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1.
Pathol Oncol Res ; 26(4): 2483-2487, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32572820

RESUMO

The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51 years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2 mm (p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.


Assuntos
Melanoma/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Adulto Jovem
2.
J Am Acad Dermatol ; 79(4): 706-713, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29673774

RESUMO

BACKGROUND: Nodal melanocytic nevi (NNs) encountered during sentinel lymph node biopsy (SLB) for malignant melanoma are usually difficult to distinguish from metastatic melanoma. However, NNs have not been well studied in acral lentiginous melanoma (ALM) in Asian populations. OBJECTIVE: To investigate the clinical characteristics and significance of NNs in SLB specimens from patients with ALM. METHODS: We retrospectively analyzed 84 patients with ALM who underwent SLB between June 2010 and July 2017. RESULTS: Of the 84 patients with ALM, 9 (10.7%) had NNs in their SLB specimens. NNs were significantly more common in SLB specimens than in specimens not obtained by SLB. The presence of pre-existing melanocytic lesions was found to be associated with NNs (P < .001). The 5-year overall survival was significantly higher in patients with ALM with NNs than in patients with a positive SLB result (P = .047). Distant recurrence in patients with ALM with NNs was significantly lower than in patients a positive SLB result (P = .03). LIMITATIONS: The small sample size, single-center study design, and retrospective nature of the study were the limitations. CONCLUSION: In Asian populations, the prevalence of NNs in ALM is similar to that reported in Europe and the United States. The rates of distant recurrence and overall survival in patients with ALM who have NNs are similar to those of patients who do not have metastatic melanoma.


Assuntos
Sarda Melanótica de Hutchinson/patologia , Melanoma/patologia , Nevo Pigmentado/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , China , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Hospitais Universitários , Humanos , Sarda Melanótica de Hutchinson/mortalidade , Sarda Melanótica de Hutchinson/cirurgia , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Excisão de Linfonodo/mortalidade , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/cirurgia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/cirurgia , Estatísticas não Paramétricas , Taxa de Sobrevida , Melanoma Maligno Cutâneo
4.
Br J Dermatol ; 176(5): 1247-1258, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27718503

RESUMO

BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.


Assuntos
Biomarcadores Tumorais/metabolismo , Canais de Cálcio Tipo T/metabolismo , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutâneas/diagnóstico , Proliferação de Células/fisiologia , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Melanoma/mortalidade , Recidiva Local de Neoplasia/etiologia , Nevo Pigmentado/mortalidade , Prognóstico , Neoplasias Cutâneas/mortalidade , Regulação para Cima
5.
Clin Exp Dermatol ; 41(7): 709-16, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27663144

RESUMO

BACKGROUND: In malignant melanoma (MM), the proteins SOX10, ABCB5 and CD271 are strongly expressed, and are associated with tumour-initiating potential and stem cell-like properties. AIM: To compare SOX10, ABCB5 and CD271 expression profiles in melanocytic naevi and MM at different stages, and to correlate these with survival data. METHODS: Immunohistochemistry was performed for SOX10, ABCB5 and CD271 expression in common naevi (n = 14), dysplastic naevi (n = 11), primary MM (n = 39), lymph node metastases (n = 14) and distant metastases (n = 14). Data were assessed using univariate and multivariate statistics. RESULTS: Compared with melanocytic naevi, there was significantly higher SOX10 expression in primary melanomas, lymph node metastases and distant metastases. ABCB5 had significantly higher expression in primary melanomas, lymph node metastases and distant metastases compared with melanocytic naevi. CD271 expression was significantly increased in dysplatic naevi, lymph node metastases and distant metastases. Using multivariate analysis, SOX10 was demonstrated to be a significant independent positive predictor for metastatic disease. CONCLUSIONS: SOX10, ABCB5 and CD271 proteins are strongly expressed in advanced MM, whereas SOX10 appears to be the most suitable marker for independent prediction of metastatic disease. Our data indicate that SOX10, ABCB5 and CD271 might play a role in MM progression.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adapaleno/metabolismo , Melanoma/metabolismo , Nevo Pigmentado/metabolismo , Fatores de Transcrição SOXE/metabolismo , Neoplasias Cutâneas/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Adulto Jovem
6.
Am J Surg Pathol ; 39(3): 405-15, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25517953

