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Magnetic Resonance Imaging of Breast Cancer: Factors Affecting The Accuracy of Preoperative Lesion Sizing
Magnetic Resonance Imaging of Breast Cancer: Factors Affecting The Accuracy of Preoperative Lesion Sizing
Acta Radiologica
2015, Vol. 56(3) 260–268
! The Foundation Acta Radiologica
Magnetic resonance imaging of breast 2014
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DOI: 10.1177/0284185114524089
of preoperative lesion sizing acr.sagepub.com
Abstract
Background: Accurate preoperative sizing of breast cancer with imaging modalities has a great importance in the
surgical planning.
Purpose: To assess the influence of tumor size and histology on the accuracy of measurement of cancer local extension
by magnetic resonance imaging (MRI).
Material and Methods: One hundred and eighty-six patients with primary breast cancer, for a total of 221 lesions,
were included in this retrospective study. Tumors were divided into five histological groups: invasive ductal carcinoma
(IDC), IDC with extensive intraductal component (EIC), invasive lobular carcinoma (ILC), ductal carcinoma in situ
(DCIS), and ‘‘other histology’’ (mucinous, papillary, medullary, tubular, and apocrine breast cancer). Microscopic meas-
urement of the largest diameter of tumors at pathology was chosen as reference standard and compared with MRI
measurement. Concordance was defined as a difference 5 mm between MRI and pathology.
Results: The mean size of tumors at pathology was 24.8 19.4 mm, while at MRI it was 29.7 20 mm (P < 0.05), with a
significant overestimation of MRI. MRI–pathology concordance was found in 98/221 cases (44.3%), while MRI over-
estimated the size of 81/221 tumors (36.7%). The extent of overestimation was significantly different among the five
histological groups (P < 0.05). At multivariate analysis, DCIS histology was the factor more significantly associated with
MRI–pathology discordance (P ¼ 0.0005), while the influence of tumor dimension at pathology was less significant
(P ¼ 0.0073).
Conclusion: DCIS histology is strongly associated with discordance between MRI and pathology sizing of breast cancer.
Lesion size can also influence the accuracy of MRI measurements, but to a lesser extent.
Keywords
MRI, invasive breast cancer, ductal carcinoma in situ, tumor size, pathology
Date received: 22 September 2013; accepted: 24 January 2014
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Mennella et al. 261
surgical planning to evaluate the local extent of the clear and precise measurement of the largest diameter
disease and to assess the presence of synchronous of the lesion size in the postoperative pathology report
tumors. The potential for under- or overestimation of were excluded.
tumor size on MR images has been investigated in dif-
ferent previous studies, which yielded mixed results
(4–9). In more recent works (8,9), there is evidence
that lesion size can influence the accuracy of MRI
Pathology
measurements. In a retrospective study on 77 patients, Histopathological reports of all enrolled patients were
Onesti et al. (8) compared the preoperative tumor size retrieved from our institutional pathology database
measured on MR images to the tumor size at final path- and carefully reviewed. Patients with bilateral, multi-
ology. Stratifying their patient cohort according to the focal, and multicentric lesions were identified. The
MRI tumor size ( 2.0 cm and >2.0 cm), the authors presence of two or more foci of cancer within the
found a greater difference between the two measure- same breast quadrant was defined as multifocal dis-
ments (i.e. MRI/pathology difference) in the group of ease, while the presence of two or more foci of cancer
lesions larger than 2.0 cm. in different quadrants of the same breast was defined
Grimsby et al. (9) investigated on 190 patients the as multicentric disease. Tumors were classified accord-
correlation between MRI and pathology tumor sizing, ing to five histological subgroups, including invasive
finding concordance within 0.5 cm in 53% of cases, ductal carcinoma (IDC), invasive ductal carcinoma
while MRI overestimated 33% and underestimated with extensive intraductal component (EIC), invasive
15% of tumors. Among tumors overestimated by lobular carcinoma (ILC), ductal carcinoma in situ
MRI, 65% had additional significant findings in the (DCIS), and other histological types (mixed IDC/
breast tissue around the main lesion: satellite lesions, ILC, mucinous, papillary, medullary, tubular, and
DCIS, and/or lymphovascular invasion, but tumor apocrine breast carcinoma). The second subgroup,
histology was not found to be a source of discordance represented by EIC, was defined, according to Berg
between MRI and pathology tumor sizing. The aim of et al. (10), as ductal carcinoma with an invasive com-
our study was to re-assess on a large number of lesions ponent, where at least 25% of the tumor was DCIS
the hypothesis that histological subtype may influence with or without additional discrete foci of DCIS out-
the discrepancy between MRI and pathology measure- side the main tumor mass. Consistent with the
ments. The second objective was to verify if the discrep- common practice of the pathology service of our insti-
ancy between MRI and pathology tumor sizing is tution, all surgical specimens were received with orien-
more affected by tumor dimensions or histological tation and examined in fresh state. Specimens were cut
subtype. into 5-mm thick levels along their longest axis (i.e.
