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。     

Stromal CD10 expression in mammary fibroadenomas and phyllodes tumours

BACKGROUND/AIMS: CD10 (CALLA) has recently been reported to be expressed in spindle cell neoplasia, and has been used to differentiate endometrial stromal sarcoma from leiomyoma and leiomyosarcoma. In the breast, myoepithelial cells express CD10, but there are few studies of the expression of CD10 in mammary fibroepithelial lesions. METHODS: Stromal CD10 expression was studied in 181 mammary phyllodes tumours (102 benign, 51 borderline malignant, and 28 frankly malignant) and 33 fibroadenomas using immunohistochemistry, to evaluate whether differences in expression correlated with the degree of malignancy. RESULTS: There was a progressive increase in the patients' age and tumour size, from fibroadenoma to phyllodes tumours with an increasing degree of malignancy (p < 0.001). Stromal CD10 expression was positive in one of 33 fibroadenomas, six of 102 benign phyllodes tumours, 16 of 51 borderline malignant phyllodes tumours, and 14 of 28 frankly malignant phyllodes tumours. The difference was significant (p < 0.001) and an increasing trend was established. Strong staining was seen in subepithelial areas with higher stromal cellularity and activity. Stromal CD10 expression had a high specificity (95%) for differentiating between benign lesions (fibroadenomas and benign phyllodes tumours) and malignant (borderline and frankly malignant) phyllodes tumours. CONCLUSIONS: CD10 may be a useful adjunct in assessing malignancy in mammary fibroepithelial lesions.     

Multinucleated stromal giant cells in mammary phyllodes tumours

Mammary phyllodes tumour (PT) is an uncommon fibroepithelial neoplasm with a prominent stromal component. We report five cases of PT (one benign, three borderline, one malignant) with giant cells in the stroma. All occurred in adults and ranged from 1.8 to 4.0 cm in size. The overall cellularity, stromal cell pleomorphism and mitotic count was higher for the malignant and borderline than the benign PT. The giant cell number ranged from 18 to 35 cells per 10 high power fields, but there was no relationship between this number and the grade of the PT. Most giant cells were subepithelial, with multiple nuclei arranged in a linear or irregular pattern, and moderate amount of cytoplasm. The immunohistochemical profile of the giant cells was similar to the stromal cells. In all cases, both giant cells and stromal cells expressed vimentin strongly but not desmin; in two cases, both cell populations expressed actin weakly. The respective percentage of giant cells and stromal cells expressing MIB1 was also similar. This suggests that these giant cells do not represent a different, more active stromal population, despite the more bizarre appearance. In view of the small number of cases, the significance of such giant cells on the prognosis of PT remains uncertain.     

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.     

Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours

BACKGROUND AND AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. METHOD: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours.     

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.     

Increased c-kit (CD117) expression in malignant mammary phyllodes tumors.

Mammary phyllodes tumors are uncommon stromal neoplasms, and are divided into benign, borderline and malignant groups basing on histologic criteria. While benign phyllodes tumors may recur, borderline phyllodes tumors show higher propensity to recur locally and rarely metastasize, and malignant phyllodes tumors show even higher chances of local recurrences or distant metastases. c-kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117) and is a marker for gastrointestinal stromal tumors (GIST). With the advent of therapeutic agent targeted at this receptor for GIST, we investigated 179 phyllodes tumors (101 benign, 50 borderline, 28 malignant) for c-kit expression using immunohistochemistry. The staining was compared to the degree of malignancy, and to the degree of stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. The overall positive rate for c-kit was 29% (52/179) and 17% (17/101), 24% (12/50) and 46% (13/28), respectively, for benign, borderline malignant and frank malignant phyllodes and the differences between all categories were significant (chi2=13.844, P=0.001). In mammary phyllodes tumors, there was increasing c-kit expression with increasing degree of malignancy, up to 46% in malignant cases. This provides strong evidence that c-kit receptor mediated tyrosine kinase involvement in the pathogenesis of phyllodes tumors, and the therapeutic agent, STI571, Glivec, may be a potentially useful drug for its management.     

