Invited. Challenges to Interpretation of Breast MRI

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1 JOURNAL OF MAGNETIC RESONANCE IMAGING 13: (2001) Review Invited Challenges to Interpretation of Breast MRI Karen Kinkel, MD,* and Nola M. Hylton, PhD This review describes the current knowledge and challenges of lesion interpretation with MRI of the breast according to different image interpretation strategies. Particular emphasis is given to patient- and tumor-related factors that influence image interpretation. The impacts of the menstrual cycle, prior surgery, radiation therapy, and chemotherapy are summarized. Particular enhancement features of ductal carcinoma in situ (DCIS) or invasive lobular carcinoma are described. Finally, an adequate diagnosis at MRI of the breast should take into account the results of the patient s history, physical examination, and all imaging tests performed before MRI. J. Magn. Reson. Imaging 2001;13: Wiley-Liss, Inc. Index terms: breast neoplasm; MRI; tissue characterization; staging; interpretation ALTHOUGH IMAGE ACQUISITION TECHNIQUES for MRI of the breast vary internationally, image interpretation follows similar rules. At a recent international consensus meeting, experts pointed out that both kinetic and morphologic enhancement characteristics are used to characterize enhancing lesions of the breast at MRI (1). In the absence of scientific evidence, the relative importance of kinetic and morphologic features for breast cancer diagnosis is unclear. In addition to differences arising from imaging strategies, the interpretation of enhancing lesions on breast MRI is challenged by many patient-related factors, such as the menstrual cycle (2), recent breast surgery (3) or chemotherapy. Moreover, patients evaluated by MRI for an indeterminate lesion of the breast usually present with a considerably higher pretest probability of breast cancer than do patients undergoing a screening mammogram. The complexity of the interpretation process in a clinical situation is partly due to a necessary integration of the results of prior imaging or clinical examination. Indeed, the probability of breast cancer increases with suspicious findings at physical examination, mammography, and ultrasound. Therefore, final image interpretation of breast lesions seen at MRI should take into account the patient s personal history, with complete knowledge of the results of all other tests. Department of Radiology, University of California San Francisco, San Francisco, California. *Address reprint requests to: K.K., Department of Radiology, University Hospital Geneva (HCUG), 24 rue Micheli-du-Crest, 1211 Genève 14, Switzerland. Karen.Kinkel@hcuge.ch Received September 19, 2000; Accepted October 20, Tumor-related factors, such as the type of histologic tumor and the degree of tumor differentiation, contribute to the biological heterogeneity of breast cancer. Interpretation rules established on series of patients presenting with a similar clinical problem might not apply to all breast cancers, due to differences in tumor histology and enhancement characteristics. This review describes the current knowledge and challenges of lesion interpretation with MRI of the breast according to different image interpretation strategies, with particular emphasis on patient- and tumorrelated factors influencing image interpretation. INTERPRETATION RULES FOR BREAST LESION IDENTIFICATION AND CHARACTERIZATION Lesion identification at MRI of the breast depends on contrast-enhancement within the breast after intravenous injection of contrast material. As both normal breast tissue and breast lesions will enhance after contrast administration, the detection of a malignant lesion within normal breast tissue is based on the earlier and stronger enhancement of malignant lesions as well as the morphologic features of the enhancing lesion. Differences in MR enhancement characteristics between benign and malignant breast lesions are believed to rely on differences in vascularity, vessel permeability, and extracellular diffusion space (4). There have been substantial research efforts over the past 10 years to identify the most significant features for diagnosing breast cancer with MRI. Sudden strong enhancement within the first 2 minutes was suggested first (5), followed by a quantitative malignancy threshold, initially compared to fat (6) and later expressed as the percentage of signal intensity increase relative to the signal intensity before contrast injection (7). However, using a quantitative enhancement rate for lesion differentiation was disappointing due to overlapping enhancement rates between malignant and benign tumors, such as fibroadenomas and proliferative and nonproliferative dysplasia (8). Although ultrafast protocols showed excellent initial results in sensitivity (95%) and specificity (86%) (9), the limited coverage of the breast and the low sensitivity for ductal carcinoma in situ (DCIS) (76%) (10) prevented a broader acceptance of such techniques. A peripheral washout sign, defined by early increase and a delayed decrease of enhancement at the periphery of the tumor, and corresponding to high peripheral 2001 Wiley-Liss, Inc. 821

