Efficacy of the Isaacs Endometrial Cell Sampler in the cytologic detection of endometrial abnormalities

The efficacy of the Isaacs Endometrial Cell Sampler to obtain specimens for cytologic examination to detect both hormonal disturbances and precursors of malignancy of the endometrium was assessed in 120 symptomatic women. Correlation of the cytologic results with the histologic diagnosis on curettage specimens showed a diagnostic accuracy of 96.3%. The cytologic criteria for diagnosing samples obtained with the Isaacs device are presented.     

The exfoliating cervical epithelial surface in dysplasia, carcinoma in situ and invasive squamous carcinoma. I. Scanning electron microscopic study.

The exfoliating epithelial surface in cone specimens of the human cervix with histologically normal epithelium, squamous metaplasia, dysplasia, carcinoma in situ and in cervical biopsies with invasive squamous carcinoma was studied by scanning electron-microscopy (SEM). A cobblestone-like surface with anisovillosis seems to herald the appearance of malignant cells on the exfoliating epithelial surface. Post-scanning histologic examination served as a diagnostic reference for the SEM findings.     

The "suspicious" gynecologic smear

"Suspicious" gynecologic smears from 842 patients over a seven-year period were analyzed for their causes and outcomes. The frequency of the cytologic diagnosis of "suspicious" ranged between 0.5% in 1979 and 1.44% in 1975 of all smears examined. Review of the smears showed that this classification was used to report a variety of conditions, including equivocal possible precancerous changes as well as the presence of severe inflammation, degenerative or atrophic changes, abnormal glandular cells and metaplasia. The cytologic follow-up, following anti-inflammatory or hormonal therapy, showed a conversion to negative findings in 65.1% of all cases, usually within 12 months. In 294 cases, histologic analysis became necessary, revealing precancerous changes or cancer in 147 patients (17.5% of the study group). Smears of postmenopausal women with suspicious glandular or endometrial cells received special analysis. Significant numbers of such cases had histologic findings positive for malignancy (20% of smears with glandular cells and 21.3% with endometrial cells), as did also smears showing post-irradiative changes (34.6%) or atrophic and degenerative changes (17.1%). Therefore, "suspicious" smears in these groups were considered to indicate an increased risk of malignancy. A regimen for the proper management of cases with "suspicious" smears has been established.     

An estrogen-regulated protein in normal and malignant endometrium

The presence and distribution of a protein with a mol. wt of 24,000 (24K) was determined in endometrial biopsies from regularly cycling women and in women with endometrial carcinoma. This protein, of as yet unknown function and originally found in a breast cancer cell line, was detected by immunohistochemistry using a monoclonal antibody. In regularly cycling women, the 24K protein began to appear in the glandular epithelium during the late proliferative phase and decreased after ovulation. In contrast, in the superficial epithelium, the strongest immunostaining was observed during the secretory phase. Superficial epithelial cells expressed maximal 24K immunoreactivity around day 21 of the cycle and it was clearly seen in the bulbous projections of the apical cytoplasm. These results suggest that the 24K protein may be a marker for hormonal events in the endometrium during the menstrual cycle. In endometrial carcinoma, 24K was correlated with low tumor histologic grade, few mitotic figures, few nucleoli and a low degree of nuclear pleomorphism. These data suggest that 24K may be a potential marker of tumor differentiation.     

Colonic cytology. A retrospective study with histopathologic correlation

Three hundred sixty cytologic specimens obtained by colonoscopic brushing from 336 patients were compared with biopsy specimens simultaneously obtained for histologic examination. Of the cytologic specimens, 160 (44%) were positive for malignant cells, 37 (10%) contained suspicious cells, 54 (15%) had atypical glandular cells, 107 were cytologically negative, and 2 were considered unsatisfactory. Eight-four percent of the patients with cytologically positive smears and 54% of those with suspicious smears had malignant neoplasms in the simultaneously obtained tissue biopsies. Of the patients with follow-up, all with cytologically positive findings and nine with suspicious findings on the initial cytologic examination and simultaneous negative tissue biopsies, were subsequently found to have carcinoma of the colon. Cytology proved to have a sensitivity of 0.73 and a specificity of 1.00 while tissue biopsy showed a sensitivity of 0.81 and a specificity of 1.00. By combining the two methods, the sensitivity increased to 0.92. It is concluded that cytologic examination of colonic brushings is a highly accurate and reliable technique for the detection of malignant neoplasms of the colon and can preempt the use of biopsy forceps.     

