Cytologic diagnosis of metastatic malignant phyllodes tumor of the breast in pleural effusion

A 54‐year‐old woman presented with a left breast mass, discovered 4 years ago but was static until 2 months before presentation, when it showed a rapid increase in size and became painful. Mammography showed a large lobulated mass with internal cystic components (BI‐RADS 4B). A biopsy was performed, followed by modified radical mastectomy. The histologic diagnosis was malignant phyllodes tumor (PT). The patient developed local recurrence 4 months later while on adjuvant radiotherapy and she had a salvage resection. Two months later, she developed massive left pleural effusion. Pleural fluid cytology showed single discohesive markedly atypical cells with hyperchromatic and enlarged nuclei, irregular nuclear membrane, and distinct macronucleoli. Multinucleated forms were also seen. The mononuclear and multinucleated tumor cells cytomorphologically resembled that of the recurrent tumor, indicative of recurrence. Positron emission tomography/computed tomography confirmed recurrence at the left pleura. The patient opted for palliative care and succumbed 1 month later. The current case demonstrated a rare clinical presentation of recurrent malignant PT as massive unilateral malignant pleural effusion. Correlation with previous histologic and cytologic specimens may be useful as similar cytologic features could be identified in subsequent recurrent tumors.     

Increased microvessel density in malignant and borderline mammary phyllodes tumours

AIMS: Tumour vascularity is considered a prognostic indicator in breast carcinoma, but its utility in mammary phyllodes tumour has not been explored. The authors report the correlation between intratumoral microvessel density and the histological grade of phyllodes tumour. METHODS AND RESULTS: Forty cases of phyllodes tumour were reviewed for stromal cellularity, overgrowth, cytological pleomorphism, mitotic count and margin pattern. Using established criteria, these were diagnosed as benign (n=28), borderline (n=10) and malignant (n=2). Microvessel density was counted on CD31-stained slides as the number of vessels per high power field. For benign phyllodes tumour, the range was 7-26.2 (mean 13.1); for borderline phyllodes tumour the range was 17.2-32.5 (mean 22.4); for malignant phyllodes tumour the range was 25.9-33.3 (mean 29.6). The difference between the benign and borderline groups was significant (P < 0.0001) but that between the borderline and malignant groups was not, due to the small number of malignant cases. CONCLUSIONS: There is a significant difference in stromal microvessel density between benign and borderline phyllodes tumour. Although the small number of cases of malignant phyllodes tumour limits further interpretation, we believe that microvessel density can be used as an additional objective histological parameter in the evaluation of phyllodes tumour.     

Prognostic factors of phyllodes tumor of the breast

The phyllodes tumor is characterized by its tendency to recur locally and occasionally to metastasize. The purpose of the present paper was to assess the prognostic value of clinical-morphological characteristics in patients with phyllodes tumor. Forty-seven cases of phyllodes tumors was studied; the World Health Organization classification was used and follow up was obtained. A total of 51%, 28% and 21% of the tumors were classified as benign, borderline and malignant, respectively. The adherence (P = 0.01), size >10 cm (P = 0.001), high mitotic activity (P = 0.03), infiltrative tumor margin (P = 0.0002) and type of surgery in malignant tumors (P = 0.02) proved to be good predictors of relapse. The presence of pain (P = 0.03), postmenopausal status (P < 0.04), heavy cellular pleomorphism (P = 0.007), high mitotic activity (P = 0.002), tumoral grade (P = 0.006) and metastasis (P < 0.00001) were prognostic factors of poor survival. Tumoral grade and some clinical-morphological characteristics of patients with phyllodes tumors have a significant impact on the prediction of its biological behavior.     

