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PubMed2001

Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: immunohistochemical and flow cytometric study of 118 cases.

The goal of this study was the prognostic evaluation of histology, mitotic rate, S-phase fraction (SPF) and expression of proliferative antigen Ki67 and p53 protein in phyllodes tumor of the breast. The study was performed in the group of 118 patients with phyllodes tumor treated by surgery from 1952 to 1998. Mitotic rate was assessed on the representative histological specimens. Expressions of Ki67 and p53 were evaluated by immunohistochemistry on a section from the corresponding paraffin blocks which were also used for flow cytometric DNA evaluation. Histologically, 52 tumors were benign (LGM), 24 borderline malignancies (BM) while among 42 malignant tumors, 20 were monomorphous (HGM) and the remaining 22 revealed heterologic elements (HGH). Tumor recurrencies occurred in 17 patients, predominantly during the first three years after surgery, and 13 patients died of the tumor (1 BM, 12 both malignant variants). Multivariate analysis demonstrated mitotic rate, SPF and p53 expression as independent prognostic parameters for the disease-free survival. Histological tumor type and expression of Ki67 influenced independently the overall survival. In conclusion, the histological type of tumor phyllodes forms the basis for the prognosis of clinical outcome, but the indicators of the proliferative activity, especially Ki67 index, are valuable prognostic factors among patients with malignant variant of phyllodes tumor of the breast. Expression of the p53 protein in tumor cells could be also useful when the percentage of cells and intensity of expression are considered.

Adolescent↗
PubMed2004

Expression of p53 protein and Ki-67 antigen in phyllodes tumor of the breast.

BACKGROUND: Phyllodes tumors (PT) of the breast are uncommon, and it is often difficult to predict their clinical behavior from histologic features in individual cases. In addition to routine morphology, the studies of p53 protein and Ki-67 antigen expression in PT may be useful to differentiate benign from malignant tumors. METHODS: Immunohistochemical analyses using monoclonal antibody to label p53 protein and another monoclonal antibody MIB-1 to label Ki-67 antigen were performed on the tissue sections of 63 PT from 56 patients. The percentages of positive staining tumor cells were compared with the tumor gradings and clinical outcomes. RESULTS: According to histologic criteria, this series contained 50 benign and 13 malignant tumors. The p53 protein expression showed a significant difference between benign and malignant lesions. Within the group of benign lesions, 5 out of 50 (10%) tumors had p53 expression > 10%, whereas nine out of 13 (69%) malignant tumors revealed p53 expression > 10% (p < 0.005). The Ki-67 antigen was also well correlated with tumor grading. Eleven out of 13 (85%) malignant tumors but only 8 out of 50 (16%) benign tumors showed Ki-67 antigen increased > 10% (p < 0.005). Three patients progressed from benign to malignant tumors. All the first and recurrent tumors in these 3 patient showed Ki-67 > 10%. CONCLUSIONS: P53 protein and Ki-67 antigen expression are correlated with the histology grading. In tumors with benign morphology but having a Ki-67 antigen > 10%, it is necessary to treat the patient and follow up properly to avoid recurrence and malignant transformation.

Adolescent↗
PubMedDate not supplied

A cell line derived from a clinically benign phyllodes tumor: characterization and implications.

Phyllodes are uncommon tumors of the breast. Improved understanding of their behavior is hampered by the paucity of good laboratory models. We have developed two cell lines, by both xenograft and direct cell culture, derived from a histologically benign phyllodes tumor. Both cell lines have the same characteristics and growth kinetics. They grow as monolayers of spindle-shaped cells, with surface markers consistent with a mesenchymal origin. They do not express either estrogen or progesterone receptors. The cells have a relatively short doubling time of just over 1.5 days, and show a stimulatory effect with the addition of insulin. Karyotype analysis reveals the absence of one X chromosome.

Animals↗
PubMed1996

Phyllodes Tumor of the Breast: Pathology, Histogenesis, Diagnosis, and Treatment.

Phyllodes tumor of the breast is histologically unique in that it is composed of epithelial and stromal components. The histogenesis of this disease has remained largely unknown but recently we have obtained interesting information through clonal analysis, and have been able to show a difference in the histogenesis between phyllodes tumor and fibroadenoma. Elucidation of histogenesis would difinitely improve our understanding of the biological behavior of this disease and also help to establish the most appropriate treatment strategy. The pathology, histogenesis, diagnosis, and treatment of phyllodes tumor are reviewed in this paper. Our hypothesis on the histogenesis of this disease is also presented.

