B re a s t M a g n e t i c Re s o n a n c e Imaging Management of an Enhancing Focus Richard Ha, MDa,*, Christopher Comstock, MDb KEYWORDS Breast magnetic resonance imaging Focus Kinetics
KEY POINTS Managing a small enhancing lesion defined as a focus on breast magnetic resonance (MR) imaging remains a challenge because of lack of clear established guidelines. As the spatial resolution of breast MR imaging continues to improve, small lesions measuring 4 to 5 mm can be considered small masses and managed accordingly relying on morphologic characteristics. T2 signal intensity and interval change are potential important characteristics of an enhancing focus with predictive value for malignancy and warrant further investigation in a larger study. Kinetic analysis is likely not specific for malignancy and should not be used solely to guide management of an enhancing focus.
The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) breast magnetic resonance (MR) imaging lexicon defines a focus as a small isolated dot of enhancement, generally less than 5 mm, that is too small to apply definitive morphologic descriptors or region of interest (ROI) dynamic data.1 No set criteria for appropriate management are available in the most recent MR imaging BI-RADS lexicon, which promotes the standardization of lesion descriptors and assessment categories based on the results of the ACR BI-RADS Committee.2,3 Published studies regarding an enhancing focus identified on breast MR imaging are reviewed to develop a possible management strategy.
CLINICAL SIGNIFICANCE OF AN ENHANCING FOCUS Although a focus commonly represents a benign cause, such as an intramammary lymph node, papilloma, small fibroadenoma, or fibrocystic change, malignancy has been reported.4–10 Published literature regarding the malignancy rate of an enhancing focus is variable, ranging from 0.6% to 23%.4–10 A study by Liberman and colleagues in 20064 retrospectively studied 666 consecutive nonpalpable, mammographically occult lesions detected by MR imaging in 429 women who had diagnostic MR imaging–guided needle localization and surgical biopsy at Memorial Sloan Kettering Cancer Center during a 35-month period. Of the lesions,
No grants. No disclosures. a Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, 10th Floor, New York, NY 10032, USA; b Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA * Corresponding author. E-mail address: [email protected] Radiol Clin N Am - (2014) -–http://dx.doi.org/10.1016/j.rcl.2014.01.001 0033-8389/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
radiologic.theclinics.com
INTRODUCTION
2
Ha & Comstock 11.1% (74/666) measured 5 mm or less and could have been categorized as enhancing foci. Of these small lesions, 9.5% (7/74) yielded malignancy on subsequent MR imaging–guided biopsy (pathology of the 7 malignant lesions: 5 ductal carcinoma in situ [DCIS] and 2 invasive ductal carcinoma [IDC]). Excluding the 5-mm lesions, the malignancy rate of lesions measuring 4 mm or less was 2.7% (1/37, pathology: DCIS). Weinstein and colleagues in 20105 published an ACR Imaging Network–conducted, prospective multi-institutional MR imaging screening trial of the contralateral breast in women with recent diagnosis of breast cancer. There were 145 BI-RADS 3 lesions in 106 patients. Of 145 BI-RADS 3 lesions, there were 47 foci of enhancement (32.4%). The 1 patient who developed breast malignancy (DCIS) initially had an enhancing focus that was characterized as probably benign and recommended for short-term follow-up. The overall malignancy rate of foci was 2.1% (1/47). Eby and colleagues in 20096 evaluated lesions assessed as BI-RADS 3. Three hundred sixty-two lesions were assessed in 236 patients. The 362 lesions included 168 (46%) foci. Of 168 foci, a single focus of enhancement initially measuring 5 mm and characterized as probably benign showed enlargement on subsequent MR imaging examinations with MR imaging–guided vacuum-assisted biopsy yielding low-grade DCIS. The overall cancer yield of foci was very low, at 0.6% (1/168). Higher malignancy rates were observed in more recent studies by Abe and colleagues in 2010,8 Jansen and colleagues in 2011,9 and Raza and colleagues in 2012.10 Their malignancy rates in foci ranged from 15% to 20.6%.7 In combining results of these and the previously mentioned 3 studies, the overall malignancy rate of an enhancing focus is 8.4% (39/467), with 21 invasive cancers and 14 DCIS (Table 1).
Based on published literature, it is clear that malignancy can present as an enhancing focus on breast MR imaging measuring 5 mm or less with most being clinically significant invasive cancers (see Table 1). To develop a strategy of managing these lesions, characteristics of an enhancing focus associated with malignancy from those associated with benignity are further evaluated.