Comparative study of histological features between core needle biopsy and surgical excision in phyllodes tumor

We analyzed histopathological features of core needle biopsy (CNB) and surgical excision specimen comparatively in 129 patients with surgically proven phyllodes tumor (PT). Stromal characteristics including cellularity, atypia, mitosis, overgrowth, tissue fragmentation, and the tumor margin were assessed. Benign/borderline/malignant phyllodes tumor (PT) were diagnosed in 90 (69.8%)/30 (23.3%)/9 (7.0%) patients. Among the 90 cases of benign PTs, 67 cases (74.4%) were diagnosed concordantly in CNB. For borderline and malignant PTs, three out of eight (26.6%) and four out of nine (44.4%) cases were diagnosed concordantly in CNBs. All 50 cases of discordant diagnosis were underestimated in matched CNBs, especially in their stromal cellularity and mitosis. The size of tumor is larger in discordant cases of PT (P= 0.013). The concordant rate of diagnosis between CNB and surgical excision was about 60% and accordingly, grading of PT based on the histological findings in CNBs has limitation. The discordance comes from heterogeneous stromal properties of PTs.     

An update on the classification of phyllodes tumours of the breast

Phyllodes tumour (PT) is a rare fibroepithelial neoplasm of the breast, histologically categorized into 3 grades, namely benign, borderline and malignant; each with distinct clinical behaviour and implications for management. This article addresses challenges in the diagnosis, grading and management of PT in excisional and core needle biopsy specimens, with a brief review of recent molecular findings.     

Malignant phyllodes tumor of the breast with expression of osteonectin and vinculin

Phyllodes tumor is a very rare neoplasm which accounts for 2.5% of all fibroepithelial lesions of the breast. The mesenchymal component of a malignant phyllodes tumor frequently contains heterologous components. We report a case of malignant phyllodes tumor. The patient was a 40-year-old woman with a lump on the left breast. Histological examination revealed the lump to be a malignant phyllodes tumor with foci of liposarcomatous differentiation. The mesenchymal tumor cells, including those in the liposarcomatous components, were found to express vimentin, osteonectin and vinculin. However, they showed no immunoreaction to CAM 5.2, desmin, alpha-smooth muscle actin (ASMA), neuron-specific enolase (NSE) nor S-100. Ultrastructurally, the mesenchymal tumor cells were found to have abundant cytoplasmic organelles, but there was no evidence showing their differentiation to myofibroblasts. Further studies will be necessary to elucidate the significance of vinculin and osteonectin expression in malignant phyllodes tumor.     

Expression of Yes-associated protein (YAP) in breast phyllodes tumor

This study aimed to identify expression profiles of Yes-associated protein (YAP) and its phosphorylated form (pYAP) in phyllodes tumor (PT) of human breast and verify the clinical implications. We selected PTs from the pathologic archive and reviewed the histologic features (141 benign, 27 borderline, and 15 malignant). We made tissue microarray (TMA) block from the formalin-fixed paraffin-embedded (FFPE) tissue corresponding to the representative section. Using TMA block, we performed immunohistochemical staining of YAP and pYAP. In the stromal component, expressions of YAP and pYAP were increased in borderline/malignant PT with comparison of benign PT (P = 0.002, and P < 0.001, respectively). In the epithelial component, cytoplasmic expression of YAP was highest in borderline PT (P = 0.001). Stromal YAP expression (P < 0.001) and stromal pYAP expression (P = 0.042) were associated with shorter disease-free survival (DFS) and stromal pYAP expression (P = 0.001) was associated with shorter overall survival (OS) in univariate Cox analysis. In multivariate Cox analysis, stromal YAP expression was an independent prognostic factor associated with shorter DFS (Hazard ration: 3.206, 95% CI: 1.000-10.27, P = 0.050). In conclusion, expression level of YAP in stromal component was increased along with histologic grade of PT and YAP expression in PT was related to tumor progression and poor prognosis.     

