[ON THE SUBJECT OF RECURRING MAMMARY FIBROEPITHELIAL NEOPLASMS, WITH FALSE ASPECTS OF STROMAL MALIGNANCY (CYSTOSARCOMA PHYLLODES OF J. MUELLER, ADENOSARCOMA)].
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Adenosarcoma↗
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Results for “Neoplasms, Fibroepithelial”
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Multinucleated stromal giant cells in mammary fibroepithelial neoplasms. A study of 11 patients.
Multinucleated stromal giant cells (MSGCs) found in otherwise-banal breast tissue have only rarely been mentioned in specific lesions. We describe unilateral fibroepithelial tumors with MSGCs in 11 women who were 23 to 60 years old (mean age, 42 years). The tumors ranged from 1.7 to 9.0 cm in greatest dimension (mean, 3.7 cm) and were classified on the basis of stromal cellularity, infiltration at the margin, cellular pleomorphism, and mitoses independently of MSGCs. Using these criteria, there were four fibroadenomas, one benign cystosarcoma, and four low-grade and two high-grade malignant cystosarcomas. The MSGCs had hyperchromatic or vesicular nuclei, many with clear nuclear inclusions. The nuclei were often arranged in a semicircular or florette pattern. The MSGCs, although widely distributed, tended to cluster. They accounted for most of the stromal cellularity in the fibroadenomas, numbering focally up to 10 per high-power field. The benign and low-grade malignant cystosarcomas had fewer MSGCs. The MSGCs contributed least to the cellularity in the high-grade cystosarcomas. Five patients had no further therapy. Five patients underwent wide excision and one patient had a mastectomy. Follow-up extended to 8 years (median follow-up, 4 years). There were no recurrences, and all patients were alive with no evidence of disease. The results of this study lead us to conclude that the diagnosis and grading of fibroepithelial tumors of the breast depend on the cellularity and pleomorphism of the stroma, exclusive of MSGCs. Cystosarcomas that have MSGCs do not have an especially malignant clinical course.
Adult↗
Malignant phyllodes tumours show stromal overexpression of c-myc and c-kit.
Phyllodes tumours are fibroepithelial neoplasms of the breast, the stroma of which can undergo malignant progression to sarcoma. The frequency of malignant lesions varies in different series from 5% to 30%. The aim of this study was to elucidate potential molecular mechanisms in the progression to malignancy in phyllodes tumours. c-myc and c-kit were studied at the protein, RNA(c-myc only) and DNA level. We chose to study c-myc as we have previously shown that Wnt signalling is important in benign, but not malignant, phyllodes tumours. If c-myc is constitutively activated in malignant tumours, this may provide an explanation for why the Wnt pathway is no longer important in these tumours. c-kit is a membrane-bound tyrosine kinase receptor and overexpression is characteristic of gastrointestinal stromal tumours. A previous report suggested that this may also be the case in malignant phyllodes tumours, and we wished to confirm this. We assessed expression of c-myc and c-kit in 30 phyllodes tumours (10 malignant) using in situ hybridization (c-myc) and immunohistochemistry (c-myc and c-kit). 9/10 malignant tumours showed c-myc expression in the stroma, compared to 7/20 benign tumours (p = 0.006, Fisher's exact test). Stromal c-kit expression was found in 5/10 malignant tumours, compared to 1/20 benign tumours (p = 0.008, Fisher's exact test). One tumour had high-level amplification of c-myc, but we found no evidence of mutations of c-kit. We hypothesize that the overexpression of c-myc may drive stromal proliferation in malignant phyllodes tumours, and that c-kit overexpression contributes to the growth of these lesions. c-kit may also be a new therapeutic target in these tumours.
Breast Neoplasms↗
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.
Breast Neoplasms↗
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↗
Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal mucinous carcinoma: case report and review of 49 cases of extramammary Paget's disease.
