Melanoma nodular de la región acral con metástasis distal

The tumor genetics of acral melanoma: What should a dermatologist know?

Sentinel lymph node biopsy (SLNB) is useful for staging of patients with melanoma. Although SLNB is mostly performed under general anesthesia (GA), tumescence local anesthesia (TLA) can also be used. However, less data are available regarding feasibility of SLNB under TLA. Here we present a post-operative follow-up of 150 patients. We prospectively analyzed data from 150 patients with primary cutaneous malignant melanoma. We assessed pain, post-operative complications and patients' satisfaction after SLNB under TLA. 32% of the patients reported post-operative pain within the first 48h after SLNB. Seroma was the most frequent complication, as 29 seromas after SLNB were observed. Wound infection was observed in 3.3% of the patients. 98.7% of the patients were satisfied with SLNB under TLA. SLNB under TLA is a safe and feasible option and should be considered for patients with melanoma. Especially with multimorbid or elderly patients, the risks of GA can be avoided.

33755 Patterns and prognosis of distant metastases of melanoma subtypes in the Surveillance, Epidemiology, and End Results database

Simple SummaryIncreased sun exposure and sunburns lead to higher numbers of moles as well as melanomas and non-melanoma skin cancers. Scientists are unsure whether there is a difference between being in the sun very often (chronic sun damage) and being in the sun for too long at certain times (intermittent exposure) in terms of the individual melanoma risk. In this study, we used light microscopy to look at typical connective tissue changes in the skin that occur with long-term sun exposure. We analyzed whether these changes are correlated with different subtypes of melanomas and whether they are associated with sun-exposed body sites (chronic exposure) and shaded body sites (intermittent exposure). Our results show that tissue changes near moles and melanomas as well as subtypes of melanomas vary, regardless of patient age and tumor site. This finding is important because it sheds light on the biological effects of sunlight on pigment cells, which are the source of moles and melanomas. Moreover, it emphasizes the need to more clearly differentiate among the subtypes of melanomas.(1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure in nevi and different clinical melanoma subtypes (i.e., superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), acral lentiginous melanoma (ALM), and lentigo maligna melanoma (LMM)) with respect to clinical variables (age, sex, and body site). (2) Methods: We defined a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 595 melanocytic lesions from 559 patients with their clinical variables. (3) Results: The TEG was correlated with age and UV-exposed body sites. Furthermore, the TEG was significantly higher in LMM than in all other types of melanomas and the TEG in NMM was higher than in SSM, irrespective of patient age and tumor site. (4) Conclusions: High cumulative UV exposure is more strongly associated with LMM and NMM than with other melanoma subtypes.

The histological subtype is not considered one of the major prognostic factors in melanoma, yet it is known to have an impact on survival. The aim of this study was to investigate the clinical significance of histological subtypes and the possible impacts of clinicopathological factors on the course of melanoma patients of all stages. A total of 1017 cutaneous melanoma patients were analyzed retrospectively. Four major melanoma histotypes that were studied in this study were as follows: (1) superficial spreading melanoma (SSM), (2) nodular melanoma (NM), (3) acral lentiginous melanoma (ALM), and (4) lentigo maligna melanoma (LMM). Unlike SSMs and LMMs, there were statistically significant correlations between NMs and ALMs and most aggressive histopathological prognostic indicators, such as higher Clark level ( P = 0.0001), thick Breslow depth ( P = 0.0001), presence of ulceration ( P = 0.0001), and lymphovascular invasion ( P = 0.0001). Furthermore, NMs and ALMs were also associated with advanced clinical stages, that is, node involvement and metastasis. Relapse rates for nonmetastatic melanomas were higher in NMs (39.6%) and ALMs (35.3%) than in SSMs (24.3%) and LMMs (10.3%) ( P = 0.0001). Additionally, 5-year relapse-free survival rates were 90.5%, 70.5%, 55.7%, and 50.5% in LMMs, SSMs, ALMs, and NMs, respectively ( P = 0.0001). Moreover, 5-year overall survival rates plummeted from 84.3% in LMMs to 74.8%, 64.3%, and 46% in SSMs, ALMs, and NMs, respectively ( P = 0.0001). In conclusion, we observed that the histologic subtype was an independent predictor for relapse and outcome for cutaneous melanoma patients. Both NM and ALM had unfavorable prognoses, and they were associated with known poor pathological and clinical indicators.

