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BACKGROUND: Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated. OBJECTIVE: We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma. METHODS: Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models. RESULTS: MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p < 0.001). In a multivariable competing risk model, selection for SLNB omission was an independent predictor of death from non-melanoma causes (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.3, p < 0.001). After incorporation of the MSK FI score into the multivariable model in this subset, MSK FI (HR 2.4, 95% CI 1.5-4.1, p < 0.001), but not SLNB omission, was an independent predictor of poorer OS. CONCLUSION: We observed worse OS in patients with thick melanoma selected not to undergo SLNB, which was attributed to death due to non-melanoma causes. Formal assessment of frailty may provide an objective prognostic measure to guide selective use of SLNB in these patients.
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Fragilidade , Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Tomada de Decisões , Humanos , Melanoma/cirurgia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Digital papillary adenocarcinoma (DPA) is a rare, aggressive neoplasm of sweat gland origin. It can recur at local, regional, or distant sites. There is limited knowledge about the role of sentinel lymph node biopsy (SLNB) in predicting recurrence in these patients. We present our experience with this uncommon tumor to evaluate the role of SLNB in predicting outcome. METHODS: Medical records of all patients who underwent surgical treatment for biopsy-proven upper extremity DPA at the study institution were reviewed. Descriptive statistics and Fisher's exact test were used to analyze data. RESULTS: Twenty-one patients were identified. Most patients were male (71%), and the median age was 51 years. SLNB was performed in 18 patients; three were positive for nodal metastatic disease (17%). At a median follow-up of 53 months, there were no local recurrences and two cases of systemic recurrence. No patient with a negative sentinel lymph node has evidence of metastasis or recurrence. Fisher's exact test demonstrated a significant association between a positive SLNB and recurrence (P = .02). CONCLUSION: SLNB revealed metastatic disease in 17% of patients with DPA and appears to predict systemic recurrence in this small series.
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Adenocarcinoma Papilar/patologia , Linfonodos/patologia , Recidiva Local de Neoplasia/patologia , Biópsia de Linfonodo Sentinela/métodos , Adenocarcinoma Papilar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: This guideline reviews the evidence for the use of definitive and postoperative radiation therapy (RT) in patients with basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on indications for RT in the definitive and postoperative setting for BCC and cSCC, as well as dose-fractionation schemes, target volumes, basic aspects of treatment planning, choice of radiation modality, and the role of systemic therapy in combination with radiation. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: The guideline recommends definitive RT as primary treatment for patients with BCC and cSCC who are not surgical candidates while conditionally recommending RT with an emphasis on shared decision-making in those situations in which adequate resection can lead to a less than satisfactory cosmetic or functional outcome. In the postoperative setting, a number of indications for RT after an adequate resection are provided while distinguishing the strength of the recommendations between BCC and cSCC. One key question is dedicated to defining indications for regional nodal irradiation. The task force suggests a range of appropriate dose-fractionation schemes for treatment of primary and nodal volumes in definitive and postoperative scenarios. The guideline also recommends against the use of carboplatin concurrently with adjuvant RT and conditionally recommends the use of systemic therapies for unresectable primaries where treatment may need escalation. CONCLUSIONS: Defining the role of RT in the management of BCC and cSCC has been hindered by a lack of high-quality evidence. This document synthesizes available evidence to define practice guidelines for the most common clinical situations. We encourage practitioners to enroll patients in prospective trials and to approach care in a multidisciplinary fashion whenever possible.
