Fine needle aspiration cytology of a thyroid metastasis of metaplastic breast carcinoma: a case report

BACKGROUND: Metaplastic breast carcinoma is defined as mesenchymal and/or squamous cell components associated with ductal carcinoma. Because of the heterogeneous nature of this tumor, cytologic interpretation on fine needle aspirates can be quite challenging. This is especially true of metastatic lesions of this rare tumor type. Metastasis to the thyroid has not been previously reported. CASE: A 57-year-old woman with a history of metaplastic breast carcinoma for which she underwent mastectomy, chemotherapy and radiation therapy 2 years earlier presented with a fast-growing left thyroid mass with progressive hoarseness and dysphasia. Clinical presentation and findings from a neck computed tomographic scan were strongly suggestive of a primary thyroid malignancy. The aspirate specimen was composed of scant, highly atypical epithelial cells in a background of an abundant chondromyxoid matrix and scattered, benign follicular cells. A literature review confirmed the novelty of this case. CONCLUSION: This case emphasizes the value of clinical information and the importance of generous sampling in achieving a correct diagnosis of metastatic metaplastic carcinoma.     

Metaplastic carcinoma of the breast in an HIV-positive patient: a case report

BACKGROUND: Metaplastic carcinoma of the breast is a rare neoplasm that causes diagnostic difficulty on fine needle aspiration smears. Breast carcinoma in HIV-infected patients occurs at a relatively early age, with increased bilateral disease, unusual histology, and early metastatic spread with a poor outcome. CASE: A case of metaplastic carcinoma of the breast arose in a 36-year-old woman who was seropositive for HIV. In the absence of a sarcomatous component and presence of obvious ductal differentiation on aspirates, a diagnosis of high grade infiltrating duct carcinoma, not otherwise specified, was made on fine needle aspiration cytology (FNAC). CONCLUSION: This case underlines the limitations of FNAC in the diagnosis of metaplastic carcinoma of the breast. It also shows that it is imperative to maintain a high index of suspicion for rare pathologies in immunocompromised patients.     

Fibromatosislike metaplastic carcinoma of the breast as a diagnostic pitfall for fine needle aspiration cytology: a case report

BACKGROUND Metaplastic carcinomas of the breast are uncommon, and most display marked cellular atypia. Recently, a low grade fibromatosis-like metaplastic carcinoma was found and displayed little nuclear atypia. CASE A 74-year-old woman presented with a 2.5-cm, palpable breast nodule. Mammogram was reported as suspicious for malignancy. Cytologic examination revealed smears of low cellularity with most cells lying in clusters and having a round or oval shape. Rare cells had a "spindle" shape. Nuclear features were low grade. Rare individual cells had retained cytoplasm. Lumpectomy revealed a fibromatosis-like metaplastic carcinoma. CONCLUSION: Cytologically, fibromatosis-like metaplastic carcinomas are low grade lesions producing smears of relatively low cellularity. Separation from ductal carcinomas is necessary because fibromatosis-like metaplastic carcinomas rarely metastasize to lymph nodes.     

Medullary breast carcinoma: prognostic implications of p53 expression

Medullary breast carcinoma (MBC) is a rare pathological type of breast cancer. The rate of p53 protein accumulation is higher in MBC than in common invasive ductal carcinoma. Whether this particular feature of MBC influences the outcome after treatment is unknown. We retrospectively analyzed the characteristics, treatment and outcome of 71 patients with MBC treated between 1981 and 1996. The median age was 51 years (range 27-81) and the median clinical tumor size was 25 mm (range 0-70 mm). Breast-conserving treatment was offered when possible: 55 patients had undergone a tumorectomy and radiotherapy while 16 patients had undergone a mastectomy. p53 protein accumulation was determined by immunohistochemistry on paraffin-embedded tumor specimens from 58/71 samples available for this study. The median follow-up for the 56 survivors was 113 months (range 30-241). The 10-year survival and metastasis-free survival rates were 81% and 81.4%, respectively. The local recurrence rate was 16.4%. The two factors predicting outcome were pathological axillary node involvement in the 60 patients who underwent axillary dissection and adjuvant chemotherapy. p53 accumulation was found in 33/58 patients (57%). p53 status was not predictive of survival nor of distant or local recurrences. We confirm that medullary breast carcinoma has a favorable prognosis despite its aggressive pathological features. p53 protein accumulation, found in the majority of MBCs, was not related to outcome.     