CHARACTERISTICS OF FOCI: EXAMINATION INDICATION Raza and colleagues in 201210 retrospectively reviewed 565 lesions that underwent biopsy with MR guidance and identified 68 lesions measuring 5 mm or less in 61 patients. The malignancy rate of lesions measuring 5 mm or less was 20.6%. The highest prevalence of cancers was in the same quadrant as the newly diagnosed breast cancer, emphasizing the importance of the context in which breast lesions are identified and supporting management of additional indeterminate findings in patients with known cancer with a definitive tissue diagnosis rather than shortterm follow-up.
CHARACTERISTICS OF FOCI: KINETIC ANALYSIS Kinetic analysis was reviewed for its potential role in evaluating an enhancing focus. Specifically, the delayed enhancement pattern was analyzed, which has been reported to have high specificity and high positive predictive value for malignancy.11 A study by Eby and colleagues in 20096 investigated breast MR imaging BI-RADS 3 lesions. The 362 BI-RADS 3 lesions included 168 (46%) foci. Of those with kinetic analysis (275 of 362 lesions), 60% showed persistent enhancement, 17%
Table 1 Malignancy rates of an enhancing focus
Study
Number of Foci (£5 mm)
Malignancy Rate, n/N (%)
DCIS
IDC
ILC
IDC/ILC Mixed
Liberman et al,4 2006 Han et al,7 2008 Eby et al,6 2009 Abe et al,8 2010 Weinstein et al,5 2010 Jansen et al,9 2011 Raza et al,10 2012 Total
74 21 168 50 47 39 68 467
7/74 (9.5) 4/21 (19) 1/168 (0.6) 3/50 (15) 1/47 (2.1) 9/39 (23) 14/68 (20.6) 39/467 (8.4)
5 NS 1 1 1 5 1 14
2 NS
NS
NS
0
0 1 2 3
Abbreviation: NS, Not specified.
2 0 3 9 16
2 2
Breast Magnetic Resonance Imaging plateau enhancement, and 23% washout enhancement. All 69 foci (in 54 patients) with persistent enhancement pattern were benign. The 1 malignant focus showed washout enhancement pattern. The investigators concluded that assigning foci with 100% persistent enhancement to the BIRADS 2 category would have decreased the frequency of BI-RADS 3 assessment and maintained a likelihood of malignancy in less than 2% of cases. However, since 2009, several studies have emerged showing significant malignancy potential of persistently enhancing foci, ranging from 11.1% to 18.7%.8–10 One of the studies by Jansen and colleagues in 20119 performed kinetic analysis, yielding a malignancy rate of 18.7% for persistently enhancing foci, 20% for plateau enhancement, and 33.3% for washout enhancement. The delayed enhancement pattern was not specific for malignancy. All 5 studies that investigated the role of kinetic analysis in evaluating an enhancing focus showed no statistical difference between groups of foci with persistent enhancement compared with foci with washout enhancement (Table 2). Additional evaluation comparing groups of foci with persistent enhancement compared with foci with washout enhancement and plateau enhancement also showed no statistical difference (see Table 2). Similarly, kinetic analysis was not specific in our preliminary study performed at Memorial Sloan Kettering Cancer Center (Ha and colleagues, Radiological Society of North America [RSNA] 2011). We identified 2 malignant foci with persistent enhancement pattern and 2 malignant foci with washout enhancement pattern. The 2 groups were not statistically different. In addition, as the 2
malignant foci with the benign appearing enhancement pattern increased in size on follow-up MR imaging examination, the enhancement pattern changed to the expected washout pattern of malignancy. These results suggest that small malignant lesions do not always show expected enhancement pattern related to increased tumor angiogenesis but instead can have a benign appearing enhancement pattern. Until more definitive, larger studies are performed, kinetic analysis is likely not specific for malignancy and should not be used solely to guide management.