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.     

乳腺叶状肿瘤的形态学和免疫组织化学研究

目的观察乳腺叶状肿瘤（phyllodes tumours,PTs）的形态学和免疫组织化学特征,并探讨其诊断标准。方法对21例PTs进行组织学观察和免疫组化SP法检测,并选取5例乳腺纤维腺瘤和5例乳腺腺病标本作为对照组。使用一抗包括CK-pan、EMA、SMA、p53、S-100蛋白、CD117、CD34、CD99、bc l-2、ER、PR、K i-67、CD10。结果21例PTs大体上均表现为界限清楚的肿块,且呈分叶状。肿瘤由具有双层排列的上皮成分以及过度生长的间质成分组成。根据间质的过度生长程度、细胞的异型程度、核分裂数、肿瘤边缘情况、有无异源性成分以及肿瘤性坏死等继发性改变将其分为良性、交界性和恶性3个级别。间质细胞免疫组化表达情况：CKpan：0/21、EMA：0/21、SMA：17/21、CD117：6/21、CD34：18/21、S-100蛋白：2/21、CD99：13/21、CD10：8/21、PR：5/21、ER：4/21、p53：18/21、K i-67：3%~10%、bc l-2：15/21。结论PTs的诊断主要依据组织学观察,免疫组化CD117、CD34、CD99、CD10、bc l-2的检测可以起到一定的辅助作用。     

CD34<Superscript>+</Superscript> fibrocytes in invasive ductal carcinoma,ductal carcinoma in situ,and benign breast lesions

The present study was undertaken in order to elucidate the question of whether the distribution of stromal CD34+ fibrocytes and smooth muscle actin (SMA)-reactive myofibroblasts differs between benign and malignant lesions of the breast. We investigated a total of 31 ductal carcinomas and 27 specimens with benign lesions of the breast (ductal hyperplasia, sclerosing adenosis, fibroadenoma, phyllodes tumor) and compared the distribution of CD34+ fibrocytes and SMA-reactive myofibroblasts. The stroma of normal breast tissue contained CD34+ fibrocytes, whereas SMA-reactive myofibroblasts were absent. All benign breast lesions exhibited stromal CD34+ fibrocytes and few lesions (fibroadenomas and phyllodes tumor) showed additional SMA-reactive myofibroblasts. In invasive breast cancer the stroma was devoid of CD34+ fibrocytes but a varying number of stromal SMA-reactive myofibroblasts was detectable. In the setting of the present study the loss of CD34+ fibrocytes was specific for invasive breast cancer and ductal carcinoma in situ, whereas SMA-reactive myofibroblasts were observed in different benign and malignant lesions. These findings may be helpful tools in distinguishing benign breast lesions (e.g., sclerosing adenosis) from invasive breast cancer and in characterizing stromal remodeling associated with invasive cancer.     

Phyllodes tumor of the seminal vesicle: case report and literature review

A 39-year-old man presented with urinary retention and lower abdominal discomfort at our hospital, and a computed tomography scan showed a huge cystic mass posterior to the urinary bladder. During surgical exploration, a mass superior to the prostate in the region of the left seminal vesicle was found. Histologically, the tumor was characterized by cystically dilated or slit-like glands mixed in a densely cellular stroma with pleomorphism and resembled those of phyllodes tumor of the breast or prostate. The glandular epithelium within the tumor showed focal lipofuscin pigment and negative staining for prostate specific antigen (PSA). The stromal cells showed positive immunoreactivity for vimentin and CD34, and focal positive reactions for desmin and alpha-smooth muscle actin. Mitosis was present 0 to 1 per 10 high power fields of magnification in the stromal cells. Approximately 20% of the stromal cells were positive for progesterone receptor. The patient is alive with no evidence of disease 12 months after surgery. Mixed epithelial-stromal tumors of the seminal vesicle are extremely rare. A combination of stromal cellularity, atypia and mitosis might be used for the histological grading, and a prostatic origin might be excluded by the location of the primary lesion itself and by the failure to show PSA.     

