Noninvasive in vivo tomographic optical imaging of cellular morphology in the breast: possible convergence of microscopic pathology and macroscopic radiology

This article presents a pilot study of multispectral diffuse optical tomography for noninvasively imaging volume fraction and mean size of cellular scattering components in the breast. Cellular morphology images for a total of 14 cases (four malignant breast and ten benign lesions) were obtained. Analyzing the images based on the pathological findings of the cases studied, we found that light scattering in the breast was contributed from both the nucleus and organelles such as mitochondria and nucleolus. Based on the image analysis of these 14 cases, we found that the differences in the mean size and volume fraction between the malignant and benign lesions are significant. The contrast ratio of the average mean size and volume fraction between malignant and benign lesions were calculated to be 3.38 and 2.63. These initial results suggest that cellular mean size and volume fraction may be two new criteria that could be used to differentiate malignant from benign lesions.     

The significance of the diagnosis of atypia in breast fine-needle aspiration

The diagnosis of atypia in breast fine-needle aspiration (FNA) continues to be an area of debate in cytology practice. The aim of this study was to assess the clinical significance of this term and to evaluate potential morphological criteria, which would determine the patient's outcome. A computer-based search was carried out to retrieve breast FNAs performed between 1990 and 2000 that were diagnosed as atypical. Cases followed by surgical resection were reexamined for the presence of morphological features potentially differentiating benign and malignant lesions. Out of 1,568 breast FNAs, there were 64 cases (4%) with a diagnosis of atypia. Thirty-eight cases had surgical follow-up material that revealed malignancy in 14 cases (37%) and benign lesions in 24 cases (63%). The benign diagnostic categories included fibrocystic change (12/24), fibroadenoma (3/24), tubular adenoma (2/24), and nonspecific findings (7/24). The malignant diagnoses included ductal carcinoma (9/14), lobular carcinoma (3/14), ductal carcinoma in situ (DCIS; 1/14), and tubular carcinoma (1/14). The evaluation of cytological criteria used to differentiate benign from malignant lesions (i.e., cellularity, loss of cohesion, myoepithelial cells, nuclear enlargement, nuclear overlap, prominent nucleoli) revealed significant overlap between benign and malignant cases, particularly in cases of fibroadenoma, tubular adenoma, and proliferative breast disease. The surgical follow-up of four hypocellular cases revealed lobular carcinoma in two cases and ductal carcinoma in the remaining two cases. Our study confirmed that the diagnosis of atypia is clinically significant because it is associated with a high probability of malignancy. No morphological criterion is able to reliably differentiate benign and malignant lesions in cases diagnosed with atypia. Diagnosis of atypia is particularly significant in hypocellular cases. We recommended that breast FNAs with a diagnosis of atypia be evaluated further histologically.     

乳腺叶状肿瘤的临床病理学研究

目的 探讨乳腺叶状肿瘤的病理形态学特点,分类和诊断标准,与复发转移的关系及其临床意义。方法 采用回顾性分析的方法对203例有随1访（6－372个月）资料的叶状肿瘤作了详细形态学持征的分析和分类研究,统计学聚类判别分析（SPSS软件10．0版）。结果 良性133例（复发28例）,交界性42例（复发19例,死亡2例）,恶性28例（复发18例,死亡15例）。统计学分析结果显示,肿瘤生长方式,瘤细胞异型性,核分裂象计数和肿瘤性坏死所组成的变量子集分类错判率为零。以此4项为主,完善了病理组织学诊断标准。良性,交界笥和恶性组间复发率,转移和死亡率差异均有显著性意义。肿瘤复发随术式的扩大而减少,2次以上复发占53．85％（35／65）。结论 此瘤可分为良性,低度恶性（交界性）及恶性三种类别。肿瘤生长方式,瘤细胞异型性,核分裂象和肿瘤性坏死是诊断此瘤并对其进行分级（分类）的重要依据。提示首次术式的选择的重要性,良性叶状肿瘤应选择肿物扩大切除术,对于复发的交界性和恶性肿瘤应作乳房切除术。     

Differential pattern of perivascular type IV collagen deposits in phyllodes tumors of the breast.

