Ann Surg Oncol DOI 10.1245/s10434-014-4362-6
ORIGINAL ARTICLE – BREAST ONCOLOGY
Evaluation of Malignancy Risk Stratification of Microcalcifications Detected on Mammography: A Study Based on the 5th Edition of BI-RADS Soo-Yeon Kim, MD1, Ha Yan Kim, MS2, Eun-Kyung Kim, MD, PhD1, Min Jung Kim, MD, PhD1, Hee Jung Moon, MD, PhD1, and Jung Hyun Yoon, MD1 1
Department of Radiology, Severance Hospital, Research Institute of Radiological Science, College of Medicine, Yonsei University, Seoul, Korea; 2Biostatistics Collaboration Unit, Medical Research Center, College of Medicine, Yonsei University, Seoul, Korea
ABSTRACT Background. The 5th edition of Breast Imaging Reporting and Data System subdivides suspicious calcifications into two categories: 4B—amorphous, coarse heterogeneous, and fine pleomorphic calcifications; 4C—fine linear or fine linear branching calcifications. We investigated whether these revised categories are appropriate for malignancy risk stratification. Methods. We studied 246 patients (mean age 48.2 years) with suspicious microcalcifications detected on mammography who underwent stereotactic biopsy (n = 154) or surgical excisional biopsy with preoperative mammogramguided needle localization (n = 92). Pre-biopsy mammograms were reviewed retrospectively, and imaging features were analyzed according to the revised morphology and distribution descriptors. Pathological results of stereotactic biopsy and surgical excision were considered, with the surgical results being the reference standard. Positive predictive values (PPVs) were calculated and compared using the v2 test or Fisher’s exact test. Results. Overall PPV of suspicious microcalcifications was 22.4 %. PPVs of morphology descriptors were as follows: amorphous 7.9 %, coarse heterogeneous 17.8 %, fine pleomorphic 63.2 %, fine linear/fine linear branching 100 % (p \ 0.001). PPVs of distribution descriptors were as follows: regional 8.8 %, grouped 14.3 %, linear 87.5 %, segmental 63.6 % (p \ 0.001). For morphology and
Ó Society of Surgical Oncology 2015 First Received: 4 November 2014 J. H. Yoon, MD e-mail: [email protected]
distribution descriptors combinations, PPVs for amorphous/regional and amorphous/grouped microcalcifications were 4.2 and 7.6 %, resepectively. The PPV for fine pleomorphic/linear or segmental was 93.8 %. Conclusions. Subcategorization of morphology descriptors for suspicious microcalcifications is needed because of the different PPVs for amorphous, coarse heterogeneous, and fine pleomorphic microcalcifications. Combining morphology and distribution descriptors for suspicious microcalcifications provides accurate risk stratification.
The Breast Imaging Reporting and Data System (BIRADS) was developed by the American College of Radiology (ACR) in an effort to standardize the assessment and description of the findings and the recommendations for management.1 According to prior studies, the final assessment categories of the BI-RADS lexicon are useful and effective in malignancy risk stratification of breast lesions.2–6 Regarding suspicious microcalcifications, four morphology descriptors were used in the 4th edition of BIRADS: amorphous, coarse heterogeneous, fine pleomorphic, fine linear/fine linear branching.7 Morphology descriptors were further subdivided into two groups: those of intermediate concern (amorphous and coarse heterogeneous) and others with a higher probability of malignancy (fine pleomorphic and fine linear/fine linear branching).7 Results of several studies have reported the positive predictive value (PPV) of amorphous, coarse heterogeneous, fine pleomorphic, and fine linear/fine linear branching microcalcifications to be approximately 21, 13, 29, and 70 %, respectively.4,8–10 In 2013, the 5th edition of BI-RADS (BI-RADS-5) was released, with several changes concerning suspicious
S.-Y. Kim et al.
microcalcifications seen on mammography.1 One major change was elimination of the subdivisions ‘‘intermediate concern’’ and ‘‘higher probability of malignancy.’’ The 2013 edition indicates that the three calcification types (amorphous, coarse heterogeneous, fine pleomorphic) with similar PPVs lower than 50 % should be assessed as category 4B (moderate suspicion for malignancy, PPV range [10 and B50 %), whereas fine linear/fine linear branching, with a higher PPV of 70 %, should be assessed as category 4C (high suspicion for malignancy but not highly suggestive of malignancy, PPV [ 50 to \95 %).1 These recommendations, suggested in BI-RADS-5, are based on results of a few published studies with relatively small sample sizes.4,8–10 Although the three morphology descriptors are grouped in the same category (4B), we have found differences in the PPVs of the descriptors, especially when combined with distribution patterns. Appropriate malignancy risk stratification for each descriptor is essential for reaching a final assessment, which ultimately leads to appropriate patient management, including planning follow-up strategies after biopsy or surgery. To date, no studies have verified the changes regarding suspicious microcalcifications in BI-RADS-5. Therefore, we investigated whether the revised recommendations in BI-RADS-5 for assessing suspicious microcalcifications are appropriate for malignancy risk stratification. MATERIALS AND METHODS This study had a retrospective design and was approved by the institutional review board of Severance Hospital, Seoul, Korea. Neither patient approval nor informed consent was required for the review of medical records or images. Informed consent was signed and obtained from all patients for image-guided percutaneous biopsy or surgery prior to the procedures. Patients Between June 2010 and June 2012, suspicious microcalcifications were detected on mammography in 375 women at our institution. The women then underwent stereotactic biopsy (n = 204) or surgical excisional biopsy with preoperative mammogram-guided needle localization (n = 171). Among them, patients were excluded because (1) the microcalcifications were associated with masses and the true characteristics of the microcalcifications could not be confirmed on pathology (n = 79); (2) they had a mammographic follow-up interval of \12 months after being diagnosed with benign pathology by stereotactic biopsy (n = 46); (3) they had been diagnosed as having malignancy on stereotactic biopsy but did not undergo
