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.     

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.     

Malignant phyllodes tumor of the prostate

Phyllodes tumor of the prostate is rare. We have recently experienced a case of phyllodes tumor of the prostate in a 57-year-old man who complained of urinary retention for 1 year. The epithelial components were positive reactivity for prostate specific antigen. The stromal cells showed nuclear atypia with increased mitotic activity. The tumor was diagnosed as a malignant phyllodes tumor as it invaded into the urinary bladder and rectum, and grew rapidly immediately after operation. We describe the morphological features and immunohistochemical findings of malignant phyllodes tumor and review the literature.     

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.     

Immunohistochemical study of MIB1 expression in phyllodes tumor and fibroadenoma

The histogenesis of phyllodes tumor (PT) and fibroadenoma (FA) is closely related, and discrimination between them by histopathological analysis is sometimes problematic. Moreover, objective criteria by which to categorize the grade of malignancy in PT are still controversial. The aim in this study is to clarify whether immunohistochemical evaluation using the MIB1 antibody, which reacts with the ki-67 antigen, correlates with the histological grade of malignancy in PT, and can discriminate between PT and FA. The 47 cases of phyllodes tumor (PT) were categorized into three groups (malignant, 4 cases; borderline, 6 cases; benign, 37 cases) according to the criteria proposed by Azzopardi (1979) and were investigated by immunohistochemistry. There were significant differences in stromal MIB1-index among the three groups (P < 0. 0001), and, unexpectedly, benign PT was easily divided into two groups according only to the MIB1-index. There were significant differences in the stromal MIB1-index (P < 0.001) and stromal cellularity (P < 0.01) between the two benign PT groups. A total of 478 cases of FA was reviewed and these were divided into 403 conventional fibroadenomas (CFA), 36 cellular fibroadenomas (CEFA) and 39 fibroadenomas with focal phyllodes structure (FAPS). All cases of CEFA and FAPS, and 140 cases of CFA were studied by immunohistochemistry. The 21/215 (9.8%) cases of FA, which were designated as FAMIB, showed a high stromal MlB1-index (more than 10/0.0625 mm2). Conversely, 77% cases of FA showed no MIB1-positive stromal cells. The incidence of MIB1-positive epithelium of FAMIB was much higher than that of FA. These results suggest that high proliferative activity may be present in both stromal and epithelial cells of FAMIB. Our study suggests that immunohistochemical evaluation using MIB1 antibody correlates with the histological grade of malignancy in PT, and can select FA with high proliferative activity. However, new objective diagnostic factors useful for discriminating FA from benign PT with a low MIB1-index should be developed.     

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.     

Malignant phyllodes tumor of the prostate: retrospective review of specimens obtained by sequential transurethral resection

A case of malignant phyllodes tumor of the prostate in a 67-year-old man is reported. The patient was referred to a hospital for urinary retention. From material taken at three transurethral resections of the prostate (TURP), a histological diagnosis of benign prostatic hyperplasia was made. However, at the fourth TURP, phyllodes tumor was diagnosed due to the presence of elongated epithelial ducts and proliferating cellular stroma with mitosis and nuclear atypia. Two months later, total cystoprostatectomy was performed. Histologically, the tumor was composed of dysplastic stromal cells and irregularly elongated epithelial ducts. Five months later the patient developed multiple lung and pelvic lymph node metastases and died. This report documents progression to a higher histological grade of prostatic phyllodes tumor documented with sequential pathological findings obtained from four TURP and surgical specimens over about 3 years.     

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.     

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.     

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.     

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。     

乳腺叶状肿瘤患者不同病理分型的超声表现

目的 探讨不同病理学分型的乳腺叶状肿瘤的彩色多普勒超声表现。方法 回顾性研究。纳入江阴市中医院及东南大学医学院附属江阴医院2008年1月—2018年9月49例经手术治疗及病理证实为乳腺叶状肿瘤的患者。49例患者均为女性,年龄17～74(45.78±10.50)岁;术后病理分型诊断为良性乳腺叶状肿瘤20例(40.81%)、交界性21例(42.86%)、恶性8例(16.33%)。采用美国放射学会超声乳腺影像报告和数据系统(BI-RADS)标准进行评估,并比较良性、交界性及恶性三种病理亚型的肿瘤病灶最大径线、超声BI-RADS分类、血供差异,以及不同大小肿瘤超声声像图表现差异。结果 三种病理亚型肿瘤病灶最大径线分别为(3.57±2.17)cm、(5.00±3.71)cm及(2.88±1.52)cm,差异无统计学意义(F=2.083, P＞0.05);49例患者超声BI-RADS分类,0类6例、3类24例、4类12例、5类7例,三种病理亚型的超声BI-RADS分类差异具有统计学意义(H=22.732, P＜0.05);良性、交界性及恶性肿瘤的富血供率分别为35.00%(7/20)、52.45%(11/21)及8/8,差异有统计学意义(χ²=12.782, P＜0.01)。超声灰阶声像图显示,病灶最大径≥5 cm的肿瘤内部液化发生率为6/10,高于最大径＜5 cm肿瘤液化发生率17.9%(7/39),差异有统计学意义(χ²=5.224, P＜0.05)。结论 当乳腺肿瘤在超声声像图上表现为分叶状、囊性变时要考虑叶状肿瘤的可能,应用超声BI-RADS分类可能有助于鉴别良性、交界性及恶性乳腺叶状肿瘤,当乳腺内病灶呈现富血供时要考虑恶性可能,但该病确诊仍需依靠病理。     

