Current views on cervical intraepithelial neoplasia.
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Carcinoma in Situ↗
Biomedical subjects
C H Buckley
Publications and source records attributed to C H Buckley.
Lipid-rich residual bodies in human myometrium: qualitative observations.
Uterine leiomyomata and histologically normal myometrium were examined by light and electron microscopy. All myometrial samples contained smooth muscle cells with distinctive cytoplasmic inclusions located at the nuclear poles. These were seen in only one case in routine paraffin wax sections, where they appeared as clear vacuoles, but they were more obvious in epoxy resin sections stained with toluidine blue. Staining with Oil Red O and for acid phosphatase was positive at the site of the vacuoles. In ultrathin sections, these structures possessed a single membrane and contained abundant lipid droplets, with a sparse, coarsely granular matrix. They were designated as lipid-rich residual bodies. Such organelles were all but absent from leiomyomata. Lipid-rich residual bodies with the features described here have not been studied in detail before in smooth muscle cells of the human myometrium. The possibility that they arise from the cyclical stimulation of lipid synthesis by ovarian hormones is discussed.
Acid Phosphatase↗
Do AgNOR counts reflect cellular ploidy or cellular proliferation? A study of trophoblastic tissue.
There is considerable debate as to whether AgNOR counts reflect cellular ploidy or cellular proliferation. Trophoblastic tissue from hydropic abortions and from hydatidiform moles offers an excellent model for analysing this problem. Thus, complete moles show considerable cell proliferation but are diploid, whilst partial moles show markedly less cell proliferation but are triploid: hydropic abortuses are diploid and show no cellular proliferation. AgNOR counts in villous cytotrophoblastic cells from hydropic abortions and from complete hydatidiform moles are similar, but those in partial hydatidiform moles are 50 per cent higher than in either hydropic abortions or complete moles. Thus, in non-neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation.
Abortion, Spontaneous↗
Serum PP14 levels in a patient with Turner's syndrome pregnant after frozen embryo transfer.
Data are presented on serum levels of the pregnancy-associated placental protein (PP14) in an XO mother, pregnant after frozen embryo transfer. Steroid replacement before and during early pregnancy was provided with transdermal oestradiol and vaginal micronized progesterone. Characterization of a pre-treatment cycle indicated a physiological response by the endometrium. The pregnancy was associated with normal maternal blood levels of all hormones considered responsible for maintenance of early gestation but with consistently subnormal serum levels of PP14. Hitherto, PP14 has been believed to be an endometrial protein arising from the decidua during pregnancy, under the influence of ovarian steroids. The findings in this case suggest that other factors are involved in its production, possibly under the control of, or originating from, the maternal ovary.
Adult↗
Nucleolar organiser regions in normal, hyperplastic, and neoplastic endometria.
Nucleolar organiser regions (NORs) can be visualised by a silver stain that shows NOR-associated proteins as black intranuclear dots (AgNORs). NORs are loops of DNA that transcribe to ribosomal RNA, and the number of AgNORs is thought to reflect cellular proliferative activity. A study of AgNOR counts in normal, hyperplastic, and neoplastic endometria is reported. The highest AgNOR counts were found in normal proliferative endometrium and in well-differentiated endometrioid adenocarcinomas that were invading the myometrium. A mean AgNOR count of greater than 9 in curettage material from an atypical proliferative lesion of the endometrium is highly suggestive of an invasive neoplasm.
Adenocarcinoma↗
Current problems in the pathology of intra-epithelial lesions of the uterine cervix.
Problems in the interpretation and diagnosis of intraepithelial lesions of the uterine cervix include interobserver differences in respect of grading, uncertainty as to the significance of human papillomavirus infection and debate about the current terminology. The role of human papillomaviruses in cervical intra-epithelial neoplasia (CIN) remains unclear and the specific type of virus present does not correlate closely with the behaviour of these lesions. There are defects in the current terminology and in proposed new terminology for CIN; it is suggested that the term 'borderline CIN' should be introduced in cases where there is uncertainty as to whether or not CIN 1 is superimposed on a flat condyloma.
Cervix Uteri↗
Tamoxifen and endometriosis. Case report.
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Adult↗
Experience with a 'physiological' steroid replacement regimen for the establishment of a receptive endometrium in women with premature ovarian failure.
