RESUMO
Mikulicz's disease is considered one of the IgG4-related diseases that are characterized by elevated serum IgG4 concentrations and the immunohistochemical finding of IgG4-positive plasma cells. The IgG4-related diseases often exhibit a wide variety of eosinophil infiltration. A 66-year-old male with Mikulicz's disease developed multiple, nonpruritic, red papules on the left opisthotic region 2 years after diagnosis. A biopsy of the skin lesions revealed follicle-like formation in the dermis and subcutaneous tissue containing nodular lymphocytic infiltration with numerous eosinophils and plasma cells, predominately around venules, mimicking angiolymphoid hyperplasia with eosinophilia (ALHE). Immunohistochemically, most IgG-expressing plasma cells were positive for IgG4 (IgG4/IgG ratio = 72%). Our patient appeared to have a condition associated with the IgG4-related diseases. Caution should be exercised in diagnosing skin lesions of the IgG4-related diseases, which are confusingly similar in appearance and histology to ALHE.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Imunoglobulina G/sangue , Dermatopatias/diagnóstico , Idoso , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Biópsia , Diagnóstico Diferencial , Eosinófilos/patologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina G/análise , Imuno-Histoquímica , Masculino , Doença de Mikulicz/diagnóstico , Doença de Mikulicz/tratamento farmacológico , Doença de Mikulicz/patologia , Plasmócitos/patologia , Prednisolona/uso terapêutico , Dermatopatias/tratamento farmacológico , Dermatopatias/patologiaRESUMO
Polycomb-group proteins Bmi1 and EZH2 are involved in the malignant transformation and biological aggressiveness of several human carcinomas. We herein examined the significance of the Bmi1 and EZH2 expression in hepatocellular carcinoma (HCC) and its preneoplastic lesions, dysplastic nodules. The expression of Bmi1 and EZH2 were examined immunohistochemically in HCC (n=27) and dysplastic nodules (n=14), and combined hepatocellular and cholangiocarcinoma (HC-CC) (n=14). The effect of Bmi1 and EZH2 knockdown was examined in cultured HCC cells (HuH7 and HepG2) using siRNA. It was determined that Bmi1 was constantly expressed in cholangiocytes, but not in hepatocytes, and EZH2 was detected in neither cholangiocytes nor hepatocytes. Bmi1 and EZH2 were overexpressed in HCC and more extensively in HC-CC (P<0.01). Interestingly, Bmi1 and EZH2 were not overexpressed in the dysplastic nodules. The expression of Bmi1 and EZH2 was heterogeneous and associated with vascular infiltration, the histological grades, and the cell proliferation activity in HCC and HC-CC. In cultured carcinoma cells overexpressing Bmi1 and EZH2, knockdown of Bmi1 and EZH2 resulted in decreased cell proliferation activities. Therefore, the overexpression of polycomb-group proteins Bmi1 and EZH2 is associated with the malignant progression of HCC, thereby reflecting the aggressive biological behavior in HCC and HC-CC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Transformação Celular Neoplásica/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/metabolismo , Ductos Biliares Intra-Hepáticos/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/metabolismo , Proteínas de Ligação a DNA/genética , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Humanos , Imuno-Histoquímica , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Proteínas Nucleares/genética , Complexo Repressor Polycomb 1 , Complexo Repressor Polycomb 2 , Proteínas Proto-Oncogênicas/genética , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genéticaRESUMO
Xanthogranulomatous cholecystitis (XGC) is characterized by the infiltration of numerous foamy macrophages. Bacterial infection is thought to be involved in the pathogenesis of XGC. Using XGC and cultured murine biliary epithelial cells (BEC), the participation of E. coli and the role of the scavenger receptor class A (SCARA), as well as chemokine(C-X-C motif) ligand 16 (CXCL16) and its receptor chemokine(C-X-C motif) receptor 6 (CXCR6), were examined in the pathogenesis of XGC. E. coli components and genes were detected in XGC on immunohistochemistry and polymerase chain reaction (PCR), respectively. SCARA-recognizing E. coli was found in foamy macrophages aggregated in xanthogranulomatous lesions. CXCL16, which functions as a membrane-bound molecule and soluble chemokine to induce adhesion and migration of CXCR6(+) cells, was detected on gallbladder epithelia, and CXCR6(+)/CD8(+) T cells and CXCR6(+)/CD68(+) macrophages were also accumulated. In cultured BEC, CXCL16 mRNA and secreted soluble CXCL16 were constantly detected and upregulated by treatment with E. coli and lipopolysaccharide through Toll-like receptor 4. These suggest that SCARA in macrophages is involved in the phagocytosis of E. coli followed by foamy changes and that bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16-CXCR6 interaction and formation of the characteristic histology of XGC.