Silver-binding nucleoli and nucleolar organizer regions in fine needle aspiration cytology of the breast

Silver staining was used to demonstrate nucleoli and nucleolar organizer regions (NORs) in cytopreparations from breast fine needle aspiration (FNA) biopsies, with the resulting black dots being a combination of silver-binding nucleoli and dispersed NORs. Discrete black dots in 200 nuclei were manually counted in 25 silver-stained biopsies; the cytologic diagnoses were made on routine Papanicolaou-stained cytopreparations from the same aspirates. Although malignant breast lesions showed higher counts than did benign breast disease, an overlap of one malignant and three benign lesions occurred. Therefore, the method cannot be recommended for reliably discriminating between malignant and benign routine breast specimens obtained by FNA; it may have some value in assessing tumor behavior.     

Significance of AgNOR measurement in thyroid lesions

OBJECTIVE: To evaluate the discriminating potential of AgNOR area measurement and count in thyroid tumors using static cytometry equipment. STUDY DESIGN: Slides were analyzed by a computerized system for image analysis, CAS 200 (Becton & Dickinson, U.S.A.), using the Cell Measurement computer program (CAS 200, Becton & Dickinson). The argyrophilic reaction (NORs) was evaluated with a 400-fold amplification directly from the computer monitor. RESULTS: Thirty-three cases were analyzed for AgNOR staining. The cases studied included 3 goiters, 10 follicular adenomas, 6 Hürthle adenomas, 4 follicular carcinomas, 7 papillary carcinomas, and 3 Hürthle carcinomas. A total of 6,600 nuclei were evaluated. For statistical purposes, lesions were classified as benign and malignant, and both the number and the area of counted NORs showed very similar values. The NORs median among 19 benign tumors was 1.484 (SD +/- 0.265) and of 14 malignant tumors was 1.436 (SD +/- 0.414); the NORs areas were 2.6584 (SD +/- 1.0653) and 2.3643 (SD +/- 0.6320), respectively. CONCLUSION: Our results showed that AgNOR evaluation was not a significant parameter to discriminate between malignant and benign thyroid lesions.     

AgNOR染色对甲状腺良、恶性病变诊断价值的研究

本文应用ＡｇＮＯＲ染色技术对７３例甲状腺良恶性病变石蜡切片核仁组成区变化进行观察,其中包括亚急性甲状腺炎５例、腺瘤２５例、结节性甲状腺肿７例、甲状腺癌３６例,结果表明亚急性甲状腺炎、腺瘤、结节性甲状腺肿,细胞核内的ＡｇＮＯＲ颗粒均数及形态与甲状腺癌的均数及形态比较有显著性差异（Ｐ＜０．０１）。我们认为此方法对于区别甲状腺良、恶性病变有一定参考价值。     

Classification of breast lesions based on a dual S-shaped logistic model in dynamic contrast enhanced magnetic resonance imaging

This study proposes a novel dual S-shaped logistic model for automatically quantifying the characteristic kinetic curves of breast lesions and for distinguishing malignant from benign breast tumors on dynamic contrast enhanced (DCE) magnetic resonance (MR) images. D(α,β) is the diagnostic parameter derived from the logistic model. Significant differences were found in D(α,β) between the malignant benign groups. Fisher's Linear Discriminant analysis correctly classified more than 90% of the benign and malignant kinetic breast data using the derived diagnostic parameter (D(α,β)). Receiver operating characteristic curve analysis of the derived diagnostic parameter (D(α,β)) indicated high sensitivity and specificity to differentiate malignancy from benignancy. The dual S-shaped logistic model was effectively used to fit the kinetic curves of breast lesions in DCE-MR. Separation between benign and malignant breast lesions was achieved with sufficient accuracy by using the derived diagnostic parameter D(α,β) as the lesion's feature. The proposed method therefore has the potential for computer-aided diagnosis in breast tumors.     

Interphasic nucleolar organizer region distribution as a diagnostic parameter to differentiate benign from malignant epithelial tumors of human intestine

The distribution of the interphasic nucleolar organizer regions (NORs) has been investigated in five hyperplastic polyps, five adenomatous polyps and fifteen colonic adenocarcinomas. The study was performed using electron microscopy and paraffin-embedded sections stained for Ag-NOR proteins. Malignant tumor cells were characterized by a large number of NORs which were small in size and showed a scattered distribution. Nuclei of both types of polyp had only a small number of large-sized NORs in a clustered distribution. In two adenomatous polyps, cells were also observed with an NOR distribution pattern intermediate between that of frankly benign and malignant lesions.     