Immunohistological localization of human endometrial secretory protein, 'pregnancy-associated endometrial alpha 2-globulin' (alpha 2-PEG), during the menstrual cycle

The distribution of alpha 2-PEG, a human analogue of beta-lactoglobulin, in endometrium at different phases of the cycle was determined using immunohistochemistry with monoclonal and polyclonal antibodies. In the epithelial cells of glands in the functional zone of the endometrium, alpha 2-PEG was first detectable from Days 19 to 21 during the mid-luteal phase and maximal immunostaining was observed during the end of the late luteal phase. Intense staining in the glandular secretions and weaker staining in surface luminal epithelial cells during this period were observed. A minor population of basal glands contained alpha 2-PEG during the follicular phase. These results suggest that alpha 2-PEG synthesis by the glandular epithelium of the regenerated endometrium is hormonally regulated. Maximal staining occurring during the late luteal phase suggests that regulation may be related to the hormonal requirement for pre-decidualization rather than that required for histologically defined glandular epithelial secretion.     

Immunohistochemical localization of P-glycoprotein in adult human ovary and female genital tract of patients with benign gynecological conditions

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein, which mediates active cellular efflux of certain cytotoxic agents. Two mouse monoclonal antibodies (MAb), C219 and JSB-1, were used to identify P-glycoprotein in frozen tissue from the female genital tract of 14 women with benign gynecological conditions; multiple samples from several sites in the genital tract were available from seven patients. P-glycoprotein was detected in the ovarian surface epithelium in four of 14 cases, in the Fallopian tube in three of five cases, in occasional epithelial cells of the endometrial glands in two of five cases, in some endocervical glandular epithelium in three of five cases, in ectocervical squamous epithelium in one of the two cases, and in luteinized cells of the eight cases in which a corpus luteum was present in the specimen. Positive staining with these two MAb was also observed in some endothelial cells in the cortex of the ovary and in the stromal tissue of the myometrium, endometrium, and endocervix. These studies suggest that, if epithelial ovarian cancers are derived from the surface epithelial cells of the ovary, a small proportion of the cancers might be expected to retain the phenotype found in non-cancerous cells and to express P-glycoprotein.     

Significance of nipple discharge clinical patterns in the selection of cases for cytologic examination

The cytodiagnostic significance of the clinical patterns (types and sites) of nipple discharges was studied in 5,305 cytologically examined discharges from 3,687 women in a consecutive series of 50,181 self-referred women in whom 1,062 breast cancers were detected. The clinical patterns were correlated with cytologic and histologic results in both the whole series and in 119 biopsied cases, and the relative risk of association with breast cancer was calculated for each pattern. As a whole, aside from the pattern, cases with nipple discharges showed a higher relative risk (48.5) than did asymptomatic cases, but a bloody nipple discharge was by far more frequently associated with cancer than was any other pattern, being present in 70% of the cancer cases and in almost all cancer cases with suspicious cytologic findings in the discharge smear. The presence of a nipple discharge, being associated with a higher risk of breast cancer, is an indication for a careful physical examination; systematic cytologic examination should be limited only to bloody discharges. Since cancer is rare in cases with nonbloody discharges and is difficult to detect in cytologic smears of such discharges, systematic cytologic examination of all nipple discharges would not be cost-effective.     

Cytologic characteristics of Wilms' tumors in fine needle aspirates. A study of ten cases

The cytologic findings observed in fine needle aspiration (FNA) biopsy smears from ten cases of Wilms' tumor are reported. Blastemal cells, small, round cells with slightly oval nucleoli and fine, evenly dispersed chromatin, were recognized in all cases. Stromal (90%) and epithelial components (40%) were also present. Additional recognizable features were anaplasia (in two of three cases having histologic anaplasia), rosettes (four cases), necrosis (six cases) and inflammatory cells (six cases). In six cases, small fragments of tissue were also recovered for histologic examination after paraffin embedding. There were no complications attributable to the procedure. FNA cytology may be used as the sole diagnostic procedure for Wilms' tumors when preoperative chemotherapy protocols are in use.     

Intraoperative cytologic crush preparation findings in craniopharyngioma: a study of 72 cases

OBJECTIVE: To describe the intraoperative crush preparation and the cytologic features of craniopharyngioma and the differential diagnosis. STUDY DESIGN: Twelve cases of craniopharyngioma were diagnosed by crush preparation cytology in the Department of Pathology, Shiraz Medical School, and formed the basis of this study. The patients' ages ranged from 7 to 43 years; 3 were female and 9 male. The cytologic findings together with the histologic findings were studied. RESULTS: All cases had a high yield of cells, consisting of honeycomb sheets of epithelial cells with and without palisading rows of cells, papillary clusters, squamous cell clusters, anucleated squames, calcification, multinucleated giant cells, cholesterol crystals, glandular or rosettelike structures, ciliated columnar cells and spindle cells. The smears were diagnosed as suggestive of craniopharyngioma. Histologic sections confirmed the cytologic diagnoses. CONCLUSION: Intraoperative cytologic crush preparation findings are helpful in the diagnosis of craniopharyngioma, when combined with clinical information. Crush preparation cytology is important in the diagnosis of central nervous system tumors.     

