Digital Mammography Versus Contrast Enhanced Spectral Mammography in the Evaluation of Cases with Suspicious Breast Calcifications and Impact on Surgeon’s Decision.

Digital Mammography Versus Contrast Enhanced Spectral Mammography in the Evaluation of Cases with Suspicious Breast Calcifications and Impact on Surgeon’s Decision. | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Digital Mammography Versus Contrast Enhanced Spectral Mammography in the Evaluation of Cases with Suspicious Breast Calcifications and Impact on Surgeon’s Decision. Marwa Elsayed AbdelRahman Ibrahim, Marwa Mohamed Taher Elsayad, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5340228/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Digital mammography (DM) remains the gold standard for detecting breast microcalcifications, its ability to differentiate between benign and malignant types based solely on morphology and distribution can be limited. Contrast-enhanced spectral mammography (CESM) emerges as a promising approach by incorporating pathological contrast enhancement, potentially leading to a more confident diagnosis compared to DM, and offering a faster and potentially more cost-effective alternative to breast magnetic resonance imaging. Patients and methods: This cross-sectional study included 50 female patients with suspicious breast calcifications (BIRADS 4B, 4C, 4, or 5). CESM was performed, and images were analyzed for lesion characteristics. Histopathological results served as the gold standard for comparison, guiding surgical decisions and treatment plans. Results: This study included 50 patients who had suspicious breast calcifications detected by DM, with 54 breast lesions. All patients performed DM and CESM. None of them had adverse reactions. Out of the 54 identified breast lesions, 19/54, 35% were benign and 35/54, 65% were malignant. The calculated sensitivity, specificity, positive and negative predictive values and total accuracy of DM were 91.4%, 70.8%, 62.7%, 93.9%, and 78% respectively as compared to 85.7%, 90.7%, 83.3%, 92.2%, and 89% for CESM. When adding CESM to DM the calculated diagnostic indices were raised to 100%, specificity was 90.7 %, PPV was 83.3% and NPV raised to 100%. Conclusion: Combining CESM with DM while evaluating suspicious breast microcalcifications can increase both the sensitivity and specificity of cancer detection. CESM significantly influenced surgical decisions in cases where multicentricity was detected by CESM but missed in initial mammography reports, particularly in patients with dense breasts. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction The presence of breast calcifications can be a significant indicator of early-stage breast cancer, including ductal carcinoma in situ (DCIS) and even non-palpable invasive forms [1]. Moreover, it was found that breast microcalcification is an independent risk factor for breast cancer, and its risk is elevated when combined with breast density [2] . While digital mammography (DM) remains the gold standard for detecting breast microcalcifications, its ability to differentiate between benign and malignant types based solely on morphology and distribution can be limited. Contrast-enhanced spectral mammography (CESM) emerges as a promising approach by incorporating pathological contrast enhancement, potentially leading to a more confident diagnosis compared to DM, and offering a faster and potentially more cost-effective alternative to breast magnetic resonance imaging (MRI) (3). CESM offers the potential to overcome limitations of DM while providing a faster and more cost-effective alternative to MRI [4, 5]. Additionally, CESM allows for a single scan to assess both microcalcification morphology (using low-energy imaging) and lesion function [5, 6]. This study aims to evaluate the diagnostic accuracy of CESM compared to mammography in identifying suspicious breast calcifications and determining lesion extent. We further investigate the impact of CESM findings on surgeon decision-making. Patients and methods This cross-sectional study was conducted from January 2023 to December 2023 at the female imaging units of the Radiology Departments at Ain-Shams University Hospitals and the National Cancer Institute, Cairo, Egypt. The study was approved by the relevant ethics committees. Participants: Adult female patients were included if they had: Suspicious breast calcifications (BIRADS 4B or 4C) identified during a mammogram screening. A breast mass with suspicious calcifications (BIRADS 4 or 5) identified by mammography. Patients with either non suspicious microcalcifications or contraindications to contrast injection like renal dysfunction, pregnancy, allergies to contrast medium were excluded. Fifty eligible patients were selected using a convenience sampling method and provided written informed consent before undergoing contrast-enhanced spectral mammography (CESM). CESM Procedure: A certified technician performed CESM on a Senographe Pristina mammography system (GE Healthcare) following these steps: An intravenous (IV) line was placed in the patient's arm. A non-ionic iodine contrast agent (Ultravist or Omnipaque 300) was injected at a dose of 1.5 ml/kg body weight. High-energy and low-energy digital mammograms were acquired before and after contrast administration. Subtraction images, in the standard positions CC and MLO with compression so that the breast parenchyma becomes less visible, were created to isolate the iodine signal, highlighting areas of blood vessel growth (angiogenesis). The entire procedure took approximately 7-10 minutes. Image Analysis & Interpretation: Mammograms and CESM images were evaluated by radiologists for: Lesion size, location, shape, margins, and density. Calcification characteristics on mammography which include distribution and morphology were analyzed and categorized to ACR BIRADS Lexicon 2013 (7). Enhancement pattern is evaluated for CESM images and was analyzed and categorized according to ACR BIRADS for CEM 2022 (8). The contralateral breast served as the control for comparison. Histopathological Correlation: In cases with BIRADS IV or V lesions, by mammography and ultrasound examination and/or CESM, results were compared to histopathological report. Lesions were biopsied under US guidance “if the lesion is seen with US” and if only seen by mammograpgy, stereotactic biopsy was done using true cut needle biopsy (via 14 -18-gauge needles) or referred for surgical excision. Histopathological results served as the gold standard for this study. For patients with suspicious breast calcifications which turned out to be benign lesions by biopsy or patients with malignant lesions that were referred to oncology department for neoadjuvant chemotherapy, the histopathological results were based on core needle biopsies. For malignant cases that were elected for surgery without prior neoadjuvant chemotherapy, the final surgical specimens were used. Statistical Analysis: Sensitivity, specificity, positive and negative predictive values and total accuracy were estimated taking the probability of malignancy; micro-calcific clusters as detected by mammography were considered as positive test results, while mass or non mass enhancement detected by CESM were considered as positive test results. The diagnostic indices +/- 95% confidence interval, were calculated for mammography and CESM alone and when combining them together. P-value was considered significant if ≤0.05. Wilcox-signed rank test was used to compare largest diameter by both DM and CESM in comparison to histopathology. Non parametric correlation analysis using spearman rho test was used to test association of tumor size by different measures (DM, CESM and histopathology). All statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, NY, USA) and SPSS version 27.0, Statistical Package for the Social Science (Chicago, ILI). Results This study included 50 patients who had suspicious breast calcifications detected by DM, with 54 breast lesions. All patients performed DM, and CESM. None of them had adverse reactions. The ages ranged from 30–76 years with a mean age 53. We classified the 50 cases into 4 groups according to the breast density. Out of the 50 cases, 5 cases (10%) were classified as ACR A, 11 cases (22%) were classified as ACR B, 29 cases (58%) were classified as ACR C and 5 cases (10%) were classified as ACR D. According to the lesion location, we classified the detected 54 lesions into 5 groups and further according to their final diagnosis either by pathological assessment of biopsy and surgical samples ( Table 1 ). Table 1 Distribution of benign and malignant groups within the studied population according to the site of their suspected lesions. Site of lesion Total no. Benign Malignant UOQ 21 7 14 UIQ 2 0 2 LOQ 2 0 2 LIQ 6 3 3 CENTRAL 14 8 6 MULTICENTERIC 9 1 8 According to final histopathological diagnosis, 35 lesions turned out to be malignant. Invasive duct carcinoma was the most common final histopathological diagnosis upon the “malignant lesions” group, while mucinous adenocarcinoma was the least common ( Table 2 ). Table 2 Final histopathological diagnosis upon the “malignant lesions” group: Final histopathological diagnosis Number of lesions (total = 35) DCIS 4 IDC 20 DCIS + IDC 6 Invasive lobular carcinoma 4 Mucinous adenocarcinoma 1 Out of the 54 detected lesions, microacalcifications were isolated presenting findings in only 6 cases, other findings are listed in ( Table 3 ). These microacalcifications were divided according to their pattern and distribution according to ACR BI-RADS lexicon 2022, details provided in ( Table 4 ). Table 3 Associated DM findings among studied lesions DM associated findings No of lesions (total 54) % Isolated suspicious calcifications 6 11.1% + Masses 23 42.6% + Focal asymmetry 14 24.5% + Architectural distortion 10 25.9% +Internal mammary lymph nodes 2 