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Understanding local spreading patterns of melanomas is a precondition for the localized surgical treatment and histopathologic investigation. We used hematoxylin and eosin-stained paraffin sections for a two-phase, cellular and microscopic study of patterns of lateral spread in superficial spreading melanomas (SSMs), nodular melanomas (NMs), lentigo maligna melanomas (LMMs), and acral lentiginous melanomas (ALMs). Complete histologic examination of vertical excisional margins was carried out with paraffin sections 5 mm beyond the clinical tumor border of 1395 SSMs, 376 NMs, 179 LMMs, 46 ALMs, and 37 acrally located SSMs or NMs. Further sections of embedded material were analyzed when tumor-positive margins were found. In case of continuous tumor spread, reoperations were continued until the tissue was free of tumor cells. In case of noncontinuity, a final excision was made to a minimum safety margin of 10 to 20 mm. Concentrically consecutive, 5-microm thick hematoxylin and eosin-stained sections were taken from the outside of a 10-mm safety margin inward to the clinical borders of 34 SSMs, five NMs, 10 LMMs, and five ALMs. Noncontinuous subclinical spread was found in all SSMs and NMs in the form of few isolated cell nests at the epidermis-dermis junction. Ninety-two percent of these were located within 6 mm of the central tumor. All LMMs and ALMs showed a clearly demonstrable, uninterrupted spread into the periphery at the epidermis-dermis junction, too, usually in groups of outgrowths. The probability of finding these outgrowths 5 mm beyond the clinical tumor border was 54% in LMM and ALM. Complete histologic examination of vertical excisional margins (micrographic surgery) is therefore the therapy of choice only for LMM and ALM and is inefficient for SSM and NM.

BackgroundCONCORD‐3 highlighted wide disparities in population‐based 5‐year net survival for cutaneous melanoma during 2000–2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma.ObjectivesWe aimed to assess whether the differences in morphology may explain global variation in survival.MethodsPatients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722–8723, 8726–8727, 8730, 8740–8741, 8746, 8761, 8770–8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All‐ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death.ResultsWorldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010–2014, age‐standardized 5‐year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes.ConclusionsThis study provides the broadest picture of distribution and population‐based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment.What is already known about this topic?The histopathological features of cutaneous melanoma vary markedly worldwide.The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin.What does this study add?We aimed to assess the extent to which these differences in morphology may explain international variation in survival when all histological subtypes are combined.This study provides, for the first time, international comparisons of population‐based survival at 5 years for the main histological subtypes of melanoma for over 1.5 million adults diagnosed during 2000–2014.This study highlights the less favourable distribution of histological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas.We found that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma compared with superficial spreading melanoma.

BRAF mutations are present in two thirds of cutaneous melanomas and many of the rest have NRAS mutations. However, cutaneous melanoma is a heterogeneous disease with many clinicopathologic subtypes. Of these, the majority fits into four categories: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma (ALM). Thus far, there is very limited data combining BRAF and NRAS mutation analysis to explore differences between cutaneous melanoma subtypes. The aim of this study was to address this issue. The frequency of BRAF and NRAS hotspot mutations, in exons 15 and 2, respectively, was assessed in 59 cutaneous melanomas comprising superficial spreading, nodular, lentigo maligna, and ALM using single-strand conformational polymorphism and RFLP-PCR analysis. Only 2 of 21 (9.5%) ALM showed BRAF exon 15 mutation compared with 9 of 14 (64.3%) superficial spreading malignant melanomas, 4 of 11 (36.4%) nodular melanomas, and 7 of 13 (53.4%) lentigo maligna melanomas (P < 0.01). However, our key finding is that the combined analysis of BRAF exon 15 and NRAS exon 2 showed that there were no significant differences in the overall mutation frequency between subtypes. In particular, 9 of 19 (47.4%) ALM without BRAF exon 15 mutation had an NRAS exon 2 mutation. We show that the overall BRAF/NRAS frequency in mutation hotspots is not significantly different among cutaneous melanoma subtypes. These data show that mitogen-activated protein kinase pathway activation may be important in all major subtypes of cutaneous melanoma, although the mechanism by which this is achieved varies.