乳腺良恶性病变剪切波弹性成像的典型表现及其鉴别诊断价值

目的:观察乳腺良恶性病变的剪切波弹性成像(SWE)的典型表现,探讨SWE对乳腺良恶性病变的鉴别诊断价值。方法:选取2017年6月～2019年6月我院收治的162例行SWE检查的乳腺肿块患者,经组织活检或病理证实良性肿块105例(良性组)、恶性肿块57例(恶性组)。对比良、恶性组SWE的典型表现、SWE参数[最大值(Emax)、最小值(Emin)、平均值(Emean)、标准差(SD)、病灶与邻近脂肪弹性比值(SWE-Ratio)]的差异,分析SWE鉴别诊断乳腺良恶性病变的价值。结果:恶性组乳腺肿块"硬边征"检出率、Ⅲ型～Ⅴ型弹性图像检出率、Emax、Emean、SD、SWE-Ratio均高于良性组(P0.05),Emin低于良性组(P0.05)。Logistic多元回归分析结果显示,"硬边征"、Emax、Emean、SWE-Ratio与病理诊断乳腺肿块性质独立相关(P0.05)。受试者工作特征(ROC)曲线分析结果显示,"硬边征"、Emax、Emean、SWE-Ratio鉴别诊断乳腺良恶性病变的曲线下面积(AUC)分别为0.923、0.686、0.873、0.879。结论:SWE是诊断乳腺良恶性病变的有效影像手段,SWE的"硬边征"、SWE-Ratio、Emean对乳腺良恶性病变具有较高的鉴别价值。     

Levels of circulating cell-free serum DNA in benign and malignant breast lesions

PURPOSES OF THE STUDY: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. BASIC PROCEDURES: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. MAIN FINDINGS: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. PRINCIPAL CONCLUSION: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.     

乳腺癌AgNOR计数与癌胚抗原的免疫组化研究

应用核仁组成区嗜银蛋白（ＡｇＮＯＲ）技术及癌胚抗原（ＣＥＡ）免疫组化染色对９８例乳腺良、恶性病变进行对比研究。结果表明：ＡｇＮＯＲ计数与肿瘤增殖活跃程度及生物学行为是一致的。乳腺癌中ＡｇＮＯＲ计数显著高于良性病变（Ｐ＜０．０１）。浸润癌ＡｇＮＯＲ计数比其他类型乳腺癌高。ＣＥＡ染色在乳腺良性病变中基本阴性,恶性病变中阳性率８０．８％。乳腺癌中ＡｇＮＯＲ计数与ＣＥＡ分布之间呈线性相关（ｒ＝０．８２,Ｐ＜０．０５）。ＣＥＡ阳性乳腺癌组与ＣＥＡ阴性组ＡｇＮＯＲ计数差异显著（Ｐ＜０．０５）。提示：ＡｇＮＯＲ定量研究和ＣＥＡ分布在乳腺良、恶性病变的鉴别及肿瘤恶性程度的研究中具有相似的参考价值。     

Automated analysis of rat breast tumors. Comparison of four methods

Chemically-induced malignant rat breast tumors pose diagnostic dilemmas since the majority are well-differentiated, noninvasive papillary lesions that are barely distinguishable from benign papillary lesions. This study compared several automated modalities to see which best separated benign from malignant breast tumors. Thirty-three carcinogen-induced rat breast tumors (13 adenomas, 10 papillary carcinomas and 10 invasive carcinomas) were evaluated by static (image) cytometry (ICM) of integrated optical density, by flow cytometry (FCM) and by two automated morphometric protocols, contextual analysis and single-gland analysis. DNA ploidy analysis, by either ICM or FCM, did not discriminate between the benign and malignant tumors. Contextual analysis correctly identified 11 of 13 benign and 17 of 20 malignant lesions (P less than .01). Single-gland analysis correctly identified all 13 benign and 17 of 20 malignant lesions (P less than .01). No method distinguished invasive from noninvasive carcinomas. The data suggest that architectural features are more important than nuclear features in differentiating benign from malignant rat breast tumors.     

