RESUMO
OBJECTIVE: The purpose of this study was to evaluate the prognostic value of 10-MHz sonography in measuring melanoma thickness before biopsy or excision. SUBJECTS AND METHODS: Fifty-four patients with lesions suggestive of melanoma participated in the study. Lesions were measured on sonography using a 10-MHz linear transducer before routine biopsy and histopathologic analysis. Sonographic measurements were compared with histopathologic results (Breslow index) using Pearson's correlation coefficient and concordance analysis. Additional statistical analyses included sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 10-MHz sonography in identifying lesions > 1 mm thick. RESULTS: Histopathologic analysis identified all 54 lesions as melanoma. On sonography, 34 lesions measured < or = 1 mm and 20 lesions, > 1 mm. Histopathologic analysis showed 32 lesions with a Breslow index of < or = 1 mm and 22 lesions with a Breslow index of > 1 mm. The median thickness of the 54 lesions was 1.33 mm (range, 0-5 mm) by the Breslow index compared with 1.85 mm (range, 0-4.8 mm) by sonography. Comparison of sonographic measurements and Breslow index values gave a correlation coefficient of 0.93 and a concordance coefficient of 0.99. Overall, sonographic measurements showed 86% sensitivity, 97% specificity, 93% accuracy, 95% positive predictive value, and 91% negative predictive value in identifying lesions with a Breslow index of > 1 mm. CONCLUSION: In our series of 54 melanomas, 10-MHz sonography measured lesion thickness with good accuracy compared with histopathology. Sonography was effective in discriminating between tumors < or = 1 mm thick and those > 1 mm thick.
Assuntos
Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prognóstico , Sensibilidade e Especificidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , UltrassonografiaRESUMO
OBJECTIVE: It was the aim of this study to analyze the clinical value of the determination of serum S-100beta protein in high-risk melanoma patients. PATIENTS AND METHODS: Patients were tested for serum S-100beta protein by luminoimmunometric assay after melanoma surgical excision, before starting interferon-alpha2b and every 3 months thereafter, until treatment was completed. RESULTS: Ninety-seven patients were included in the study. Median follow-up was 62.9 months (range 32.7-87.4). High baseline S-100beta levels were associated with positive lymph node status (p = 0.02). High S-100beta levels (during therapy) showed a relation with positive lymph node status (p = 0.014), number of positive lymph nodes (p = 0.01), macroscopic lymph node involvement (p = 0.002) and second melanoma diagnosis at study entry (p = 0.001). By univariate analysis, high baseline S-100beta levels were associated with disease-free survival (p = 0.004) and overall survival (p = 0.0007). Similarly, high S-100beta levels during therapy were associated with disease-free survival (p < 0.0001) and overall survival (p < 0.0001). In the multivariate analysis, high S-100beta levels during therapy (hazard ratio 1.017, 95% CI 1.008-1.026; p < 0.0001) and high baseline S-100beta levels (hazard ratio 3.31, 95% CI 1.10-9.89; p = 0.032) were independent prognostic factors for overall survival when compared with low levels while on therapy and low baseline S-100beta levels, respectively. CONCLUSIONS: These results provide evidence of the clinical usefulness of serum S-100beta level determination in high-risk melanoma patients. S-100beta serum determination should be considered to be included in clinical trials that test adjuvant therapies in melanoma patients.
Assuntos
Melanoma/sangue , Fatores de Crescimento Neural/sangue , Proteínas S100/sangue , Neoplasias Cutâneas/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Proteínas Recombinantes , Risco , Subunidade beta da Proteína Ligante de Cálcio S100 , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Resultado do TratamentoRESUMO
Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Sarda Melanótica de Hutchinson/tratamento farmacológico , Sarda Melanótica de Hutchinson/radioterapia , Sarda Melanótica de Hutchinson/secundário , Interferon alfa-2 , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Radioterapia Adjuvante , Proteínas Recombinantes , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/radioterapiaRESUMO
BACKGROUND: Surgical therapy plays an important role in the management of selected patients with metastatic melanoma. PURPOSE: A retrospective review of 13 patients who underwent surgical resection of lung metastases from melanoma from 1996 to 2003 was performed. The aim of the study was to analyze the clinical outcome and survival time. MATERIALS AND METHODS: Mean age was 45 years old (range: 31-64). Complete tumour resection was confirmed histologically. Nine patients presented one single pulmonary lesion, two lesions (n = 3) and three lesions (n = 1) but in all cases confined in the same pulmonary lobe. RESULTS: Median survival time (MST) for the entire group was 20 months (95% confidence interval (CI): 16-24 months). The median time to disease progression after lung metastasectomy was 5 months (95% CI: 3-7 months). MST, according to the prognostic groups proposed by the International Registry of Lung Metastases, was 17 months (95% CI: 6-28 months) for group I (n = 6), MST of 20 months (95% CI: 16-24 months) for group II (n = 5) and MST of 4 months for group III (n = 2), without differences statistically significant (log-rank p = 0.423). MST regarding the time of disease free interval from diagnostic of primary tumour and lung metastases (< 36 months [n = 5] vs > 36 months [n = 8]) was 20 months and 17 months respectively, without differences statistically significant (log rank p = 0.222). CONCLUSIONS: Surgical resection when feasible provides survival rates superior to any available nonsurgical therapy. In carefully selected patients, when the resection is performed with curative intent, it may result in improved survival.
Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Melanoma/secundário , Melanoma/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians. This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet. According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P<0.001). Ulceration was present in 33.3%, 2.9% in SSM, 38.6% in ALM, and 76.9% in NM (P<0.001). A total of 29.3% relapsed (7.3% of SSM, 35% of ALM and 55% of NM) and 24.2% died because of AM. In multivariate analysis, age at diagnosis, Breslow, and histopathological subtype were independent prognostic factors for both disease-free and AM-specific survival. The ALM and NM subtypes presented poorer outcome after weighting Breslow and age (P=0.02). Histological subtype of AM could have an impact on biological behavior, ALM and NM subtypes presenting a poorer prognosis after adjusting for age and Breslow's thickness.
Assuntos
Pé/patologia , Mãos/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Melanoma Maligno CutâneoRESUMO
PURPOSE: We have studied a consecutive case series of patients with multiple primary melanoma (MPM) for the involvement of the melanoma susceptibility loci CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients with two primary melanomas, 14 with three, five with four, one with five, two with six, and one with seven) were included. RESULTS: Seven different CDKN2A germline mutations were identified in 17 patients (16.3%). In total, we identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon 1beta frameshift mutation. The age of onset was significantly lower and the number of primary melanomas higher in patients with mutations. CDKN2A mutations were more frequent in patients with familial history of melanoma (35.5%) compared with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to 10.64; P = .001), and in patients with more than two melanomas (39.1%) compared with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to 6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs than in the control population (P = .05). A variant of uncertain significance, A127S, was also detected in one patient. No CDK4 mutations were identified, suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM patients are good candidates for CDKN2A mutational screening. These patients and some of their siblings should be included in a program of specific follow-up with total body photography and digital dermoscopy, which will result in the early detection of melanoma in this subset of high-risk patients and improve phenotypic characterization.
Assuntos
Genes p16 , Melanoma/genética , Melanoma/patologia , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
The aim of this study was to determine the efficacy and tolerability of a biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and temozolomide, in patients with metastatic melanoma. Treatment consisted of temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4), interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon-alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six patients were included. Patients with poor prognostic factors were not excluded. Seventeen patients (47%) had been treated previously in an adjuvant setting with interferon-alpha. Four patients (11%) had been treated previously with chemotherapy and six (17%) had been treated with other biochemotherapy regimens. The distribution by American Joint Committee on Cancer staging was as follows: M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%). At inclusion, seven patients (19.4%) had cerebral metastases that had previously been treated with whole brain radiotherapy. For thirty-four evaluable patients, seven (20.5%) achieved an objective response. Overall, metastatic disease was substantially decreased or temporarily stabilized in 11 patients (32.4%; 95% confidence interval, 17.4-50.5). Responses were observed for all locations. The central nervous system was the initial site of relapse in two responding patients. The median survival was 10 months. The main toxicities noted were haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a modest activity despite the poor prognosis of our patient population. The low haematological toxicity rate obtained suggests that higher doses could be tried.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Melanoma/tratamento farmacológico , Adulto , Idoso , Neoplasias Encefálicas/radioterapia , Cisplatino/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Feminino , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Proteínas Recombinantes , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Temozolomida , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