surgery (n = 4). Thus, a total of 246 lesions from 246 patients (154 with stereotactic biopsy, 92 with surgical excisional biopsy under preoperative mammogram-guided needle localization) were included in this study (Fig. 1a). The mean age of the included patients was 48.2 years (range 29–69 years). Image Interpretation Mammography was performed with one of two dedicated digital mammography units (Senographe DS, GE Medical Systems, Milwaukee, WI, USA; Lorad Selenia, Hologic, Danbury, CT, USA). Standard mediolateral oblique and craniocaudal mammograms and magnification views with 90° lateral and craniocaudal projections were obtained for all patients. Two radiologists specializing in breast imaging with 1 and 6 years of experience (S.Y.K. and J.H.Y., respectively) independently reviewed the mammograms and categorized the microcalcifications according to morphology and distribution descriptors. Each was blinded to the pathology results. If the descriptor interpretation of the lesion differed between the two radiologists, consensus was reached after discussion. Microcalcifications were analyzed according to morphology (amorphous, coarse heterogeneous, fine pleomorphic, fine linear/fine linear branching) and distribution (diffuse, regional, grouped, linear, segmental) based on BI-RADS-5.1 Each reviewer selected the most appropriate descriptor for each lesion. In cases of microcalcifications with several descriptors, the most suspicious feature was considered in the analysis1 because management of microcalcifications should be based on the most suspicious descriptor applied to the mammographic finding of concern.9 Data and Statistical Analysis Histopathological results from stereotactic biopsy or surgery were considered the standard reference. Microcalcifications diagnosed as benign on stereotactic biopsy that did not show significant changes on follow-up mammography performed at least 12 months after biopsy were considered benign.1 Lesions diagnosed as invasive carcinoma on stereotactic biopsy or surgery were considered malignant. For lesions diagnosed as high-risk lesions on stereotactic biopsy or excisional biopsy—atypical ductal hyperplasia, intraductal papilloma, mucocele-like lesion, radial scar, lobular carcinoma in situ, atypical lobular hyperplasia, ductal carcinoma in situ (DCIS)—the final diagnosis was based on the pathological results to determine further surgical management. The PPV was calculated for each morphology and distribution descriptor, a combination of morphology and distribution descriptors, and categorization according to the 4th and 5th editions of BI-RADS and the subcategorization
Stratification of Microcalcifications FIG. 1 a Study population of this study. b A 45-year-old woman had suspicious microcalcifications in the left breast. Magnified craniocaudal mammogram shows fine pleomorphic and grouped calcifications. Stereotactic biopsy revealed atypical ductal hyperplasia with microcalcification, which was upgraded to focal ductal carcinoma in situ (\0.5 cm) based on the surgical findings. c A 45-year-old woman had suspicious microcalcifications in the left breast. Magnified mediolateral mammogram shows amorphous microcalcifications in grouped distribution. Final assessment for the microcalcifications seen on mammography was category 4A. Stereotactic biopsy was performed, and pathology revealed stromal fibrosis with microcalcifications, which was considered concordant with the imaging features. The patient was followed with mammography 30 months after biopsy and showed no changes on serial follow-up
A
375 women with suspicious microcalcification on mammography Microcalcifications with mass (n=79)
Surgery not performed after diagnosis of high risk lesion or malignancy on stereotactic biopsy (n=4)
Mammography follow-up less than 12 months after stereotactic biopsy (n=46)
FINAL INCLUSION (n=246)
Surgical excisional biopsy after mammogram-guided needle localization (n=92)
Stereotactic biopsy (n=154) Benign (n=105)
Stable on 12 months F/U (n=105), Figure 1c
High-risk lesion (n=16)
Surgery (n=16)
Malignancy (n=33)
Surgery (n=33)
Benign (n=57)
High-risk lesion (n=14)
Malignancy (n=21)
High-risk lesion (n=15) Malignancy (n=1, Figure 1b)
B C
suggested by this study. The v2 test was used to analyze the differences in PPVs of suspicious microcalcifications between individual descriptors or in combination. The CochranArmitage trend test was used to evaluate the trend between malignancy and the morphology, distribution descriptors, or combined morphology and distribution descriptors. All analyses were performed with SAS version 9.2 software (SAS Institute, Cary, NC, USA). A value of p \ 0.05 was considered to indicate a statistically significant difference. RESULTS Overall Biopsy Results Among the 246 lesions, 55 were malignant (DCIS in 45, invasive carcinomas in 10), and 191 were benign (benign in 162, high-risk lesions in 29: atypical ductal hyperplasia in
12, intraductal papilloma in 9, mucocele-like lesion in 4, radial scar in 2, lobular carcinoma in situ in 1, and atypical lobular hyperplasia in 1). The overall PPV of suspicious microcalcifications included in this study was 22.4 % (55/ 246). There were 16 high-risk lesions detected on stereotactic biopsy. Surgery was performed on all of them. One of them was upgraded to DCIS because of the surgcal findings (Fig. 1b). Follow-up mammography was performed to evaluate the 105 benign lesions diagnosed by stereotactic biopsy. The mean follow-up of these lesions was 26.4 ± 10.3 months (range 12–56 months). PPV According to Morphology, Distribution, and Combined Descriptors The PPVs for morphology descriptors were as follows (Table 1): amorphous 7.9 % (10/127), coarse heterogeneous
S.-Y. Kim et al. TABLE 1 PPV according to the morphology and distribution descriptors Descriptor
Benign
Malignant DCIS
Total
PPV (%)
Benign
High-risk lesion
Invasive carcinoma
100 (61.7 %)
17 (58.6 %)
8 (17.8 %)
2 (20.0 %)
127 (51.6 %)
51 (31.5 %) 11 (6.8 %)
9 (31.0 %) 3 (10.3 %)
11 (24.5 %) 20 (44.4 %)
2 (20.0 %) 4 (40.0 %)
73 (29.7 %) 38 (15.4 %)
6 (13.3 %)
2 (20.0 %)
8 (3.3 %)
100.0 (8/8)
3 (1.2 %)
0.0 (0/3)
\0.001
Morphology Amorphous Coarse heterogeneous Fine pleomorphic Fine linear or Fine linear branching
