HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance

Ovarian fibroma with metaplastic bone tissue: Case report

Fibromas are benign tumors of the ovary and arising from the stromal component of the ovary. Nearly half of the cases (40%) have tumor bigger than 10 cm in diameter. Only one third of the cases have smaller than 3 cm and they are rarely bilateral (5% of cases) In microscopic examination fibromas consist of cellular bundles and intersecting strips of hyaline-appearing collagen and fibrous tissue. Mitoses are rare, but occasionally fibromas may be hypercellular and/or show substantial mitotic activity. Dystrophic calcifications, focal necrosis and hemorrhage are common. In this report we described a case of unilateral fibroma of ovary that was found incidentally by laparoscopic surgery for chronic pelvic pain with pathologically consisting metaplastic bone tissue. Copyright © 2011 by Türkiye Klinikleri

Chondromatous differentiation in clear cell carcinoma of the ovary: A rare finding challenging the differential diagnosis

Objective: Ovarian surface epithelial tumors rarely have heterologous elements including bone or cartilage that may appear histologically benign or malignant. There are a few case reports in the literature of ovarian tumors containing chondromatous areas. Case: We report a clear cell carcinoma of the bilateral ovary showing chondromatous differentiation in a 56-year-old woman. Histopathologic study of the specimen showed clear cell carcinoma with many small foci of chondromatous differentiation. Immunohistochemical studies demonstrated positivity for S-100 confirming the diagnosis. The patient was alive with disease on chemotherapy for 16 months. Conclusion: A rare case of benign appearing chondromatous differentiation in an ovarian clear cell carcinoma of the ovary is described, and the significance of this finding is discussed. © 2008 Springer-Verlag

Breast A Study of 20 Cases with Histologic Correlation

ObjectiveTo analyze fine needle aspiration cytology (FNAC) mater material from 20 cases of histologically verified medullary carcinoma (MC) of the breast and correlate the cytomorphologic features with histologic appearance to improve the diagnostic sensitivity and specificity of FNAC.Study DesignWe reviewed the cytologic features of 20 cases of MC of the breast in the archives of Ege University Hospital between 1994 and 2006.ResultsTwenty patients with an aspirate and confirmed diagnosis of MC were identified. Patient age was 30-74 years (mean, 48). The initial cytologic diagnoses were positive for cancer in 17 cases, atypical/suspicious for cancer in 2 cases and negative for cancer in 1 case. The cytologic picture was characterized by cellular smears composed of highly atypical epithelial tumor cells in loosely cohesive sheets and lying singly, admixed with polymorphous lymphocytes, plasma cells and neutrophils. Tumor cells had predominantly abundant finely granular, eosinophilic cytoplasm and moderate to marked nuclear pleomorphism with prominent nucleoli. Histologic examination confirmed that 11 cases were atypical MC and 9 were pure MC.ConclusionBreast MC is a rare, distinct category that appears to have rather characteristic cellular features. Familiarity with the cell components is a prerequisite in cytologic accuracy. (Acta Cytol 2009;53:165173

case report and review of the literature

A case of mature cystic teratoma that contained florid vascular proliferation is reported. The ovarian tumor occurred in a 9-year-old girl; symptoms consisted of vomiting, abdominal pain and a palpable mass. The microscopic findings were mostly typical of a mature cystic teratoma, but also abundant vascular proliferation mimicking hemangioma in association with mature neural tissue was observed. There was a disorganized arrangement of medium- and large-sized spaces lined by cuboidal endothelial cells. Immunohistochemical staining for vascular proliferation showed immunoreactivity for CD31 and smooth muscle actin. Florid vascular proliferation may be seen in association with neural tissue of ovarian teratomas and should not be mis-diagnosed as immature teratoma or a vascular neoplasm

Lipoadenofibroma of the endometrium: A rare variant of benign mullerian mixed tumor

Objective: Adenofibroma is a form of mixed mesodermal tumor in which epithelial and stromal components are benign, and usually arises in the endometrium of postmenopausal women. We report a case of lipoadenofibroma of the endometrium that appeared as an intracavitary mass, which is very unusual because endometrioid adenofibroma rarely contains mature adipose tissue, only the second such case described in detail. Case: An endometrial polypoid mass measuring 1,5 cm with maximum diameter was found incidentally during total abdominal hysterectomy for keratinizing large cell carcinoma of the cervix in a 60-year-old woman. The endometrial polypoid mass was found to be a lipoadenofibroma composed predominantly of collagenated fibrous stroma populated by cystically dilated and occasionally crowded glands lined with proliferative endometrium, intermingled with abundant mature adipose tissue. Conclusion: We suggest that uterine adenofibromas with lipomatous areas belong to the family of mixed tumor of Mullerian origin. We discuss the pathogenesis of this entity and review the previously documented similar cases. © 2008 Springer-Verlag

Unilateral salpingitis due to enterobius vermicularis

WOS: 000086376500017PubMed ID: 10782420A case of unilateral salpingitis caused by Enterobius vermicularis presenting as a painful adnexal mass in a 28-year-old woman is reported

Breast A Study of 20 Cases with Histologic Correlation

ObjectiveTo analyze fine needle aspiration cytology (FNAC) mater material from 20 cases of histologically verified medullary carcinoma (MC) of the breast and correlate the cytomorphologic features with histologic appearance to improve the diagnostic sensitivity and specificity of FNAC.Study DesignWe reviewed the cytologic features of 20 cases of MC of the breast in the archives of Ege University Hospital between 1994 and 2006.ResultsTwenty patients with an aspirate and confirmed diagnosis of MC were identified. Patient age was 30-74 years (mean, 48). The initial cytologic diagnoses were positive for cancer in 17 cases, atypical/suspicious for cancer in 2 cases and negative for cancer in 1 case. The cytologic picture was characterized by cellular smears composed of highly atypical epithelial tumor cells in loosely cohesive sheets and lying singly, admixed with polymorphous lymphocytes, plasma cells and neutrophils. Tumor cells had predominantly abundant finely granular, eosinophilic cytoplasm and moderate to marked nuclear pleomorphism with prominent nucleoli. Histologic examination confirmed that 11 cases were atypical MC and 9 were pure MC.ConclusionBreast MC is a rare, distinct category that appears to have rather characteristic cellular features. Familiarity with the cell components is a prerequisite in cytologic accuracy. (Acta Cytol 2009;53:165173

Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous features: a report of 2 cases.

BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs) include both benign and malignant entities, such as benign soft tissue giant cell tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of breast cancer. CASES: We report the cytologic features, pathologic findings and immunohistochemical profile in 2 cases of this unusual variant of breast carcinoma. Two women aged 53 and 50 years women presented with a history of left and right breast lump but no local lymphadenopathy, respectively. Fine needle aspiration cytology (FNAC) of both cases revealed abundant MGC with highly pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous differentiation with multinucleated syncytiotrophoblast-like giant cells is extremely rare in breast tumors. Although rare, FNAC of breast cancer with pleomorphic MGC requires careful search for differential diagnosis; breast carcinoma with giant cell features (choriocarcinomatous features, OGC features) must be differentiated from metastatic tumors and other breast lesions containing giant cells