Breast pathology and reduction mammaplasty

Breast cancer is the tumor with the highest prevalence and incidence in women. Reduction mammaplasty is one of the most common procedures performed in Brazil by the plastic surgeon, and it is not uncommon for the surgeon to find a breast tumor during the operation or afterward, when the histopathological report is received. In this study, 2488 patient files were reviewed retrospectively. All patients had undergone reduction mammaplasty at the senior author's private clinic (the Ivo Pitanguy Clinic) between January of 1957 and December of 2002. Resected breast tissue was examined histopathologically. The objective of this study was to verify the occurrence of breast carcinoma found accidentally postoperatively. The senior author's team performed all of the operations and the same pathologist performed every histopathological examination. The histopathological test results were divided into two groups: benign lesions and tumors. The highest frequency of breast pathology was benign lesions, and of them, 80.8 percent involved fibrocystic changes and fibroadiposity. The tumor group was subdivided into benign tumors and malignant tumors. Among the benign tumors, fibroadenoma was the one most common, in 2.2 percent. The frequency of malignant tumors was 0.5 percent of all patients. Most of the histopathological lesions were found in patients between 30 and 50 years of age. A reduced number of patients had no lesions (3.7 percent). Lack of a pathological investigation or a cursory or hurried examination of any mammary tissue by the pathologist may overlook important lesions. In the analysis of these statistics, the concept of normal breast tissue was questioned.     

The Clinical Significance of Real-Time Contrast-Enhanced Ultrasonography in the Differential Diagnosis of Breast Tumor

The objective of this study was to investigate the clinical significance of real-time contrast-enhanced ultrasonography in the differential diagnosis of breast tumor. Fifty-seven breast tumor patients with 63 lesions were studied. Among the lesions, 34 are malignant and 29 are benign. A Philips iU-22 ultrasound scanner with L12-5 probe was used. Bolus SonoVue was injected via antecubital vein. Dynamic imaging was stored and analyzed with QLAB software. Parameters including initial time of perfusion (ITP), time to peak (TTP), peak intensity (PI), the enhancement pattern and the wash out pattern (WP) of contrast agent were observed. Results showed that about 85.3% of the malignant lesions showed heterogeneous enhancement and 79.3% of the benign ones showed homogeneous enhancement. The persistence time of the contrast agents was clearly longer inside the malignant lesion than inside the benign ones. Nevertheless, there were no significant differences in the value as ITP and TTP between the malignant and the benign lesions, while the PI value of the malignant lesions was significantly higher than the benign lesions. This study suggested that real-time contrast-enhanced ultrasonography is helpful to the differential diagnosis of breast tumors; however, the WP of the contrast agent inside the lesion also seems to be an important factor.     

Wavelet-Based 3D Reconstruction of Microcalcification Clusters from Two Mammographic Views: New Evidence That Fractal Tumors Are Malignant and Euclidean Tumors Are Benign

The 2D Wavelet-Transform Modulus Maxima (WTMM) method was used to detect microcalcifications (MC) in human breast tissue seen in mammograms and to characterize the fractal geometry of benign and malignant MC clusters. This was done in the context of a preliminary analysis of a small dataset, via a novel way to partition the wavelet-transform space-scale skeleton. For the first time, the estimated 3D fractal structure of a breast lesion was inferred by pairing the information from two separate 2D projected mammographic views of the same breast, i.e. the cranial-caudal (CC) and mediolateral-oblique (MLO) views. As a novelty, we define the “CC-MLO fractal dimension plot”, where a “fractal zone” and “Euclidean zones” (non-fractal) are defined. 118 images (59 cases, 25 malignant and 34 benign) obtained from a digital databank of mammograms with known radiologist diagnostics were analyzed to determine which cases would be plotted in the fractal zone and which cases would fall in the Euclidean zones. 92% of malignant breast lesions studied (23 out of 25 cases) were in the fractal zone while 88% of the benign lesions were in the Euclidean zones (30 out of 34 cases). Furthermore, a Bayesian statistical analysis shows that, with 95% credibility, the probability that fractal breast lesions are malignant is between 74% and 98%. Alternatively, with 95% credibility, the probability that Euclidean breast lesions are benign is between 76% and 96%. These results support the notion that the fractal structure of malignant tumors is more likely to be associated with an invasive behavior into the surrounding tissue compared to the less invasive, Euclidean structure of benign tumors. Finally, based on indirect 3D reconstructions from the 2D views, we conjecture that all breast tumors considered in this study, benign and malignant, fractal or Euclidean, restrict their growth to 2-dimensional manifolds within the breast tissue.     