2 822 Kinkel and Hylton and low central microvessel density (11), was proposed as another kinetic candidate to increase specificity for better lesion characterization (12). The use of peripheral washout as a sign of malignancy resulted in a sensitivity of 51% and a specificity of 100% on delayed contrast-enhanced MR images ( 10 minutes). The new interest in longer time-signal intensity curves resulted in a study demonstrating a diagnostic value of the shape of the time-signal intensity curve greater than the initial enhancement rate (13). A curve demonstrating delayed washout enhancement (loss of signal intensity) or plateau enhancement was considered indicative of malignancy. The shape of the curve increased the specificity obtained with the initial enhancement rate from 37% to 83% without any change in sensitivity (91%). Quantitative approaches have included various parametric methods computing factors such as the maximal enhancement rate, maximal slope of enhancement and rate of washout enhancement (14 16). However, subjective image interpretation remained superior to the isolated use of quantitative indices obtained by computation (17). Part of the subjective image interpretation in the study of Mussurakis et al. (17) was due to the integration of a morphological feature analysis to the final lesion diagnosis. Several studies described architectural features associated with a specific finding, such as linear enhancement in DCIS (18), rim enhancement in invasive cancer (19), internal septation in fibroadenomas, and absent enhancement within hyalinized fibroadenomas (20). In addition, T2-weighted pulse sequences were shown to help differentiate fibroadenomas from cancer, particularly in patients younger than 40 years (21). In those patients, fibroadenomas tended to demonstrate higher signal intensities compared to normal breast parenchyma than did breast cancer on T2-weighted images. Other architectural features that were highly predictive of malignant disease included spiculated margins (76 88%) and peripheral rim enhancement in the presence of weaker central lesion enhancement (79 92%) (22). One major difficulty in MRI interpretation of the breast is determining the significance and rank of individual kinetic and morphologic factors provided by MRI of the breast, resulting in a final probability of malignancy. Two studies using logistic regression methods proposed interpretation models that concentrated on the interpretation of focal mass enhancement (23 24). The first published model for lesion characterization retained three enhancement characteristics identified on a post-contrast high spatial resolution image. Lesion interpretation was obtained by first considering the margin of the lesion, followed by the presence or absence of internal septations and the degree of enhancement at 2 4 minutes after contrast injection (25). Internal septation (indicative of benign disease) was applied to lesions with lobulated or irregular margins, whereas a moderate or strong degree of enhancement (indicative of malignant disease) was applied to lesions with spiculated margins or lobulated margins and no internal septation. A final probability of malignancy was given for each terminal node of the model. The performance of the model was tested prospectively, with a sensitivity of 96% and a specificity of 79%. The second model used one pre- and two post-contrast acquisitions at intermediate spatial resolution (24). In this study, the malignancy threshold that classified a specific margin as malignant depended on the presence or absence of washout enhancement at 7.5 minutes after contrast injection. Lesions without washout were qualified as malignant only in the presence of spiculated margins, whereas lesions with washout were qualified as malignant if their margins were not smooth. This interpretation model for focal mass enhancement incorporated both kinetic and morphologic enhancement characteristics, and demonstrated a sensitivity of 97% and a specificity of 96%. However, testing in a prospective study was not performed. Nonfocal mass enhancement qualified as foci of enhancement, linear, regional, segmental, patchy, or diffuse enhancement have rarely been included in interpretation models in MRI of the breast. These features have been considered, however, in the development of a standardized lexicon for reading and reporting breast MRI images (1). PATIENT-RELATED FACTORS Physical Examination It is reasonable to believe that earlier studies, including patients with palpable findings only (26) or excluding patients with nonpalpable clusters of microcalcification at mammography (17), overestimated the diagnostic performance of MRI by eliminating potential candidates of nonfocal enhancement. Indeed, studies concentrating