Deposition of basement membrane extracellular matrix is influenced by adjacent tumor cells, and in some cases, the pattern of type IV collagen deposit is characteristic in malignant tumors. In this report, we analyzed the difference in type IV collagen deposition patterns between benign and malignant phyllodes tumors (PTs) of the breast. Of the 15 cases of PTs, 8 cases were benign PTs and 7 cases were malignant PTs. Three cases of other primary sarcomas of the breast (stromal sarcoma, angiosarcoma and osteosarcoma) and 2 cases of fibroadenomas were studied for comparison. The malignant PTs were distinguished from benign ones by increased mitotic figures, cellular atypism, and a higher proliferation index of stromal cells. Immunohistochemical staining against type IV collagen in malignant PTs revealed extensive to moderate deposition of type IV collagen around the small blood vessels in duplicate or multilayering pattern, while benign PTs showed minimal deposition in a single linear pattern. All of the three cases of other sarcomas revealed multilayering or meshwork pattern of type IV collagen around the blood vessels. The deposition of type IV collagen around the blood vessels may reflect the malignant behavior of the stromal tumors of the breast.     

Cystosarcoma phylloides of the breast and its mimics. An immunohistochemical and ultrastructural study

Cystosarcoma phylloides of the breast is a tumor composed of breast ducts and a cellular stromal component that can be benign or malignant. The origin of the stromal cells is controversial. We undertook an immunohistochemical and ultrastructural study of 11 cases of cystosarcoma phylloides to assess the histogenesis of the stromal component. By light microscopy, 4 were diagnosed as benign, and 7 were diagnosed as malignant. Antibodies to vimentin, desmin, actin, high- and low-molecular-weight keratins, and S100 protein were used for immunohistochemical staining. In the 4 benign cases of cystosarcoma phylloides, the stromal cells stained positively only for vimentin. In the malignant tumors, the spindle cell component stained for vimentin in all the cases. In addition, the malignant stromal cells coexpressed desmin in two cases and keratin and S 100 protein in another case. By electron microscopy the stromal component in the benign case and in two of five malignant cases was composed of a mixture of fibroblasts and myofibroblasts. The entire neoplastic stroma in two other malignant cases showed features of smooth-muscle differentiation, whereas in another case all the stromal cells showed myoepithelial differentiation. Thus, in benign and malignant cystosarcoma phylloides, the stromal component consists of a mixture of fibroblasts and myofibroblasts. Leiomyosarcomas and myoepitheliomas can mimic malignant cystosarcoma phylloides, but immunohistochemistry and electron microscopy can differentiate these entities. This is important since their biologic behavior is different.     

Patterns of p53 expression in phyllodes tumors of the breast--an immunohistochemical study.

Authors performed an immunohistochemical analysis using monoclonal antibody to p53 protein on 15 cases of benign and malignant phyllodes tumor of the breast along with a review of other conventional clinicopathological parameters to investigate the meaning of p53 expression. The cases were composed of 8 benign and 7 malignant lesions. The pattern of p53 expression showed a statistically significant difference between these benign and malignant lesions (p < 0.005). None of the benign cases expressed p53 whereas 6 out of 7 malignant cases did. Among malignant phyllodes tumors, the pattern of expression was diffuse and strong in two cases while granular and relatively weak in the remaining 4 cases. p53 expression seemed to be a unique feature of malignant phyllodes tumors, thereby, one of the most significant parameters for the differentiation of benign and malignant phyllodes tumors of the breast.     

单克隆抗体SC13A和SC3A在乳腺疾病中的免疫组化研究

本文以免疫组化法分别研究了McAb SC 13A和SC 3A与134例12种不同组织学类型乳腺疾病的反应性。结果显示,这2株McAb与乳腺癌的阳性反应率分别为89.5％和94.7％,其中强阳性各占68.5％和76.3％;反应范围>50％的分别为52.6％和72.3％。这2株McAb的反应结果相似(P>0.05)。在乳腺良性病变中,其阳性率分别为22.4％和48.3％,后者明显高于前者,与乳腺癌比较的差异均有非常显著意义(P<0.01)。表明这2株McAb识别的抗原在乳腺癌中均有较高的表达,但在良性病变中亦有一定的表达,为其进一步深入研究提供了一种新而有用的标志物。     

Expert system support using Bayesian belief networks in the diagnosis of fine needle aspiration biopsy specimens of the breast.