0
0
7.9 (10/127) 17.8 (13/73) 63.2 (24/38) \0.001
Distribution Diffuse
3 (1.9 %)
0
0
0
Regional
29 (17.9 %)
2 (6.9 %)
2 (4.4 %)
1 (10.0 %)
34 (13.8 %)
8.8 (3/34)
Grouped
123 (75.9 %)
21 (72.4 %)
21 (46.7 %)
3 (30.0 %)
168 (68.3 %)
14.3 (24/168)
Linear
1 (0.6 %)
Segmental
6 (3.7 %)
Total
p
162
0 6 (20.7 %) 29
6 (13.3 %)
1 (10.0 %)
8 (3.3 %)
16 (35.6 %)
5 (50.0 %)
33 (13.4 %)
63.6 (21/33)
10
246
22.4 (55/246)
45
87.5 (7/8)
PPV positive predictive value, DCIS ductal carcinoma in situ
17.8 % (13/73), fine pleomorphic 63.2 % (24/38), fine linear/fine linear branching 100 % (8/8). The PPVs showed significant differences between the morphology descriptors (p \ 0.001). The PPVs of morphology descriptors showed an increasing trend toward malignancy from amorphous to fine linear/fine linear branching microcalcifications, with statistical significance (p \ 0.001). The PPVs for the distribution descriptors were as follows (Table 1): regional 8.8 % (3/34), grouped 14.3 % (24/ 168), linear 87.5 % (7/8), segmental 63.6 % (21/33). The PPVs showed significant differences between the distribution descriptors (p \ 0.001). The PPVs for distribution descriptors showed an increasing trend toward malignancy from regional to linear distribution, with statistical significance (p \ 0.001). Table 2 demonstrates the PPVs of the combined morphology and distribution descriptors of suspicious microcalcifications. The PPVs of amorphous/regional and amorphous/grouped (Fig. 1c) microcalcifications were 4.2 and 7.6 %, respectively. The PPVs of coarse heterogeneous/linear or segmental, fine pleomorphic/linear or segmental microcalcifications were 50.0 and 93.8 %, respectively. Statistically significant differences were seen in the PPVs among the categories of combined morphology and distribution descriptors (p \ 0.001). There was a linear increasing trend for the combined descriptors, with statistical significance (p \ 0.001). DISCUSSION BI-RADS-5 subdivides suspicious calcifications into two categories: category 4B (amorphous, coarse heterogeneous, and fine pleomorphic) and category 4C (fine
linear/fine linear branching calcifications.1 The PPVs for microcalcifications with suspicious morphology in our study are as follows: 7.9 % for amorphous, 17.8 % for coarse heterogeneous, 63.2 % for fine pleomorphic, and 100 % for fine linear/fine linear branching. They display an increasing trend toward showing significance for supporting the usefulness of morphology descriptors in malignancy risk stratification. When applying the PPV for the final assessment category recommended by BI-RADS-5 to each morphology descriptor, amorphous calcifications should be assessed as category 4A, coarse heterogeneous as 4B, and fine pleomorphic or fine linear/fine linear branching as category 4C. Although we agree that all microcalcifications showing suspicious morphology should undergo biopsy, the results of our study show that the possibility of malignancy for each suspicious morphology are somewhat different, and they should not be considered equally. The likelihood of malignancy for final assessments recommended by BI-RADS-5 was 2–10 % for category 4A and 10–50 % for category 4B.1 Although benign pathology results for category 4A lesions may be regarded concordant, and conservative follow-up with imaging can be confidently considered, clinicians may be reluctant to consider that benign pathology results are concordant with category 4B lesions. In addition, the PPV for fine pleomorphic microcalcifications was 61.5 % in this study, exceeding the 10–50 % range recommended for category 4B. Therefore, they should be placed in category 4C. Although category 4B has a fair chance of having benign pathology, category 4C contains a significantly higher possibility of malignancy in which benign pathology results should alarm clinicians. Therefore, we believe that a subdivision of the morphology descriptors for suspicious
Stratification of Microcalcifications TABLE 2 PPV according to the combination of descriptors Morphology and distribution
Pathology Benign
Total
PPV (%)
p
\0.001
Malignancy
Benign
High-risk lesion
DCIS
Invasive carcinoma
Diffuse
1 (0.6)
0
0
0
1 (0.4)
0 (0/1)
Regional Grouped
22 (13.6) 73 (45.1)
1 (3.4) 12 (41.4)
0 6 (13.3)
1 (10.0) 1 (10.0)
24 (9.8) 92 (37.4)
4.2 (1/24) 7.6 (7/92)
Linear/segmental
4 (2.5)
4 (13.8)
2 (4.4)
0 (0.0)
10 (4.1)
20.0 (2/10)
2 (1.2)
0
0
0 (0.0)
2 (0.8)
0.0 (0/2)
Regional
7 (4.3)
1 (3.4)
2 (4.4)
0 (0.0)
10 (4.1)
20.0 (2/10)
Grouped
40 (24.7)
6 (20.7)
5 (11.1)
2 (20.0)
53 (21.5)
13.2 (7/53)
Linear/segmental
2 (1.2)
2 (6.9)
4 (8.9)
0 (0.0)
8 (3.3)
50.0 (4/8)
Diffuse
NA
NA
NA
NA
NA
NA
Regional
NA
NA
NA
NA
NA
NA
Grouped
10 (6.2)
3 (10.3)
9 (20.0)
0
22 (8.9)
40.9 (9/22)
Linear/segmental
1 (0.6)
0
11 (24.4)
4 (40.0)
16 (6.5)
93.8 (15/16)
Diffuse
NA
NA
NA
NA
NA
NA
Regional Grouped
NA 0
NA 0
NA 1 (2.2)
NA 0
NA 1 (0.4)
NA 100.0 (1/1)
Amorphous
Coarse heterogeneous Diffuse
Fine pleomorphic
Fine linear, fine linear branching
Linear/segmental Total
0
0
5 (11.1)
2 (20.0)
7 (2.8)
100.0 (7/7)
162
29
45
10
246
22.4 (55/246)
Raw data are in parentheses NA not applicable
microcalcifications is needed for appropriate patient management according to the biopsy results. BI-RADS does not provide recommendations on how to apply distribution descriptors for suspicious microcalcifications as they did for morphology descriptors. Nevertheless, distribution descriptors are also helpful for predicting malignancy risk as was found in previous studies.1,4,9,10 The PPVs of the distribution descriptors in our study were as follows: regional 8.8 %, grouped 14.3 %, segmental 63.6 %, and linear 87.5 %, indicating a linear increasing trend, with statistical significance. Because we use combinations of morphology and distribution descriptors to assess microcalcifications on mammography during daily practice, we chose to analyze the PPVs of combined morphology and distribution descriptors for the suspicious microcalcifications included this study. Several studies have proposed a systematic approach for predicting malignancy of suspicious microcalcifications using morphology and distribution descriptors.11,12 These studies, however, did not show PPVs for combinations of descriptors, nor did they propose a subcategorization system using these combinations.