5-mm slicing technique), according to Egan et al.
(11). Formalin fixation happened only after the cut
sections of each specimen were obtained. In this
Material and Methods
way, tissue shrinkage and the potential change in
This was a retrospective, single-center, institutional size of tumors did not occur as a result of specimen
review board approved study within a breast surgery fixation prior to cut. The measurements were then
specialty practice. All women who had a newly diag- calculated by multiplying number of levels showing
nosed, biopsy-proven, primary breast cancer with a cancer by the thickness of each level. In situ compo-
positive MRI before surgical treatment were identified nents were included in the analysis. The largest dimen-
by performing a search in our single-institution radi- sion of tumor size was used as reference standard. In
ology database from January 2007 to December 2012. the case of multifocal disease, the final pathology size
Different data were collected for all patients, including was obtained by summing the major microscopic
age, tumor size on both MRI and final pathology, dimension of different tumor foci within the same
histological characteristics of the tumor, type of surgi- breast quadrant. On the other hand, in the case of
cal intervention (i.e. lumpectomy, quadrantectomy, or multicentric disease, different tumor foci were con-
mastectomy), and the presence of neoadjuvant chemo- sidered and measured as separate lesions.
therapy. Patients who received neoadjuvant chemother-
apy before surgery were excluded, since it has been
previously demonstrated that this factor is a source of
MRI technique
discordance between preoperative MRI tumor sizing
and final pathology measurements (9). To compare Written informed consent was obtained from all
cancer sizing by MRI with pathology, only the largest patients before MRI. Breast MRI examinations were
diameter of lesion size was used. Patients without a performed on a 1.5 T MRI scanner (Avanto, Siemens,
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262 Acta Radiologica 56(3)
Erlangen, Germany) with the patient in the prone pos- lesions from surrounding parenchyma (12). On the
ition in a dedicated phased-array breast coil, using the other hand, what should be the best time interval for
following MRI protocol: performing MRI after a biopsy procedure remains
unclear, and no previous work has given a precise
. T2-weighted Turbo Inversion Recovery Magnitude response to this question. On the use of MRI in assess-
(TIRM) axial sequence (repetition time, 8950.00 ms; ing residual disease after positive tumor margins in
echo time, 87.00 ms; matrix size, 380 384; elliptical breast-conserving surgery, EUSOBI (European
filter; slice thickness, 4.00 mm; interval, 0.00 mm; dis- Society of Breast Imaging) suggests to respect a time
tance factor, 25%; overlapping, 1 mm; field of view interval of 1 month between surgery and diagnostic
[FOV], 340 mm; FOV phase, 100%; flip angle, 120 ; MRI (13), since postsurgical inflammatory edema can
voxel size, 0.9 0.9 1.6 mm) artificially increase lesion’s size. In the case of VABB,
. T1-weighted (T1W) three-dimensional (3D) fat- which can be considered quite an invasive procedure,
suppressed FLASH (fast low-angle shot pulse we routinely respect this time interval of 1 month.
sequence) imaging of both breasts in the axial
plane (repetition time, 3.99 ms; echo time, 1.36 ms;
flip angle, 12 ; single acquisition of signal; rectangu-
Interpretation of MRI examinations
lar FOV, 32–36 cm; matrix size, 400 400; slice All breast MRI examinations were reviewed in consen-
thickness, 1.6 mm; interval, 0.00 mm). Contrast- sus on a dedicated workstation by two radiologists (AG
enhanced dynamic breast MRI was performed with and TM) with 8 and 20 years of experience in the field
the acquisition of one precontrast 3D FLASH of breast diseases, who had access to previous imaging
sequence and five sequences during the intravenous records of each patient.
injection of paramagnetic contrast medium The dynamic sequence was examined with subtrac-
(0.1 mmol/kg of gadobenate dimeglumine [Gd- tion and maximum intensity projection (MIP) tech-
BOPTA]). Imaging volumes were acquired at 1, 2, niques. Time-enhancement kinetic curves were
3, 4, and 5 min after injection. Contrast medium generated to assist in the interpretation. Cancer exten-
speed injection was standardized at 3 mL/s and fol- sion on MR images was defined in the early phase of
lowed by injection of a 20 mL saline flush at same dynamic studies as well-enhanced areas, including
flow rate. linear or clumped enhanced areas, according to
Kuroki et al. (6). The greatest dimension of tumor
The overall acquisition time of the MRI protocol was size was measured by means of an electronic
17–20 min. It is well known that increased enhancement digital caliper and compared with the microscopic size
after biopsy can make it difficult to differentiate breast (Figs. 1 and 2).
Fig. 1. Transverse T1W 3D FLASH subtraction MR image (a) shows an irregular-shaped periareolar lesion in the left breast, with a
largest diameter of 80.12 mm. (b) The surgical specimen. (c) The histopathologic section (hematoxylin and eosin, 10x) reveals an
invasive ductal carcinoma not otherwise specified with high grade of nuclear polymorphism, low grade of differentiation (Nottingham
grading: G3), and no appreciable intraductal spread (DCIS component < 25%). It was ER (estrogen-receptor) negative, and Ki-67
positive (proliferative activity: 42%).
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Mennella et al. 263
Fig. 2. Transverse T1W 3D FLASH subtraction MR image (a) shows a lobulated lesion in the outer quadrants of the right breast, with
a largest diameter of 26.49 mm. (b) The surgical specimen. (c) The histopathologic section (hematoxylin and eosin, 20x) reveals an
invasive lobular carcinoma with the typical pattern of linear growth. It is characterized by high grade of nuclear polymorphism, low
grade of differentiation (Nottingham grading: G3), negativity for ER (estrogen receptors), and positivity for Ki-67 (proliferative
activity: 15%).
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264 Acta Radiologica 56(3)
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Mennella et al. 265
Fig. 4. Bland-Altman plots for Group 1 (lesions 20 mm) (a) and Group 2 (lesions > 20 mm) (b). The graphs display a scatter diagram
of the differences plotted against the averages of the two measurements. Horizontal lines are drawn at the mean difference, and at the
limits of agreement, which are defined as the mean difference plus and minus 1.96 times the standard deviation of the differences. The
mean difference between MRI and pathology sizing is greater for Group 1 than for Group 2.
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266 Acta Radiologica 56(3)
histological type, do not seem to influence MRI–path- DCIS, and/or lymphovascular invasion in tissue sur-
ology discordance. However, the authors did not per- rounding the main tumor. This observation encouraged
form a multivariate or logistic regression analysis. In us to consider tumors with an extensive intraductal
the present study, we aimed to assess, on a relatively component (EIC) as a distinct histological group,
large number of primary breast carcinomas (i.e. 221 according to Berg et al. (10). There is a robust evidence
lesions), what is the best predictor of MRI–pathology that two major limitations of breast MRI are a signifi-
discordance between tumor size and histology. Both cant rate of false positives (16–21), and a trend of over-
EIC and DCIS lesions were well represented in our estimation of lesion’s size by MRI (8,9). In previous
study cohort (10.41% and 13.57%, respectively), thus studies (6,20), lesions with ‘‘non-mass-like’’ enhance-
allowing us to assess the influence of an ‘‘in situ’’ com- ment were identified as a challenging subgroup causing
ponent on the accuracy of MRI measurements. We a high proportion of false-positive diagnoses at diag-
found that MRI overestimated the size of 81/221 nostic breast MRI. To this regard, MR-directed
tumors (36.7%); this figure of overestimation is similar ‘‘second-look’’ US may help in avoiding false positives
to those reported by Onesti et al. (8) (i.e. 35%) and by and is a useful tool for decision-making as part of the
Grimsby et al. (9) (i.e. 33%), since they defined con- diagnostic workup. Nevertheless, a successful MRI–
cordance between measurements as a difference within ultrasound correlation is neither easy nor immediate
5 mm, with a method similar to ours. Kuroki et al. cited (22–24). We found that DCIS histology is the strongest
a 93.5% concordance using a limit of 15 mm, which independent predictor of discrepancy between MRI
could represent a substantial discordance in the clinical and pathology sizing of breast tumors, and this may
setting (6). In our study, the mean overestimation was be due to different factors. DCIS lesions have been
larger in the group of tumors >20 mm (P < 0.05), thus found to exhibit ‘‘non-mass-like’’ enhancement at a
underscoring the importance of lesion’s size in deter- high rate, ranging between 69% and 90% in previous
mining the accuracy of MRI measurements. studies (25–28). Despite the fact that we did not sys-
Interestingly, in a recent work (15), the authors found tematically consider lesion shape and morphology in
that the mean difference in sizing between MRI and our analysis, we can reasonably hypothesize that also
histology was only 2 mm, which corresponded to a this feature may have contributed to the MRI overesti-
non-significant size overestimation by MRI. Grimsby mation of DCIS lesions (Figs 6 and 7). Another plaus-
et al. (9) found that, among patients with tumor size ible explanation for MRI overestimation may be the
overestimated by MRI, 65% had satellite lesions, background contrast enhancement of breast
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Mennella et al. 267
Fig. 6. Transverse T1W 3D FLASH subtraction MR image (a) shows a lesion with a largest diameter of 20 mm in the outer quadrants
of the left breast, characterized by ‘‘non-mass-like’’ enhancement. (b) The surgical specimen. (c) The histopathologic section
(hematoxylin and eosin, 10x) reveals a pure DCIS. In the case of this relatively small lesion, MRI–pathology difference was 10 mm,
which corresponded to 50% of the MRI size of the tumor.
Fig. 7. Transverse T1W 3D FLASH subtraction MR image (a) shows a huge lesion with a largest diameter of 105 mm in the outer
quadrants of the right breast, characterized by ‘‘non-mass-like’’ enhancement. (b) The surgical specimen. (c) The histopathologic
section (hematoxylin and eosin, 20x) reveals a pure DCIS. This case was characterized by an important MRI–pathology difference
of 45 mm.
parenchyma adjacent to DCIS foci, which may become associated to discordance between MRI and pathology
more evident due to benign proliferation (i.e. adenosis, sizing of breast cancer. Lesion size can also influence
fibrocystic changes), presence of high-risk lesions (i.e. the accuracy of MRI measurements, but to a lesser
atypical ductal hyperplasia), granulation tissue, or foci extent.
of liponecrosis (29).
A limitation of our study is related to the potentially
Funding
problematic nature of determining an accurate path-
ology size for DCIS lesions (30). However, the standar- This research received no specific grant from any
funding agency in the public, commercial, or not-for-profit
dized, accurate system of specimen analysis, which is
sectors.
routinely performed by our pathology service, may
have reduced this source of bias. In addition, the micro-
scopic measurement has been shown to be more accur- References
ate than tumor sizing on gross specimens (30). 1. Association of Breast Surgery at Baso 2009. Surgical
In conclusion, the results of our study suggest that guidelines for the management of breast cancer. Eur J
DCIS histology is a factor independently and strongly Surg Oncol 2009;35:1–22.
Downloaded from acr.sagepub.com at Univ of Connecticut / Health Center / Library on May 30, 2015
268 Acta Radiologica 56(3)
2. Hata T, Takahashi H, Watanabe K, et al. Magnetic res- detection of multifocal and multicentric cancer. J Clin
onance imaging for preoperative evaluation of breast Oncol 2008;26:3248–3258.
cancer: a comparative study with mammography and 17. Pengel KE, Loo CE, Teertstra HJ, et al. The impact of
ultrasonography. J Am Coll Surg 2004;198:190–197. preoperative MRI on breast-conserving surgery of inva-
3. Boetes C, Veltman J, van Die L, et al. The role of MRI in sive cancer: a comparative cohort study. Breast Cancer
invasive lobular carcinoma. Breast Cancer Res Treat Res Treat 2009;116:161–169.
2004;86:31–37. 18. Bilimoria KY, Cambic A, Hansen NM, et al. Evaluating
4. Blair S, McElroy M, Middleton MS, et al. The efficacy of the impact of preoperative breast magnetic resonance
breast MRI in predicting breast conservation therapy. imaging on the surgical management of newly diagnosed
J Surg Oncol 2006;94:220–225. breast cancers. Arch Surg 2007;142:441–445. (discussion
5. Partridge SC, Gibbs JE, Lu Y, et al. Accuracy of MR 445–447).
imaging for revealing residual breast cancer in patients 19. Zhang Y, Fukatsu H, Naganawa S, et al. The role of
who have undergone neoadjuvant chemotherapy. Am J contrast-enhanced MR mammography for determining
Roentgenol 2002;179:1193–1199. candidates for breast conservation surgery. Breast
6. Kuroki Y, Nawano S, Hasebe T, et al. Efficacy of MR Cancer 2002;9:231–239.
mammography (MRM) in providing preoperative locor- 20. Baltzer PA, Benndorf M, Dietzel M, et al. False-positive
egional information on breast cancer: correlation findings at contrast-enhanced breast MRI: a BI-RADS
between MRM and histological findings. Magn Reson descriptor study. Am J Roentgenol 2010;194:1658–1663.
Med Sci 2002;1:73–80. 21. Liberman L, Morris EA, Lee MJ, et al. Breast lesions
7. Cheung YC, Wan YL, Lo YF, et al. Preoperative mag- detected on MR imaging: features and positive predictive
netic resonance imaging evaluation for breast cancers value. Am J Roentgenol 2002;179:171–178.
after sonographically guided core-needle biopsy: a com- 22. Girardi V, Carbognin G, Camera L, et al. Multifocal,
parison study. Ann Surg Oncol 2004;11:756–761. multicentric and contralateral breast cancers: breast
8. Onesti JK, Mangus BE, Helmer SD, et al. Breast cancer MR imaging in the preoperative evaluation of patients
tumor size: correlation between magnetic resonance ima- with newly diagnosed breast cancer. Radiol Med
ging and pathology measurements. Am J Surg 2011;116:1226–1238.
2008;196:844–850. 23. Destounis S, Arieno A, Somerville PA, et al. Community-
9. Grimsby GM, Gray R, Dueck A, et al. Is there concord- based practice experience of unsuspected breast magnetic
ance of invasive breast cancer pathologic tumor size with resonance imaging abnormalities evaluated with second-
magnetic resonance imaging? Am J Surg look sonography. J Ultrasound Med 2009;28:1337–1346.
2009;198:500–504. 24. Abe H, Schmidt RA, Shah RN, et al. MR-directed
10. Berg WA, Gutierrez L, NessAiver MS, et al. Diagnostic (‘‘Second-Look’’) ultrasound examination for breast
accuracy of mammography, clinical examination, US, lesions detected initially on MRI: MR and sonographic
and MR imaging in preoperative assessment of breast findings. Am J Roentgenol 2010;194:370–377.
cancer. Radiology 2004;233:830–849. 25. Tozaki M, Fukuda K. High-spatial-resolution MRI of
11. Egan RL. Multicentric breast carcinomas: clinical-radio- non-masslike breast lesions: interpretation model based
graphic-pathologic whole organ studies and 10-year sur- on BI-RADS MRI descriptors. Am J Roentgenol
vival. Cancer 1982;49:1123–1130. 2006;187:330–337.
12. Liberman L, Morris EA, Dershaw DD, et al. Ductal 26. Orel SG, Mendonca MH, Reynolds C, et al. MR imaging
enhancement on MR imaging of the breast. Am J of ductal carcinoma in situ. Radiology 1997;202:413–420.
Roentgenol 2003;181:519–525. 27. Marcotte-Bloch C, Balu-Maestro C, Chamorey E, et al.
13. Mann RM, Kuhl CK, Kinkel K, et al. Breast MRI: MRI for the size assessment of pure ductal carcinoma in
guidelines from the European Society of Breast situ (DCIS): a prospective study of 33 patients. Eur J
Imaging. Eur Radiol 2008;18:1307–1318. Radiol 2011;77:462–467.
14. D’Agostino RB, Belanger A, D’Agostino RB Jr. A sug- 28. Mai KT, Yazdi HM, Burns BF, et al. Pattern of distri-
gestion for using powerful and informative tests of nor- bution of intraductal and infiltrating ductal carcinoma: a
mality. The American Statistician 1990;44:316–321. three-dimensional study using serial coronal giant sec-
15. Gruber IV, Rueckert M, Kagan KO, et al. Measurement tions of the breast. Hum Pathol 2000;31:464–474.
of tumour size with mammography, sonography and 29. Esserman LJ, Kumar AS, Herrera AF, et al. Magnetic
magnetic resonance imaging as compared to histological resonance imaging captures the biology of ductal carcin-
tumour size in primary breast cancer. BMC Cancer oma in situ. J Clin Oncol 2006;24:4603–4610.
2013;13:328. 30. Behjatnia B, Sim J, Bassett LW, et al. Does size matter?
16. Houssami N, Ciatto S, Macaskill P, et al. Accuracy and Comparison study between MRI, gross, and microscopic
surgical impact of magnetic resonance imaging in breast tumor sizes in breast cancer in lumpectomy specimens.
cancer staging: systematic review and meta-analysis in Int J Clin Exp Pathol 2010;3:303–309.
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