CHARACTERISTICS OF FOCI: T2-WEIGHTED SIGNAL INTENSITY Kuhl and colleagues in 199912 performed one of the first studies to investigate the possible role of using T2 signal intensity to improve diagnostic accuracy of lesions identified on breast MR imaging. In this study, 2 independent radiologists rated the lesions (101 malignant, 104 benign) as having either a low or a high T2 signal with respect to the adjacent glandular tissue. Breast cancers were isointense or hypointense with respect to breast parenchyma in 87% of cases and fibroadenomas were hyperintense in 71%. T2 signal intensity was determined to be helpful in distinguishing between fibroadenomas and breast cancers. Malich and colleagues in 200413 also evaluated the potential role of T2-weighted signal intensity in lesion assessment. The study yielded similar results, with most (74%, 313/426) of malignant lesions showing T2 hypointensity and less than 2% (8/426) of malignant lesions showing T2 hyperintensity. These results suggest inherent
Table 2 Kinetic analysis (delayed enhancement pattern)
Study Han et al,7 2008 Eby et al,6 2009 Abe et al,8 2010 Jansen et al,9 2011 Raza et al,10 2012
Type I Curve with Cancer, n/N (%)
Type II Curve with Cancer, n/N (%)
Type III Curve with Cancer, n/N (%)
Type I Curve vs Type III Curvea
Type I Curve vs Type II D III Curvea
0/6 (0)
2/9 (22.2)
0/1 (0)
P 5 1.0
P 5 .500
0/69 (0)
0/21 (0)
1/30 (3.3)
P 5 .30
P 5 .4250
1/7 (14.3)
0/29 (0)
2/14 (14.3)
P 5 1.0
P 5 .3704
3/16 (18.7)
2/10 (20)
2/6 (33.3)
P 5 .5853
P 5 1.0
5/27 (18.5)
2/21 (9.5)
7/20 (35)
P 5 .3111
P 5 1.0
Type I curve, persistent enhancement pattern; type II curve, plateau enhancement pattern; type III curve, washout enhancement pattern. a Statistical analysis (Fisher exact test, significant if 2-tailed P value .05).
3
4
Ha & Comstock differences in internal composition of malignant lesions that lack signal intensity on T2-weighted images and support categorizing an enhancing focus with T2 hyperintensity as benign. There are reported cases of breast cancers that can show areas of high T2 signal intensity, including triple-negative tumors, mucinous tumors, and papillary carcinomas.14–16 However, the lesions in these studies were not foci but larger masses, and in triple-negative cancers, the large irregular areas of high T2 signal intensity pathologically correlated with internal necrosis and not necessarily the lesion itself. More studies are needed to determine if an enhancing focus with a corresponding T2 hyperintensity can be managed as a benign finding, which could decrease unnecessary follow-up studies, whereas an enhancing focus with T2 hypointensity may warrant at least short-term follow-up if not managed by a biopsy.
CHARACTERISTICS OF FOCI: SIZE Since the introduction of the term focus defined as “a small isolated dot of enhancement, generally less than 5 mm in size, that is too small to apply definitive morphologic descriptors or ROI dynamic data” in the MR imaging lexicon in 2003, there have been ongoing technical advances in breast MR imaging, resulting in improved spatial resolution.17–19 As a result, morphologic features can sometimes be evaluated in small lesions measuring 5 mm or less. A study by Raza and colleagues10 showed that margin could be defined as irregular or spiculated in 60.3% (41/68) of malignant foci that were identified in their study. With expected continued improvement in resolution, lesions measuring 4 to 5 mm could be defined as small masses and lesions measuring 3 mm or less as foci. This development would be in keeping with the intended definition of a focus, which is an enhancing lesion that is too small to characterize with low malignancy potential.
CHARACTERISTICS OF FOCI: INTERVAL CHANGE AND NUMBER Interval change is another characteristic to consider, especially in patients undergoing breast MR imaging for high-risk screening. Our preliminary study (Ha and colleagues, RSNA 2011) performed at Memorial Sloan Kettering Cancer Center shows significant malignant potential of an enhancing focus that is either new or enlarging. When combined with T2 hypointensity, the malignancy rate was as high as 27.2%, indicating the need for biopsy rather than short-term follow-up.
Also in our preliminary study, malignancy was identified only when 1 or 2 discrete foci were followed. No malignancy was present when 3 or more similar appearing foci were present on the initial breast MR imaging. As more foci are present, these are probably no longer unique and are often described as being part of the normal background parenchymal enhancement, previously described as a stippled pattern, with low likelihood of malignancy. In the new updated lexicon, the enhancing focus will be described as a unique finding, separate from background parenchymal enhancement (Morris MD, updated breast MR imaging lexicon, personal communication, 2013).