3.7% + Dilated ducts 2 3.7% + Parenchymal edema 1 1.85% + Skin thickening 1 1.85% Table 4 DM findings among studied lesions regarding micro-calcifications form and distribution: Form of calcification Number of lesions (total 54) Coarse heterogeneous 16 Amorphous 9 Fine pleomorphic 29 Fine linear branching 9 Distribution of microcalcifications Number of lesions (Total = 54) Diffuse 4 Regional 7 Grouped 34 Ductal linear 5 Segmental 8 Study participants were 50 females with positive lesions on one side of the breast by mammography. Contralateral breast was considered the control side mammography examination. Four patients out of 50 had bilateral breast lesions. So we considered to have 54 malignant lesions and 46 controls. Moreover, three cases showed more than one lesion on ipsilateral breast with contrast uptake on CESM and were subsequently found malignant by pathology. Upon a second look on initial mammography scans, we discovered suspicious microcalcifications that were missed in initial report of mammography either due to dense breast or due to lesion small size, or they were considered as benign looking calcifications on mammography but had contrast uptake by CESM and turned malignant by pathology. These lesions were considered false negative for mammography. Upon correlating the mammography findings to the final diagnoses, 32 lesions were true positives, 19 lesions were false positives, 3 lesions were false negatives and 46 lesions were true negatives. Regarding contrast mammo findings, 36 (66.6%) lesions showed contrast uptake and 18 (33.3%) lesions showed no contrast uptake. Enhancing lesions were classified into enhancing mass lesions 13 (36.1%), enhancing non mass lesions 17 (47.2%) and lesions that showed both mass and non-mass uptake 5 (16.6%) (Fig. 1) . Out of the 23 lesions that showed non mass enhancement pattern, focal NME pattern was most common that was represented by 8 lesions, followed by regional NME representing 6 cases then comes segmental NME (Fig. 2) representing 5 cases followed by linear, diffuse, combined linear with diffuse and combined focal with diffuse each represented by1 lesion for each. Upon correlation with pathology results or follow up, 72.2% of lesions that showed no contrast uptake were benign with 37.8% showed malignancy with no contrast enhancement on mammography (Fig. 3) . While 92.3% enhancing mass lesions, and 100% of lesions that showed both mass and non-mass enhancement were malignant. Regarding the diagnostic indices of digital mammography and contrast mammography performance in assessment of micro-calcifications, they are summarized in (Table 5 ). Table 5 Results of digital mammography DM versus contrast enhanced spectral mammography CESM in the evaluation of patients with suspicious breast calcifications. Accuracy measures Digital mammography CESM (%) (95% CI) (%) (95% CI) Sensitivity 91.4% (76.9–98.2) 85.7% (69.7–95.2) Specificity 70.8% (59.7–81.8) 90.7% (83.7–97.8) PPV 62.7% (49.5–76.0) 83.3% (71.2–95.5) NPV 93.9% (83.1–98.7) 92.2% (82.7–97.4) Total accuracy 78% (69.9–86.1) 89.0% (82.9–95.1) Combining digital mammography and contrast mammography, sensitivity was raised to 100%, specificity was 90.7%, PPV was 83.3% and NPV raised to 100%. Size correlation by digital mammography versus CESM Accurate lesion sizing through excision biopsy was obtained for 23 lesions out of the 36 malignant lesions detected in our study population. One of the study limitations was the wide time interval between both the DM and the CESM examination and the surgical excision biopsy for the other 13 malignant lesions detected, as those cases were referred to neoadjuvant chemotherapy after histopathological diagnosis. Those 13 cases were excluded from size correlation study. Wilcox-signed rank test was used to compare largest diameter by both DM and CESM in correlation to histopathology. Non-parametric correlation analysis using spearman rho test was used to test association of tumor size by different measures (DM, CESM and histopathology). Results showed that size of tumor by CESM was more correlated to that by pathology, correlation coefficient (r = 0.86), than that between DM and pathology, (r = 0.588), ( Fig. 4 , Fig. 5 ). Also, mean difference in diameter between CESM and histopathology was 1.28 mm, while it was 2.8 mm between DM and histopathology. Yet, these differences showed no significant effects on surgical decision making ( Tables 6 & 7 ). Table 6 Comparison of largest diameter (cm) of breast lesions by DM and after surgical dissection. N Mean Standard deviation Median Minimum Maximum P value Largest diameter by DM 23 5.517 3.1628 5.000 1.3 13.5 0.487 Largest diameter by pathology 23 5.239 3.1066 5.000 2.0 14.0 P value is significant ≤ 0.05, test statistics used for paired data comparison is Wilcoxon signed rank test Table 7 Comparison of largest diameter (cm) of breast lesions by CESM and after surgical dissection. N Mean Standard deviation Median Minimum Maximum P value Largest diameter by CESM 18 4.900 2.6090 4.500 1.0 9.0 0.777 Largest diameter by pathology 18 5.028 2.6415 4.500 2.0 10.0 P value is significant ≤ 0.05, test statistics used for paired data comparison is Wilcoxon signed rank test Cronbach's Alpha as a measure of reliability or repeatability was found to be 0.740 between size measurement by DM and pathology, indicating acceptable reliability. On the other hand Cronbach's Alpha was 0.92 between CESM and pathology, indicating excellent reliability. CESM examination impact on surgical decision for cases with suspicious breast microcalcifications: Regarding the size of tumor by CESM, even though it was more correlated to that by pathology than that between DM and pathology. Yet these minute differences in measurements (less than 4 mms) did not affect the surgical decision making. However, results of CESM showed that false positive rate (9.3%) is significantly lower than that in DM (29.2%), which means that if a surgical decision is prompted it is better to be with CESM. Also, 3 cases that showed multicentricity detected by CESM but missed in initial mammography reports significantly affected the surgical decision making (upgrading from BCS to total mastectomy) (Fig. 6). These cases either had dense breasts or were misdiagnosed as benign calcific lesions in initial DM report. Discussion Calcifications and microcalcifications (<0.5 mm) are very common in breast tissues and are easily detected on mammograms as small bright spots. Mammography is often the only diagnostic method that can identify this type of BC manifestation (9) Neraly 55% of non-palpable breast cancers present in the form of microcalcifications without any other breast abnormality, and more than 80% of in situ breast neoplasms present also only as microcalcifications [10]. Microcalcifications are usually classified as benign or suspicious according to their morphology and distribution [11]. Interpreting microcalcifications seen in mammograms can present a challenge for radiologists [12]. The radiologists should balance the risk of unnecessary biopsies for benign lesions with the underestimation of potentially pathological microcalcifications [13]. Contrast-enhanced spectral mammography (CESM), which has recently evolved and becomes increasingly used in clinical practice, could provide a valid asset [14]. Contrast-enhanced spectral mammography (CESM) builds upon the foundation of mammography (MG) by incorporating iodinated contrast media. Similar to contrast-enhanced magnetic resonance imaging (CE-MRI), CESM leverages the principle of tumor angiogenesis for image enhancement. Breast tumors are characterized by extensive neoangiogenesis, resulting in a dense network of immature and leaky blood vessels. These leaky vessels allow for the extravasation of contrast media into the tumor interstitium, leading to increased signal intensity and improved visualization of the malignancy [15]. In this study, we investigated the utility of contrast-enhanced spectral mammography (CESM) in evaluating suspicious breast calcifications. Our findings provide valuable insights into the diagnostic accuracy and clinical impact of CESM compared to digital mammography (DM). In our study the ages ranged from 30 - 76 years with a mean age 53, while in a study done by Houben et al., 2019 , to assess the diagnostic accuracy of contrast mammography in cases with suspicious calcifications, the ages ranged from 49 to 75 years with mean age 60.5 years. On another study by Nicosia et al., 2023 also about the role of CEM in microcalcifications assessment, the ages ranged from 45 to 59 years with mean age 51 years [1, 6]. Out of the 50 cases, 34 female had dense breast “including ACR C and D” in our study representing 68% of our study population. This is comparable to Nicosia et al., 2023 who found that 78% of their cases had breast density classified as ACR C and D [6]. As regarding lesion location, we found that 38.8 % of lesions were in UOQ which was the most frequent among all other sites. While Nicosia et al., 2023 found that about59.9 % of lesions were detected at the UOQ [6]. We had 65 % of lesions diagnosed as “malignant lesions” by final histopathology. While Houben et al., 2019 , had only 44% lesions diagnosing as malignant out of the suspicious calcified lesions studied [1]. Yet Nicosia et al., 2023 found that 66% were malignant [6]. 