Expression of hyaluronic acid and its receptors, CD44s and CD44v6, in normal, hyperplastic, and neoplastic endometrium

The interaction between epithelial tumor cells and their surrounding stroma is important in tumor progression and metastasis. This is accomplished through a number of transmembrane receptors that interact with stromal extracellular matrix molecules. One of these receptors, CD44, binds to extracellular matrix component hyaluronic acid (HA). The purpose of this study was to evaluate the significance of HA, CD44s, and CD44v6 in benign, hyperplastic, atypical, and malignant endometrial epithelia. Archival paraffin-embedded cell blocks from proliferative endometrium (n = 11), secretory endometrium (n = 12), simple hyperplasia (n = 13), complex hyperplasia without atypia (n = 9), complex hyperplasia with atypia (n = 17), and adenocarcinoma (n = 21) were stained for HA, CD44s, and CD44v6. HA was detected throughout the normal menstrual cycle but was more intense during the secretory phase. Only during the secretory phase was CD44s expressed in the stromal cells in 11 cases (92%), whereas CD44v6 was detected in glandular epithelium in 9 (75%). CD44s was expressed in the glandular epithelium in 2 (15%) cases of simple hyperplasia, 4 (44%) of complex hyperplasia without atypia, 14 (82%) of complex hyperplasia with atypia, and in 16 (76%) of adenocarcinoma. CD44v6 was expressed in the glandular epithelium in 1 (11%) case of complex hyperplasia without atypia, 17 (100%) cases of complex hyperplasia with atypia, and in 18 (86%) cases of adenocarcinoma, but in none of the cases of simple hyperplasia. The endometrial stromal cells expressed CD44v6 in 1 (8%) case of simple hyperplasia, 6 (67%) of complex hyperplasia without atypia, 8 (47%) of complex hyperplasia with atypia, and in 3 (14%) of adenocarcinoma. We concluded that in the normal menstrual cycle, the timing of peak staining of HA and CD44s in the stroma and the up-regulation of CD44v6 in secretory glands are coincident with the period in which the endometrium is most receptive to embryo implantation. HA is more abundant in the stroma adjacent to the tumor, suggesting that interactions between tumor cells and stromal HA promote tumorigenesis. With progression from hyperplasia and with increasing atypia to adenocarcinoma, levels of stromal HA, glandular CD44v6, and glandular and stromal CD44s all increase. Thus, HA and CD44 are both involved in the development and progression of endometrial cancer.     

Ubiquitin carboxy-terminal hydrolase L1 may be involved in the development of mammary phyllodes tumors

Phyllodes tumors (PTs) are characterized by co-proliferation of the stroma and epithelium, with the stroma being the neoplastic element. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme that was originally considered to be a neuronal-specific marker, but later reports have shown both tumorigenic and antitumorigenic roles for UCHL1. Although a role for UCHL1 has been explored in many cancers, a study on PTs has never been reported. We assessed UCHL1 expression in 49 cases of PTs and 16 fibroadenomas using immunohistochemistry and examined associations with clinicopathological features. In normal breast, strong staining for UCHL1 was consistently observed in the nerve bundles, if present, in breast stroma. Scattered stromal cells showed negative to weak staining. The ductal and lobular units, in contrast, showed no staining. In contrast to the 16 fibroadenomas, of which only 3 showed mild staining, UCHL1 expression was consistently observed in all 49 PTs. There was a significantly increasing trend of UCHL1 expression with increasing PT grade (P?<?0.001); strong staining was observed in 24 % of benign PTs, but was present in 56 and 90 % of borderline and malignant PTs, respectively. Consistently, UCHL1 was focally positive in regions of benign to borderline malignancy, but strongly and diffusely immunoreactive in regions of malignancy in cases of malignant PTs. In addition to PT grade, UCHL1 expression correlated with increasing stromal atypia (P?=?0.01), but not with other clinicopathological parameters. In conclusion, the consistent expression of UCHL1 in PTs and an increasing trend of UCHL1 expression with an increasing PT grade suggest a role for UCHL1 in the pathogenesis and malignant progression of PTs.     

