Bilateral Nephroblastic Tumors and a Complex Renal Vascular Anomaly in a Patient With a Mosaic RASopathy: Novel Histopathologic Features and Molecular Insights.
Pediatr Dev Pathol
; 24(3): 235-240, 2021.
Article
em En
| MEDLINE
| ID: mdl-33538228
ABSTRACT
Mosaic RASopathies are an emerging group of disorders characterized by mosaic or post-zygotic activating mutations in genes of the RAS/MAPKinase signaling pathway. The phenotype is highly variable, ranging from limited or localized forms to cases with a syndromic presentation with extensive or multiorgan involvement, and also overlaps with other mosaic disorders. While there are several reports of malignancies in patients with mosaic RASopathies, specifically rhabdomyosarcoma and transitional urothelial carcinoma, the lifetime risk and molecular mechanisms that lead to the development of malignancies remain unclear. We report a 22-month-old boy with a somatic RASopathy due to an underlying KRAS p.G12D mutation who presented with a large unilateral epidermal nevus, asymmetric lower limb overgrowth with lytic and sclerotic bone lesions, capillary malformation, bilateral nephrogenic rests and Wilms tumors, and a novel complex renal vascular anomaly that resembles Fibro-Adipose Vascular Anomaly (FAVA). This report further expands the phenotypic spectrum of somatic RASopathies, and discusses the potential phenotypic and pathogenetic overlap with PIK3CA-related overgrowth disorders, specifically CLOVES. The occurrence of a secondary cancer hotspot mutation (FBXW7 p.R479G) in the Wilms tumor, but not the associated nephrogenic rest, moreover suggests that additional driver mutations are involved in the development of Wilms tumor in somatic overgrowth disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas p21(ras)
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Tumor de Wilms
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Malformações Vasculares
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Rim
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Neoplasias Renais
Limite:
Child, preschool
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Dev Pathol
Assunto da revista:
PATOLOGIA
/
PEDIATRIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Canadá