65.5 % of malignant lesions in our study were diagnosed IDC and DCIS alone was found only in 5.7% while both DCIS and IDC were found combined in about 11.4%. Houben et al., 2019, had DCIS in (50.4%) of malignant lesions group. They had 27 IDC cases, 2 cases of ILC, only 1 case of invasive mucinous carcinoma and another case of intraductal papillary carcinoma [1]. However, we no cases of intraductal papillary carcinoma were diagnosed in our study. Although invasive lobular carcinoma (ILC) typically presents on mammography as masses, asymmetries, architectural distortion, and rarely as microcalcifications [16], we observed 4 cases of ILC. We found 42.6% of all lesions presented with associated mass lesions, while only 2.7 % of lesions in the study by Nicosia et al., 2023 presented by microcalcificaions with associated masses [6]. In our study, the predominant morphology of microcalcifications in the lesions was fine pleomorphic, accounting for 53.7%. The most frequent distribution pattern observed was grouped microcalcifications, present in 62.9% of cases. Unlike many similar studies that primarily focused on categorizing microcalcifications as either suspicious or non-suspicious, our research emphasizes the specific morphology and distribution patterns. The diagnostic performance parameters for assessing breast calcifications using digital mammography (DM) were as follows: sensitivity of 91.43%, specificity of 70.77%, positive predictive value (PPV) of 62.75%, negative predictive value (NPV) of 93.88%, and overall accuracy of 78%. Houben et al. (2019) reported similar results for low-energy (LE) images, with a sensitivity of 90.8%, PPV of 54.1%, and NPV of 84.2%. However, their study’s specificity (39%) was significantly lower than that observed in our study [1]. Houben et al. (2019) reported that 76.8% of lesions showed enhancement on CESM [1]. In our study, 66.6% of lesions exhibited enhancement, with the non-mass enhancement (NME) pattern being the most common. Louka et al. (2020) found that 96.2% of malignant lesions (25 out of 26 cases) showed enhancement on CESM in patients with BI-RADS 4, 5, and 6 mammographic suspicious breast calcifications [17]. CESM demonstrated significantly higher specificity than DM, with 90.7% (83.7–97.8) compared to 70.8% (59.7–81.8), p-value < 0.05. Houben et al. (2019) found no significant difference between the specificity of LE and HE images of CESM (39% vs. 36.6%) [1]. Although CESM’s PPV appeared higher than DM’s (83.3% vs. 62.7%), the overlapping confidence intervals indicated no significant difference. CESM had a significantly lower false positive rate (9.3%) compared to DM (29.2%), suggesting CESM is preferable for surgical decisions. Houben et al. (2019) found no significant difference in false positive rates between CESM (36.37%) and DM (34%) [1]. Sensitivity and NPV were comparable between DM and CESM, aligning with Houben et al. (2019) [1]. Total accuracy was higher with CESM, though not significantly, likely due to the small sample size. Louka et al. (2020) reported higher sensitivity (96%) for CESM in detecting malignant lesions with suspicious microcalcifications [17]. Our results are consistent with Cheung et al. (2016), who found CESM provided additional enhancement information for accurate cancer diagnosis in lesions with microcalcifications, reporting a sensitivity of 89%, specificity of 87%, PPV of 77%, and NPV of 95% [18]. Cheung et al. (2021) also reported a sensitivity of 93%-100% and specificity of 63%-88%, showing significant improvement over DM [19]. Shetat et al. (2021) found CESM valuable for assessing suspicious microcalcifications, with non-mass enhancement indicating high-grade DCIS or invasive components, and enhancement paucity favoring benign or low-grade DCIS [3]. Ploumen et al. (2023) found that CESM enhancement and calcification features help differentiate between invasive breast cancer, DCIS, and benign lesions, with enhancement absence in calcifications mainly associated with low-grade DCIS, consistent with our results [20]. We evaluated combined results of DM and CESM in the evaluation of suspicious breast calcifications, they showed sensitivity 100% with CI (90-100), specificity 90.7% with CI (59.7-77.6), PPV 83.3 % with confidence interval (52.1-77.6) and NPV 100% with CI (92.3-100). To our knowledge previous papers of same interest didn’t study combined use of both techniques. The main objective of pre-operative breast imaging is to assess the extent of the disease after an initial diagnosis. Accurately measuring the tumor size and determining its progression through T staging are essential for planning surgery, whether or not neoadjuvant chemotherapy is involved for breast cancer patients[21] . Specimen radiography is useful for diagnosing suspicious microcalcifications but cannot predict the likelihood of invasive ductal carcinoma (IDC) underestimation. This determination requires microscopic histopathological analysis. To prevent underestimation, it is essential to accurately target the biopsy and obtain invasive tissue for microscopic evaluation. Not all microcalcifications in specimens contain invasive elements. Contrast-enhanced spectral mammography (CESM) can aid in identifying biopsy sites by highlighting enhancement features such as masses and solid enhancements, thereby improving the diagnosis of invasive disease [18 &19] . Our findings indicate that the tumor size measured by CESM showed a stronger correlation with pathology (r = 0.858) compared to DM (r = 0.588). The reliability of size measurements between DM and pathology was acceptable (Cronbach’s Alpha = 0.740), while the reliability between CESM and pathology was excellent (Cronbach’s Alpha = 0.92). These results align with Cheung et al.'s 2021 study, which demonstrated that CESM features can accurately predict IDC underestimation [19]. The mean difference in tumor diameter between CESM and histopathology was 1.28 mm, compared to 2.8 mm between DM and histopathology. However, these differences did not significantly impact surgical decision-making, as surgeons typically ensure an oncologically safe margin of over 4 mm around the calcifications [22]. Our results align with Cheung et al. (2015), who found that CESM provides a more accurate assessment of disease extent compared to DM, with mean differences of 0.5 mm for CESM and 4.2 mm for DM [23]. Similarly, Houben et al. (2019) reported that CESM reduces measurement error in disease extent assessment, though it may slightly overestimate the extent. These minor discrepancies did not significantly impact surgical decision-making [1]. Houben et al. (2019) took into account the impact of their findings on surgical decision-making, as this is the most relevant outcome when assessing the extent of the disease. Their study found no significant statistical differences in surgical treatment plans based on LE images or the entire CESM exam. We concur with their conclusions regarding the impact of size estimation on surgical outcomes. However, in our study, CESM detected multicentricity in three cases initially missed by DM, leading to a significant change in surgical decisions, upgrading from breast-conserving surgery (BCS) to primary mastectomy. This aspect was not considered by Houben et al. (2019) [1]. Our study had several limitations. The sample size was limited, and the patients were not consecutive. The patient population was a selected group recalled from a national screening program, where screening radiologists decide on recalls. Different radiologists might select different patients, but this is standard practice in our program. CESM was not mandatory before biopsy in current clinical practice, and some patients were hesitant to undergo contrast medium injection. Additionally, the wide time interval between CESM examinations and surgical excision biopsy was a limitation, and 13 cases referred to neoadjuvant chemotherapy after histopathological diagnosis were excluded from the size correlation study. In conclusion, our study demonstrated that CESM is more specific than DM in evaluating suspicious breast microcalcifications. While other accuracy measures showed no significant differences between the two modalities, the tumor size measured by CESM correlated more closely with pathology than DM. These minor differences in measurements did not impact surgical decision-making. However, CESM significantly influenced surgical decisions in cases where multicentricity was detected by CESM but missed in initial mammography reports, particularly in patients with dense breasts or misdiagnosed benign calcific lesions. Declarations Author Contribution M.E.A.I. wrote main manuscript, helped in collecting and reporting cases.M.M.T.E. collected cases and data M.H.M.H. reporting cases, revising the scientific content.A.GE.O. helped in correlating with surgical decision and also revised manuscript.O.H.O. Revised manuscript, cases reporting and data management References Houben IP, Vanwetswinkel S, Kalia V, et al. (2019) Contrast-enhanced spectral mammography in the evaluation of breast suspicious calcifications: diagnostic accuracy and impact on surgical management. Acta Radiol 60(9):1110-1117. Epub 2019 Jan 24. Kim S, Tran TXM, Song H, Park B (2022) Microcalcifications, mammographic breast density, and risk of breast cancer: a cohort study. Breast Cancer Res 24:96. 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(2016) Dual-energy contrast-enhanced spectral mammography: enhancement analysis on BI-RADS 4 non-mass microcalcifications in screened women. PLoS One 11(9):e0162740. Cheung YC, Chen K, Yu CC, et al. (2021) Contrast-enhanced mammographic features of in situ and invasive ductal carcinoma manifesting microcalcifications only: help to predict underestimation? Cancers 13(17):4371. Ploumen RA, de Mooij CM, Gommers S, et al. (2023) Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis. Eur Radiol 33:1-3. Youn I, Choi S, Choi YJ, et al. (2019) Contrast enhanced digital mammography versus magnetic resonance imaging for accurate measurement of the size of breast cancer. Br J Radiol 92(1098):20180929. Lobbes MB, Vriens IJ, van Bommel AC, et al. (2017) Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers. Breast Cancer Res Treat 162:353-364. Cheung YC, Tsai HP, Lo YF, et al. (2015) Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. Eur Radiol 26:1082-1089. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5340228","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":378726208,"identity":"523aa87c-155a-4f6f-8a9e-ae969fb33c3a","order_by":0,"name":"Marwa Elsayed AbdelRahman Ibrahim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5ElEQVRIiWNgGAWjYDCCA1CaD0R8AGI2dmK1sAEx4wwQg5kULcw8IBYhLXy3Tyd+rmyzk2MTO3zss82vbfJ8zAyMHz7m4NYieS53s+TZtmRjNum05Nm5fbcN25gZmCVnbsOtxeAM7wbJxm3MiW3SOcbMuT23GYFa2Jh58WvZ/LNxW309WItlz217YrRsA9pyOIENpIXhx+1EglokgVosG/8dN2wD+oWxt+F2chszYzNev/ABHXaz4Uy1PL908mGGH39u285vbz744SMeLaiAsQ1MNhCrHgT+kKJ4FIyCUTAKRgoAAMVdTPCRWZhLAAAAAElFTkSuQmCC","orcid":"","institution":"Ain Shams University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Marwa","middleName":"Elsayed AbdelRahman","lastName":"Ibrahim","suffix":""},{"id":378726209,"identity":"1d880ae8-d8e9-41bd-8ccd-fa091ff371d7","order_by":1,"name":"Marwa Mohamed Taher Elsayad","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marwa","middleName":"Mohamed Taher","lastName":"Elsayad","suffix":""},{"id":378726210,"identity":"fb8aeec3-8900-425d-9078-1c5c536fe718","order_by":2,"name":"Maha Hussein Mohamed Helal","email":"","orcid":"","institution":"National cancer Institute, Egypt","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maha","middleName":"Hussein Mohamed","lastName":"Helal","suffix":""},{"id":378726211,"identity":"49b7f9cf-9a69-4d32-85fc-588ff9962e98","order_by":3,"name":"Ahmed Gamal Eldeen Othman","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Gamal Eldeen","lastName":"Othman","suffix":""},{"id":378726212,"identity":"5f3e3768-58d9-46ac-9086-f27859d28eba","order_by":4,"name":"Omar Hussein Omar","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Omar","middleName":"Hussein","lastName":"Omar","suffix":""}],"badges":[],"createdAt":"2024-10-27 08:08:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5340228/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5340228/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":70953965,"identity":"cd05e49b-b6be-4e0a-b2a8-1bc965e580ee","added_by":"auto","created_at":"2024-12-09 14:05:11","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1381288,"visible":true,"origin":"","legend":"\u003cp\u003e42 year old female presented with large right breast lump. (A) CC and (B) LMO views of digital mammography showing right breast heterogeneously dense breast showing large mass with partially non circumscribed ill-defined margins located centrally and extending to UOQ with associated extensive areas of pleomorphic micro-calcifications with regional distribution seen in both UOQ and LIQ. (C) and (D) representing CC and MLO views of contrast mammography showing confluent enhancing masses with the central one show negative contrast on posterior aspect as it is representing a complex cystic lesion with associated LIQ regional non mass enhancement. This patient turned to be a multi-centric invasive ductal carcinoma (IDC).\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/aa8951ead4f84c8ce0250e0c.jpg"},{"id":70953968,"identity":"a5ba25d5-419f-4396-999f-97225310c4af","added_by":"auto","created_at":"2024-12-09 14:05:11","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1625707,"visible":true,"origin":"","legend":"\u003cp\u003e48 year old female with known right breast cancer.\u003cstrong\u003e \u003c/strong\u003e(A) CC and (B) LMO views of digital mammography of left breast showing segmental pleomorphic micro-calcifications in UOQ. C) \u0026amp; (D) representing CC and MLO views of contrast mammography showing segmental clumped enhancement. This patient upon biopsy had combined DCIS and IDC.\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/de7e4a54455a99bd22ec1de1.jpg"},{"id":70955288,"identity":"2c24eb73-c91c-447c-9846-1e045f6c0be7","added_by":"auto","created_at":"2024-12-09 14:13:11","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1358519,"visible":true,"origin":"","legend":"\u003cp\u003e45 year old female had right sided US guided biopsy from suspicious breast lesion that turned to be IDC. (A) MLO \u0026amp; (B) CC views of left breast showing dense breast and extensive area of pleomorphic micro-calcifications having linear pattern. (C) Zoomed view at area of calcifications with a clip seen at the posterior extent. (D) \u0026amp; (E) representing CC and MLO views of CEM showing no enhancement corresponding to noted calcifications. These calcifications on biopsy showed DCIS.\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/374110adb4b6328f0a75d01f.jpg"},{"id":70953966,"identity":"da5373bf-20b8-4434-b2a9-88501991d71e","added_by":"auto","created_at":"2024-12-09 14:05:11","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":148145,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between lesion largest diameter by DM and by pathology.\u003c/p\u003e","description":"","filename":"figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/3544f057655ba050db437243.jpg"},{"id":70953964,"identity":"a0b8e9e1-16d0-4bc3-b003-b55740441ff6","added_by":"auto","created_at":"2024-12-09 14:05:11","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":148562,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between lesion largest diameter by CESM and by pathology.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/db9ead03da7f30e0e8efcb1a.jpg"},{"id":70955287,"identity":"7cdde49d-ce47-42e4-8b40-6fd6c8818d5f","added_by":"auto","created_at":"2024-12-09 14:13:11","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1230968,"visible":true,"origin":"","legend":"\u003cp\u003e34 year old female presented with right breast lump. A) CC and (B) LMO views of digital mammography of left breast showing asymmetry seen at inner half of breast on CC view and seen central along the nipple line of MLO view with associated 3 grouped pleomorphic micro-calcifications seen around the lesion “arrowed”. (C) Zoomed view of asymmetry and micro-calcifications. (D) And (E) representing CC and MLO views of CEM showing mass enhancing lesion corresponding to area of asymmetry central and extending to upper quadrant and on CC view located on inner part of breast with associated extensive clumped non mass enhancement with segmental distribution at LIQ. This case had a multi-centric IDC.\u003c/p\u003e","description":"","filename":"figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/dfe81754720f25ce8a66d7eb.jpg"},{"id":70956615,"identity":"c1317af2-ea80-4bb6-8d16-5c48916e9f4f","added_by":"auto","created_at":"2024-12-09 14:29:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":6767417,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5340228/v1/689cb520-fbc9-4bcf-bbc9-e4c9d669ac4f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Digital Mammography Versus Contrast Enhanced Spectral Mammography in the Evaluation of Cases with Suspicious Breast Calcifications and Impact on Surgeon’s Decision.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe presence of breast calcifications can be a significant indicator of early-stage breast cancer, including ductal carcinoma in situ (DCIS) and even non-palpable invasive forms \u003cstrong\u003e[1].\u003c/strong\u003e Moreover, it was found that breast microcalcification\u0026nbsp;is an independent risk factor for breast cancer, and its risk is elevated when combined with breast density\u0026nbsp;\u003cstrong\u003e[2]\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eWhile digital mammography (DM) remains the gold standard for detecting breast microcalcifications, its ability to differentiate between benign and malignant types based solely on morphology and distribution can be limited. Contrast-enhanced spectral mammography (CESM) emerges as a promising approach by incorporating pathological contrast enhancement, potentially leading to a more confident diagnosis compared to DM, and offering a faster and potentially more cost-effective alternative to breast magnetic resonance imaging (MRI)\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(3).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCESM offers the potential to overcome limitations of DM while providing a faster and more cost-effective alternative to MRI [4, 5]. Additionally, CESM allows for a single scan to assess both microcalcification morphology (using low-energy imaging) and lesion function [5, 6].\u003c/p\u003e\n\u003cp\u003eThis study aims to evaluate the diagnostic accuracy of CESM compared to mammography in identifying suspicious breast calcifications and determining lesion extent. We further investigate the impact of CESM findings on surgeon decision-making.\u003c/p\u003e\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Patients and methods","content":"\u003cp\u003eThis cross-sectional study was conducted from January 2023 to December 2023 at the female imaging units of the Radiology Departments at Ain-Shams University Hospitals and the National Cancer Institute, Cairo, Egypt. The study was approved by the relevant ethics committees.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eParticipants:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eAdult female patients were included if they had:\u003c/p\u003e\u003cul\u003e\n \u003cli\u003eSuspicious breast calcifications (BIRADS 4B or 4C) identified during a mammogram screening.\u003c/li\u003e\n \u003cli\u003eA breast mass with suspicious calcifications (BIRADS 4 or 5) identified by mammography.\u003c/li\u003e\n\u003c/ul\u003e\u003cp\u003ePatients with either non suspicious microcalcifications or contraindications to contrast injection like renal dysfunction, pregnancy, allergies to contrast medium were excluded.\u003c/p\u003e\u003cp\u003eFifty eligible patients were selected using a convenience sampling method and provided written informed consent before undergoing contrast-enhanced spectral mammography (CESM).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCESM Procedure:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA certified technician performed CESM on a Senographe Pristina mammography system (GE Healthcare) following these steps:\u003c/p\u003e\u003col\u003e\n \u003cli\u003eAn intravenous (IV) line was placed in the patient's arm.