Benign phyllodes tumor of the breast recurring as a malignant phyllodes tumor and spindle cell metaplastic carcinoma

SummaryWe report a unique case of a 59-year-old woman diagnosed with a benign phyllodes tumor (PT), which recurred twice in the same location over a 7-year period: first as a malignant PT and then as a malignant PT with coexisting spindle cell metaplastic breast carcinoma (MBC). The MBC was differentiated from the malignant PT by expression of cytokeratins (CKs) AE1/AE3, CK MNF-116, CK 5/6, and p63. Somatic mutation analysis using a next-generation sequencing platform revealed a shared mutation in F-box and WD repeat domain containing 7, a tumor suppressor gene that encodes a ubiquitin ligase–associated protein, in the original benign PT and the first recurrent malignant PT. Chromosomal microarray analysis showed shared genetic gains and losses between the malignant PT and MBC. This case highlights the utility of immunohistochemistry to differentiate malignant PT from spindle cell MBC, describes a novel mutation in PT, and demonstrates a biologic relationship between these 2 entities.