Eighteen women with a premature menopause underwent assessment of serial serum oestradiol (E2) and progesterone levels and endometrial histology and function. Patients received continuous transdermal E2, and progesterone either orally or vaginally for 14 days. Physiological levels of E2 were attained. Significantly higher levels of progesterone were achieved with vaginal progesterone (P less than 0.01). Endometrial biopsies obtained during E2 replacement demonstrated normal proliferative features. Expression of an oestrogen related antigen (ER-Ag) was localized in the cytoplasm of the epithelium. After 3 days of progesterone replacement the endometrium showed normal secretory features and expression of ER-Ag in the stroma as well as in the glands. After 7 days of progesterone supplementation, vaginal administration produced a more consistent physiological appearance than oral administration. Thus transdermal E2 combined with vaginal progesterone is a highly satisfactory combination for establishing a physiological endometrium in women with premature ovarian failure.
Administration, Intravaginal↗
Five year follow-up and dose delivery analysis of cisplatin, iproplatin or carboplatin in combination with cyclophosphamide in advanced ovarian carcinoma.
Eighty eight patients with FIGO stage IIb/c (postoperative residual) or III/IV epithelial ovarian cancer were randomised to receive cycles of cyclophosphamide (600 mg/m2) with either iproplatin (240 mg/m2), cisplatin (100 mg/m2) or carboplatin (300 mg/m2). A total of six cycles were given at monthly intervals. Patients were well-balanced for major prognostic factors. There was no significant difference in overall response rate (iproplatin arm, 64.3%, cisplatin arm 72.7% and carboplatin arm 66.7%). There were more complete remissions on the carboplatin arm, 45.8% compared with 21.4% on iproplatin and 22.7% on cisplatin but the difference was not statistically significant (p = 0.11). With a median follow up of 50 months the median survival for the iproplatin arm is 18 months, for the cisplatin arm 19 months and for the carboplatin arm 24 months (p = 0.15). Toxicity was greatest with cisplatin and least with carboplatin. Myelotoxicity limited the dose delivery of iproplatin as measured by total dose, dose intensity and dose intensity product. Carboplatin is at least as effective and less toxic than cisplatin when used in conjunction with cyclophosphamide for the treatment of ovarian carcinoma, and this analogue has been selected for dose intensification studies in this tumour at the Christie Hospital.
Adult↗
Luteal phase defect: the possibility of an immunohistochemical diagnosis.
Monoclonal antibody D9B1 has been shown to bind to a carbohydrate epitope associated with high molecular weight secretory sialoglycoprotein(s) of human endometrium. The authors demonstrate that, in a group of 28 patients diagnosed on the basis of histopathologic assessment as exhibiting luteal phase defect, 68% reveal significantly diminished expression of the epitope. Furthermore, histologic assessment of the secretory activity in single glands does not correlate simply with the level of expression of the epitope. Of specimens from patients complaining of infertility, 92% showed defective production of the D9B1 epitope. Thus, D9B1 immunohistochemistry provides a new molecular criterion for defective endometrial function.
Antibodies, Monoclonal↗
Subinvolution of the uteroplacental arteries in the human placental bed.
Subinvolution of the uteroplacental arteries of the placental bed is a recognized cause of post partum haemorrhage causing significant morbidity. Whilst the physiological changes in these arteries during pregnancy and the part played by endovascular trophoblast migration are well documented, the sequence of events during involution and the pathophysiology of subinvolution are unknown. Using immunohistochemical techniques we have studied uteroplacental arteries in the placental bed in 25 cases of post partum haemorrhage and compared the subinvoluted vessels with normally involuted vessels. Non-involuted vessels were present in 22 test cases; these abnormal vessels were filled with thrombus and no endothelial lining was detected. Extravillous perivascular trophoblast was usually present in the walls of these abnormal vessels and in some cases was seen in an endovascular position. Subinvolution of placental site vessels may represent an abnormal interaction between maternal uterine cells and fetal trophoblast.
Adult↗
The role of postoperative alkylating agent therapy in early-stage epithelial ovarian cancer.
Forty-six patients with early (Stage I and II) ovarian cancer referred as free of residual disease after primary surgery, selected for high-risk features, were treated with adjuvant single-agent alkylating therapy comprising either intravenous cyclophosphamide (1 g/m2) in 36 patients, or oral melphalan (0.2 mg/kg daily for 5 days) in eight. Cyclophosphamide was repeated every 3 weeks for 10 cycles and melphalan every 6 weeks for 12 cycles. With a median follow-up of 36+ months, 18 patients have relapsed. The actuarial 5-year relapse-free survival was 48% and the overall 5-year survival was 54%; median survival was 84 months. Pretreatment FIGO stage was the single most important predictor of relapse-free and overall survival duration. For patients with Stage IA and IB tumours the 5-year actuarial relapse-free survival was 89%; for patients with stage IC and II (all substages), the 5-year relapse-free survival was 24% (P = 0.001). For this latter group adjuvant single alkylating agent therapy was not adequate and alternative therapeutic regimens are required. The problem of suboptimal primary surgical staging is also addressed.
