Phyllodes tumor of the breast clinical experience and outcomes: A retrospective cohort tertiary hospital experience.

BACKGROUND: Phyllodes tumor (PT) accounts for <1% of all breast tumors worldwide. Based on their microscopic features, these tumors are classified into benign, borderline, and malignant. This study aimed at evaluating the clinical experience and the clinicopathologic features of PT. METHODS: A retrospective cohort study of 46 female patients with histologically diagnosed PT. Data collection and evaluation was done on patient demographics, preoperative radiological assessment and pathology, surgical procedure, post-surgery pathological evaluation, radiation therapy (RT), and follow-up. RESULTS: The median age at diagnosis was 42 years and young premenopausal patients (median age 35 years) had malignant PT. Forty-five patients underwent core needle biopsy (CNB) with high sensitivity and the positive predictive value (82.2% and 97.4% respectively). Thirty-nine patients (86.7%) underwent conservative surgery and 6 (13.3%) had a mastectomy. Twenty-seven (58.6%) were classified as benign, 11 (23.9%) as borderline and only 8 (17.4%) as malignant PT. Malignant PT had the greatest median tumor size (13 cm). Mortality and recurrence rates were 4.3% and 2.2% respectively. RT was administered in 6 patients (13.0%), 5 having malignant and 1 borderline PT. The metastatic rate was found to be 6.5%. CONCLUSION: PT are rare breast tumors with variable biologic behavior and heterogenous clinicopathological findings. Young, premenopausal women with large tumors may have malignant PT with a risk of recurrence and metastasis. Core needle biopsy is a reliable tool for diagnosis of PT with strict follow-up recommended for large tumors diagnosed as fibroadenoma on CNB. Surgical management must ensure a tumor-free margin on excision to reduce recurrence.

First case of primary phyllodes tumor of the pancreas: case report and findings of immunohistochemical and ultrastructural studies.

A 37-year-old Japanese man with a solid and cystic pancreatic mass was referred to our hospital. Computed tomography revealed a well-demarcated solid and cystic mass measuring approximately 3.0 cm in diameter in the pancreatic body. The patient underwent middle segment pancreatectomy, and the retrieved tumor specimen was found to be a well-demarcated solid and cystic lesion measuring 3.0 x 3.0 cm. On histological examination, the cyst walls were found to be lined with a monolayer of non-atypical tall columnar epithelial cells. The solid areas surrounded the cystic ones and showed storiform proliferation of spindle cells that contained round, oval, or elongated nuclei and were present among abundant collagen fibers. The solid areas sent phylloid projections into the cystic spaces and the main pancreatic duct. The spindle cells were found to be diffusely positive for alpha-smooth muscle actin, desmin, and h-caldesmon on immunohistochemical analysis. Electron microscopy revealed that these cells possessed well-developed myofilaments with dense bodies, pinocytic vesicles, and basal lumina. Neither metastasis nor local invasion was detected. After the operation (4 years), tumor recurrence has not occurred. The main differential diagnoses of spindle cell tumors are leiomyomas, leiomyosarcomas, inflammatory myofibroblastic tumors, solitary fibrous tumors, extra-gastrointestinal stromal tumors, and schwannomas. However, the histological findings in the present case differed from those of these tumors. The present lesion is the first reported case of a primary pancreatic phyllodes tumor.

Aggressive giant fibroepithelial lesion with unusual vascular stroma--a case report.