压迫式弹性成像与声脉冲辐射力成像技术在乳腺肿瘤良恶性鉴别中的价值比较

目的:探讨分析压迫式弹性成像（CE）与声脉冲辐射力成像（ARFI）技术在乳腺肿瘤良恶性鉴别中的价值。方法:选择门诊或住院行超声检查发现的有乳腺肿块患者71例共89个病灶,经病理组织学确认良性病灶57个,恶性病灶32个。对各病灶进行彩色多普勒超声检查,并采取CE及ARFI技术,分别计算病灶弹性应变率比值（SR）及声触诊组织定量（VTQ）值,采用ROC曲线分析SR、VTQ对良恶性肿瘤的诊断效能。结果:恶性组病灶VTQ值与SR值均显著高于良性组（P<0.05）。采用ROC曲线分析VTQ、SR对乳腺良恶性肿瘤诊断效能,VTQ诊断曲线下面积（AUC）为0.918,95% CI为0.871~0.980（P<0.05）,最佳截断值为3.97,在此最佳截断值下,VTQ诊断敏感性94.64%、诊断特异性90.63%;SR诊断AUC为0.899,95% CI为0.854~0.956（P<0.05）,最佳截断值为4.12,在此最佳截断值下,SR诊断敏感性92.86%、诊断特异性84.38%。VTQ和SR诊断敏感性、特异性比较差异无统计学意义（P>0.05）。结论:两种超声诊断技术对乳腺良恶性肿瘤均具有较高的诊断价值,其诊断效能相似,临床上可联合使用,以实现优势互补,提高对乳腺癌的早期检出率。     

乳腺上皮样型管周间质肉瘤病理特征及与叶状肿瘤比较观察

目的 探讨乳腺上皮样型管周间质肉瘤的临床病理特点及与叶状肿瘤的关系。方法 采用HE、特殊染色、免疫组化染色(CK，EMA，S-100蛋白，SMA，Vim，Des，MG，CD34，CD99，CD117，PR，HMB45)对1例乳腺上皮样型管周间质肉瘤与5例叶状肿瘤(良性、交界性各1例，恶性3例)做比较性观察。结果 乳腺管周间质肉瘤(上皮样型)有独特的镜下图像：①显著的多角形(上皮样)细胞绕导管或小管的上皮肌上皮层呈间质性增生，无叶状结构；②组织学模式有袖套状、花冠状、菊形团状、结节状、融合结节状和片状浸润；③瘤细胞形态有：多角形(大、小)、柱状和梭形。多角形细胞呈上皮样形态，异型明显，核分裂象多见(10～30个／10HPF，个别区域达6个／1HPF)，病理性核分裂象易见，在浸润灶内见肿瘤性坏死；④瘤细胞Vim弥漫阳性、EMA灶性阳性、CD99和CD117灶性弱阳性、CD34少数阳性，CK、SMA、S-100蛋白、Des、MG、PR、HMB45均阴性。5例叶状肿瘤均具备叶状结构、间质过度增生、细胞密集(异质性分布)、核分裂象2～10个／10HPF等诊断要素。在3例恶性叶状肿瘤中，2例有极少的上皮样袖套状病灶，2例有梭形细胞袖套状病灶。结论 乳腺上皮样型管周间质肉瘤是一种极罕见的恶性纤维上皮肿瘤亚型，它可能是恶性叶状肿瘤的最早期病变，也可能是一种独特的类型。     

An immunohistochemical study of metaplastic spindle cell carcinoma, phyllodes tumor and fibromatosis of the breast