Administration, Oral↗
Is needle aspiration of ovarian cysts adequate for diagnosis?
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Biopsy, Needle↗
Pathological prognostic indicators in cervical cancer with particular reference to patients under the age of 40 years.
The presence of lymph node metastases in patients with cervical cancer is an important predictor of death and recurrence of disease. Lymph node metastases are more common in patients with mucus-secreting carcinomas than in women with pure squamous carcinomas even in what appears, clinically, to be early stage disease: such neoplasms are more frequent in women under the age of 40 years. The recognition of mucus secretion in a carcinoma and the detection of vascular permeation adjacent to the primary neoplasm identifies the patient at greatest risk of having pelvic lymph node metastases.
Adenocarcinoma↗
Placentation in the fallopian tube.
The processes of implantation and placentation have been studied in 105 tubal pregnancies. Successful placentation occurred only with plicomural or mural implantations and in these the early development of the placenta occurred in the tube in exactly the same way as it does in the uterus, although tubal placentation was usually membranaceous in nature, possibly because of an inadequate blood supply. Invasion of the placental bed by interstitial extravillous cytotrophoblast occurred in the tube in the same manner as it does in the uterus whereas extravillous trophoblast invaded tubal vessels in the same fashion as it does the spiral arteries in the uterus. Subsequent development of the placenta in the tube differed from that in the uterus in so far as villous invasion of the tubal tissues, with consequent development of the placenta in the subserosa or on the serosa, was common. The ability of the blastocyst to implant in the tube with subsequent normal placentation indicates that these processes are purely a function of trophoblastic tissue, with maternal tissues playing only a passive role.
Decidua↗
The prognostic significance of lymphatic vascular space invasion in endometrial adenocarcinoma.
In a histopathological review of 171 cases of endometrial adenocarcinoma, 42 neoplasms demonstrated lymphatic and/or vascular invasion. This finding was significantly correlated with depth of myometrial involvement and stage of disease at operation. Tumour cell type, and histological grade were correlated to a much lesser extent, whilst the patient's age bore no relation. Prognosis was significantly poorer in patients whose adenocarcinomas had invaded lymphatic and/or vascular spaces compared to those whose neoplasms had not. These observations emphasize the importance of considering lymphatic/vascular invasion in staging endometrial adenocarcinomas.
Adenocarcinoma↗
An immunohistochemical study of steroid binding by endometrial glandular epithelial cells throughout the menstrual cycle.
An immunohistochemical technique was used to demonstrate oestrogen and progesterone binding by endometrial glandular epithelial cells at various stages of the menstrual cycle. A cross-section of steroid binding sites, including low affinity, concentration dependent Type II and III binding sites, were demonstrated but only in cells which contain the classical high affinity receptor. The technique demonstrated both free binding sites and receptor-hormone complexes within the cytoplasm but was poorly effective in demonstrating nuclear complexes. Oestrogen binding sites were shown to reach a peak during the late proliferative and early secretory phases of the cycle: oestrogen binding capacity remained high during the mid and late secretory phases. Progesterone binding capacity rose progressively throughout the proliferative and early secretory phase.
Adult↗
An immunohistochemical study of the incidence and significance of human gonadotrophin and prolactin binding sites in normal and neoplastic human ovarian tissue.
An immunoperoxidase technique has been utilised for the demonstration of follicle stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PRL) binding sites in normal human ovaries and in a wide range of benign and malignant epithelial tumours of the ovary. The incidence of FSH, LH and PRL binding was, respectively, 32%, 41% and 39% in normal ovaries, 30%, 18.5% and 22.5% in benign epithelial tumours and 51%, 32% and 43% in malignant epithelial neoplasms. The incidence of FSH binding was significantly higher in malignant epithelial neoplasms than in either normal ovaries or benign epithelial tumours but otherwise no correlation was found between hormone binding capacity and the degree of malignancy of epithelial ovarian tumours, the histological type of the tumour, the degree of differentiation of the malignant epithelial tumours or the presence or absence of metastatic disease. Well differentiated malignant tumours did, however, tend to stain more strongly than did poorly differentiated neoplasms, thus suggesting that the number of binding sites per cell tends to decrease with decreasing degrees of differentiation.
Adenocarcinoma↗