The stroma of fibroadenoma and phyllodes tumor usually consists of fibroblastic proliferation. Rarely the stroma contains bundles of smooth muscle. Pseudoangiomatous hyperplasia of the mammary stroma has been described in fibroadenomas. However, true benign vascular stroma has not been reported. We report a case of a 34-year-old Chinese woman who presented with a large mass occupying the entire left breast. Left mastectomy was performed and showed a large, well-circumscribed, lobulated, rubbery-firm tumor measuring 13 x 10 x 6 cm. Microscopic examination revealed a fibroepithelial tumor formed by an organoid pattern of ductal structures with a very striking stromal appearance composed of extensive vascular proliferation and that demonstrated strong immunoreactivity for CD31, CD34, and Factor VIII. Ultrastructural examination revealed intercellular junctions, basal lamina, pinocytotic vesicles, and Weibel-Palade bodies in the cells lining the vascular spaces, confirming their endothelial nature. These findings rule out the diagnosis of pseudoangiomatous hyperplasia. The patient developed local recurrence a year later, and the resection showed malignant phyllodes tumor with ductal carcinoma in situ. The extensive vascular stroma noted in the primary tumor may have played a role in the malignant transformation of the epithelial and stromal components in this tumor.

Cytofluorometric nuclear DNA content analysis of breast tissues after frozen section diagnosis.

OBJECTIVE: To establish a suitable method for measurement of nuclear DNA content in breast tissues from frozen storage after frozen section diagnosis. STUDY DESIGN: For fundamental research, rat liver samples preserved in a deep freezer were used. Four protocols were used (1. fixation with 70% ethanol followed by naked nuclei preparation; 2. fixation with 10% neutral buffered formalin followed by naked nuclei preparation; 3. preparation for naked nuclei prior to fixation with 70% ethanol; and 4. preparation for naked nuclei prior to fixation with 70% neutral buffered formalin). For clinical research, 13 separate fresh frozen breast tissue samples were analyzed after frozen section diagnosis. One contained a malignant phyllodes tumor (MPT) consisting of 2 components, benign epithelial cells and malignant stromal cells; 3 were benign tumors containing fibroadenoma; and 9 cases were carcinomas, consisting of 5 scirrhous, 3 papillotubular and 1 mucinous. RESULTS: Protocols 1, 2 and 3 were not suitable methods for our purpose because remaining cytoplasm or cohesive nuclei were observed. In protocol 4 the cytoplasm was completely undetectable, and nuclei were suitably separated for nuclear DNA content measurement. Benign epithelial cell component nuclei presented a diploid pattern, and the malignant stromal cell component nuclei indicated a euploid pattern in MPT. All 3 cases of benign constituents in fibroadenoma showed a diploid pattern, as did the 3 carcinoma cases (1 mucinous, 1 scirrhous and 1 papillary). Four scirrhous and 2 papillary carcinomas showed an aneuploid pattern. CONCLUSION: Our findings show that it is possible to measure nuclear DNA content of human frozen storage tissues after frozen section diagnosis.

Recurrent phyllodes tumor in a man.

The case of a 35-year-old man with a borderline-type cystosarcoma phyllodes is presented. Four years after the primary excision of the tumor, wide excision of a local recurrence and postoperative radiotherapy were performed. No repeated relapse was observed during a 5-year follow-up. Neither significant endocrine changes nor genetic alteration could be proven. However, a slightly increased SHBG concentration was detected, resulting in a decreased biologically available androgen level reduced testosterone/SHBG index. This phenomenon might be a consequence of the chronic liver disease of the patient due to his type II diabetes mellitus and alcohol abuse. In addition to the conventional histopathological examinations, immunohistochemical and electron-microscopic investigations were carried out on tissue sections, and the steroid receptors, EGF receptors and EGF-like activity of the tumor were also studied.

Scanning electron microscopic analysis of breast aspirates.

Scanning electron microscopic analysis (SEM) of 50 pre-selected breast aspirates was performed after light microscopy and cytomorphological evaluation. SEM analysis of these aspirates revealed the presence of microvilli (mv), microprojections, blebs and irregular contours in malignant cells. Benign cells were regular, globular and smooth. SEM provided additional morphologic data which if used in conjunction with light microscopy can assist in reaching a correct diagnosis.

Recurring phyllodes tumor in aberrant breast tissue of the vulva.