on patients with nonpalpable mammographic abnormalities demonstrated a relatively high prevalence (41%, 40/98) of nonfocal early enhancement and a particularly low specificity (47%, 37/79) (27). With the increased use of mammography to detect breast cancer at an early stage, this MR lesion type is more likely to be identified and to challenge image interpretation. With increased spatial resolution and the systematic use of a lexicon for lesion description (1), the collection of standardized enhancement characteristics of nonfocal lesion enhancement might improve the development of interpretation rules in the near future. Menstrual Cycle The menstrual cycle also impacts lesion interpretation at MRI of the breast. Transient enhancing foci (smaller than 5 mm) have been described in healthy premenopausal volunteers during each phase of the cycle, with a higher incidence in the first and fourth week of the cycle (2). The study reported up to 60 enhancing foci in 16 of 20 healthy premenopausal women. Because the amount of normal enhancement increases in the second half of the cycle, the sensitivity of MRI for identifying moderately enhancing suspicious lesions may be decreased. In patients with fibrocystic changes, benign enhancement features also decrease specificity (28). This phenomena, which is particularly important during the second half of the cycle, could be minimized if both the enhancement pattern and the percentage en-

3 Challenges to Interpretation of Breast MRI 823 Table 1 MR Enhancement Characteristics of Lobular Cancer at MR Imaging of the Breast in 38 Patients With 50 Lesions Abnormal enhancement: present 46/50 (92%) absent 4/50 (8.0%) Lesion type: Ductal enhancement 4/46 (8.7%) Irregular mass 2/46 (4.3%) Spiculated mass 12/46 (26.1%) Segmental enhancement 2/46 (4.3%) Regional enhancement 23/46 (50%), 13/23 (56.6%) homogeneous, 5/23 (21.7%) heterogeneous 4/23 (17.4) clumped 1/23 (4.3%) stippled Patchy enhancement 3/46 (6.5%) Enhancement degree: moderate 13/46 (28.3%) strong 33/46 (71.7%) Enhancement pattern: progressive 12/46 (26.1%) plateau 1/46 (2.2%) washout 33/46 (71.7%) hancement were considered in characterizing enhancing lesions of the breast (28). Recommendations for breast MRI should include scheduling during the second week of the cycle whenever possible. In patients with unexpected enhancement in a quadrant without clinical or mammographic concern, the MR examination might be repeated during the other half of the cycle in order to rule out false positive results. Hormonal Therapy In postmenopausal women, there are to date no reports on the influence of hormone replacement therapy or tamoxifen (a chemotherapeutic and chemopreventive agent known to reduce local recurrence of breast cancer) on the enhancement of normal breast parenchyma. Until now, we have ignored how MR enhancement characteristics might be influenced by the use of such medication. Surgery and Radiation Therapy Enhancement of postsurgical granulation tissue can also reduce the diagnostic performance of MRI of the breast in patients scheduled soon after excisional biopsy (29). A recent report found that waiting 1 month after surgery before performing breast MRI reduced false positive findings (3). Both surgery and radiation therapy induce local inflammation and necrosis that could modify the MR enhancement characteristics of normal and malignant breast tissue. There has been no study describing normal temporal changes of MR enhancement characteristics under radiation therapy. Heywang et al (30) described strong enhancement in 62 patients after tumorectomy and radiation therapy. Based on the enhancement degree, the differentiation between tumor recurrence and scar was reported to be impossible during the first 9 months, possible in twothirds of patients seen at 9 18 months after surgery, and excellent in patients scheduled 18 months after the end of the treatment. This report resulted in the widespread recommendation against contrast-enhanced MRI of the breast for at least 9 months following radiation therapy. Chemotherapy The diagnostic criteria used at MRI before the administration of chemotherapy are similar to those used for lesion characterization. However, those criteria are likely to underestimate the assessment of tumor extent after the administration of chemotherapy (31). Indeed, cell death, necrosis, and reduced vascular permeability might modify the enhancement characteristic of residual tumor, leading to possible underestimation of the extent of tumor if prechemotherapy kinetic diagnostic criteria are applied (31,32). To assess the extent of residual tumor, diagnostic criteria for patients after chemotherapy need to be developed. In a study of 30 patients, the correlation of MR enhancement after chemotherapy with residual disease determined by serial sectioning of mastectomy specimens was described (33). Unfortunately, the study did not specify the diagnostic criteria for residual disease. To develop or adapt existing