The diagnosis of metaplastic (sarcomatoid) carcinoma (MSC) of breast often requires immunohistochemistry with a cytokeratin (CK) panel to distinguish them from phyllodes tumors (PT), primary sarcomas, and fibromatoses. CK staining may be heterogeneous in metaplastic carcinomas. The aim of the study was to investigate the theory that MSCs show evidence of myoepithelial differentiation and to evaluate immunohistochemical markers that may be helpful in distinguishing MSCs from PT and fibromatosis. We reviewed histology and performed immunohistochemistry for AE1/AE3, 34betaE12, CK5 and CK14, Cam5.2, CK7 and CK19, epithelial membrane antigen (EMA) (B55), smooth muscle actin (SMA), S100, desmin, vimentin, CD31, CD34, and bcl-2 on paraffin-embedded tissue from 18 MSCs, 26 PTs, and 8 fibromatoses. We assessed staining by using a semiquantitative method. Sarcomatous areas in MSCs were positive for 34betaE12 in 11 cases; for SMA in 10; for CK5 in 7; for CK14 in 6; for Cam5.2, AE1/AE3, and S100 in 5; and for CK7 and CK19 in 3. No CK expression was seen in stromal areas in PT or in fibromatoses. CD34 and bcl-2 were more frequently expressed in spindle cell areas in PTs (18 and 12 of 26, respectively) than in MSCs (0 and 2 of 18, respectively). MSCs show strong evidence of myoepithelial differentiation. CD34 and, to a lesser extent, bcl-2 positivity in PTs may be helpful in differentiating these two lesions from MSCs, particularly in small biopsies, because CK staining in MSCs may be heterogeneous. In our hands, 34betaE12 was the CK most frequently expressed in sarcomatoid areas in MSCs.     

计算机辅助系统在诊断乳腺良恶性肿瘤中的应用

目的:探讨计算机辅助诊断系统在良恶性肿瘤检测与特征提取基础上的分类对于乳腺肿瘤的诊断价值。方法:回顾性分析乳腺超声检查发现肿瘤且经过病理学证实的617例患者影像资料,采用手工提取的方式得到乳腺超声图像的感兴趣区域及病灶轮廓,再利用方向梯度直方图（HOG）、局部二值模式（LBP）和灰度共生矩阵（GLCM）3个特征进行乳腺肿瘤的良恶性病变真假阳性检测;最后用受试者操作特征曲线（ROC）分别分析每个特征对于两类病变判别的诊断性能和应用所有特征集合的分类诊断性能。结果:多特征融合方法的各项诊断效能及ROC曲线下面积（AUC）值均优于单特征LBP、HOG、GLCM（P值均<0.05）。与人工诊断相比,多特征融合的敏感性无显著差异,但特异度显著升高达98.57%（Z值=2.25, P<0.05）,同时AUC值为0.985,显著优于人工诊断的0.910（Z值=1.99, P<0.05）。结论:计算机辅助系统乳腺超声肿瘤良恶性检测的算法是有效的,能够对乳腺癌鉴别诊断提供有益的参考。     

Cytogenetic findings in phyllodes tumor and fibroadenomas of the breast

The cytogenetic data on fibroadenomas and cystosarcoma phyllodes tumor of the breast, which are both biphasic breast tumors composed of epithelial and stromal components, are quite limited. In this study, we report on clonal chromosomal alterations in three fibroadenomas and one cystosarcoma phyllodes analyzed by GTG banding. The fibroadenomas presented mostly numerical abnormalities involving chromosomes 16, 18, and 21. One case presented a deletion on 17p. The cystosarcoma phyllodes presented numerous numerical abnormalities, mostly chromosome gains, and several marker chromosomes.     

改进型深度学习模型在乳腺肿瘤良恶性鉴别中的应用

目的:解决传统方法在临床中对病理图像检测不足以及人工判断导致的错误判断等问题。方法:使用乳腺肿瘤细胞数据集,首先对数据集进行数据增强,增强后数据集为原来的2倍,将增强后数据集输入到本文提出的模型中进行训练。结果:经过100次迭代,训练集的准确率为97.44%,在测试集中准确率为96.4%,召回率为95.5%,与同类型文献相比都有明显提高。结论:本文章提出的改进型卷积神经网络具有收敛快,泛化好等特点。可以对乳腺肿瘤细胞的良恶性进行有效的辨识分类。     

Malignant phyllodes tumor of the breast with predominant chondrosarcomatous differentiation

Malignant phyllodes tumor of the breast is a rare biphasic neoplasm, the stromal component of which may show homologous and heterologous sarcomatous elements. We present a case of a histologically malignant phyllodes tumor with sarcomatous overgrowth, affecting a 37-year-old woman in whom a chondrosarcomatous component constituted over 80% of the tumor volume. A malignant phyllodes tumor displaying a predominant chondrosarcomatous component is indeed rare, and the differential diagnosis could well affect the therapeutic approach, mainly with regard to metaplastic carcinoma and primary chondrosarcoma of the mammary gland. Thus, it is important to sample the tumor thoroughly to detect the presence of any area of typical phyllodes tumor, which could be very small. Immunohistochemical stains also should be performed so as to exclude a malignant epithelial component. After the final morphological diagnosis, our patient underwent a complete mastectomy without axillary disection. One year later, no local recurrence or metastasis was apparent.     