Identification of BCOX1, a novel gene overexpressed in breast cancer

The identification of tumor-associated antigens, which are specifically expressed in cancer tissues, is of utmost important for immunotherapy of breast cancer. We have combined in silico screening and experimental expression analysis to identify genes that are differentially expressed in breast carcinomas compared with their corresponding normal tissues. Using these approaches, we identified a novel gene, BCOX1, with overexpression in breast carcinoma. BCOX1 was highly homologous to KIAA0100, a hypothetical gene located on chromosome 17q11.2. RNA in situ hybridization shows that BCOX1 mRNA signal is mainly located in the cytoplasm of breast carcinoma epithelial cells, but not in those of normal epithelial cells, stroma cells and lymphocytes. Furthermore, mRNA expression of BCOX1 was moderately elevated in ductal in situ carcinoma (DCIS), peaked in invasive breast carcinoma (IBC) and metastatic breast carcinoma cells (MET) whereas absent in benign ductal epithelial cells. The predicted BCOX1 open reading frame of 666 bp encodes a putative protein of 222 amino acid residues with a calculated molecular weight of 2,4920 Da and a PI of 5.86. Computational analyses predict that the putative BCOX1 protein is a cytoplasmic protein. The functional relevance of this novel gene is yet to be determined. This study warrants further investigations to explore the molecular functions of BCOX1, and to determine its potential diagnostic and therapeutic applications for breast cancer.     

Clinicopathological Features and Prognosis of Metaplastic Breast Carcinoma: Experience of a Major Chinese Cancer Center

Metaplastic breast carcinoma (MBC) is a rare heterogeneous group of primary breast malignancies, with low hormone receptor expression and poor outcomes. To date, no prognostic markers for this tumor have been validated. The current study was undertaken to evaluate the clinicopathologic characteristics, the response to various therapeutic regimens and the prognosis of MBCs in a large cohort of patients from Tianjin Medical University Cancer Hospital in China. Ninety cases of MBCs diagnosed in our hospital between January 2000 and September 2014 were retrieved from the archives. In general, MBCs presented with larger size, a lower rate of lymph node metastasis, and demonstrated more frequent local recurrence/distant metastasis than 1,090 stage-matched cases of invasive carcinoma of no specific type (IDC-NST), independent of the status of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expressions. The five-year disease-free survival (DFS) of MBC was significantly worse than IDC-NST. Using univariate analysis, lymph node metastasis, advanced clinical stage at diagnosis, high tumor proliferation rate assessed by Ki-67 labeling, and epidermal growth factor receptor (EGFR) overexpression/gene amplification were associated significantly with reduced DFS, while decreased OS was associated significantly with lymph node metastasis and EGFR overexpression/gene amplification. With multivariate analysis, lymph node status was an independent predictor for DFS, and lymph node status and EGFR overexpression/gene amplification were independent predictors for OS. Histologic subtyping and molecular subgrouping of MBCs were not significant factors in prognosis. We also found that MBCs were insensitive to neoadjuvant chemotherapy, routine chemotherapy, and radiation therapy. This study indicates that MBC is an aggressive type of breast cancer with poor prognosis, and that identification and optimization of an effective comprehensive therapeutic regimen is needed.     

Cytologic diagnosis of male breast cancer with nipple discharge. A case report

The cytologic findings in a nipple discharge from a male patient with breast cancer are described. Malignant epithelial cells and cell clusters believed to be derived from ductal carcinoma were observed. The subsequent mastectomy specimen contained a ductal carcinoma with minute foci of stromal invasion.     

