Accuracy of mammography and magnetic resonance imaging to diagnose underlying malignancy in Paget's disease of the nipple: a systematic review and meta-analysis

Background: Paget's disease (PD) of the nipple is a less common type of breast cancer. Often it is accompanied by underlying malignancy and identification of this prior to surgery plays an important role in the surgical assessment. Until now no agreement about a standard diagnostic program exists. A few smaller studies of the accuracy of mammography (MMG) and magnetic resonance imaging (MRI) to determine presence and extent of underlying malignancy in patients with PD have been published. The aim of this study was to pool the published evidence with a systematic review and meta -analysis. Methods: EMBASE, Medline, Cochrane Library, Google Scholar, ClinicalTrials.gov and WHO International Clinical Trial Registry Platform were searched, and 719 published articles identified. Only six fulfilled the inclusion criteria; were prospective/retrospective, included patients with biopsy -proven PD and had preoperative MMG and/or MRI performed. Findings from diagnostic imaging were correlated to postoperative histopathology to determine sensitivity and specificity. Risk of bias and applicability were assessed independently by the two authors using QUADAS-2 which is divided into patient selection, index test, reference standard and flow and timing. Results: The six studies included 125 patients combined. A total of 73 and 47 patients remained for pooled calculations for MMG and MRI, respectively. The total sensitivity [95% confidence interval (CI)] of MMG and MRI was 39% (95% CI: 27-51%) and 68% (95% CI: 52-81%), respectively. The difference was significant (P=0.0025). The total specificity (95% CI) of MMG and MRI was 100% (95% CI: 54-100%) and 100% (95% CI: 29-100%), respectively. Risk of bias assessment indicated an intermediate risk of bias in the patient selection, and intermediate or high in the index test. Both the reference standard and flow and timing had a low risk of bias. Discussion: Although a small sample and wide 95% CIs, this systematic review and meta -analysis propose that MRI is significantly superior in diagnosing underlying malignancy in patients with PD compared to MMG alone. It therefore seems to improve decision making in surgical assessment of PD.