Regional Grouped Amorphous
Category 4A Linear Segmental
Coarse heterogeneous
Regional Grouped Linear Segmental
Category 4B
Grouped Fine pleomorphic
Linear Segmental Category 4C
Fine linear or Fine linear branching
Grouped Linear Segmental
FIG. 2 Subcategorization of suspicious microcalcifications according to the combination of morphology and distribution
Based on our results, we suggest subcategorization for suspicious calcifications (Fig. 2). First, amorphous calcifications in regional (PPV 4.2 %) or grouped (PPV 7.6 %) distribution can be classified as category 4A. Second,
S.-Y. Kim et al. TABLE 3 PPVs of 246 suspicious microcalcifications according to the 4th and 5th editions of BI-RADS and in this study Parameter
Pathology
PPV (%)
Benign
Malignant
Intermediate concern
176 (92.1 %)
23 (41.8 %)
11.6
Higher probability of malignancy
15 (7.9 %)
32 (58.2 %)
68.1
Category 4B
191 (100 %)
47 (85.5 %)
19.7
Category 4C
0
8 (14.5 %)
100.0
108 (56.5 %)
8 (14.5 %)
6.9
Category 4B
82 (42.9 %)
24 (43.6 %)
22.6
Category 4C
1 (0.5 %)
23 (41.8 %)
95.8
4th BI-RADSa
5th BI-RADS
b
This studyc Category 4A
a
4th BI-RADS: intermediate concern (amorphous and coarse heterogeneity). Higher probability of malignancy (fine pleomorphism and fine linear or fine linear branching)
b
5th BI-RADS: category 4B (amorphous, coarse heterogeneity, and fine pleomorphism). Category 4C (fine linear branching)
c
This study: as presented in Fig. 2
amorphous calcifications in linear/segmental distribution (PPV 20.0 %) or coarse heterogeneous calcifications regardless of distribution and fine pleomorphic calcifications in grouped distribution (PPV 40.9 %) can be categorized as category 4B. Lastly, fine pleomorphic calcifications in linear/segmental distribution (PPV 93.8 %) and fine linear/fine linear branching calcification, regardless of distribution, should be categorized as 4C. Table 3 summarizes the categorization of suspicious microcalcifications according to the 4th and 5th editions of BI-RADS and the subcategorization using combinations of morphology and distribution descriptors proposed in this study. The subcategorizations we are suggesting may be more feasible than the categorizations suggested by BI-RADS because both the morphology and distribution of microcalcifications are considered. Also, the PPVs of the subcategories proposed in this study are within the range of categories 4A–4C recommended by BI-RADS, further supporting the use of combined morphology and distribution descriptors for risk stratification of suspicious microcalcifications. Our results show a relatively lower PPV (7.9 %) for amorphous calcifications and a higher PPV (63.2 %) for fine pleomorphic calcifications compared to previously published data of PPVs of 21.0 % for amorphous and 29.0 % for fine pleomorphic calcifications.1,4,8–10 In contrast, the 7.9 % PPV for amorphous microcalcifications in our study was in a range similar to those cited in other recent studies, 6.5–9.8 %.12,13 Inter-observer reliability has been reported to be fair for evaluating morphology of calcifications (k = 0.31–0.40),12,14–16 which may have been responsible for the differences in PPVs among studies. In addition, the subdivision of coarse heterogeneous
from fine pleomorphic was not applied in some studies,13,17,18 which may have been the reason for differences in PPVs regarding the morphology descriptor. Further prospective studies including larger study populations are anticipated to validate our results. We acknowledge several limitations to our study. First, unavoidably uneven distributions of suspicious microcalcifications were included in this study, with a high incidence of amorphous morphology and grouped distribution and a low incidence of fine linear/fine linear branching morphology and linear distribution. Second, because of the retrospective study design, case selection bias may have occurred because we included only patients who underwent imaging-guided biopsy or surgery for suspicious microcalcifications. Third, interobserver variability is a well-known problem when characterizing microcalcifications,12,14–16 which may have affected our results. We did not analyze the interobserver variability among the radiologists who had been involved in the imaging analysis. To overcome this problem, consensus was reached after discussion for discrepant cases between the two radiologists involved in the imaging review. CONCLUSIONS Subcategorization of morphology descriptors for suspicious microcalcifications is needed because of the different PPVs in amorphous, coarse heterogeneous, and fine pleomorphic microcalcifications. Combining morphology and distribution descriptors for suspicious microcalcifications provides accurate risk stratification that can be applied when deciding upon further patient management.
Stratification of Microcalcifications DISCLOSURE
The authors declare no conflicts of interest.
REFERENCES 1. American College of Radiology. Breast Imaging Reporting and Data System, 5th edn. Reston: American College of Radiology, 2013. 2. Orel SG, Kay N, Reynolds C, Sullivan DC. BI-RADS categorization as a predictor of malignancy 1. Radiology. 1999;211:845–50. 3. Zonderland HM, Pope Jr TL, Nieborg AJ. The positive predictive value of the Breast Imaging Reporting and Data System (BIRADS) as a method of quality assessment in breast imaging in a hospital population. Eur Radiol. 2004;14:1743–50. 4. Liberman L, Abramson AF, Squires FB, Glassman J, Morris E, Dershaw D. The Breast Imaging Reporting and Data System: positive predictive value of mammographic features and final assessment categories. AJR Am J Roentgenol. 1998;171:35–40. 5. Lacquement MA, Mitchell D, Hollingsworth AB. Positive predictive value of the Breast Imaging Reporting and Data System. J Am Coll Surg. 1999;189:34–40. 6. Obenauer S, Hermann K, Grabbe E. Applications and literature review of the BI-RADS classification. Eur Radiol. 2005;15:1027–36. 7. American College of Radiology. Breast Imaging Reporting and Data System, 4th edn. Reston: American College of Radiology, 2003. 8. Berg WA, Arnoldus CL, Teferra E, Bhargavan M. Biopsy of amorphous breast calcifications: pathologic outcome and yield at stereotactic biopsy 1. Radiology. 2001;221:495–503. 9. Burnside ES, Ochsner JE, Fowler KJ, et al. Use of microcalcification descriptors in BI-RADS 4th edition to stratify risk of malignancy. Radiology. 2007;242:388–95.
10. Bent CK, Bassett LW, D’Orsi CJ, Sayre JW. The positive predictive value of BI-RADS microcalcification descriptors and final assessment categories. AJR Am J Roentgenol. 2010;194:1378–83. 11. Mu¨ller-Schimpfle M, Wersebe A, Xydeas T, et al. Microcalcifications of the breast: how does radiologic classification correlate with histology? Acta Radiol. 2005;46:774–81. 12. Youk JH, Son EJ, Kim JA, et al. Scoring system based on BIRADS lexicon to predict probability of malignancy in suspicious microcalcifications. Ann Surg Oncol. 2012;19:1491–8. 13. Torres-Tabanera M, Ca´rdenas-Rebollo J, Villar-Castan˜o P, et al. Analysis of the positive predictive value of the subcategories of BI-RADSÒ 4 lesions: preliminary results in 880 lesions. Radiologı´a (English Edition). 2012;54:520–31. 14. Berg WA, Campassi C, Langenberg P, Sexton MJ. Breast Imaging Reporting and Data System: inter- and intraobserver variability in feature analysis and final assessment. AJR Am J Roentgenol. 2000;174:1769–77. 15. Gu¨lsu¨n M, Demirkazık FB, Arıyu¨rek M. Evaluation of breast microcalcifications according to Breast Imaging Reporting and Data System criteria and Le Gal’s classification. Eur J Radiol. 2003;47:227–31. 16. Lazarus E, Mainiero MB, Schepps B, Koelliker SL, Livingston LS. BI-RADS lexicon for US and mammography: interobserver variability and positive predictive value 1. Radiology. 2006;239: 385–91. 17. Uematsu T, Kasami M, Yuen S. Usefulness and limitations of the Japan mammography guidelines for the categorization of microcalcifications. Breast Cancer. 2008;15:291–7. 18. Kettritz U, Morack G, Decker T. Stereotactic vacuum-assisted breast biopsies in 500 women with microcalcifications: radiological and pathological correlations. Eur J Radiol. 2005;55:270–6.
