Bilateral malignant phyllodes tumours.

We report a rare example of bilateral primary malignant phyllodes tumours. The diagnosis was supported by the identification of a benign epithelial element in each lesion. The case illustrates the typical dimorphic features of malignant phyllodes tumours. A contralateral tumour should not be regarded as metastatic without histological confirmation.     

PHYLLODES TUMOURS: A CLINICOPATHOLOGICAL REVIEW OF 30 CASES

Thirty cases of phyllodes tumour (cystosarcoma phyllodes) of the breast that presented to the Clinical Oncology Unit at Guy's Hospital were reviewed. Tumours were classified as benign, malignant or borderline according to the following histological criteria: mitotic rate, nuclear pleomorphism, stromal overgrowth and tumour margins. In 14 (46.5%) cases the tumours were considered histologically benign, in 11 (36.5%) malignant, and in five (17%) borderline. Recurrence was seen in a similar proportion of patients with tumours classified as benign (21 %) and malignant (18 %) according to histological criteria. Malignant lesions tended to recur earlier. Infiltrating tumour margins were noted in all patients and stromal overgrowth in all hut one in whom recurrence was observed. Risk of recurrence also appeared to he related to tumour size. Only one patient developed distant metastases and died of her disease. Because of treatment variation no conclusion can he made regarding optimal therapy but the importance of adequate clearance, either through wide excision or mastectomy, is emphasized for all phyllodes tumours irrespective of histological features.     

Primary breast sarcoma: A review of 33 cases with immunohistochemistry and prognostic factors

The clinical and pathological features of 33 previously untreated patients with primary breast sarcoma were retrospectively analysed to evaluate the prognostic significance of histologic variables on survival. The series comprised 17 cystosarcomas phyllodes and 16 stromal sarcomas (excluding angiosarcomas).All tumors were reviewed and classified in similar fashion to extramammary soft tissue sarcomas. In addition, immunohistochemical studies were performed on paraffin sections with a panel of several antibodies directed against cytoskeletal filaments and cellular enzymes; five cases were also examined by electron microscopy.Most tumors were malignant fibrous histiocytoma (21 cases) and fibrosarcoma (6 cases) types. Surgery was the main therapy. Metastasis-free survival rate was significantly correlated only with histological grade, consisting of tumor differentiation, tumor necrosis, and mitotic activity. Courses and survivals of the cystosarcoma and stromal groups were identical, questioning the clinical value of this pathologic distinction. All local recurrence, metastasis, or death occurred within 30 months, though follow-up was much longer.Immunohistochemistry was disappointing for identification of specific histologic sub-types.     

Beta-catenin abnormalities and associated insulin-like growth factor overexpression are important in phyllodes tumours and fibroadenomas of the breast

The aim of this study was to assess the expression of IGF-I and IGF-II in phyllodes tumours and fibroadenomas and to see if there is any correlation between nuclear beta-catenin expression and IGF-I and IGF-II expression in these tumours. In a previous study, it has been shown that Wnt signalling is important in the pathogenesis of phyllodes tumours of the breast. Epithelial Wnt5a overexpression and stromal Wnt2 overexpression were associated with abnormal, nuclear localization of beta-catenin in the stromal cells of these tumours. However, not all tumours with beta-catenin accumulation showed Wnt overexpression. One other possible cause of beta-catenin accumulation is overexpression of insulin-like growth factors (IGFs), as both IGF-I and IGF-II have been shown to stabilize beta-catenin. In this study, 30 fibroadenomas of the breast were assessed for beta-catenin expression using immunohistochemistry and the results were compared with previous data from 119 phyllodes tumours. In situ hybridization was used to assess IGF-I and IGF-II expression in 23 phyllodes tumours and 16 fibroadenomas. Nineteen phyllodes tumours (83%) showed widespread overexpression of IGF-II and 5/23 (22%) showed widespread overexpression of IGF-I. IGF-I expression correlated with nuclear beta-catenin staining in phyllodes tumours. Malignant phyllodes tumours showed no or little IGF-I expression. There was a degree of nuclear beta-catenin expression in the stroma (weak in 33%, moderate in 27%, and strong in 40%) in all fibroadenomas and nuclear beta-catenin staining correlated with IGF-I overexpression. Extensive IGF-II overexpression was also found in the majority of fibroadenomas (12/16). These results support the hypothesis that IGF-I and IGF-II overexpression may be important in the pathogenesis of fibroepithelial neoplasms of the breast and that IGF-I overexpression is likely to be contributing to the nuclear beta-catenin localization observed in the tumours.     