kinetic and morphologic diagnostic criteria for the diagnosis of residual cancer, careful correlation between MRI and histopathology is required. The value of MRI in diagnosing residual disease in patients after chemotherapy will remain questionable until clear diagnostic criteria indicative of residual disease are developed. Other authors have been interested in the change of MR enhancement characteristics of breast cancer during chemotherapy. Certain spatial distributions of the initial enhancement appeared to be more indicative of the histopathological response to chemotherapy than were the pattern of shrinkage or the change in kinetic enhancement characteristics (34). However, the prognostic value of MRI characteristic in patients treated with chemotherapy remains unknown until long-term data correlating MRI characteristics with overall or disease-free survival become available. TUMOR-RELATED FACTORS The interpretation of MR images of the breast is considerably challenged by certain types of breast cancer, particularly invasive lobular carcinoma and DCIS. When MRI is required to diagnose the extent of cancer, the particular tumor type and its most frequent MRI presentation will influence lesion characterization for staging at MRI. Lobular Cancer Invasive lobular cancer represents about 5% of all breast cancers, and is frequently associated with delayed diagnosis and multifocal disease. MRI characteristics of invasive lobular cancer have been described in two European studies. Both studies included patients without prior histopathologic diagnosis and used dynamic diagnostic criteria alone (27,35). One study of 23 lobular cancers described 19 lesions as demonstrating

4 824 Kinkel and Hylton Figure 1. A 65-year-old patient with a normal mammogram and a palpable mass in the right upper outer quadrant. Sagittal 3D gradient echo MR image before (a), and 2 min 30 sec (b) and 7 min 30 sec (c) after I.V. contrast media administration. Segmental heterogeneous enhancement (arrow, b) with decrease in signal intensity at 7 min 30 sec (washout enhancement pattern) (c) is identified in the upper and retroareolar breast extending up to the nipple. Histopathology of the mastectomy specimen confirmed lobular cancer with posterior invasion of the nipple.

5 Challenges to Interpretation of Breast MRI 825 Figure 2. A 50-year-old patient with suspicious microcalcification in the left retroareolar region at mammography. Sagittal 3D gradient echo MR image before (a), and 2 min 30 sec (b) and 7 min 30 sec (c) after I.V. contrast media administration. Irregular linear enhancement is identified in the retroareolar region at 2 min 30 sec after contrast injection (arrow, b) and corresponded to DCIS without invasion at histopathology. At 7 min 30 sec (c) this feature has partially vanished, which might correspond to partial voluming or washout enhancement pattern. focal enhancement (83%), two lesions with diffuse enhancement (8.5%), and two lesions without any enhancement (8.5%) (35). Early enhancement was missing in 2/8 (25%) nonpalpable lobular cancers (27) and classified as false negative at MRI with dynamic criteria alone (overall sensitivity 6/8, 75%). In a recent study using morphologic diagnostic criteria, the author assessed preoperatively the extent of lobular cancer that was previously diagnosed at biopsy (36). The accuracy was not limited by low sensitivity, as with previous reports of MRI for lobular cancer, and reached 85% (17/20) in this study, with an overestimation of the extent of disease in 2/20 patients (10%) and an underestimation in one patient (1/20, 5%). The discrepancy between the low sensitivity of MRI for lobular cancer in a diagnostic situation and an adequate accuracy for the diagnosis of the extent of lobular cancer is most likely the result of different interpretation rules. Indeed, Rodenko et al (36) used morphologic criteria alone, including diffuse stippled enhancement within the list of suspicious MR findings for residual lobular cancer. In other diagnostic models, this lesion type has been considered typical for benign changes (25). The downside of diagnostic criteria chosen to maintain high sensitivity is possible overstaging. If pretreatment MRI characterizes associated benign disease as multifocal lobular cancer, the use of MRI will result in a certain number of unnecessary mastectomies without a demonstrated benefit in increased survival (37). Therefore, diagnostic criteria for staging and assessing the extent of known breast cancer should optimize specificity. Specific criteria for staging have not been addressed in the literature to date. A retrospective analysis of breast MR images from an institutional database at UCSF, with standardized lesion description and histopathologic correlation, showed data in 38 patients with 50 lesions of lobular cancer (38). Four of the 50 lesions showed no enhancement, confirming a previous study showing false negative findings in 8% of patients with lobular cancer (35).

