Anette Lynge Nielsen

Malignant giant cell tumor of synovium and locally destructive pigmented villonodular synovitis: Ultrastructural and immunohistochemical study and review of the literature

The first reported case of an intraarticular malignant giant cell tumor of synovium studied with electron microscopic and immunohistochemical examination is presented, together with a case of diffuse intraarticular pigmented villonodular synovitis with extensive bone destruction. The malignant case was dominated by uniform cells positive for histiocytic markers, the fine structure showing a gradual change from cells dominated by organelles serving a secretory function to cells with phagocytic activity. The reported cases of giant cell tumor of the tendon sheath indicate that the pertinent histologic changes regarding malignancy are an increase in cell polymorphism and in the number of mitoses, and a decrease in the number of multinucleated giant cells.

Plasma oestrogens in postmenopausal women with endometrial cancer

Objective To study plasma levels of oestrogens and androgens, sex hormone‐binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer.

Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: Correlations with stage and other clinicopathologic features

Abstract OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely ( p p CONCLUSION: The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior.

Evaluation of the reproducibility of the revised 1988 international federation of gynecology and obstetrics grading system of endometrial cancers with special emphasis on nuclear grading

An intraobserver and interobserver analysis of the reproducibility of the revised 1988 International Federation of Gynecology and Obstetrics (FIGO) grading system of endometrial cancers was performed in 47 endometrial cancers (94 biopsy specimens). In the revised FIGO grading system the growth pattern still serves as the basic parameter, but nuclear atypia inappropriate for the architectural grade, raises the grade by 1. Ninety‐four slides were graded twice by two pathologists. Analysis by the kappa statistics (corrected for agreement by chance) showed an acceptable result for interobserver reproducibility: kappa value 0.65 (95% confidence interval, 0.480 to 0.818). Further study showed this to be a reflection of the reproducibility of the architectural grade: kappa 0.70 (95% confidence interval, 0.565 to 0.850), whereas the reproducibility of the nuclear grade was poor: kappa value 0.55 (95% confidence interval, 0.383 to 0.713). Review of the literature showed great variability in the definition of nuclear grading, indicating that the revised 1988 FIGO grading system is not applicable as standard of reference for studies of endometrial cancers, before agreeing to the definition of inappropriate nuclear atypia. Cancer 68:2303–2309, 1991.

Estrogen and progesterone receptors in endometrial carcinoma: comparison of immunohistochemical and biochemical analysis.

SummaryIn 159 endometrial carcinomas, estrogen (ER) and progesterone receptors (PR) were determined biochemically by dextran-coatcd charcoal (DCC) assay and immunohistochemically (ICA) on frozen sections. ICA receptor content was estimated by a total histologie score (HSCORE), including all tissue components, and by a cancer HSCORE, including malignant cells only. These scores were closely correlated. A single biopsy was found to be representative for each tumor. ER-DCC status was positive in 90.3% and PRDCC status in 92.2% of the tumors. ER total HSCORE was positive in 47% and PR total HSCORE in 89% of tumors. ER and PR correlated inversely with tumor grade (p < 0.001). Correlations were found between ER and PR content determined by either method (DCC: r = 0.77; ICA: r = O.SO), as well as between DCC and ICA content (ER: r = 0.52; PR: r = 0.76). The association between DCC and ICA was affected by the tumor grade: the DCC values decreased relatively more than total HSCOREs with increasing grade. The sensitivity of ICA against DCC assay was 56% for ER and 86% for PR. Maximal agreement between receptor status as determined by ICA and by DCC would result from a DCC cutoff level of 130 fmol/mg for ER and 114 fmol/mg for PR.