A 20-year-old nulligravida woman presented with bilateral cystic nodules of the vulva, diagnosed after simple excision as benign phyllodes tumor. Breast tissue, which also displayed fibrocystic changes, was also recognized. Follow-up at 2 months revealed no evidence of disease; however, 8 months after surgery she returned with a new mass in the vulva. This was excised and found to be recurrent phyllodes tumor. Although somewhat more cellular than the first lesions, it also was deemed to be benign based on histological features supported by flow cytometric DNA studies.

Cystosarcoma phyllodes of the seminal vesicle.

An unique case of high-grade phyllodes tumor (cystosarcoma phyllodes) arising in the seminal vesicle is reported. A 61-year-old man had symptoms of urinary obstruction, and ultrasonography and computed tomography showed a large mass posterior to the bladder. Using cystoprostatoseminovesiculectomy, a high-grade phyllodes tumor of the left seminal vesicle was found that did not involve the bladder or prostate. Histologically, the tumor consisted of benign irregular slit-like glands set in a mitotically active cellular sarcomatous stroma. The epithelium displayed intense cytoplasmic immunoreactivity with all keratin proteins (AE1/AE3, CAM 5.2, and high-molecular-weight keratin [clone 34 beta E12]). The stromal cells were strongly positive for vimentin, and approximately 30% were positive for muscle-specific actin and desmin. Four years after resection, a lung metastasis was removed, which was histologically and immunohistochemically identical to the seminal vesicle tumor. This case represents the malignant end of the range of phyllodes tumors (cystosarcoma phyllodes). Like similar tumors in the breast and prostate, phyllodes tumors of the seminal vesicle should be considered high-grade lesions (malignant) in which there is significant mitotic activity, stromal pleomorphism, and stromal overgrowth.

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.

Fine needle aspiration cytology of phyllodes tumor. Potential diagnostic pitfalls.

We reviewed the fine needle aspiration cytologic findings in six cases of phyllodes tumor (PT). The average age of the patients at the time of the diagnosis was 47 years. Two cases were correctly diagnosed cytologically; both were malignant histologically. Of the histologically benign tumors, two were misdiagnosed as carcinoma, and a third was considered suspicious for carcinoma. The remaining case was diagnosed descriptively as "benign duct epithelium." Possible reasons for overdiagnosis include high cellularity of the smears, the presence of atypical ductal hyperplasia, paucity of the stromal component in the aspirates and occasional dissociation of epithelial cells. Recommendations are offered to prevent misdiagnosis. The cytologic differential diagnosis between fibroadenoma and PT is discussed briefly, and the considerable cytologic overlap that can occur is emphasized. The specific cytologic diagnosis of PT is not possible in many cases, but the presence of certain cytologic features in the correct clinical setting allows the diagnosis to be suggested.

Cystosarcoma phyllodes. Diagnosis by fine needle aspiration cytology.

The cytologic features of 10 benign, 2 borderline and 5 malignant phyllodes tumors were studied, and an attempt was made to correlate the cytologic findings with corresponding histologic categories. Seventy-five percent of the benign and borderline tumors were interpreted as benign cystosarcoma phyllodes on fine needle aspiration cytology. Eighty percent of the malignant phyllodes tumors were identified as malignant lesions cytologically. The cytologic features assessed were the epithelial:stromal ratio and morphology of the stromal component, including the degree of atypia, mitotic activity, capillary vessels traversing the stromal fragments, presence of foamy macrophages, histiocytic giant cells and bipolar naked nuclei. A diagnosis of phyllodes tumor was suggested cytologically by the presence of both epithelial and stromal elements; the stroma was present as cellular "phyllodes fragments" and isolated mesenchymal cells. The parameters suggesting malignancy were extreme paucity or absence of epithelial elements and stromal cells in diffuse sheets and clusters less cohesive than normal, with marked stromal atypia and mitotic activity.

The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes.

A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow-up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high-risk patients, local recurrence is another indication that metastasis is likely.

[A case report of phylloides tumor of the prostate: review of the literature and analysis of bizarre giant cell origin].