ORIGINAL ARTICLE – BREAST ONCOLOGY
Evaluation of Malignancy Risk Stratification of Microcalcifications Detected on Mammography: A Study Based on the 5th Edition of BI-RADS Soo-Yeon Kim, MD1, Ha Yan Kim, MS2, Eun-Kyung Kim, MD, PhD1, Min Jung Kim, MD, PhD1, Hee Jung Moon, MD, PhD1, and Jung Hyun Yoon, MD1 1
Department of Radiology, Severance Hospital, Research Institute of Radiological Science, College of Medicine, Yonsei University, Seoul, Korea; 2Biostatistics Collaboration Unit, Medical Research Center, College of Medicine, Yonsei University, Seoul, Korea
ABSTRACT Background. The 5th edition of Breast Imaging Reporting and Data System subdivides suspicious calcifications into two categories: 4B—amorphous, coarse heterogeneous, and fine pleomorphic calcifications; 4C—fine linear or fine linear branching calcifications. We investigated whether these revised categories are appropriate for malignancy risk stratification. Methods. We studied 246 patients (mean age 48.2 years) with suspicious microcalcifications detected on mammography who underwent stereotactic biopsy (n = 154) or surgical excisional biopsy with preoperative mammogramguided needle localization (n = 92). Pre-biopsy mammograms were reviewed retrospectively, and imaging features were analyzed according to the revised morphology and distribution descriptors. Pathological results of stereotactic biopsy and surgical excision were considered, with the surgical results being the reference standard. Positive predictive values (PPVs) were calculated and compared using the v2 test or Fisher’s exact test. Results. Overall PPV of suspicious microcalcifications was 22.4 %. PPVs of morphology descriptors were as follows: amorphous 7.9 %, coarse heterogeneous 17.8 %, fine pleomorphic 63.2 %, fine linear/fine linear branching 100 % (p \ 0.001). PPVs of distribution descriptors were as follows: regional 8.8 %, grouped 14.3 %, linear 87.5 %, segmental 63.6 % (p \ 0.001). For morphology and
Ó Society of Surgical Oncology 2015 First Received: 4 November 2014 J. H. Yoon, MD e-mail: [email protected]
distribution descriptors combinations, PPVs for amorphous/regional and amorphous/grouped microcalcifications were 4.2 and 7.6 %, resepectively. The PPV for fine pleomorphic/linear or segmental was 93.8 %. Conclusions. Subcategorization of morphology descriptors for suspicious microcalcifications is needed because of the different PPVs for amorphous, coarse heterogeneous, and fine pleomorphic microcalcifications. Combining morphology and distribution descriptors for suspicious microcalcifications provides accurate risk stratification.
The Breast Imaging Reporting and Data System (BIRADS) was developed by the American College of Radiology (ACR) in an effort to standardize the assessment and description of the findings and the recommendations for management.1 According to prior studies, the final assessment categories of the BI-RADS lexicon are useful and effective in malignancy risk stratification of breast lesions.2–6 Regarding suspicious microcalcifications, four morphology descriptors were used in the 4th edition of BIRADS: amorphous, coarse heterogeneous, fine pleomorphic, fine linear/fine linear branching.7 Morphology descriptors were further subdivided into two groups: those of intermediate concern (amorphous and coarse heterogeneous) and others with a higher probability of malignancy (fine pleomorphic and fine linear/fine linear branching).7 Results of several studies have reported the positive predictive value (PPV) of amorphous, coarse heterogeneous, fine pleomorphic, and fine linear/fine linear branching microcalcifications to be approximately 21, 13, 29, and 70 %, respectively.4,8–10 In 2013, the 5th edition of BI-RADS (BI-RADS-5) was released, with several changes concerning suspicious
S.-Y. Kim et al.
microcalcifications seen on mammography.1 One major change was elimination of the subdivisions ‘‘intermediate concern’’ and ‘‘higher probability of malignancy.’’ The 2013 edition indicates that the three calcification types (amorphous, coarse heterogeneous, fine pleomorphic) with similar PPVs lower than 50 % should be assessed as category 4B (moderate suspicion for malignancy, PPV range [10 and B50 %), whereas fine linear/fine linear branching, with a higher PPV of 70 %, should be assessed as category 4C (high suspicion for malignancy but not highly suggestive of malignancy, PPV [ 50 to \95 %).1 These recommendations, suggested in BI-RADS-5, are based on results of a few published studies with relatively small sample sizes.4,8–10 Although the three morphology descriptors are grouped in the same category (4B), we have found differences in the PPVs of the descriptors, especially when combined with distribution patterns. Appropriate malignancy risk stratification for each descriptor is essential for reaching a final assessment, which ultimately leads to appropriate patient management, including planning follow-up strategies after biopsy or surgery. To date, no studies have verified the changes regarding suspicious microcalcifications in BI-RADS-5. Therefore, we investigated whether the revised recommendations in BI-RADS-5 for assessing suspicious microcalcifications are appropriate for malignancy risk stratification. MATERIALS AND METHODS This study had a retrospective design and was approved by the institutional review board of Severance Hospital, Seoul, Korea. Neither patient approval nor informed consent was required for the review of medical records or images. Informed consent was signed and obtained from all patients for image-guided percutaneous biopsy or surgery prior to the procedures. Patients Between June 2010 and June 2012, suspicious microcalcifications were detected on mammography in 375 women at our institution. The women then underwent stereotactic biopsy (n = 204) or surgical excisional biopsy with preoperative mammogram-guided needle localization (n = 171). Among them, patients were excluded because (1) the microcalcifications were associated with masses and the true characteristics of the microcalcifications could not be confirmed on pathology (n = 79); (2) they had a mammographic follow-up interval of \12 months after being diagnosed with benign pathology by stereotactic biopsy (n = 46); (3) they had been diagnosed as having malignancy on stereotactic biopsy but did not undergo
