RESUMO
AIMS: Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs. METHODS AND RESULTS: Eleven MFAs from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture-microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR1A mutation. Upon histological re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR1A somatic mutation was restricted to the stromal component. CONCLUSION: MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers.
Assuntos
Neoplasias da Mama/genética , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Fibroadenoma/genética , Adulto , Mama/patologia , Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Fibroadenoma/classificação , Fibroadenoma/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Complexo Mediador/genética , Microdissecção , Pessoa de Meia-Idade , Mutação , Análise de Sequência de DNARESUMO
Reportamos caso clínico de una mujer de 22 años quien presentó un fibroadenoma mixoide de localización mamaria. Previamente se había diagnosticado un microadenoma pituitario y tiroiditis con bocio difuso leve. Se realizó un estudio multidisciplinario para descartar otras localizaciones de tumores mixoides en el contexto del infrecuente síndrome de Carney.
We report a 22-year-old woman, who presented a myxoid fibroadenoma affecting the breast. Previously a pituitary microadenoma and thyroiditis with mild diffuse goiter was diagnosed. A multidisciplinary study was performed to rule out the location of other myxoid tumors in the context of infrequent Carney syndrome.