A case of phylloides tumor of the prostate in a 58-year-old male is presented. The tumor was composed of columnar cystic folds and pleomorphic stromal elements including bizarre giant cells. Electron microscopic examination, which was performed using specimens embedded in paraffin blocks, revealed that the bizarre giant cells originated from the smooth muscle. The postoperative course was uneventful, with no evidence of local recurrence or metastasis for more than 2 years after operation.

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.

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.

Coexistence of intracytoplasmic lumens and membrane-bound vesicles in an invasive carcinoma arising in a cystosarcoma phyllodes.

An unusual invasive breast carcinoma, arising in a cystosarcoma phyllodes and characterized by a variable cytoplasmic appearance and mucin content, was evaluated to determine the nature of the secretory material within the cells as well as the type of secretory organelle at the ultrastructural level. Histochemical studies revealed both acidic (sialic acid) and neutral mucin within the tumor cells. Ultrastructural analysis revealed secretory material within membrane-bound vesicles in some cells and within intracytoplasmic lumens in others; some cells contained both membrane-bound vesicles and intracytoplasmic lumens simultaneously. The Golgi derivation of the intracytoplasmic lumens was supported by their presence within or near hyperplastic Golgi complexes. The histochemical characteristics of the secretory material is correlated with their ultrastructural site of accumulation.

A human breast stromal sarcoma cell line with features of malignant cystosarcoma phyllodes.

A cell line was established from a portion of a 25-cm stromal sarcoma of the left breast of a 65-year-old woman. The clinical course was rapid with tumor recurrence on the chest wall less than 1 month after mastectomy. Other cutaneous and abdominal metastases occurred shortly thereafter, and death followed within 3 months despite chemotherapy. The cultured cells, designated RW-972, produced large amounts of acid mucopolysaccharides (hyaluronic acid) and mimicked the aggressive growth characteristics seen in the patient. After injection into nude mice, the tumor grew rapidly and occasionally produced metastases. This unique cell line, RW-972, presumably derived from the stromal component of a human malignant cystosarcoma phyllodes, might be useful in studies of experimental therapy of this rare tumor type and of lobular stromal cells of breast. It may also be used to investigate hyaluronic acid production by tumor cells.

Ultraestructura del cistosarcoma phyllodes maligno: presentación de 4 casos / Ultrastructure of malignant cystosarcoma phyllodes: report of 4 cases

Se presentan 4 casos de cistosarcoma phyllodes maligno, estudiados en el microcospio electrónico, después del estudio preliminar en el microscopio óptico. Desde el punto de vista ultraestructural los hallazgos permiten diferenciarlo del tumor phyllodes benigno, ya que los fibroblastos presentan mayor indiferenciación hacia la célula mesenquimatosa primitiva que en la variedad benigna

Ultraestructura del cistosarcoma phyllodes maligno. presentación de 4 casos / Ultrastructure of malignant cystosarcoma phyllodes: report of 4 cases

Se presentan 4 casos de cistosarcoma phyllodes maligno, estudiados en el microcospio electrónico, después del estudio preliminar en el microscopio óptico. Desde el punto de vista ultraestructural los hallazgos permiten diferenciarlo del tumor phyllodes benigno, ya que los fibroblastos presentan mayor indiferenciación hacia la célula mesenquimatosa primitiva que en la variedad benigna

Histopathological and clinical correlations of cystosarcoma phyllodes.

We performed a detailed retrospective analysis of 25 patients treated primarily at Northwestern Memorial Hospital, Chicago, for cystosarcoma phyllodes. Histopathological evaluation correlated well with malignancy, but clinical suspicion did not. Pathological studies indicated that high-grade tumors, necrosis, infiltrating margin, and the presence of more than one mesenchymal element were often associated with aggressive behavior. Flow-cytometric analyses of DNA aneuploidy and proliferative index supported the grading system we used, since all four malignant cases examined showed high proliferative index, and three of the four cases showed aneuploidy. None of the low-grade cases, including the recurrent ones, showed increased proliferative index or aneuploidy. We believe that flow-cytometric analysis ought to be performed on cases in which there is doubt regarding the potential malignancy.