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Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Medicina Baseada em Evidências/normas , Radioterapia (Especialidade)/normas , Neoplasias Cutâneas/terapia , Fracionamento da Dose de Radiação , Medicina Baseada em Evidências/métodos , Humanos , Seleção de Pacientes , Radioterapia (Especialidade)/métodos , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/normas , Sociedades Médicas/normas , Estados UnidosRESUMO
Closed suction drains (CSD) are commonly used in ventral hernia repair (VHR), with or without prolonged postoperative prophylactic antibiotics (PPA) for the duration of their use. We examine the evidence that PPA with CSD reduce surgical site infection (SSI) in patients undergoing VHR. We also examine the evidence assessing the association between SSI and CSD in VHR. A systematic review of PubMed, CIHNL, and Cochrane databases was performed to identify studies analyzing rates of SSI with CSD in patients undergoing abdominal VHR and related procedures with or without the concomitant use of PPA. The primary outcome was the rate of SSI. Five studies totaling 772 patients were identified, 525 patients were confirmed to have CSD, and 434 patients received prolonged antibiotics while drains were in place. PPA had no significant effect on SSI in two studies and were associated with decreased SSI in one study (Odds ratio 0.235, 95% confidence interval 0.090-0.617, P = 0.003). Two studies documented a higher rate of SSI in patients with CSD (79% vs 49% and 19% vs 10%) on univariate analysis. One study demonstrated a very low risk of SSI despite CSD (4.2%) and another demonstrated no increased risk with or without CSD. The use of drains is not clearly associated with an increased risk of SSI in VHR, and there is limited evidence to support antibiotic use while the drains are in place to decrease the potential risk. Prospective randomized studies are needed to more clearly assess these associations.
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Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Hérnia Ventral/cirurgia , Herniorrafia , Cuidados Pós-Operatórios/métodos , Sucção/métodos , Infecção da Ferida Cirúrgica/prevenção & controle , Antibacterianos/uso terapêutico , Esquema de Medicação , Humanos , Cuidados Pós-Operatórios/instrumentação , Sucção/instrumentação , Infecção da Ferida Cirúrgica/epidemiologia , Resultado do TratamentoRESUMO
The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.
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Fracionamento Celular/métodos , Exossomos/metabolismo , Nanopartículas , Neoplasias/metabolismo , Proteínas/metabolismo , Animais , Biomarcadores/metabolismo , DNA/genética , DNA/metabolismo , Metabolismo Energético , Exossomos/classificação , Exossomos/genética , Exossomos/patologia , Feminino , Glicômica , Glicosilação , Células HCT116 , Humanos , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Neoplasias/genética , Neoplasias/patologia , Células PC-3 , Fenótipo , Proteômica , RNA/genética , RNA/metabolismo , Transdução de Sinais , Distribuição TecidualRESUMO
Both the combination of nivolumab + ipilimumab and single-agent anti-PD-1 immunotherapy have demonstrated survival benefit for patients with advanced melanoma. As the combination has a high rate of serious side effects, further analyses in randomized trials of combination versus anti-PD-1 immunotherapy are needed to understand who benefits most from the combination. Clinical laboratory values that were routinely collected in randomized studies may provide information on the relative benefit of combination immunotherapy. To prioritize which clinical laboratory factors to ultimately explore in these randomized studies, we performed a single-center, retrospective analysis of patients with advanced melanoma who received nivolumab + ipilimumab either as part of a clinical trial (n = 122) or commercial use (n = 87). Baseline routine laboratory values were correlated with overall survival (OS) and overall response rate (ORR). Kaplan-Meier estimation and Cox regression were performed. Median OS was 44.4 months, 95% CI (32.9, Not Reached). A total of 110 patients (53%) responded (CR/PR). Significant independent variables for favorable OS included the following: high relative eosinophils, high relative basophils, low absolute monocytes, low LDH, and a low neutrophil-to-lymphocyte ratio. These newly identified factors, along with those previously reported to be associated with anti-PD-1 monotherapy outcomes, should be studied in the randomized trials of nivolumab + ipilimumab versus anti-PD-1 monotherapies to determine whether they help define the patients who benefit most from the combination versus anti-PD-1 alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Técnicas de Laboratório Clínico/métodos , Imunoterapia/métodos , Ipilimumab/uso terapêutico , Melanoma/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Ipilimumab/farmacologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Nivolumabe/farmacologia , Estudos Retrospectivos , Adulto JovemRESUMO