超声造影增强模式在乳腺良恶性肿块鉴别诊断中的价值

目的探讨超声造影增强模式对乳腺良恶性肿块鉴别诊断的价值。方法选择40例经病理组织检查证实的乳腺肿瘤患者,均为女性,年龄25～54岁,平均年龄35岁。其中良性肿块25例,恶性肿块15例。使用Siemens Sequoia 512彩色多普勒超声诊断仪,造影剂采用SonoVue,行超声造影增强方式检查。结果乳腺良恶性肿块超声增强方式不同,良性肿块以整体不同程度地均匀型增强改变为主(80%,20/25),恶性肿块主要表现为不均匀增强或周边增强(86.7%,13/15)。结论乳腺良恶性肿块超声造影增强模式不同,可为鉴别诊断提供帮助。     

Analysis of histological features in needle core biopsy of breast useful in preoperative distinction between fibroadenoma and phyllodes tumour

Morgan J M, Douglas‐Jones A G & Gupta S K
(2010) Histopathology 56 , 489–500 Analysis of histological features in needle core biopsy of breast useful in preoperative distinction between fibroadenoma and phyllodes tumour Aims: Fine Needle Aspiration Cytology (FNAC) has been replaced by Needle core biopsy (NCB) as the pathological investigation of choice in pre‐operative diagnosis of breast lesions. Despite the greater yield of material with spatial information, the distinction between fibroepithelial lesions of the breast, fibroadenoma (FA) and benign phyllodes tumour (PT), remains problematic. The aim of this study was to confirm a set of histological features which may assist in the pre‐operative distinction between FA and PT on NCB and to explore novel strategies to refine the analysis of the data. Methods: Previously defined histological criteria were applied to 112 NCBs of fibroepithelial lesions of the breast. Contingency tables for frequency analysis, logistic regression, receiver operating characteristic (ROC) and linear discriminant analysis were used. Results: Frequency analysis identifying significant differences agreed with published data. Correct categorisation was possible in 95% of cases using logistic regression analysis (age and mitotic index) and in 94% using discriminant analysis (age, mitoses and %stroma). ROC analysis identified cut off values (between FA and PT) for age (50–55 years), %stroma (85–90) and mitoses (≥1/2.2 mm²). Conclusion: The results confirm previously published observations and provide novel putative predictive tools, to be tested prospectively.     

The coexistence of invasive ductal carcinoma and malignant phyllodes tumor with liposarcomatous and chondrosarcomatous differentiation in the same breast in a post-osteosarcoma case

Malignant phyllodes tumors of the breast are rare biphasic neoplasms, the stromal component of which may show homologous and heterologous sarcomatous elements. Malignant epithelial transformation is rare. It has been reported in a few cases of in situ and infiltrating ductal or lobular carcinoma. Rarely, breast carcinomas and phyllodes tumors may also develop in the same breast independent of each other. To our knowledge, this is the first case of two different types of tumor occurring in the same breast at the same time in a post-osteosarcoma case.     

mRNA expression profiling of phyllodes tumours of the breast: identification of genes important in the development of borderline and malignant phyllodes tumours

