Incidental Internal Mammary Lymph Nodes Visualized on Screening Breast MRI

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1 Women s Imaging Original Research Mack et al. MRI of Internal Mammary Lymph Nodes Women s Imaging Original Research Meghan Mack 1 Alison Chetlen 2 Jason Liao 3 Mack M, Chetlen A, Liao J Keywords: breast MRI, internal mammary lymph nodes, normal values, screening DOI: /AJR Received July 27, 2014; accepted after revision November 18, Presented at 2015 ARRS annual meeting, Toronto, ON, Canada. 1 Penn State College of Medicine, 500 University Dr, Hershey, PA Address correspondence to M. Mack (mmack@hmc.psu.edu). 2 Department of Radiology, Penn State Milton S. Hershey Medical Center, Penn State Hershey Breast Imaging, Hershey, PA. 3 Division of Biostatistics and Bioinformatics, Penn State Hershey Cancer Institute, Penn State College of Medicine. AJR 2015; 205: X/15/ American Roentgen Ray Society Incidental Internal Mammary Lymph Nodes Visualized on Screening Breast MRI OBJECTIVE. The frequency of visualization and size of internal mammary lymph nodes in women undergoing high-risk screening breast MRI is unknown. When these nodes are discovered on staging MRI of newly diagnosed breast cancer patients, management could present a treatment dilemma because normal size criteria do not exist. The aim of this study was to establish the average size and frequency of internal mammary lymph nodes observed in asymptomatic high-risk women undergoing screening breast MRI. MATERIALS AND METHODS. We conducted a retrospective review of 108 women at high risk for breast cancer who underwent screening breast MRI between January 2010 and January Patients with new or previous diagnosis of breast cancer, prior nonbreast malignancy affecting the thorax or mediastinum, or previous radiation to the thorax were excluded. The presence, diameter, laterality, intercostal space, relationship to the internal mammary vessels, age, morphology, and clinical history of internal mammary lymph nodes were recorded. RESULTS. Internal mammary lymph nodes were visualized in 50 of 108 high-risk patients, with an average size of 4.5 mm (range [± SD], 2 9 ± 1.59 mm). In the 50 women who had internal mammary lymph nodes visible on MRI, an average of 1.4 nodes (range, 1 3 nodes) were present. Internal mammary lymph nodes were more frequently visualized on the left (p < 0.001), at the second and third intercostal spaces (p = 0.007), and medial to the internal mammary vessels (p < 0.001). CONCLUSION. In this small cohort, 1 3 presumed normal internal mammary lymph nodes measuring 2 9 mm (mean diameter 4.5 mm) were detected in about half of asymptomatic high-risk women presenting for screening MRI of the breasts. T he frequency of detection of internal mammary lymph nodes in high-risk screening breast MRI examinations is unknown. If internal mammary lymph nodes are detectable in the absence of disease, their detection on diagnostic staging breast MRI in a new breast cancer patient may simply be physiologic rather than a sign of metastasis. Incidentally visualized internal mammary lymph nodes have occasionally been reported on screening and diagnostic MRI, and cadaver studies have examined the average number of internal mammary lymph nodes in the population on the basis of gross dissection [1 4]. That they are detectable in the absence of disease suggests some level of physiologic presence. However, the frequency and characteristics of incidental internal mammary lymph nodes visualized on MRI in asymptomatic women has not been previously evaluated. Therefore, when inter- nal mammary lymph nodes are visualized on staging MRI of a newly diagnosed breast cancer, their significance is uncertain. It is important to identify the characteristics of nonmetastatic physiologic internal mammary lymph nodes. Internal mammary lymph nodes detected on breast MRI examinations at the time of a new cancer diagnosis can alter the breast cancer staging if metastasis to an internal mammary lymph node is suspected. The presence of an internal mammary lymph node in a newly diagnosed breast cancer patient can also create a treatment dilemma because visualization of an internal mammary lymph node on staging breast MRI does not necessarily signify metastatic disease [5]. The decision to treat internal mammary lymph nodes is further complicated by conflicting studies regarding the survival benefits of the various treatment methods and concern for side effects [6 11]. Radiation therapy is often recommended AJR:205, July

