乳腺导管原位癌研究新进展

随着乳腺摄片筛查技术的广泛应用,发现近年乳腺导管原位癌(ductal carcinoma in situ,DCIS)的发病率明显增高.上世纪70年代初期,乳腺癌病例中的DCIS低于1%,而目前则占20%～30%[1].DCIS是一组异质性病变,特征是局限于乳腺导管的恶性上皮细胞克隆性增生,光镜下尚未突破基膜.从理论上讲,DCIS缺乏转移潜能且仅外科手术切除即可治愈.然而,DCIS常常以原位癌或浸润性癌形式复发,因此DCIS是潜在的致死性疾病[2].     

乳腺纤维腺瘤内癌20例临床病理分析

目的探讨乳腺纤维腺瘤内癌的临床病理学特征、诊断及鉴别诊断、治疗及预后。方法回顾性分析20例乳腺纤维腺瘤内癌的临床病理学特征、诊断及鉴别诊断、治疗及预后,并复习相关文献。结果患者平均年龄30.8岁。6例行单纯肿物切除术,8例行保乳手术,6例行单纯乳房切除术。患者均未出现淋巴结转移。20例均为纤维腺瘤内癌:4例为小叶原位癌;15例为导管原位癌,低级别13例,中级别2例,其中5例腺瘤外乳腺组织亦有低级别导管原位癌;1例为浸润性导管癌。20例纤维腺瘤内癌的ER、PR均弥漫一致阳性。患者中位随访时间27.5个月,均未出现复发及远处转移。结论纤维腺瘤内癌的形态特点为纤维腺瘤的背景上出现原位癌或浸润癌,预后好。治疗上推荐保乳手术,术后可辅以放疗。     

24例乳腺原位癌临床治疗疗效分析

目的探讨手术治疗对乳腺原位癌临床疗效和预后的影响。方法选择24例乳腺原位癌患者,16例实施单乳切除术(66.7%),4例改良根治术(16.7%),4例行保乳手术(16.7%),对于淋巴结转移患者术后辅以化学治疗,对保乳患者术后给予全乳放疗,对临床疗效及预后情况,进行回顾性分析。结果24例乳腺原位癌患者中,20例乳腺导管原位癌,4例乳腺小叶原位癌。经过单乳切除术、改良根治术、保乳手术等综合治疗,平均随访5年,1例保乳术后5年局部复发,行乳房单切治愈,余均健在。结论采取合适的手术方式,彻底切除肿瘤病灶,辅以放疗及内分泌治疗,是提高乳腺原位癌患者预后的关键。     

导管内原位癌几种分类方法

导管内原位癌几种分类方法詹钅容洲导管内原位癌（ｄｕｃｔａｌｃａｒｃｉｎｏｍａｉｎｓｉｔｕ，ＤＣＩＳ）的定义是乳腺导管上皮细胞的恶性增生，且局限在导管的基底膜之内，不侵犯间质。导管内原位癌是疾病的谱系，不同类型的导管内原位癌其生物学行为差异很大，其分子...     

乳腺原位癌的起源和发展

目的：探讨乳腺原位癌的起源和发展,兼论乳腺癌组织学分类。方法：观察５０例乳腺原位癌ＨＥ染色切片,部分切片做Ｗｅｉｇｒｅｔ弹力纤维当构及ｖａｎＧｉｅｓｏｎ胶原染色。：５０例导管在位癌中３８例（７６％）合并有小叶原位大部分导管原位癌癌巢不是在导管内,而是在小叶的位置,其壁上无弹力纤维包绕。结论：导管原位癌和小叶原位癌无题自末梢导管小叶单位发性。小叶原位癌可能是原位癌的早期阶段,可在原位发展为导管原位癌     

乳腺超声检查中BI-RADS分级诊断标准对乳腺原位癌的诊断价值

目的 探究应用BI-RADS分级诊断标准来诊断乳腺原位癌的超声诊断价值,以提升超声工作者对规范乳腺诊断标准认识和运用,提高彩色多普勒超声对乳腺原位癌的诊断能力。方法 选取2015年5月~2018年5月在我院通过手术及病理结果证实为乳腺原位癌的患者37例,系统回顾了根据病灶所显示出的不同声像图特征,综合分析采用BI-RADS超声分级诊断,探讨误诊主要原因。结果 37例乳腺原位癌病例中,超声诊断准确率为75.36%（28/37）,4例未定,5例误诊,其中1例误诊为导管内乳头状瘤,1例误诊为导管浸润癌,1例误诊为导管局部扩张,2例误诊为瘤样增生。结论 彩色多普勒超声诊断仪采用BI-RADS分级诊断方法,较大提高了乳腺原位癌的检出率,联合其它辅助检查可明显提高检出率,在指导临床对患者乳腺疾病的评估起到重要作用。     

乳腺导管内增生性病变是乳腺癌前驱病变

乳腺导管内增生性病变是一组发生于终末导管小叶单位且限定于乳腺导管小叶系统的增生性病变,表现为细胞形态多样性和组织结构多样性,包括普通型导管增生(usual ductal hyperplasia, UDH)、不典型导管增生(atypical ductal hyperplasia, ADH)、不典型平坦上皮增生(flat epithelial atypia, FEA)和导管原位癌(ductal carcinoma in situ, DCIS).     