Differentiation of tumours of ductal and lobular origin: I. Proteomics of invasive ductal and lobular breast carcinomas

The vast majority of invasive breast tumors are ductal and lobular breast carcinomas. Despite the many similarities, some clinical follow-up data and the patterns of metastases suggest that these histological subtypes of breast cancer are biologically distinct. Few papers, however, describe immunohistochemical markers useful for differentiation of these carcinomas. Many investigations suggest that E cadherin protein expression is lost in lobular but not in ductal carcinoma. The absence of E-CD, as a partial loss of epithelial differentiation, may account for the extended spread of lobular carcinoma in situ and the peculiar diffuse invasion mode of invasive lobular carcinoma. Some investigations report the significance of E-CD associated proteins alpha-, beta-, gamma-catenin expression, as well as the usefulness of cytokeratins 5, 6, 8, 7 and thrombospondin in differentiating histological types of breast invasive carcinomas. Several reports have suggested the possibility that invasive ductal and lobular cancers differ with respect to expression of antigens involved in proliferation and cell cycle regulation. It has been shown that vascular endothelial growth factor expression, also the expression of maspin, a tumour suppressor gene product, is higher in ductal, than in lobular carcinoma. Expression of NKX3.1, a member of the NK-class of homeodomain, is highly restricted and is found primarily in lobular carcinoma. Some histological and immunohistochemical characteristics of pleomorphic lobular carcinoma are also discussed.     

Fine needle aspiration cytology of high grade mucoepidermoid carcinoma of the breast: a case report

BACKGROUND: Primary mucoepidermoid carcinoma of the breast is a very unusual tumor. It is often misdiagnosed, masquerading under different diagnoses. The cytologic assessment is especially difficult when the lesion is high grade. One reported case was initially diagnosed by fine needle aspiration cytology. CASE: A 69-year-old woman presented with a 6 x 4-cm tumor located in the upper outer quadrant of the right breast. The first cytologic diagnosis suggested ductal carcinoma with atypical squamous metaplasia; further review disclosed that the clusters of epithelial ductal cells displayed a mixed pattern of glandular, squamous and intermediate cells. There also was a scant intracellular and extracellular mucous substance, confirming the diagnosis of mucoepidermoid carcinoma. Histochemistry and immunohistochemistry, performed on the tumor and lymph node metastases, showed cellular staining for periodic acid-Schiff, and keratin, epithelial membrane antigen and carcinoembryonic antigen demonstrated the epithelial origin. The high expression of Ki-67, as well as the finding of 24 metastasized nodes in the axilla, demonstrated the tumor's aggressiveness. CONCLUSION: Fine needle aspiration cytology is a very reliable tool in achieving a fast and accurate diagnosis of primary mucoepidermoid carcinoma of the breast.     

Aquaporin-5: a marker protein for proliferation and migration of human breast cancer cells

Aquaporin (AQP) is a family of transmembrane proteins for water transport. Recent studies revealed that AQPs are likely to play a role in tumor progression and invasion. We aimed to examine the potential role of AQP5 in the progression of human breast cancer cells. Expression of AQP5 mRNA and protein was seen in human breast cancer cell line (both MCF7 and MDA-MB-231) by RT-PCR and immunoblotting analysis. Immunoperoxidase labeling of AQP5 was observed at ductal epithelial cells of human breast tissues. In benign tumor, AQP5 labeling was mainly seen at the apical domains of ductal epithelial cells. In contrast, in invasive ductal carcinoma, prominent AQP5 labeling was associated with cancer cells, whereas some ducts were unlabeled and apical polarity of AQP5 in ducts was lost. Cell proliferation (BrdU incorporation assay) and migration of MCF7 cells were significantly attenuated by lentivirus-mediated AQP5-shRNA transduction. Hyperosmotic stress induced by sorbitol treatment (100 mM, 24 h) reduced AQP5 expression in MCF7 cells, which was also associated with a significant reduction in cell proliferation and migration. Taken together, prominent AQP5 expression in breast cancer cells with the loss of polarity of ductal epithelial cells was seen during the progression of breast carcinoma. shRNA- or hyperosmotic stress-induced reduction in AQP5 expression of MCF7 cells was associated with significantly reduced cell proliferation and migration. In conclusion, AQP5 overexpression is likely to play a role in cell growth and metastasis of human breast cancer and could be a novel target for anti-breast cancer treatment.     