2 Mack et al. for metastatic disease involving the internal mammary lymph nodes, with cardiotoxicity and pulmonary toxicity as potential complications [9, 12]. This study evaluates the frequency of incidental internal mammary lymph nodes visualized in high-risk screening breast MRI examinations and assesses the average size, location, and morphology of the nodes. Knowledge of the characteristics of normal incidentally detected internal mammary lymph nodes on breast MRI examinations will establish normal reference criteria that will potentially guide the optimal management of an individual patient s disease. Materials and Methods Study Patients We performed a retrospective HIPAA-compliant institutional review board approved study of 108 asymptomatic women between the ages of 22 and 79 years who presented for a high-risk screening breast MRI examination between January 1, 2010, and January 1, In total, 1633 of 2020 MRI examinations were excluded because they did not have a final BI-RADS [13] category 1 assessment. Of the remaining 387 examinations, 231 were further excluded because of a previous diagnosis of breast cancer; previous radiation to the thorax; or presentation for diagnostic MRI because of pain, palpable abnormality, or diagnostic dilemma. The remaining 156 MRI examinations consisted of the 108 most recent highrisk MRI examinations and 48 prior (older comparison) MRI examinations from these 108 patients. These 108 patients included asymptomatic women who underwent a screening high-risk breast MRI because of increased risk of breast cancer (National Cancer Institute lifetime risk 20% identified by the Gail model). The Gail model is a breast cancer risk assessment tool that estimates a woman s lifetime risk of developing breast cancer on the basis of previous pathology or radiation, genetic predisposition to breast cancer, age, age at first menstrual period and live birth, number of first-degree relatives affected by breast cancer, number of positive and negative breast biopsies, and ethnicity [14]. The women in this study who were identified as having a lifetime risk of 20% or greater included those with a strong family history; known genetic mutation (such as BRCA1 mutation, BRCA2 mutation, Cowden syndrome, CDH1 mutation); or prior high-risk breast pathology, such as lobular carcinoma in situ, atypical lobular hyperplasia, or atypical ductal hyperplasia. Of the 108 patients in the sample population, 26 (24%) had known genetic mutation, 68 (63%) had a strong family history of breast cancer without a known genetic mutation, and the remaining 14 (13%) had a history of high-risk breast pathology. Patients were excluded if they were pregnant or had a new or previous diagnosis of breast cancer; history of a prior nonbreast malignancy that affected the thorax or mediastinum; prior systemic malignancy, including lymphoma, leukemia, or sarcoma; or previous radiation therapy to the thorax. Men were also excluded. Imaging All patients in the study underwent breast MRI with a 1.5-T scanner (Magnetom Espree, Siemens Healthcare). Subjects lay in the prone position with a dedicated breast coil. Two-dimensional acquired axial T1-weighted (TR/TE, 776/15; matrix, ; slice thickness, 3 mm), axial T2-weighted with fat saturation (TR/TE, 7290/82; matrix, ; slice thickness, 3 mm), and 3D acquired axial T1-weighted with dynamically contrast-enhanced fat saturation images (TR/TE, 4.37/1.5; matrix, ; slice thickness, 1.2 mm) were obtained. Acceleration image acquisition was used for the 3D contrast-enhanced sequences (ipat, Siemens Healthcare) with an acceleration factor of 2. Three-dimensional volume-rendered images of both breasts were also obtained on a separate workstation. Each patient received 20 ml of gadopentetate dimeglumine IV (Magnevist, Berlex) as the contrast agent injected at a bolus at a rate of 2 ml/s followed by a saline flush, with four, 1-minute contrast-enhanced sequences beginning 20 seconds after the initiation of the injection. The slice thickness of the axial T1-weighted sequences was 3 mm; the slice thickness of the axial contrast-enhanced fat-saturated images was 1.2 mm. Only axial images were reviewed because our institution s protocol for breast MRI does not image or reconstruct in the sagittal or coronal plane. All images were reviewed on a high-resolution monitor. Findings were recorded using mammography reporting software (MagView). The 2D acquired T1-weighted, 2D acquired T2-weighted, and 3D acquired contrast-enhanced fat-saturated T1-weighted axial sequences were reviewed by a dedicated fellowship-trained breast radiologist who was blinded to the patient s clinical history. The parasternal area was adequately visualized and assessed despite cardiac