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PubMed1993

Phyllodes tumors.

Phyllodes tumors are rare lesions of the breast with unpredictable behavior. A review of 18 patients with phyllodes tumors was performed to determine if pathologic and cellular characteristics correlated with clinical behavior and to determine the influence of the extent of the operation performed on clinical outcome. Local excision, primarily breast biopsy, was performed in 14 of the 18 patients. At a median follow-up of 26 months (range: 3 to 164 months), there have been three recurrences, two in patients with low-grade tumors and one in a patient with a high-grade lesion, who eventually died as a result of widespread metastases. Recurrences were noted from 2 to 56 months after the original operation. Poor correlation was noted between standard pathologic criteria or flow cytometry and the risk of recurrence. Phyllodes tumors exhibit a wide spectrum of clinical behavior. Most patients will not experience a recurrence, but even small, low-grade tumors may recur if inadequately excised. Occasional patients have extremely aggressive disease that may result in death.

Adolescent↗

PubMed2006

Immunohistochemical expression of heparan sulfate correlates with stromal cell proliferation in breast phyllodes tumors.

Phyllodes tumors are fibroepithelial neoplasms typified by stromal proliferation. We have previously shown the role of pathologic parameters and the prognostic significance of p53 and CD117 protein expression in these tumors. In this study, we evaluated the expression of heparan sulfate, which has been implicated in many biological processes such as cell adhesion, embryogenesis, and tumorigenesis (including malignant transformation of mammary cells) in 232 breast phyllodes tumors. We used a monoclonal antibody, 10E4, to examine the localization of heparan sulfate in phyllodes tumors by immunohistochemistry. The immunoreactivity of both epithelial and stromal components was examined and analyzed with pathological parameters and other immunohistochemical markers, including p53, MIB1, bcl2, and CD117. Stromal 10E4 expression was significantly associated with tumor grade, stromal p53, and MIB1 expression in proliferating cells, suggesting that heparan sulfate may participate in malignant tumor growth.

Antibodies, Antinuclear↗

PubMed1988

Phyllodes tumor (cystosarcoma phyllodes) of the breast. A clinicopathologic study of 45 cases.

The correlation between the histology and biologic behavior of phyllodes tumor was studied in order to establish the histologic criteria of this tumor, particularly its malignant counterpart. A preliminary analysis of five tumors with metastases revealed that a single essential indicator of malignant potential was the presence of a disproportionate overgrowth of the stromal elements at the expense of the ductal element. The presence or absence of such stromal overgrowth in the tumor showed a positive correlation with the degree of stromal atypism and the rate of mitoses. Seventeen out of 45 tumors were determined to be malignant, on the basis of our criteria. The arrangement of the stromal component in malignant phyllodes tumors was usually one of the particular sarcomatous types, with or without the focal areas of one of the specified types of sarcoma. On the other hand, 24 tumors recurred locally but never metastasized, and were preferentially interpreted to be benign phyllodes tumor. Histologically, these tumors had a general architecture resembling that of fibroadenoma but were characterized by high cellularity expressed by the distinct formation of bundles or fascicles of stromal tumor cells. The remaining four tumors seemed to form a borderline phyllodes tumor subset. A follow-up study revealed that, irrespective of the mode of therapy, the outcome of patients with phyllodes tumor was well correlated with the histologic criteria we proposed.

Adolescent↗

PubMedDate not supplied

Bilateral breast tumors, malignant phyllodes tumor and invasive lobular carcinoma in a 46,XX/46,XY mosaic female with family history of breast cancer.

Bilateral breast tumors, a malignant phyllodes tumor in the right breast and an invasive lobular carcinoma in the left breast, occurred in a 47-year-old woman with 46XX/46XY mosaic karyotype in her peripheral blood lymphocytes and intersex external genitalia. Postmortem examination revealed bilateral ovotestis. Three of the patient's sisters also had breast cancer. In situ hybridization with a Y-specific probe revealed Y-chromosome-specific signal in both tumors, suggesting that the clonal origin of tumors in this patient was Y-containing cells. Androgen-receptor polymorphism also revealed a monoallelic X chromosome pattern in the recurrent phyllodes tumor tissue taken at autopsy, in addition to loss of heterozygosity demonstrated at locus TP53. The slippage of the CA repeats in the tumor was also shown at the loci of D5S82 and D11S527. The mechanistic basis for the occurrence of bilateral malignant tumors of the breast, XX/XY mosaicism, and familial clustering of breast cancer is still unknown. The present study, however, suggests that the sex chromosome abnormality may have modified the cancer phenotype in a manner similar to breast cancer in Klinefelter's syndrome (though phenotypically male) and the Y chromosome may have promoted cell growth.

