胃高级别上皮内瘤变患者的胃活检与术后病理诊断的对比

2000年WHO肿瘤新分类把上皮内瘤变的定义应用到胃肠道上皮癌前病变的诊断中,以取代既往使用的异型增生等术语,同时推荐使用二级分级标准,即低级别上皮内瘤变和高级别上皮内瘤变,用高级别上皮内瘤变作为替代既往的重度异型增生和原位癌的诊断[1].温州医学院附属第三医院自2002年使用这一诊断标准以来,经胃镜钳取活组织病理诊断为胃高级别上皮内瘤变48例,现将其与患者手术后病理结果进行对照分析,以探讨对胃高级别上皮内瘤变病变的新认识.     

乳腺癌癌前病变的病理诊断

1　乳腺癌癌前病变的概念　　乳腺癌是乳腺上皮细胞增生及不典型增生的基础上逐步发展而成的。一般把某些在组织形态学有一定程度异型或增生活跃 ,经随访有一部分发展成癌的乳腺增生性病变称为乳腺癌癌前病变。正确认识乳腺癌的癌前病变 ,对于早期发现、早期诊断乳腺癌和做好二级预防工作均有重要的现实意义。但迄今为止 ,有关乳腺癌癌前病变的具体内容尚未完全统一 ,究其原因主要是由于不同学者在研究观察方法、诊断标准及随访时间不同所致。目前多数意见认为不典型导管上皮增生、不典型小叶增生及乳头状瘤病应视为乳腺癌的癌前病变[1] 。…     

CXCR4在乳腺癌中的表达及意义

目的：研究CXCR4在人乳腺癌及癌前病变中的表达情况,并分析其与乳腺癌相关临床病理指标之间的关系。方法：采用免疫组织化学方法（IHC）研究CXCR4在23例乳腺导管上皮增生,26例重度不典型导管上皮增生,34例乳腺导管内癌（DCIS）和126例浸润性乳腺癌组织中的表达差异情况;分析浸润性乳腺癌中CXCR4表达与腋窝淋巴结受累数目、临床分期、肿瘤直径、组织学分级等临床病理指标的相关性。结果：CXCR4在乳腺导管上皮增生、重度不典型导管上皮增生、乳腺导管内癌、浸润性乳腺癌组织中的阳性表达率依次为8.70%、23.08%、56.25%、60.32%,表达水平呈现增高趋势,具有随病变恶性程度加重而逐步增高的趋势（P〈0.05）;但导管内癌和浸润性乳腺癌两组表达水平无明显差别。CXCR4在浸润性乳腺癌中的表达与腋窝淋巴结受累数目、临床分期呈正相关,与肿瘤直径、组织学分级无明显相关性。淋巴结阳性组浸润性乳腺癌CX-CR4阳性表达率高于淋巴结阴性组（P〈0.05）。结论：CXCR4可能是乳腺癌发生的早期分子事件;CXCR4在浸润性乳腺癌中的表达与乳腺癌进展的临床病理指标相关,可作为乳腺癌的诊断指标;CXCR4可能成为乳腺癌治疗的新靶点。     

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1　乳腺癌癌前病变的治疗　　乳腺良性疾病较为常见 ,患良性病者乳腺癌的发病率较常人高 1 7～ 4 5倍 ,但哪些乳腺良性疾病有恶变倾向 ,被视为癌前病变 ,尚无统一认识。目前大多数学者认为属于乳腺癌癌前病变者主要有乳腺非典型增生 ,大导管乳头状瘤及乳头状瘤病 ,囊性增生病以及腺纤维瘤等。1 1　乳腺非典型增生　　乳腺非典型增生包括导管上皮非典型增生及小叶非典型增生。此病病人与同期同年龄非此病病人相比患乳腺癌的危险性增加 4～ 5倍 ,尤其是 40～ 5 0岁伴有乳腺癌家族史病人 ,在切除增生行病检后 10～ 15年约 2 0 %发生乳腺癌[1] …     

人乳头状瘤病毒16、18型在乳腺浸润性导管癌和导管非典型增生中的表达及意义

目的:探讨乳腺浸润性导管癌、导管不典型增生和良性上皮增生中人乳头瘤病毒(HPV)16、18型感染的差异.方法:用原位杂交法检测乳腺病变组织中HPV 16、18型表达.结果:HPV 16、18型感染率、共同感染率和总感染率在乳腺浸润性导管癌和导管非典型增生中均高于良性上皮增生.结论:HPV 16、18型感染与乳腺癌前病变有关,是乳腺癌发病的高危因素.     

