RESUMO
Metastasis is generally considered a characteristic of malignant tumors. Herein, we describe a patient with more than one hundred discrete Spitz nevi scattered all over her skin. Molecular analysis from three of the lesions identified a ROS1 fusion oncogene with identical genomic breakpoints, indicating that the nevi arose from a single transformed melanocyte and then disseminated throughout the integument. The demonstration of widespread distribution of a benign tumor with limited proliferative capability indicates that metastatic dissemination is not contingent on full malignant transformation. Thus, eruptive Spitz nevus is a striking example of benign metastasis, demonstrating that metastasis can occur before malignant transformation.
Assuntos
Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias Cutâneas/secundário , Feminino , Humanos , Melanoma/genética , Pessoa de Meia-Idade , Prognóstico , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Neoplasias Cutâneas/genéticaAssuntos
Biomarcadores Tumorais/sangue , Carcinoma de Células em Anel de Sinete/secundário , Linfonodos/patologia , Melanoma/secundário , Neoplasias Primárias Desconhecidas/sangue , Neoplasias Cutâneas/secundário , Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Biópsia por Agulha , Carcinoma de Células em Anel de Sinete/patologia , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Melanoma/patologia , Estadiamento de Neoplasias , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Toxic shock syndrome (TSS) may be mediated by superantigen-activated T cells, a theory we tested in rabbits, which are more susceptible to the lethal effects of superantigens, such as TSS toxin-1 (TSST-1), than are mice. Rabbits exposed to 10 cGy of total body irradiation exhibited T cell deficiency, with profound depletion of splenic lymphocytes and circulating CD4(+) lymphocytes, as well as an inability to manifest delayed-type hypersensitivity. Nevertheless, these rabbits remained completely susceptible to TSST-1, indicating that TSS can occur in the setting of marked immunosuppression.
Assuntos
Toxinas Bacterianas , Ciclosporina/farmacologia , Enterotoxinas/efeitos da radiação , Enterotoxinas/toxicidade , Imunossupressores/farmacologia , Choque Séptico/mortalidade , Irradiação Corporal Total , Animais , Feminino , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Coelhos , Choque Séptico/imunologia , Choque Séptico/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade , Superantígenos/efeitos da radiação , Superantígenos/toxicidade , Linfócitos TRESUMO
Superantigens (SAGs) aberrantly alter immune system function through simultaneous interaction with lateral surfaces of MHC class II molecules on APCs and with particular variable regions of the TCR beta-chain (Vbeta). To further define the interface between the bacterial SAG toxic shock syndrome toxin-1 (TSST-1) and the TCR, we performed alanine scanning mutagenesis within the putative TCR binding region of TSST-1 along the central alpha helix adjacent to the N-terminal alpha helix and the beta7-beta9 loop as well as with two universally conserved SAG residues (Leu(137) and Tyr(144) in TSST-1). Mutants were analyzed for multiple functional activities, and various residues appeared to play minor or insignificant roles in the TCR interaction. The locations of six residues (Gly(16), Trp(116), Glu(132), His(135), Gln(136), and Gln(139)), each individually critical for functional activity as well as direct interaction with the human TCR Vbeta2.1-chain, indicate that the interface occurs in a novel region of the SAG molecule. Based on these data, a model of the MHC/TSST-1/TCR ternary complex predicts similarities seen with other characterized SAGs, although the CDR3 loop of Vbeta2.1 is probably involved in direct SAG-TCR molecular interactions, possibly contributing to the TCR Vbeta specificity of TSST-1.