Breast Neoplasms↗

PubMed2004

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.

Adolescent↗

PubMed2006

Amplifications of the epidermal growth factor receptor gene (egfr) are common in phyllodes tumors of the breast and are associated with tumor progression.

Phyllodes tumors of the breast are rare biphasic tumors with the potential for invasion and metastatic spread. An important role of the epidermal growth factor receptor (EGFR) in phyllodes tumors has been proposed. However, detailed pathogenetic mechanisms remained unclear. We investigated 58 phyllodes tumors of the breast (40 benign, 10 borderline and eight malignant) by means of egfr fluorescence in situ hybridization (FISH) and gene dosage PCR for a regulatory sequence within intron 1 of egfr. Immunohistochemical staining was performed for EGFR, p16, p21, p27, p53, c-myc, Cyclin A, Cyclin D1, Cyclin E, c-kit and Ki67. Immunopositivity for EGFR was detected in 19% of phyllodes tumors (75% of all malignant tumors) in stromal tumor cells but not in the epithelial component. Whole-gene amplifications were seen by FISH in 15.8% (in stromal cells only) and intron 1 amplifications by gene dosage PCR in as much as 41.8% of all phyllodes tumors. Significant correlations were seen between tumor grade on the one hand and EGFR overexpression (P=0.001) and intron 1 amplifications (P<0.05) on the other. EGFR overexpression further correlated positively with immunohistochemical staining for p53, p16, Cyclin A, Cyclin E, Ki67 and c-kit. Presence of intron 1 amplifications correlated with p16 (P<0.01), p21 (P=0.009) and p53 immunoreactivity (P<0.001). Neither EGFR overexpression nor whole-gene amplification was observed in a control series of 167 fibroadenomas and only one of 43 (2.3%) exhibited intron 1 amplification in gene dosage PCR. In conclusion, our results show for the first time that activating mutations in and overexpression of egfr are associated with the progression in grade of phyllodes tumors of the breast. The observed association between intron 1 amplification and overexpression of EGFR provides further insight into regulation mechanisms of EGFR overexpression.

Base Sequence↗

PubMed2000

[Primary breast tumor and malignant phyllodes tumor of the breast-- two rare cases demonstrated by technetium 99m scintimammography].

Breast cancer can be detected by scintimammography using Tc-99m sestamibi (MIBI). The method is highly accurate, sensitive and specific. Histologically, most of the tumors have been adenocarcinomas. We present 2 women with rare breast tumors, primary squamous cell carcinoma and malignant phyllodes tumor. In both, mammography and cytological biopsy were not diagnostic, but MIBI scintimammography demonstrated focal uptake in the diseased breast.

Breast Neoplasms↗

PubMed1992

Abundant expression of immunoreactive endothelin 1 in mammary phyllodes tumor: possible paracrine role of endothelin 1 in the growth of stromal cells in phyllodes tumor.

Immunoreactive endothelin 1 (irET-1) concentrations were measured in extracts prepared from 4 phyllodes tumors and 14 fibroadenomas. irET-1 was detectable in all tissue extracts by specific radioimmunoassay, and the mean concentration of irET-1 was 18-fold and 27-fold higher in tissue extracts from phyllodes tumors than in those from intracanalicular fibroadenomas and pericanalicular fibroadenomas, respectively. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay in the extracts from phyllodes tumors revealed one major irET-1 component corresponding to human standard ET-1. Furthermore, immunocytochemical staining for ET-1 revealed that numerous ET-1-immunoreactive cells were seen in the epithelial cells but not in the stromal cells, suggesting that ET-1 is synthesized by the epithelial component of phyllodes tumors. A possible paracrine role of ET-1 in the growth of this rare tumor which is characterized by its prominent stromal cellularity is discussed.

Adenofibroma↗

PubMed1999

Surgical management of phyllodes tumors.