SUMMARY Managing a small enhancing lesion defined as a focus on breast MR imaging remains a challenge because of lack of clear established guidelines. More studies are needed that distinguish specific characteristics of an enhancing focus associated with malignancy from those associated with benignity to determine appropriate management criteria. As the spatial resolution of breast MR imaging continues to improve, small lesions measuring 4 to 5 mm may be considered small masses and managed accordingly, relying on morphologic characteristics. Otherwise, T2 signal intensity and interval change are potential important characteristics with predictive value for malignancy and warrant further investigation in a larger sample size. Kinetic analysis is likely not specific for malignancy and should not be used solely to guide management of an enhancing focus.
REFERENCES 1. American College of Radiology. Breast imaging reporting and data system (BI-RADS). 4th edition. Reston (VA): American College of Radiology; 2003. 2. Ikeda DM, Baker DR, Daniel BL. Magnetic resonance imaging of breast cancer: clinical indications and breast MRI reporting system [review]. J Magn Reson Imaging 2000;12(6):975–83. 3. Ikeda DM, Hylton NM, Kinkel K, et al. Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies. J Magn Reson Imaging 2001;13: 889–95. 4. Liberman L, Mason G, Morris EA, et al. Does size matter? Positive predictive value of MRI-detected breast lesions as a function of lesion size. AJR Am J Roentgenol 2006;186:426–30. 5. Weinstein SP, Hanna LG, Gatsonis C, et al. Frequency of malignancy seen in probably benign lesions at
Breast Magnetic Resonance Imaging
6.
7.
8.
9.
10.
11.
12.
contrast-enhanced breast MR imaging: findings from ACRIN 6667. Radiology 2010;255(3):731–7. Eby PR, DeMartini WB, Gutierrez RL, et al. Characteristics of probably benign breast MRI lesions. AJR Am J Roentgenol 2009;193(3):861–7. Han BK, Schnall MD, Orel SG, et al. Outcome of MRI-guided breast biopsy. AJR Am J Roentgenol 2008;191(6):1798–804. Abe H, Schmidt RA, Shah RN, et al. MR-directed (“second-look”) ultrasound examination for breast lesions detected initially on MRI: MR and sonographic findings. AJR Am J Roentgenol 2010;194(2):370–7. Jansen SA, Shimauchi A, Zak L, et al. The diverse pathology and kinetics of mass, nonmass, and focus enhancement on MR imaging of the breast. J Magn Reson Imaging 2011;33(6):1382–9. Raza S, Sekar M, Ong EM, et al. Small masses on breast MR: is biopsy necessary? Acad Radiol 2012;19(4):412–9. Kuhl CK, Schild HH, Morakkabati N. Dynamic bilateral contrast-enhanced MR imaging of the breast: trade-off between spatial and temporal resolution. Radiology 2005;236(3):789–800. Kuhl CK, Klaschik S, Mielcarek P, et al. Do T2weighted pulse sequences help with the differential diagnosis of enhancing lesions in dynamic breast MRI? J Magn Reson Imaging 1999;9(2):187–96.
13. Malich A, Fischer DR, Wurdinger S, et al. Potential MRI interpretation model: differentiation of benign from malignant breast masses. AJR Am J Roentgenol 2005;185(4):964–70. 14. Uematsu T, Kasami M, Yuen S. Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology 2009;250(3): 638–47. 15. Gu¨nhan-Bilgen I, Zekioglu O, Ustu¨n EE, et al. Invasive micropapillary carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation. AJR Am J Roentgenol 2002;179(4):927–31. 16. Monzawa S, Yokokawa M, Sakuma T, et al. Mucinous carcinoma of the breast: MRI features of pure and mixed forms with histopathologic correlation. AJR Am J Roentgenol 2009;192(3):W125–31. 17. Kuhl CK. Breast MR imaging at 3T. Magn Reson Imaging Clin N Am 2007;15(3):315–20. 18. Nnewihe AN, Grafendorfer T, Daniel BL, et al. Custom-fitted 16-channel bilateral breast coil for bidirectional parallel imaging. Magn Reson Med 2011;66(1):281–9. 19. Elsamaloty H, Elzawawi MS, Mohammad S, et al. Increasing accuracy of detection of breast cancer with 3-T MRI. AJR Am J Roentgenol 2009;192(4): 1142–8, J Magn Reson Imaging 1999;9(2):187–96.