乳腺导管原位癌病理形态及c—erbB—2,p53和PCN…

目的：对乳腺导管原位癌进行病理形态分析，并行ｃ－ｅｒｂＢ－２、ｐ５３癌基因蛋白、增殖细胞抗原（ＰＣＮＡ）表达以及相关性的研究，以期为临床判断潜在恶性程度及预后提供参考指标。方法：运用病理形态分析以及枸橼酸－微波－ＡＢＣ免疫组化法对２５例 马林固定、石蜡包蛙乳腺导管原位癌组织进行回顾性研究。结果：（１）２５例乳腺原位导管癌ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率分别为３６．０％，４０．０和４０     

乳腺囊内型乳头状癌

乳腺囊内型乳头状癌(intracystic papillary carcinomas,IPC)传统上被作为导管原位癌(ductal carcinoma in situ,DCIS)的亚型,其特征是乳头状癌出现在囊性扩张的导管内。新近研究提示并非所有IPC均是原位癌。作者使用5种肌上皮标记(smooth muscle myosin heavy chain、calponin     

乳腺微乳头型导管内癌治疗后胸壁复发为浸润性微乳头状癌1例

乳腺导管内癌是一种常见的乳腺原位癌, 因肿瘤未突破基底膜, 手术切除通常有效, 少部分复发, 极少部分以浸润癌复发。本文报道1例微乳头型乳腺导管内癌, 乳腺改良根治术和内分泌治疗4年后出现同侧胸壁浸润性微乳头状癌复发, 再次行化疗+放疗+内分泌治疗后随访3年无异常。本文回顾其临床病理资料并复习相关文献, 以提高对该病的认识, 并探讨可能的治疗方案。     

D2-40 expression by breast myoepithelium: potential pitfalls in distinguishing intralymphatic carcinoma from in situ carcinoma

Lymphovascular invasion is an adverse prognostic factor in breast cancer. The lymphatic endothelial marker D2-40 has been shown to improve accuracy in detecting lymphovascular invasion. In addition to marking lymphatic endothelium, D2-40 has been cursorily noted to react with breast myoepithelium. The extent of this expression and the potential for misinterpreting in situ carcinoma as lymphovascular invasion because of D2-40-positive myoepithelium have not been formally addressed. The aim of this study was to determine the scope of breast myoepithelial expression of D2-40 and to identify problematic patterns of expression by in situ carcinoma that could be confused with lymphovascular invasion. We evaluated the distribution and intensity of D2-40 immunohistochemical expression in breast myoepithelium in normal breast (n = 50), proliferative fibrocystic changes (n = 10), ductal carcinoma in situ (n = 35), and lobular carcinoma in situ (n = 5). All cases of normal breast exhibited a variable degree of D2-40 expression by myoepithelium. The distribution was patchy and the intensity was less than that of the adjacent lymphatic endothelium. Larger ducts were more often positive than terminal ducts and lobules. D2-40 marked 77% of ductal carcinoma in situ cases and all lobular carcinoma in situ cases to a variable degree. Only a minority of involved ducts were reactive in each positive case; the intensity was weak to moderate. Although the tumor growth pattern generally enabled distinction of ductal carcinoma in situ from lymphovascular invasion, D2-40 myoepithelial expression in small ducts completely filled by solid-pattern ductal carcinoma in situ mimicked the pattern expected for lymphovascular invasion. Morphology of these myoepithelial cells was not diagnostically helpful as their compressed, stretched-out shape mimicked that of endothelium. Myoepithelial markers (p63 and smooth muscle myosin) confirmed each diagnosis of ductal carcinoma in situ. Lobular carcinoma in situ posed similar problems. The interpretation of D2-40 in the breast requires awareness that myoepithelium may also be immunoreactive. Solid-pattern ductal carcinoma in situ and lobular carcinoma in situ may be misinterpreted as lymphovascular invasion. We recommend that myoepithelial markers be used in conjunction with D2-40 to distinguish solid intralymphatic tumor emboli from solid pattern in situ carcinoma.     

