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Italian Journal of Dermatology and... Jun 2021Despite the rapid recent advances in molecular analysis of tumors, which allow large-scale and high-resolution genomics, the "gold standard" for melanoma diagnosis... (Review)
Review
Despite the rapid recent advances in molecular analysis of tumors, which allow large-scale and high-resolution genomics, the "gold standard" for melanoma diagnosis continues to be histopathology, in conjunction with clinical characteristics and sometimes with important support of immunohistochemistry. Observations, where postulated that cutaneous melanomas may arise through two distinct pathways, discoveries such as that BRAF mutations were mostly common in melanomas on sun-exposed skin with little solar elastosis and seminal works for melanoma progression and evolution set the groundwork for the new WHO Classification of Melanoma: a classification of melanoma that not only encompasses histologic but also clinical, epidemiologic, and genetic characteristics. The melanomas were divided into those etiologically related to sun exposure and those that are not, based on their mutational signatures, anatomic site, and epidemiology. On the basis of degree of associated solar elastosis melanomas on the sun exposed skin were further divided by the histopathologic degree of cumulative solar damage (CSD) of the surrounding skin, into low and high CSD. On the low-CSD group of melanomas are included superficial spreading melanomas, while the high-CSD melanomas encompasses lentigo maligna and desmoplastic melanomas. The "non-CSD" classification includes acral melanomas, some melanomas in congenital nevi, melanomas in blue nevi, Spitz melanomas, mucosal melanomas, and uveal melanomas. Nodular and nevoid melanoma may occur in any pathway. A group of intermediate tumors termed melanocytoma is proposed for tumors that in addition to mutations that activate the MAPK pathway, harbor multiple driver mutations, and they are either low-grade or high-grade, to indicate that they may carry a higher risk of malignant transformation. In this review a summary of the most recent WHO classification of melanoma is provided. A short analysis of essential histopathologic prognostic parameters is also provided. The new classification of melanoma discriminates distinct types of melanoma based on their clinicopathologic, and genomic characteristics. Undoubtedly, melanoma research will continue to evolve as new clinical, pathological, molecular data accumulates. The challenge of the forthcoming years is to better characterize the intermediate category of melanocytic lesions.
Topics: Humans; Hutchinson's Melanotic Freckle; Melanoma; Prognosis; Skin Neoplasms; Uveal Neoplasms
PubMed: 33982546
DOI: 10.23736/S2784-8671.21.06958-3 -
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 -
Saudi Medical Journal Apr 2016Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at...
Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.
Topics: Aged; Humans; Male; Melanoma; Mouth Neoplasms
PubMed: 27052289
DOI: 10.15537/smj.2016.4.15017 -
Frontiers in Oncology 2021The "multidimensional" World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous... (Review)
Review
The "multidimensional" World Health Organization (WHO) classification 2018 of melanocytic tumors encompasses nine melanoma pathways (seven of which for cutaneous melanoma) according to a progression model in which morphologically intermediate melanocytic tumors are cosidered as simulators and/or precursors to melanoma. These "intermediates" can be subclassified into: i) a "classical" subgroup (superficial/thin compound: dysplastic nevus), which is placed within the morphologic and molecular progression spectrum of classical (Clark's and McGovern's) melanoma subtypes (superficial spreading and, possibly, nodular); and ii) a "non-classical" subgroup (thick compound/dermal: "melanocytomas") whose genetic pathways diverge from classical melanoma subtypes. Such a progression model is aimed at giving a conceptual framework for a histopathological classification; however, routine clinicopathological practice strongly suggests that most melanomas arise and that the vast majority of nevi are clinically stable or even involuting over time. Clinicopathological correlation can help identify some severely atypical but benign tumors (: sclerosing nevus with pseudomelanomatous features) as well as some deceptively bland melanomas (: lentiginous melanoma; nested melanoma), thereby addressing some ambiguous cases to a correct clinical management. The recently available adjuvant therapy regimens for melanoma raise the problem of a careful distinction between severely atypical (high grade) melanocytoma and "classical" melanoma: conventional morphology can guide an algorithmic approach based on an antibody panel (anti-mutated BRAF, BAP1, PRAME, ALK, TRKA, MET, HRAS-WT, ROS; beta catenin; R1alpha; p16; HMB45; Ki67), a first-line molecular study (identification of hot spot mutations of and ) and an advanced molecular study (sequencing of ; fusions studies of ); as a final step, next-generation sequencing can identify melanocytic tumors with rare genetic signatures and melanocytic tumors with a high tumor mutation burden which should be definitely ascribed to the category of classical melanoma with the respective therapeutic options.