5
KEY POINTS Managing a small enhancing lesion defined as a focus on breast magnetic resonance (MR) imaging remains a challenge because of lack of clear established guidelines. As the spatial resolution of breast MR imaging continues to improve, small lesions measuring 4 to 5 mm can be considered small masses and managed accordingly relying on morphologic characteristics. T2 signal intensity and interval change are potential important characteristics of an enhancing focus with predictive value for malignancy and warrant further investigation in a larger study. Kinetic analysis is likely not specific for malignancy and should not be used solely to guide management of an enhancing focus.
The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) breast magnetic resonance (MR) imaging lexicon defines a focus as a small isolated dot of enhancement, generally less than 5 mm, that is too small to apply definitive morphologic descriptors or region of interest (ROI) dynamic data.1 No set criteria for appropriate management are available in the most recent MR imaging BI-RADS lexicon, which promotes the standardization of lesion descriptors and assessment categories based on the results of the ACR BI-RADS Committee.2,3 Published studies regarding an enhancing focus identified on breast MR imaging are reviewed to develop a possible management strategy.
CLINICAL SIGNIFICANCE OF AN ENHANCING FOCUS Although a focus commonly represents a benign cause, such as an intramammary lymph node, papilloma, small fibroadenoma, or fibrocystic change, malignancy has been reported.4–10 Published literature regarding the malignancy rate of an enhancing focus is variable, ranging from 0.6% to 23%.4–10 A study by Liberman and colleagues in 20064 retrospectively studied 666 consecutive nonpalpable, mammographically occult lesions detected by MR imaging in 429 women who had diagnostic MR imaging–guided needle localization and surgical biopsy at Memorial Sloan Kettering Cancer Center during a 35-month period. Of the lesions,
No grants. No disclosures. a Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, 10th Floor, New York, NY 10032, USA; b Memorial Sloan Kettering Cancer Center, 300 East 66th Street, New York, NY 10065, USA * Corresponding author. E-mail address: [email protected] Radiol Clin N Am - (2014) -–http://dx.doi.org/10.1016/j.rcl.2014.01.001 0033-8389/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
radiologic.theclinics.com
INTRODUCTION
2
Ha & Comstock 11.1% (74/666) measured 5 mm or less and could have been categorized as enhancing foci. Of these small lesions, 9.5% (7/74) yielded malignancy on subsequent MR imaging–guided biopsy (pathology of the 7 malignant lesions: 5 ductal carcinoma in situ [DCIS] and 2 invasive ductal carcinoma [IDC]). Excluding the 5-mm lesions, the malignancy rate of lesions measuring 4 mm or less was 2.7% (1/37, pathology: DCIS). Weinstein and colleagues in 20105 published an ACR Imaging Network–conducted, prospective multi-institutional MR imaging screening trial of the contralateral breast in women with recent diagnosis of breast cancer. There were 145 BI-RADS 3 lesions in 106 patients. Of 145 BI-RADS 3 lesions, there were 47 foci of enhancement (32.4%). The 1 patient who developed breast malignancy (DCIS) initially had an enhancing focus that was characterized as probably benign and recommended for short-term follow-up. The overall malignancy rate of foci was 2.1% (1/47). Eby and colleagues in 20096 evaluated lesions assessed as BI-RADS 3. Three hundred sixty-two lesions were assessed in 236 patients. The 362 lesions included 168 (46%) foci. Of 168 foci, a single focus of enhancement initially measuring 5 mm and characterized as probably benign showed enlargement on subsequent MR imaging examinations with MR imaging–guided vacuum-assisted biopsy yielding low-grade DCIS. The overall cancer yield of foci was very low, at 0.6% (1/168). Higher malignancy rates were observed in more recent studies by Abe and colleagues in 2010,8 Jansen and colleagues in 2011,9 and Raza and colleagues in 2012.10 Their malignancy rates in foci ranged from 15% to 20.6%.7 In combining results of these and the previously mentioned 3 studies, the overall malignancy rate of an enhancing focus is 8.4% (39/467), with 21 invasive cancers and 14 DCIS (Table 1).
Based on published literature, it is clear that malignancy can present as an enhancing focus on breast MR imaging measuring 5 mm or less with most being clinically significant invasive cancers (see Table 1). To develop a strategy of managing these lesions, characteristics of an enhancing focus associated with malignancy from those associated with benignity are further evaluated.