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a noninflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated with improved survival of the mice. To translate these findings into a clinical setting, 26 patients with advanced melanoma were treated locally by isolated limb infusion with the nitrogen mustard alkylating agent melphalan followed by systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II trial. This combination of local chemotherapy with systemic checkpoint blockade inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23% partial response rate) and a 58% progression-free survival at 1 year. The clinical response was associated with increased T-cell infiltration, similar to that seen in the murine models. Together, our findings suggest that local chemotherapy combined with checkpoint blockade-based immunotherapy results in a durable response to cancer therapy. Cancer Immunol Res; 6(2); 189-200. ©2018 AACR.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno CTLA-4/antagonistas & inibidores , Melanoma/tratamento farmacológico , Melanoma/terapia , Animais , Antígeno CTLA-4/imunologia , Linhagem Celular Tumoral , Terapia Combinada , Dactinomicina/administração & dosagem , Humanos , Imunoterapia/métodos , Ipilimumab/administração & dosagem , Masculino , Melanoma/imunologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Melfalan/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The diagnosis of a single small pink papule poses a real challenge to the clinician, as the differential diagnosis of such lesions includes benign entities such as a neurofibroma or hemangioma, as well as aggressive and potentially fatal skin malignancies such as amelanotic melanoma or Merkel cell carcinoma (MCC). The absence of a benign vascular pattern and the presence of atypical vascular features under dermoscopy direct the clinician to proceed to histologic evaluation in order to rule out a malignant process in such lesions. The diagnosis of MCC is particularly problematic, given that this tumor usually lacks specific clinical diagnostic features. Low clinical suspicion for MCC may result in delayed diagnosis and poor outcomes. The dermoscopic features of MCC are also non-specific, most commonly including milky-red areas and linear irregular vessels. We report a patient who presented with two discrete pink papules on different digits that appeared three years apart. Dermoscopy helped to diagnose a harmless hemangioma in the first lesion, and a MCC in the latter. The malignant tumor was diagnosed and excised expeditiously, with no evidence of metastatic spread.
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BACKGROUND: Outcomes of surgical trials hinge on surgeon selection and their underlying expertise. Assessment of expertise is paramount. We investigated whether surgeons' performance measured by the fundamentals of laparoscopic surgery (FLS) assessment program could predict their performance in a surgical trial. METHODS: As part of a prospective multi-institutional study of minimally invasive inguinal lymphadenectomy (MILND) for melanoma, surgical oncologists with no prior MILND experience underwent pre-trial FLS assessment. Surgeons completed MILND training, began enrolling patients, and submitted videos of each MILND case performed. Videos were scored with the global operative assessment of laparoscopic skills (GOALS) tool. Associations between baseline FLS scores and participant's trial performance metrics were assessed. RESULTS: Twelve surgeons enrolled patients; their median total baseline FLS score was 332 (range 275-380, max possible 500, passing >270). Participants enrolled 87 patients in the study (median 6 per surgeon, range 1-24), of which 72 (83%) videos were adequate for scoring. Baseline GOALS score was 17.1 (range 9.6-21.2, max possible score 30). Inter-rater reliability was excellent (ICC = 0.85). FLS scores correlated with improved GOALS scores (r = 0.57, p = 0.05) and with decreased operative time (r = -0.6, p = 0.02). No associations were found with the degree of patient recruitment (r = 0.02, p = 0.7), lymph node count (r = 0.01, p = 0.07), conversion rate (r = -0.06, p = 0.38) or major complications(r = -0.14, p = 0.6). CONCLUSIONS: FLS skill assessment of surgeons prior to their enrollment in a surgical trial is feasible. Although better FLS scores predicted improved operative performance and operative time, other trial outcome measures showed no difference. Our findings have implications for the documentation of laparoscopic expertise of surgeons in practice and may allow more appropriate selection of surgeons to participate in clinical trials.