Diagnostic stromal histomorphology in fibroepithelial breast lesions: a fresh perspective

Histopathologic parameters were studied in fibroepithelial breast lesions comprising of Fibroadenomas (FAs), Juvenile cellular fibroadenomas (JCFs) as well as benign, borderline and malignant phyllodes tumours (B/Bo/MPTs). H & E stained sections of 67 cases (25 ICFA, 5 Mixed FA, 10 PCFA, 12 JCF and 15 PT) were retrieved from archival material and the microscopic features of each lesion, reviewed by two independent observers. A diagnosis was arrived at by consensus. Diagnostic criteria were laid down for each of the above lesions based on a statistical analysis of data obtained from a previously drawn up semiquantitative grading system for various stromal histomorphologic parameters. An increasing grade of stromal cellularity, pleomorphism, overgrowth and mitotic index was observed, from the benign to the borderline and overtly malignant lesions included in the spectrum. A semiquantitative grading of relevant stromal histomorphologic variables was found to be of immense diagnostic significance in fibroepithelial breast lesions and served to elucidate cases falling into the diagnostic grey zones of the spectrum.     

Malignant phyllodes tumours of the breast display increased stromal p53 protein expression

AIMS: To determine the variation in p53 protein expression in phyllodes tumours and fibroadenomas of the breast. METHODS AND RESULTS: Fifteen phyllodes tumours (six malignant, nine benign) and 20 fibroadenomas were examined for p53 expression by immunohistochemistry. Five of the six malignant phyllodes tumours showed moderate or strong p53 positivity at sites of peri-epithelial stromal condensation and atypia. All 20 fibroadenomas, nine benign phyllodes tumours and one malignant phyllodes tumour showed either negativity or focal weak nuclear positivity of scattered stromal cells. CONCLUSIONS: Increased p53 immunoreactivity is present in malignant phyllodes tumours in contrast to benign phyllodes tumours and fibroadenomas. Malignant phyllodes tumours display a distinctive pattern of p53 immunostaining which may be of diagnostic value. These findings suggest that p53 protein may be important in the progression of benign to malignant phyllodes tumours.     

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.     

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.     

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.     

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.     

Correlation of p53 and MIB-1 expression with both the systemic recurrence and survival in cases of phyllodes tumors of the breast

Phyllodes tumors are rare primary tumors of the breast. The study aimed at evaluating the immunohistochemical features of phyllodes tumors of the breast that may be useful for predicting the clinical outcome. We examined the immunohistochemical expression of the epidermal growth factor receptor (EGFR), HER2/neu, CD117/c-kit, p53, and MIB-1, and analyzed correlations between the immunohistochemical findings and the clinical outcome. The study included 41 patients with phyllodes tumor (20 benign, 5 borderline, and 16 malignant). Systemic recurrence occurred in 9 patients. The 2-year survival rate was 84%, and the 2-year recurrence-free survival rate was 77%. Six patients developed systemic recurrence within the first year after surgery. None of the phyllodes tumors was positive for HER2/neu or CD117/c-kit. Positive staining for p53 was seen in 10 phyllodes tumors (24%), and the median MIB-1 index was 10%. Both p53 expression and the MIB-1 index, but not the expression status of EGFR, were significantly correlated with the recurrence-free and overall survival. p53 expression status and MIB-1 index may be significant prognostic factors in patients with phyllodes tumors, and careful postoperative follow-up may be important in those cases showing positive expression of p53 and/or MIB-1 index.