Assuntos
Carcinoma de Células Escamosas , Melanoma Amelanótico , Melanoma , Neoplasias Cutâneas , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Melanoma Amelanótico/diagnóstico , Melanoma Amelanótico/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologiaRESUMO
Early diagnosis of melanoma is critical for improved survival. However, the biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment, including the keratinocytes, are poorly defined. To address this, we used spatial transcript profiling that maintains the morphological tumor context to measure the expression of >1,000 RNAs in situ in patient-derived formalin-fixed, paraffin-embedded tissue sections in primary melanoma and melanocytic nevi. We profiled 134 regions of interest (each 200 µm in diameter) enriched in melanocytes, neighboring keratinocytes, or immune cells. This approach captured distinct expression patterns across cell types and tumor types during melanoma development. Unexpectedly, we discovered that S100A8 is expressed by keratinocytes within the tumor microenvironment during melanoma growth. Immunohistochemistry of 252 tumors showed prominent keratinocyte-derived S100A8 expression in melanoma but not in benign tumors and confirmed the same pattern for S100A8's binding partner S100A9, suggesting that injury to the epidermis may be an early and readily detectable indicator of melanoma development. Together, our results establish a framework for high-plex, spatial, and cell typeâspecific resolution of gene expression in archival tissue applicable to the development of biomarkers and characterization of tumor microenvironment interactions in tumor evolution.
Assuntos
Melanoma , Nevo Pigmentado , Neoplasias Cutâneas , Biomarcadores/metabolismo , Calgranulina A/genética , Humanos , Melanócitos/metabolismo , Melanoma/patologia , Nevo Pigmentado/patologia , RNA/metabolismo , Neoplasias Cutâneas/patologia , Microambiente Tumoral/genéticaAssuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Imuno-Histoquímica/métodos , Melanoma/diagnóstico , Neoplasias Cutâneas/patologia , Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Dermatologia/normas , Gerenciamento Clínico , Detecção Precoce de Câncer/métodos , Humanos , Melanoma/metabolismo , Melanoma/terapia , Patologia/normas , Estudos ProspectivosAssuntos
Síndrome de Costello/genética , Síndrome de Costello/patologia , Predisposição Genética para Doença/epidemiologia , Nevo Pigmentado/patologia , Neoplasias Cutâneas/genética , Proteínas ras/genética , Adolescente , Adulto , Distribuição por Idade , Criança , Síndrome de Costello/diagnóstico , Feminino , Heterozigoto , Humanos , Incidência , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nevo Pigmentado/epidemiologia , Nevo Pigmentado/genética , Prognóstico , Doenças Raras , Distribuição por Sexo , Transdução de Sinais/genética , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologiaRESUMO
Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common.