Psammoma bodies in fine needle aspirates from thyroids containing nontoxic hyperplastic nodular goiters

Psammoma bodies present in fine needle aspiration (FNA) smears with typical cytologic features of colloid goiter from five patients raised the possibility of coexistent papillary carcinoma. However, subsequent careful histologic examination of the entire thyroidectomy specimens did not show occult carcinoma in any of the cases. The psammoma bodies were identified in the stroma next to the foci of papillary hyperplasia in each case. They were small, often equal in size to or slightly larger than the follicular epithelial cell nuclei, and could be misinterpreted as epithelial cell nuclei. These findings suggest that the presence of psammoma bodies in an FNA smear cytologically consistent with a colloid goiter should raise the possibility of coexistent papillary hyperplasia or neoplasia. However, because of the strong statistical association of psammoma bodies with malignant thyroid neoplasms, histologic confirmation is mandatory in such cases.     

Immunocytochemical studies on the distribution pattern of daunomycin in rat gastrointestinal tract

The cancer drug daunomycin is used in treatment of leukemia but possesses severe side effects that involve the gastrointestinal tract. We therefore used a newly developed immunocytochemical procedure to determine the distribution of DM in the gastrointestinal tracts of rats after i.v. injection. Two hours after injection, DM was diffusely distributed in nuclei and most parts of the cytoplasm of intestinal epithelial cells. The cytoplasmic immunoreactivity for DM was most pronounced in small granules of the apical cytoplasm. Sixteen hours after injection, DM immunostaining was by and large absent in the villous epithelium but persisted in the intestinal crypts. In addition, staining was also detected in endothelial cells, scattered cells of the lamina propria and in smooth muscle cells. After 5 days, only little staining for DM remained. Similar findings were made in the colon. In the gastric mucosa, DM accumulation persisted at 16 h in some glandular cells but was lost from the surface epithelium. No staining was detected in saline-injected control rats. The distribution of DM accumulation correlated partially with the distribution of apoptotic cells as detected by the TUNEL procedure. Our results pinpoint that DM may exert prolonged effects on glandular and regenerative cells of the gastrointestinal tract—an observation that may explain the gastrointestinal toxicity of the drug. It seems possible that DM accumulation in surface epithelial cells is rapidly cleared through drug transporters.     

The Human Endometrium Expresses the Glycoprotein Mucin-1 and Shows Positive Correlation for Thomsen-Friedenreich Epitope Expression and Galectin-1 Binding

Mucin 1 (MUC1) is a glycoprotein in human endometrium and is abundant at the luminal epithelial surface in the receptive phase. It has a highly glycosylated ecto-domain that contains keratan sulfate chains, that disappears at the time of implantation. In addition, the glycoforms on MUC1 differ in fertile and infertile women. Therefore the aims of this study were investigations on glycosylation of MUC1 with the Thomsen-Friedenreich (TF) epitope on normal human endometrium throughout the menstrual cycle and binding of galectin-1 on the TF epitope in the endometrium and the expression of galectin-1 on the human oocyte. Human endometrial tissue was obtained from 54 premenopausal patients and was immunohistochemically analyzed with monoclonal antibodies against MUC1, TF epitope, galectin-1, and biotinylated galectin-1. In addition, human oocytes were analyzed for TF, galectin-1 expression, and galectin-1 binding. We identified a significant upregulation of MUC1 and TF epitope and, in addition, galectin-1 binding in glandular epithelium and epithelial apical surface tissue from proliferative to secretory phase. With double staining experiments, we identified a coexpression of TF and MUC1 in the early secretory phase and galectin-1 binding to TF during the same period of time. In addition we identified TF epitope and galectin-1 expression plus binding on the human oocyte and irregularly fertilized oocytes. Upregulation of TF epitope on the glandular epithelium and epithelial apical surface tissue in the secretory phase and binding of galectin-1 at the same time show the possibility of galectin-1–mediated trophectoderm binding to the endometrium within the window of implantation. (J Histochem Cytochem 57:871–881, 2009)     

Polymorphous low grade adenocarcinoma of the salivary gland. Diagnosis by fine needle aspiration cytology

