These proteins include vascular endothelial growth factor (VEGF), Hypoxia-inducible factor-1a, Platelet-derived growth factor, endothelin-1, and nitrogen oxide synthase. The increased expression of these angiogenic factors reflects the increased angiogenesis seen in higher grade phyllodes tumors. Genes that have been associated with an higher incidence of phyllodes tumors include Mediator Complex Subunit 12 (MED12) exon 2, Telomerase Reverse Transcriptase (TERT) promoter, and Retinoic Acid Receptor Alpha (RARA); important genes for regulating DNA synthesis. The current theory behind the development of phyllodes tumors involves the interaction between each of these pathways to some degree and how they alter the normal interaction of the breast epithelial-stromal tissue. Diagnosis Diagnostic Techniques Radiographical imaging is the first-line test for identifying a phyllodes tumor. Despite their propensity to grow rapidly and deform the overlying breast tissue, approximately 20% of phyllodes tumors can present as a nonpalpable mass on screening mammography. Other imaging tools used to assess the size and spread of a phyllodes tumor include ultrasound and magnetic resonance imaging (MRI). None of these imaging tools are definitive tests for differentiating a phyllodes tumor from a benign fibroadenoma. Phyllodes tumors can only be diagnosed histologically, as they tend to have many overlapping features with other breast masses on physical examination and radiological imaging. A core needle biopsy is the primary tool used to provide a definitive diagnose for a phyllodes tumors. Other biopsy techniques include fine needle aspiration and excisional biopsy. Following biopsy, histological and gross examination is performed which helps clinicians better grade and classify the phyllodes tumor. Classification Phyllodes tumors are part of a group of breast diseases called cellular fibroepithelial lesions. This term incorporates a spectrum of diseases ranging from a benign fibroadenoma to a malignant phyllodes tumor, with numerous variants in between. They are classified by ICD-O, not by MeSH. Phyllodes tumors may be considered benign, borderline, or malignant depending upon their histological features, including stromal cellularity, infiltration of the epithelial-stromal interface, and mitotic activity. Due to their propensity to metastasize and grow quickly, almost all phyllodes tumors are regarded as having malignant potential and treated accordingly. A large case series from the M.D. Anderson Cancer Centre reported the incidence of each type of phyllodes tumor as benign (58%), borderline (12%), and malignant (30%). Malignant phyllodes tumors can behave similarly to sarcomas leading to development of blood-borne metastases. Approximately 10% of phyllodes tumor develop distant metastases and this occurrence is higher (20%)