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Competência Clínica , Laparoscopia/educação , Excisão de Linfonodo/métodos , Melanoma/cirurgia , Feminino , Virilha/cirurgia , Humanos , Laparoscopia/normas , Excisão de Linfonodo/normas , Linfonodos/patologia , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/educação , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Duração da Cirurgia , Complicações Pós-Operatórias , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Minimally invasive inguinal lymph node dissection (MILND) is a novel approach to inguinal lymphadenectomy. SAFE-MILND (NCT01500304) is a multicenter, phase I/II clinical trial evaluating the safety and feasibility of MILND for patients with melanoma in a group of surgeons newly adopting the procedure. METHODS: Twelve melanoma surgeons from 10 institutions without any previous MILND experience, enrolled patients into a prospective study after completing specialized training including didactic lectures, participating in a hands-on cadaveric laboratory, and being provided an instructional DVD of the procedure. Complications and adverse postoperative events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: Eighty-seven patients underwent a MILND. Seventy-seven cases (88.5%) were completed via a minimally invasive approach. The median total inguinal lymph nodes pathologically examined (SLN + MILND) was 12.0 (interquartile range 8.0, 14.0). Overall, 71% of patients suffered an adverse event (AE); the majority of these were grades 1 and 2, with 26% of patients experiencing a grade 3 AE. No grade 4 or 5 AEs were observed. CONCLUSIONS: After a structured training program, high-volume melanoma surgeons adopted a novel surgical technique with a lymph node retrieval rate that met or exceeded current oncologic guidelines and published benchmarks, and a favorable morbidity profile.
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Excisão de Linfonodo/métodos , Melanoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Seguimentos , Virilha , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Subtypes of melanoma, such as mucosal, uveal, and acral, are believed to result in worse prognoses than nonacral cutaneous melanoma. After a diagnosis of distant metastatic disease, however, the overall survival of patients with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma has not been directly compared. MATERIALS AND METHODS: We conducted a single-center, retrospective analysis of 3,454 patients with melanoma diagnosed with distant metastases from 2000 to 2013, identified from a prospectively maintained database. We examined melanoma subtype, date of diagnosis of distant metastases, age at diagnosis of metastasis, gender, and site of melanoma metastases. RESULTS: Of the 3,454 patients (237 with mucosal, 286 with uveal, 2,292 with nonacral cutaneous, 105 with acral cutaneous, and 534 with unknown primary melanoma), 2,594 died. The median follow-up was 46.1 months. The median overall survival for those with mucosal, uveal, acral, nonacral cutaneous, and unknown primary melanoma was 9.1, 13.4, 11.4, 11.7, and 10.4 months, respectively. Patients with uveal melanoma, cutaneous melanoma (acral and nonacral), and unknown primary melanoma had similar survival, but patients with mucosal melanoma had worse survival. Patients diagnosed with metastatic melanoma in 2006-2010 and 2011-2013 had better overall survival than patients diagnosed in 2000-2005. In a multivariate model, patients with mucosal melanoma had inferior overall survival compared with patients with the other four subtypes. CONCLUSION: Additional research and advocacy are needed for patients with mucosal melanoma because of their shorter overall survival in the metastatic setting. Despite distinct tumor biology, the survival was similar for those with metastatic uveal melanoma, acral, nonacral cutaneous, and unknown primary melanoma. IMPLICATIONS FOR PRACTICE: Uveal, acral, and mucosal melanoma are assumed to result in a worse prognosis than nonacral cutaneous melanoma or unknown primary melanoma. No studies, however, have been conducted assessing the overall survival of patients with these melanoma subtypes starting at the time of distant metastatic disease. The present study found that patients with uveal, acral, nonacral cutaneous, and unknown primary melanoma have similar overall survival after distant metastases have been diagnosed. These findings provide information for oncologists to reconsider previously held assumptions and appropriately counsel patients. Patients with mucosal melanoma have worse overall survival and are thus a group in need of specific research and advocacy.
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Melanoma/mortalidade , Neoplasias Primárias Desconhecidas/mortalidade , Neoplasias Cutâneas/mortalidade , Neoplasias Uveais/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders (CD30(+) LPD), including primary cutaneous anaplastic large cell lymphoma (CALCL) and lymphomatoid papulosis (LyP), comprise the second most common group of cutaneous T-cell lymphomas (CTCL). The etiology of these disorders is not known. Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are forms of regional chemotherapy used to treat recurrent tumors of the extremity, most commonly, melanoma. Secondary malignancy following regional therapy is rarely reported. METHODS/RESULTS: We identified two cases of CD30(+) LPD arising in the affected limbs of patients treated with ILP/ILI. We subsequently performed CD30 immunohistochemical stains on 11 pre- and post-treatment skin specimens from melanoma patients treated with ILP/ILI and found that 5 of the 11 cases showed an increase in CD30(+) lymphocytes following ILP/ILI. CONCLUSIONS: We hypothesize that ILP/ILI causes upregulation of CD30 expression in the extremities of treated patients, and suggest that this may be a marker of treatment response. However, a rare but long-term effect may be an increased risk of T-cell cutaneous lymphoproliferative disease in the affected limb.