HYPOTHESIS: Although phyllodes tumors have minimal metastatic potential, we hypothesized that they have a proclivity for local recurrence and should be excised with a wide margin. We reviewed the clinical and radiological appearance of phyllodes tumors and analyzed the role of surgical treatment in their management. DESIGN: Medical records, imaging studies, pathology reports, and interventions were reviewed. SETTING: A large tertiary care teaching hospital. PATIENTS: Between 1980 and 1997, 40 patients with phyllodes tumors were identified through the tumor registry at the Massachusetts General Hospital, Boston. MAIN OUTCOME MEASURES: Surgical resection margins, rates of local recurrence, incidence of distant metastases, and survival. RESULTS: All 40 patients were female, with a mean age of 41 years. Each patient had a palpable mass or a mammographic finding that was indistinguishable from a fibroadenoma on examination. Tumor size ranged from 5 mm to 28 cm. Local recurrence correlated with excision margins (P<.05), but not with tumor grade or size. Local recurrence occurred in 5 patients, each of whom had positive margins or margins less than 1 cm after excision. After reexcision with a 1-cm margin, these individuals remained free of recurrence. One patient developed metastatic disease after total mastectomy and died after chemotherapy. CONCLUSIONS: Phyllodes tumors mimic fibroadenomas and are often excised with close margins. Primary excision or reexcision with a 1-cm margin is recommended. Mastectomy is indicated for patients with large lesions. Lymph node metastases are unusual and occur secondary to necrotic tumor. Chemotherapy is based on guidelines for the treatment of sarcomas, not breast adenocarcinoma.

Adolescent↗

PubMed2006

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.

Adult↗

PubMed2003

Phyllodes tumor of breast.

Phyllodes tumors account for 0.3%-0.5% of all the breast tumors. They are usually benign but malignant variants exist and have the potential to metastasize. Surgery is the mainstay of treatment as there is no proven benefit of adjuvant chemotherapy or radiotherapy. Wider excision with 1 cm clear margins is recommended in cases where the resection margins are involved. Simple mastectomy is recommended even for large benign tumors as there is increased likelihood of recurrence. We are presenting a case of 42 years old female with benign phyllodes tumor and a brief review of literature on the subject.

Adult↗

PubMed1999

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.

Biomarkers, Tumor↗

PubMed1996

[Diagnostic imaging of phyllodes tumors: preliminary observations].

Phyllodes tumors are rare fibro-epithelial neoplasms; they may be classified as benign, borderline and malignant according to their histologic features of mitotic index, stroma pleomorphism and lesion outline. Their epidemiology is rather different from that of other breast neoplasms, since these lesions most frequently affect white Latin women 45 to 49 years old. The incidence of metastases is strictly correlated with the degree of histologic aggressiveness, although even small lesions, either borderline or with low malignancy, may metastasize. To assess the incidence of this neoplasm and its metastases and to investigate the role of diagnostic imaging, we retrospectively reviewed 8000 mammograms, 2000 sonograms, 1000 color-Doppler sonograms and 4500 CT scans of the chest; 7 phyllodes tumors and 2 metastases were detected. This neoplasm showed no specific characteristics either at mammography or at sonography, whereas rich neovascularization with venous flow and low resistance arterial flow were shown at color-Doppler US. Secondary lesions, first diagnosed at radiography and then studied with CT for number, size and lymph node involvement were: a large solitary mass with no involvement of mediastinal nodes, which was observed 36 months after surgical ablation of the primary lesion and multiple small lesions, involving both lungs, with no mediastinal metastases, diagnosed 42 months after surgical removal of the primary lesion. In both cases the primary neoplasm was histologically classified as borderline and responded to adjuvant therapy. Therefore, our work confirms the polymorphic nature of this condition which is rather difficult to diagnose and whose prognosis is unpredictable. However, even though color-Doppler US may open new diagnostic perspectives, the reliability of conventional radiography and CT in the follow-up of these lesions is nowadays a matter of fact. In our opinion, every case should be followed-up, regardless of the histologic classification of the primary tumor.

Adolescent↗

PubMed2006

Amplifications of EGFR gene and protein expression of EGFR, Her-2/neu, c-kit, and androgen receptor in phyllodes tumor of the prostate.

