Endocrine cells in a normal breast and non-cancerous breast lesion.

The authors confirmed the presence of endocrine cells for the first time in a normal breast as well as in a non-cancerous lesion of the breast. One hundred and eighty-eight blocks of normal breast tissues in 44 cases and 74 blocks of non-cancerous lesions in 35 cases were examined. Argyrophil cells were found in one block from a normal breast and in one block from a phyllodes tumor. Argyrophil cells in the normal breast showed positive reaction to anti-endocrine granule constituent (EGC) antibody with immunohistochemical method. Argyrophil cells found in the phyllodes tumor gave positive reaction to both anti-EGC and anti-serotonin antibodies. The present study is thought to be the first report in the literature of serotonin-positive cells in a non-cancerous breast lesion, a phyllodes tumor.     

Fibroepithelial lesions of the breast with pleomorphic stromal giant cells: a clinicopathologic study of 4 cases and review of the literature

Pleomorphic stromal giant cells are occasionally found as an incidental finding in breast tissue but are only rarely seen in fibroepithelial lesions. In this report, we describe 4 fibroadenoma-like lesions of the breast with pleomorphic stromal giant cells. Two cases had focal stromal hypercellularity, one of which was with architectural features borderline between a fibroadenoma and a phyllodes tumor, but none was considered diagnostic of phyllodes tumor. One lesion had up to 4 mitotic figures per 10 high-power fields, including rare atypical mitotic figures. The remaining 3 cases lacked mitotic activity. Follow-up for 3 cases at 16 to 59 months revealed no evidence of tumor recurrence. The fourth case was lost to follow-up. It appears that the presence of pleomorphic stromal giant cells in an otherwise benign fibroepithelial lesion has no adverse clinical significance. The clinicopathologic features of each case are discussed, and a review of the literature is provided.     

Pseudoangiomatous stromal hyperplasia of the breast-cytological features of two cases and review of literature

Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a lesion characterized on histology by the presence of anastomosing slit like spaces embedded in a hyalinized fibrous stroma. Till date, the cytological features of PASH have been described in only 12 cases, of which two cases were diagnosed on aspiration cytology as suspicious for carcinoma and in one case, for phyllodes tumor. We describe the FNAC findings of two of our cases of PASH. The first case was diagnosed as a phyllodes tumor and the other case as a benign proliferative breast disease, possibly a fibroadenoma. A review of the published literature on cytology of PASH shows the morphological variations that can exist in the cytology smears of this lesion. FNAC findings of PASH are non-specific, and the role of FNAC in PASH is to confirm the benign nature of the lesion, rather than provide a definitive pre-surgical diagnosis.     

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.     

Cell blocks of breast FNAs frequently allow diagnosis of invasion or histological classification of proliferative changes

Two major limitations of breast fine needle aspiration (FNA) compared with core needle biopsies (CNB) are the inability to determine whether a cancer is invasive and to classify proliferative lesions. We studied 40 consecutive "rapid cell blocks" from breast FNAs with surgical pathology follow-up to test whether cell blocks can overcome these limitations. Of 25 carcinomas, invasion could be identified in the cell block sections in 11 (44%). One cystosarcoma phyllodes was suspected based on the cell block sections. Cell blocks from 12 of 14 benign breast FNAs showed sufficient cells to assign a histologic diagnosis of no hyperplasia (1 case, confirmed on follow-up) and usual hyperplasia (11 cases; confirmed in eight of 11 on follow-up). Specific histologic diagnoses included intraductal papilloma (2 cases), and in situ lobular neoplasia (2 cases). Cell blocks complement smears and monolayers and appear to overcome major limitations of breast FNA.     

Malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report

Breast tumors, particularly of stromal origin, containing multinucleated osteoclast-like giant cells (OLGC) are rarely reported in the literature. We report here the first case of a malignant phyllodes tumor associated with OLGC occurring in a 43 year-old African woman who presented with a painful palpable mass of the outer upper quadrant of the right breast. After surgical excision, histological examination showed a malignant phyllodes tumor in which the stromal component displayed evident sarcomatous changes and was densely populated with benign multinucleated OLGC. These cells expressed the CD68 histiocytic marker. No evidence of osseous or cartilaginous differentiation was seen throughout the lesion. This lesion ressembles giant cell tumor of bone. However, the nature of the OLGC is not well precised yet.     