\u003c/li\u003e\n \u003cli\u003eA non-ionic iodine contrast agent (Ultravist or Omnipaque 300) was injected at a dose of 1.5 ml/kg body weight.\u003c/li\u003e\n \u003cli\u003eHigh-energy and low-energy digital mammograms were acquired before and after contrast administration.\u003c/li\u003e\n \u003cli\u003eSubtraction images, in\u0026nbsp;the standard positions CC and MLO with compression so that the breast parenchyma becomes less visible,\u0026nbsp;were created to isolate the iodine signal, highlighting areas of blood vessel growth (angiogenesis).\u003c/li\u003e\n \u003cli\u003eThe entire procedure took approximately 7-10 minutes.\u003c/li\u003e\n\u003c/ol\u003e\u003cp\u003e\u003cstrong\u003eImage Analysis \u0026amp; Interpretation:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eMammograms and CESM images were evaluated by radiologists for:\u003c/p\u003e\u003cul\u003e\n \u003cli\u003eLesion size, location, shape, margins, and density.\u003c/li\u003e\n \u003cli\u003eCalcification characteristics on mammography which include distribution and morphology were analyzed and categorized to ACR BIRADS Lexicon 2013 \u003cstrong\u003e(7).\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003eEnhancement pattern is evaluated for CESM images and was analyzed and categorized according to ACR BIRADS for CEM 2022 \u003cstrong\u003e(8).\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\u003cp\u003eThe contralateral breast served as the control for comparison.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eHistopathological Correlation:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn cases with BIRADS IV or V lesions, by mammography and ultrasound examination and/or CESM, results were compared to histopathological report. Lesions were biopsied under US guidance “if the lesion is seen with US” and if only seen by mammograpgy, stereotactic biopsy was done using true cut needle biopsy (via 14 -18-gauge needles) or referred for surgical excision.\u0026nbsp;\u003c/p\u003e\u003cp\u003eHistopathological results served as the gold standard for this study. For patients with suspicious breast calcifications which turned out to be benign lesions by biopsy or patients with malignant lesions that were referred to oncology department for neoadjuvant chemotherapy, the histopathological results were based on core needle biopsies. For malignant cases that were elected for surgery without prior neoadjuvant chemotherapy, the final surgical specimens were used.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eStatistical Analysis:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eSensitivity, specificity, positive and negative predictive values and total accuracy were estimated taking the probability of malignancy; micro-calcific clusters as detected by mammography were considered as positive test results, while mass or non mass enhancement detected by CESM were considered as positive test results. The diagnostic indices +/- 95% confidence interval, were calculated for mammography and CESM alone and when combining them together. P-value was considered significant if ≤0.05.\u003c/p\u003e\u003cp\u003eWilcox-signed rank test was used to compare largest diameter by both DM and CESM in comparison to histopathology. Non parametric correlation analysis using spearman rho test was used to test association of tumor size by different measures (DM, CESM and histopathology).\u003c/p\u003e\u003cp\u003eAll statistical calculations were done using computer programs Microsoft Excel 2007 (Microsoft Corporation, NY, USA) and SPSS version 27.0, Statistical Package for the Social Science (Chicago, ILI).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study included 50 patients who had suspicious breast calcifications detected by DM, with 54 breast lesions. All patients performed DM, and CESM. None of them had adverse reactions. The ages ranged from 30\u0026ndash;76 years with a mean age 53.\u003c/p\u003e \u003cp\u003eWe classified the 50 cases into 4 groups according to the breast density. Out of the 50 cases, 5 cases (10%) were classified as ACR A, 11 cases (22%) were classified as ACR B, 29 cases (58%) were classified as ACR C and 5 cases (10%) were classified as ACR D.\u003c/p\u003e \u003cp\u003eAccording to the lesion location, we classified the detected 54 lesions into 5 groups and further according to their final diagnosis either by pathological assessment of biopsy and surgical samples \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of benign and malignant groups within the studied population according to the site of their suspected lesions.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSite of lesion\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal no.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUOQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUIQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLOQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLIQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCENTRAL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMULTICENTERIC\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAccording to final histopathological diagnosis, 35 lesions turned out to be malignant. Invasive duct carcinoma was the most common final histopathological diagnosis upon the \u0026ldquo;malignant lesions\u0026rdquo; group, while mucinous adenocarcinoma was the least common \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eFinal histopathological diagnosis upon the \u0026ldquo;malignant lesions\u0026rdquo; group:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFinal histopathological diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of lesions (total\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCIS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDCIS\u0026thinsp;+\u0026thinsp;IDC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMucinous adenocarcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOut of the 54 detected lesions, microacalcifications were isolated presenting findings in only 6 cases, other findings are listed in \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e These microacalcifications were divided according to their pattern and distribution according to ACR BI-RADS lexicon 2022, details provided in \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociated DM findings among studied lesions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM associated findings\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo of lesions\u003c/p\u003e \u003cp\u003e(total 54)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsolated suspicious calcifications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.1%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Masses\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42.6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Focal asymmetry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24.5%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Architectural distortion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+Internal mammary lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Dilated ducts\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Parenchymal edema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.85%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e+ Skin thickening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.85%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDM findings among studied lesions regarding micro-calcifications form and distribution:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eForm of calcification\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber of lesions\u003c/p\u003e \u003cp\u003e(total 54)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoarse heterogeneous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmorphous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFine pleomorphic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFine linear branching\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDistribution of microcalcifications\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNumber of lesions\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e(Total\u0026thinsp;=\u0026thinsp;54)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiffuse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrouped\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuctal linear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSegmental\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eStudy participants were 50 females with positive lesions on one side of the breast by mammography. Contralateral breast was considered the control side mammography examination. Four patients out of 50 had bilateral breast lesions. So we considered to have 54 malignant lesions and 46 controls.\u003c/p\u003e \u003cp\u003eMoreover, three cases showed more than one lesion on ipsilateral breast with contrast uptake on CESM and were subsequently found malignant by pathology. Upon a second look on initial mammography scans, we discovered suspicious microcalcifications that were missed in initial report of mammography either due to dense breast or due to lesion small size, or they were considered as benign looking calcifications on mammography but had contrast uptake by CESM and turned malignant by pathology. These lesions were considered false negative for mammography.\u003c/p\u003e \u003cp\u003eUpon correlating the mammography findings to the final diagnoses, 32 lesions were true positives, 19 lesions were false positives, 3 lesions were false negatives and 46 lesions were true negatives.