Assuntos
Ictiose Lamelar , Ictiose , Ceratodermia Palmar e Plantar , Humanos , Água , Proteínas de MembranaAssuntos
Linfangioma , Neoplasias Cutâneas , Dermoscopia , Humanos , Linfangioma/diagnóstico por imagemAssuntos
Artrite Psoriásica , Infecções por Mycobacterium não Tuberculosas , Mycobacterium marinum , Artrite Psoriásica/tratamento farmacológico , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Fator de Necrose Tumoral alfaRESUMO
Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK. Here, we showed that each skin lesion of DSAP exhibited an individual second hit genetic change in the wild-type allele of the corresponding gene specifically in the epidermis, indicating that a postnatal second hit triggering biallelic deficiency of the gene is required for porokeratosis to develop. Most skin lesions exhibited one of two principal second hits, either somatic homologous recombinations rendering the monoallelic mutation biallelic or C>T transition mutations in the wild-type allele. The second hits differed among DSAP lesions but were identical in those of congenital LP, suggesting that DSAP is attributable to sporadic postnatal second hits and congenital LP to a single second hit in the embryonic period. In the characteristic annular skin lesions of DSAP, the central epidermis featured mostly second hit keratinocytes, and that of the annular ring featured a mixture of such cells and naïve keratinocytes, implying that each lesion reflects the clonal expansion of single second hit keratinocytes. DSAP is therefore a benign intraepidermal neoplasia, which can be included in the genetic tumor disorders explicable by Knudson's two-hit hypothesis.
Assuntos
Carboxiliases/genética , DNA/genética , Epiderme/patologia , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Poroceratose/genética , Carboxiliases/metabolismo , Análise Mutacional de DNA , Epiderme/enzimologia , Feminino , Heterozigoto , Humanos , Linhagem , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Poroceratose/enzimologia , Poroceratose/patologiaAssuntos
Alopecia em Áreas/patologia , Polipose Intestinal/patologia , Pólipos Intestinais/patologia , Prednisolona/uso terapêutico , Administração Oral , Alopecia em Áreas/diagnóstico , Alopecia em Áreas/fisiopatologia , Biópsia por Agulha , Dermoscopia/métodos , Endoscopia Gastrointestinal/métodos , Humanos , Imuno-Histoquímica , Polipose Intestinal/diagnóstico , Pólipos Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Doenças Raras , Resultado do TratamentoRESUMO
Human papillomavirus (HPV) has been detected in some cases of Bowen's disease, particularly on the fingers and genitalia. HPV-58 is classified as a high-risk mucosal type and accounts for a high percentage of cervical cancer in Asia. Moreover, several HPV-58 lineages, including sublineage A1, have a high prevalence in Asia. However, the nature of HPV-58-associated skin cancer is still unknown. Here, we report a case of a Japanese patient with multiple Bowen's disease on the fingers. A 33-year-old man presented with multiple reddish-brown scaly plaques on his left middle finger and right ring finger. All lesions were surgically excised, and the diagnosis of Bowen's disease was made. We performed Sanger sequencing using DNA extracted from paraffin-embedded samples and identified HPV-58 sublineage A1. Additionally, we review previous reports on HPV-58-associated skin cancers, including our case, showing a high regional prevalence in Asia. Further studies would be needed to reveal the relationship between HPV-58 lineages and carcinogenesis in the skin.
Assuntos
Doença de Bowen/virologia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Neoplasias Cutâneas/virologia , Adulto , Biópsia , Doença de Bowen/diagnóstico por imagem , Doença de Bowen/patologia , DNA Viral/isolamento & purificação , Dermoscopia , Dedos , Humanos , Masculino , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico por imagem , Infecções por Papillomavirus/patologia , Pele/diagnóstico por imagem , Pele/patologia , Pele/virologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologiaAssuntos
Neoplasias da Mama/patologia , Carcinoma Basocelular/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Dermoscopia , Neoplasias Cutâneas/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/secundário , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Mamilos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/secundário , Pigmentação da PeleAssuntos
Síndrome de Costello/genética , Doenças do Cabelo/genética , Ceratodermia Palmar e Plantar/genética , Mosaicismo , Nevo/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Biópsia , Síndrome de Costello/patologia , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Ceratodermia Palmar e Plantar/patologia , Mutação , Pele/patologia , Sequenciamento do ExomaRESUMO
Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is essential for significant suppression of HaCaT proliferation under starvation conditions. Ribosomal RNA transcription and protein synthesis were suppressed by starvation combined with knockdown of KPNA (including KPNA2) expression. KPNA2 localized to the nucleolus and interacted with proteins associated with mRNA processing, ribonucleoprotein complex biogenesis, chromatin modification, and transcription, as demonstrated by tandem affinity purification and mass spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein synthesis in tumor cells.