motion present on all breast MRI examinations. The MRI examinations included in the final dataset were evaluated for the presence of visible internal mammary lymph nodes on axial T1- weighted images and axial fat-saturated T1 contrast-enhanced images. If present, the laterality, intercostal space, morphology, largest diameter approximated to the nearest millimeter, and position with respect to the internal mammary blood vessels were recorded from the first contrast-enhanced axial fat-saturated T1-weighted sequence, which had a slice thickness of 1.2 mm. The patient s clinical history obtained through our electronic medical record, including any genetic predisposition to breast cancer, family history, and prior breast biopsy results, was also recorded. Some of the patients in the final dataset had undergone more than one MRI examination that was assigned BI-RADS category 1 between 2010 and In these instances, only the most recent MRI was included in the final dataset of 108 cases. If internal mammary lymph nodes were detected on that patient s most recent MRI, her prior MRI examinations were reviewed to determine whether the internal mammary lymph nodes were present or changed over time. Statistical Analysis Descriptive statistical analysis was performed at Hershey Medical Center and included frequency of internal mammary lymph nodes, size distribution, laterality, intercostal space, and position with respect to the blood vessels. The laterality was further evaluated for a difference in frequency between the left and right side using fixed-effects and randomeffects models, with a null hypothesis that lymph nodes were distributed evenly between the left and right. Intercostal space distribution was determined by a two-sample Kolmogorov-Smirnov test, with a null hypothesis that lymph nodes were distributed evenly among the first four intercostal spaces. The distribution of lymph nodes with respect to the internal mammary blood vessels was determined using a Fisher exact test, with the null hypothesis that lymph nodes were distributed evenly at positions medial to, lateral to, and in between the blood vessels. A difference in size between lymph nodes found in the different distributions (left vs right, intercostal space, and position with respect to internal mammary blood vessels) was evaluated using a fixed-effects and random-effects model, with a null hypothesis that the sizes were equal within each distribution. Results Frequency Internal mammary lymph nodes were visualized in 50 of the 108 women (46%). Thirty percent (15/50) of women had more than one visible internal mammary lymph node: 12 of those 15 women had two internal mammary lymph nodes, and three had three internal mammary lymph nodes. Therefore, if a patient had visible internal mammary lymph node on a high-risk screening MRI examination, an average of 1.4 lymph nodes (68 total internal mammary lymph nodes in 50 patients with visible internal mammary lymph nodes) were seen. 210 AJR:205, July 2015

3 MRI of Internal Mammary Lymph Nodes Size The average (mean) size of all lymph nodes measured in their greatest diameter was 4.50 mm (range, 2 9 ± 1.59 mm). The average size of lymph nodes varied according to laterality, intercostal space, and position with respect to the internal mammary blood vessels (Table 1). Laterality Internal mammary lymph nodes were more frequently found on the left side of the thorax than on the right (p < 0.001). Of the 68 total internal mammary lymph nodes visualized in the 50 patients in this study, 48 (71%) were seen on the left, and 20 (29%) were seen on the right. In the patients with multiple internal mammary lymph nodes, 11 of the 15 patients had lymph nodes bilaterally, whereas the remaining four patients had multiple nodes only on the left side. Thirty of 50 (60%) women with lymph nodes had exclusively left lymph nodes, and nine (18%) had exclusively right lymph nodes. Intercostal space positions Internal mammary lymph nodes were not distributed equally between the first four intercostal spaces (two-sided Komolgorov-Smirnov test, p = 0.007). Internal mammary lymph nodes were found most frequently in the second intercostal space (caudal to the second rib), followed closely by the third intercostal space. Of the 68 internal mammary lymph nodes, 32 (47%) were seen in the second intercostal space, and 31 (46%) were seen in the third intercostal space. Three nodes (4%) were found in the fourth intercostal space, and two (3%) were found in the first intercostal space. In the second intercostal space, 24 of 32 nodes (75%) were found on the left, and eight (25%) were found on the right. In the third intercostal space, 21 nodes (68%) were found on the left, and 10 (32%) were found on the right. The three internal mammary lymph nodes in the fourth intercostal space were seen on the left, and the two internal mammary lymph nodes seen in the first intercostal space were seen on the right. Internal mammary lymph nodes were not visualized in the fifth intercostal space. Position of internal mammary lymph nodes with respect to internal mammary blood vessels The lymph nodes were classified as being medial to, lateral to, or between and slightly anterior to the internal mammary blood vessels (Fig. 1). The most common location for an internal mammary lymph node was medial to the blood vessels (p < 0.001). Of the 68 internal mammary lymph nodes, 47 (69%) were medial, 18 (27%) were lateral, and three (4%) were between the blood vessels. TABLE 1: Average Size of Internal Mammary Lymph Nodes by Location Location Mean Size (mm) Range (mm) Laterality (p = 0.59) Left Right Intercostal space (p = 0.089) First Second Third Fourth Position relative to internal mammary blood vessels (p = 0.69) Medial Lateral Between Fig. 1 Drawing shows distribution of incidentally visualized internal mammary lymph nodes. Vertical lines represent internal mammary blood vessels. Thirty-nine of the 47 medial nodes (83%) were found on the left side, and the remaining eight (17%) were found on the right side. Nine of the 18 lateral nodes (50%) were found on the left, and the remaining nine (50%) were found on the right. All three nodes that were in between the internal mammary blood vessels were found on the right side. One (33%) was at the second intercostal space, and two (67%) were found at the third intercostal space. Of those that were left and medial with respect to the internal mammary blood vessels, 20 of 39 (51%) were found at the second intercostal space, 17 (44%) were found at the third intercostal space, and two (5%) were found in the fourth intercostal space. None were found at the first intercostal space. Of the nine internal mammary lymph nodes found on the left and lateral to the blood vessels, four (44%) were found at the second intercostal space, four (44%) were found at the third intercostal space, and one (12%) was found at the fourth intercostal space. Of the eight internal mammary lymph nodes that were on the right side of the thorax and medial to the blood vessels, four (50%) were at the second intercostal space, and three (37%) were at the third intercostal space. The remaining internal mammary lymph node (13%) was found at the first intercostal space. Of the nine internal mammary lymph nodes that were on the right side of the thorax and lateral to the blood vessels, three (33%) were at the second intercostal space and five (56%) were at the third intercostal space. The remaining internal mammary lymph node (11%) was found at the first intercostal space. Figures 2 through 5 reflect the variety of internal mammary lymph node distributions in asymptomatic women who presented for screening breast MRI. Age of the Patient The mean age of the 108 women included in the study was 48.6 years (range, years). There was no statistically significant difference between the average age of the sample (48.6 years) and the average age of the patients in the sample who had visible lymph nodes (49.2 years). There was also no statistically significant difference between the average age of patients with internal mammary lymph nodes on the left (49.3 years) and the average age of patients with internal mammary lymph nodes on the right (48.5 years). The average patient age was also similar for the second (48.4 years) and third (48.5 years) intercostal spaces. AJR:205, July

4 Mack et al. Fig year-old woman with strong family history of breast cancer. This 3D acquired contrast-enhanced T1-weighted fat-saturated axial MR image (TR/TE, 4.37/1.5; matrix, ; slice thickness, 1.2 mm; accelerated image acquisition technique ipat [Siemens Healthcare], 2) shows 6-mm right-sided internal mammary lymph node (arrow) with normal morphology located in second intercostal space, situated lateral to internal mammary blood vessels. Morphology None of the 68 internal mammary lymph nodes had abnormal morphology, such as a necrotic center or thickened cortex with loss of the fatty hilum. All internal mammary lymph nodes had either a visible fatty hilum or a normally shaped lobular or oval appearance with circumscribed margins. Chronicity and Comparison With Previous MRI Examinations Forty-three patients had previous MRIs in the time range of the study with findings that were designated as BI-RADS category 1, and 17 of those 43 (40%) had one or more detectable internal mammary lymph nodes at the Fig year-old woman with strong family history of breast cancer. This 3D acquired contrast-enhanced T1-weighted fat-saturated axial MR image (TR/TE, 4.37/1.5; matrix, ; slice thickness, 1.2 mm; accelerated image acquisition technique ipat [Siemens Healthcare], 2) shows bilateral internal mammary lymph nodes (arrows): 3-mm right-sided internal mammary lymph node with normal morphology located in third intercostal space situated medial to internal mammary blood vessels and 5-mm left-sided internal mammary lymph node with normal morphology located in third intercostal space situated medial to internal mammary blood vessels. Note variant anatomy of three internal mammary vessels on right. Fig year-old woman with strong family history of breast cancer. This 3D acquired contrastenhanced T1-weighted fat-saturated axial MR image (TR/TE, 4.37/1.5; matrix, ; slice thickness, 1.2 mm; accelerated image acquisition technique ipat [Siemens Healthcare], 2) shows 5-mm left-sided internal mammary lymph node (arrow) with normal morphology located in second intercostal space, situated medial to internal mammary blood vessels. most recent MRI. In this group, there were a total of 20 internal mammary lymph nodes, for an average of 1.2 internal mammary lymph nodes per person (20 total internal mammary lymph nodes of 17 MRI examinations with visible internal mammary lymph nodes). A review of these patients previous MRI studies showed that all 20 internal mammary lymph nodes had been present at the time of the prior studies, and all but one, which had decreased in size on the most recent MRI examination, were unchanged. Fig year-old woman with strong family history of breast cancer. This 3D acquired contrastenhanced T1-weighted fat-saturated axial MR image (TR/TE, 4.37/1.5; matrix, ; slice thickness, 1.2 mm; accelerated image acquisition technique ipat [Siemens Healthcare], 2) shows bilateral internal mammary lymph nodes (arrows): 5-mm right-sided internal mammary lymph node with normal morphology located in third intercostal space situated lateral to internal mammary blood vessels and 8-mm left-sided internal mammary lymph node with normal morphology located in third intercostal space situated medial to internal mammary blood vessels. Discussion Our study evaluated the average size and frequency of incidentally-visualized internal mammary lymph nodes in asymptomatic women to establish criteria that could help guide management of internal mammary lymph nodes detected on staging MRI for newly diagnosed breast cancer. Incidental internal mammary lymph nodes, found in 46% of women in our study, are a relatively common finding in women presenting for highrisk screening MRI. The axilla and internal mammary lymph nodes comprise the primary lymphatic drainage of the breast. Axillary lymph nodes are responsible for 75% of the lymph drainage of the ipsilateral breast, and the internal mammary lymph nodes are responsible for draining much of the remainder [15, 16]. Several previous studies have explored the frequency of lymphatic drainage to internal mammary lymph nodes [16 18]. Primary breast cancers arising in the central and inner portions of the breast spread more frequently and at an earlier stage to the internal mammary lymph nodes than do similar lesions arising in the outer portion of the breast. Of 725 radical mastectomies performed by Urban and Marjani [16] over a 20-year period in patients with medial and central breast malignancies, 33% showed internal mammary lymph node involvement and 47% showed axillary involvement. The internal mammary lymph nodes alone were pathologically positive in 8% of the patients. As the location of the primary tumor moves laterally within the breast, the relative involvement of internal mammary lymph nodes versus axillary lymph nodes diminishes so that almost no lesions presenting in the outer quadrant with negative axillary lymph nodes show internal mammary lymph node involvement [16]. Although a correlation between primary tumor location and nodal basin involved exists, it has been shown that primary tumors arising in any quadrant can drain to either set or both sets of lymph nodes [17, 19]. Researchers using lymphoscintigraphy have determined similar patterns of drainage to the internal mammary lymph nodes and have also noted that internal mammary lymph node involvement without axillary involvement is rare [17]. Evaluating nodal involvement in breast cancer is important because it can alter the staging if metastasis to lymph nodes is suspected [20]. The breast cancer automatically becomes a stage III cancer if the internal mammary lymph nodes are involved [21]. According to the sixth edition of the AJCC Cancer Staging Manual for Breast Cancer, metastases to the internal mammary lymph nodes are classified as N1, N2, or N3 on the 212 AJR:205, July 2015

5 MRI of Internal Mammary Lymph Nodes basis of the size of the primary lesion and presence or absence of concurrent axillary nodal involvement [22]. The pathologic diagnostic criterion for lymph node metastasis according to the AJCC 6th edition is a cluster of malignant cells greater than 0.2 mm in the lymph node [23]. If axillary lymph nodes are negative, a positive internal mammary lymph node is considered an axillary node in staging and thus would be N1, provided that it is greater than 0.2 mm, even though the axillary nodes are negative [22]. Metastatic involvement of lymph nodes also has prognostic significance [20]. Although it was previously thought that breast cancer spread to the rest of the body through the regional lymph nodes, breast cancer is now considered to metastasize through the blood, and lymph node involvement is an indicator of poor prognosis rather than a passageway for distant disease [24]. Internal mammary lymph node involvement alone, although rare, has been found to carry similar or worse prognostic implications compared with axillary node involvement alone [15, 19, 25]. Concurrent internal mammary lymph node and axillary node metastasis has proven to be more serious in terms of overall survival when compared with involvement of only one of the nodal basins [17]. In addition to having staging and prognostic significance, the presence of internal mammary lymph nodes on staging breast MRI can influence treatment considerations because their presence may signify metastatic spread of the primary tumor [5]. Treatment of breast carcinoma that has apparently spread to the internal mammary lymph nodes is controversial. The location of internal mammary lymph nodes near the heart, lungs, and ribs can make excisional treatment difficult, and surgical excision of internal mammary lymph nodes includes potential complications, such as pneumothorax. In addition, the survival benefit afforded by surgical excision of internal mammary lymph nodes has not been conclusively shown [6, 26]. Because the benefit is unclear and potential complications surround internal mammary node excision, most internal mammary lymph node metastasis patients are treated with adjuvant chemotherapy or radiation rather than surgical dissection [27]. The current National Comprehensive Cancer Network Clinical Practice Guidelines recommend the use of radiotherapy when internal mammary lymph node metastasis is suspected clinically [23]. Although some studies have found no survival benefit [7, 8], several others have shown that survival was greatly improved by the administration of radiation to the internal mammary lymph nodes [9 11]. Even though radiation can provide excellent local control to those with metastatic disease, potential complications exist. Radiation can cause cardiac toxicity, such as ischemic heart disease, and radiation pneumonitis. The finding that internal mammary lymph nodes were more frequently detected on the left side than on the right was surprising. This finding is significant because radiation to normal incidentally-visualized left-sided internal mammary lymph nodes could result in cardiac complications [9, 12]. Prior studies have reported that superior internal mammary lymph nodes are more frequently involved in metastasis than are inferior internal mammary lymph nodes [18, 28]. Although a prior study stated that the first intercostal space is most frequently involved in metastasis and another found that the second intercostal space is a more common location, both of these studies discovered a high frequency of metastases in both the first and second intercostal spaces [15, 29 31]. A more recent study that focused primarily on the second and third intercostal spaces also described the second intercostal space as the most common location for metastasis, followed closely by the third [10]. In our study, we also found the second and third intercostal spaces to be the most common locations for incidental internal mammary lymph nodes, but we found very few incidentally visualized internal mammary lymph nodes in the first intercostal space. This suggests that this is not a common location for incidental physiologic internal mammary lymph nodes to be visualized on breast MRI. Therefore, if one or more internal mammary lymph nodes are seen in the first intercostal space on staging breast MRI, they should be viewed with suspicion and may warrant further investigation. The determination of the average size of 4.5 mm for incidentally-visualized nonmetastatic internal mammary lymph nodes is not only important for comparison with metastatic internal mammary lymph nodes but also for assessing the ability of modern detection methods to evaluate internal mammary lymph nodes. On PET, internal mammary lymph nodes with suspected metastases are typically thought to be those with 18 F-FDG uptake clearly greater than the adjacent background in the first fifth intercostal spaces along the lateral sternal border [23, 32]. However, a limitation of PET is that the resolution is poor for structures that are less than 8 mm [33]. Because we found that most internal mammary lymph nodes (64/68, 94%) are less than 8 mm, the sensitivity of PET to detect the true metabolic activity of internal mammary lymph nodes may be low. Previous studies have reported internal mammary lymph nodes both medial to and lateral to the internal mammary blood vessels, with most located medially overall [4, 15, 29]. We also visualized most internal mammary lymph nodes located medial to the internal mammary blood vessels. The analysis of each patient s prior MRI studies from our population supports that some internal mammary lymph nodes are physiologically present in an asymptomatic population of women. Each internal mammary lymph node that was visualized on a patient s current MRI examination was also seen on her prior MRI examinations. Internal mammary lymph nodes were present and unchanged over time, which supports the conclusion that internal mammary lymph nodes have a physiologic consistent presence in approximately half the population. Limitations Because this is the first study, to our knowledge, to examine incidentally visualized internal mammary lymph nodes on breast MRIs in asymptomatic women, further research could compare this population with women with newly diagnosed breast cancer. All nodes in our study were presumed normal; no reference standard proof of normalcy exists for the nodes detected in this exercise. Including BI-RADS category 2 patients in addition to BI-RADS category 1 patients would have improved the utility of this study; however, we chose to exclude all women with any breast finding, benign or malignant, for this initial study. A further limitation was our inability to assess very small (< 2 mm) physiologic lymph nodes because the slice thickness of our MR images was 1.2 mm. Additionally, visualization of the parasternal area is always somewhat challenging because of cardiac motion. Although cardiac gating is technically possible, it would add significant time to the study and be uncomfortable for the patient who would by lying prone on the breast coil and wearing ECG leads. Another option to improve visualization of the parasternal area would be to place a posterior saturation band across the heart to reduce cardiac motion artifact; however, visualization of the axillary regions would be compromised. Neither method would be practical in a high- AJR:205, July

6 Mack et al. volume practice because patient comfort and efficiency of MRI are valued. Finally, because the number of subjects was rather small and from a single institution, the work needs to be replicated in a much larger sample from additional institutions. Future studies are needed to validate internal mammary lymph node assessment in patients with newly diagnosed breast cancer undergoing breast MRI. Because of the significant impact that suspected metastasis to the internal mammary lymph nodes can have on staging, prognosis, and treatment considerations, accurate detection and identification of potential metastasis to internal mammary lymph nodes is critical to optimal management and patient care. Most prior studies have focused on characteristics of internal mammary lymph nodes in cases of a newly diagnosed breast cancer [1, 15, 16, 23, 32]. By describing the average size and frequency of internal mammary lymph nodes detected on screening MRI of asymptomatic women, our study provides reference criteria to aid in the evaluation of internal mammary lymph nodes visualized on high-risk screening MRI examinations as well as staging breast MRI in a newly diagnosed breast cancer patient. Conclusion In this small cohort, 1 3 presumed normal internal mammary lymph nodes measuring 2 9 mm (mean diameter, 4.5 ± 1.59 mm) were detected in about half of asymptomatic high-risk women presenting for screening MRI of the breasts. References 1. Rinaldi P, Costantini M, Belli P, et al. Extra-mammary findings in breast MRI. Eur Radiol 2011; 21: Rausch DR. Spectrum of extra-mammary findings on breast MRI: a pictorial review. Breast J 2008; 14: Webb WR, Higgins CB. Thoracic imaging: pulmonary and cardiovascular radiology. Philadelphia, PA: Lippincott Williams & Wilkins, Stibbe EP. The internal mammary lymphatic glands. J Anat 1918; 52(Pt 3): Cranenbroek S, van der Sangen MJ, Kuijt GP, Voogd AC. Diagnosis, treatment and prognosis of internal mammary lymph node recurrence in breast cancer patients. Breast Cancer Res Treat 2005; 89: Freedman GM, Fowble BL, Nicolaou N, et al. Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist? Int J Radiat Oncol Biol Phys 2000; 46: Laino C. Radiation treatment of internal mammary nodes has no impact on long-term survival. Oncol Times UK 2010; 7:8 8. Fowble B, Hanlon A, Freedman G, et al. Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer. Int J Radiat Oncol Biol Phys 2000; 47: Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366: Veronesi U, Arnone P, Veronesi P, et al. The value of radiotherapy on metastatic internal mammary nodes in breast cancer: results on a large series. Ann Oncol 2008; 19: Chen RC, Lin NU, Golshan M, Harris JR, Bellon JR. Internal mammary nodes in breast cancer: diagnosis and implications for patient management a systematic review. J Clin Oncol 2008; 26: Giordano SH, Kuo YF, Freeman JL, Buchholz TA, Hortobagyi GN, Goodwin JS. Risk of cardiac death after adjuvant radiotherapy for breast cancer. J Natl Cancer Inst 2005; 97: Morris E, Cornstock C, Lee C, et al. ACR BI-RADS atlas, breast imaging reporting and data system. Reston, VA: American College of Radiology, Gail MH, Brinton LA, Byar DP, et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: Morrow M, Foster RS. Staging of breast cancer: a new rationale for internal mammary node biopsy. Arch Surg 1981; 116: Urban JA, Marjani MA. Significance of internal mammary lymph node metastases in breast cancer. Am J Roentgenol Radium Ther Nucl Med 1971; 111: Byrd DR, Dunnwald LK, Mankoff DA, et al. Internal mammary lymph node drainage patterns in patients with breast cancer documented by breast lymphoscintigraphy. Ann Surg Oncol 2001; 8: Estourgie SH, Nieweg OE, Olmos RA, Rutgers EJ, Kroon BB. Lymphatic drainage patterns from the breast. Ann Surg 2004; 239: Sugg SL, Ferguson DJ, Posner MC, Heimann R. Should internal mammary nodes be sampled in the sentinel lymph node era? Ann Surg Oncol 2000; 7: Chatzopoulos SE, Behranwala KA, Jayia P, Al_ Mufti R, Cleator SJ, Hadjiminas DJ. should internal mammary lymph node biopsy be a routine step in recurrent breast cancer? Report of three cases with negative axilla and positive internal mammary node. World J Oncol 2011; 2: Egner JR. AJCC cancer staging manual. JAMA 2010; 304: Singletary SE, Connolly JL. Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J Clin 2006; 56: Choi JE. The metastatic rate of internal mammary lymph nodes when metastasis of internal mammary lymph node is suspected on PET/CT. J Breast Cancer 2013; 16: Jatoi I, Hilsenbeck SG, Clark GM, Osborne CK. Significance of axillary lymph node metastasis in primary breast cancer. J Clin Oncol 1999; 17: Veronesi U, Cascinelli N, Greco M, et al. Prognosis of breast cancer patients after mastectomy and dissection of internal mammary nodes. Ann Surg 1985; 202: Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R. The dissection of internal mammary nodes does not improve the survival of breast cancer patients: 30-year results of a randomised trial. Eur J Cancer 1999; 35: Koo MY, Lee SK, Bae SY, et al. Long-term outcome of internal mammary lymph node detected by lymphoscintigraphy in early breast cancer. J Breast Cancer 2012; 15: Jatoi I. Internal mammary sentinel nodes in primary breast cancer. Curr Med Res Opin 2003; 19: PubMed doi: / Marks LB, Hebert ME, Bentel G, Spencer DP, Sherouse GW, Prosnitz LR. To treat or not to treat the internal mammary nodes: a possible compromise. Int J Radiat Oncol Biol Phys 1994; 29: Caceres E. Incidence of metastasis in the internal mammary chain in operable cancer of the breast. Surg Gynecol Obstet 1959; 108: Urban JA, Baker HW. Radical mastectomy in continuity with en bloc resection of the internal mammary lymph-node chain: a new procedure for primary operable cancer of the breast. Cancer 1952; 5: Bellon JR, Livingston RB, Eubank WB, et al. Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC). Am J Clin Oncol 2004; 27: Penhoet EE, Petitti DB, Joy JE. Saving women s lives: strategies for improving breast cancer detection and diagnosis. Washington, DC: National Academies Press, AJR:205, July 2015

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