Journal Article↗
PubMed2000

Malignant phyllodes tumor metastatic to the forearm: a case report.

We describe the cytological features of a malignant phyllodes tumor, in a 40-yr-old female, that metastasized to the forearm, and we correlate these findings with the criteria suggested by other authors for predicting the clinical and metastatic behavior of this tumor. The diagnosis of metastasis was based on fine-needle aspiration (FNA) cytology. One year prior, the patient had undergone mastectomy of the left breast for malignant phyllodes tumor, as proven by histopathology. The patient then presented with right forearm swelling, 1 yr later. FNA cytology was performed, and the diagnosis was metastatic malignant phyllodes tumor. Histologic review of the breast tumor revealed stromal overgrowth, which is the most important histologic criterion for predicting the metastatic behavior of malignant phyllodes tumor as reported by some authors.

Adult↗
PubMedDate not supplied

Malignant phyllodes tumor with pleomorphic liposarcomatous stroma diagnosed by fine needle aspiration cytology: a case report.

BACKGROUND: Liposarcomatous differentiation within a phyllodes tumor is extremely rare. Cytologic and histologic findings of a case of malignant phyllodes tumor with liposarcomatous stroma of the breast are presented. CASE: A 45-year-old female had a malignant phyllodes tumor with pleomorphic liposarcomatous stroma diagnosed by fine needle aspiration (FNA) cytology. The cytologic findings were representative of the histologic features. CONCLUSION: Malignant phyllodes tumor of the breast can be diagnosed by FNA. It is very important to acknowledge the morphologic variants of sarcomatous stroma and to recognize the cytologic features of such rare tumors to prevent misdiagnosis as primary sarcomas of the breast. Preoperative diagnosis is important in planning the most appropriate type of treatment. It is also important to follow patients for long periods for recurrence and metastasis after surgery for this tumor.

Biopsy, Needle↗
PubMed1989

[Phyllodes breast tumors].

Phyllodes tumors represent a particular class in breast pathology. They are defined as bi-tissue, fibro-epithelial tumors, similar to fibro-adenomas, but their connective tissue component is greatly predominant. They are infrequent as they represent only 3% of breast tumors. They mainly occur during the premenopausal period, since alteration of the hormonal balance may play a role. The authors feel that they represent only a type of the evolution of the fibroadenomas with a relationship, in time, following the sequence: fibroadenomaphyllodes tumor-sarcoma. The diagnosis is exclusively made by histology and there is no pathognomonic sign, whether it is clinical or mammographic. The course is essentially characterized by the possibility of local recurrences, sometimes numerous, and by the occurrence of metastases in case of malignant phyllodes tumor. These two possibilities are correlated with the histological stage of the tumor. The treatment is definitely surgical, possibly mastectomy in case of large or aggressively active tumor.

Breast Neoplasms↗
PubMed1992

Malignant phyllodes tumor of the prostate. A case report with immunohistochemical and ultrastructural studies.

Phyllodes tumor of the prostate is a rare neoplasm with cellular or sarcomatoid stroma and hyperplastic glands. This lesion shares many histologic features with cystosarcoma phyllodes of the breast. Although a malignant variant of phyllodes tumor of the prostate has been described, the majority of cases have been clinically benign. We report an unusual case of phyllodes tumor of the prostate in which the stromal component underwent malignant degeneration, a finding not previously described (to our knowledge). Immunohistochemical and ultrastructural studies demonstrated smooth-muscle differentiation of the stromal cells.

Aged↗
PubMed2002

Complex karyotype in a low grade phyllodes tumor of the breast.

Cytogenetic analysis of a phyllodes tumor of low grade malignancy disclosed the karyotype 52-55,XX, -1,+5,+7,+9,+10,+11,-15,+18,-19,+20,der(21)t(1;21)(p13;q22),+mar1x 2-4,+mar2[cp18]/46,XX. This study shows that a complex chromosome karyotype can be found in low-grade phyllodes tumors and is not necessarily a sign of extreme malignancy of these neoplasms.

Biopsy↗
PubMed2000

Platelet-derived growth factor expression in phyllodes tumors and fibroadenomas of the breast.