\u003c/p\u003e \u003cp\u003eRegarding contrast mammo findings, 36 (66.6%) lesions showed contrast uptake and 18 (33.3%) lesions showed no contrast uptake. Enhancing lesions were classified into enhancing mass lesions 13 (36.1%), enhancing non mass lesions 17 (47.2%) and lesions that showed both mass and non-mass uptake 5 (16.6%) \u003cb\u003e(Fig.\u0026nbsp;1)\u003c/b\u003e. Out of the 23 lesions that showed non mass enhancement pattern, focal NME pattern was most common that was represented by 8 lesions, followed by regional NME representing 6 cases then comes segmental NME \u003cb\u003e(Fig.\u0026nbsp;2)\u003c/b\u003e representing 5 cases followed by linear, diffuse, combined linear with diffuse and combined focal with diffuse each represented by1 lesion for each.\u003c/p\u003e \u003cp\u003eUpon correlation with pathology results or follow up, 72.2% of lesions that showed no contrast uptake were benign with 37.8% showed malignancy with no contrast enhancement on mammography \u003cb\u003e(Fig.\u0026nbsp;3)\u003c/b\u003e. While 92.3% enhancing mass lesions, and 100% of lesions that showed both mass and non-mass enhancement were malignant.\u003c/p\u003e \u003cp\u003eRegarding the diagnostic indices of digital mammography and contrast mammography performance in assessment of micro-calcifications, they are summarized in (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResults of digital mammography DM versus contrast enhanced spectral mammography CESM in the evaluation of patients with suspicious breast calcifications.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAccuracy measures\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDigital mammography\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCESM\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91.4%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(76.9\u0026ndash;98.2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85.7%\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(69.7\u0026ndash;95.2)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSpecificity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e70.8%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(59.7\u0026ndash;81.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e90.7%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e(83.7\u0026ndash;97.8)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePPV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e62.7%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(49.5\u0026ndash;76.0)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e83.3%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e(71.2\u0026ndash;95.5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNPV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e93.9%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(83.1\u0026ndash;98.7)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e92.2%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e(82.7\u0026ndash;97.4)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal accuracy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e78%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e(69.9\u0026ndash;86.1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e89.0%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e(82.9\u0026ndash;95.1)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCombining digital mammography and contrast mammography, sensitivity was raised to 100%, specificity was 90.7%, PPV was 83.3% and NPV raised to 100%.\u003c/p\u003e\n\u003ch3\u003eSize correlation by digital mammography versus CESM\u003c/h3\u003e\n\u003cp\u003eAccurate lesion sizing through excision biopsy was obtained for 23 lesions out of the 36 malignant lesions detected in our study population.\u003c/p\u003e \u003cp\u003eOne of the study limitations was the wide time interval between both the DM and the CESM examination and the surgical excision biopsy for the other 13 malignant lesions detected, as those cases were referred to neoadjuvant chemotherapy after histopathological diagnosis. Those 13 cases were excluded from size correlation study.\u003c/p\u003e \u003cp\u003eWilcox-signed rank test was used to compare largest diameter by both DM and CESM in correlation to histopathology. Non-parametric correlation analysis using spearman rho test was used to test association of tumor size by different measures (DM, CESM and histopathology).\u003c/p\u003e \u003cp\u003eResults showed that size of tumor by CESM was more correlated to that by pathology, correlation coefficient (r\u0026thinsp;=\u0026thinsp;0.86), than that between DM and pathology, (r\u0026thinsp;=\u0026thinsp;0.588), \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAlso, mean difference in diameter between CESM and histopathology was 1.28 mm, while it was 2.8 mm between DM and histopathology. Yet, these differences showed no significant effects on surgical decision making \u003cb\u003e(\u003c/b\u003eTables\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e\u0026amp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of largest diameter (cm) of breast lesions by DM and after surgical dissection.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLargest diameter by DM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.1628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.487\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLargest diameter by pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.1066\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eP value is significant\u0026thinsp;\u0026le;\u0026thinsp;0.05, test statistics used for paired data comparison is Wilcoxon signed rank test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of largest diameter (cm) of breast lesions by CESM and after surgical dissection.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStandard deviation\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLargest diameter by CESM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.900\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.6090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.777\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLargest diameter by pathology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.028\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.6415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eP value is significant\u0026thinsp;\u0026le;\u0026thinsp;0.05, test statistics used for paired data comparison is Wilcoxon signed rank test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCronbach's Alpha as a measure of reliability or repeatability was found to be 0.740 between size measurement by DM and pathology, indicating acceptable reliability.\u003c/p\u003e \u003cp\u003eOn the other hand Cronbach's Alpha was 0.92 between CESM and pathology, indicating excellent reliability.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCESM examination impact on surgical decision for cases with suspicious breast microcalcifications:\u003c/h2\u003e \u003cp\u003eRegarding the size of tumor by CESM, even though it was more correlated to that by pathology than that between DM and pathology. Yet these minute differences in measurements (less than 4 mms) did not affect the surgical decision making.\u003c/p\u003e \u003cp\u003eHowever, results of CESM showed that false positive rate (9.3%) is significantly lower than that in DM (29.2%), which means that if a surgical decision is prompted it is better to be with CESM.\u003c/p\u003e \u003cp\u003eAlso, 3 cases that showed multicentricity detected by CESM but missed in initial mammography reports significantly affected the surgical decision making (upgrading from BCS to total mastectomy) \u003cb\u003e(Fig.\u0026nbsp;6).\u003c/b\u003e These cases either had dense breasts or were misdiagnosed as benign calcific lesions in initial DM report.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eCalcifications and microcalcifications (\u0026lt;0.5 mm) are very common in breast tissues and are easily detected on mammograms as small bright spots. Mammography is often the only diagnostic method that can identify this type of BC manifestation (9)\u003c/p\u003e\n\u003cp\u003eNeraly 55% of non-palpable breast cancers present in the form of microcalcifications without any other breast abnormality, and more than 80% of in situ breast neoplasms present also only as microcalcifications [10]. Microcalcifications are usually classified as benign or suspicious according to their morphology and distribution [11].\u003c/p\u003e\n\u003cp\u003eInterpreting microcalcifications seen in mammograms can present a challenge for radiologists [12]. The radiologists should balance the risk of unnecessary biopsies for benign lesions with the underestimation of potentially pathological microcalcifications [13].\u003c/p\u003e\n\u003cp\u003eContrast-enhanced spectral mammography (CESM), which has recently evolved and becomes increasingly used in clinical practice, could provide a valid asset [14]. Contrast-enhanced spectral mammography (CESM) builds upon the foundation of mammography (MG) by incorporating iodinated contrast media. Similar to contrast-enhanced magnetic resonance imaging (CE-MRI), CESM leverages the principle of tumor angiogenesis for image enhancement. Breast tumors are characterized by extensive neoangiogenesis, resulting in a dense network of immature and leaky blood vessels. These leaky vessels allow for the extravasation of contrast media into the tumor interstitium, leading to increased signal intensity and improved visualization of the malignancy [15].\u003c/p\u003e\n\u003cp\u003eIn this study, we investigated the utility of contrast-enhanced spectral mammography (CESM) in evaluating suspicious breast calcifications. Our findings provide valuable insights into the diagnostic accuracy and clinical impact of CESM compared to digital mammography (DM).