C erbB 2, ER及PR表达在乳腺导管内癌与浸润性导管癌的对照研究

目的：探讨乳腺导管内癌与浸润性导管癌组织中C erbB 2, ER, PR表达的差异。方法：应用免疫组化法检测34例乳腺导管内癌及40例浸润性导管癌中C erbB 2, ER, PR表达。结果：乳腺导管内癌中C erbB 2, ER, PR阳性表达率分别为44.1%, 58.8%, 55.9%, 而在浸润性导管癌中分别为52.5%, 55%和62.5%。上述3种标记物的表达在两类型癌间均无统计学差异。结论：C erbB 2, ER, PR在乳腺导管内癌与浸润性导管癌中的表达相似, 它们可望作为乳腺癌预后和疗效的指标。     

乳腺癌癌前病变及早期乳腺癌诊断与治疗

近年来乳腺癌癌前病变及早期乳腺癌的诊断及治疗取得了显著进展。目前公认的癌前病变有：（1）小叶及导管不典型增生；（2）柱状上皮不典型增生；（3）小叶原位癌；（4）乳头状病变；（5）异常增生放射状疤痕。p53和HER2可用于监测其转变为癌的过程。切除癌前病变是最有效的治疗方法。早期乳腺癌可通过普查、乳腺检查、影像学检查、导管内窥镜、肿瘤标志物及病理学检查诊断。局部切除加放疗、单纯乳房切除、局部切除加根据激素受体情况酌情内分泌治疗是原位癌主要治疗方法。早期浸润性乳腺癌推荐保乳根治术＋术后放疗、酌情化疗和／或内分泌治疗，可以避免致残性的手术，获得好的生活质量及长期存活。     

乳管镜协助硬膜外麻醉导管引导定位切除乳管内病变

目的探讨乳管镜协助下硬膜外麻醉导管引导定位切除乳管内病变的价值。方法纤维乳管镜诊断为乳管内肿瘤45例,定位其深度及体表方向。拔出乳管镜,在同一溢液导管内插入硬膜外麻醉导管做支撑引导,插入深度与纤维乳管镜插入深度一致。沿标记方向放射状切开乳头乳晕皮肤,硬膜外麻醉导管作支撑引导,解剖病变导管并切除。结果乳管镜诊断:导管内乳头状瘤41例,导管内多发乳头状瘤2例,乳头状瘤病2例。乳管镜诊断与病理诊断符合率:乳头状瘤95%(39/41),多发性乳头状瘤50%(1/2),乳头状瘤病50%(1/2);诊断不符合者:病理诊断导管扩张,上皮增生2例,多发性导管内乳头状瘤伴非典型导管上皮增生、部分重度增生1例,乳腺癌1例。术后乳头乳房形态良好。结论乳管镜协助下硬膜外麻醉导管引导下行乳管内病变切除术,定位准确,病变切除容易,美容效果好,便于在基层医院开展。     

新辅助化疗对乳腺癌雌孕激素受体表达的影响

目的：探讨新辅助化疗对乳腺癌雌孕激素受体表达的影响。方法：应用免疫组化方法检测60例新辅助化疗治疗的乳腺癌和84例未术前化疗的乳腺癌标本化疗前或术前和术后ER、PR的表达情况,比较两组ER、PR表达变化的差异。结果：新辅助化疗组ER、PR的阳性率分别从化疗前的51.67%、43.33%变为术后的71.67%、56.67%,而对照组基本没变化;新辅助化疗组ER、PR表达状态发生改变分别为26.67%、16.67%,表达强度改变为38.33%、43.33%,对照组ER、PR表达状态发生改变分别为3.57%、1.19%,表达强度改变为11.9%、11.9%,差异具有显著性（P〈0.01）。结论：新辅助化疗影响乳腺癌雌孕激素受体的表达并有可能上调激素受体表达。     