Low-grade periductal stromal sarcoma of the breast with myxoid features: Immunohistochemistry

A 52-year-old woman was admitted with a painful right breast tumor measuring more than 20 cm in largest diameter, which ulcerated the overlying skin. The lesion had appeared 4 years previously but the patient hesitated to seek medical care due to 'fear of cancer'. Microscopically, the tumor was composed of spindle cells that formed cuffs around multiple open tubules and ducts set in an abundant, myxoid stroma. The spindle cells had significant atypia with nuclear pleomorphism, occasional cytoplasmic vacuolation and moderate mitotic activity. The ducts and lobules surrounded by the proliferating tumor cells had minimal distortion, with a pericanalicular growth pattern devoid of the phyllodes pattern. The tumor had a multinodular growth pattern with coalesced and individual tumor nodules, the latter being found mostly at the periphery of the lesion. On immunohistochemistry the tumor cells were positive for smooth muscle actin, CD34, and vimentin, and focally positive for CD10. A diagnosis of low-grade periductal stromal sarcoma (PDSS) with myxoid features was established. PDSS is a distinct low-grade breast sarcoma, the appropriate diagnosis of which requires extensive tumor sampling and additional broad immunohistochemistry. PDSS should not be confused with other spindle cell breast tumors because they require different treatment.     

人体乳腺硬癌癌细胞器形态结构的定量研究

目的:区分乳腺正常细胞器和各期乳腺癌细胞器之间的差异,从而建立检查量化指标。方法:本文对女性乳腺硬癌癌细胞器线粒体,溶酶体的16个形态参数进行体视学统计分析。结果:发现癌细胞与正常细胞比较,其线粒体、溶酶体的体积、表面积和面数密度等形态参数存在高度显著差异和显著差异。结论:探讨了癌细胞的线粒体,溶酶体形态变异与功能之间的关系,为乳腺癌临床诊断提供了重要的定量依据。     

CD10, actin, and vimentin expression in breast phyllodes tumors correlates with tumor grades of the WHO grading system

The discrimination of borderline from malignant primary breast phyllodes (PT) tumor is still unclear. We studied 22 PT cases to investigate the immunohistochemical expression (staining of stromal CD10, SMA [smooth muscle actin], and vimentin) as well as the features of focal glandular atypia to determine whether these correlated with the histopathologic grading system. In our results, the stromal staining of CD10 was positive in 4 of 6 malignant and 2 of 5 borderline PT cases, but negative in all benign PT cases. Stromal actin and intraglandular vimentin-expressive tumor cells were found in 5 of 6 malignant PT cases but not in borderline and benign PT cases. There is a significant difference in the panel of stromal CD10, actin, and vimentin expression between borderline and malignant PT (p<0.05). Besides, the progression of malignant potential breast phyllodes tumor may cause glandular epithelium atypia with loss of polarity.     

Malignant phyllodes tumor with liposarcomatous components: a case report with cytological presentation

Cytological and histological findings of a rare case of a malignant phyllodes tumor (with liposarcomatous components) of the breast are presented. The atypia of the stromal cells and naked nuclei in a lesion considered benign clinically and on imaging alerted us to the possibility of a phyllodes tumor, despite the low cellularity of the preoperative fine-needle aspiration smears. The excisional biopsy was histologically diagnosed as malignant phyllodes tumor with liposarcomatous components. Peculiar atypical cells with large, pale, transparent cytoplasm, or with intranuclear chromatolytic areas similar to intranuclear cytoplasmic inclusions, in addition to atypical lipoblasts revealed in imprint smears from the excised tumor, may be important for cytopathologists to achieve a definitive cytological diagnosis, and also to observe patients over long periods for recurrences and metastasis after surgery for this rare breast tumor.     

Breast stromal fibroblasts from histologically normal surgical margins are pro‐carcinogenic

There is evidence that normal breast stromal fibroblasts (NBFs) suppress tumour growth, while cancer‐associated fibroblasts (CAFs) promote tumourigenesis through functional interactions with tumour cells. Little is known about the biology and the carcinogenic potential of stromal fibroblasts present in histologically normal surgical margins (TCFs). Therefore, we first undertook gene expression analysis on five CAF/TCF pairs from breast cancer patients and three NBF samples (derived from mammoplasties). This comparative analysis revealed variation in gene expression between these three categories of cells, with a TCF‐specific gene expression profile. This variability was higher in TCFs than in their paired CAFs and also NBFs. Cytokine arrays show that TCFs have a specific secretory cytokine profile. In addition, stromal fibroblasts from surgical margins expressed high levels of α‐SMA and SDF‐1 and exhibited higher migratory/invasiveness abilities. Indirect co‐culture showed that TCF cells enhance the proliferation of non‐cancerous mammary epithelial cells and the epithelial‐to‐mesenchymal transition of breast cancer cells. Moreover, TCF and CAF cells increased the level of PCNA, MMP‐2 and the phosphorylated/activated form of Akt in normal breast luminal fibroblasts in a paracrine manner. Furthermore, TCFs were able to promote the formation and growth of humanized orthotopic breast tumours in nude mice. Interestingly, these TCF phenotypes and the extent of their effects were intermediate between those of NBFs and CAFs. Together, these results indicate that stromal fibroblasts located in non‐cancerous tissues exhibit a tumour‐promoting phenotype, indicating that their presence post‐surgery may play important roles in cancer recurrence. © 2013 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.     