AIM--To develop an expert system model for the diagnosis of fine needle aspiration cytology (FNAC) of the breast. METHODS--Knowledge and uncertainty were represented in the form of a Bayesian belief network which permitted the combination of diagnostic evidence in a cumulative manner and provided a final probability for the possible diagnostic outcomes. The network comprised 10 cytological features (evidence nodes), each independently linked to the diagnosis (decision node) by a conditional probability matrix. The system was designed to be interactive in that the cytopathologist entered evidence into the network in the form of likelihood ratios for the outcomes at each evidence node. RESULTS--The efficiency of the network was tested on a series of 40 breast FNAC specimens. The highest diagnostic probability provided by the network agreed with the cytopathologists' diagnosis in 100% of cases for the assessment of discrete, benign, and malignant aspirates. Atypical probably benign cases were given probabilities in favour of a benign diagnosis. Suspicious cases tended to have similar probabilities for both diagnostic outcomes and so, correctly, could not be assigned as benign or malignant. A closer examination of cumulative belief graphs for the diagnostic sequence of each case provided insight into the diagnostic process, and quantitative data which improved the identification of suspicious cases. CONCLUSION--The further development of such a system will have three important roles in breast cytodiagnosis: (1) to aid the cytologist in making a more consistent and objective diagnosis; (2) to provide a teaching tool on breast cytological diagnosis for the non-expert; and (3) it is the first stage in the development of a system capable of automated diagnosis through the use of expert system machine vision.     

应用细针吸取细胞技术诊断乳腺导管病变的细胞学指标

目的 探讨采用细针吸取细胞学(FNAC)诊断乳腺导管病变的有效和联合的指标,以建立有效的乳腺导管病变FNAC诊断模式.方法 收集澳门镜湖医院6年内400例有随访结果的乳腺FNAC病例作回顾性分析.按组织学诊断结果分为导管上皮非增生性病变(104例)和增生性病变(163例)及癌(133例)三组,对涂片进行60个细胞学指标分析,再根据各指标的程度或量采用半定量分级评估.以组织学诊断结果为金标准对病变分类,研究各指标对诊断导管病变的意义.采用Logistic多重回归模型和分类树模型进行统计学分析.结果 (1)400例良、恶性病变组,上皮细胞团中掺杂肌上皮细胞(P<0.05)、上皮细胞排列成大的细胞团(P<0.05)、上皮细胞排列成小的细胞团(P<0.05)、细胞质内空泡(P<0.05)和细胞套细胞(P<0.1)为有统计学意义的鉴别诊断指标.最重要的鉴别指标为上皮细胞团中有无掺杂有肌上皮细胞.良性病变的诊断指标为上皮细胞团中掺杂有肌上皮细胞,联合大量的上皮细胞排列成大的细胞团,94.4%为良性病变,中等至大量的上皮细胞排列成小的细胞团,倾向为增生性病变;癌的诊断指标为上皮细胞团中无掺杂肌上皮细胞,上皮细胞排列成小的细胞团,细胞质内空泡和细胞套细胞.上皮细胞团中无掺杂肌上皮细胞时,癌占81.3%.(2)267例非增生性和增生性良性导管上皮病变组,上皮细胞团中见不规则的细胞间腔隙(P=0.001)、上皮细胞团成松散排列(P<0.05)和细胞核深染(P<0.1)为诊断增生的有意义指标.两结构指标在涂片中出现的量越多,越提示为增生.单一上皮细胞团中见不规则的细胞间腔隙,增生性病变占70.1%;当中等至大量时增生占82.7%,若同时伴上皮细胞团成松散排列,诊断增生的阳性预测价值为87.5%.(3)伴不典型细胞学改变的35例中,组织学诊断26例增生,多为导管上皮增生性纤维腺瘤,极少数为不典型增生或癌.结论 在乳腺病变FNAC诊断中,结构指标较细胞指标更重要,联合指标和对其量的评估可更有效地鉴别良恶性病变、非增生性和增生性良性病变;对伴不典型细胞学改变的病例应避免误诊为癌,均应组织活检.     

Fractal dimensions of breast lesions on cytology smears

In the present study, box-counting fractal dimensions of benign and malignant cells of breast tumors on cytology material were measured and compared. We selected fine-needle aspiration cytology smears of 14 cases of histopathology-proven infiltrating duct carcinomas and 7 cases of fibroadenoma of the breast. Five cells were randomly selected from each case. Box-counting fractal dimensions of all cells were measured with the help of an image cytometer (Leica, Cambridge, UK), using Quantimet 600 software (Leica). In total, 70 malignant cells and 35 benign cells were studied. The mean fractal dimensions of malignant cells and benign cells were 0.9571 +/- 0.1265 and 0.8354 +/- 0.1367, respectively. There was significant difference in the fractal dimension of malignant and benign cells (P = 0.006, Mann-Whitney nonparametric test). The measurement of fractal dimension may be helpful in discriminating malignant from benign cells. This may be another discriminating feature of malignant cells, along with classic image morphometry based on Euclidean geometry.     