Cystosarcoma phyllodes of the breast: a cytologic and clinicopathologic study of 23 cases

Twenty-three cases of cystosarcoma phyllodes of the breast were studied clinically and by fine-needle aspiration (FNA) cytology as well as by tumor histology. The median patient age was 52 yr. The total actuarial survival at 5 yr was 90%, and the recurrence-free survival was 70%. A combination of stromal elements (tissue fragments and/or single spindle cells) and epithelial tissue was required to make the diagnosis on smear material. In FNA smears, stromal elements were absent in two cases, and ductal elements were not seen in three. Thus, the dimorphic pattern essential to this diagnosis was not present in five (22%) cases. An evaluation of tumor factors reported to be of prognostic significance was performed on histologic sections of resected tumors. Comparison of these data with FNA results indicates that little prognostic information can be obtained from FNA alone in most cases.     

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.     

Phyllodes tumor of the prostate

In this report, we describe a case of phyllodes tumor of the prostate with a high value of prostate-specific antigen (PSA). A 47-year-old man with symptoms of hematospermia presented with a steadily elevated serum PSA value of 60.76 ng/mL (normal range, < 4 ng/mL). A needle biopsy revealed atypical stromal cells without any evidence of malignancy. After radical prostatectomy, the tumor measured 2.9 cm in diameter and consisted of a single nodule composed of irregular, elongated epithelial ducts and atypical stromal cells with enlarged, occasionally multinucleated, pleomorphic, or hyperchromatic nuclei. Immunohistochemistry showed that the atypical stromal cells were positive for vimentin, androgen receptor, estrogen receptor, progesterone, and 5α-reductase, but negative for MIB-1, PSA, SMA, p53, desmin, CD34, c-kit, CD10, S-100, and EGFR. Excess PSA might be secreted by hyperplastic luminal cells driven by 5α-reductase-positive stromal and epithelial cells. Array-comparative genomic hybridization (array CGH) for genomic alterations revealed a gain of 11p13, which includes the WT1 gene, and a loss of 1p36.23 and 12p12.1. After surgery, the serum PSA value rapidly decreased to within the normal range; no recurrence or distant metastasis was noted after 2 years of follow up.     

Cytogenetic findings in phyllodes tumors of the breast: Karyotypic complexity differentiates between malignant and benign tumors

Clonal karyotypic abnormalities were detected in short-term cell cultures from six phyllodes tumors of the breast. Whereas all five benign tumors had simple chromosomal changes, the highly malignant one had a near-triploid stemline, indicating that karyotypic complexity is a marker of malignancy in phyllodes tumors. Interstitial deletions of the short arm of chromosome 3, del(3)(p12p14) and del(3) (p21p23), were the only aberrations in two benign tumors. Cytogenetic polyclonality was detected in three benign tumors: two had cytogenetically unrelated clones, whereas the third had three different, karyotypically related cell populations as evidence of clonal evolution. The finding of clonal chromosome abnormalities in both the epithelial and connective tissue components of the phyllodes tumors indicates that they are genuinely biphasic, that is, that both components are part of the neoplastic parenchyma.     

Malignant phyllodes tumor following irradiation of the breast

This is a case report of malignant phyllodes tumor (cystosarcoma phyllodes) which appeared 15 years following medical irradiation of the breast for presumable carcinoma which had not been histologically or cytologically confirmed prior to treatment. Histology of the phyllodes tumor disclosed remnant of fibroadenoma in one area, and it is believed that the latter gave rise to the malignant phyllodes tumor within the field of irradiation. In view of recent popularity of the limited surgery and postoperative irradiation in treatment of breast carcinoma the possibility of malignant transformation of fibroadenoma left in situ is raised.