BACKGROUND: Anogenital Paget's disease (PD) may be accompanied by varying degrees of epidermal hyperplasia. The histological changes can be reminiscent of fibroepithelioma of Pinkus. METHODS: We present a case of perianal PD associated with fibroepitheliomatous epidermal hyperplasia in a 76-year-old-man with an underlying rectal mucinous carcinoma. We also carried out a retrospective analysis of 51 biopsies from 49 cases of extramammary PD to see whether particular epidermal changes occur in association with PD in different anatomic locations. RESULTS: A tumor, 3 cm in diameter, was noted in the patient's perianal skin. Histologically, it was composed of anastomosing thin epithelial strands with follicular differentiation. Paget's cells were distributed in the epithelial strands of this tumor as well as in the surrounding epidermis and anal epithelia. In our series of extramammary PD, epidermis was hyperplastic in two of two perianal cases, 26 of 43 genital skin samples, and one of six axillary PD biopsies. The stroma beneath the hyperplastic epidermis tended to be rich in thin collagen fibers and fibroblasts. CONCLUSIONS: Anogenital PD was more frequently associated with epidermal hyperplasia than axillary PD. Fibroepitheliomatous hyperplasia may be induced by the altered stroma associated with PD.
Adenocarcinoma, Mucinous↗
p53 and c-kit (CD117) protein expression as prognostic indicators in breast phyllodes tumors: a tissue microarray study.
Breast phyllodes tumors are fibroepithelial neoplasms whose clinical behavior is difficult to predict on histology. There is relatively scant data on the role of biological markers. In this study, we determined if p53 and CD117 (c-kit) protein expression was predictive of behavior in a series of 335 phyllodes tumors diagnosed at the Singapore General Hospital, using immunohistochemistry on tissue microarrays. Representative areas from 250 (75%) benign, 54 (16%) borderline and 31 (9%) malignant phyllodes tumors were selected for construction of tissue microarrays using the 2 mm punch. Immunohistochemistry for p53 and CD117 was carried out using the streptavidin-biotin method. Staining proportion and intensity of both epithelial and stromal elements were analyzed. p53 immunostaining was observed in the epithelium of 28 (10%) of 278 microarrays; myoepithelium of 53 (21%) of 251 microarrays; and stromal cells in 105 (36%) of 289 microarrays. CD117 immunohistochemical reactivity was noted in epithelial and stromal components of 175 (of 267, 66%) and 17 (of 273, 6%) microarrays, respectively. Stromal p53 and CD117 protein expression was associated with tumor grade (P < 0.05). Of 43 (13%) women who suffered recurrences during the follow-up period, CD117 stromal staining predicted recurrent disease (P<0.05), but p53 was not correlative. We conclude that tissue microarrays are a convenient method for evaluating immunostaining results of large numbers of phyllodes tumors. Although positive p53 stromal immunohistochemical detection may corroborate histologic malignancy, it is CD117 protein expression in phyllodes tumor stromal cells that may be of potential utility in predicting recurrent disease.
Adolescent↗
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↗
Landscape of genetic alterations affecting cancer genes in primary and advanced malignant phyllodes tumours.
BACKGROUND: Malignant phyllodes tumours (MPT) are aggressive breast fibroepithelial neoplasms. Their rarity has limited their genetic characterization, and associations with genetic ancestry and progression drivers remain poorly understood. Prior studies suggest two evolutionary pathways according to MED12 mutational status. We sought to determine the repertoire of somatic genetic alterations in cancer genes in primary versus metastatic/recurrent MPTs, and according to MED12 mutational status and genetic ancestry. MATERIALS AND METHODS: We analysed the paired tumour-normal targeting sequencing data (up to 505 cancer-related genes) of 31 MPTs (primary, n = 20; metastatic/recurrent, n = 11). RESULTS: Metastatic/recurrent MPTs harboured a numerically higher frequency of genetic alterations in CDKN2A/2B (55% vs. 25%). Moreover, analysis of an MPT case with paired primary and metastatic samples revealed a CDKN2A/2B homozygous deletion restricted to the metastatic sample, suggesting a role for CDKN2A/2B in progression. Compared with MED12-wild type MPTs, MED12-mutant MPTs had higher tumour mutation burden (P = 0.002), frequency of TERT promoter (82% vs. 35%; P = 0.02) and RB1 mutations (45% vs. 5%; P = 0.01). Genetic alterations in the PI3K pathway, including PIK3CA and PTEN, were only present in MED12-wild type MPTs, and absent in MED12-mutant cases (15% vs. 0%; P > 0.05). Furthermore, genetic alterations in EGFR were restricted to MPTs from patients of European genetic ancestry and absent in those of Asian ancestry (43% vs. 0%; P > 0.05). CONCLUSIONS: Taken together, the repertoire of genetic alterations in primary and metastatic/recurrent MPTs shows overlap, and CDKN2A/2B homozygous deletions may play a role in progression. Additionally, molecular profiles of MPTs may vary according to genetic ancestry and MED12 mutational status.
Humans↗
Unguioblastoma and unguioblastic fibroma--an expanded spectrum of onychomatricoma.
Onychomatricoma is a rare tumor that appears to originate from cells of the nail matrix. Three cases of onychomatricoma that met Perrin et al.'s1 histologic criteria of onychomatricoma are described. However, using a single term to classify all three tumors ignores the apparent microscopic differences that exist among them. To demonstrate better the spectrum of so-called onychomatricoma and properly acknowledge the noticeable disparity among our cases, a series of terms is proposed. This terminology is based on the histologic spectrum of epithelial-stromal ratio of stromal cellularity and of extent nuclear pleomorphism. Use of such criteria has a precedent in the classification of follicular and odontogenic fibroepithelial neoplasms. This new nomenclature includes "unguioblastoma" for tumors with a predominant epithelial component and "unguioblastic fibroma" for tumors where a cellular stroma is more prominent and characteristic. The term "atypical unguioblastic fibroma" is used to describe a third rare neoplasm, in which the cellular stroma shows nuclear pleomorphism and atypia with an increase of mitotic activity.
Adult↗
Malignant phyllodes tumor of the breast metastatic to the parotid gland diagnosed by fine needle aspiration biopsy. A case report.
BACKGROUND: Phyllodes tumor (cystosarcoma phyllodes) is a rare fibroepithelial neoplasm of the breast. Malignant phyllodes tumor is characterized by an infiltrative border and marked degree of hypercellular stromal overgrowth with > 5 mitoses per 10 high-power fields. Distant metastasis occurs in 10-20% of patients with malignant phyllodes tumor. The most common sites of distant metastases are the lungs, bone and abdominal viscera. Although theoretically any organ may have metastasis, the parotid gland has not been documented before in the English-language literature. CASE: A 40-year-old, Caucasian woman with a history of malignant phyllodes tumor of the left breast presented with a mass on the right side of the parotid gland. Fine needle aspiration biopsy of the mass revealed abundant discohesive spindle cells showing moderate nuclear pleomorphism with occasional mitoses. No epithelial elements were seen. A diagnosis of malignant spindle cell tumor consistent with metastatic malignant phyllodes tumor was made. Histology confirmed the cytologic diagnosis. CONCLUSION: Fine needle aspiration biopsy is accurate and efficient in conjunction with clinical information in the diagnosis of malignant phyllodes tumor of the breast metastatic to the parotid gland.
Adult↗
Malignant phyllodes tumor with heterologous liposarcomatous differentiation and tubular adenoma-like epithelial component.
Phyllodes tumor of the breast is a biphasic fibroepithelial neoplasm. A 30-year-old woman presented with a 1-year history of a palpable, asymptomatic right breast mass without axillary lymphadenopathy and family history of breast carcinoma. Malignant phyllodes tumor was diagnosed. The authors present not previously described histological appearance of this tumor where an epithelial component was identical to that of a tubular adenoma of the breast, with the review of the literature. This is in addition to very rare liposarcomatous stromal differentiation in the malignant phyllodes tumor.
Journal Article↗
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.
Adolescent↗
[Phyllodes tumor and pregnancy. A report of a case].
