Phyllodes Tumors of the Breast: The Role of Immunohistochemistry in Diagnosis

Abstract

Phyllodes tumors of the breast are uncommon fibroepithelial neoplasms, typified by hypercellular stroma and elongated ducts with irregular leaf-like patterns due to stromal proliferation. Its numbers are much fewer than breast carcinomas, with a proportion of only 1.5% compared to breast carcinomas. Phyllodes tumors have a higher frequency in Asian women (Tan et al., 2005b). Classification into three categories of benign, borderline, and malignant is based on a spectrum of histological features such as stromal hypercellularity and cytologic atypia, stromal overgrowth, mitotic rate, and nature of microscopic margins. However, there are still difficulties in accurate categorization of phyllodes tumors and predicting their clinical outcome. Histologic features such as grade (Moffat et al., 1995; Reinfuss et al., 1996), stromal overgrowth (Chaney et al., 2000), tumor necrosis and heterologous stromal elements (Cohn-Cedermark et al., 1991), as well as a combination of morphologic parameters (Moffat et al., 1995), are reported to be predictive. However, specific parameters that are associated with recurrence are not agreed upon; with a substantial number of reports concluding that adequate margins are the most important (Barth, 1999; Kleer et al., 2001; Tan et al., 2005b), and that histologic factors have an inconsistent influence on biologic behavior. Biological markers have been studied in phyllodes tumors using immunohistochemistry, with p53 perhaps being the most widely evaluated (Feakins et al., 1999; Kuenen-Boumeester et al., 1999; Tse et al., 2002; Millar et al., 1999). Whilst p53 expression in stromal cells has been associated with malignant histological features, it does not appear to predict likelihood of recurrence. c-kit (CD117) expression is also reported in the stroma of malignant phyllodes tumors (Sawyer et al., 2003; Chen et al., 2000), and CD117 stromal staining has been shown to correlate with disease recurrence (Tan et al., 2005d). Other studies have demonstrated that heparan sulfate expression (Koo et al., 2006), epidermal growth factor receptor 19 Phyllodes Tumors of the Breast: The Role of Immunohistochemistry in Diagnosis