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Antígeno Ki-1/metabolismo , Linfócitos/metabolismo , Linfoma Anaplásico de Células Grandes/diagnóstico , Papulose Linfomatoide/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias Cutâneas/metabolismo , Antineoplásicos Alquilantes/uso terapêutico , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Feminino , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/metabolismo , Papulose Linfomatoide/metabolismo , Masculino , Melanoma/patologia , Melanoma/terapia , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Segunda Neoplasia Primária/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
BACKGROUND: The benefit of completion lymph node dissection (CLND) in melanoma patients with a positive sentinel lymph node (SLN) remains unknown. METHODS: We identified patients with a positive SLN from 1994 to 2012. Patient and tumor characteristics, reasons for not undergoing CLND, patterns of recurrence, and melanoma-specific survival data were analyzed. RESULTS: Of 4,310 patients undergoing SLN biopsy (SLNB), 495 (11 %) had a positive SLN-167 (34 %) patients underwent nodal observation and 328 (66 %) had immediate CLND. Patients in the no-CLND group were older (66 vs. 56 years; p < 0.001) and more likely to have lower extremity lesions (57 vs. 42 %; p = 0.006). There were no differences in tumor thickness, Clark level of invasion, ulceration, or SLN tumor burden. Median follow-up was 23 and 80 months for the no-CLND and CLND groups, respectively, and median time to recurrence was similar at 9 and 12 months, respectively (p = 0.48). There was no difference in local and in transit recurrence rates between groups (16 %, no CLND, and 18 %, CLND; p = 0.48). Nodal disease as a site of first recurrence occurred in 15 % of patients in the no-CLND group and 6 % of CLND patients (p = 0.002). In contrast, systemic recurrences occurred in 8 % of no-CLND patients compared with 27 % of CLND patients (p < 0.001). While median recurrence-free survival was higher after CLND (34.5 vs. 20.9 months; p = 0.02), melanoma-specific survival was similar (not reached, no CLND vs. 110 months, CLND; p = 0.09). CONCLUSIONS: Immediate CLND after a positive SLNB is associated with fewer initial nodal basin recurrences but similar melanoma-specific survival. These results support ongoing equipoise in the Multicenter Selective Lymphadenectomy Trial II (MSLT-II).
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Excisão de Linfonodo/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Biópsia de Linfonodo Sentinela , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Carga Tumoral , Adulto JovemRESUMO
The diagnosis of metastatic melanoma can be complicated by absent characteristic cytology, melanin, or antigen expression in a suspect tumor, putting the pathologist at risk for incorrectly diagnosing recurrent melanoma while missing a second malignancy. We report a 69-year-old man with a history of acral melanoma, metastatic to inguinal nodes, presenting with an ipsilateral thigh nodule. Histology showed a proliferation of pleomorphic cells in the dermis and subcutis, suspicious for melanoma. S100, Melan-A, and HMB-45 immunohistochemistry were negative. However, microphthalmia-associated transcription factor and CD117 labeled the neoplasm, prompting consideration of a late metastatic melanoma with loss of antigen expression. Subsequent immunolabeling for CD4, CD43, and CD30 and clonal T-cell gene rearrangements enabled the correct diagnosis of cutaneous anaplastic large cell lymphoma. This case illustrates a pitfall in evaluating tumors in patients with known metastatic melanoma, and emphasizes the need for broad-spectrum immunohistochemistry in cases that are not clear-cut.
