Histopathological diagnosis of 50 asymmetric densities revealed 35 (70%) benign lesions and 15 (30%) malignant lesions. This is in agreement with a study done by Sickles, who reported that asymmetric densities are almost benign [5]. Similarly, Badawi, and Amin showed in their study on 86 female patients with asymmetric density that 72% of cases were attributed to benign mammary changes [12] (Figs. 4, 5, 6, 7, and 8).
In the present study, there was no statistically significant difference between malignant and benign lesions according to the type of asymmetry. However, the likelihood of malignant etiology was higher with focal asymmetry and developing asymmetry than with one view and global asymmetry. Youk et al. reported that the likelihood of cancer varies depending on the type of asymmetry [6]. Sickles reported that the likelihood of malignancy for one view asymmetry, non-palpable and palpable global asymmetry, focal asymmetry, and developing asymmetry were 1.8%, 0%, 7.5%, 0.67%, and 12.8%, respectively [5].
In our study, the final mammographic assessment was achieved after evaluation of the presence or absence of other associated suspicious findings as suspicious calcification, skin and nipple changes, and suspicious lymph nodes, and there was a statistically significant difference between benign and malignant lesions according to the final mammographic BIRADS assessment. This is in concordance with Wessam et al. who concluded from their study that focal and global asymmetries with other suspicious mammographic findings were statistically significant for malignancy, and there was a significant correlation between asymmetry associated with distortion, suspicious calcification, skin/nipple changes, and malignancy. Focal and global asymmetries with no other associated mammographic findings were significantly correlated with a benign pathology [13]. Similarly, Harvey et al. considered focal asymmetry as being more suspicious than global asymmetry, especially if companion parenchymal distortion is present [14].
In our study, the histopathological diagnosis of 35 benign lesions revealed that the most frequent lesions were focal fibrocystic disease 12 (34.2%), inflammatory changes 9 (25.7%) (chronic mastitis, periductal mastitis and inflammatory changes with abscess formation), and postoperative sequelae 5 (14.2%) either postoperative seroma, organized hematoma, or fibrotic surgical scar (postoperative granulation tissue). This agrees with Badawi and Amin’s and Moy et al.’s studies which showed that fibrocystic changes represented the most common cause of mammographic asymmetric breast densities [12, 15]. Wessam et al.’s study showed that inflammatory causes (granulomatous mastitis and breast abscess) were the most common benign etiology of asymmetric densities [13].
The pathologic results of 15 malignant lesions revealed that the most common malignant lesion was invasive duct carcinoma 7 (46.6%). This agrees with Moy et al.’s study which showed that invasive ductal carcinoma being the most common malignant cause of asymmetric densities [15] and in concordance with Wessam et al.’s study which showed that invasive ductal carcinoma and invasive lobular carcinoma were the most common malignant etiologies of asymmetric densities. In our study, only one case (6.6%) was invasive lobular carcinoma [13]. In a study done by Brenner, he found that infiltrating lobular carcinoma lacks adhesive substances on the cell membrane and often invade the breast as cords of cells without creating a recognizable mass. So, he considered that a focal asymmetric density or density that is increasing in size is often associated with the diagnosis of infiltrating lobular carcinoma [16].
The calculated sensitivity and specificity of mammography in the characterization of benign and malignant asymmetries were 47% and 91.5%, respectively. The positive predictive value was 70%, negative predictive value 80%, and accuracy 78%. Our results were nearly the same as Moy et al. who reported sensitivity 33.3%, specificity 80.7%, and accuracy 78.3% [15]. On the other hand, Wessam et al. reported higher sensitivity being 97.8%, with specificity 81.8%, PPV 93.7%, and NPV 93% [13].
MRI examination showed that from 50 lesions, 25 (50%) masses were found (16 “64%” were benign and 9 “36%” malignant) and 25 (50%) were non-mass-like enhancement (19 “76%” were benign and 6 “24%” malignant). There was no significant correlation between the type of enhancement and malignant pathology. Wessam et al. reported that any enhancing asymmetry with mass or non-mass enhancement was significantly correlated with malignant pathology [13].
Regarding kinetic curve assessment, type III was significantly correlated to malignant pathology for the pathologically proved 15 malignant lesions (9 of them showed type III curve, and 6 showed type II curve). On the other hand, type I curve was significantly correlated with benign pathology. There was statistically significant difference between benign and malignant according to type of curve. Tozaki and Fukuda’s and Yabuuchi et al.’s studies on 45 NME lesions revealed no significant difference in kinetic curve assessment between benign and malignant lesions, yet they attributed this to the dual tendency of non-invasive ductal carcinoma to show both persistent and plateau/washout patterns [17, 18].