6 826 Kinkel and Hylton Table 2 Enhancement Characteristics of DCIS at Dynamic High Resolution MR Imaging of the Breast in 32 Patients With Pure DCIS and No Invasion at Final Histopathology Abnormal enhancement: Present 29/32 (90.6%) Absent 3/32 (9.4%) Number of MR lesion types (within the enhancing area of the breast with DCIS at histopathology) One 14/29 (48.3%) 7/14 regional enhancement 3/14 ductal enhancement 3/14 focal mass enhancement 1/14 foci of enhancement Two 11/29 (37.9%) 8/11 regional and ductal enhancement 3/11 regional and focal mass enhancement Three 4/29 (13.8%) 4/4 regional, ductal and focal mass enhancement Regional enhancement in DCIS 22/48 (46%) Stippled 4/22 Clumped 1/22 Heterogeneous 6/22 Homogeneous 1/22 Ductal enhancement in DCIS 15/48 (31%) Shape Linear 4/15 Linear branching 11/15 Margin Regular 0/15 Irregular 15/15 Focal mass enhancement in DCIS 10/48 (21%) Margin Spiculated 3/10 Irregular 2/10 Lobulated 3/10 Smooth 2/10 Foci of enhancement in DCIS 1/48 (2%) Size 4 mm This percentage is higher than the false negative rate reported for MRI in patients with invasive ductal carcinoma. In order to describe invasive lobular cancer at MRI, all MR lesion types corresponding to invasive lobular cancer were listed according to the new MRI lexicon (Table 1) (unpublished data). The most common lesion type was regional enhancement (23/46, 50%), which is considered suspicious in 22/23 (96%) patients due to either a homogeneous presentation (13/23, 57%) or washout enhancement pattern (17/23, 74%). Stippled enhancement was identified in only one patient. Suspicious focal mass enhancement (14/46, 30%) was the second most frequent MR lesion type for invasive lobular cancer, with either spiculated margins (12/14, 86%) or irregular margins with washout enhancement pattern (2/14, 14%). Other less common lesion types included ductal (4/46), segmental (2/46 [Fig. 1]) or patchy (2/46) enhancement. The distribution of the morphologic MR lesion types for invasive lobular cancers in the study by Sittek et al (35) differed from our findings and found a large majority of focal mass enhancement (19/21, 90.5%) and a small proportion of diffuse enhancement (2/21, 9.5%). We conclude that the combined use of morphological and dynamic diagnostic criteria might allow a better lesion characterization for patients with invasive lobular carcinoma. Lobular Cancer in Situ (LCIS) Very little data are available concerning the diagnosis of lobular carcinoma in situ (LCIS) at MRI. LCIS belongs to the benign group of tissue abnormalities, and is often considered to be one among many other risk factors for invasive breast cancer rather than as a precursor of breast cancer (39). The incidental detection of LCIS warrants clinical and mammographic observation without surgical treatment (40). Patients with invasive breast cancer and associated LCIS have no differences in survival compared with patients without associated LCIS (41). In one study correlating MR enhancement features with histopathology, LCIS is listed among benign findings that showed no or very little enhancement at MRI (25). However, a description of morphological enhancement features corresponding to LCIS is not provided in this study. Ductal Carcinoma in Situ The histopathology of ductal disease of the breast encompasses a wide range of increasingly aggressive types of lesions, starting with borderline lesions such as atypical ductal hyperplasia (known as a risk factor for invasive breast cancer), DCIS, and invasive ductal carcinoma of the breast. A certain proportion of DCIS is thought to develop into invasive ductal carcinoma after an unknown period of time. According to initial results using dynamic criteria alone, the sensitivity of MRI is significantly lower in patients with DCIS than in patients with invasive ductal carcinoma. The false negative rate in patients with invasive ductal carcinoma was reported as approximately 4% in one study vs. 23% in patients with DCIS (10). The reported sensitivity of MRI for DCIS using dynamic criteria alone is therefore estimated at about 77%. Studies with high spatial resolution MRI have obtained similar rates of sensitivity. Orel et al (42) described abnormal enhancement in 10/13 (77%) patients with pure DCIS (42). Absent enhancement was noted in three lesions with a mean size of 3.7 mm, and might have resulted from partial volume averaging of surrounding structures. The most frequent morphologic feature of DCIS at MRI is non-focal enhancement. Two studies, with a total of 36 patients with pure DCIS, described linear enhancement in 46 60% (18,42) Another study that assessed the extent of pure DCIS at MRI identified clumped regional enhancement in 4/5 patients (80%) and associated linear enhancement in 1/5 patients (20%) (43). Unpublished data from our institutional database, which includes 32 patients with pure DCIS at histopathology, confirm this distribution of MR lesion types with 77% nonfocal (46% regional enhancement and 31% linear enhancement [Fig. 2]) and 23% focal enhancement (Table 2). The most frequent presentation of regional enhancement was clumped (50%), an MRI feature of DCIS that has also been noted in patients with fibrocystic disease (25) (Fig. 3).