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Linfoma Anaplásico de Células Grandes/diagnóstico , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Antígeno Ki-1/metabolismo , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Masculino , Melanoma/metabolismo , Melanoma/patologia , Melanoma/secundário , Fator de Transcrição Associado à Microftalmia/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
First-degree relatives (FDRs) of melanoma survivors are at heightened risk for developing melanoma, but use sun protection inconsistently. To develop appropriate interventions, in this article we identify factors related to sun protection inconsistency in melanoma FDRs using ethnographic decision tree modeling. We conducted in-home interviews with 25 melanoma FDRs balanced across gender and sunbathing attitudes and identified factors related to daily decision making about use of sunscreen, shade seeking, hats, and clothing. Results indicated primary facilitators for sun protection involved water settings and sunny weather. Physical activities such as exercise served to promote as well as inhibit sun protection. If participants anticipated shade cover, they tended to forgo other sun protection. The use of hats and clothing was often dictated by nonsun-protection goals. Understanding factors related to inconsistent sun protection with detail and nuance is an important prerequisite to interventions aimed to improve sun-protection maintenance in this population.
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Exposição Ambiental/prevenção & controle , Promoção da Saúde/métodos , Melanoma/epidemiologia , Assunção de Riscos , Protetores Solares , Raios Ultravioleta/efeitos adversos , Adulto , Idoso , Antropologia Cultural , Tomada de Decisões , Árvores de Decisões , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Melanoma/genética , Melanoma/prevenção & controle , Pessoa de Meia-Idade , Roupa de Proteção , Sobreviventes , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Current therapy for intermediate thickness melanoma involves wide local excision with sentinel lymph node biopsy (SLNB). SLNB provides important prognostic information and immediate regional lymphadenectomy for a positive sentinel lymph node (SLN) may improve survival and identifies patients who are candidates for adjuvant therapy and/or clinical trials. The head and neck site is unique because of its complex lymphatic drainage pattern to multiple nodal basins and because of the risk of site-specific morbidity associated with regional lymphadenectomy when compared to other body sites. The goal of this study is to report the results of SLNB for head and neck cutaneous melanoma in locating the sentinel node and to report on the prognostic implications of SLNB for this cohort of patients. METHODS: A prospectively entered melanoma database was used to review consecutive patients with head and neck cutaneous melanoma undergoing SLNB at Memorial Sloan-Kettering Cancer Center between 1996 and 2007. The database, along with a retrospective chart review, was used to evaluate the success of SLNB at locating an SLN and the success rate of frozen section and permanent section analysis at diagnosing metastatic disease. Recurrence at all sites including the nodal basin and status at last follow-up was recorded. Characteristics of the patients' primary melanoma were included. Descriptive statistics along with univariate and multivariate survival analysis were performed. RESULTS: Between 1996 and 2007, 234 patients with a diagnosis of head and neck cutaneous melanoma underwent SLNB and had at least 1 month of follow-up. At least 1 SLN was identified in 218 of these patients (93%) by lymphoscintigraphy. In 16 patients, no SLN was found. These patients had a much shorter time to recurrence (4.75 months) than either the SLN-positive group (10.7 months) or the SLN-negative group (26.0 months). They had a disease-specific survival (DSS) in between the SLN-positive and SLN-negative group. Of the patients in whom an SLN was identified, 28 patients (12%) had at least 1 positive SLN. Of these, the SLNs of 14 patients (50%) were identified on frozen section; 14 (50%) could only be identified after further sectioning or immunohistochemical analysis postoperatively. Among 190 patients with a negative SLNB, 12 patients had recurrences in the nodal basin. This resulted in a sensitivity of 70%, a negative predictive value of 94%, and a false-negative rate of 30%. The 3-year disease-free survival for SLN-negative and SLN-positive patients was 84% (p < .031) and 58% (p < .102), respectively. The 3-year melanoma-specific survival was 98% (p < .012) and 75% (p < .201), respectively. CONCLUSION: The SLN status is an important predictor of survival. The technique, performed in the head and neck is complex and associated with a high false-negative rate.