RESUMO

Differentiating proliferative nodules (PNs) from melanomas arising in congenital nevi (CN) is a considerable challenge for dermatopathologists. Most of the specimens dermatopathologists assess that deal with this differential diagnosis involve proliferations of melanocytes arising in the dermis. In this study, we compare the clinical, histologic, and molecular findings of these 2 conditions. In our database, we found 22 examples of PNs arising in the dermis of CN and 2 cases of lethal melanomas arising from the dermis/epidermis of CN of children. Importantly, we found that among dermal melanocytic proliferations arising from CN in children, PNs are far more common than lethal melanomas. Clinically, multiplicity of lesions favored a diagnosis of PNs, whereas ulceration was infrequent in PNs compared with lethal melanomas. Histologically, PNs showed several distinct patterns including expansile nodules of epithelioid melanocytes with mitotic counts lower than that seen in the melanomas (1.67 vs. 12.5 mitoses/mm), a small round blue cell pattern often highly mitotically active, neurocristic-like, blue nevus-like, a nevoid melanoma-like pattern, or an undifferentiated spindle cell pattern. The lethal melanomas both featured expansile nodules of epithelioid melanocytes with high mitotic counts (range, 5 to 20 mitoses/mm) and an ulcerated overlying epidermis. At the molecular level, the PNs showed mostly whole chromosomal copy number aberrations, which in some cases were accompanied by rare partial chromosomal aberrations, whereas both lethal melanomas showed highly elevated copy number aberrations involving 6p25 without gains of the long arm of chromosome 6.


Assuntos
Proliferação de Células , Melanócitos/patologia , Melanoma/patologia , Nevo Intradérmico/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adolescente , Fatores Etários , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Aberrações Cromossômicas , Cromossomos Humanos Par 6 , Hibridização Genômica Comparativa , Diagnóstico Diferencial , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Masculino , Melanoma/mortalidade , Índice Mitótico , Nevo Intradérmico/congênito , Nevo Intradérmico/mortalidade , Nevo Pigmentado/congênito , Nevo Pigmentado/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/mortalidade , Úlcera Cutânea/patologia , Fatores de Tempo , Adulto Jovem
7.
Can J Ophthalmol ; 49(5): 464-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25284104

RESUMO

OBJECTIVE: This study aimed to assess the ocular and metastatic outcomes of patients with choroidal indeterminate melanocytic lesions treated by primary transpupillary thermotherapy (TTT). DESIGN: Retrospective case series. PARTICIPANTS: Eight patients presenting choroidal indeterminate melanocytic lesions treated by primary TTT. METHODS: A retrospective chart review was conducted for patients with a newly diagnosed choroidal indeterminate melanocytic lesion treated by at least 3 TTT sessions from 2002 to 2011. Best-corrected visual acuity and lesion dimensions were measured at baseline and during follow-up. Complications were recorded including lesion growth, metastasis, melanoma-related mortality, and treatment-related complications. RESULTS: Mean initial thickness was 2.0 ± 0.8 mm. Patients had an average of 3.0 ± 0.9 risk factors for lesion growing. Three patients (38%) had lesion growth. Two patients (25%) had severe visual loss (>1.0 logMAR) directly related to TTT treatment. There were no fatalities due to metastasis. CONCLUSIONS: Despite careful patient selection and systematic treatment with at least 3 TTT sessions, the use of primary TTT to treat patients with choroidal indeterminate melanocytic lesions with ≥ 1 risk factor for lesion growth yielded poor local lesion control and the possibility for severe ocular complications.


Assuntos
Neoplasias da Coroide/terapia , Hipertermia Induzida/métodos , Nevo Pigmentado/terapia , Adulto , Idoso , Neoplasias da Coroide/mortalidade , Neoplasias da Coroide/patologia , Feminino , Seguimentos , Humanos , Hipertermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Pupila , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Acuidade Visual/fisiologia
8.
Graefes Arch Clin Exp Ophthalmol ; 252(2): 359-65, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24276560