This study showed that dynamic contrast-enhanced MRI had sensitivity and specificity in the characterization of benign and malignant lesions of 100% and 74.3%, respectively. The positive predictive value was 62.5%, negative predictive value was 100%, and accuracy was 82%. Moy et al. had emphasized on the role of MRI as a problem solver in cases of inconclusive mammographic findings including breast asymmetries. They reported sensitivity of 100%, specificity 91.7%, negative predictive value 100%, positive predictive value 40%, and accuracy 92.2% [15].
The mean ADC value for benign lesions was 1.59 ± 0.4 × 10–3 mm2/s, and for malignant lesions, it was 0.82 ± 0.3 × 10–3 mm2/s. For benign lesions, the ADC value was ranging from 0.63 × 10−3 mm2/s to 2.01 × 10−3 mm2/s, and for malignant lesions, it was ranging from 0.38 × 10−3 mm2/s to 2.21 × 10−3 mm2/s. Abd El-Aleem et al. reported a nearly similar ADC values. The mean ADC value for benign lesions was 1.54 ± 0.43 × 10–3 mm2/s. The mean ADC value for malignant lesions was 0.93 ± 0.42 × 10–3 mm2/s. The range of ADC values for malignant lesions was 0.51–1.35, and for benign lesions was 0.86–1.97 [19].
This study showed that the best ADC cutoff value to differentiate between benign and malignant lesions was 1.10 × 10–3 mm2/s with sensitivity 80%, specificity 88.6%, positive predictive value 75%, negative predictive value 91%, and accuracy 86%. Abd El-Aleem et al. reported an ADC value of 1.26 × 10−3 mm2/s as a cutoff value to differentiate between benign and malignant lesions with sensitivity and specificity of 89% and 94.7%, respectively [19]. Similarly, Yabuuchi et al. reported the ADC value of less than 1.3 × 10–3 mm2/s was a significant factor indicating malignancy among the non-mass enhancement lesions [18].
The majority of benign lesions 31/35 (88.6%) had the ADC value above the calculated cutoff value of 1.1 × 10–3 mm2/s, while only 4/35 (11.4%) had ADC value below the cutoff value (the lesions were chronic breast abscesses). This is in agreement with Rubesova et al. who reported that inflammatory changes can show low ADC values, probably due to high cellularity, fibrosis, and leukocytes [10]. Similarly, Abd El-Aleem et al. reported one false positive with low ADC value, and it was mastitis [19].
In our study, the majority of malignant lesions 12/15 (80%) had the ADC value below the calculated cutoff value of 1.1 × 10–3 mm2/s, while only 3/15 (20%) had the ADC value above the cutoff value (the lesions were atypical ductal hyperplasia and ductal carcinoma in situ). Woodhams et al. illustrated that mass-forming DCIS will show high signal intensity in DWI due to its relatively high cellularity. However, the signal intensity of low-grade DCIS with low cellularity may be ambiguous. Moreover, DWI has a low spatial resolution, and thus, small cancer foci such as DCIS may not be depicted. DCIS and invasive lobular carcinoma may contain interspersed normal fibroglandular tissue or fat tissue, which can increase the ADC value [20].
Lima et al. reported false negative cases comprised a small IDC and a DCIS presenting as NME with borderline ADC values [21]. Similarly, Guo et al. reported that DCIS and malignant phyllodes tumor with bleeding show high ADC values as a result of the strong effects of magnetic susceptibility. Malignant phyllodes tumor can have high ADC values due to cystic areas inside the tumor [22].
Yabuuchi et al. illustrated that non-mass enhancement lesions can form large non-compact lesions, with normal parenchyma in the center of the tumor. Thus, a lesser diffusion restriction occurs. This has been reported for several pathologic and normal states, including DCIS, LCIS, atypical ductal hyperplasia, papillomas, hormonal changes, and fibrocystic disease [18].
Woodhams et al. reported one false negative result with a high ADC value was a mucinous carcinoma, owing to its mucinous content and low cellularity [20]. However, in our study, the depicted case of mucinous carcinoma had an ADC value of 0.56 × 10–3 mm2/s.
The best specificity and accuracy measures were achieved by the use of the combined protocol of DCE-MRI and DWI. The calculated sensitivity and specificity were 93.3% and 94.3%, respectively. The positive predictive value was 87.5%, negative predictive value 97.1%, and accuracy 94%. DWI was a useful adjunctive measure that maintained the high sensitivity, increased specificity, and maximized the overall diagnostic accuracy of the breast MRI examination. Yabuuchi et al. reported that the combination of morphology and ADC values had a high prediction probability for malignancy and showed the high accuracy [18].