\u003c/p\u003e\n\u003cp\u003eIn our study the ages ranged from 30 - 76 years with a mean age 53, while in a study done by \u003cstrong\u003e\u003cem\u003eHouben et al., 2019\u003c/em\u003e\u003c/strong\u003e, to assess the diagnostic accuracy of contrast mammography in cases with suspicious calcifications, the ages ranged from 49 to 75 years with mean age 60.5 years. On another study by \u003cstrong\u003e\u003cem\u003eNicosia et al., 2023\u003c/em\u003e\u003c/strong\u003e also about the role of CEM in microcalcifications assessment, the ages ranged from 45 to 59 years with mean age 51 years\u0026nbsp;[1,\u0026nbsp;6].\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOut of the 50 cases, 34 female had dense breast “including ACR C and D” in our study representing 68% of our study population. This is comparable to \u003cstrong\u003e\u003cem\u003eNicosia et al., 2023\u003c/em\u003e\u003c/strong\u003e who found that 78% of their cases had breast density classified as ACR C and D\u0026nbsp;[6].\u003c/p\u003e\n\u003cp\u003eAs regarding lesion location, we found that 38.8 % of lesions were in UOQ which was the most frequent among all other sites. While \u003cstrong\u003e\u003cem\u003eNicosia et al., 2023\u0026nbsp;\u003c/em\u003e\u003c/strong\u003efound that about59.9 % of lesions were detected at the UOQ\u0026nbsp;[6].\u003c/p\u003e\n\u003cp\u003eWe had 65 % of lesions diagnosed as “malignant lesions” by final histopathology. While \u003cstrong\u003e\u003cem\u003eHouben et al., 2019\u003c/em\u003e\u003c/strong\u003e, had only 44% lesions diagnosing as malignant out of the suspicious calcified lesions studied\u0026nbsp;[1]. Yet \u003cstrong\u003e\u003cem\u003eNicosia et al., 2023\u0026nbsp;\u003c/em\u003e\u003c/strong\u003efound that 66% were malignant\u0026nbsp;[6].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e65.5 % of malignant lesions in our study were diagnosed IDC and DCIS alone was found only in 5.7% while both DCIS and IDC were found combined in about 11.4%. \u003cstrong\u003e\u003cem\u003eHouben et al., 2019,\u003c/em\u003e\u003c/strong\u003e had DCIS in (50.4%) of malignant lesions group. They had 27 IDC cases, 2 cases of ILC, only 1 case of invasive mucinous carcinoma and another case of intraductal papillary carcinoma [1]. However, we no cases of intraductal papillary carcinoma were diagnosed in our study.\u003c/p\u003e\n\u003cp\u003eAlthough invasive lobular carcinoma (ILC) typically presents on mammography as masses, asymmetries, architectural distortion, and rarely as microcalcifications [16], we observed 4 cases of ILC. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found 42.6% of all lesions presented with associated mass lesions, while only 2.7 % of lesions in the study by \u003cstrong\u003e\u003cem\u003eNicosia et al., 2023\u003c/em\u003e\u003c/strong\u003e presented by microcalcificaions with associated masses\u0026nbsp;[6].\u003c/p\u003e\n\u003cp\u003eIn our study, the predominant morphology of microcalcifications in the lesions was\u0026nbsp;fine pleomorphic, accounting for 53.7%. The most frequent distribution pattern observed was grouped microcalcifications, present in 62.9% of cases. Unlike many similar studies that primarily focused on categorizing microcalcifications as either suspicious or non-suspicious, our research emphasizes the specific morphology and distribution patterns.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe diagnostic performance parameters for assessing breast calcifications using digital mammography (DM) were as follows: sensitivity of 91.43%, specificity of 70.77%, positive predictive value (PPV) of 62.75%, negative predictive value (NPV) of 93.88%, and overall accuracy of 78%. Houben et al. (2019) reported similar results for low-energy (LE) images, with a sensitivity of 90.8%, PPV of 54.1%, and NPV of 84.2%. However, their study’s specificity (39%) was significantly lower than that observed in our study\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eHouben et al. (2019) reported that 76.8% of lesions showed enhancement on CESM\u0026nbsp;[1]. In our study, 66.6% of lesions exhibited enhancement, with the non-mass enhancement (NME) pattern being the most common. Louka et al. (2020) found that 96.2% of malignant lesions (25 out of 26 cases) showed enhancement on CESM in patients with BI-RADS 4, 5, and 6 mammographic suspicious breast calcifications\u0026nbsp;[17].\u003c/p\u003e\n\u003cp\u003eCESM demonstrated significantly higher specificity than DM, with 90.7% (83.7–97.8) compared to 70.8% (59.7–81.8), p-value \u0026lt; 0.05. Houben et al. (2019) found no significant difference between the specificity of LE and HE images of CESM (39% vs. 36.6%)\u0026nbsp;[1]. Although CESM’s PPV appeared higher than DM’s (83.3% vs. 62.7%), the overlapping confidence intervals indicated no significant difference. CESM had a significantly lower false positive rate (9.3%) compared to DM (29.2%), suggesting CESM is preferable for surgical decisions. Houben et al. (2019) found no significant difference in false positive rates between CESM (36.37%) and DM (34%)\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eSensitivity and NPV were comparable between DM and CESM, aligning with Houben et al. (2019)\u0026nbsp;[1]. Total accuracy was higher with CESM, though not significantly, likely due to the small sample size. Louka et al. (2020) reported higher sensitivity (96%) for CESM in detecting malignant lesions with suspicious microcalcifications\u0026nbsp;[17].\u003c/p\u003e\n\u003cp\u003eOur results are consistent with Cheung et al. (2016), who found CESM provided additional enhancement information for accurate cancer diagnosis in lesions with microcalcifications, reporting a sensitivity of 89%, specificity of 87%, PPV of 77%, and NPV of 95%\u0026nbsp;[18]. Cheung et al. (2021) also reported a sensitivity of 93%-100% and specificity of 63%-88%, showing significant improvement over DM\u0026nbsp;[19].\u003c/p\u003e\n\u003cp\u003eShetat et al. (2021) found CESM valuable for assessing suspicious microcalcifications, with non-mass enhancement indicating high-grade DCIS or invasive components, and enhancement paucity favoring benign or low-grade DCIS\u0026nbsp;[3]. Ploumen et al. (2023) found that CESM enhancement and calcification features help differentiate between invasive breast cancer, DCIS, and benign lesions, with enhancement absence in calcifications mainly associated with low-grade DCIS, consistent with our results\u0026nbsp;[20].\u003c/p\u003e\n\u003cp\u003eWe evaluated combined results of DM and CESM in the evaluation of suspicious breast calcifications, they showed sensitivity 100% with CI (90-100), specificity 90.7% with CI (59.7-77.6), PPV 83.3 % with confidence interval (52.1-77.6) and NPV 100% with CI (92.3-100). To our knowledge previous papers of same interest didn’t study combined use of both techniques.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main objective of pre-operative breast imaging is to assess the extent of the disease after an initial diagnosis. Accurately measuring the tumor size and determining its progression through T staging are essential for planning surgery, whether or not neoadjuvant chemotherapy is involved for breast cancer patients[21]\u003cstrong\u003e\u003cem\u003e.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSpecimen radiography is useful for diagnosing suspicious microcalcifications but cannot predict the likelihood of invasive ductal carcinoma (IDC) underestimation. This determination requires microscopic histopathological analysis. To prevent underestimation, it is essential to accurately target the biopsy and obtain invasive tissue for microscopic evaluation. Not all microcalcifications in specimens contain invasive elements. Contrast-enhanced spectral mammography (CESM) can aid in identifying biopsy sites by highlighting enhancement features such as masses and solid enhancements, thereby improving the diagnosis of invasive disease\u0026nbsp;[18 \u0026amp;19]\u003cstrong\u003e\u003cem\u003e.\u003c/em\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur findings indicate that the tumor size measured by CESM showed a stronger correlation with pathology (r = 0.858) compared to DM (r = 0.588). The reliability of size measurements between DM and pathology was acceptable (Cronbach’s Alpha = 0.740), while the reliability between CESM and pathology was excellent (Cronbach’s Alpha = 0.92). These results align with Cheung et al.'s 2021 study, which demonstrated that CESM features can accurately predict IDC underestimation\u0026nbsp;[19].\u003c/p\u003e\n\u003cp\u003eThe mean difference in tumor diameter between CESM and histopathology was 1.28 mm, compared to 2.8 mm between DM and histopathology. However, these differences did not significantly impact surgical decision-making, as surgeons typically ensure an oncologically safe margin of over 4 mm around the calcifications\u0026nbsp;[22].\u003c/p\u003e\n\u003cp\u003eOur results align with Cheung et al. (2015), who found that CESM provides a more accurate assessment of disease extent compared to DM, with mean differences of 0.5 mm for CESM and 4.2 mm for DM\u0026nbsp;[23]. Similarly, Houben et al. (2019) reported that CESM reduces measurement error in disease extent assessment, though it may slightly overestimate the extent. These minor discrepancies did not significantly impact surgical decision-making\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eHouben et al. (2019)\u0026nbsp;took into account the impact of their findings on surgical decision-making, as this is the most relevant outcome when assessing the extent of the disease. Their study found no significant statistical differences in surgical treatment plans based on LE images or the entire CESM exam. We concur with their conclusions regarding the impact of size estimation on surgical outcomes. However, in our study, CESM detected multicentricity in three cases initially missed by DM, leading to a significant change in surgical decisions, upgrading from breast-conserving surgery (BCS) to primary mastectomy. This aspect was not considered by Houben et al. (2019)\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eOur study had several limitations. The sample size was limited, and the patients were not consecutive. The patient population was a selected group recalled from a national screening program, where screening radiologists decide on recalls. Different radiologists might select different patients, but this is standard practice in our program. CESM was not mandatory before biopsy in current clinical practice, and some patients were hesitant to undergo contrast medium injection. Additionally, the wide time interval between CESM examinations and surgical excision biopsy was a limitation, and 13 cases referred to neoadjuvant chemotherapy after histopathological diagnosis were excluded from the size correlation study.