7 Challenges to Interpretation of Breast MRI 827 Figure 3. A 55-year-old patient with a palpable lump in the right upper outer quadrant, a normal mammogram and ultrasound, and indeterminate findings at fine-needle aspiration. Sagittal 3D gradient echo MR image before (a), and 2 min 30 sec (b) and 7 min 30 sec (c) after I.V. contrast media administration. Progressive clumped segmental enhancement (arrow) is identified in the upper outer quadrant, corresponding to benign fibrocystic changes at histopathology. Irregular linear enhancement in the deep retroareolar breast (arrowhead) disappeared at a subsequent MR follow-up. The most common presentation of DCIS at mammography, described as clusters of microcalcification, can overlap with the mammographic presentation of benign tissue abnormalities. Due to the excellent tolerance, low cost and availability of stereotaxic biopsy procedures under mammography, MRI is usually not used for further characterization of suspicious microcalcifications of the breast. One study using dynamic criteria (enhancement earlier than 90 seconds), obtained a sensitivity of 95% and a specificity of 51% for the diagnosis of cancer in patients with isolated clusters of microcalcification (44). False positive findings were mainly due to early enhancement in benign fibrocystic changes. In a study of 51 patients diagnosed with DCIS alone at core biopsy (N 17) or surgical biopsy (N 34), the extent of residual DCIS evaluated at histopathology was compared with MRI characteristics 2 4 weeks after biopsy (45). Irregular linear enhancement, and clumped, heterogeneous, and homogeneous regional or segmental enhancement were used to diagnose DCIS. The value of MRI in the diagnosis of multicentric DCIS depended on the type of prior biopsy (surgical vs. core) that the patient underwent before MRI. In patients diagnosed with core biopsy, the positive predictive value of subsequent MRI was 100% vs 60% in patients diagnosed with a surgical biopsy. False-positive findings were identified only in patients with prior surgical biopsy, and correlated with granulation tissue at subsequent histopathology. These findings are similar to those obtained at MRI for patients diagnosed with other types of cancer soon after surgery (29,46). Therefore, if multicentric suspicious enhancement is identified at

8 828 Kinkel and Hylton Figure 4. A 60-year-old patient with a core biopsy demonstrating DCIS. Sagittal 3D gradient echo MR image before (a), and 2 min 30 sec (b) and 7 min 30 sec (c) after I.V. contrast media administration. Irregular linear enhancement within the upper inner quadrant is best seen at 2 min 30 sec after contrast injection (arrow, b) and corresponded to unicentric high-grade DCIS at histopathology. The anterior small spiculated mass with central washout enhancement pattern at 7 min 30 sec (arrowhead, c) corresponded to an associated focus of invasive ductal carcinoma. MRI performed for staging following biopsy, a MRI guided biopsy might be required. The diagnosis of associated occult invasion is particularly important before surgical treatment of patients with extensive DCIS or diagnosis by needle biopsy alone. Preoperative knowledge of occult invasion in patients diagnosed with DCIS could allow axillary dissection at the time of initial surgery. In a study evaluating occult invasion by MRI, suspicious focal mass enhancement was used as a diagnostic criteria indicative of associated occult invasion in a group of 51 patients with a preoperative diagnosis of pure DCIS (24) (Fig. 4). The positive predictive value of this diagnostic criteria remained low (60% in the core biopsy group and 33% in the surgical biopsy group) due to suspicious focal mass enhancement in both DCIS and scar tissue. To optimize the interpretation criteria for the diagnosis of associated occult invasion, larger studies will be necessary. CONCLUSIONS The interpretation of MR images of the breast remains a challenging task. Although the integration of patientrelated factors might improve the diagnostic performance of MRI, the biological heterogeneity of breast cancer accounts in part for the difficulty of maintaining high specificity for lesion characterization. Researchers may contribute to increased knowledge in the interpretation of MRI of the breast by using a standardized lexicon for lesion description and by defining more precise diagnostic criteria. Those criteria might need to be adapted to the specific clinical situation, requiring either high specificity (staging), high sensitivity (screening), or both (characterization). Combined research efforts should collect data from larger numbers of patients to allow the use of appropriate statistical methods to optimize diagnostic criteria for specific clinical situations.