Standard antineoplastic treatment for metastatic melanoma is ineffective in the large majority of patients. Therefore, alternative approaches need to be investigated. STI571 is a new antineoplastic compound, which selectively inhibits the tyrosine kinase activity of ABL, c-Kit and platelet-derived growth factor receptor (PDGFR). Melanoma may express all of these proteins. The aim of this study was to investigate whether STI571 inhibits the in-vitro growth of melanoma cells. Nineteen cell lines were obtained from four primary and 15 metastatic melanomas of cutaneous origin. The percentages of positive cells for the putative targets of STI571 were as follows: ABL, 41-100%; c-Kit, 8-97%; PDGFR-alpha, 41-98%; PDGFR-beta, 51-99%. 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium (MTT) and viability assays showed that STI571 clearly inhibits the proliferation of eight of the 19 (42.1%) cell lines. No relationship could be established between the expression of c-Kit, ABL, PDGFR-alpha or PDGFR-beta and the response of cell lines to STI571. Our study shows, for the first time, an antiproliferative effect of STI571 on human melanoma cell lines of cutaneous origin, raising the possibility of the future clinical use of STI571. The identification of the target of STI571 in human cutaneous melanoma cells would allow the selection of patients who could benefit from this treatment.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Melanoma/metabolismo , Piperazinas/farmacologia , Pirimidinas/farmacologia , Benzamidas , Western Blotting , Linhagem Celular Tumoral , Análise Mutacional de DNA , Citometria de Fluxo , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Proteínas Oncogênicas v-abl/metabolismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismoRESUMO
INTRODUCTION: Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. MATERIALS AND METHOD: We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n = 11) and 30 Gy/10 fractions (n = 10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. RESULTS: Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2- 6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0-7 months) without statistically significant differences (Log rank p = 0.74). There was one complete response and two partial responses. CONCLUSIONS: The results suggest that MST was not significantly affected by the total dose/fractionation schedule.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Irradiação Craniana , Dacarbazina/análogos & derivados , Melanoma/secundário , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Cisplatino/administração & dosagem , Estudos de Coortes , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Tábuas de Vida , Masculino , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Pessoa de Meia-Idade , Seleção de Pacientes , Modelos de Riscos Proporcionais , Proteínas Recombinantes , Estudos Retrospectivos , Análise de Sobrevida , Temozolomida , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
PURPOSE: To evaluate the clinical significance of the detection of circulating melanoma cells in patients treated with adjuvant interferon and to determine their potential value as a marker of interferon response. PATIENTS AND METHODS: We prospectively analyzed 616 peripheral-blood samples from 120 melanoma patients with stage IIA (n = 33), IIB (n = 22), III (n = 50), or IV (surgically resected) (n = 15) disease receiving adjuvant interferon alfa-2b therapy. Tyrosinase mRNA was assayed by reverse transcriptase polymerase chain reaction (RT-PCR) as a marker of circulating melanoma cells before the start of interferon and every 2 to 3 months thereafter. RESULTS: With a median follow-up time of 32.3 months (range, 7.1 to 77.5 months), 47 patients (39.8%) relapsed and 31 (26%) died. During adjuvant interferon treatment, 76 patients (64%) had undetected circulating melanoma cells and 44 patients (36%) had a positive RT-PCR result in at least one sample. Actuarial 5-year disease-free survival was 62% in patients with persistently negative RT-PCR during interferon treatment and 38% for patients with positive RT-PCR during interferon (P =.02). Actuarial 5-year overall survival was 75% and 50%, respectively (P =.03). CONCLUSION: Patients with melanoma and tyrosinase mRNA detected in the blood during adjuvant interferon therapy had a worse prognosis compared with patients with undetected tyrosinase mRNA during treatment. Further investigation into the detection of circulating melanoma cells as a surrogate marker of response to adjuvant interferon therapy is warranted.
Assuntos
