【作者】 周洁；

【导师】 刘士远；

【作者基本信息】 第二军医大学 ， 影像医学与核医学， 2012， 博士

【摘要】 研究背景乳腺疾病的发病率在全球范围内均有上升趋势，尤其是乳腺癌已成为妇女第一位恶性肿瘤，在很多国家仍是死亡率最高的癌症。对于肿瘤小于1cm的乳腺癌患者，无论肿瘤分化级别的高低，其10年生存率均可达95%。而当肿瘤介于2～5cm之间的患者，10年生存率仅为60%。因此，早期诊断是治愈乳腺癌、改善乳腺癌预后的关键。乳腺X线摄影检查作为乳腺癌的最重要的筛检手段、诊断方法在国内、外已越来越得到广泛的应用，而“局灶性不对称”（Focal Asymmetry，FA）征象是乳腺X线摄影中较为特殊且难以定性诊断的问题之一。这一征象往往可以是早期浸润性乳腺癌及不典型乳腺癌在乳腺X线摄影中的唯一表现；同时它也可以是乳腺炎、纤维化、不典型增生、脂肪坏死和硬化性腺病等良性疾病的常见表现。关于该征象的临床及影像学研究国内尚无相关报道。目前，乳腺动态增强磁共振检查及三维彩色多普勒超声检查被认为是乳腺X线摄影检查重要的辅助诊断方法；尤其是乳腺增强磁共振检查在部分发达国家已经较为广泛的应用于乳腺癌高危人群的筛查中；它具备了足够的空间和时间分辨率，通过对病变的内部结构、形态、边缘及增强后形态分布、增强后动态曲线综合评判乳腺疾病的良、恶性。本研究旨在采用动态增强磁共振及彩色多普勒超声技术，对乳腺X线摄影中局灶性不对称征象进行影像研究，比较良性、恶性病变间的差异，为乳腺癌的早期诊断提供影像学依据。第一部分乳腺X线摄中不对称征象的影像学特征及临床意义研究目的：通过对局灶性不对称征象的X线表现与病理对照研究，探讨良、恶性病变的影像学差异及X线摄影术对该征象的定性诊断价值。材料与方法：搜集2008年1月到2012年2月间，在同济大学附属上海市东方医院医学影像科行双侧乳腺X线检查的6158位女性患者的影像学相关资料。具有不对称征象的患者1088人（17.67%）：其中局灶性不对称征象978人（15.88%），整体性不对称征象82人（1.33%）。⑴由2名高年资影像诊断医生共同阅片，并根据ACR乳腺实质分型法对所有受检者的乳腺实质进行分类；研究局灶性不对称征象在不同年龄组及不同乳腺分型中的分布情况。⑵对经手术病理证实的114例良、恶性病变在X线摄影中的影像学特征并进行差异统计学分析，筛选有意义的征象，比较其诊断价值。按照患者的乳腺实质分型、年龄及各影像学征象的有无，将患者分为不同组别，评价局灶性不对称征象与上述诸因素之间的关系。结果：局乳腺实质的分型随着年龄的变化而不同。局灶性不对称征象多见于41～59岁的围绝经期女性，尤其是该年龄组的少量腺体型。良、恶性局灶性不对称征象在不同年龄组及不同实质分型中的分布无显著统计学差异。良、恶性病变在乳腺X线摄影检查中的皮下脂肪凹陷征（3/79vs.4/35）征象；边缘锐利（1/79vs.0/35）、清楚（29/79vs.14/35）、模糊（49/79vs.21/35）；高密度（21/79vs.11/35）、等密度（42/79vs.19/35）、低密度（16/79vs.5/35）；星空征（30/79vs.9/35）等征象的差异性无统计学意义；恶性局灶性不对称征象往往伴有恶性或中间型钙化（37.1%）。结论：各年龄段女性在X线摄影中表现为不同的腺体类型。局灶性不对称征象是围绝经期女性乳腺X线摄影检查的一个常见的特殊征象。伴有钙化的局灶性不对称征象往往提示恶性可能。第二部分动态增强磁共振及超声对乳腺X线摄影中局灶性不对称征象的定性诊断价值研究研究目的：探讨3.0T动态增强乳腺MRI、超声检查及联合试验方法对乳腺X线摄影中局灶性不对称征象（无钙化等伴随征象）的定性诊断价值。材料与方法：回顾性分析了自2008年1月到2011年8月间，具备三种乳腺影像学资料、临床检查、手术及病理资料的48例女性患者。其乳腺X线摄影、动态增强MRI及超声检查均由2名高年资影像诊断医生进行共同阅片，并分别进行BI-RADS分类。分析不同检查及试验方法对于良性及恶性局灶性不对称征象的定性诊断价值，并绘制其ROC曲线；并将不同方法的诊断结果与病理进行KAPPA分析。结果：48位女性中37位（77.1%）有明显临床症状的患者进行了手术治疗，11位患者行穿刺活检术。15例恶性肿瘤：9例浸润性导管癌、3例浸润性混合性腺癌、2例浸润性小叶癌和1例导管内乳头状瘤恶变。33例良性：9例腺病、6例腺病伴到导管增生、5例慢性炎症、4例脂肪坏死、2例非哺乳期乳腺炎、2例导管内乳头状瘤、1例腺病伴纤维腺瘤、1例纤维上皮样肿瘤、1例纤维腺瘤、1例慢性肉芽肿和1例化脓性炎症。动态增强乳腺MRI的ROC曲线下面积为0.903，（95%可信区间为:0.815，0.991;p=0.000)。乳腺超声检查的ROC曲线下面积为0.765，（95%可信区间为:0.610，0.919;p=0.004)。平行诊断试验的ROC曲线下Area=0.818，（95%可信区间0.702，0.934;p=0.002）系列诊断试验的ROC曲线下Area=0.785，（95%可信区间0.623，0.947；p=0.002）。MRI的Kappa值最大，为0.719。结论：动态增强MRI可用于乳腺X线摄影中局灶性不对称征象定性诊断，且具较高准确性。更多还原

【Abstract】 BackgroundThe the tendency of breast disease incidence is on a rise on a global scale. Breastcancer has the highest morbidity among all the tumors in women remains a leading causeof cancer deaths among women in many parts of the world. Women with invasive breastcancers (whether the cancer is low or high grade) of1cm or smaller have a95%chance ofsurvival at10years, while those with invasive cancers2–5cm in size just have60%survival at10years (1).Therefore early diagnosis is the key of therapy of breast cancer andimprovement of prognosis on breast cancer.Mammography is currently the most effective method for early detection anddiagnosis