剪切波弹性成像在乳腺实性病变良恶性鉴别中的诊断价值

目的:探讨剪切波弹性成像在乳腺实性病变良恶性鉴别中的诊断价值。方法:收集2012年3月-2013年6月于我院收治的乳腺实性病变患者54例,共65个病灶,先后给予乳腺二维超声检查与剪切波弹性成像检查,采用弹性模量值与钼靶BI-RADS分级方法诊断,比较两种方法诊断的准确性。结果:良性病灶组弹性最小、最大值以及平均值、标准差与恶性病灶组比较差异具有统计学意义(P0.05);ROC曲线分析显示,在乳腺实性病变良恶性的鉴别中,弹性最大值明显优于平弹性均值;剪切波弹性成像对乳腺实性病变良恶性鉴别的敏感度、特异度、准确度、阳性预测值、阴性预测值高于二维超声技术(P0.05)。结论:剪切波弹性成像在乳腺实性病变良恶性鉴别中具有良好的诊断价值,能够提高诊断的准确性。     

剪切波弹性成像定量参数对乳腺肿块良恶性的鉴别价值及其与组织Ki-67和C-erbB-2表达的关系研究

摘要 目的：探讨剪切波弹性成像（SWE）定量参数对乳腺肿块良恶性的鉴别价值,分析其与组织Ki-67和表皮生长因子受体2（C-erbB-2）表达的关系。方法：选择2021年1月至2022年1月于湖南省妇幼保健院超声医学科行乳腺SWE检查的106例乳腺肿块患者,根据术后或组织活检的病理检查结果分为恶性组59例和良性组47例。对比恶性组和良性组SWE参数的差异以及不同Ki-67和C-erbB-2表达乳腺癌病灶SWE参数的差异。Spearman分析乳腺癌病灶SWE参数与乳腺癌组织Ki-67和C-erbB-2表达的相关性。绘制受试者工作特征（ROC）曲线分析乳腺病灶SWE参数鉴别乳腺肿块良恶性的价值。结果：恶性组AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 高于良性组（P＜0.05）。联合AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 鉴别乳腺肿块良恶性的曲线下面积为0.841,高于单独参数鉴别的0.657、0.599、0.642、0.609（P＜0.05）。Ki-67阳性组、C-erbB-2阳性组AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 高于阴性组（P＜0.05）。乳腺癌病灶AE-max、Shell1 E _max 、Shell2 E _max 、Shell3 E _max 与Ki-67和C-erbB-2表达均呈正相关（P＜0.05）。结论：乳腺恶性肿块与良性肿块的SWE参数存在明显差异,且与乳腺癌组织的Ki-67、C-erbB-2阳性表达有关,乳腺SWE检查有助于鉴别乳腺肿块良恶性。     

Expression of iron-related proteins in feline and canine mammary gland reveals unexpected accumulation of iron

Dysregulation of cellular iron homeostasis in human breast cancer is reflected by the altered expression of regulatory proteins. The expressions of iron-related proteins in the mammary glands of cats and dogs have not been assessed. We evaluated the expressions of ferritin, ferroportin, hepcidin and transferrin receptor 1 in benign and malignant mammary gland lesions in cats and dogs. Iron deposition was detected using Perls’ Prussian blue staining. We found no major differences in the expression of iron-related proteins between benign and malignant mammary gland lesions in either cats or dogs; however, these species exhibited accumulation of iron in benign lesions. Our findings provide an explanation for the absence of higher iron requirements by tumor cells in these animals. Further investigation of local iron homeostasis in cats and dogs and differences in their physiology compared to human breast cancer is required.     