RESUMO

BACKGROUND: Since it has been observed that melanocytic lesions can alter their appearance during pregnancy, we analyzed whether hormone receptors are expressed in conjunctival nevi as well as conjunctival melanoma. We further analyzed whether the number of estrogen (ER) or progesterone receptors (PR) might be associated with the disease course in conjunctival melanoma. METHODS: Twenty-seven paraffin-embedded samples of conjunctival nevi and 27 conjunctival melanoma specimens were examined using immunohistological analysis with antibodies against PR and ER. The percentage of stained cells were analyzed, taking into account patient gender and age. Out of the melanoma group, all patients with complete data for tumor thickness, tumor localization, age at diagnosis, gender, and follow-up including recurrence, metastasis and tumor-related death were included in the second part of the study (n = 15), where hormone receptor rates were associated with tumor outcome, regarding recurrences, metastasis or death. Written consent was received from all included patients. RESULTS: Both nevi and melanomas showed high rates of PR- and ER-positive cells. In Nevi, 64 ± 25 % of cells stained positive for PR and 35 ± 34 % for ER. In melanoma specimens, 68 ± 30 % showed PR and 44 ± 34 % ER expression. Differences between men and women in expression rates were not statistically significant. Out of 15 melanoma patients (nine female, six male), 53 % (five women and three men) experienced 1-4 recurrences, and four patients developed metastases. The median estimated survival time was 12.2 years. A multivariate survival model taking into account known risk factors for prognosis in conjunctival melanoma confirmed tumor location to be an important predictive factor for outcome (p = 0.05). The rate of PR or ER did not show a statistically significant correlation with the disease course in our cohort. CONCLUSIONS: We observed that conjunctival melanocytic lesions express hormone receptors, which could explain why these tumors can alter their appearance under hormonal changes. Regarding the prognosis of conjunctival melanoma, no statistically significant correlation between hormone receptor expression and event-free survival was found in this analysis.


Assuntos
Neoplasias da Túnica Conjuntiva/metabolismo , Melanoma/metabolismo , Nevo Pigmentado/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Túnica Conjuntiva/mortalidade , Neoplasias da Túnica Conjuntiva/patologia , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Inclusão em Parafina , Taxa de Sobrevida
9.
Am J Dermatopathol ; 35(5): 569-75, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23221472

RESUMO

Distinct genetic aberrations between melanomas in different anatomical locations have been confirmed in recent years. However, the associations between immunohistochemical expression, tumor sites, and clinical parameters are not clear. We examined the correlation of protein expression and gene mutation of c-kit with clinicopathological parameters and lesion locations in patients with malignant melanoma (MM). We collected 170 melanocytic lesions, including 106 cutaneous MM from acral melanoma (AM) and nonacral melanoma (NAM) sites, 24 dysplastic nevi, and 40 common melanocytic nevi. Tissue microarray was constructed, and immunohistochemical expression for c-kit was assessed with correlation with clinical parameters. Mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing was also analyzed. Immunostaining scores for c-kit were found to be statistically higher in Dysplastic Nevi than in common melanocytic nevi and MM. In addition, cytoplasmic c-kit staining was significantly correlated with poor survival in patients with AM but not in those with NAM. Twenty-nine cases of MM (including 9 NAM and 20 AM) are analyzed for mutation in exons 11, 13, 17, and 18 of KIT gene in genomic DNA by polymerase chain reaction sequencing, and no genetic mutation is found. Our findings confirm that KIT mutations, in contrast to previous white cohorts, are not common in both AM and NAM of the Chinese and do not necessarily correlate with c-kit expression. The significantly different association between the expression of c-kit immunoreactivities and the mortality risks of melanomas on acral versus nonacral sites might change site-specific targeted therapeutic concepts in melanoma in the future.


Assuntos
Biomarcadores Tumorais/análise , Síndrome do Nevo Displásico/enzimologia , Melanoma/enzimologia , Nevo Pigmentado/enzimologia , Proteínas Proto-Oncogênicas c-kit/análise , Neoplasias Cutâneas/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Povo Asiático/genética , Sequência de Bases , Biomarcadores Tumorais/genética , Biópsia , Criança , Análise Mutacional de DNA , Síndrome do Nevo Displásico/etnologia , Síndrome do Nevo Displásico/genética , Síndrome do Nevo Displásico/mortalidade , Síndrome do Nevo Displásico/patologia , Síndrome do Nevo Displásico/terapia , Éxons , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Melanoma/etnologia , Melanoma/genética , Melanoma/mortalidade , Melanoma/patologia , Melanoma/terapia , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Nevo Pigmentado/etnologia , Nevo Pigmentado/genética , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Nevo Pigmentado/terapia , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Taiwan/epidemiologia , Análise Serial de Tecidos , Adulto Jovem
10.
Anal Quant Cytopathol Histpathol ; 34(4): 204-13, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23016467