of breast cancer. Focal Asymmetry (FA) as one of the special mammographicabnormalities can be difficult to evaluate and occasionally remain inconclusive despite athorough diagnostic evaluation.It can be the only clue to diagnosis of early invasive cancerand unusual breast cancers. But, focal asymmetry may be the common sign of mastitis,fibrosis, adenosis with ductal hyperplasia, fat necrosis sclerosing adenosis. And there is nosystematic study reported in China.Currently, contrast-enhanced MRI and breast sonography have been found to beuseful adjuncts to mammography. Especially, CE MR has been accepted as a powerful toolto help with the detection, diagnosis, and staging of breast cancer. In many parts of theworld, it has been used as a screening method of breast cancer in high risk women. MRIhas a sufficient spatial and temporal resolution to show the internal structure, shape, edgeand enhanced dynamic curve of abnormal, which is essential for Difference of benign andmalignant.This study is focused on imaging and pathology control study on focal aymmetry withCE-MRI and breast US, by comparing the benign lesions and malignant lesions, to provideimageology evidence for early diagnosis and early treatment of breast cancer. PART Ⅰ: Focal Asymmetry on Mammography：Imaging features and clinicalsignificancePURPOSE: Observation of the Imaging features and genotyping of asymmeties onmammography, and investigate its clinical significance and the limitations and pitfalls ofmammography.METHOD AND MATERIALS: We searched mammographic imagings and clinicaldatas of all6，158women with or without symptoms who underwent bilateralmammography examination at Shanghai East Hospital, TongJi University School ofMedicine from Janurary,2008to February,2012. Two Experienced radiologists read theimages together and classfied parenchymal pattern, according to BI-RADS ofACR.Asymmetry has been observed in1088women (17.67%), including978(15.88%)cases of focal asymmetry and82(1.33%) cases of global asymmetry. All patients weredivided into various groups, according to the patient’s age, parenchymal pattern of ACR.We evaluated the distribution of focal asymmetry in different ages and parenchymalpatterns. As for all114patients with histological diagnosis, we choose some morphologicfeatures. Then, all patients were divided into various groups, according to the patient’s age,parenchymal pattern of ACR, and with (or without) morphologic features.And analyzemorphologic features and synthetically evaluate the clinical application of mammographyon differential diagnosis of focal asymmetry.Then, we evaluated the relationship betweenthe demonstration of the focal asymmetry and all the relative factors.RESULTS: The demonstration ratio of the faocal asymmetry on mammmography hasobvious correlation with age and parenchymal pattern. The results analysis fordifferentiation of benign