Multifocal intrafollicular granulosa cell tumor of the ovary associated with an unusual germline p53 mutation.

A 23-year-old woman presented with a 7 cm right multicystic mass in the ovary, which corresponded microscopically to an unusual lesion consisting of a multifocal granulosa cell tumor with intrafollicular ('in situ') growth involving two-thirds of mature follicles. Stromal invasion was found in only one area where neoplastic follicles coalesced. Granulosa cells had atypical, bizarre TP53 positive nuclei with hyperchromatism, abundant mitoses and numerous hyaline globules. The contralateral ovary was normal. From the age of 10 years, the patient had a complex medical history of multiple tumors, including telangiectatic osteosarcoma, typical and malignant phyllodes tumor, reticulohistiocytoma of skin, carcinomas of the breast and lipo- and leiomyosarcoma. The female genital tract also harbored myometrial leiomyomas and an early endometrial carcinoma. Retrospective histologic study of all mesenchymal neoplasms in this patient showed, the conspicuous presence of similar bizarre TP53 positive cells with hyaline globules in all the mesenchymal neoplasms. In the genetic study, a germline p53 gene mutation was detected in exon 10, codon 336, generating a stop codon in the oligomerization domain of the protein (E336X). A further p53 mutation was found in exon 7 in the granulosa cell tumor. Mutation occurred de novo since there was no history of tumors in any family members, all of whom had a wild-type p53. Although this patient shows a typical tumor phenotype of Li Fraumeni syndrome, the germline mutation corresponded to a highly unusual mutated domain, which is similar to the one found in childhood malignant adrenocortical tumor; also a rare neoplasm that originates in adrenocortical cells; which are closely related, both functionally and embryologically, to granulosa cells.     

The impact of large sections on the study of in situ and invasive duct carcinoma of the breast

Large histologic sections (LHSs) are increasingly used in the study of normal and neoplastic breast tissue. LHSs allow the direct visualization of a large part of the breast glandular tree. Accordingly, LHSs have shown that in situ and invasive lobular carcinoma is a multilobar (and hence multifocal) neoplastic lesion in more than 50% of the cases, and that poorly differentiated duct carcinoma in situ (DCIS grade 3) is frequently unifocal, whereas it is often multifocal when the in situ lesion is a well-differentiated type (DCIS grade 1). Forty-five mastectomies were studied with large sections. Mastectomies were performed when quadrantectomy did not guarantee radical excision of the tumor with adequate cosmesis because of the large size of the lesion or because the neoplastic lesion was located below the nipple. Excluded were cases of lobular neoplasia or invasive lobular carcinoma, because they were reported separately, and cases of mastectomies performed for sarcoma or recurrent phyllodes tumor. All cases had undergone a preoperative diagnostic procedure (fine needle aspiration), and the relative positive material was reviewed. All 45 cases showed in situ duct carcinoma and 37 showed evidence of invasive duct carcinoma. Forty-two cases of DCIS were multifocal, whereas only 4 invasive duct carcinoma were shown as multifocal. When DCIS lesions were subdivided into 3 grades, no statistical significance was seen among the 3 groups of DCIS in regard to multifocality. Nevertheless, DCIS grade 1 was a widespread condition involving more than one lobe and quadrant, whereas DCIS grades 2 and 3 appeared more localized. DCIS grade 1 was more similar to that previously observed in lobular in situ neoplasia/lobular in situ carcinoma. In 66.6% of the cases, DCIS foci were found within the invasive areas, indicating a more than fortuitous occurrence (2-sided P=.0357).     

Argyrophil cells in normal endometrial glands

Summary Normal endometrium from one hundred normal cases were examined histologically, using sections stained with the Grimelius method. Endocrine cells were demonstrated in 4 cases. Immunohistochemically, these cells were positive for anti-serotonin and anti-somatostatin antisera. Argyrophil granules were also observed in supranuclear or subnuclear regions of glandular cells in 17 cases, and argyrophilia was present in the apical region including the brush borders or microvilli of glandular cells in 6 cases. In these latter 23 cases argyrophilia seemed to be nonspecific, having no relation to endocrine type secretory granules, judging from the electronmicroscopic observations on the silver-impregnated sections. The presence of endocrine cells and the pattern of argyrophilia in glandular cells were similar to those found previously in endometrial glandular adenocarcinomas with argyrophil cells. This is the first report on the occurrence of endocrine cells in normal endometrial glands.     