surgery (n = 4). Thus, a total of 246 lesions from 246 patients (154 with stereotactic biopsy, 92 with surgical excisional biopsy under preoperative mammogram-guided needle localization) were included in this study (Fig. 1a). The mean age of the included patients was 48.2 years (range 29–69 years). Image Interpretation Mammography was performed with one of two dedicated digital mammography units (Senographe DS, GE Medical Systems, Milwaukee, WI, USA; Lorad Selenia, Hologic, Danbury, CT, USA). Standard mediolateral oblique and craniocaudal mammograms and magnification views with 90° lateral and craniocaudal projections were obtained for all patients. Two radiologists specializing in breast imaging with 1 and 6 years of experience (S.Y.K. and J.H.Y., respectively) independently reviewed the mammograms and categorized the microcalcifications according to morphology and distribution descriptors. Each was blinded to the pathology results. If the descriptor interpretation of the lesion differed between the two radiologists, consensus was reached after discussion. Microcalcifications were analyzed according to morphology (amorphous, coarse heterogeneous, fine pleomorphic, fine linear/fine linear branching) and distribution (diffuse, regional, grouped, linear, segmental) based on BI-RADS-5.1 Each reviewer selected the most appropriate descriptor for each lesion. In cases of microcalcifications with several descriptors, the most suspicious feature was considered in the analysis1 because management of microcalcifications should be based on the most suspicious descriptor applied to the mammographic finding of concern.9 Data and Statistical Analysis Histopathological results from stereotactic biopsy or surgery were considered the standard reference. Microcalcifications diagnosed as benign on stereotactic biopsy that did not show significant changes on follow-up mammography performed at least 12 months after biopsy were considered benign.1 Lesions diagnosed as invasive carcinoma on stereotactic biopsy or surgery were considered malignant. For lesions diagnosed as high-risk lesions on stereotactic biopsy or excisional biopsy—atypical ductal hyperplasia, intraductal papilloma, mucocele-like lesion, radial scar, lobular carcinoma in situ, atypical lobular hyperplasia, ductal carcinoma in situ (DCIS)—the final diagnosis was based on the pathological results to determine further surgical management. The PPV was calculated for each morphology and distribution descriptor, a combination of morphology and distribution descriptors, and categorization according to the 4th and 5th editions of BI-RADS and the subcategorization
Stratification of Microcalcifications FIG. 1 a Study population of this study. b A 45-year-old woman had suspicious microcalcifications in the left breast. Magnified craniocaudal mammogram shows fine pleomorphic and grouped calcifications. Stereotactic biopsy revealed atypical ductal hyperplasia with microcalcification, which was upgraded to focal ductal carcinoma in situ (\0.5 cm) based on the surgical findings. c A 45-year-old woman had suspicious microcalcifications in the left breast. Magnified mediolateral mammogram shows amorphous microcalcifications in grouped distribution. Final assessment for the microcalcifications seen on mammography was category 4A. Stereotactic biopsy was performed, and pathology revealed stromal fibrosis with microcalcifications, which was considered concordant with the imaging features. The patient was followed with mammography 30 months after biopsy and showed no changes on serial follow-up
A
375 women with suspicious microcalcification on mammography Microcalcifications with mass (n=79)
Surgery not performed after diagnosis of high risk lesion or malignancy on stereotactic biopsy (n=4)
Mammography follow-up less than 12 months after stereotactic biopsy (n=46)
FINAL INCLUSION (n=246)
Surgical excisional biopsy after mammogram-guided needle localization (n=92)
Stereotactic biopsy (n=154) Benign (n=105)
Stable on 12 months F/U (n=105), Figure 1c
High-risk lesion (n=16)
Surgery (n=16)
Malignancy (n=33)
Surgery (n=33)
Benign (n=57)
High-risk lesion (n=14)
Malignancy (n=21)
High-risk lesion (n=15) Malignancy (n=1, Figure 1b)
B C
suggested by this study. The v2 test was used to analyze the differences in PPVs of suspicious microcalcifications between individual descriptors or in combination. The CochranArmitage trend test was used to evaluate the trend between malignancy and the morphology, distribution descriptors, or combined morphology and distribution descriptors. All analyses were performed with SAS version 9.2 software (SAS Institute, Cary, NC, USA). A value of p \ 0.05 was considered to indicate a statistically significant difference. RESULTS Overall Biopsy Results Among the 246 lesions, 55 were malignant (DCIS in 45, invasive carcinomas in 10), and 191 were benign (benign in 162, high-risk lesions in 29: atypical ductal hyperplasia in
12, intraductal papilloma in 9, mucocele-like lesion in 4, radial scar in 2, lobular carcinoma in situ in 1, and atypical lobular hyperplasia in 1). The overall PPV of suspicious microcalcifications included in this study was 22.4 % (55/ 246). There were 16 high-risk lesions detected on stereotactic biopsy. Surgery was performed on all of them. One of them was upgraded to DCIS because of the surgcal findings (Fig. 1b). Follow-up mammography was performed to evaluate the 105 benign lesions diagnosed by stereotactic biopsy. The mean follow-up of these lesions was 26.4 ± 10.3 months (range 12–56 months). PPV According to Morphology, Distribution, and Combined Descriptors The PPVs for morphology descriptors were as follows (Table 1): amorphous 7.9 % (10/127), coarse heterogeneous
S.-Y. Kim et al. TABLE 1 PPV according to the morphology and distribution descriptors Descriptor
Benign
Malignant DCIS
Total
PPV (%)
Benign
High-risk lesion
Invasive carcinoma
100 (61.7 %)
17 (58.6 %)
8 (17.8 %)
2 (20.0 %)
127 (51.6 %)
51 (31.5 %) 11 (6.8 %)
9 (31.0 %) 3 (10.3 %)
11 (24.5 %) 20 (44.4 %)
2 (20.0 %) 4 (40.0 %)
73 (29.7 %) 38 (15.4 %)
6 (13.3 %)
2 (20.0 %)
8 (3.3 %)
100.0 (8/8)
3 (1.2 %)
0.0 (0/3)
\0.001
Morphology Amorphous Coarse heterogeneous Fine pleomorphic Fine linear or Fine linear branching