乳腺癌癌前病变的治疗

病理组织学检查是诊断癌前病变的最可靠标准。目前公认的癌前病变有: （1）小叶及导管不典型增生; （2） 柱状上皮不典型增生; （3） 小叶原位癌; （4） 乳头状病变;（5） 异常增生放射状瘢痕。治疗癌前病变的最有效方法是手术切除。但是必须权衡手术范围与外形美观之间的矛盾,既不要切除范围过大,造成不必要的组织缺失,也不要切除范围过小而留下复发隐患。导管原位癌是乳腺癌的早期阶段,但是,纯粹的导管原位癌不具有侵袭性,被看作癌前病变和癌的中间状态。手术切除、放疗加降低风险的内分泌治疗是导管原位癌主要治疗方法。     

Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy.

OBJECTIVE: The purpose of the study is to evaluate the prevalence of occult breast carcinoma in surgical breast biopsies performed on nonpalpable breast lesions diagnosed initially as atypical ductal hyperplasia (ADH) by core needle biopsy. BACKGROUND: Atypical ductal hyperplasia is a lesion with significant malignant potential. Some authors note that ADH and ductal carcinoma in situ (DCIS) frequently coexist in the same lesion. The criterion for the diagnosis of DCIS requires involvement of at least two ducts; otherwise, a lesion that is qualitatively consistent with DCIS but quantitatively insufficient is described as atypical ductal hyperplasia. Thus, the finding of ADH in a core needle breast biopsy specimen actually may represent a sample of a true in situ carcinoma. METHODS: Between May 3, 1994, and June 12, 1996, image-guided core biopsies of 510 mammographically identified lesions were performed using a 14-gauge automated device with an average of 7.5 cores obtained per lesion. Atypical ductal hyperplasia was found in 23 (4.5%) of 510 lesions, and surgical excision subsequently was performed in 21 of these cases. In these 21 cases, histopathologic results from core needle and surgical biopsies were reviewed and correlated. RESULTS: Histopathologic study of the 21 surgically excised lesions having ADH in their core needle specimens showed seven (33.3%) with DCIS. CONCLUSIONS: In the authors' patient population, one third of patients with ADH at core biopsy have an occult carcinoma. A core needle breast biopsy finding of ADH for nonpalpable lesions therefore warrants a recommendation for excisional biopsy.     

When pathological and radiological correlation is achieved,excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted

BackgroundThe diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up.MethodsA retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded.Results2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41–70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision.     

DCIS and LCIS are confusing and outdated terms. They should be abandoned in favor of ductal intraepithelial neoplasia (DIN) and lobular intraepithelial neoplasia (LIN)

The terms ductal and lobular intraepithelial neoplasia (DIN and LIN) were introduced by Tavossoli 15 years ago, who proposed they should replace, respectively, ductal and lobular carcinoma in situ (DCIS and LCIS). This proposal has been slowly gaining ground. We argue that DCIS and LCIS should now be definitively abandoned. Bringing together ‘in situ’ and other entities into the simpler and more logical DIN/LIN framework–as has been done with intraepithelial neoplasias of cervix, vagina, vulva, prostate, and pancreas–would eliminate the artificial and illogical distinctions between ‘not cancers’ (e.g. flat epithelial atypia, atypical ductal hyperplasia–now classified as low grade DIN) and ‘cancers’ (e.g. DCIS–now considered medium–high grade DIN). Elimination of the term ‘carcinoma’ from entities that cannot metastasize will reduce confusion among health professionals and patients, and contribute to reducing the risk of overtreatment, as well as reducing adverse psychological reactions in patients.     

Follow-up surgical excision is indicated when breast core needle biopsies show atypical lobular hyperplasia or lobular carcinoma in situ: a correlative study of 33 patients with review of the literature

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.     