and malignant focal asymmetry showed that the morphologicfeature of calcification had high specificity for identification of malignant tumors. Themorphologic features of density, hook sign, the degree of edge and the miky way have nostriking significance. CONCLUSION: Breast parenchymal pattern changes with age. Focal asymmetry isfrequently seen in women of perimenopausal period. And, focal asymmetry withcalcification on mammography may be a clue of malignant.PART Ⅱ: Focal Asymmetry on Mammography：Comparison of ContrastEnhanced MR Imaging, Ultrasonographic Findings and PathologicPURPOSE: To retrospectively compare the diagnostic results of dynamiccontrast-enhanced MR imaging at3.0T, ultrasonographic findings and conjoined test methodsfor the differentiation of malignant from benign lesions which were mammographicallydetected as focal asymmetry(without calcifications, architectural distortion, or associatedmass), with pathology records used as the reference standard.METHOD AND MATERIALS: This retrospective study was institutional review boardapproved. Informed consent was obtained from patients. The study population was derivedfrom all women with or without symptoms who underwent mammography at ShanghaiEast Hospital, TongJi University School of Medicine from Janurary1,2008, to February28,2011. Contrast-enhanced MRI, US, and clinical history were evaluated in48womenwith focal asymmetry on mammography. Two experienced radiologists analyzed the MRI,ultrasonographic findings and provided BI-RADS assessment categories. Diagnosticconfidence was compared by using a receiver operating characteristic (ROC) analysis andKappa analysis.RESULTS: Lumpectomy was performed in37(77.1%) women with obvious symptoms ofall these48cases. The other11patients had puncture biopsy. Fifteen cases of cancerincluding nine invasive ductal carcinoma, two invasive lobular carcinoma, onedeteriorative intraductal papilloma, and three mixde type carcinomas were identified. Ofall these48cases,33cases of benign were identified, including nine adenosis, six adenosiswith ductal hyperplasia, four fat necrosis, two mastitis, two intraductal papilloma, oneadenosis with fibroadenoma, one fibroepithelial tumour, one fibroadenoma,one chronic granuloma, five adenosis with chronic mastitis, and one purulent inflammation. The areaunder the ROC curve for MRI was0.903(95%confidence interval:0.815,0.991; p=0.000).The area under the ROC curve for US was0.765(95%confidence interval:0.610,0.919;p=0.004). The area under the ROC curve for parallel test was0.818(95%confidenceinterval:0.702,0.934; p=0.000). The area under the ROC curve for series test was0.785(95%confidence interval:0.623,0.947; p=0.002). The Kappa value of MRI is0.719which is the highest one of all。CONCLUSION: DCE-MRI can be used as a problem-solving modality to the standarddiagnostic procedures of the focal asymmetry.更多还原