Antineoplásicos/uso terapêutico , Interferon-alfa/uso terapêutico , Melanoma/sangue , Monofenol Mono-Oxigenase/sangue , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Neoplasias Cutâneas/sangue , Análise Atuarial , Biomarcadores Tumorais/sangue , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Interferon alfa-2 , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Estudos Prospectivos , Proteínas Recombinantes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Metastases to the hand and wrist are rare, with fewer than 200 cases reported in the literature. Phalanges are more commonly involved than metacarpal and wrist. The lung, breast and kidneys are the more common sites of primary lesions than metastasize in the hand. We present an exceptional case of melanoma that metastasized to the capitate. Melanoma can give bone metastases, but we are not aware of reports of this tumour metastatising to the carpal bones. In our knowledge, we have only found a report of metastases in the capitate, a clear-cell sarcoma of the right foot, a tumour close to melanoma with some cytogenetic differences. Hand metastases in a patient who is suffered melanoma should be ruled out if a lytic aggressive lesion appears on x-ray film or positive technetium bone scan is demonstrated.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Capitato/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Melanoma/secundário , Articulação do Ombro/patologia , Adulto , Feminino , Humanos , Metástase Linfática , RadiografiaRESUMO
INTRODUCTION: Metastatic melanoma has an ominous prognosis. Bio-chemotherapy regimens can increase the response rate but with a high degree of toxicity due, mainly, to the use of high-dose intravenous interleukin-2. OBJECTIVES: To test the feasibility and activity profile of a bio-chemotherapy regimen of low-dose subcutaneous interleukin-2. MATERIAL AND METHODS: Administration scheme: dacarbazine at 200 mg/m2/d on days 1-4, cisplatin at 20 mg/m2/d intravenous on days 1-4, vinblastine at 1.5 mg/m2/d on days 1-4, IL-2 at 4.5 MUI/m2/d subcutaneous on days 5-8, IFN-alpha at 5 MU subcutaneous on days 5-9, 11, 13, 15 of every 21-day cycle. RESULTS: Objective response was obtained in 11 patients (39.3%; 95%CI: 21-59) including 4 with complete response (14.3%; 95%CI: 4-33). With an extended follow-up of 49 months and 60 months, respectively, 2 patients continue with complete response. The main toxicities were haematological: grade 3-4 neutropenia in 8.2% of cycles, thrombocytopenia in 1.2% and anaemia in 3.2%. CONCLUSIONS: The regimen is safe and has a good activity profile. The presence of long-term survivors, despite the use of lower doses and subcutaneous IL-2, is encouraging.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Imunológicos/uso terapêutico , Interleucina-2/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Análise de Sobrevida , Vimblastina/administração & dosagemRESUMO
Intramedullary spinal cord metastases (ISCMs) are extremely rare. An exact diagnosis may be difficult even when the primary tumour is known. Patients usually present with back pain and signs and symptoms of spinal cord compression, such as hemiparesis or hemisensory impairments. Magnetic resonance imaging (MRI) is considered to be the main diagnostic tool for intramedullary lesions as it is very sensitive, but non-specific, in distinguishing between ISCMs and primary cord tumours. Optimal treatment in patients with ISCMs remains controversial. We report a case of ISCMs of melanoma, with a review of the clinical and radiological characteristics of these medullary lesions and their prognosis, as well as the different therapeutic approaches.
Assuntos
Neoplasias Encefálicas/patologia , Melanoma/patologia , Neoplasias da Medula Espinal/secundário , Neoplasias Encefálicas/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Malignant melanoma (MM) early lymph node (LN) metastasis usually appears first in the sentinel LN (SLN). Breslow thickness is the main factor considered in the selection of patients to be submitted to SLN biopsy. The present study aimed to describe other independent prognostic factors useful in SLN candidate selection. During one year, 94 MM patients (90 primary cutaneous MM with Breslow thickness > or = 0.76 mm, and four cutaneous relapses), were submitted to SLN biopsy in the Melanoma Unit at the Hospital Clinic, Barcelona, Spain. The prognostic factors studied were: Breslow thickness, Clark's level of invasion, mitotic rate, cellular type (small, epithelioid, fusocellular, sarcomatoid), vertical growth phase, regression > 50%, severe vascularization, infiltrate (lymphocytic, plasmocytic), ulceration, neurotropism, intravascular/intraneural invasion, protein p16 expression and recurrence. Nineteen SLN (20.2%) were positive and 75 (79.8%) negative. No positive SLN occurred in MM with Breslow thickness < or = 1.0 mm. Breslow thickness > or = 2 mm (P = 0.005), severe vascularization (P = 0.005), small cell (P = 0.000) and ulceration (P = 0.005) were significant prognostic factors by univariate analysis. Small cell (P = 0.008) and ulceration (P = 0.05) were also significant prognostic factors in a multivariate analysis. The probability of finding a positive SLN for small cell was 56.9% [95% confidence interval (CI), 26.8-82.6%]. The probability of positive SLN for ulceration was 35.5% (95% CI, 14.2-64.7%). For small cell and ulceration together the probability increased to 86.3% (95% CI, 54.3-97.1%). The results of this study corroborated ulceration as a prognostic factor for SLN candidate selection and for the first time we have described small cell melanoma morphology as a significant factor associated with positive SLN.
