that presents at birth or shortly after birth as light brown to black patches or plaques, covering...
Congenital melanocytic nevus (CMN) is a proliferation of melanocytes that presents at birth or shortly after birth as light brown to black patches or plaques, covering any part of the body occasionally exhibiting hypertrichosis. The estimated prevalence of such large forms is 0.002% of the births, resulting from mutations of genes coding for NRAS and KRAS proteins, usually during the first twelve weeks of pregnancy. Giant CMN also known as "bathing trunk nevus," "giant hairy nevus", and "nevus pigmentosus et pilosus" has highest potential to turn into malignant melanoma. We present a case of a 7 year old boy who came to our clinic with complaints of itching over his left shoulder and back for 4 months duration. He gave history of black patches on those areas since birth that gradually grew in size and attained the current presentation. On examination, well demarcated black patches were noted over his left shoulder, arm, trunk (A) and extending from nape of the neck and the entire back with excessive hair growth (B). A diagnosis of congenital melanocytic nevus was established and since it could potentially evolve into a melanoma, prophylactic surgery with skin grafting was suggested but the patient's parents refused. Hence dermabrasion was done to lighten the dark pigmentation and reduce hair growth within nevi. Parents were counselled about complications of CMN and advised to follow up with a dermatologist regularly. Clinicians should scrupulously examine the child to facilitate timely surgical intervention thereby reducing morbidity and mortality associated with this condition.
Topics: Child; Humans; Infant, Newborn; Male; Melanocytes; Melanoma; Nevus, Pigmented; Skin Neoplasms; Skin Transplantation
PubMed: 34887981
DOI: 10.11604/pamj.2021.40.107.26779 -
Indian Journal of Ophthalmology Dec 2019Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina... (Review)
Review
Melanocytoma is a deeply pigmented variant of melanocytic nevus that classically occurs in the optic disk, sometimes with contiguous involvement of the adjacent retina or choroid. Historically, this tumor was often confused with malignant melanoma both clinically and histopathologically. Today, however, it is generally recognized by its typical clinical features that differ from most melanomas and erroneous enucleation is rarely done. Histopathologically, melanocytoma is composed of intensely pigmented round to oval nevus cells with benign features. Although traditionally believed to be a relatively stationary lesion, it is now known to exhibit minor enlargement in 10--15% of cases and can cause minor visual loss by a variety of mechanisms. In rare instance, it can induce severe visual loss due to spontaneous necrosis of the lesion or compressive optic neuropathy. More importantly, it can exhibit malignant transformation into melanoma in 1--2% of cases. Ophthalmologists should be familiar with melanocytoma of the optic disk and affected patients should be followed periodically.
Topics: Cell Transformation, Neoplastic; Humans; Melanoma; Nevus, Pigmented; Optic Disk; Optic Nerve Neoplasms
PubMed: 31755427
DOI: 10.4103/ijo.IJO_2039_19