Malignant phyllodes tumor and invasive lobular breast carcinoma: Morpho-molecular characterization of an uncommon collision tumor and review of the literature

Phyllodes tumor (PT) of the breast is a biphasic neoplasia composed of mesenchymal and epithelial cells. PTs are graded as benign, borderline or malignant according to histological criteria. Invasive lobular carcinoma (ILC) is a special breast cancer subtype defined by non-cohesive growth and loss of E-cadherin. PT is treated by resection. ILC is treated by resection and adjuvant endocrine therapy with or without chemotherapy. Collision tumors composed of PT and concurrent ILC are rare. Due to their dissociated growth, ILC cells may escape histologic detection when admixed with PTs. Here we report the case of a 71-years-old female diagnosed with a PT/ILC collision tumor. The patient presented with a tumor in the right breast. A core needle biopsy showed mesenchymal spindle cell proliferates suspicious for a PT. The resection specimen confirmed a malignant PT with stromal overgrowth. Unexpectedly, the resection specimen also revealed sparse infiltrates of ILC admixed with the PT. Immunohistochemistry of mesenchymal PT cells and ILC cells was consistent with the histomorphological diagnosis. Molecular analyses demonstrated a IDH1 variant of unknown significance and GNAS gene mutation in microdissected PT tissue. ILC tissue showed wild-type IDH1 and GNAS, but harbored CDH1/E-cadherin and TP53 gene mutations, arguing against clonal relatedness of the two lesions. Review of the literature identified six reported PT/ILC collision tumors, involving three benign, two borderline and one malignant PT. In summary, this is the second report on a malignant PT/ILC collision tumor. Correct histologic diagnosis of PT/ILC collision tumors is clinically relevant, because adjuvant endocrine therapy is mandatory for ILC.