Feulgen DNA content and mitotic activity in proliferative breast disease. A comparison with ductal carcinoma in situ

Nuclear Feulgen DNA content was measured by cytophotometry and the number of mitoses per 40 high power fields was determined in hyperplastic and atypical hyperplastic lesions of fibrocystic disease in 18 patients, in ductal carcinoma in situ in 14 patients and in ductal carcinoma in situ associated with infiltrating carcinoma in 11 patients. These parameters were also investigated in the hyperplastic lesions accompanying ductal carcinoma in situ and ductal carcinoma in situ associated with infiltrating carcinoma. The nuclear Feulgen DNA content could not discriminate between atypical hyperplasia and ductal carcinoma in situ. Although differences in the mitotic count between hyperplastic and atypical breast lesions were not statistically significant, there was a statistically significant greater mitotic count in ductal carcinoma in situ alone or associated with infiltrating carcinoma. These findings suggest that the mitotic count is useful for the differential diagnosis between atypical hyperplasia and ductal carcinoma in situ. In addition, hyperplastic lesions associated with ductal carcinoma in situ, with or without infiltrating carcinoma, exhibited a statistically significant higher mitotic count than those in benign fibrocystic disease. Hyperplastic breast lesions exhibiting high mitotic counts may indicate the presence of a neighbouring ductal malignancy and suggest an increased proliferative activity in breast tissue in the neighbourhood of malignancy.     

The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast.

HER2/neu overexpression/amplification is seen more frequently in ductal carcinoma in situ, particularly high-grade ductal carcinoma in situ (50-60%), than in invasive ductal carcinoma of the breast (25-30%). To date, however, the role of HER2/neu in the progression of in situ to invasive disease has not been clarified. Two hundred fifty-one breast tumors were retrieved from the pathology files at Mount Sinai Hospital. These included 91 cases of ductal carcinoma in situ, 136 cases of invasive ductal carcinomas with associated ductal carcinoma in situ, and 24 cases of pure invasive carcinomas. All cases were reviewed and stained with two monoclonal antibodies to HER2/neu (CB11 and TAB250). Immunohistochemical staining was recorded using a semiquantitative scoring system (1). Representative cases were also investigated using fluorescence in situ hybridization. HER2/neu protein overexpression (defined as immunohistochemical staining with score of >or=5) was seen in 34% of cases of pure ductal carcinoma in situ, 17% of invasive carcinomas with associated ductal carcinoma in situ, and 12.5% of pure invasive carcinomas (P =.01). Sixty percent of cases of high-grade ductal carcinoma in situ showed HER2/neu protein overexpression, versus 29% of high-grade invasive carcinomas with associated ductal carcinoma in situ and 22% of high-grade pure invasive ductal carcinomas (P =.02). The concordance between the immunohistochemical staining in the in situ and invasive components of individual tumors was 90%. Thirty-three cases were also evaluated by fluorescence in situ hybridization and showed concordance between the immunohistochemical results and the degree of gene amplification in 91% of cases, whereas 3 of 33 cases showed HER2/neu gene amplification (HER2/CEP17 = 2.3-3.7) by fluorescence in situ hybridization in the absence of positive immunohistochemical staining. One case showed HER2/neu gene amplification in the associated ductal carcinoma in situ (HER2/CEP17 ratio = 6.5), with no evidence of gene amplification in the invasive tumor (HER2/CEP17 ratio = 1.14). Multiple genetic events are required for the development of an invasive phenotype. The findings from this study suggest that the genetic event of HER2/neu gene amplification/protein overexpression may not play a key role in the progression of ductal carcinoma in situ to invasive carcinoma and that other molecular alterations may be more important in the initiation of invasion in ductal carcinoma of the breast.     

Mucocele-like tumor of the breast associated with ductal carcinoma in situ and mucinous carcinoma : a case report

Mucocele-like tumor (MLT) of the breast is a rare neoplasm. Although this lesion was considered benign when first described, the concept of a pathologic continuum with mucinous carcinoma was evident in subsequent reports. Only a few cases of MLT have been reported in Korea. We describe a case of MLT associated with ductal carcinoma in situ and mucinous carcinoma in a 34-yr-old female. Histological examination showed multiple mucus-filled cysts of varying size. Extravasated mucin was present in the surrounding stroma. The lining of the cysts in most areas were of flat or cuboidal epithelium and devoid of cellular atypia. The lining epithelium showed proliferative change ranging from atypical ductal hyperplasia to ductal carcinoma in situ, micropapillary type. A microscopic focus of mucinous carcinoma within MLT was also noted. None of the lesions exhibited epithelial reactivity for p53 protein. The patient is alive and well without evidence of disease 54 months after initial treatment. This case supports the concept that MLT encompasses a spectrum of pathologic lesions including benign tumor, atypical ductal hyperplasia, ductal carcinoma in situ, and mucinous carcinoma.     

Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.     