0
0
7.9 (10/127) 17.8 (13/73) 63.2 (24/38) \0.001
Distribution Diffuse
3 (1.9 %)
0
0
0
Regional
29 (17.9 %)
2 (6.9 %)
2 (4.4 %)
1 (10.0 %)
34 (13.8 %)
8.8 (3/34)
Grouped
123 (75.9 %)
21 (72.4 %)
21 (46.7 %)
3 (30.0 %)
168 (68.3 %)
14.3 (24/168)
Linear
1 (0.6 %)
Segmental
6 (3.7 %)
Total
p
162
0 6 (20.7 %) 29
6 (13.3 %)
1 (10.0 %)
8 (3.3 %)
16 (35.6 %)
5 (50.0 %)
33 (13.4 %)
63.6 (21/33)
10
246
22.4 (55/246)
45
87.5 (7/8)
PPV positive predictive value, DCIS ductal carcinoma in situ
17.8 % (13/73), fine pleomorphic 63.2 % (24/38), fine linear/fine linear branching 100 % (8/8). The PPVs showed significant differences between the morphology descriptors (p \ 0.001). The PPVs of morphology descriptors showed an increasing trend toward malignancy from amorphous to fine linear/fine linear branching microcalcifications, with statistical significance (p \ 0.001). The PPVs for the distribution descriptors were as follows (Table 1): regional 8.8 % (3/34), grouped 14.3 % (24/ 168), linear 87.5 % (7/8), segmental 63.6 % (21/33). The PPVs showed significant differences between the distribution descriptors (p \ 0.001). The PPVs for distribution descriptors showed an increasing trend toward malignancy from regional to linear distribution, with statistical significance (p \ 0.001). Table 2 demonstrates the PPVs of the combined morphology and distribution descriptors of suspicious microcalcifications. The PPVs of amorphous/regional and amorphous/grouped (Fig. 1c) microcalcifications were 4.2 and 7.6 %, respectively. The PPVs of coarse heterogeneous/linear or segmental, fine pleomorphic/linear or segmental microcalcifications were 50.0 and 93.8 %, respectively. Statistically significant differences were seen in the PPVs among the categories of combined morphology and distribution descriptors (p \ 0.001). There was a linear increasing trend for the combined descriptors, with statistical significance (p \ 0.001). DISCUSSION BI-RADS-5 subdivides suspicious calcifications into two categories: category 4B (amorphous, coarse heterogeneous, and fine pleomorphic) and category 4C (fine
linear/fine linear branching calcifications.1 The PPVs for microcalcifications with suspicious morphology in our study are as follows: 7.9 % for amorphous, 17.8 % for coarse heterogeneous, 63.2 % for fine pleomorphic, and 100 % for fine linear/fine linear branching. They display an increasing trend toward showing significance for supporting the usefulness of morphology descriptors in malignancy risk stratification. When applying the PPV for the final assessment category recommended by BI-RADS-5 to each morphology descriptor, amorphous calcifications should be assessed as category 4A, coarse heterogeneous as 4B, and fine pleomorphic or fine linear/fine linear branching as category 4C. Although we agree that all microcalcifications showing suspicious morphology should undergo biopsy, the results of our study show that the possibility of malignancy for each suspicious morphology are somewhat different, and they should not be considered equally. The likelihood of malignancy for final assessments recommended by BI-RADS-5 was 2–10 % for category 4A and 10–50 % for category 4B.1 Although benign pathology results for category 4A lesions may be regarded concordant, and conservative follow-up with imaging can be confidently considered, clinicians may be reluctant to consider that benign pathology results are concordant with category 4B lesions. In addition, the PPV for fine pleomorphic microcalcifications was 61.5 % in this study, exceeding the 10–50 % range recommended for category 4B. Therefore, they should be placed in category 4C. Although category 4B has a fair chance of having benign pathology, category 4C contains a significantly higher possibility of malignancy in which benign pathology results should alarm clinicians. Therefore, we believe that a subdivision of the morphology descriptors for suspicious
Stratification of Microcalcifications TABLE 2 PPV according to the combination of descriptors Morphology and distribution
Pathology Benign
Total
PPV (%)
p
\0.001
Malignancy
Benign
High-risk lesion
DCIS
Invasive carcinoma
Diffuse
1 (0.6)
0
0
0
1 (0.4)
0 (0/1)
Regional Grouped
22 (13.6) 73 (45.1)
1 (3.4) 12 (41.4)
0 6 (13.3)
1 (10.0) 1 (10.0)
24 (9.8) 92 (37.4)
4.2 (1/24) 7.6 (7/92)
Linear/segmental
4 (2.5)
4 (13.8)
2 (4.4)
0 (0.0)
10 (4.1)
20.0 (2/10)
2 (1.2)
0
0
0 (0.0)
2 (0.8)
0.0 (0/2)
Regional
7 (4.3)
1 (3.4)
2 (4.4)
0 (0.0)
10 (4.1)
20.0 (2/10)
Grouped
40 (24.7)
6 (20.7)
5 (11.1)
2 (20.0)
53 (21.5)
13.2 (7/53)
Linear/segmental
2 (1.2)
2 (6.9)
4 (8.9)
0 (0.0)
8 (3.3)
50.0 (4/8)
Diffuse
NA
NA
NA
NA
NA
NA
Regional
NA
NA
NA
NA
NA
NA
Grouped
10 (6.2)
3 (10.3)
9 (20.0)
0
22 (8.9)
40.9 (9/22)
Linear/segmental
1 (0.6)
0
11 (24.4)
4 (40.0)
16 (6.5)
93.8 (15/16)
Diffuse
NA
NA
NA
NA
NA
NA
Regional Grouped
NA 0
NA 0
NA 1 (2.2)
NA 0
NA 1 (0.4)
NA 100.0 (1/1)
Amorphous
Coarse heterogeneous Diffuse
Fine pleomorphic
Fine linear, fine linear branching
Linear/segmental Total
0
0
5 (11.1)
2 (20.0)
7 (2.8)
100.0 (7/7)
162
29
45
10
246
22.4 (55/246)
Raw data are in parentheses NA not applicable
microcalcifications is needed for appropriate patient management according to the biopsy results. BI-RADS does not provide recommendations on how to apply distribution descriptors for suspicious microcalcifications as they did for morphology descriptors. Nevertheless, distribution descriptors are also helpful for predicting malignancy risk as was found in previous studies.1,4,9,10 The PPVs of the distribution descriptors in our study were as follows: regional 8.8 %, grouped 14.3 %, segmental 63.6 %, and linear 87.5 %, indicating a linear increasing trend, with statistical significance. Because we use combinations of morphology and distribution descriptors to assess microcalcifications on mammography during daily practice, we chose to analyze the PPVs of combined morphology and distribution descriptors for the suspicious microcalcifications included this study. Several studies have proposed a systematic approach for predicting malignancy of suspicious microcalcifications using morphology and distribution descriptors.11,12 These studies, however, did not show PPVs for combinations of descriptors, nor did they propose a subcategorization system using these combinations.