高频超声结合BI-RADS分级在乳腺良恶性病变中的应用价值

目的 探讨高频超声结合BI-RADS分级在乳腺良恶性病变诊断的应用价值。方法 选取2016年3月~2017年10月东莞市石碣镇参与“两癌”筛查乳腺体检者2874例,应用超声检查双乳情况。对2874例乳腺体检者进行随访,其中经穿刺检查或手术切除肿物组织病理检查发现,恶性肿瘤17例。以病理诊断结果为对照,评估高频超声结合BI-RADS分级在乳腺良恶性病变诊断的应用价值。结果 乳腺恶性病变的高频超声高评分的例数高于良性病变,差异有统计学意义（P＜0.05）;乳腺恶性病变BI-RADS评分Ⅳ级例数高于良性病变,差异有统计学意义（P＜0.05）;高频超声评分与BI-RADS分级诊断乳腺病变的灵敏度、特异度、准确率、阳性预测值及阴性预测值之间比较,差异无统计学意义（P＞0.05）;两种方法联合诊断时,其灵敏度、特异度、准确率、阳性预测值及阴性预测值均较单独高频超声评分诊断、单独BI-RADS分级诊断有不同程度的提高,其中两种方法联合诊断时灵敏度和阳性预测值与两种方法单独诊断比较,差异有统计学意义（P＜0.05）。结论 高频超声检查与BI-RADS评分分级在鉴别诊断乳腺肿块良恶性上具有较高的临床价值,但仍存在一定局限性,两者联合应用在一定程度上能提高乳腺良恶性病变的诊断准确率,是较为理想的检查手段。     

CD34, CD117, and Ki-67 expression in phyllodes tumor of the breast: an immunohistochemical study of 33 cases

Phyllodes tumors (PTs) of the breast are biphasic lesions, comprising an epithelial component set within a neoplastic spindle-celled stroma. These tumors have been classified as benign, borderline, and malignant based on a combination of histological criteria, including stromal cellularity, nuclear pleomorphism, mitotic rate, stromal overgrowth, and margin appearance. The aim of this study was to evaluate the expression of CD34, CD117 (c-kit), and Ki-67 in PT of the breast and attempt to correlate the staining pattern with tumor grade by morphology. Immunohistochemical expression of CD117, CD34, and Ki-67 was studied on formalin-fixed, paraffin-embedded archival tissue material from 33 cases of PT. Histologically, there were 21 benign, 6 borderline, and 6 malignant (high-grade) tumors. All 6 histologically malignant PTs were positive for CD117 (100%), but only 1 marked with CD34 (16.7%). Borderline PTs frequently coexpressed CD34 and CD117 (66.7%). The benign PTs, on the other hand, most commonly (52.4%) showed a CD34(+)/CD117(-) immunoprofile with 33.3% cases coexpressing the markers: that is, CD34(+)/CD117(+). Although most benign PTs (80.6%) showed a Ki-67 of <2%, a few cases showed slightly higher proliferation indices. This study indicates that CD34 and CD117 are differentially expressed in benign and malignant PTs. These markers, therefore, in combination, may be used as an adjunct to morphology in the subclassification of PTs.     

Expression of prolactin receptors in normal, benign, and malignant breast tissue: an immunohistological study