Metastases to breast simulating ductal carcinoma in situ: report of two cases and review of the literature

The breast is an uncommon site for metastases. Nevertheless, it is important to differentiate primary from secondary tumors of the breast, because clinical management and expected outcomes are vastly different. We report two examples of tumors with a papillary histologic pattern metastasizing to the breast. One of the cases occurred in a 31-year-old woman with a primary renal cell carcinoma, the other was in a 42-year-old woman with an ovarian papillary serous adenocarcinoma. In the first case, the patient's previous history of cancer was not known to the pathologist. The cases highlight the difficulty in distinguishing primary from metastatic tumors in the breast. In both cases the tumors infiltrated in a pattern that mimicked in situ ductal carcinoma changes. Additionally, in both cases, the metastasizing tumor was unusual with the tumor cells diffusely permeating the lymphatic spaces, not in a solid mass. These cases and a review of the literature indicated that breast metastases, although rare, must be recognized and differentiated from primary breast tumors to avoid unnecessary radical surgery to the breast. Moreover, the presence of changes similar to in situ carcinoma of the breast are not conclusive evidence that one is evaluating a primary breast carcinoma. When there is any unusual histomorphology, a good degree of suspicion is necessary. Ann Diagn Pathol 5:15-20, 2001.     

Signet-ring cell carcinoma of the breast

Primary signet-ring cell carcinoma of the breast is a very rare tumor and is not recognized as an independent entity of the World Health Organization classification of breast tumor. Primary signet-ring cell carcinoma of the breast is usually considered as a variant of mucinous carcinoma or lobular carcinoma and usually originates from the lobular epithelium. A case of primary signet-ring cell carcinoma of the breast in a 68-year-old woman is presented. Histologically, the majority of neoplastic cells had an intracytoplasmic mucin collection. The histological presence of ductal carcinoma in situ, absence of lobular lesion and immunoreactivity for estrogen and progesterone receptors implicated the tumor cells arising from ductal epithelium. The papillary or organoid growth pattern is characteristic in this case. The patient underwent a modified radical mastectomy and was subsequently followed up for 6 months.     

Frequent E-cadherin gene inactivation by loss of heterozygosity in pleomorphic lobular carcinoma of the breast.

Pleomorphic lobular carcinoma of the breast is a variant of infiltrating lobular carcinoma that has poor prognosis. The pleomorphic appearance of this variant hinders its correct identification and differentiation from ductal carcinoma. The analysis of E-cadherin glycoprotein expression is a powerful tool for distinguishing lobular from ductal carcinomas, because complete loss of E-cadherin expression occurs in most infiltrating lobular tumors and lobular carcinomas in situ, but not in ductal tumors. In the present study, we have evaluated E-cadherin expression by immunohistochemistry in a series of 29 pleomorphic lobular breast carcinomas, including 7 cases with an in situ component. Complete loss of E-cadherin expression was observed in all the cases (29/29, 100%), in invasive and in situ components. To understand better the mechanisms underlying E-cadherin inactivation in this tumor type, the frequency of loss of heterozygosity at the E-cadherin gene locus (16q22.1) was analyzed. All informative tumors (27/27, 100%) showed loss of heterozygosity, thus implying a strong association between loss of E-cadherin expression and loss of heterozygosity at 16q22.1. Moreover, loss of heterozygosity was detected in all in situ components analyzed. These results imply that in terms of E-cadherin inactivation, pleomorphic lobular tumors are identical to classic infiltrating lobular carcinomas and distinct from ductal tumors, and therefore they should be considered a variant of lobular carcinoma of the breast, despite their aggressive behavior.     

40 years of progress in breast imaging

In the sixties, mammary diagnosis is just clinical, then the low contrast mammography, not very efficient, appears in the seventies. During the eighties, the ultrasound is set up while modern mammography with high contrast allows the non palpable breast lesions diagnosis. In the nineties years the mammography come before the clinical examination within the context of the breast cancer screening program. Some histological correlation are more specific about the ductal carcinoma in situ grading with microcalcifications, while new techniques (MRI, CT) are evaluated. At present the stereotactic large core breast biopsies benefit from the digital prone table, allow a histological diagnosis and avoid surgical excision of some indeterminate images. After the pernicious effects of imaging, we assess the progress according to the cancerous disease results. We also consider the problem of over-diagnosis and over-treatment of ductal carcinoma in situ.     

Colocalized granular cell tumor and infiltrating ductal carcinoma of the breast

A 57-year-old woman presented with a 2-year history of a palpable mass in the upper inner quadrant of the right breast. A 1.1-cm, poorly circumscribed, firm tumor nodule was noted, consisting of 2 histologically distinct lesions in the same location, with some areas showing purely well-differentiated invasive ductal carcinoma and others composed of granular cell tumor. In 1 area, the 2 tumors collided and infiltrated each other. The invasive ductal carcinoma was admixed with ductal carcinoma in situ of solid and cribriform types. To our knowledge, this is the first case report demonstrating colocalization of these 2 neoplasms, which raises questions regarding causal relationship. We also review the literature on granular cell tumor of the breast.