Fine-needle aspiration cytology of phyllodes tumors

Breast lesions with a significant spindle cell or mesenchymal component are not commonly encountered in fine-needle aspiration (FNA) cytologic material and include a heterologous variety of benign and malignant conditions, with phyllodes tumors (PTs) being the foremost differential diagnostic consideration. This study comprises 28 tumors diagnosed histologically as PT in which FNAC material was available for review. Histological sections and cytological smears from these cases were retrieved and subjected to detailed morphological review. Cytological parameters assessed included ratio of stroma to epithelium, pattern characteristics and cytological characteristics of the stromal, and epithelial components and the background cells. Large and hypercellular stroma fragments, dissociated spindle and plump stromal cells, often accompanied by large, folded sheets of epithelium were cytological features that characterized PT. Smears from malignant PT showed predominantly or solely mesenchymal components. FNAC was a highly reliable procedure for the diagnosis of PT, giving an accuracy rate of 92.8%.     

Malignant phyllodes tumour with a noninvasive ductal carcinoma component

 A malignant phyllodes tumour with a noninvasive ductal carcinoma component is reported. The patient was an 80-year-old Japanese woman with a breast tumour detected by routine physical examination. A simple mastectomy was performed. The excised tumour was 10.5×9.4×5.4 cm in size and bulged into the skin with ulceration. The macroscopic appearance was that of a phyllodes tumour. Histologically the tumour consisted mainly of stromal components with a leaf-like structure lined by atypical ductal epithelium. The epithelial component showed gradual evolution to intraductal papillary carcinoma in a few areas. The stromal component was composed mainly of fibrosarcoma with areas of osteosarcoma and rhabdomyosarcoma. Neither stromal invasion of intraductal carcinoma nor transition between the stromal and epithelial elements was seen. Three months after the operation, death occurred, with multiple pulmonary and subcutaneous metastases. This case probably represents malignant change in both the stromal and the epithelial components of a phyllodes tumour. Since the two elements were independent, the possibility that a phyllodes tumour may be one of the origins of true carcinosarcoma is raised. Received: 11 March 1997 / Accepted: 5 May 1997     

The Wnt pathway, epithelial-stromal interactions, and malignant progression in phyllodes tumours

In a previous study of phyllodes tumours, it has been shown that both the stroma and the epithelium can exhibit distinct molecular changes, suggesting that both are part of the neoplastic process. In view of this finding, it was decided to study stromal-epithelial interactions in these tumours by examining the Wnt-APC-beta-catenin pathway. Beta-catenin and cyclin D1 immunohistochemistry was performed on 119 phyllodes tumours. Eighty-six (72%) showed stromal nuclear beta-catenin localization and in 57% the staining was moderate or strong; however, of the eight malignant tumours in the series, seven showed absent or weak nuclear staining (p<0.025). In no tumour was nuclear beta-catenin staining seen in the epithelial component. Moderate or strong stromal cyclin D1 staining correlated with nuclear stromal beta-catenin staining (p<0.05). Forty-five of the tumours, including two malignant lesions, were screened for beta-catenin exon 3 mutations using SSCP and sequencing, but none was found. Loss of heterozygosity (LOH) of the marker D5S346 was used to infer APC mutation, but only one (benign) tumour showed LOH. Wnt2 and Wnt5a mRNA was localized by in situ hybridization in 13 cases (three malignant) chosen to reflect the different beta-catenin staining patterns. There was an association between strong nuclear beta-catenin staining of stromal cells and epithelial Wnt5a expression (p<0.0015). These data suggest that stromal proliferation in benign phyllodes tumours relies on abnormalities in the Wnt pathway which result not from mutation, but from Wnt5a expression in the epithelium. In the progression to malignancy, the stromal proliferation appears to become independent of the Wnt pathway and, presumably, of the epithelial component of these tumours.     

22例乳腺叶状肿瘤诊治分析

目的：分析乳腺叶状肿瘤的病理特征和临床表现，探讨诊治方法。方法：回顾性分析22例经病理证实的乳腺叶状肿瘤。结果：行乳房肿瘤扩大切除术9例，乳房切除术4例，乳房改良根治术2例，行乳房肿瘤局部切除术7例，4例乳房肿瘤局部切除术后出现复发，局部复发率19％，结论：乳腺叶状肿瘤术前确诊较困难，其局部复发与是否手术彻底切除密切相关，对病理诊断为巨纤维腺瘤者，局部切除术后应加强随访。     

Cystosarcoma phyllodes: Our institutional experience

Twenty‐six patients of Cystosarcoma phyllodes, treated between July 1994 and July 2001, were analysed retrospectively. Median age at presentation was 38 years (range 13?61 years). Mean size of the lesion was 6 cm. There were 77% left‐sided lesions and 23% right‐sided lesions. Histologically, 58% lesions were benign, 11% borderline and 31% malignant lesions. All patients underwent definitive surgical procedure in the form of wide local excision or mastectomy. Four patients received postoperative radiotherapy. Median follow‐up period was 35 months. Six patients showed recurrence, and four of these were malignant. Median disease‐free survival period was 34 months.     

Osteogenic pulmonary metastases originating from a phyllodes tumour of the breast with osteosarcomatous differentiation

Malignant phyllodes tumour is an uncommon breast neoplasm which undergoes osteosarcomatous differentiation in 1.3% of cases. We document the plain film, CT and scintigraphic features of a case of pulmonary metastases from this rare primary tumour.