Phyllodes tumor is a rare breast fibroepithelial neoplasm of the breast, predominant in females (0.3 to 0.5%). Few cases have been described in males. Phyllodes tumor during pregnancy grows fast and its size is relatively big. These tumors can be classified as benign, malignant or neighboring. A 32-year-old patient at 23.4 week of gestation was admitted in the National Institute of Perinatology with a rapidly growing mass in the right breast; diagnosis confirmed by ultrasound study reporting echoic images on right breast, 10 x 10 cm the greatest and 3x3 cm the smallest. A simple mastectomy was performed at the 26.6 week of gestation on the right breast. A possible phyllodes tumour in the right breast was observed during surgery, weight 9.6 pounds, with partial infiltration to major pectoral muscle. Pathology reported a benign phyllodes tumor in the right breast, with surgical borders free of tumor. Phyllodes tumor is rare and can occur during pregnancy. It is unknown if the tumor is hormone-dependent. The growth of a tumor on a subsequent pregnancy is not necessarily associated with recurrency or with a new disorder on the patient, who has had a complete excision.
Adult↗
[Cystosarcoma phylloides of the breast. Analysis of 58 cases].
Cystosarcoma phylloides (c.p.) is a rare fibroepithelial neoplasm of the mammary gland exhibiting considerable histological variations ranging from the aspect of hypercellular fibroadenoma to that of pleomorphic sarcoma. In this study, 58 cases of c.p. were graded according to their histology into 3 groups of increasing malignancy-benign tumors: 23 cases (42%), borderline tumors: 16 cases (27%) and malignant tumors: 18 cases (31%). Their clinical properties and evolution have been compared. These tumors were found exclusively in women, most often during the 5th and 6th decade of life (age range from 19 to 81 years). In two thirds of the cases, the history of the disease was shorter than 6 months. The symptoms were generally scant. Only in 2 cases were severe local lesions observed. The postoperative clinical course has been followed for at least 5 years in 32 instances. Recurrences were observed in 5 patients, the histology being as a rule the same as that of the primary tumor. The 12 patients with benign tumors are well 5 years or more after operation. One of the patients presenting a malignant tumor died of lung embolism soon after mastectomy. 2 out of 10 patients with borderline tumors died within 6 years with metastases of the mammary tumor. Our analysis confirms the experience that c.p. are relatively benign but often recurring neoplasms that rarely disseminate. As far as prognosis and treatment are concerned, tumors of questionable dignity should be considered malignant. To avoid such vague terms as "benign or malignant c.p." we support OBERMANN'S suggested separation of c.p. into "cellular fibroadenoma" and "periductal fribrosarcoma". Wide local excision for small and benign tumors is recommended. All other forms require simple mastectomy. Prophylactic dissection of the axillary lymph nodes is not necessary as these tumors usually disseminate hematogenously. Roentgen therapy or chemotherapeutic agents are not useful in treatment.
Adult↗
Lesions of the breast in children exclusive of typical fibroadenoma and gynecomastia. A clinicopathologic study of 113 cases.
This large series of cases demonstrates that the breast of the child or adolescent is the potential site for a number of interesting lesions exclusive of fibroadenoma and gynecomastia. Adenoma of the nipple, juvenile papillomatosis, and juvenile or cellular fibroadenoma should be correctly diagnosed to insure conservative surgical management and appropriate clinical follow-up. The results of the Juvenile Papillomatosis Registry suggest that this lesion is a morphological marker of potentially more serious breast disease in the future. Recognition of a cellular fibroepithelial neoplasm, especially in young black females, as a cellular fibroadenoma will hopefully eliminate the need for the diagnosis of "benign" cytosarcoma phyllodes. On occasion, the equivocal case may be labeled a "phyllodes tumor fo indeterminate biologic behavior." Those neoplasms with stromal atypia and mitotic activity, overgrowth of stroma with epithelial dissociation, and sarcomatous elements are appropriately designated as cytosarcoma phyllodes. In contrast to vascular tumors of the breast in adults, the majority of vascular lesions in the child's breast are bening and represent either a capillary or a histiocytoid hemangioma. Our experience and reports in the literature support the conclusion that most malignancies of the breast in children are metastatic. Rhabdomyosarcoma was the most common example in our study, but secondary involvement by acute leukemia or malignant lymphoma also occurs.
Adenofibroma↗
Dermoscopy of fibroepithelioma of pinkus.
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Aged↗
Giant myxomatous fibroadenoma of the breast; report of 11 cases.
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Breast↗