Assuntos
Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Metástase Linfática , Melanoma/mortalidade , Melanoma/secundário , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Neoplasias Cutâneas/mortalidade , Análise de SobrevidaRESUMO
BACKGROUND: Completion lymph node dissection (CLND), although considered a standard approach for patients with melanoma and a positive sentinel lymph node (SLN), is not performed in as many as 50% of indicated cases. This study evaluates the outcome of patients who had a positive SLN but did not undergo CLND at Memorial Sloan-Kettering Cancer Center. METHODS: A prospective database was used to identify all patients with a positive SLN from 1992 to 2008. Patient and tumor characteristics, number of positive SLNs, recurrence pattern, reason for not performing a CLND, and current status were evaluated. RESULTS: There were 2269 patients who underwent SLN biopsy. Three hundred thirteen had a positive SLN, of whom 271 (87%) had a CLND and 42 (13%) did not. Patients in the no-CLND group were older (median age 70 vs. 56 years, P < .01), and had a trend toward thicker melanomas (3.5 vs. 2.8 mm, P < .06). A significantly higher percentage of no- CLND patients had lower-extremity melanomas (40% vs. 13% CLND; P < .01). The most common reason for not performing a CLND was patient refusal (45%). There were similar rates and patterns of recurrence between the two groups. Recurrence-free survival and disease-specific survival were also similar between the groups. CONCLUSIONS: It remains unclear whether CLND must be performed in all melanoma patients with a positive SLN. For selected informed patients who choose not to participate in the Multicenter Selective Lymphadenectomy Trial II trial, or in centers where the trial is not available, nodal observation may be an acceptable option.
Assuntos
Excisão de Linfonodo , Melanoma/cirurgia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
While sentinel lymph node biopsy (SLN) is a highly accurate and well-tolerated procedure for patients with cutaneous melanoma, the role of the completion lymph node dissection (CLND) for patients with positive SLN biopsy remains unknown. This study aimed to look at the prognostic value of a positive nonsentinel lymph node (NSLN). A prospectively maintained database identified 222 patients with cutaneous melanoma and a positive SLN biopsy, without evidence of distant disease. All of these patients underwent CLND, and 37 patients (17%) had positive NSLN. With median follow-up of 33 months, patients with negative NSLN had median survival of 104 months, while patients with positive NSLN had median survival of 36 months (p < 0.001). There were no survivors in the patients with positive NSLN beyond 6 years. When patients with an equal number of positive nodes were analyzed, the presence of a positive NSLN was still associated with worse melanoma-specific survival (66 months for NSLN- versus 34 months for NSLN+, p = 0.04). While increasing age, tumor thickness, and male sex were associated with an increased risk of death on multivariate analysis, a positive NSLN was the most important predictor of survival (hazard ratio 2.5). We conclude that positive NSLN is an independent predictor of disease-specific survival in patients with cutaneous melanoma.
Assuntos
Linfonodos/patologia , Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Melanoma/secundário , Melanoma/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Survival of patients with stage IV melanoma is poor. In the current American Joint Committee on Cancer (AJCC) staging system, site of distant disease and lactate dehydrogenase (LDH) are the only prognostic factors included for stage IV disease. We sought to validate the current AJCC staging system in a contemporary, prospectively collected cohort of patients and explore additional factors that may influence prognosis. METHODS: Our prospective database was searched to identify patients with stage IV melanoma; only patients seen at our institution before developing stage IV disease were included (n = 589). Demographic, clinical, and tumor characteristics were abstracted. Univariate and multivariate assessment of prognostic factors associated with survival were performed by Cox regression. RESULTS: Overall median survival was 9 months. Differential survival by AJCC substage was observed (P < .001). For each site of disease described within the AJCC staging system, an abnormal LDH level was associated with a poorer prognosis. By multivariate analysis, older age at diagnosis (as a continuous variable, hazard ratio [HR] 1.02, 95% confidence interval [95% CI]) 1.01-1.02), an abnormal LDH (HR 1.42, 95% CI 1.11-1.82), site of disease (lung HR 1.22, 95% CI .89-1.66; other viscera 1.61, 95% CI 1.18-2.21), more than one organ involvement (HR 1.27, 95% CI 1.01-1.60), and more than one metastasis (HR 2.27, 95% CI 1.65-3.14) were independently associated with poorer survival. Sex, antecedent stage, and disease-free interval were not statistically significant. CONCLUSION: In our patient cohort, the AJCC staging system was valid. The strongest predictor of survival-the number of metastases present at the diagnosis of stage IV disease-represents a variable to consider in future staging systems.