Surgical upgrade rate of breast atypia to malignancy: An academic center's experience and validation of a predictive model

Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are commonly seen on breast core needle biopsy (CNB). Many institutions recommend excision of these lesions to exclude malignancy. A retrospective chart review was performed on patients who had ADH, ALH, or LCIS on breast CNB from 1/1/08 to 12/31/10 who subsequently had surgical excision of the biopsy site. Study objectives included determining upgrade to malignancy at surgical excision, identification of predictors of upgrade, and validation of a recently published predictive model. Clinical and demographic factors, pathology, characteristics of the biopsy procedure and visible residual lesion were recorded. T test and chi‐squared test were used to identify predictors. Classification tree was used to predict upgrade. 151 patients had mean age of 53 years. The mean maximum lesion size on imaging was 11 mm. The primary atypia was ADH in 63.6%, ALH in 27.8%, and LCIS in 8.6%. 16.6% of patients had upgrade to malignancy, with 72% DCIS and 28% invasive carcinoma. Risk factors for upgrade included maximum lesion size (P = .002) and radiographic presence of residual lesion (P = .001). A predictive model based on these factors had sensitivity 78%, specificity 80% and AUC = 0.88. Validating a published nomogram with our data produced accuracy figures (AUC = 0.65) within published CI of 0.63‐0.82. In CNB specimens containing ADH, ALH, or LCIS, initial lesion size and presence of residual lesion are predictors of upgrade to malignancy. A validated model may be helpful in developing patient management strategies.     

High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma

This study was undertaken to determine the morphologic features and frequency of putative precursor lesions involved in the development of some pure forms of special types and low grade breast carcinoma. We reviewed 147 successive tumor cases, comprising tubular carcinoma (TC); pure type (n=56) and mixed type (n=20), invasive lobular carcinoma (ILC); classic type (n=57), and tubulolobular carcinoma (TLC; n=14). The presence of preinvasive lesions including columnar cell lesions (CCLs), usual epithelial hyperplasia, ductal carcinoma in situ (DCIS), and lobular neoplasia (LN) was determined. Estrogen receptor and E-cadherin immunohistochemistry was performed. Ninety-five percent (95%) of pure TCs had associated CCLs with the majority showing flat epithelial atypia. Atypical ductal hyperplasia (ADH)/DCIS was present in 89% patients. Colocalization of CCL, ADH/DCIS, and TC was seen in 85% patients, all displaying the same cytologic-nuclear morphology in most cases. LN was seen in 16%. In ILC, 91% cases showed LN. CCL and ADH/DCIS were seen in 60% and 42% cases, respectively. E-cadherin was positive in TLC but reduced in TC and completely absent in ILC. In conclusion, our findings support the hypothesis that CCLs are associated with pure and mixed forms of TC, and that LN is involved in ILC development. Our observations suggest that these lesions represent family members of low grade precursor, in situ and invasive neoplastic lesions of the breast. Molecular studies are being performed to substantiate the hypothesis that tubular and lobular carcinomas have direct evolutionary links to CCLs and flat epithelial atypia.     

Expression patterns of biologic markers in small breast cancers and preneoplastic breast lesions

When does proliferating breast epithelium turn malignant? Single parameter analyses have not answered this question. We have tried to answer this through an analysis of immunohistochemical staining patterns in the following morphologically defined breast lesions: atypical ductal hyperplasia (ADH, 23 cases), papilloma (12 cases), ductal cancer in situ (DCIS, 28 cases), and mammographically detected small primary cancers (34 cases). The seven antibodies used were c-neu, bcl-2, p53, p21, CD44, MIB 1, and FAS. Staining patterns were compared within groups and between groups of lesions. Interesting differences in staining patterns were seen between invasive ductal cancer and invasive lobular cancer: invasive lobular cancer was less p53-positive and more CD44-positive than invasive ductal cancer. We found no common pattern in the different proliferating epithelia to show when they become malignant.     