RESUMO

OBJECTIVE: To explore the relationship between the immunohistochemical expression of E-cadherin and the relevant clinicopathologic features in various types of melanocytic nevi and cutaneous malignant melanoma (CMM). STUDY DESIGN: Using standard immunohistochemical techniques, we examined 30 CMMs, 30 melanocytic nevi and 10 sex- and age-matched volunteers for the expression of E-cadherin. RESULTS: A total of 90% of melanocytic nevi and all dysplastic nevi showed positive cytoplasmic immunoreactivity for E-cadherin with decreased intensity at the deeply located cells. A significant difference was noticed between types of CMM regarding the pattern of immunostaining of E-cadherin (p < 0.01), whereas all nodular malignant melanomas (NMMs) express the membranous pattern in contrast to the cytoplasmic one in other types of CMM. Reduced overall survival was significantly associated with advanced stage, late Clark level and membranous pattern of E-cadherin expression. CONCLUSION: E-cadherin expression in nevi is related to the degree of melanocytic maturation. Qualitative changes in the expression and cellular localization of E-cadherin are observed in melanoma that may reflect different stages of progression with molecular changes and may imply a prognostic marker.


Assuntos
Caderinas/biossíntese , Melanoma/metabolismo , Nevo Pigmentado/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Caderinas/análise , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
11.
Am J Dermatopathol ; 32(8): 809-14, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20885286

RESUMO

Many of the histopathologic criteria used to diagnose melanoma overlap with atypical but otherwise benign naevi such as dysplastic or Spitz naevi. Galectin-3 is a member of the galectin gene family and is expressed at elevated levels in a variety of neoplastic cell types. The aim of the present study was to investigate the diagnostic value of galectin-3 expression compared with homatropine methyle bromide-45(HMB-45) (one of the established and widely used immunohistochemical melanocytic markers) together with assessment of its prognostic value in melanoma lesions. This study was carried out on 21 cases of melanoma and 20 benign pigmented naevi. Galectin-3 was expressed in all the examined benign and malignant melanocytic lesions. The nucleocytoplasmic pattern of galectin-3 appeared in malignant cases only with 42.86% sensitivity, 100% specificity, and 70.73% accuracy. This pattern tended to be associated with thick melanoma (P = 0.08) and reduced survival (P = 0.22). The intensity of galectin-3 assessed by H-score was significantly of higher values in malignant lesions compared with benign lesions (P < 0.0001). The best cut-off value for discrimination between benign and malignant melanocytic lesions was 295 with 95% sensitivity, 70% specificity, and 83% accuracy. The diagnostic power of galectin-3 in distinguishing between benign and malignant melanocytic lesions relies on the pattern and the intensity of its expression. The nucleocytoplasmic pattern of galectin-3 expression carries greater probability of a malignant phenotype and a poor prognostic impact on patients' outcome.


Assuntos
Biomarcadores Tumorais/análise , Galectina 3/análise , Melanócitos/química , Melanoma/química , Nevo Pigmentado/química , Neoplasias Cutâneas/química , Tropanos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Egito , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanócitos/patologia , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Sensibilidade e Especificidade , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Adulto Jovem
12.
Arch Ophthalmol ; 128(8): 996-1000, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20696999