The development of normal breast tissue and the pathogenesis of various tumors are influenced by growth factor-mediated epithelial-stromal interactions. Similar interactions may occur in fibroepithelial breast tumors. We have studied the expression of platelet-derived growth factor (PDGF) and PDGF beta receptor (PDGFRbeta) in 46 phyllodes tumors (18 benign, 15 borderline, 13 malignant), 11 fibroadenomas, and 6 samples of normal breast. There was neoplastic stromal cell positivity for PDGFRbeta in almost 50% of phyllodes tumors and for PDGF in 24%. Both were associated with prominent nuclear pleomorphism (P<.01), PDGF with high grade (P<.01), and a higher mean Ki-67 labeling index (P = .013), and PDGFRbeta with conspicuous stromal overgrowth (P<.01). Co-positivity for stromal PDGF and PDGFRbeta was found in 15% of phyllodes tumors, and for epithelial PDGF and stromal PDGFRbeta in 43%. Both types of co-positivity were associated with prominent nuclear pleomorphism and the latter type with conspicuous stromal overgrowth (all P<.01). Follow-up of 41 phyllodes tumors showed that disease-related death was associated with established histologic features of malignancy including mitotic count, stromal overgrowth, an infiltrative tumor margin, and nuclear pleomorphism. In addition, stromal PDGFRbeta positivity (P =.013) and epithelial PDGF/stromal PDGFRbeta co-positivity (P =.0075) were associated with disease-related death. Stromal PDGF and PDGFRbeta expression in fibroadenomas was less common and less extensive (P<.05) than in phyllodes tumors. The results suggest that PDGF influences the pathogenesis of fibroepithelial breast tumors and that PDGF-dependent paracrine and autocrine mechanisms may operate. Also, it is possible that assessment of PDGF and PDGFRbeta expression could contribute to the management of these tumors in the future.

Breast↗
PubMedDate not supplied

Fine needle aspiration cytology of malignant phyllodes tumor with liposarcomatous stroma of the breast. A case report.

BACKGROUND: Liposarcoma arising within a phyllodes tumor is extremely rare. To the best of our knowledge, a malignant phyllodes tumor with liposarcomatous stroma diagnosed by fine needle aspiration (FNA) has not been reported before. CASE: A 39-year-old female had a malignant phyllodes tumor with liposarcomatous stroma diagnosed by FNA cytology. Two subtypes of liposarcomatous stroma, including lipomalike differentiated and myxoid, were found in the aspirates. The cytologic findings were very representative of the histologic features. CONCLUSION: It is very important to recognize the cytologic features of such rare tumors. An accurate diagnosis preoperatively by FNA permits better therapy planning.

Adult↗
PubMed1998

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.

Biopsy↗
PubMed1999

[Pulmonary metastatic malignant phyllodes tumor showing multiple thin walled cavities].

A 52-year-old woman who had undergone a partial mastectomy 1 year earlier because of benign phyllodes tumor was admitted because of dry cough and abnormal chest radiograph findings. Chest computed tomograms demonstrated multiple thin-walled cavities and nodules. Clinical examinations and transbronchial biopsy specimens failed to provide a conclusive diagnosis. However, the pulmonary thin-walled cavities enlarged, and a nodular shadow revealed cavitary formation. An open lung biopsy was performed to diagnose the pulmonary lesions. Although biopsy specimens disclosed the infiltration of poorly differentiated adenocarcinoma cells in pleura and pulmonary parenchyma, no primary site was detected. The patient did not respond to systemic chemotherapy (CDDP and VP-16), and died of respiratory failure due to advanced pulmonary metastasis. Autopsy demonstrated marked tumor invasion of the lungs, myocardium, and bone. We analyzed malignant cells in lung tissues at autopsy by immunohistochemistry, and found identical malignant cells in surgical samples obtained during the patients earlier mastectomy. A diagnosis of pulmonary metastasis from malignant phyllodes tumor of the breast was made. Thin walled cavitary lesions from malignant phyllodes tumor are rare; however, pulmonary metastasis of malignant phyllodes tumor should be considered one disease that exhibits thin-walled cavities as a radiographic manifestation.

Adenocarcinoma↗
PubMed1997

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.

Breast Neoplasms↗
PubMed2006

Successful therapy of a malignant phyllodes tumor of the prostate after postoperative local failure.

