Though PND is most commonly caused by benign breast disorders, its association with malignancy risk is a serious issue that may necessitate major duct excision for exclusion [12]. The urge to achieve a systematic approach in the workup and management of PND is increasing, especially given the high prevalence of PND-related complaints.
In general, CESM has been used a problem-solving tool to detect breast lesions given its ability to assess the morphological criteria and enhancement patterns of different lesions, similar to MRI. Our study attempted to evaluate the added value of incorporating CESM in the diagnostic workup of PND, especially if the sono-mammographic findings were inconclusive and could alter the treatment strategy (or not).
It was noted that most of the malignant lesions we encountered in our study presented with bloody nipple discharge (77.8%). This finding was in accordance with those of Chen et al. [1], who stated that there is an association between the color of nipple discharge and breast cancer risk. Yet, based on our study, discharge color does not exclude malignancy, as noted in 18 malignant cases (22.2%) that presented with non-bloody discharge. Similarly, Abdalla et al. [13] noted that non-bloody discharge does not exclude breast cancer; as such, both bloody and non-bloody (serous and serosanguinous) PND should still be fully investigated.
PND is caused by a wide range of benign and malignant breast disorders. Despite the fact that PND is most commonly caused by benign breast disorders, we encountered 81 malignant cases, representing 57.9% of all cases identified in our study. This may be related to patients’ decreased awareness of PND, and they may have also presented with a more advanced clinical condition. Benign causes were encountered in 59 cases (42.1%), with the most commonly identified benign cause being intra-ductal papilloma (21.4%). The most common malignant cause was DCIS (17.2%).
Based on the findings from our study, the sensitivity of cytology when detecting malignancies was 40.7%, while its specificity was 93.3%. These rates are in accordance with the findings of Leong et al. [14], who stated that negative cytology findings should not exclude malignancy and that the results should be correlated with clinical and radiological findings.
The sensitivity and specificity of sono-mammography in our study were 92.6% and 54.2%, respectively. False-negative cases typically featured dense breasts that showed bilateral diffuse calcification or asymmetries that did not show suspicious ultrasound abnormalities. Yet, this finding does not influence the fact that the use of ultrasound as a complementary method to mammography has increased the diagnostic sensitivity when assessing PND. Paula and Campos [15] stated that mammography alone had a low sensitivity (20–25%) given its challenges assessing the retroareolar area. Similarly, Abdallah et al. [13] assessed the combined use of mammography and ultrasound in their study and found that when combined, their sensitivity was 80%.
Many studies, like those carried out by Paula and Campos [15], Zaky et al. [16], and Panzironi et al. [17], have studied the role of MRI as a problem-solver in cases of PND. They concluded that a higher sensitivity was achieved using contrast-enhanced MRI. Based on its ability to assess the neoangiogenesis of lesions (similar to MRI), we thought to study CESM as an alternative method to MRI given its wider availability, lower cost, and higher tolerance among patients. To our knowledge, this is the first study to have evaluated the role of CESM in detecting malignancies among cases presenting with PND.
The interpretation of CESM findings depends on the analysis of morphological criteria and enhancement patterns, as based on the MRI BI-RADS lexicon. In the current study, a non-circumscribed margin (77.5%) was most commonly encountered with malignant masses, while a circumscribed margin (70.4%) was most commonly encountered with benign masses. Regarding non-mass enhancements, linear distribution was most commonly seen with malignant lesions (34.4%), followed by regional non-mass enhancements (26.2%) and segmental non-mass enhancements (13.1%), yet this distribution is also most commonly found in benign lesions (24.0%), which can explain the increased number of false-positive cases (27 cases). These are similar to the worrisome criteria detected by MRI in patients with PND, which included the “non-mass enhancement” of segmental and linear distribution [17]. Based on the findings from our study, the false-negative cases were mainly attributed to bilateral symmetrical diffuse or nodular enhancement, which was falsely estimated to be background parenchymal enhancement with fibroadenosis.
In our study, the sensitivity and specificity of CESM were 97.5% and 54.2%, respectively, with an overall accuracy of 79.3%. The lower specificity of CESM may be related to non-circumscribed margins, which may be encountered with enhancing intra-ductal papillomas; it might also be associated with the distribution of non-mass enhancements associated with some benign processes, which were comparable with malignant ones. To date, we found that CESM, unlike MRI, has not been widely studied in patients presenting with PND. In 2020, Hegazy et al. [18] performed a study comparing MRI and CESM in the evaluation of intra-ductal papilloma; the authors concluded that MRI had a higher sensitivity and lower specificity when compared to CESM.
In their 2019 study, Xing et al. [19] concluded that CESM led to altering treatment plans to include more extensive surgery +/− neoadjuvant chemotherapy in 57.0% of cases diagnosed with breast cancer. In our study, CESM was able to detect multifocality in 24.1%, multicentricity in 43.0%, diffuse abnormalities in 8.9%, and bilaterality in 20.2%, while sono-mammography detected multifocality in 20.5%, multicentricity in 37.2%, diffuse abnormalities in 3.8%, and bilaterality in 17.9%. These findings emphasize the role of CESM in the delineation of disease extent, allowing for proper planning and tailoring of treatment strategies that can suit each patient.
This study has two main limitations. The first limitation is the sample size which is considered small to drive a conclusion of incorporating CESM in the diagnostic workup of PND cases. The second limitation is our inability to compare the diagnostic performance of CESM with contrast-enhanced MRI examination due to the limited number of cases performing both modalities. We believe that more work still needs to be done to determine if CESM can be an alternative to contrast-enhanced MRI examination as a problem-solving tool.