Immunohistochemical localization of apelin in human normal breast and breast carcinoma

The peptide apelin is a high-affinity ligand for the G-protein coupled receptor APJ. Apelin/APJ signaling plays important roles in blood pressure regulation, body fluid homeostasis, and cardiovascular development. More recently, it has been recognized that apelin/APJ signaling may also be involved in tumor angiogenesis. Studies in experimental animals have shown that apelin is abundantly secreted in the milk, and the mammary gland contains high level of pre-proapelin mRNAs and apelin protein. High level of apelin mRNA is expressed in cultured human breast carcinoma cell line (Hs 578T). However, the status of apelin expression and localization in human breast carcinoma has not been studied. In the present study immunohistochemistry was performed to investigate the expression and localization of apelin in normal human breast tissue and breast carcinoma. Cytoplasmic apelin immunoreactivity was detected in the ductal and lobular epithelial cells and vascular endothelial cells of the normal breast tissue. The myoepithelial cells were negative. The malignant tumor cells of invasive ductal or lobular carcinoma also expressed similar level of immunoreactive apelin. The fuctional significance of apelin expression in normal nonlactating breast and breast carcinoma warrants further investigation.     

Fine needle aspiration cytology of lactating adenoma of the breast. A comparative light microscopic and morphometric study

Six cases of lactating adenoma of the female breast diagnosed by fine needle aspiration (FNA) were reviewed. The FNA cytologic diagnostic features included a usually moderately cellular aspirate with an abundant foamy background material, intact epithelial lobules or acini and small groups and solitary epithelial cells that contained uniform nuclei, fine chromatin and prominent nucleoli. When present, the cytoplasm was finely vacuolated or wispy; many nuclei appeared stripped of their cytoplasm. These features were compared light microscopically with the cytopathologic features of six cases of invasive well-differentiated ductal adenocarcinoma, seven cases of invasive lobular carcinoma, one case of granulocytic sarcoma and one case of primary histiocytic lymphoma of the breast. In addition, cytomorphometric analysis demonstrated no statistically significant differences in the nuclear areas of lactating adenoma as compared with those of well-differentiated ductal carcinoma and lobular carcinoma.     

Malignancy-associated changes in breast tissue detected by image cytometry.

In several tissues, nuclear differences have been described in normal-appearing cells from patients with invasive carcinomas compared to cases without invasive carcinoma, a phenomenon known as malignancy-associated changes (MACs). The aim of this study was to determine the presence of malignancy-associated changes in breast tissue. Image cytometry was performed on Feulgen stained tissue sections of patients with usual ductal hyperplasia with (n = 30) or without (n = 41) adjacent invasive breast carcinoma. Nuclear features of normal-appearing cells as well as of usual ductal hyperplastic cells were separately compared between the two groups. Many features of normal-appearing epithelial cells were significantly different between cases with and without invasive cancer. Significant differences were also found by measuring ductal hyperplastic nuclei instead of normal-appearing nuclei. Cases with or without cancer could be distinguished with a classification accuracy of 80% by discriminant analysis using 2 nuclear features derived from ductal hyperplastic cells. In conclusion, image cytometry on breast tissue sections shows that malignancy-associated changes can be found in normal as well as in usual ductal hyperplastic breast cells. This could be clinically relevant for the detection of occult breast cancer, for the prediction of risk in these lesions, and to monitor the effect of chemopreventive agents.     