Human papillomavirus type 16/18 in uterine cervical adenocarcinoma in situ and adenocarcinoma a study by in situ hybridization with biotinylated DNA probes

The distribution of human papillomavirus (HPV) DNA type 16/18 in the paraffin sections of 11 adenocarcinomas (AC), 4 adenocarcinomas in situ (AIS), and 2 adenosquamous carcinomas (AC/SCC) of the cervix was examined by in situ hybridization (ISH) with biotinylated DNA probes (B‐probes). Four AC, four AIS, and one AC/SCC were positive. These results show that B‐probes are an acceptable alternative to both ISH with radiolabeled probes and Southern blot hybridization (SBH), which are difficult to apply in routine pathologic laboratories. Cervical tissues infiltrated with endometrial AC were negative for HPV DNA 16/18, and it is suggested that the presence of HPV DNA 16/18 in uterine AC may be helpful in discriminating cervical AC from endometrial AC.

Expression of epidermal growth factor receptors in human endometrial carcinoma

SummaryLittle data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent at the cell membranes, with a varying pattern in individual carcinomas. EGF-R expression was not correlated with histologie grade, surgical stage, or estrogen/progesterone receptor status evaluated immunohisto-chemically or biochemically in adjacent tissue sections of the tumor. Ten of 13 (77%) atrophic/inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas.

Expression of MIB-1 (paraffin ki-67) and AgNOR morphology in endometrial adenocarcinomas of endometrioid type.

Cell kinetic information is an important adjuvant to histologic grading and to stage in some malignant tumors. Some studies have shown that in endometrial carcinomas, flow cytometric S-phase correlates with known prognostic parameters. In the current study, the expression of silver-stained nucleolar organizer regions (AgNORs) and MIB-1 (ki-67-paraffin) was assessed on paraffin sections in 112 endometrial adenocarcinomas of endometrioid type (EC) (49 hormone users, 63 nonusers). The AgNOR morphology correlated significantly with MIB-1, mitotic count, and nuclear and architectural grade, but not with stage or previous hormone treatment. MIB-1 correlated with all the above parameters except myometrial invasion and stage. Only myometrial invasion and stage correlated with short-term outcome; in such cases tumors from hormone users and nonusers were pooled. The median MIB-1 value was significantly lower in EC from hormone users compared with EC from nonusers; moreover, when tumors from hormone users and nonusers with poor outcome were examined separately, only 29% (four of 14) of the tumors expressed MIB-1 less than the medians in the respective groups, indicating that a prognostic cutoff point may be different in the two groups. Because hormone replacement therapy is very common, this observation has implication for future studies of growth fraction in EC. This is the first study to show that AgNOR morphology is significantly correlated with other markers of growth fraction and histologic grade.

Malignant bronchial oncocytoma: case report and review of the literature.

An oncocytoma of the bronchus with an infiltrative growth pattern and a lymph node metastasis were examined by light and electron microscopy. Lobectomy, with removal of all tumor-bearing tissue, was the only treatment. Two years after surgery the patient had no local recurrences or metastases.

Endometrial adenocarcinoma of endometrioid subtype with squamous differentiation: an immunohistochemical study of MIB-1 (ki-67 paraffin), cathepsin D, and C-erbB-2 protein (p185).

Differences in the immunohistochemical expression of Cathepsin D, C-erbB-2 protein (p185), and growth fraction (MIB-1) in glandular and squamous epithelium in adenocarcinoma of endometrioid subtype were studied together with Cathepsin D in macrophages. The findings were correlated with conventional prognostic parameters. A search for human papilloma virus (HPV) (probes 6/11, 16/18, and 31/33/51) by in situ hybridization was also performed. Formalin-fixed and paraffin-embedded tissues from 61 adenocarcinomas with > 10% squamous epithelium were studied. MIB-1 was very low in squamous epithelium, no correlation was found between MIB-1 in squamous and glandular epithelium, and only the glandular epithelium correlated with depth of invasion and stage, indicating that glands are most important with regard to prognosis. Cathepsin D expression in macrophages was significantly increased in advanced stage and may be of prognostic value, but more studies on tissue sections are needed to evaluate the relationship between its expression in tumor cells and other cells. p185 showed no value as a prognosticator. Finally, our study found HPV infrequently in endometrial carcinomas.