Assuntos
Metástase Linfática/diagnóstico , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Úlcera/patologia , Humanos , Metástase Linfática/patologia , Estadiamento de Neoplasias , Probabilidade , PrognósticoRESUMO
BACKGROUND AND OBJECTIVE: Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma. Temozolomide (TMZ) displays efficacy for the treatment of metastatic melanoma. Our objective was to evaluate the potential benefit of TMZ administered along with WBRT. PATIENTS AND METHOD: We have conducted a retrospective study in a group of 26 patients comparing WBRT (n = 10) (20 Gy/5 fr) with WBRT+TMZ (n = 16) administered as a single chemotherapeutic agent (200 mg/m2) or in combination with chemoimmunotherapy (150 mg/m2). RESULTS: The median survival of the total group (n = 26) was 3 months (CI 95%, 2-4 months). The median survival of the WBRT+TMZ group was 6 months (CI 95%, 0-12 months), while the median survival of the WBRT group was 1 month (CI 95%, 1-2 months) (p < 0.0001). The analysis of survival at different time intervals (90, 180 and 270 days) showed a clear benefit for the group treated with WBRT + TMZ (p = 0.016). CONCLUSIONS: These results suggests a benefit of TMZ added to WBRT in terms of long-term survival for patients with melanoma brain metastases.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/radioterapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , TemozolomidaAssuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Antibioticoprofilaxia , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , TemozolomidaAssuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Melanoma/terapia , Neoplasias Cutâneas/patologia , Lobo Temporal , Neoplasias Encefálicas/secundário , Terapia Combinada , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Indução de Remissão , TemozolomidaRESUMO
S-100 serum concentrations were analyzed in 39 healthy people, 130 patients with benign diseases and 304 patients with malignancies, including 49 patients with locoregional diseases and 255 with advanced diseases. S-100 was determined by a commercial immunoluminometric assay, and 0.20 ng/ml was considered to be the upper limit of normality. In none of the healthy people was S-100 higher than 0.2 ng/ml. Slightly high S-100 concentrations were found in 33 out of 130 patients (25%) with benign diseases (mean 0.21 +/- 0.45 ng/ml). Significantly higher S-100 serum levels were found in patients with liver cirrhosis (63%, 10/16) (p = 0.024) or renal failure (45%, 8/18) (p = 0.03) than in patients with other benign diseases or in healthy people. Abnormal S-100 serum levels were found in 68 of the patients (22.5%) with malignancy (mean 1.01 +/- 5.9 ng/ml). The highest S-100 concentrations were found in patients with malignant melanomas (p = 0.001). Excluding melanoma patients, the S-100 serum levels in patients with malignancies were not related to tumor origin or stage but were clearly related to the site of metastasis, with patients with liver metastases showing higher values than patients with metastases without liver involvement (p = 0.02). No statistical differences were found among patients with liver cirrhosis, primary liver cancer or liver metastases. In conclusion, S-100 is a useful marker for melanoma, but abnormal levels of this tumor marker may be found in benign and malignant diseases associated with liver or renal injury.
Assuntos
Rim/metabolismo , Fígado/metabolismo , Neoplasias/diagnóstico , Proteínas S100/sangue , Adulto , Idoso , Química Clínica/métodos , Reações Falso-Positivas , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Pessoa de Meia-Idade , Neoplasias/sangueRESUMO
The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called "in-transit nodes" or "interval nodes" and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of (99m)Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary.
Assuntos
Linfonodos/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Melanoma/secundário , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/diagnóstico por imagem , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Linfonodos/patologia , Metástase Linfática , Melanoma/epidemiologia , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Cintilografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Espanha/epidemiologiaRESUMO
Scintigraphic identification of the sentinel lymph node is achievable in nearly all patients with malignant melanoma. However, in a very small number of cases the sentinel node fails to be detected, and sometimes recurrence appears during follow-up in patients who had previously tested negative for metastatic disease. The purpose of this study was to review our experience in order to isolate the reasons for erroneous sentinel lymph node identification. The evaluation involved 435 consecutive malignant melanoma patients with AJCC stages I and II (clinically negative nodes) and Breslow thickness >0.76 mm. Lymphoscintigraphy was performed the day before surgery by intradermal administration of technetium-99m labelled nanocolloid. Dynamic and static images were obtained. The sentinel node was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. After removal, routine histopathological examination with haematoxylin-eosin (H-E) and immunohistochemistry with S 100 and HMB45 (IHC) were performed. In those patients who developed regional recurrences during follow-up, sentinel nodes were further evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Lymphoscintigraphy visualised at least one sentinel node in 434 out of 435 patients (99.8%). Uptake in in-transit sentinel lymph nodes was observed in 32 patients (7.4%). During surgery, localisation and removal of sentinel nodes was successful in 430/435 patients (98.8%). A total of 790 sentinel lymph nodes were harvested, with a mean of 1.8 per patient. Routine histopathological examination with H-E or IHC revealed metastatic disease in 72 patients (16.8%). During a mean follow-up of 26 months, seven of those patients with a negative sentinel node developed regional lymph node metastases. In five of them RT-PCR was positive for micrometastases within the sentinel node. In conclusion, erroneous sentinel lymph node identification can be due to changes in the surgical team, difficult lymph node location or absence of a thorough histological study. Nevertheless, it is not possible to explain completely why, in a very small percentage of cases, the sentinel node is erroneously identified.