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our study demonstrated that CESM is more specific than DM in evaluating suspicious breast microcalcifications. While other accuracy measures showed no significant differences between the two modalities, the tumor size measured by CESM correlated more closely with pathology than DM. These minor differences in measurements did not impact surgical decision-making. However, CESM significantly influenced surgical decisions in cases where multicentricity was detected by CESM but missed in initial mammography reports, particularly in patients with dense breasts or misdiagnosed benign calcific lesions.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eM.E.A.I. wrote main manuscript, helped in collecting and reporting cases.M.M.T.E. collected cases and data M.H.M.H. reporting cases, revising the scientific content.A.GE.O. helped in correlating with surgical decision and also revised manuscript.O.H.O. Revised manuscript, cases reporting and data management\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHouben IP, Vanwetswinkel S, Kalia V, et al. (2019) Contrast-enhanced spectral mammography in the evaluation of breast suspicious calcifications: diagnostic accuracy and impact on surgical management. Acta Radiol 60(9):1110-1117. Epub 2019 Jan 24.\u003c/li\u003e\n\u003cli\u003eKim S, Tran TXM, Song H, Park B (2022) Microcalcifications, mammographic breast density, and risk of breast cancer: a cohort study. Breast Cancer Res 24:96.\u003c/li\u003e\n\u003cli\u003eShetat O, Moustafa A, Zaitoon S, et al. (2021) Added value of contrast-enhanced spectral mammogram in assessment of suspicious microcalcification and grading of DCIS. Egypt J Radiol Nucl Med 52:186.\u003c/li\u003e\n\u003cli\u003eCozzi A, Magni V, Zanardo M, et al. (2022) Contrast-enhanced mammography: A systematic review and meta-analysis of diagnostic performance. Radiology 302:568-581.\u003c/li\u003e\n\u003cli\u003eCoffey K, Jochelson M (2022) Contrast-enhanced mammography in breast cancer screening. Eur J Radiol 156:110513.\u003c/li\u003e\n\u003cli\u003eNicosia L, Bozzini A, Signorelli G, et al. (2023) Contrast-Enhanced Spectral Mammography in the Evaluation of Breast Microcalcifications: Controversies and Diagnostic Management. Healthcare 11:511.\u003c/li\u003e\n\u003cli\u003eAmerican College of Radiology (2013) BI-RADS Atlas: Breast Imaging Reporting and Data System. 5th ed. Reston, VA: American College of Radiology.\u003c/li\u003e\n\u003cli\u003eAmerican College of Radiology. Breast Imaging Reporting \u0026amp; Data System (BI-RADS\u0026reg;). https://www.acr.org/Clinical-Resources/Reporting-and-Data-Systems/Bi-Rads.\u003c/li\u003e\n\u003cli\u003eBalamou C, Ko\u0026iuml;vogui A, Rymzhanova R, et al. (2022) Breast cancer incidence by age at discovery of mammographic abnormality in women participating in French organized screening campaigns. Public Health 202:121-130. doi: 10.1016/j.puhe.2021.11.012.\u003c/li\u003e\n\u003cli\u003eZhang L, Hao C, Wu Y, et al. (2019) Microcalcification and BMP-2 in breast cancer: Correlation with clinicopathological features and outcomes. Onco Targets Ther 12:2023-2033. doi: 10.2147/OTT.S187835.\u003c/li\u003e\n\u003cli\u003eSickles EA, D\u0026rsquo;Orsi CJ, Bassett LW (2013) ACR BI-RADS Atlas, Breast Imaging Reporting and Data System. 5th ed. Reston, VA: American College of Radiology. ACR BI-RADS Mammography; pp. 134-136.\u003c/li\u003e\n\u003cli\u003eLuiten JD, Voogd AC, Luiten EJT, et al. (2020) Recall and Outcome of Screen-detected Microcalcifications during 2 Decades of Mammography Screening in the Netherlands National Breast Screening Program. Radiology 294:528-537. doi: 10.1148/radiol.2020191266.\u003c/li\u003e\n\u003cli\u003eHofvind S, Ponti A, Patnick J, et al. (2012) False-positive results in mammographic screening for breast cancer in Europe: A literature review and survey of service screening programmes. J Med Screen 19:57-66. doi: 10.1258/jms.2012.012083.\u003c/li\u003e\n\u003cli\u003eJames JJ, Tennant SL (2018) Contrast-Enhanced Spectral Mammography (CESM). Clin Radiol 73:715-723. doi: 10.1016/j.crad.2018.05.005.\u003c/li\u003e\n\u003cli\u003eGhaderi KF, Phillips J, Perry H, et al. (2019) Contrast-Enhanced Mammography: Current Applications and Future Directions. RadioGraphics 39:1907-1920. doi: 10.1148/rg.2019190079.\u003c/li\u003e\n\u003cli\u003eManning P, Fazeli S, Lim V, et al. (2022) Invasive Lobular Carcinoma: A Multimodality Imaging Primer. RadioGraphics 42:E115-E116.\u003c/li\u003e\n\u003cli\u003eLouka AL, Nassef HH (2020) Diagnosis of Breast Microcalcifications with Contrast Enhanced Digital Mammography and Histopathological Correlation. Med J Cairo Univ 88(September):1561-1569.\u003c/li\u003e\n\u003cli\u003eCheung YC, Juan YH, Lin YC, et al. (2016) Dual-energy contrast-enhanced spectral mammography: enhancement analysis on BI-RADS 4 non-mass microcalcifications in screened women. PLoS One 11(9):e0162740.\u003c/li\u003e\n\u003cli\u003eCheung YC, Chen K, Yu CC, et al. (2021) Contrast-enhanced mammographic features of in situ and invasive ductal carcinoma manifesting microcalcifications only: help to predict underestimation? Cancers 13(17):4371.\u003c/li\u003e\n\u003cli\u003ePloumen RA, de Mooij CM, Gommers S, et al. (2023) Imaging findings for response evaluation of ductal carcinoma in situ in breast cancer patients treated with neoadjuvant systemic therapy: a systematic review and meta-analysis. Eur Radiol 33:1-3.\u003c/li\u003e\n\u003cli\u003eYoun I, Choi S, Choi YJ, et al. (2019) Contrast enhanced digital mammography versus magnetic resonance imaging for accurate measurement of the size of breast cancer. Br J Radiol 92(1098):20180929.\u003c/li\u003e\n\u003cli\u003eLobbes MB, Vriens IJ, van Bommel AC, et al. (2017) Breast MRI increases the number of mastectomies for ductal cancers, but decreases them for lobular cancers. Breast Cancer Res Treat 162:353-364.\u003c/li\u003e\n\u003cli\u003eCheung YC, Tsai HP, Lo YF, et al. (2015) Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. Eur Radiol 26:1082-1089.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5340228/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5340228/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Digital mammography (DM) remains the gold standard for detecting breast microcalcifications, its ability to differentiate between benign and malignant types based solely on morphology and distribution can be limited. Contrast-enhanced spectral mammography (CESM) emerges as a promising approach by incorporating pathological contrast enhancement, potentially leading to a more confident diagnosis compared to DM, and offering a faster and potentially more cost-effective alternative to breast magnetic resonance imaging.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and methods: \u003c/strong\u003eThis cross-sectional study included 50 female patients with suspicious breast calcifications (BIRADS 4B, 4C, 4, or 5). CESM was performed, and images were analyzed for lesion characteristics. Histopathological results served as the gold standard for comparison, guiding surgical decisions and treatment plans.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThis study included 50 patients who had suspicious breast calcifications detected by DM, with 54 breast lesions.\u0026nbsp; All patients performed DM and CESM. None of them had adverse reactions. Out of the 54 identified breast\u0026nbsp;lesions, 19/54, 35% were benign and 35/54, 65% were malignant. The calculated\u0026nbsp;sensitivity, specificity, positive and negative predictive values and total accuracy of DM were \u0026nbsp;91.4%, 70.8%, 62.7%,\u0026nbsp;93.9%, and 78% respectively as compared to 85.7%,\u0026nbsp;90.7%, 83.3%,\u0026nbsp;92.2%,\u0026nbsp;and\u0026nbsp;89% for CESM.\u0026nbsp;When adding CESM to DM the calculated diagnostic indices were raised to\u0026nbsp;100%, specificity was 90.7 %, PPV was 83.3% and NPV raised to 100%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Combining CESM with DM while evaluating suspicious breast microcalcifications can increase both the sensitivity and specificity of cancer detection. CESM significantly influenced surgical decisions in cases where multicentricity was detected by CESM but missed in initial mammography reports, particularly in patients with dense breasts.\u003c/p\u003e","manuscriptTitle":"Digital Mammography Versus Contrast Enhanced Spectral Mammography in the Evaluation of Cases with Suspicious Breast Calcifications and Impact on Surgeon’s Decision.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-09 14:05:06","doi":"10.21203/rs.3.rs-5340228/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f4490d4c-6f11-4f90-8de0-a9e347410184","owner":[],"postedDate":"December 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-09T14:05:08+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-09 14:05:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5340228","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5340228","identity":"rs-5340228","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}