Regional Grouped Amorphous
Category 4A Linear Segmental
Coarse heterogeneous
Regional Grouped Linear Segmental
Category 4B
Grouped Fine pleomorphic
Linear Segmental Category 4C
Fine linear or Fine linear branching
Grouped Linear Segmental
FIG. 2 Subcategorization of suspicious microcalcifications according to the combination of morphology and distribution
Based on our results, we suggest subcategorization for suspicious calcifications (Fig. 2). First, amorphous calcifications in regional (PPV 4.2 %) or grouped (PPV 7.6 %) distribution can be classified as category 4A. Second,
S.-Y. Kim et al. TABLE 3 PPVs of 246 suspicious microcalcifications according to the 4th and 5th editions of BI-RADS and in this study Parameter
Pathology
PPV (%)
Benign
Malignant
Intermediate concern
176 (92.1 %)
23 (41.8 %)
11.6
Higher probability of malignancy
15 (7.9 %)
32 (58.2 %)
68.1
Category 4B
191 (100 %)
47 (85.5 %)
19.7
Category 4C
0
8 (14.5 %)
100.0
108 (56.5 %)
8 (14.5 %)
6.9
Category 4B
82 (42.9 %)
24 (43.6 %)
22.6
Category 4C
1 (0.5 %)
23 (41.8 %)
95.8
4th BI-RADSa
5th BI-RADS
b
This studyc Category 4A
a
4th BI-RADS: intermediate concern (amorphous and coarse heterogeneity). Higher probability of malignancy (fine pleomorphism and fine linear or fine linear branching)
b
5th BI-RADS: category 4B (amorphous, coarse heterogeneity, and fine pleomorphism). Category 4C (fine linear branching)
c
This study: as presented in Fig. 2
amorphous calcifications in linear/segmental distribution (PPV 20.0 %) or coarse heterogeneous calcifications regardless of distribution and fine pleomorphic calcifications in grouped distribution (PPV 40.9 %) can be categorized as category 4B. Lastly, fine pleomorphic calcifications in linear/segmental distribution (PPV 93.8 %) and fine linear/fine linear branching calcification, regardless of distribution, should be categorized as 4C. Table 3 summarizes the categorization of suspicious microcalcifications according to the 4th and 5th editions of BI-RADS and the subcategorization using combinations of morphology and distribution descriptors proposed in this study. The subcategorizations we are suggesting may be more feasible than the categorizations suggested by BI-RADS because both the morphology and distribution of microcalcifications are considered. Also, the PPVs of the subcategories proposed in this study are within the range of categories 4A–4C recommended by BI-RADS, further supporting the use of combined morphology and distribution descriptors for risk stratification of suspicious microcalcifications. Our results show a relatively lower PPV (7.9 %) for amorphous calcifications and a higher PPV (63.2 %) for fine pleomorphic calcifications compared to previously published data of PPVs of 21.0 % for amorphous and 29.0 % for fine pleomorphic calcifications.1,4,8–10 In contrast, the 7.9 % PPV for amorphous microcalcifications in our study was in a range similar to those cited in other recent studies, 6.5–9.8 %.12,13 Inter-observer reliability has been reported to be fair for evaluating morphology of calcifications (k = 0.31–0.40),12,14–16 which may have been responsible for the differences in PPVs among studies. In addition, the subdivision of coarse heterogeneous
from fine pleomorphic was not applied in some studies,13,17,18 which may have been the reason for differences in PPVs regarding the morphology descriptor. Further prospective studies including larger study populations are anticipated to validate our results. We acknowledge several limitations to our study. First, unavoidably uneven distributions of suspicious microcalcifications were included in this study, with a high incidence of amorphous morphology and grouped distribution and a low incidence of fine linear/fine linear branching morphology and linear distribution. Second, because of the retrospective study design, case selection bias may have occurred because we included only patients who underwent imaging-guided biopsy or surgery for suspicious microcalcifications. Third, interobserver variability is a well-known problem when characterizing microcalcifications,12,14–16 which may have affected our results. We did not analyze the interobserver variability among the radiologists who had been involved in the imaging analysis. To overcome this problem, consensus was reached after discussion for discrepant cases between the two radiologists involved in the imaging review. CONCLUSIONS Subcategorization of morphology descriptors for suspicious microcalcifications is needed because of the different PPVs in amorphous, coarse heterogeneous, and fine pleomorphic microcalcifications. Combining morphology and distribution descriptors for suspicious microcalcifications provides accurate risk stratification that can be applied when deciding upon further patient management.
Stratification of Microcalcifications DISCLOSURE
The authors declare no conflicts of interest.
REFERENCES 1. American College of Radiology. Breast Imaging Reporting and Data System, 5th edn. Reston: American College of Radiology, 2013. 2. Orel SG, Kay N, Reynolds C, Sullivan DC. BI-RADS categorization as a predictor of malignancy 1. Radiology. 1999;211:845–50. 3. Zonderland HM, Pope Jr TL, Nieborg AJ. The positive predictive value of the Breast Imaging Reporting and Data System (BIRADS) as a method of quality assessment in breast imaging in a hospital population. Eur Radiol. 2004;14:1743–50. 4. Liberman L, Abramson AF, Squires FB, Glassman J, Morris E, Dershaw D. The Breast Imaging Reporting and Data System: positive predictive value of mammographic features and final assessment categories. AJR Am J Roentgenol. 1998;171:35–40. 5. Lacquement MA, Mitchell D, Hollingsworth AB. Positive predictive value of the Breast Imaging Reporting and Data System. J Am Coll Surg. 1999;189:34–40. 6. Obenauer S, Hermann K, Grabbe E. Applications and literature review of the BI-RADS classification. Eur Radiol. 2005;15:1027–36. 7. American College of Radiology. Breast Imaging Reporting and Data System, 4th edn. Reston: American College of Radiology, 2003. 8. Berg WA, Arnoldus CL, Teferra E, Bhargavan M. Biopsy of amorphous breast calcifications: pathologic outcome and yield at stereotactic biopsy 1. Radiology. 2001;221:495–503. 9. Burnside ES, Ochsner JE, Fowler KJ, et al. Use of microcalcification descriptors in BI-RADS 4th edition to stratify risk of malignancy. Radiology. 2007;242:388–95.
10. Bent CK, Bassett LW, D’Orsi CJ, Sayre JW. The positive predictive value of BI-RADS microcalcification descriptors and final assessment categories. AJR Am J Roentgenol. 2010;194:1378–83. 11. Mu¨ller-Schimpfle M, Wersebe A, Xydeas T, et al. Microcalcifications of the breast: how does radiologic classification correlate with histology? Acta Radiol. 2005;46:774–81. 12. Youk JH, Son EJ, Kim JA, et al. Scoring system based on BIRADS lexicon to predict probability of malignancy in suspicious microcalcifications. Ann Surg Oncol. 2012;19:1491–8. 13. Torres-Tabanera M, Ca´rdenas-Rebollo J, Villar-Castan˜o P, et al. Analysis of the positive predictive value of the subcategories of BI-RADSÒ 4 lesions: preliminary results in 880 lesions. Radiologı´a (English Edition). 2012;54:520–31. 14. Berg WA, Campassi C, Langenberg P, Sexton MJ. Breast Imaging Reporting and Data System: inter- and intraobserver variability in feature analysis and final assessment. AJR Am J Roentgenol. 2000;174:1769–77. 15. Gu¨lsu¨n M, Demirkazık FB, Arıyu¨rek M. Evaluation of breast microcalcifications according to Breast Imaging Reporting and Data System criteria and Le Gal’s classification. Eur J Radiol. 2003;47:227–31. 16. Lazarus E, Mainiero MB, Schepps B, Koelliker SL, Livingston LS. BI-RADS lexicon for US and mammography: interobserver variability and positive predictive value 1. Radiology. 2006;239: 385–91. 17. Uematsu T, Kasami M, Yuen S. Usefulness and limitations of the Japan mammography guidelines for the categorization of microcalcifications. Breast Cancer. 2008;15:291–7. 18. Kettritz U, Morack G, Decker T. Stereotactic vacuum-assisted breast biopsies in 500 women with microcalcifications: radiological and pathological correlations. Eur J Radiol. 2005;55:270–6.
