RESUMO
BACKGROUND: Patients presenting with early-stage melanoma (AJCC pT1b-pT2a) reportedly have a relatively low risk of a positive SNB (~5-10%). Those patients are usually found to have low-volume metastatic disease after SNB, typically reclassified to AJCC stage IIIA, with an excellent prognosis of ~90% 5-year survival. Currently, adjuvant systemic therapy is not routinely recommended for most patients with AJCC stage IIIA melanoma. The purpose was to assess the SN-positivity rate in early-stage melanoma and to identify primary tumor characteristics associated with high-risk nodal disease eligible for adjuvant systemic therapy METHODS: An international, multicenter retrospective cohort study from 7 large-volume cancer centers identified 3,610 patients with early primary cutaneous melanomas 0.8-2.0 mm in Breslow thickness (pT1b-pT2a; AJCC 8th edition). Patient demographics, primary tumor characteristics, and SNB status/details were analyzed. RESULTS: The overall SNB-positivity rate was 11.4% (412/3610). Virtually all SNB-positive patients (409/412; 99.3%) were reclassified to AJCC stage IIIA. Multivariate analysis identified age, T-stage, mitotic rate, primary site and subtype, and lymphovascular invasion as independent predictors of sentinel node status. A mitotic rate of >1/mm2 was associated with a significantly increased SN-positivity rate and was the only significant independent predictor of high-risk SNB metastases (>1 mm maximum diameter). CONCLUSIONS: The new treatment paradigm brings into question the role of SNB for patients with early-stage melanoma. The results of this large international cohort study suggest that a reevaluation of the indications for SNB for some patients with early-stage melanoma is required.
Assuntos
Melanoma , Neoplasias Cutâneas , Adjuvantes Imunológicos , Estudos de Coortes , Humanos , Melanoma/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/cirurgia , Melanoma Maligno CutâneoRESUMO
Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly implicated in MCC pathogenesis. Currently, little is known regarding the virus-host cell interactions which support virus replication and virus-induced mechanisms in cellular transformation and metastasis. Here we identify a new function of MCPyV small T antigen (ST) as an inhibitor of NF-κB-mediated transcription. This effect is due to an interaction between MCPyV ST and the NF-κB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits IκB kinase α (IKKα)/IKKß-mediated IκB phosphorylation, which limits translocation of the NF-κB heterodimer to the nucleus. Regulation of this process involves a previously undescribed interaction between MCPyV ST and the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein phosphatase 2A (PP2A) Aß, but not PP2A Aα. Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell.
Assuntos
Antígenos Virais de Tumores/metabolismo , Carcinoma de Célula de Merkel/metabolismo , Quinase I-kappa B/metabolismo , Poliomavírus das Células de Merkel/metabolismo , Infecções por Polyomavirus/metabolismo , Infecções Tumorais por Vírus/metabolismo , Antígenos Virais de Tumores/genética , Carcinoma de Célula de Merkel/genética , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/virologia , Linhagem Celular , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/imunologia , Imunidade Inata , Poliomavírus das Células de Merkel/genética , NF-kappa B/genética , NF-kappa B/imunologia , Fosforilação , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Ligação Proteica , Infecções Tumorais por Vírus/genética , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologiaRESUMO
PURPOSE: Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy. METHODS: Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and survival outcomes were analyzed. RESULTS: Three thousand six hundred seven patients were included. The median follow-up was 34 months. Pairwise disease comparison demonstrated no significant survival difference between N1a and N2a subgroups. Survival analysis identified a SN tumor deposit maximum dimension of 0.3 mm as the optimal cut point for stratifying survival. Five-year disease-specific survival rates were 80.3% and 94.1% for patients with SN metastatic tumor deposits ≥ 0.3 mm and < 0.3 mm, respectively (hazard ratio, 1.26 [1.11 to 1.44]; P < .0001). Similar findings were seen for overall disease-free and distant metastasis-free survival. There were no survival differences between the AJCC IB patients and low-risk (< 0.3 mm) AJCC IIIA patients. The newly identified high-risk (≥ 0.3 mm) subgroup comprised 271 (66.4%) of the AJCC IIIA cohort, whereas only 142 (34.8%) patients had SN tumor deposits > 1 mm in maximum dimension. CONCLUSION: Patients with AJCC IIIA melanoma with SN tumor deposits ≥ 0.3 mm in maximum dimension are at higher risk of disease progression and may benefit from adjuvant systemic therapy or enrollment into a clinical trial. Patients with SN deposits < 0.3 mm in maximum dimension can be managed similar to their SN-negative, AJCC IB counterparts, thereby avoiding regular radiological surveillance and more intensive follow-up.
Assuntos
Melanoma , Neoplasias Cutâneas , Adulto , Humanos , Estados Unidos , Micrometástase de Neoplasia/patologia , Extensão Extranodal , Estadiamento de Neoplasias , Melanoma/tratamento farmacológico , Medição de Risco , Neoplasias Cutâneas/tratamento farmacológico , PrognósticoRESUMO
The optimal treatment for type II endoleaks remains unclear. The present report describes a case of ischemic skin ulceration after glue embolization of a type II endoleak with challenging access in a multiply comorbid 82-year-old woman with an expanding aneurysm sac 3 years after endovascular aneurysm repair. Embolization was performed from a proximal position with an n-butyl cyanoacrylate/Ethiodol mixture to allow flow into the endoleak because direct sac puncture was hazardous. One week after intervention, an eschar, which progressed to superficial necrosis as a result of partial nontarget delivery of sclerosant, developed over the left iliac crest. The eschar was self-limiting, with complete resolution by 6 months.