Abstract
BackgroundThe accurate graduation of a phyllodes tumor (PT) is critical for effective treatment as it allows correct surgical management, and avoids inadequate excision for malignant or borderline PT, or surgical overtreatment in benign PT. PTs of the breast are notoriously difficult to classify, and reliable differentiation of a benign PT from a borderline or malignant PT can be problematic, especially among relatively inexperienced pathologists. Although several authors acknowledge a strong relationship between the immunohistochemical expression of p53 and Ki-67 and the histopathological grade of PT—with potential impact on diagnostic accuracy—the literature lacks consensus about which cutoff defines a positive index test. The objective of this study is to establish a practical application score that increases the graduation accuracy of PT through the appropriate use of these auxiliary methods.MethodsA retrospective study cohort of 146 pathology reviewed PTs surgically removed between January 2000 and December 2015. The Ki-67 test was considered positive if > 10% of neoplastic cells showed nuclear staining. The p53 test was considered positive if > 10% of neoplastic nuclear cells showed nuclear staining in a moderate or strong intensity.ResultsOf the 146 PT cases reviewed, 110 were classified as benign, 16 as borderline, and 20 as malignant. The correlation between age and size with benign, borderline, and malignant subgroups was statistically significant (p < 0.001). Significance was observed in the expression of both Ki-67 and p53 in the comparison of benign, borderline, and malignant PT with p < 0.001 and a 95% confidence interval (CI). When correlating the presence of positivity in either of the two index tests with the diagnosis of borderline or malignant PT, we reached a sensitivity of 100% and a specificity of 91.8 (p < 0.001; 95% CI).ConclusionWe propose a practical methodology to achieve an accurate grade of PT, based on clearly defined and easy to apply cutoffs of a simple immunohistochemical panel of Ki-67 and p53. A PT positive for either of the index tests should be graded as borderline or malignant, so pathologists can use this test to improve accuracy. We hope this new approach might provide the basis for the development of standardization in using p53 and Ki-67 for grading PT.
Highlights
A phyllodes tumor (PT) is the least common lesion in the category of fibroepithelial tumors of the breast, which has fibroadenoma as its common exponent (Tan et al 2016; Mishra et al 2013)
All cases were considered to be originally correctly diagnosed as PT, and the agreement between grades was achieved in 92.5%
Death was associated with disease progression in 6 patients, and among 10 alive patients 5 had recurrence, in the malignant PT group
Summary
A phyllodes tumor (PT) is the least common lesion in the category of fibroepithelial tumors of the breast, which has fibroadenoma as its common exponent (Tan et al 2016; Mishra et al 2013). Complete surgical resection is the established treatment for breast PT, since residual PT at the excision margins is a strong predictor of local recurrence; there is a consensus that benign PTs benefit from more conservative treatment (Tan et al 2016; Lakhani 2012; Tan et al 2012; Yonemori et al 2006; Tremblay-LeMay et al 2017; Shaaban and Barthelmes 2017). The objective of this study is to establish a practical application score that increases the graduation accuracy of PT through the appropriate use of these auxiliary methods
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