Numerical abnormalities of chromosomes 7, 18, and x in precancerous breast disease defined by fluorescent in situ hybridization

Nonrandom numerical chromosomal abnormalities (NCA) are frequent in invasive breast cancer, but little is known about such changes in microscopic precursor lesions. Mammographically detected "suspicious" breast lesions were localized by specimen radiology of sliced breast tissue. The slices containing the lesion were imprinted onto coated slides by gentle scraping. The corresponding hematoxylin and eosin stained histologic sections and Diff-Quik stained imprints were used for classification as ductal hyperplasia (DH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS). Additional slide imprints were evaluated for copy number of chromosomes 7, 18, and X by using fluorescent in situ hybridization with alpha satellite probes. NCA were detected in 1 of 9 (11%) cases of DH, in 2 of 8 (25%) cases of ADH, and in 14 of 16 (87%) cases of DCIS. There was selective loss (chromosome 18) in one case of DCIS; all other cases with NCA had a gain of at least one chromosome. There is a progressive increase in incidence of NCA in DH, ADH and DCIS. The majority of NCA are chromosomal gains.     

Comparison of the diagnostic accuracy of a vacuum-assisted percutaneous intact specimen sampling device to a vacuum-assisted core needle sampling device for breast biopsy: initial experience

The objective of this research was to determine whether biopsy of the breast using a percutaneous intact specimen sampling device influences the underestimation rate of ductal carcinoma in situ (DCIS) compared to a vacuum-assisted core needle biopsy (VACNB) device. This study was a retrospective comparison of two series of 800 consecutive patients that underwent stereotactic biopsy of the breast for mammographic lesions presenting as microcalcifications classified by our institution as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5. In the first series of patients (n = 800), a VACNB device was used; in the second series (n = 800), a vacuum-assisted percutaneous intact specimen biopsy (VAPIB) device was used. Initial diagnoses were made from the histopathologic examination of the tissue retrieved at biopsy. Lesions presenting as DCIS or atypical ductal hyperplasia (ADH) after percutaneous biopsy were then compared to the histopathologic analysis of specimens retrieved at surgical biopsy. DCIS upgrades were defined as cases in which the diagnosis of the stereotactic biopsy was DCIS and the diagnosis of the subsequent surgical excision was infiltrating ductal carcinoma (IDC). ADH upgrades were defined as cases in which the diagnosis of the stereotactic biopsy specimen was ADH and the diagnosis of the surgical excision was DCIS, lobular carcinoma in situ (LCIS), or IDC. The lesions retrieved by both biopsy techniques yielded a similar pathology distribution. Underestimation of DCIS occurred less frequently (p = 0.06) in the biopsy samples taken using the intact biopsy device (1/31, 3.2%) as compared to biopsy samples taken using the core needle biopsy device (7/36, 19.4%). No significant adverse events were reported. Breast biopsy can be performed safely and accurately using a vacuum-assisted percutaneous intact specimen sampling device. In this study, such a device trended toward fewer underestimations of DCIS at biopsy compared to the vacuum-assisted core needle sampling biopsy method.     

Timing of Critical Genetic Changes in Human Breast Disease

Background Breast cancer development has been characterized as a nonobligatory sequence of histological changes from normal epithelium through invasive malignancy. Although genetic alterations are thought to accumulate stochastically during tumorigenesis, little is known about the timing of critical mutations. This study examined allelic imbalance (AI) in tissue samples representing a continuum of breast cancer development to examine the evolution of genomic instability. Methods Laser-microdissected DNA samples were collected from histologically normal breast specimens (n = 25), atypical ductal hyperplasia (ADH, n = 16), ductal carcinoma-in-situ (DCIS, n = 37), and stage I to III invasive carcinomas (n = 72). Fifty-two microsatellite markers representing 26 chromosomal regions commonly deleted in breast cancer were used to assess patterns of AI. Results AI frequencies were <5% in histologically normal and ADH specimens, 20% in DCIS lesions, and approximately 25% in invasive tumors. Mann-Whitney tests showed (1) that levels of AI in ADH samples did not differ significantly from those in histologically normal tissues and (2) that AI frequencies in DCIS lesions were not significantly different from those in invasive carcinomas. ADH and DCIS samples, however, differed significantly (P < .0001). Conclusions DCIS lesions contain levels of genomic instability that are characteristic of advanced invasive tumors, and this suggests that the biology of a developing carcinoma may already be predetermined by the in situ stage. Observations that levels of AI in ADH lesions are similar to those in disease-free tissues provide a genomic rationale for why prevention strategies at the ADH level are successful and why cases with ADH involving surgical margins do not require further resection.