Phyllodes tumor of the prostate is a rare neoplasm with an unpredictable clinical behavior. It may undergo early recurrence with sarcomatous transformation or may even metastasize. Because targeted therapies have shown great success against several malignancies, there is hope that these same therapies may show similar promise in the treatment of other neoplasms. This study was undertaken to investigate both amplification of the epidermal growth factor receptor (EGFR) gene by fluorescence in situ hybridization and the overexpression of EGFR, Her-2/neu, CD117 (c-kit), and androgen receptor by immunohistochemical staining in a series of 11 phyllodes tumors of the prostate. In the stromal elements, EGFR gene amplification was present in four of 11 tumors and polysomy chromosome 7 was present in two of 11 tumors. No amplification was present in the epithelial components. Only one of 11 tumors had polysomy of chromosome 7 in the epithelial components. Immunohistochemically, in the stromal components, EGFR expression was demonstrable in four of 11 tumors and androgen receptor was demonstrated in six of 10 tumors. Neither Her-2/neu nor c-kit expression was seen in the stromal components of any of the 11 tumors. In the epithelial components, EGFR expression was present in all 11 tumors with strong staining in the basal cell layers and weak or no staining in luminal epithelium; androgen receptor expression was seen in seven of 10 tumors; Her-2/neu was weakly positive in four of 11 tumors; and c-kit expression was present focally and weakly in two of 11 cases with only 2-5% of cells staining. The highest staining intensity and the highest percentage of positively staining cells were seen with EGFR immunostaining in both the stromal and epithelial (mainly basal cells) components. Androgen receptor staining showed the next highest staining intensity and percentage of positive cells in both components. Her-2/neu and c-kit were only weakly or infrequently expressed in the epithelial components of prostatic phyllodes tumors. Our data indicate that EGFR and androgen receptor are frequently and strongly expressed in both epithelial and stromal components of prostatic phyllodes tumors. EGFR gene amplification is frequently present in prostatic phyllodes tumors and may account for one of the mechanisms leading to protein overexpression in some but not all cases. Anti-EGFR and/or antiandrogen agents may be potentially useful for management of patients with tumors expressing EGFR and/or androgen receptor.

Adult↗

PubMed2003

Tumour angiogenesis and p53 protein expression in mammary phyllodes tumors.

We examined 186 phyllodes tumors (106 benign, 51 borderline, 29 malignant) for angiogenesis by assessing stromal microvessel density by the hot spot method and assessing p53 protein expression; we correlated these factors with stromal cellularity, margin status, nuclear pleomorphism, mitosis, and stromal overgrowth. Increased degree of malignancy in phyllodes tumors is associated with increased patient age and tumor size. Microvessel density and p53 protein expression also showed a similar increase with malignancy. Using a logistic regression model, microvessel density was shown to be useful in predicting malignancy in phyllodes tumors, independent of key criteria of stromal overgrowth, nuclear pleomorphism, and mitosis. Microvessel density showed correlation with stromal cellularity and margin status, suggesting an interrelationship between these parameters. P53 protein expression showed a positive correlation with microvessel density, suggesting possible overlap in the underlying mechanism of these two factors in the pathogenesis of phyllodes tumors. The numbers of recurrences and metastases are small in our series, and no significant difference was demonstrated in microvessel density and p53 protein expression compared with the primary. We conclude that microvessel density and p53 are useful as independent criteria in evaluating malignancy in phyllodes tumors.

Adolescent↗

PubMed2001

Phyllodes tumors of the breast.

Phyllodes tumor is a rare fibroepithelial neoplasm of the breast with a very variable, but usually benign, course. Formerly known as cystosarcoma phyllodes, the designation "phyllodes tumor" with appropriate qualification regarding malignant potential based on pathologic features is now the agreed-upon term. The most important diagnostic distinction is from fibroadenoma--phyllodes tumors require complete excision with free margins even when pathologic features suggest benignity because of a proclivity to local recurrence. The most important component of therapy is wide surgical excision, and mastectomy is necessary only when free margins cannot be achieved without it. Involvement of axillary nodes is rare, and axillary dissection is not indicated. The role of radiation therapy and chemotherapy is not established and has not been studied in randomized trials due to the rarity of the tumor. At present, there is no consensus that patients with high-grade phyllodes tumors of the breast will benefit from either of these modalities.