RESUMO

OBJECTIVE: To evaluate the risk of dying of metastatic choroidal melanoma in patients with small, indeterminate, pigmented lesions of the uveal tract. METHODS: A cohort of 1063 consecutive patients were evaluated in the Ocular Oncology Clinic of the Massachusetts Eye and Ear Infirmary between January 1976 and June 1996 with definite choroidal nevus (n = 256), indeterminate lesions (n = 334), or small melanoma (n = 373). Deaths occurring up to December 1998 were identified through active follow-up or by a search of the National Death Index. Cumulative death rates were compared among diagnostic groups using the Kaplan-Meier method. RESULTS: Mean lesion diameter was 4.6 mm in the nevi, 7.0 mm in the indeterminate lesions, and 8.1 mm in the small melanomas. Patients ranged in age from 3 to 95 years (median, 64 years). A total of 15 deaths due to ocular melanoma were ascertained (median follow-up of survivors, 8.2 years), 13 in the melanoma group and 2 in the indeterminate lesion group; actuarial tumor-specific death rates at 10 years after evaluation were 5% (95% confidence interval, 3%-8%) and 1% (95% confidence interval 0%-3%), respectively. No deaths due to ocular melanoma occurred in the nevus group. CONCLUSIONS: These data document the very low malignant potential of most indeterminate melanocytic lesions of the choroid and support the current practice of monitoring these tumors, with treatment provided when growth and other signs of malignant transformation are observed.


Assuntos
Neoplasias da Coroide/mortalidade , Melanoma/mortalidade , Nevo Pigmentado/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/radioterapia , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/radioterapia , Pessoa de Meia-Idade , Nevo Pigmentado/diagnóstico , Nevo Pigmentado/radioterapia , Medição de Risco , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Estados Unidos/epidemiologia
13.
Clin Dermatol ; 27(6): 529-36, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19880040

RESUMO

Pediatric melanoma is rare but increasing in incidence. Because early diagnosis and treatment improves prognosis, clinicians need to include it as a possible diagnosis when evaluating a pigmented lesion in a pediatric patient. Some risk factors for melanoma include xeroderma pigmentosum, giant congenital melanocytic nevi, dysplastic nevus syndrome, atypical nevi, many acquired melanocytic nevi, family history of melanoma, and immunosuppression. Definitive treatment is with surgical excision. Adjuvant therapies such as chemotherapy, immunotherapy, and radiation therapy can be used in advanced cases.


Assuntos
Melanoma/patologia , Invasividade Neoplásica/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Fatores Etários , Biópsia por Agulha , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/terapia , Estadiamento de Neoplasias , Nevo Pigmentado/mortalidade , Nevo Pigmentado/terapia , Prognóstico , Medição de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Análise de Sobrevida
14.
J Am Acad Dermatol ; 61(5): 766-74, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19766348

RESUMO

BACKGROUND: Large congenital melanocytic nevi (LCMN) predispose to neurocutaneous melanocytosis (NCM), which is associated with significant morbidity and mortality. OBJECTIVE: To identify risk factors for NCM in patients with LCMN and suggest guidelines for their management. METHODS: Medical records of patients with LCMN were reviewed at Sainte-Justine Hospital between 1980 and 2006. Presence of multiple satellite nevi and posterior midline location were evaluated as risk factors for NCM using chi-square test. Magnetic resonance imaging scans were reviewed by a neuroradiologist. RESULTS: Twenty-six of 52 patients underwent radiologic investigation. Six of 26 (23%) had NCM. Patients with this condition are more likely to have multiple satellite nevi (100% vs 50%, P = .03) and have a trend to posterior midline location of their LCMN (100% vs 60%, P = .08). Patients with NCM are more likely to have both multiple satellite nevi and posterior midline location (100% vs 25%, P = .002). Radiologic findings are also presented. LIMITATIONS: This was a retrospective case series with imprecise chart data in 38% of cases. CONCLUSION: The presence of multiple satellite nevi alone or with associated posterior midline location of LCMN is associated with a higher risk of NCM. We recommend magnetic resonance imaging testing before 4 months of age in patients with these features.


Assuntos
Melanose/patologia , Síndromes Neurocutâneas/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Melanose/congênito , Melanose/mortalidade , Síndromes Neurocutâneas/congênito , Síndromes Neurocutâneas/mortalidade , Nevo Pigmentado/congênito , Nevo Pigmentado/mortalidade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/mortalidade
15.
J Cutan Pathol ; 31(10): 633-42, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15491322