9 Challenges to Interpretation of Breast MRI 829 REFERENCES 1. Ikeda et al. Development, standardization and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies. JMRI 2001;13: Kuhl CK, Bieling HB, Gieseke J, et al. Healthy premenopausal breast parenchyma in dynamic contrast-enhanced MR imaging of the breast: normal contrast medium enhancement and cyclicalphase dependency. Radiology 1997;203: Frei KA, Kinkel K, Bonel HM, Lu Y, Esserman LJ, Hylton NM. MR imaging of the breast in patients with positive margins after lumpectomy: influence of the time interval between lumpectomy and MR imaging. Am J Roentgenol 2000;175: Tofts PS, Berkowitz B, Schnall MD. Quantitative analysis of dynamic Gd-DTPA enhancement in breast tumors using a permeability model. Magn Reson Med 1995;33: Kaiser WA, Zeitler E. MR imaging of the breast: fast imaging sequences with and without Gd-DTPA. Preliminary observations. Radiology 1989;170: Heywang SH, Wolf A, Pruss E, Hilbertz T, Eiermann W, Permanetter W. MR imaging of the breast with Gd-DTPA: use and limitations. Radiology 1989;171: Kuhl CK, Seibert C, Sommer T, Kreft B, Gieseke J, Schild HH. [Focal and diffuse lesions in dynamic MR-mammography of healthy probands]. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 1995; 163: Stomper PC, Herman S, Klippenstein DL, et al. Suspect breast lesions: findings at dynamic gadolinium-enhanced MR imaging correlated with mammographic and pathologic features. Radiology 1995;197: Boetes C, Barentsz JO, Mus RD, et al. MR characterization of suspicious breast lesions with a gadolinium-enhanced Turbo- FLASH subtraction technique. Radiology 1994;193: Boetes C, Strijk SP, Holland R, Barentsz JO, Van der Sluis RF, Ruijs JH. False-negative MR imaging of malignant breast tumors. Eur Radiol 1997;7: Buadu LD, Murakami J, Murayama S, et al. Patterns of peripheral enhancement in breast masses: correlation of findings on contrast medium enhanced MRI with histologic features and tumor angiogenesis. J Comput Assist Tomogr 1997;21: Sherif H, Mahfouz AE, Oellinger H, et al. Peripheral washout sign on contrast-enhanced MR images of the breast. Radiology 1997; 205: Kuhl CK, Mielcareck P, Klaschik S, et al. Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions? [see comments]. Radiology 1999; 211: Mussurakis S, Buckley DL, Horsman A. Dynamic MRI of invasive breast cancer: assessment of three region-of-interest analysis methods. J Comput Assist Tomogr 1997;21: Hulka CA, Edmister WB, Smith BL, et al. Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis. Radiology 1997;205: Daniel BL, Yen YF, Glover GH, et al. Breast disease dynamic spiral MR imaging [see comments]. Radiology 1998;209: Mussurakis S, Buckley DL, Drew PJ, et al. Dynamic MR imaging of the breast combined with analysis of contrast agent kinetics in the differentiation of primary breast tumours. Clin Radiol 1997;52: Gilles R, Zafrani B, Guinebretiere JM, et al. Ductal carcinoma in situ: MR imaging-histopathologic correlation. Radiology 1995;196: Orel SG, Schnall MD, LiVolsi VA, Troupin RH. Suspicious breast lesions: MR imaging with radiologic-pathologic correlation. Radiology 1994;190: Hochman MG, Orel SG, Powell CM, Schnall MD, Reynolds CA, White LN. Fibroadenomas: MR imaging appearances with radiologic-histopathologic correlation. Radiology 1997;204: Kuhl CK, Klaschik S, Mielcarek P, Gieseke J, Wardelmann E, Schild HH. Do T2-weighted pulse sequences help with the differential diagnosis of enhancing lesions in dynamic breast MRI? J Mag Reson Imaging 1999;9: Nunes LW, Schnall MD, Siegelman ES, et al. Diagnostic performance characteristics of architectural features revealed by high spatial-resolution MR imaging of the breast. Am J Roentgenol 1997;169: Nunes LW, Schnall MD, Orel SG, et al. Breast MR imaging: interpretation model [see comments]. Radiology 1997;202: Kinkel K, Helbich TH, Esserman LJ, et al. Dynamic high-spatialresolution MR