Progression of fibroadenoma to phyllodes tumor demonstrated by clonal analysis.

Background: The histogeneses of fibroadenoma and phyllodes tumor of the breast appear to be closely related, but it is still unclear whether fibroadenoma can progress directly to phyllodes tumor.

Methods: This issue was studied by conducting clonal analysis of fibroadenoma and phyllodes tumors that were obtained sequentially from the same patient. One patient developed local recurrence of phyllodes tumor twice, and the other two patients each developed a phyllodes tumor after excision of a primary fibroadenoma. The method for clonal analysis was based on trinucleotide repeat polymorphism of the X chromosome-linked androgen receptor (AR) gene and on random inactivation of the gene by methylation.

Results: Clonal analysis revealed that all the three primary fibroadenomas were monoclonal and all four recurrent phyllodes tumors were also monoclonal in origin. In addition, the same allele of the AR gene was inactivated in fibroadenoma and phyllodes tumor(s) in each patient. The probability that phyllodes tumors of different origin happen to inactivate the same allele of the AR gene as fibroadenomas in every case is quite low. Rather, it is more reasonable to assume that the phyllodes tumor has the same origin as fibroadenoma.

Conclusions: These results identified monoclonal fibroadenomas that can progress to phyllodes tumors.