A 19-year-old student who had presented with acute urinary retention was referred to our hospital with biopsy diagnosis of proliferating mesenchymal tumor of the prostate. Magnetic resonance imaging showed enlarged prostatic masses. Suspecting prostate sarcoma, we performed a nerve-sparing radical prostatectomy. Histologic diagnosis of the tumor was prostatic malignant phyllodes tumor. Five months after the operation, bilateral obturator lymph node metastases appeared, which were treated with etoposide, ifosfamide, and cisplatin chemotherapy. After a good response was achieved with four cycles of the chemotherapy, pelvic irradiation was added. Since then, there has been no evidence of recurrence for more than 4 years.

Adult↗
PubMed1998

Adjuvant radiotherapy for phyllodes tumor of breast.

Our purpose was to examine the role of radiotherapy in the management of phyllodes tumor of the breast. Eight patients were treated with adjuvant radiotherapy for nonmetastatic phyllodes tumor of the breast at the M.D. Anderson Cancer Center between December 1988-August 1993. Tumors were classified as benign (n=2), borderline (indeterminate; n=1), or malignant (n=5). Median follow-up was 36.5 months. Primary surgery consisted of either lumpectomy in 2 patients or mastectomy in 6 patients. Seven patients received adjuvant radiation therapy to the breast or chest wall to a dose of 60 Gy. One patient received 50 Gy to the breast, followed by an interstitial boost of 20 Gy for a total of 70 Gy. Radiotherapy was administered for a combination of reasons, including bulky tumor volume, positive margins, recurrence, and/or malignant histology. There were no local or distant failures. This retrospective review suggests that adjuvant radiotherapy may be underutilized in the treatment of phyllodes tumor of the breast, particularly in patients with adverse features. Although treatment to the breast or chest wall (not the lymphatics) to a dose of 60 Gy appears effective, a dose-response has not been established, and lower doses (50-60 Gy) may be equally effective.

Adult↗
PubMed1989

Phyllodes tumor of the prostate: a case report.

A case of prostatic phyllodes tumor which developed in a 78-yr-old man is reported. Histologically, the tumor comprised myxomatous and cellular portions with a proliferation of atypical stromal cells. Multinucleated giant cells were occasionally present, but mitoses were rare. Fibroblastic differentiation of the tumor cells was confirmed by numerous rough endoplasmic reticulums and free ribosomes, and by immunoreactivity for vimentin. Approximately one-third of the tumor cells showed estrogen-receptor immunoreactivity at their nuclei. The patient is well, with no evidence of tumor recurrence, five years after the resection. The tumor was diagnosed as being a benign prostatic phyllodes tumor showing fibroblastic differentiation, and of an estrogen-dependent nature.

Aged↗
PubMed2006

Estrogen receptor-beta is expressed in stromal cells of fibroadenoma and phyllodes tumors of the breast.

An estrogen dependency has been suggested for the growth of fibroadenomas: however, thus far, none of the steroid hormone receptors acting on breast tissues has been demonstrated in the stroma of breast fibroepithelial lesions. In this study, the expression of estrogen receptor (ER)-alpha and -beta was investigated by immunohistochemistry in 33 fibroadenomas and in 30 benign, three borderline and seven malignant phyllodes tumors, all with spindle cell growth and in one distant metastasis. In addition, the presence of ER-beta mRNA and its variants was evaluated by RT-PCR in microdissected stroma. The possible correlation between hormone receptor expression and differentiation processes of stromal cells was investigated by smooth muscle actin and calponin immunostaining. ER-beta was the only hormone receptor expressed by stroma of fibroadenomas and phyllodes tumors, both at protein and mRNA level. The highest percentage of ER-beta was observed in fibroadenomas with cellular stroma and in phyllodes tumors. In both lesions, ER-beta-positive stromal cells showed expression of smooth muscle actin and/or calponin, as demonstrated by double immunostaining. In addition, the mean age at diagnosis was significantly lower in patients with ER-beta-positive vs ER-beta-negative fibroadenomas. In contrast, in phyllodes tumors, ER-beta expression was higher in older patients. In conclusion, (i) only ER-beta is detected in the stroma of fibroadenomas and phyllodes tumors; (ii) its expression correlates with the expression of smooth muscle markers and suggests a role of ER-beta in myofibroblastic differentiation of stromal cells. These two results, together with the young age of patients carrying fibroadenomas with highly ER-beta-positive stroma cells, may further indicate a hormone-receptor mechanism involved in regulating the growth of fibroadenomas. Conversely, the older age of patients with ER-beta-rich phyllodes tumors suggests that mechanisms, probably independent from estrogen stimulation, act on the growth of these tumors.

Actins↗