imaging of suspicious breast lesions: diagnostic criteria and interobserver variability. Am J Roentgenol 2000;175: Nunes LH, Schnall MD, Orel SG, et al. Correlation of lesion appearance and histopathologic findings for the nodes of a breast MR imaging interpretation model. Radiographics 1999;19: Flickinger FW, Allison JD, Sherry RM, Wright JC. Differentiation of benign from malignant breast masses by time-intensity evaluation of contrast enhanced MRI. Magn Reson Imaging 1993;11: Gilles R, Guinebretiere JM, Lucidarme O, et al. Nonpalpable breast tumors: diagnosis with contrast-enhanced subtraction dynamic MR imaging [published erratum appears in Radiology 1994;193(1): 285]. Radiology 1994;191: Rieber A, Merkle E, Bohm W, Brambs HJ, Tomczak R. MRI of histologically confirmed mammary carcinoma: clinical relevance of diagnostic procedures for detection of multifocal or contralateral secondary carcinoma. J Comput Assist Tomogr 1997;21: Orel SG, Reynolds C, Schnall MD, Solin LJ, Fraker DL, Sullivan DC. Breast carcinoma: MR imaging before re-excisional biopsy. Radiology 1997;205: Heywang-Kobrunner SH, Schlegel A, Beck R, et al. Contrast-enhanced MRI of the breast after limited surgery and radiation therapy. J Comput Assist Tomogr 1993;17: Rieber A, Zeitler H, Rosenthal H, et al. MRI of breast cancer: influence of chemotherapy on sensitivity. Br J Radiol 1997;70: Gilles R, Guinebretiere JM, Toussaint C, et al. Locally advanced breast cancer: contrast-enhanced subtraction MR imaging of response to preoperative chemotherapy. Radiology 1994;191: Abraham DC, Jones RC, Jones SE, et al. Evaluation of neoadjuvant chemotherapeutic response of locally advanced breast cancer by magnetic resonance imaging. Cancer 1996;78: Hylton N, Esserman L, Partridge S, et al. Chemotherapy response and prediction of survival in locally advanced breast cancer using contrast-enhanced MRI. 8th Scientific Meeting of the International Society of Magnetic Resonance in Medicine. Baltimore, p Sittek H, Perlet C, Untch M, Kessler M, Reiser M. [Dynamic MRmammography in invasive lobular breast cancer]. Rontgenpraxis 1998;51: Rodenko GN, Harms SE, Pruneda JM, et al. MR imaging in the management before surgery of lobular carcinoma of the breast: correlation with pathology. Am J Roentgenol 1996;167: Horiguchi J, Iino Y, Takei H, et al. Comparison of breast-conserving therapy with mastectomy for treatment of early breast cancer. Anticancer Res 1997;17: Leung J, Kinkel K, Wang WL, Sickles EA, Hylton NM. Morphologic and kinetic characteristics of lobular carcinoma of the breast at MR imaging. Am J Roentgenol 2000;174(S): Zurrida S, Bartoli C, Galimberti V, Raselli R, Barletta L. Interpretation of the risk associated with the unexpected finding of lobular carcinoma in situ. Ann Surg Oncol 1996;3: Carson W, Sanchez-Forgach E, Stomper P, Penetrante R, Tsangaris TN, Edge SB. Lobular carcinoma in situ: observation without surgery as an appropriate therapy. Ann Surg Oncol 1994;1: Abner AL, Connolly JL, Recht A, et al. The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy. Cancer 2000;88: Orel SG, Mendonca MH, Reynolds C, Schnall MD, Solin LJ, Sullivan DC. MR imaging of ductal carcinoma in situ. Radiology 1997; 202: Soderstrom CE, Harms SE, Copit DS, et al. Three-dimensional RODEO breast MR imaging of lesions containing ductal carcinoma in situ. Radiology 1996;201: Gilles R, Meunier M, Lucidarme O, et al. Clustered breast microcalcifications: evaluation by dynamic contrast-enhanced subtraction MRI. J Comput Assist Tomogr 1996;20: Kinkel K, Hwang H, Hylton N, Sickles E. Clinical utility of MR imaging in patients diagnosed with DCIS of the breast. Personal communication at the Swiss Society of Radiology, Bern, Switzerland, May Soderstrom CE, Harms SE, Farrell Jr RS, Pruneda JM, Flamig DP. Detection with MR imaging of residual tumor in the breast soon after surgery [see comments]. Am J Roentgenol 1997;168: