We evaluated the medical records of 1,015 patients who underwent surgery for primary breast cancer between February 2007 and August 2008 at St.

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1 Elastographic evaluation of mucinous carcinoma of the breast Miki Mori Hiroko Tsunoda Nobue Kawauchi Mari Kikuchi Satoshi Honda Koyu Suzuki Hideko Yamauchi Abstract Background Elastography is widely used as a diagnostic tool for the diagnosis of invasive breast cancer. However, no study has yet shown if elastography for diagnosing mucinous carcinoma is as useful as that for diagnosing the usual invasive carcinoma. Mucinous carcinoma is considered as a soft tumor. In this study, we used elastography to evaluate the elasticity of mucinous carcinoma. Methods Among 1,015 patients who underwent surgery for primary breast cancer between February 2007 and August 2008 in our facility, the final pathological diagnosis showed only 32 mucinous carcinomas. We evaluated 16 of the 32 mucinous carcinoma patients who underwent preoperative elastography. Results There were 13 cases of the pure-type and 3 cases of the mixed-type mucinous carcinoma. B-mode ultrasound (US) imaging showed mass formation in 16 patients. The elasticity score was 2 in 1 case (8%), 3 in 3 cases (23%), 4 in 7 cases (54%), and 5 in 2 cases (15%). The fat-to-lesion ratio (FLR) was evaluated in 7 cases. The mean value of the FLR was 12 (range 3 30). Conclusion Twelve of the 16 (75%) cases had an elastography score of 4 or 5. Although mucinous carcinoma had an elastography score similar to that of usual invasive carcinoma, elastography may be useful for distinguishing mucinous carcinoma from benign fibroadenoma. Keywords Elastography Mucinous carcinoma Ultrasonography Breast cancer Introduction Elastography was developed recently, and it has been used for clinical purposes in various fields. Elastography is being widely used in the field of breast cancer. Elastography reveals the tissue strain induced by compression, and the tissue elasticity can thereby be estimated. Before elastography was introduced, tissue hardness could be subjectively estimated only by a dynamic test. Furthermore, elastography enables an objective visual assessment. It is useful as an adjunct tool for diagnosing breast cancer. The principle of elastography is that tissue compression produces a strain (displacement) within the tissue, and this strain is smaller in harder tissues than in softer tissues. Few studies have described the elastography of mucinous carcinoma, which is a special type of breast cancer. Mucinous carcinoma is thought to be soft because it is rich in mucin. We evaluated the elastograms of mucinous carcinoma to assess if elastography is a useful tool for the diagnosis of mucinous carcinoma. Materials and methods

2 We evaluated the medical records of 1,015 patients who underwent surgery for primary breast cancer between February 2007 and August 2008 at St.Luke s International Hospital, Tokyo, Japan. This study was approved by the ethics committee of St. Luke s International Hospital. In our institution, informed consent was not obtained according to the routine practice. Thirty-two patients were diagnosed with mucinous carcinoma on the basis of the final surgical specimen. We reviewed the charts of 16 mucinous carcinoma cases, which were examined by preoperative elastography. Of the16cases, 13 cases were pure-type and 3 cases were mixed-type mucinous carcinoma. The average age of the patients was 53 years (age range years). Mean age was 48 years. The tumor sizes (T factor) in the final pathological diagnosis are listed in Table 1.The hormone statuses were positive in all the cases. Immunohistochemistry showed negative results for HER2. Therefore, all cases were classified as luminal A type. We evaluated shape in B mode, elasticity score, fat-to lesion ratio (FLR), and the blood flow rate by using HITACHI ecom EUB-7500 (Hitachi Medical Corporation, Tokyo, Japan) equipped with a transducer of 6 13 MHz (EUP-L65; Hitachi Medical Corporation, Tokyo, Japan). Elastographic evaluation was performed using this modality: the hardness of the tissue is displayed intermsofthe color tone, with increasing hardness presented in the ascending order of red, yellow, green, and blue. The strain of the tissue was evaluated according to the color pattern of the hypoechoic lesion (i.e., the area that was hypoechoic or isoechoic relative to the subcutaneous fat [except for echogenic halo] on B-mode images) and in the surrounding breast tissue where it is considered as normal breast and fat tissue. On the basis of the Tsukuba elasticity score, the hardness was classified on a five-point scale [1]. A score of 1 indicates an even strain in the entire hypo echoic lesion (i.e.,the entire lesion was even lyshaded in green).ascoreof2indicatesastraininmost portions of the hypo echoic lesion, with some areas without the strain(i.e.,the hypoechoic lesion had a mosaic pattern of green and blue).ascoreof3indicatesastrainattheperipheryofthe hypoechoic lesion, barring the center of the lesion (i.e., the peripheral part of lesion was green, and the central part was blue).a score of4indicatesnostraininthe entire hypoechoic lesion (i.e.,the entire lesion was blue, but its surrounding area was not included). A score of 5 indicates no strain in the entire hypoechoic lesion and in the surrounding area (i.e., both the entire hypoechoic lesion and its surrounding area were blue). The FLR was defined as the ratio obtained by dividing the mean strain of the fat tissue by the mean strain of the hypoechoic lesion. The strain of the subcutaneous fat tissue was determined from the region of interest (ROI) bound by the skin and mammary glands. The strain of a lesion was determined from the ROI bound by the inner margin

3 of the hypoechoic area. The cutoff point was 4.8 [2]. Results All 16 cases showed mass-forming lesions on B-mode images. The distribution of the elasticity scores is shown in Table 2. Four (25%) cases of the 16 mucinous carcinomas had a score of 2 or 3. Twelve(75%) cases had a score of 4 or 5. Of the 13 pure mucinous carcinoma cases, 1 (8%) case (Fig. 1) had a score of 2, 3 (23%) cases had a score of 3, 7 (54%) cases had a score of 4 (Fig. 2), and 2 (15%) cases had a score of 5. Of the 3 mixed mucinous carcinoma cases, 2 (67%) cases had a score of 4 and 1 (33%) case (Fig. 3) had a score of 5. FLR was obtained in 7 cases (Fig. 4). The average value was 12 (value range 3 30). Six cases had an FLR value higher than 4.8, whereas the only case with pure mucinous carcinoma had an elasticity score of 2. Discussion Mucinous carcinoma is a special type of invasive breast cancer, in which large amounts of extracellular epithelial mucin are present surrounding and within the tumor cells. The incidence of mucinous carcinoma is 2.9% of all breast cancers [3]. Mucinous carcinoma is sometimes difficult to distinguish from a benign lesion because both appear as smooth-surfaced masses. Mucinous carcinoma is considered to have less strain because of the mucin-rich tissue. No report has described the elasticity of mucinous carcinoma in a large series. Therefore, we compared the elasticity of mucinous carcinoma with that of the usual malignant lesions. Our results showed that mucinous carcinoma, both mixed mucinous carcinoma and pure-type mucinous carcinoma (which has a high amount of mucin), have a high elasticity score similar to that of the usual malignant lesions. Table 3 shows a comparison of this study with the other reports on the elasticity score of malignant lesions. The majority of the malignant lesions had a score of 4 or 5. This study shows that mucinous carcinoma has a similar strain as the usual malignant lesions. Four of 16 cases had an elasticity score of 2 and 3 in our study. These elasticity scores may have been low because the tumors were rich in mucin. The correlation between the amount of mucin and the low elasticity score is difficult to validate because the number of cases is extremely small in our study.the B-mode images of the cases with lower scores were compared with those with higher scores, but there was not any particular difference. A large sample population is needed to determine the reason for the low elasticity score. The results of our study show that elastography can be used to distinguish between mucinous carcinoma and myxomatous fibroadenoma. In B-mode images, mucinous carcinoma and myxomatous fibroadenoma are delineated as high-

4 echoic masses that have a similar circumference. Therefore, distinguishing between the 2 types of tumors is complicated. Fleury s report [9] shows that approximately 98% cases of fibroadenoma have an elasticity score of 3 or less. On the other hand, in our study, 75% of the cases with mucinous carcinoma had an elasticity score of 4 or 5 (Table 4). Elastography is considered to be a useful tool to distinguish mucinous carcinomas from fibroadenomas that are difficult to distinguish in B-mode images. The limitation of elastography is that some mucinous carcinoma shave lower scores and some fibroadenoma shave higher scores.the sample size is small in this study. We will therefore continue the study to solve this problem. Conclusion The elasticity score of mucinous carcinoma was as high as that of the usual malignant lesions. Elastography can be useful to distinguish between mucinous carcinoma and myxomatous fibroadenoma and may help to decrease the number of unnecessary biopsies. References 1. Itoh A, Ueno E, Tohno E, Kamma H, Takahashi H, Shiina T, et al. Breast disease: clinical application of US elastography for diagnosis. Radiology. 2006;239(2): Ueno E, Umemoto T, Bando H, Tohno E, Waki K, Matsumura T. New quantitative method in breast elastography: fat-lesion ratio (FLR) (abstract). In: Proceedings of the Radiological Society of North America Scientific Assembly and Meeting. Oak Brook, IL: Radiological Society of North America. 2007; Nyugankenshinnihituyonabyorigakutekitishiki, Sakamoto G. J Jpn Assoc Breast Cancer Screen. 2001;10(2): Regini E, Bagnera S, Tota D, Campanino P, Luparia A, Barisone F, et al. Role of sonoelastography in characterising breast nodules. Preliminary experience with 120 lesions. Radiology medicine. 2010;115(4): Schaefer FKW, Heer I, Schaefer PJ, Mundhenke C, Osterholz S, Order BM et al. Breast ulotrasound elastography results of 193 breast lesions in a prospective study with histopathologic correlation. Eur J Radiol. 2011;77(3): Tohno E, Ueno E. Current improvements in breast ultrasound, with a special focus on elastography. Breast Cancer. 2008;15: Zhu QL, Jiang YX, Liu JB, Liu H, Sun Q, Dai Q, et al. Real-time ultrasound elastography: its potential role in assessment of breast lesions. Ultrasound Med Biol. 2008;34: Scaperrotta G, Ferranti C, Costa C, Mariani L, Marchesini M, Suman L, et al. Role of sonoelastography in non-palpable breast lesions. Eur Radiol. 2008;18: Fleury EF, Rinaldi JF, Piato S, Fleury JC, Roveda Junior D. Appearence of breast masses on sonoelastography with special focus on the diagnosis of fibroadenomas.

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