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Critical Reviews in Eukaryotic Gene... 2020Melanoma is a skin cancer caused by a malignancy of melanocytes. Incidence of melanoma is rapidly increasing worldwide, which results in public health problems. Primary... (Review)
Review
Melanoma is a skin cancer caused by a malignancy of melanocytes. Incidence of melanoma is rapidly increasing worldwide, which results in public health problems. Primary extracutaneous melanomas can be ocular, gastrointestinal, mucosal, leptomeningeal, genitourinary, and lymphatic. The relationship between exposure to ultraviolet (UV) light and development of melanoma is intensively acute and complex, and intermittent sun exposure greatly increases the risk of melanoma. It is the fifth most common type of cancer in men number and the sixth most common in women. The diagnosis of melanoma is made through clinical assessment of the pigmented by health care professionals. Architectural features of malignant melanoma including asymmetry, confluence of growth, marked cellularity, and poor circumscription. The cytological feature of malignant melanoma include an irregular and thick nuclear membrane and prominent nucleoli. The preventive measures include reducing exposure to UV light and the sun. The early detection of skin cancer greatly reduces both short- and long-term morbidity and mortality. The treatment and follow-up with the doctor for melanoma patients may differ because of the stage of the tumor and the primary lesion. The typical therapy for malignant melanoma is surgical excision, immunotherapy such as interleukin 2 (IL-2), gene therapy, and biochemotherapy.
Topics: Female; Humans; Male; Melanoma; Skin Neoplasms
PubMed: 32894659
DOI: 10.1615/CritRevEukaryotGeneExpr.2020028454 -
In Vivo (Athens, Greece) 2014This article reviews epidemiology, risk factors, pathogenesis and diagnosis of melanoma. Data on melanoma from the majority of countries show a rapid increase of the... (Review)
Review
This article reviews epidemiology, risk factors, pathogenesis and diagnosis of melanoma. Data on melanoma from the majority of countries show a rapid increase of the incidence of this cancer, with a slowing of the rate of incidence in the period 1990-2000. Males are approximately 1.5-times more likely to develop melanoma than females, while according to other studies, the different prevalence in both sexes must be analyzed in relation with age: the incidence rate of melanoma is grater in women than men until they reach the age of 40 years, however, by 75 years of age, the incidence is almost 3-times as high in men versus women. The most important and potentially modifiable environmental risk factor for developing malignant melanoma is the exposure to ultraviolet (UV) rays because of their genotoxic effect. Artificial UV exposure may play a role in the development of melanoma. The most important host risk factors are the number of melanocytic nevi, familiar history and genetic susceptibility. A patient with a personal history of melanoma must be considered at greater risk for subsequent melanoma. Indeed approximately 1-8% of patients with prior history of melanoma will develop multiple primary melanomas. We herein review the dermatological diagnosis and classification of melanoma.
Topics: Humans; Melanoma; Risk Factors
PubMed: 25398793
DOI: No ID Found -
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 -
Cancer Aug 2016Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United... (Review)
Review
Melanomas of the choroid, ciliary body, and iris of the eye are collectively known as uveal melanomas. These cancers represent 5% of all melanoma diagnoses in the United States, and their age-adjusted risk is 5 per 1 million population. These less frequent melanomas are dissimilar to their more common cutaneous melanoma relative, with differing risk factors, primary treatment, anatomic spread, molecular changes, and responses to systemic therapy. Once uveal melanoma becomes metastatic, therapy options are limited and are often extrapolated from cutaneous melanoma therapies despite the routine exclusion of patients with uveal melanoma from clinical trials. Clinical trials directed at uveal melanoma have been completed or are in progress, and data from these well designed investigations will help guide future directions in this orphan disease. Cancer 2016;122:2299-2312. © 2016 American Cancer Society.
Topics: Chromosome Aberrations; Combined Modality Therapy; Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Testing; Humans; Melanoma; Mutation; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Research; Treatment Outcome; Uveal Neoplasms
PubMed: 26991400
DOI: 10.1002/cncr.29727 -
Plastic and Reconstructive Surgery Aug 2016After reading this article, the participant should be able to: 1. Discuss the initial management of cutaneous malignant melanoma with regard to diagnostic biopsy and... (Review)
Review
LEARNING OBJECTIVES
After reading this article, the participant should be able to: 1. Discuss the initial management of cutaneous malignant melanoma with regard to diagnostic biopsy and currently accepted resection margins. 2. Be familiar with the management options for melanoma in specific situations such as subungual melanoma, auricular melanoma, and melanoma in the pregnant patient. 3. Discuss the differentiating characteristics of desmoplastic melanoma and its treatment options. 4. List the indications for sentinel lymph node biopsy and be aware of the ongoing trials and current literature. 5. Discuss the medical therapies available to patients with metastatic melanoma.
SUMMARY
Management of the melanoma patient is a complex and evolving subject. Plastic surgeons should be aware of the recent changes in the field. Excisional biopsy remains the gold standard for diagnosis, although there is no evidence that use of other biopsy types alters survival or recurrence. Wide local excisions should be carried out with margins as recommended by National Comprehensive Cancer Network guidelines according to lesion Breslow depth, with sentinel lymph node biopsy being offered to all medically suitable candidates with intermediate thickness melanomas (1.0 to 4.0 mm), and with sentinel lymph node biopsy being considered for high-risk lesions (ulceration and/or high mitotic figures) with melanomas of 0.75 to 1.0 mm. Melanomas diagnosed during pregnancy can be treated with preoperative lymphoscintigraphy and wide local excision under local anesthesia, with sentinel lymph node biopsy under general anesthesia delayed until after delivery. Management of desmoplastic melanoma is currently controversial with regard to the indications for sentinel lymph node biopsy and the efficacy of postoperative radiation therapy. Subungual and auricular melanoma have evolved from being treated by amputation of the involved appendage to less radical procedures-ear reconstruction is now attempted in the absence of gross invasion into the perichondrium, and subungual melanomas may be treated with wide local excision down to and including the periosteum, with immediate full-thickness skin grafting over bone. Although surgical treatment remains the current gold standard, recent advances in immunotherapy and targeted molecular therapy for metastatic melanoma show great promise for the development of medical therapies for melanoma.
Topics: Biopsy; Combined Modality Therapy; Diagnosis, Differential; Disease Management; Humans; Melanoma; Skin; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 27465194
DOI: 10.1097/PRS.0000000000002367 -
Current Oncology Reports Mar 2018Mucosal melanoma is of great interest due to its aggressive behavior and less favorable prognosis. The literature is mainly case reports and case series. Here, we will... (Review)
Review
PURPOSE OF REVIEW
Mucosal melanoma is of great interest due to its aggressive behavior and less favorable prognosis. The literature is mainly case reports and case series. Here, we will collect the knowledge on mucosal melanoma from the last decade and review the literature. The main focus is being site-specific clinical features, treatment, and prognosis.
RECENT FINDINGS
The use of immunotherapy gain ground as for others subsets of melanoma. Anti-CTLA-4 and anti-PD-1/ PD-L1 blockade in mucosal melanoma have been evaluated in recent studies. Clinical trials are ongoing. The etiology of mucosal melanomas remains unknown. Head and neck mucosal melanomas are most common. Wide excision surgery is the treatment of choice. The effect of adjuvant therapy on survival remains questionable due to the limited knowledge. Radiotherapy seems to give better local control. The overall five-year survival rate for mucosal melanomas is 0-45%. Recent data indicates that this may be improved by the immunotherapy in the years to come.
Topics: Antineoplastic Agents; Humans; Immunotherapy; Melanoma; Mucous Membrane; Prognosis; Survival Rate
PubMed: 29569184
DOI: 10.1007/s11912-018-0675-0 -
American Journal of Clinical Dermatology Nov 2018This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the... (Review)
Review
This review presents the main challenges encountered when diagnosing unusual variants of malignant melanoma with the aim of raising awareness to allow application of the most appropriate treatment strategies. Although these melanomas are often rare, their misdiagnosis potentially jeopardizes patients' health and survival, and has medicolegal implications. The clinical and histologic presentations of melanoma vary greatly, and assessment of uncommon melanomas can be difficult for practitioners because of their scarcity and resemblance to other dermatologic entities. The most problematic melanoma types are desmoplastic melanoma, polypoid melanoma, primary dermal melanoma, verrucous malignant melanoma, pigmented epithelioid melanocytoma, mucosal melanoma, follicular melanoma and melanoma with non-melanocytic differentiation. The two most difficult-to-diagnose subtypes of melanoma are the nevoid and the amelanotic melanomas. Some specific attributes of these variants can be more easily recognized with digital dermatoscopy, facilitating early detection and possibly avoiding invasive procedures. Key cases with the most notable clinical, dermatoscopic, and histopathologic features are presented, highlighting the practical issues of making an accurate diagnosis and choosing the best therapy.
Topics: Clinical Decision-Making; Dermoscopy; Diagnosis, Differential; Disease Progression; Humans; Melanoma; Microscopy, Confocal; Prognosis; Skin; Skin Neoplasms; Survival Rate
PubMed: 30374898
DOI: 10.1007/s40257-018-0373-6 -
Current Treatment Options in Oncology Jan 2019Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and... (Review)
Review
Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10-15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.
Topics: Combined Modality Therapy; Humans; Immunotherapy; Japan; Melanoma; Molecular Targeted Therapy; Randomized Controlled Trials as Topic
PubMed: 30675668
DOI: 10.1007/s11864-019-0607-8 -
Archives of Pathology & Laboratory... Oct 2001The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic... (Review)
Review
CONTEXT
The rapidly developing fields of melanoma research are revolutionizing the current concepts on melanoma etiology and pathogenesis and are introducing newer diagnostic techniques and potential therapeutic approaches.
OBJECTIVES
To present the most current concepts on the etiology and pathogenesis of melanoma and to introduce the recent diagnostic techniques and the potential therapeutic approaches.
METHODS
Data sources were reports on melanoma published in the English language literature and observations made using specimens available at Harvard University, Johns Hopkins Medical Center, Albany Medical College, Loyola University Medical Center, and University of Tennessee Health Science Center.
RESULTS
Studies on melanoma containing chromosomal or genetic evaluation were selected for further analysis. Current clinical and pathologic categories with the reported genetic abnormalities were related to the latest information on pigment biology. The data extracted were used to develop a conceptual framework on the pathogenesis of melanoma; the generated model was then evaluated and used to suggest potential therapeutic approaches.
CONCLUSIONS
(1) Melanoma is not genetically homogeneous, and the existing differences between the pathologic categories, particularly in areas such as type of growth phase (radial vs vertical growth), total vertical dimension, ulceration of primary tumor, and metastatic process, have profound prognostic and therapeutic implications. (2) Chromosomal aberrations and gene mutations are found in sporadic and familial melanomas; among the most important are those affecting the 9p21, which contains the p16 locus, a site known to be critical for normal progression of the cell cycle. Aberrant p16 expression is associated with more aggressive behavior. (3) Melanoma cells possess a remarkable repertoire of biosynthetic capacities represented by the production of hormones, growth factors, and their receptors that may sustain and accelerate tumor development and progression. For example, expression of the tumoral products alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone is regulated in vitro by ultraviolet light, a known carcinogen. (4) Melanomas differ from other tumors in their intrinsic capability to express melanogenic enzymes with the corresponding structural proteins to actually synthesize melanin. Melanogenesis-related proteins are rapidly entering the clinical arena, being used not only as diagnostic markers, but also as potential targets for melanoma therapy.
Topics: Chromosome Aberrations; Chromosome Disorders; Disease Susceptibility; Female; Genetic Predisposition to Disease; Growth Substances; Humans; Immunotherapy; Male; Melanins; Melanoma; Neoplasm Metastasis
PubMed: 11570904
DOI: 10.5858/2001-125-1295-MM -
The American Journal of Dermatopathology May 2014The incidence of cutaneous malignant melanoma has rapidly increased in recent years in all parts of the world, and melanoma is a leading cause of cancer death. As even... (Review)
Review
The incidence of cutaneous malignant melanoma has rapidly increased in recent years in all parts of the world, and melanoma is a leading cause of cancer death. As even relatively small melanomas may have metastatic potential, accurate assessment of progression is critical. Although diagnosis of cutaneous malignant melanoma is usually based on histopathologic criteria, these criteria may at times be inadequate in differentiating melanoma from certain types of benign nevi. As for prognosis, tumor (Breslow) thickness, mitotic rate, and ulceration have been considered the most important prognostic indicators among histopathologic criteria. However, there are cases of thin primary melanomas that have ultimately developed metastases despite complete excision. Given this, an accurate assessment of melanoma progression is critical, and development of molecular biomarkers that identify high-risk melanoma in its early phase is urgently needed. Large-scale genomic profiling has identified considerable heterogeneity in melanoma and suggests subgrouping of tumors by patterns of gene expression and mutation will ultimately be essential to accurate staging. This subgrouping in turn may allow for more targeted therapy. In this review, we aim to provide an update on the most promising new biomarkers that may help in the identification and prognostication of melanoma.
Topics: Biomarkers, Tumor; Humans; Melanoma; Prognosis; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 24803061
DOI: 10.1097/DAD.0b013e31828a2ec5