CHARACTERISTICS OF FOCI: EXAMINATION INDICATION Raza and colleagues in 201210 retrospectively reviewed 565 lesions that underwent biopsy with MR guidance and identified 68 lesions measuring 5 mm or less in 61 patients. The malignancy rate of lesions measuring 5 mm or less was 20.6%. The highest prevalence of cancers was in the same quadrant as the newly diagnosed breast cancer, emphasizing the importance of the context in which breast lesions are identified and supporting management of additional indeterminate findings in patients with known cancer with a definitive tissue diagnosis rather than shortterm follow-up.
CHARACTERISTICS OF FOCI: KINETIC ANALYSIS Kinetic analysis was reviewed for its potential role in evaluating an enhancing focus. Specifically, the delayed enhancement pattern was analyzed, which has been reported to have high specificity and high positive predictive value for malignancy.11 A study by Eby and colleagues in 20096 investigated breast MR imaging BI-RADS 3 lesions. The 362 BI-RADS 3 lesions included 168 (46%) foci. Of those with kinetic analysis (275 of 362 lesions), 60% showed persistent enhancement, 17%
Table 1 Malignancy rates of an enhancing focus
Study
Number of Foci (£5 mm)
Malignancy Rate, n/N (%)
DCIS
IDC
ILC
IDC/ILC Mixed
Liberman et al,4 2006 Han et al,7 2008 Eby et al,6 2009 Abe et al,8 2010 Weinstein et al,5 2010 Jansen et al,9 2011 Raza et al,10 2012 Total
74 21 168 50 47 39 68 467
7/74 (9.5) 4/21 (19) 1/168 (0.6) 3/50 (15) 1/47 (2.1) 9/39 (23) 14/68 (20.6) 39/467 (8.4)
5 NS 1 1 1 5 1 14
2 NS
NS
NS
0
0 1 2 3
Abbreviation: NS, Not specified.
2 0 3 9 16
2 2
Breast Magnetic Resonance Imaging plateau enhancement, and 23% washout enhancement. All 69 foci (in 54 patients) with persistent enhancement pattern were benign. The 1 malignant focus showed washout enhancement pattern. The investigators concluded that assigning foci with 100% persistent enhancement to the BIRADS 2 category would have decreased the frequency of BI-RADS 3 assessment and maintained a likelihood of malignancy in less than 2% of cases. However, since 2009, several studies have emerged showing significant malignancy potential of persistently enhancing foci, ranging from 11.1% to 18.7%.8–10 One of the studies by Jansen and colleagues in 20119 performed kinetic analysis, yielding a malignancy rate of 18.7% for persistently enhancing foci, 20% for plateau enhancement, and 33.3% for washout enhancement. The delayed enhancement pattern was not specific for malignancy. All 5 studies that investigated the role of kinetic analysis in evaluating an enhancing focus showed no statistical difference between groups of foci with persistent enhancement compared with foci with washout enhancement (Table 2). Additional evaluation comparing groups of foci with persistent enhancement compared with foci with washout enhancement and plateau enhancement also showed no statistical difference (see Table 2). Similarly, kinetic analysis was not specific in our preliminary study performed at Memorial Sloan Kettering Cancer Center (Ha and colleagues, Radiological Society of North America [RSNA] 2011). We identified 2 malignant foci with persistent enhancement pattern and 2 malignant foci with washout enhancement pattern. The 2 groups were not statistically different. In addition, as the 2
malignant foci with the benign appearing enhancement pattern increased in size on follow-up MR imaging examination, the enhancement pattern changed to the expected washout pattern of malignancy. These results suggest that small malignant lesions do not always show expected enhancement pattern related to increased tumor angiogenesis but instead can have a benign appearing enhancement pattern. Until more definitive, larger studies are performed, kinetic analysis is likely not specific for malignancy and should not be used solely to guide management.