The cytospectrophotometric study of the DNA content in benign and malignant processes in the breast]

Cytospectrophotometric analysis of DNA content in nuclei of the epithelial cells in fibroadenoma, fibroadenomatous and breast cancer revealed that mean value of DNA content in breast cancer is reliably higher than in benign processes in breast. Modal class in fibroadenoma and fibroadenomatous formed by di- and tetraploid cells, in breast cancer-tetraploid and higher depending on histological structure of tumor. Ratio of aneuploidy is higher in invasive ductal carcinoma and scirrhus [correction of skir] in comparison with invasive lobular carcinoma and other carcinomas, that evidences higher aggressiveness of these tumors.     

Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters

Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178+/-12 for fibroadenoma; 275+/-11 for DCIS; 299+/-10 for grade I IDC; 251+/-10 for grade II IDC; and 314+/-11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors.     

E-cadherin和Cathepsin D的表达与乳腺导管癌的侵袭和淋巴结转移的关系

目的　观察上皮性钙粘素 (E cadherin)和组织蛋白酶D (CathepsinD)在乳腺导管癌中的表达并分析其与肿瘤侵袭及腋下淋巴结转移的关系。方法　应用免疫组织化学方法检测E cadherin和CathepsinD在乳腺导管癌组织中的表达。结果　乳腺导管原位癌 (carcinomainsitu ,CIS)组织中E cadherin的表达与浸润性导管癌 (infiltratingductalcarcinoma ,IDC)相比无明显差异 (P >0 0 5 )。乳腺导管癌腋下淋巴结阴性组 (nodenegativeductalcarcinoma,NNDC)中E cadherin的表达与腋下淋巴结阳性组 (nodepositiveductalcarcinoma ,NPDC)相比差异不明显 (P >0 0 5 )。乳腺导管癌间质中CathepsinD的表达CIS与IDC相比差异显著 (P <0 0 1) ,NNDC与NPDC相比差异显著 (P <0 0 5 ) ;而在癌细胞中CathepsinD的表达在上述两组中差异均不明显 (P >0 0 5 )。结论　E cadherin在乳腺导管癌的表达与肿瘤的侵袭及淋巴结转移无相关关系。CathepsinD在乳腺导管癌间质的表达与肿瘤的侵袭及淋巴结转移密切相关 ,可作为临床判定肿瘤恶性程度的一个参考指标。     

Establishment and characterization of two human breast carcinoma cell lines by spontaneous immortalization: Discordance between Estrogen, Progesterone and HER2/neu receptors of breast carcinoma tissues with derived cell lines

Background

Breast cancer is one of the most common cancers among women throughout the world. Therefore, established cell lines are widely used as in vitro experimental models in cancer research.

Methods

Two continuous human breast cell lines, designated MBC1 and MBC2, were successfully established and characterized from invasive ductal breast carcinoma tissues of Malaysian patients. MBC1 and MBC2 have been characterized in terms of morphology analysis, population doubling time, clonogenic formation, wound healing assay, invasion assay, cell cycle, DNA profiling, fluorescence immunocytochemistry, Western blotting and karyotyping.

Results

MBC1 and MBC2 exhibited adherent monolayer epithelial morphology at a passage number of 150. Receptor status of MBC1 and MBC2 show (ER⁺, PR⁺, HER2⁺) and (ER⁺, PR^-, HER2⁺), respectively. These results are in discordance with histopathological studies of the tumoral tissues, which were triple negative and (ER^-, PR^-, HER2⁺) for MBC1 and MBC2, respectively. Both cell lines were capable of growing in soft agar culture, which suggests their metastatic potential. The MBC1 and MBC2 metaphase spreads showed an abnormal karyotype, including hyperdiploidy and complex rearrangements with modes of 52–58 chromosomes per cell.

Conclusions

Loss or gain in secondary properties, deregulation and specific genetic changes possibly conferred receptor changes during the culturing of tumoral cells. Thus, we hypothesize that, among heterogenous tumoral cells, only a small minority of ER⁺/PR⁺/HER2⁺ and ER⁺/PR^-/HER2⁺ cells with lower energy metabolism might survive and adjust easily to in vitro conditions. These cell lines will pave the way for new perspectives in genetic and biological investigations, drug resistance and chemotherapy studies, and would serve as prototype models in Malaysian breast carcinogenesis investigations.