The aim of this study was to identify genes involved in the development of borderline and malignant phyllodes tumours of the breast (PTs). Expression profiling of 23 PTs (12 benign, 11 borderline/malignant) was performed using Affymetrix U133A GeneChips. mRNA expression in the borderline/malignant PTs was compared to the benign PTs. A group of 162 genes was over-expressed in the borderline/malignant group with a fold change > 2 and FDR < 0.1. Four of these genes were chosen for further investigation: PAX3, SIX1, TGFB2 and HMGA2. Over-expression was validated in a separate set of formalin-fixed, paraffin-embedded (FFPE) tumours, using either in situ hybridization or immunohistochemistry. This confirmed that expression of PAX3, SIX1, TGFB2 and HMGA2 in the stromal component of PTs was associated with the borderline/malignant phenotypes (p = 8.7 x 10(-5), p = 0.05, p = 0.009, p = 0.003, respectively; Fisher's exact test). The functional consequences of down-regulating these genes were studied using siRNA in short-term cultures and cell lines established from PTs. mRNA 'knock-down' of PAX3 resulted in significantly decreased cell proliferation in both a malignant and a borderline PT cell culture. mRNA 'knock-down' of SIX1 and HMGA2 resulted in decreased cell proliferation only in the malignant PT cell line, and 'knock-down' of TGFB2 resulted in decreased cell proliferation only in the borderline PT cell culture. This study shows that these four genes are involved in the development of borderline/malignant PTs. SIX1 over-expression was most marked in the highly malignant PTs, with particularly high expression in one case of metastatic PT. PAX3, TGFB2 and HMGA2 were expressed predominantly in borderline/malignant PTs, but showed some expression in benign tumours; they may be important in the transition from the benign to borderline/malignant phenotype.     

Pathologic, immunohistochemical, and molecular features of benign and malignant phyllodes tumors of the breast.

The histologic distinction between benign and malignant Phyllodes tumors (PT) is often difficult and arbitrary. We analyzed a group of benign and malignant PT to determine whether specific histologic features and expression of Ki-67 and p53 could be useful in distinguishing benign PT from malignant tumors. We also determined whether deletions in Chromosome 3p at the FHIT and hMLH1 loci are common abnormalities in PT. Twenty PT were histologically classified as benign (7) or malignant (13). Seven of the malignant PT were low grade, and six were high grade. Ki-67 and p53 immunohistochemistry was performed on all tumors and analyzed for the stromal and for the epithelial component. PCR-based loss of heterozygosity analyses were performed with the following markers on Chromosome 3p: D3S1478 (3p21.2--21.3), D3S1289 (3p21.1--21.2), and D3S1295 (3p14.3--21.1). The distribution of immunoreactivity for Ki-67 was analyzed by quantifying the percentage of positive nuclei and expressed as the labeling index (LI). Patients' ages ranged from 13 to 71 years (median: 51 y). After a mean follow-up period of 8 years, none of the PT metastasized, whereas three recurred locally. Although malignant PT were larger than benign PT (means, 7.1 versus 4.3 cm), this difference was not statistically significant. Five tumors had infiltrating margins, and 14 were circumscribed. The Ki-67 LI in low-grade malignant PT (16 +/- 25.5) was significantly higher than that in benign PT (3.6 +/- 4.8), whereas the LI in the high-grade malignant PT group (50 +/- 21.9) was significantly higher than that in low-grade malignant tumors (P =.012). The Ki-67 LI in the three tumors that recurred was less than 10%. Two of seven (29%) benign PT were focally positive for p53, whereas four of seven (57%) low-grade malignant and three of six (50%) high-grade malignant PT were diffusely positive for p53. The three tumors that recurred initially were histologically benign, as were two of the recurrences. One recurrent tumor evolved to a high-grade malignant PT. Margins were greater than 1 cm in all tumors except four, three of which recurred locally. No allelic loss of 3p was found. In summary, Ki-67 expression may assist in distinguishing benign from malignant PT in diagnostically difficult cases. 3p deletions do not play a significant role in the development of these tumors. Neither Ki-67 nor p53 can reliably predict recurrence. Histologically high-grade malignant PT have a favorable prognosis if widely excised. We emphasize the importance of adequate margins in the treatment of benign and malignant PT.