AIMS: Prolactin plays an important role in the proliferation and differentiation of normal breast epithelium, and possibly in the development of breast carcinoma. The effects of prolactin are mediated by its receptor; thus, alteration in the expression of this receptor could be important in studying the biology of breast cancer. This investigation was aimed at comparing the expression of prolactin receptors in normal, benign, and malignant breast tissue. MATERIAL/METHODS: The expression of prolactin receptors was studied in paraffin wax embedded sections of 102 breast biopsies (93 female and nine male), using the monoclonal antibody B6.2, and the avidin-biotin immunoperoxidase technique. Six biopsies were normal, 34 had benign lesions, and 62 were malignant. RESULTS: In normal cases, prolactin receptor positivity was seen only on the luminal borders of the epithelial cells lining ducts and acini. In most benign lesions, variable degrees of luminal and cytoplasmic staining were seen. Cells showing apocrine metaplasia and florid regular ductal epithelial hyperplasia were mostly negative. In malignant cases, the staining pattern was mostly cytoplasmic and heterogeneous. Forty one of the 59 carcinomas in women showed a degree of positivity involving 10-100% of the tumour cells. A significant direct correlation was found between prolactin receptor and oestrogen receptor staining when only cases that scored more than 100/300 for the latter receptor, using the H scoring system, were considered (p = 0.0207). No correlation was found between prolactin receptors and progesterone receptors, patient's age, tumour size, tumour grade, or axillary lymph node status. CONCLUSIONS: Prolactin receptors seem to be expressed at different cellular sites in normal, benign, and malignant breast epithelial cells. The receptor is expressed in more than two thirds of female breast carcinomas, suggesting that it may play a role in the pathogenesis of the disease. The positivity is correlated with moderate and strong staining for oestrogen receptors in tissue sections, but not with other prognostic factors.     

Aspiration biopsy of the breast tumors. Analysis of diagnostically difficult cases.

In this paper the authors described those of the breast fine needle aspirates which were difficult for interpretation e.g. clear-cut differentiation between benign and malignant character of the lesion could not be made. There were 40 such cases (1.96%) out of 2332 breast tumors biopsied between 1987-1989. In the cases that proved to be malignant on histology the authors described cytological features which speak in favour of malignancy. In the group of smears which proved to be benign on histology the authors described the features that imitate atypia and should not be misdiagnosed as malignant. The described criteria may be of some help in cytological diagnosis of breast masses.     

乳腺腺样囊性癌临床病理特点及文献复习

目的 探讨乳腺腺样囊性癌的临床病理特点及鉴别诊断要点。方法观察4例乳腺腺样囊性癌的临床病理和免疫组化特点，并复习相关文献。结果 4例乳腺腺样囊性癌大体上均表现为界限清楚的肿块。该肿瘤在结构上可以分为筛孔型、管状-小梁状型和实体型三种类型，并需与一系列乳腺良恶性病变相鉴别，如胶原小球病、筛状癌、小细胞癌等。结论 乳腺腺样囊性癌是一种少见肿瘤，具有其独特的组织病理学特点，预后较好。     

Clonal chromosomal alterations in fibroadenomas of the breast.

A cytogenetic study on short-term cell cultures from 10 fibroadenomas of the breast is reported. Clonal chromosomal alterations were observed in all cases analyzed, involving preferentially chromosomes X, 12, 14, 20, and 22. Normal karyotypes were found in 34.9% of the cells. The present findings are discussed together with the reports on fibroadenomas and other benign lesions of the breast described in the literature. Although no specific chromosome abnormality to date can be attributed to a particular type of benign breast pathology, some recurrent alterations are starting to emerge and may characterize these benign breast lesions, differentiating them from their malignant counterparts.     

Expression of Sialyl-Tn in fine-needle aspirates from mammographically detected breast lesions: A marker of malignancy?

Malignant transformation is frequently associated with abnormal expression of cell surface carbohydrates. Sialyl-Tn (STn) is a core carbohydrate antigen of tumor-associated mucin formed by the premature 2-6 sialylation of N-acetylgalactosamine. In an attempt to verify whether this antigen is restricted to malignant cells, we studied 30 cases of fine-needle aspiration (FNA) cytology from mammographically detected breast lesions. The rationale for choosing this material was the acknowledged difficulty in diagnosing cytologically small breast lesions, especially epithelial intraductal proliferations. The cases were divided in benign lesions (two fibroadenomas and ten ductal hyperplasias) and malignant lesions (16 ductal carcinomas). Ten of sixteen malignant cases (62.5%) were positive for STn. Five of fourteen benign cases (35.7%) were also positive for STn (two fibroadenomas and three ductal hyperplasias). The most consistent positive results in benign lesions resulted from cases that displayed apocrine metaplasia, although positivity has also been observed in ductal cells without metaplasia. We did not find statistical significant differences among STn expression in benign and malignant breast lesions detected by FNA (P = 0.14). Thus, we conclude that STn is neither specific nor sensitive for detection of malignancy in FNA from mammographically detected breast lesions. Diagn. Cytopathol. 1998;18:325–329. © 1998 Wiley-Liss, Inc.     

CD10, actin, and vimentin expression in breast phyllodes tumors correlates with tumor grades of the WHO grading system

The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.