CHARACTERISTICS OF FOCI: T2-WEIGHTED SIGNAL INTENSITY Kuhl and colleagues in 199912 performed one of the first studies to investigate the possible role of using T2 signal intensity to improve diagnostic accuracy of lesions identified on breast MR imaging. In this study, 2 independent radiologists rated the lesions (101 malignant, 104 benign) as having either a low or a high T2 signal with respect to the adjacent glandular tissue. Breast cancers were isointense or hypointense with respect to breast parenchyma in 87% of cases and fibroadenomas were hyperintense in 71%. T2 signal intensity was determined to be helpful in distinguishing between fibroadenomas and breast cancers. Malich and colleagues in 200413 also evaluated the potential role of T2-weighted signal intensity in lesion assessment. The study yielded similar results, with most (74%, 313/426) of malignant lesions showing T2 hypointensity and less than 2% (8/426) of malignant lesions showing T2 hyperintensity. These results suggest inherent
Table 2 Kinetic analysis (delayed enhancement pattern)
Study Han et al,7 2008 Eby et al,6 2009 Abe et al,8 2010 Jansen et al,9 2011 Raza et al,10 2012
Type I Curve with Cancer, n/N (%)
Type II Curve with Cancer, n/N (%)
Type III Curve with Cancer, n/N (%)
Type I Curve vs Type III Curvea
Type I Curve vs Type II D III Curvea
0/6 (0)
2/9 (22.2)
0/1 (0)
P 5 1.0
P 5 .500
0/69 (0)
0/21 (0)
1/30 (3.3)
P 5 .30
P 5 .4250
1/7 (14.3)
0/29 (0)
2/14 (14.3)
P 5 1.0
P 5 .3704
3/16 (18.7)
2/10 (20)
2/6 (33.3)
P 5 .5853
P 5 1.0
5/27 (18.5)
2/21 (9.5)
7/20 (35)
P 5 .3111
P 5 1.0
Type I curve, persistent enhancement pattern; type II curve, plateau enhancement pattern; type III curve, washout enhancement pattern. a Statistical analysis (Fisher exact test, significant if 2-tailed P value .05).
3
4
Ha & Comstock differences in internal composition of malignant lesions that lack signal intensity on T2-weighted images and support categorizing an enhancing focus with T2 hyperintensity as benign. There are reported cases of breast cancers that can show areas of high T2 signal intensity, including triple-negative tumors, mucinous tumors, and papillary carcinomas.14–16 However, the lesions in these studies were not foci but larger masses, and in triple-negative cancers, the large irregular areas of high T2 signal intensity pathologically correlated with internal necrosis and not necessarily the lesion itself. More studies are needed to determine if an enhancing focus with a corresponding T2 hyperintensity can be managed as a benign finding, which could decrease unnecessary follow-up studies, whereas an enhancing focus with T2 hypointensity may warrant at least short-term follow-up if not managed by a biopsy.
CHARACTERISTICS OF FOCI: SIZE Since the introduction of the term focus defined as “a small isolated dot of enhancement, generally less than 5 mm in size, that is too small to apply definitive morphologic descriptors or ROI dynamic data” in the MR imaging lexicon in 2003, there have been ongoing technical advances in breast MR imaging, resulting in improved spatial resolution.17–19 As a result, morphologic features can sometimes be evaluated in small lesions measuring 5 mm or less. A study by Raza and colleagues10 showed that margin could be defined as irregular or spiculated in 60.3% (41/68) of malignant foci that were identified in their study. With expected continued improvement in resolution, lesions measuring 4 to 5 mm could be defined as small masses and lesions measuring 3 mm or less as foci. This development would be in keeping with the intended definition of a focus, which is an enhancing lesion that is too small to characterize with low malignancy potential.
CHARACTERISTICS OF FOCI: INTERVAL CHANGE AND NUMBER Interval change is another characteristic to consider, especially in patients undergoing breast MR imaging for high-risk screening. Our preliminary study (Ha and colleagues, RSNA 2011) performed at Memorial Sloan Kettering Cancer Center shows significant malignant potential of an enhancing focus that is either new or enlarging. When combined with T2 hypointensity, the malignancy rate was as high as 27.2%, indicating the need for biopsy rather than short-term follow-up.
Also in our preliminary study, malignancy was identified only when 1 or 2 discrete foci were followed. No malignancy was present when 3 or more similar appearing foci were present on the initial breast MR imaging. As more foci are present, these are probably no longer unique and are often described as being part of the normal background parenchymal enhancement, previously described as a stippled pattern, with low likelihood of malignancy. In the new updated lexicon, the enhancing focus will be described as a unique finding, separate from background parenchymal enhancement (Morris MD, updated breast MR imaging lexicon, personal communication, 2013).