PubMed: 34277420
DOI: 10.3389/fonc.2021.675296 -
Italian Journal of Dermatology and... Jun 2021The indisputable contribution of dermatoscopy in early diagnosis of melanoma is widely recognized. In the last quinquennium, new data concerning specific melanoma...
The indisputable contribution of dermatoscopy in early diagnosis of melanoma is widely recognized. In the last quinquennium, new data concerning specific melanoma subtypes have come to light. The dermatoscopic morphology of superficial spreading melanoma (SSM) has been extensively investigated in the literature. Atypical network, irregular dots, irregular globules, irregular streaks and irregular blotch correspond to histopathologic alterations at the level of the junction, blue-white veil and atypical vessels suggest intradermal growth, whereas regression structures, negative network and white shiny streaks might reflect junctional or dermal alterations. The list of melanoma specific criteria has been recently updated to include features that typify early melanoma, such as irregular hyperpigmented areas and prominent skin markings and features seen in melanoma on sun damaged skin such as angulated lines. Nodular melanoma lacks most of the aforementioned criteria and is typified by the coexistence of blue and black color, atypical vessels and pink color. Lentigo maligna dermatoscopic criteria mainly develop at the outline of the follicular openings. However, at an early stage these features might be very subtle and the diagnosis should be based on the exclusion of benign tumors (inverse approach). Acral lentiginous melanoma is typified by a parallel ridge pattern, but also SSM criteria should be taken into consideration. The diagnosis of subungual melanoma is based on the assessment of the color and characteristics of the pigmented nail band. For the diagnosis of mucosal melanoma, the assessment of colors is more informative than the assessment of structures and the detection of blue, white or gray should raise the suspicion of melanoma. White shiny streaks and regression structures are the most common features of desmoplastic melanoma. The diagnosis of nevoid melanoma might be highly challenging and require information on the lesion's history. Melanoma on small- and medium-sized congenital nevi is typified by an eccentric location of the suspicious area, negative network and gray angulated lines. Recent advances in knowledge on the dermatoscopic characteristics of peculiar subtypes of the tumor significantly enrich the diagnostic armamentarium of clinicians. The challenge of the forthcoming years is to better characterize biologically aggressive melanomas and to optimize the screening strategies so as to identify them.
Topics: Dermoscopy; Diagnosis, Differential; Humans; Hyperpigmentation; Melanoma; Skin Neoplasms
PubMed: 33314891
DOI: 10.23736/S2784-8671.20.06784-X -
Current Treatment Options in Oncology Sep 2018Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used... (Review)
Review
Dermatoscopy (dermoscopy) improves the diagnosis of benign and malignant cutaneous neoplasms in comparison with examination with the unaided eye and should be used routinely for all pigmented and non-pigmented cutaneous neoplasms. It is especially useful for the early stage of melanoma when melanoma-specific criteria are invisible to the unaided eye. Preselection by the unaided eye is therefore not recommended. The increased availability of polarized dermatoscopes, and the extended use of dermatoscopy in non-pigmented lesions led to the discovery of new criteria, and we recommend that lesions should be examined with polarized and non-polarized dermatoscopy. The "chaos and clues algorithm" is a good starting point for beginners because it is easy to use, accurate, and it works for all types of pigmented lesions not only for those melanocytic. Physicians, who use dermatoscopy routinely, should be aware of new clues for acral melanomas, nail matrix melanomas, melanoma in situ, and nodular melanoma. Dermatoscopy should also be used to distinguish between different subtypes of basal cell carcinoma and to discriminate highly from poorly differentiated squamous cell carcinomas to optimize therapy and management of non-melanoma skin cancer. One of the most exciting areas of research is the use of dermatoscopic images for machine learning and automated diagnosis. Convolutional neural networks trained with dermatoscopic images are able to diagnose pigmented lesions with the same accuracy as human experts. We humans should not be afraid of this new and exciting development because it will most likely lead to a peaceful and fruitful coexistence of human experts and decision support systems.
Topics: Adult; Aged; Algorithms; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dermoscopy; Female; Humans; Keratosis, Actinic; Male; Melanoma; Sensitivity and Specificity; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 30238167
DOI: 10.1007/s11864-018-0573-6 -
Healthcare (Basel, Switzerland) Dec 2013Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns... (Review)
Review
Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery), treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.
PubMed: 27429256
DOI: 10.3390/healthcare2010001 -
Iranian Journal of Medical Sciences Mar 2016
PubMed: 26989291
DOI: No ID Found -
Chonnam Medical Journal Sep 2016Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic... (Review)
Review
Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians.
PubMed: 27689028
DOI: 10.4068/cmj.2016.52.3.185