3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值及较优b值下ADC值与预后因子相关性研究

摘要 目的：研究3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值及较优b值下ADC值与预后因子的相关性。方法：选取2017年11月～2019年11月于我院接受诊治的乳腺病变患者50例进行研究,将其按照良恶性差异分成恶性组40例与良性组10例,另取同期于我院体检的健康志愿者50例作为对照组。对所有人员均进行3.0 T磁共振扩散加权成像,比较不同b值下ADC值在不同乳腺组织中的差异,比较不同b值下诊断乳腺良恶性病变的效能,分析较优b值下ADC值和乳腺癌患者各项预后因子的相关性。结果：对照组、良性组、恶性组在不同b值下的ADC值均呈逐渐降低趋势（P＜0.05）;对照组、良性组、恶性组b值为1000 s/mm²下的ADC值均低于b值为600 s/mm²（P＜0.05）。b值为1000 s/mm²时诊断乳腺恶性病变的敏感度、特异度、准确度分别为92.50%、100.00%、94.00%,高于b值为600 s/mm²的70.00%、60.00%、68.00%（P＜0.05）。b值为1000 s/mm²下雌激素受体、孕激素受阳性患者的ADC值低于阴性患者,而人类表皮生长因子受体2阳性患者的ADC值高于阴性患者（P＜0.05）。经Spearman相关性分析可得,b值为1000 s/mm²下ADC值与雌激素受体、孕激素受体阳性表达均呈负相关关系,而与人类表皮生长因子受体2阳性表达呈正相关关系（P＜0.05）。结论：3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值较高,且以b值为1000 s/mm²的诊断能效较优。此外,b值下ADC值和乳腺癌部分预后因子表达状态密切相关。     

乳腺癌ConA、LCA、PSA免疫组化研究

运用ＡＢＣ法研究５０例乳腺癌三种凝集素受体（Ｌｅｃｔｉｎ－Ｒ）的表达,并以乳腺纤维瘤和乳腺小叶增生症各１０例作为对照。结果表明：该三种凝集素受体在乳腺良、恶性病变中的表达率无显著性差异。ＣＯｎＡ－Ｒ在乳腺癌以胞浆型定位为主,在纤维腺瘤则以胞膜型多见（Ｐ＜０．０５）。ＬＣＡ－Ｒ和ＰＳＡ－Ｒ在乳腺三种病变中均以胞浆型为主。ＣｏｎＡ－Ｒ与乳腺癌分化程度具良好的相关性;ＬＣＡ－Ｒ与乳腺癌瘤体大小有关。该三种凝集素受体与ＥＲ、ＰＲ及ＣＥＡ的表达未显示密切的关联。     

Cytochemistry of imprints from breast biopsies

In order to investigate the cytoplasmic features of cells from benign and malignant breast lesions, a series of cytochemical reactions was applied to 117 sets of imprints made from breast biopsies. Alkaline phosphatase was present in all benign lesions except one but absent in 56% of the carcinomas. Lipids detected by the oil red O method were significantly more common in carcinomas but also present in a substantial number of benign lesions, making this difference of minor importance in diagnostic cytology. Carcinomas with a cytoplasmic lipid content stainable with oil red O and with moderate or marked sudanophilia had a significantly higher rate of axillary lymph node metastases, illustrating the prognostic value of the lipid-staining methods. Intracytoplasmic inclusions (ICI) detected by the periodic acid Schiff (PAS) method were found in 62% of the carcinomas and in only one benign lesion, making their presence of great diagnostic value. It is concluded that the application of certain cytochemical methods may improve the diagnostic accuracy of breast cytology.     

乳腺影像报告数据系统对乳腺疾病的诊断价值

目的:探讨BI-RADS(breast imaging reporting and data system)乳腺影像报告数据系统对乳腺疾病的诊断价值。方法:采用彩色多普勒超声对75例乳腺占位性病变患者(均为女性)进行双侧乳腺探查,并采用BI-RADS乳腺影像报告数据系统进行评价。选取患者BI-RADS 3类、4类、5类的94枚病灶进行研究,以组织病理学诊断结果为金标准,来探讨其关系。结果:在94个病灶中BI-RADS诊断为3类32枚,病理学结果证明良性30枚(93.75%),恶性2枚(6.25%);BI-RADS诊断为4类的36枚,病理学结果证明良性24枚(66.67%),恶性12枚(33.33%);BI-RADS诊断为5类的26枚,病理学结果证明良性2枚(7.69%),恶性24枚(92.31%)。结论:BI-RADS乳腺影像报告数据系统可用来对各级病灶进行描述、评估,有利于提高乳腺病变影像诊断的特异性,为临床医生提供了明确的病变信息,为其进行下一步治疗措施起着重要的指导价值。     

Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.