Antineoplastic Agents↗

PubMed2004

Molecular genetic evidence for different clonal origins of epithelial and stromal components of phyllodes tumor of the prostate.

Phyllodes tumor of the prostate is a rare neoplasm, composed of epithelium-lined cysts and channels embedded in a variably cellular stroma. The pathogenetic relationship of the epithelium and stroma is unknown and whether each is a clonal neoplastic element is uncertain. We studied the clonality of phyllodes tumors from six patients who underwent either enucleation or transurethral resection as their initial treatment. This was followed by total prostatectomy in three of the patients. Laser-assisted microdissection was performed to extract epithelial and stromal components of phyllodes tumor from formalin-fixed, paraffin-embedded tissue. Polymerase chain reaction was used to amplify genomic DNA at specific loci on chromosome 7q31 (D7S522), 8p21.3-q11.1 (D8S133, D8S137), 8p22 (D8S261), 10q23 (D10S168, D10S571), 17p13 (TP53), 16q23.2 (D16S507), 12q11-12 (D12S264), 17q (D17S855), 18p11.22-p11 (D18S53), and 22q11.2 (D22S264). In each tumor, stroma and epithelium were analyzed separately. Gel electrophoresis with autoradiography was used to detect loss of heterozygosity. All tumors showed allelic loss in one or more loci of both the epithelial and stromal components. The frequency of allelic loss in the epithelial component was 2 of 5 (40%) at D7S522, 2 of 6 (33%) at D8S133, 1 of 5 (20%) at D8S137, 3 of 6 (50%) at D8S261, 4 of 4 (100%) at D10S168, 4 of 6 (67%) at TP53, 2 of 6 (33%) at D10S571, 6 of 6 (100%) at D16S507, 1 of 5 (20%) at D12S264, 1 of 6 (17%) at D17S855, 2 of 6 (33%) at D18S53, and 2 of 5 (40%) at D22S264. The frequency of allelic loss in the stromal component was 2 of 5 (40%) at D7S522, 1 of 6 (17%) at D8S133, 2 of 5 (40%) at D8S137, 3 of 6 (50%) at D8S261, 1 of 4 (25%) at D10S168, 3 of 6 (50%) at TP53, 2 of 6 (33%) at D10S571, 3 of 6 (50%) at D16S507, 1 of 5 (20%) at D12S264, 0 of 6 (0%) at D17S855, 1 of 6 (17%) at D18S53, and 0 of 5 (0%) at D22S264. The pattern of allelic loss is significantly different in both stroma and epithelium statistically; completely concordant allelic loss patterns were not seen in any tumor examined. Our data demonstrate that both epithelial and stromal components of phyllodes tumor of the prostate are clonal, supporting the hypothesis that both elements are neoplastic. While both epithelium and stroma are clonal proliferations, they appear to have different clonal origins.

Clone Cells↗

PubMed2005

Progressive deregulation of the cell cycle with higher tumor grade in the stroma of breast phyllodes tumors.

We studied cell cycle-regulating proteins in phyllodes tumor pathogenesis by immunohistochemical analysis for Ki-67, cyclin A, cyclin D1, retinoblastoma protein (pRb), p53, p16INK4A, bcl-2, and p21waf1 in the epithelium and stroma of 40 primary (benign, 21; borderline, 8; malignant, 11) and 7 recurrent tumors of different grades. In most cases, the epithelium showed no altered expression of cell cycle regulators. Stromal overexpression of p16INK4A, p53, cyclin A, pRb, and p21waf1 correlated significantly with tumor grade. The number of altered proteins in stroma increased with higher grade and was accompanied by increased proliferation. Stromal cyclin A expression was the best separating marker between tumor grades. Correlations existed between stromal overexpression of p16NK4A and p21waf1, p16INK4A and p53, and p53 and pRb. No immunostaining differences were detected between primary tumors and recurrences. Four or more altered proteins and p53 expression in the stromal component were independent negative prognosticators for disease-free survival. The stromal component of mammary phyllodes tumors displays an increasing level of cell cycle deregulation with higher tumor grade; the epithelial compartment mostly remains inconspicuous. Several combinations of aberrantly expressed cell cycle proteins seem important in the stromal progression of phyllodes tumors. The number of stromal cell cycle aberrations and stromal p53 expression might predict clinical behavior.

Biomarkers, Tumor↗