RESUMO

BACKGROUND: S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45(SKP2) is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. RESULTS: Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 +/- 0.2/85 +/- 15) to melanoma in situ (3 +/- 2/45 +/- 20) to primary cutaneous melanoma (12 +/- 9/30 +/- 25) to metastatic melanoma (25 +/- 15/15 +/- 20) (p < or = 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p < or = 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = -0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. CONCLUSIONS: Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Melanoma/metabolismo , Nevo Pigmentado/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Neoplasias Cutâneas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Inibidor de Quinase Dependente de Ciclina p27 , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Melanoma/mortalidade , Melanoma/secundário , Pessoa de Meia-Idade , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Prognóstico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Taxa de Sobrevida
16.
Cancer ; 100(11): 2442-7, 2004 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15160350

RESUMO

BACKGROUND: Meningeal melanocytomas are rare, benign central nervous system lesions with a high probability of recurrence. To the authors' knowledge, approximately 100 cases have been reported since 1972, when the entity first was described. In the current study, four therapies were compared with regard to local control and survival to identify which is best. METHODS: All reported cases were reviewed with regard to extent of resection, radiotherapy, local control, and survival. If published data were incomplete, the authors were contacted for additional data. Patients were categorized by therapy: complete resection (CTR), complete resection followed by radiotherapy (CTR-RT), incomplete resection (ITR), and incomplete resection followed by radiotherapy (ITR-RT). Local control and survival were calculated using the Kaplan-Meier method. A multivariate analysis was performed including age, gender, tumor location, confirmation of extent of resection, and treatment schedule. RESULTS: A total of 89 patients were included: 46 with CTR, 3 with CTR-RT, 23 with ITR, and 17 with ITR-RT. The 5-year local control rate was 80% after CTR, 100% after CTR-RT, and 72% after ITR-RT versus 18% after ITR (P < 0.001). The 5-year survival rate was 100% after CTR, CTR-RT, and ITR-RT, respectively, versus 46% after ITR (P < 0.001). Multivariate analysis demonstrated that therapy was the only variable that affected local control and survival significantly. In 14 patients treated with ITR-RT, RT was restricted to the tumor region. The radiation dose was 30-40 grays (Gy) in 6 patients, 45-55 Gy in 7 patients, and unknown in 1 patient. The 5-year local control rate was 86% after a dose of 45-55 Gy versus 27% after a dose of 30-40 Gy (P = 0.1). CONCLUSIONS: CTR was found to be significantly superior to ITR with regard to both local control and survival. Outcome was significantly improved by RT after ITR. Doses of 45-55 Gy appeared to be more beneficial than doses of < or = 40 Gy.


Assuntos
Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Nevo Pigmentado/radioterapia , Nevo Pigmentado/cirurgia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Criança , Terapia Combinada , Feminino , Humanos , Masculino , Neoplasias Meníngeas/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Nevo Pigmentado/mortalidade , Neoplasias da Medula Espinal/mortalidade , Neoplasias da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/cirurgia , Taxa de Sobrevida
17.
Dermatol Clin ; 20(4): 607-16, viii, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12380048

RESUMO

This article discusses the care of patients with CMN, who often require a multidisciplinary approach involving pediatricians, family physicians, internists, dermatologists, psychologists, plastic surgeons, neurologists, and radiologists. The cosmetic and psychosocial issues, combined with the knowledge of the increased risk of developing melanoma or NCM, is a huge burden that many of these patients and their families have to carry. This article describes the importance for physicians to help these patients and families come to terms with these issues, as well as remind their patients and their family members that although melanoma, NCM, or other complications can develop, most affected individuals do not develop any complications. The article mentions that there are many healthy, happy, functional adults with large, small, and multiple CMN alive today.


Assuntos
Nevo Pigmentado/congênito , Nevo Pigmentado/terapia , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia por Agulha , Criança , Pré-Escolar , Terapia Combinada/métodos , Dermatologia/métodos , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Análise de Sobrevida
18.
Melanoma Res ; 12(3): 271-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12140384