SUMMARY Managing a small enhancing lesion defined as a focus on breast MR imaging remains a challenge because of lack of clear established guidelines. More studies are needed that distinguish specific characteristics of an enhancing focus associated with malignancy from those associated with benignity to determine appropriate management criteria. As the spatial resolution of breast MR imaging continues to improve, small lesions measuring 4 to 5 mm may be considered small masses and managed accordingly, relying on morphologic characteristics. Otherwise, T2 signal intensity and interval change are potential important characteristics with predictive value for malignancy and warrant further investigation in a larger sample size. Kinetic analysis is likely not specific for malignancy and should not be used solely to guide management of an enhancing focus.
REFERENCES 1. American College of Radiology. Breast imaging reporting and data system (BI-RADS). 4th edition. Reston (VA): American College of Radiology; 2003. 2. Ikeda DM, Baker DR, Daniel BL. Magnetic resonance imaging of breast cancer: clinical indications and breast MRI reporting system [review]. J Magn Reson Imaging 2000;12(6):975–83. 3. Ikeda DM, Hylton NM, Kinkel K, et al. Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies. J Magn Reson Imaging 2001;13: 889–95. 4. Liberman L, Mason G, Morris EA, et al. Does size matter? Positive predictive value of MRI-detected breast lesions as a function of lesion size. AJR Am J Roentgenol 2006;186:426–30. 5. Weinstein SP, Hanna LG, Gatsonis C, et al. Frequency of malignancy seen in probably benign lesions at
Breast Magnetic Resonance Imaging
6.
7.
8.
9.
10.
11.
12.
contrast-enhanced breast MR imaging: findings from ACRIN 6667. Radiology 2010;255(3):731–7. Eby PR, DeMartini WB, Gutierrez RL, et al. Characteristics of probably benign breast MRI lesions. AJR Am J Roentgenol 2009;193(3):861–7. Han BK, Schnall MD, Orel SG, et al. Outcome of MRI-guided breast biopsy. AJR Am J Roentgenol 2008;191(6):1798–804. Abe H, Schmidt RA, Shah RN, et al. MR-directed (“second-look”) ultrasound examination for breast lesions detected initially on MRI: MR and sonographic findings. AJR Am J Roentgenol 2010;194(2):370–7. Jansen SA, Shimauchi A, Zak L, et al. The diverse pathology and kinetics of mass, nonmass, and focus enhancement on MR imaging of the breast. J Magn Reson Imaging 2011;33(6):1382–9. Raza S, Sekar M, Ong EM, et al. Small masses on breast MR: is biopsy necessary? Acad Radiol 2012;19(4):412–9. Kuhl CK, Schild HH, Morakkabati N. Dynamic bilateral contrast-enhanced MR imaging of the breast: trade-off between spatial and temporal resolution. Radiology 2005;236(3):789–800. Kuhl CK, Klaschik S, Mielcarek P, et al. Do T2weighted pulse sequences help with the differential diagnosis of enhancing lesions in dynamic breast MRI? J Magn Reson Imaging 1999;9(2):187–96.
13. Malich A, Fischer DR, Wurdinger S, et al. Potential MRI interpretation model: differentiation of benign from malignant breast masses. AJR Am J Roentgenol 2005;185(4):964–70. 14. Uematsu T, Kasami M, Yuen S. Triple-negative breast cancer: correlation between MR imaging and pathologic findings. Radiology 2009;250(3): 638–47. 15. Gu¨nhan-Bilgen I, Zekioglu O, Ustu¨n EE, et al. Invasive micropapillary carcinoma of the breast: clinical, mammographic, and sonographic findings with histopathologic correlation. AJR Am J Roentgenol 2002;179(4):927–31. 16. Monzawa S, Yokokawa M, Sakuma T, et al. Mucinous carcinoma of the breast: MRI features of pure and mixed forms with histopathologic correlation. AJR Am J Roentgenol 2009;192(3):W125–31. 17. Kuhl CK. Breast MR imaging at 3T. Magn Reson Imaging Clin N Am 2007;15(3):315–20. 18. Nnewihe AN, Grafendorfer T, Daniel BL, et al. Custom-fitted 16-channel bilateral breast coil for bidirectional parallel imaging. Magn Reson Med 2011;66(1):281–9. 19. Elsamaloty H, Elzawawi MS, Mohammad S, et al. Increasing accuracy of detection of breast cancer with 3-T MRI. AJR Am J Roentgenol 2009;192(4): 1142–8, J Magn Reson Imaging 1999;9(2):187–96.
5
