Myxoid Fibroadenomas Differ from Conventional Fibroadenomas: a Hypothesis Generating Study

Abstract

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. We sought to investigate the genomic landscape of MFAs and compare it to 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 tumor and matching normal tissue were subjected to massively parallel sequencing using MSK-IMPACT, an assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT were tested in samples where the stromal and epithelial components were separately laser capture microdissected. Sequencing revealed no germline PRKAR1A mutations and non-synonymous mutations detected in six MFAs. Interestingly, in three of the MFAs where 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 harboring a somatic truncating PRKAR1A mutation. Upon histologic re-review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumors 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 component seems not to harbor mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers.

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