Syk与VEGF-C在乳腺癌中的表达及临床意义

目的:检测Syk与VEGF-C在乳腺癌组织中的表达情况,探讨它们与乳腺癌病理、临床特征间的关系.方法:应用免疫组化Elvsion法检测64例乳腺癌患者手术切除的癌组织和癌周正常组织中Syk和VEGF-C的表达情况.结果:Syk在正常组织中表达的阳性率为90%,在乳腺癌组织中阳性表达率为59.37%;VEGF-C在正常组织中阳性表达率为0.0%,在乳腺癌组织中的阳性表达率为76.56%;二者比较差异均有统计学意义(P＜0.05).Syk与VEGF-C表达水平均与乳腺癌病理分级、临床分期、淋巴结转移有关(P＜0.05).结论:联合检测乳腺癌中Syk和VEGF-C表达水平,对乳腺癌的早期发现及预后判断有一定参考价值.     

"Missed" diagnoses of phyllodes tumor on breast biopsy: pathologic clues to its recognition

Fibroadenoma and phyllodes tumors of the breast exhibit a continuum of pathologic features. We examined phyllodes tumors initially called fibroadenoma for features that may accurately classify the tumor as phyllodes tumor on the first biopsy specimen. The phyllodes tumors initially called fibroadenoma for features that may accurately classify the tumor as phyllodes tumors on the first biopsy specimen are examined. Fifteen patients with phyllodes tumors were studied, initially called FA or another term short of PT. These tumors were compared with 16 true fibroadenomas, all with needle-core biopsy followed by excision. Resected phyllodes tumors were larger on average than fibroadenoma, 6.8 cm (range = 1.7-16.2 cm) versus 2.6 cm (range = 1.0-4.8 cm). In needle-core biopsy cases, sampling was limited, even in large breast masses. p53 and cleaved caspase-3 were noncontributory. Ki-67 showed higher proliferation indices in phyllodes tumors versus fibroadenoma (4.8% vs 0.6%). Features suggesting phyllodes tumors include tissue fragmentation, increased stromal cellularity especially around glands, stromal overgrowth, and increased mitoses. Increased sampling of a large tumor will likely yield more correct diagnoses.     

Malignant phyllodes tumor of the breast with expression of osteonectin and vinculin

Phyllodes tumor is a very rare neoplasm which accounts for 2.5% of all fibroepithelial lesions of the breast. The mesenchymal component of a malignant phyllodes tumor frequently contains heterologous components. We report a case of malignant phyllodes tumor. The patient was a 40-year-old woman with a lump on the left breast. Histological examination revealed the lump to be a malignant phyllodes tumor with foci of liposarcomatous differentiation. The mesenchymal tumor cells, including those in the liposarcomatous components, were found to express vimentin, osteonectin and vinculin. However, they showed no immunoreaction to CAM 5.2, desmin, alpha-smooth muscle actin (ASMA), neuron-specific enolase (NSE) nor S-100. Ultrastructurally, the mesenchymal tumor cells were found to have abundant cytoplasmic organelles, but there was no evidence showing their differentiation to myofibroblasts. Further studies will be necessary to elucidate the significance of vinculin and osteonectin expression in malignant phyllodes tumor.     

Expression of CD34 and bcl-2 in phyllodes tumours, fibroadenomas and spindle cell lesions of the breast

AIMS: Strong expression of CD34 and bcl-2 has been described in solitary fibrous tumours. It has been proposed that these lesions arise from long-lived mesenchymal cells. We tested the hypothesis that spindle cell lesions of the breast arise from similar mesenchymal cells in the mammary stroma. METHODS and RESULTS: Sections of phyllodes tumours (26), fibroadenomas (15), myofibroblastomas (two), pseudoangiomatous hyperplasia (five) and myoid hamartoma (one) were stained immunohistochemically for CD34 and bcl-2. Conventional mammary carcinoma is known to be CD34-negative: we therefore stained 11 spindle cell carcinomas and one adenosquamous carcinoma. The mammary stroma, particularly around lobules, stained for CD34. All the lesions (except the carcinomas) showed spindle cell staining for CD34. There was more staining in fibroadenomas than in phyllodes tumours (especially malignant tumours). The staining in phyllodes tumours was typically patchy. In some there was increased or decreased staining adjacent to the epithelium. There were occasional spindle cells positive for bcl-2 in the normal perilobular stroma. bcl-2 was frequently expressed in spindle cells in fibroadenomas, phyllodes tumours and pseudoangiomatous hyperplasia, and rarely in the other lesions. CONCLUSIONS: The combined expression of CD34 and bcl-2 suggests that fibroadenomas, phyllodes tumours and pseudoangiomatous hyperplasia may arise from long-lived bcl-2-positive mesenchymal cells in the breast in a manner similar to that proposed for solitary fibrous tumours. The absence of CD34 staining in spindle cell carcinomas is of potential diagnostic value in the distinction from malignant phyllodes tumours in difficult cases.