The incidence of malignant melanoma, the most lethal form of skin cancer, is increasing. Approximately 76,000 new cases of invasive melanoma and 9,000 deaths from the disease are anticipated in 2012. Melanoma, a heterogeneous and multistep disease, is one of the most frequent cancers in young adults 20-30 years of age. Identification of prognostic factors for melanoma patients and a better understanding of melanoma progression are needed. An initial radial growth phase of melanomas is followed by a vertical growth phase. Although metastatic capacity is thought to be acquired during the vertical growth phase, metastases occur in some patients with primary melanomas having a radial growth pattern. In this study of 40 melanoma patients we examined immunohistochemically detected cytoplasmic and nuclear expression of p21-activated kinase 1 (PAK 1) in FFPE archived surgical specimens of the four major subtypes of cutaneous melanoma (superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma), as well as benign nevi and normal skin, in relation to clinical outcome. The highest expression of both nuclear and cytoplasmic PAK 1 was found in superficial spreading melanomas (which comprise 70% of melanoma cases in the US) and was significantly increased relative to normal skin (P &amp;lt; 0.0001). High nuclear and cytoplasmic expression of PAK 1 relative to normal skin was found in some (8-17%) of the other forms of melanoma. Overexpression of PAK 1 was not found in lymph node or lung metastases from 13 patients. Overexpression of cytoplasmic PAK 1 in the primary tumors from 28 patients was associated with increased survival (P = 0.03). Only 25% of patients with uniformly high (3+) cytoplasmic expression of PAK 1 in their primary tumor died compared to 67% of patients with less cytoplasmic PAK 1. Similarly only 22% of patients with more than trace expression of PAK 1 in 50% of the nuclei in their primary tumor died compared to 61% of patients with less nuclear PAK 1. The difference in survival between 28 patients with high and low nuclear PAK 1 in their primary tumor approached significance (P = 0.062). Overall, patients with superficial spreading melanoma had not only the highest cytoplasmic and nuclear PAK 1 expression in their tumor, but also tended to have better survival than patients with other forms of melanoma (P = 0.07). PAK 1 has multiple cellular effects including effects on growth factor signaling, cytoskeletal signaling, oncogenic transformation and survival, and chromatin and nuclear signaling. Our data indicate that PAK 1 overexpression in primary melanomas portends increased survival for the melanoma patient, possibly reflecting the relevance of PAK 1 to the radial vs. the vertical phase of melanoma progression. Citation Format: Julia H. Carter, Nelson R. Spaulding, Bruce M. Colligan, James A. Deddens, Larry E. Douglass. Overexpression of PAK 1 is a favorable prognostic biomarker in malignant melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 22. doi:10.1158/1538-7445.AM2013-22

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.

Malignant Melanoma (MM) is the most serious skin tumor and its incidence is doubling every 10 years. MM has been classified into subtypes which include melanoma in situ, lentigo maligna melanoma, nodular melanoma, acral lentiginous melanoma, desmoplastic melanoma, superficial spreading melanoma. Although the subtypes of MM overlap, there are characteristic clinical features of each that are generally recognizable. Evaluation of pigmented lesions requires correlation of clinical findings with risk factors, family history, and histology. A representative skin biopsy should be performed on any lesion suspected of being MM, even if the possibility is remote. The earliest metastases are often in regional lymph nodes. Surgical lymphadenectomy usually can control regional disease. Liver, lung, bone, and brain are common sites of metastases [1, 2]. Conjunctival metastases from a cutaneous melanoma are a rare and ominous sign of widely disseminated disease [3–5]. Once widespread metastatic disease is established, the likelihood of cure is low. Herein, we report a rare case of MM recurred in the conjunctiva. In the summer of 1997 a 31-year-old woman noticed widening of a mole on the posterior of left arm over 6 months. She was a swimmer and scuba diver. She stated that she had a lot of moles since childhood. The nevus was operated with a wide excision and a 2 cm margin. The pathological examination revealed that it was a superficially spreading MM 1.2 mm deep. Lymph node dissection and scans showed no metastatic disease. The patient was diagnosed with localized disease of stage IB.

Cutaneous malignant melanoma in Eastern Taiwan: Clinicopathologic analysis of 56 cases

PurposeThe present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China.Materials and methodsThe database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis softwareResultsIn this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis.ConclusionsThe clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant.

Reducing mortality in individuals at high risk for advanced melanoma through education and screening