RESUMO

The clinicopathological features and prognosis of primary cutaneous malignant melanoma with benign melanocytic naevus (BMN) components are still under debate. The purpose of this study was to characterize further the clinical and histopathological features of naevus-associated melanomas, with emphasis on the BMN components, and to examine their prognosis based on a large series. Following a histopathological review of 667 consecutive cases of primary cutaneous melanoma, 148 melanomas with BMN components (22.1%) were identified for further study. A control group of 519 melanomas without BMN components seen in a similar period were also studied. Clinically, patients with melanomas containing BMN components (n = 148; age range 25-86 years, mean age 54 +/- 16 years; male to female ratio 1:1.02) presented with tumours located mainly on the trunk (34.5%), followed by the upper extremities (24.3%), lower extremities (20.3%), and head and neck (14.2%). Compared with tumours without BMN components (n = 519; age range 19-89 years, mean age 57 +/- 15 years; male to female ratio 1:1.3), melanomas with BMN components occurred in slightly younger individuals (P = 0.027). Histopathologically, BMN components mainly showed features of acquired naevi (total 87 cases; dysplastic, 80 cases; banal, seven cases) or congenital naevi (total 57 cases; superficial, 56 cases; deep, one case), but a minority of these lesions (four cases) could not be further subcategorized. Generally, melanomas containing BMN components were relatively thinner than melanomas without BMN components (mean Breslow index 0.95 +/- 0.83 mm and 1.3 +/- 1.6 mm, respectively) (P = 0.015). The follow-up data available in 69 patients with naevus-associated melanomas consistently revealed a relatively good outcome (5 year metastasis-free survival rate 93.75%), although no statistical difference in prognosis was observed between this group and a subset of 283 melanomas patients without BMN components stratified by tumour thickness. We conclude that BMN components in naevus-associated melanomas constitute a heterogeneous group morphologically, consisting mainly of dysplastic and superficial congenital naevi. This finding indicates a more important role for superficial congenital naevus as a precursor lesion of naevus-associated melanomas than presently recognized. Patients with naevus-associated melanomas generally show a good clinical outcome, reflecting their small Breslow index.


Assuntos
Síndrome do Nevo Displásico/patologia , Melanoma/patologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Tecido Adiposo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/ultraestrutura , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Melanócitos/patologia , Melanoma/mortalidade , Pessoa de Meia-Idade , Mitose , Metástase Neoplásica , Nevo Pigmentado/congênito , Nevo Pigmentado/mortalidade , Prognóstico , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida , Taxa de Sobrevida
19.
J Am Acad Dermatol ; 47(1): 77-90, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12077586

RESUMO

Congenital and infantile types of melanoma are uncommon conditions for which there are limited epidemiologic data. The number of reported cases is small with several ascribed etiologies. We review the literature and report the first documented case, to our knowledge, of pigment-synthesizing melanoma in an infant. Reported cases of congenital and infantile melanoma were identified and categorized on the basis of disease origin. Dermatopathologic specimens from an infant given a diagnosis of pigment-synthesizing melanoma are described. Disease arising from medium and large/giant congenital nevi was most common, whereas reports of de novo and transplacental disease were infrequent. Death of approximately 40% of patients was noted within 18 months of diagnosis. Male infants accounted for approximately 74% of cases. The most commonly affected anatomic sites were the head and neck. The prognosis for congenital and infantile melanoma is poor. The high incidence of head-and-neck involvement and male predominance for disease suggest dispositions for both anatomic disease localization and sex.


Assuntos
Melanoma/congênito , Nevo Pigmentado/congênito , Neoplasias Cutâneas/congênito , Biópsia por Agulha , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Melanoma/mortalidade , Melanoma/patologia , Nevo Pigmentado/mortalidade , Nevo Pigmentado/patologia , Prognóstico , Medição de Risco , Distribuição por Sexo , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Pigmentação da Pele , Análise de Sobrevida
20.
Melanoma Res ; 10(3): 265-72, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10890381

RESUMO

A new method that can dramatically improve the sensitivity and especially the specificity of skin naevi screening for melanoma by physicians is introduced. The method is based on measuring the similarity to previously classified naevi images. As more naevi are being classified, the power of the method is enhanced. Thus physicians can benefit from experience accumulated by others and the screening can be performed effectively by physicians with less experience.


Assuntos
Síndrome do Nevo Displásico/diagnóstico , Processamento de Imagem Assistida por Computador/métodos , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutâneas/diagnóstico , Síndrome do Nevo Displásico/mortalidade , Síndrome do Nevo Displásico/prevenção & controle , Humanos , Programas de Rastreamento , Melanoma/mortalidade , Melanoma/prevenção & controle , Modelos Teóricos , Nevo Pigmentado/mortalidade , Nevo Pigmentado/prevenção & controle , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/prevenção & controle
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