OBJECTIVE: To describe the fine needle aspiration cytology findings of polymorphous low grade adenocarcinoma of the salivary gland. STUDY DESIGN: The authors reviewed the cytologic findings of 5 cases of polymorphous low grade adenocarcinoma. All cases were confirmed by histologic examination. RESULTS: All cases showed similar cytologic findings. The smears had high cellularity with a population of mixed epithelial and myoepithelial cells. These cells formed branching papillae, sheets and clusters. The epithelial cells were uniform, with round to ovoid nuclei; absent or inconspicuous nucleoli; and a moderate amount of dense cytoplasm. Occasionally the cells formed spherical structures containing hyaline globules. Myxoid matrix, either dispersed in the background or interspersed with the cellular elements, was also seen often. CONCLUSION: Polymorphous low grade adenocarcinoma should be cytologically differentiated from adenoid cystic carcinoma, monomorphic adenoma and pleomorphic adenoma. Recognition of subtle cytologic features. may be useful in the differential diagnosis.     

Fine needle aspiration cytologic findings of breast mucinous neoplasms: differential diagnosis between mucocelelike tumor and mucinous carcinoma

OBJECTIVE: To report the cytologic findings of mucocelelike tumor and mucinous carcinoma. STUDY DESIGN: All mucinous neoplasms diagnosed by fine needle aspiration and confirmed by histologic examination were reviewed to detect the cytologic findings helpful for the differentiation. The cytologic findings were correlated with the histologic findings. RESULTS: Cytologically, mucinous carcinomas were highly cellular and showed many single epithelial cells and variably formed epithelial cell clusters in abundant extracellular mucin. Malignant cells exhibited round, atypical nuclei; granular chromatin; and small nucleoli. Mucocele like tumor showed low cellularity with scanty, monolayered, small sheets of epithelial cells and abundant, extracellular mucin. Myoepithelial cells were present within the epithelial cell sheets. Tumor cells were usually small, with uniform, round nuclei; fine chromatin; and absence of nucleoli. CONCLUSION: Cytologic findings of mucocelelike tumor and mucinous carcinoma were different in cellularity, shape of cell clusters and nuclear features, although mucocelelike tumors having a carcinoma component were similar to mucinous carcinoma. Awareness of the cytologic findings of breast mucinous neoplasms is important to make a specific diagnosis.     

Cytologic study of the tissue repair cells of the uterine cervix. With special reference to their origin.

In order to characterize tissue repair cells (TR) of the uterine cervix and clarify their origin, exfoliated cells obtained after laser conization for early cervical lesions were examined. One specimen was first examined by Papanicolaou staining and then examined for epithelial membrane antigen (EMA) and vimentin by immunocytochemical staining, using a restaining method. The other specimen was observed by phosphotungstic acid-hematoxylin (PTAH) staining. Morphologic findings on TR were investigated together with the histologic findings on the wound healing process. TR were classified morphologically into three groups: stromal (STR), epithelial (ETR) and of unknown origin (UTR). Validity of this classification was confirmed by the findings of immunocytochemical staining with EMA and vimentin. These cells appeared one to eight weeks after laser conization. TR with relatively large nuclei, or atypical TR (ATR), appeared when each type of TR was most plentiful, at two to five weeks. Regarding the origins of each TR, cytologic and histologic findings could be considered to offer evidence that ETR originated with hyperplasia of immature cells of the squamous epithelium or reserve cells below the columnar epithelium. The presence of myofibrils in cytoplasm, demonstrated by PTAH staining for STR and some UTR, strongly suggested the possibility that these cells were myofibroblasts in granulation tissue.     

Immunohistochemical localization of beta1 and beta4 integrins in mouse endometrium during implantation and early pregnancy

Implantation presents the remarkable synchronisation between the development of embryo and differentiation of endometrium. Cell-cell adhesion is an important phenomenon taking place during blastocyst implantation in uterine membrane. We think that the investigation of existence and the level of integrins in women can be a guide for treatment of infertility. Our purpose in this study was to show expression beta1 and beta4 integrins on gestational days 4, 6, 12 by immunohistochemical methods and to investigate whether beta4 integrin is a useful marker for receptivity. beta1 and beta4 integrin were exhibited on surface epithelium on gestational day 4. On the other hand, strong beta4 immunoreactivity was detected on surface epithelium and glandular cells on gestational day 12 but no beta1 reactivity was present in the surface epithelium and glandular cells on day 12. In conclusion, both beta1 and beta4 integrins may have a role in implantation process because positive immunoreactivity was seen on apical membrane of surface epithelium on day 4 when implantation occurred. The localization to apical pole of surface epithelium suggest a role for beta1, beta4 integrins in initial embryo and endometrium interaction. It does not seem that beta1 integrin has a role supporting pregnancy since expression of beta4 on surface epithelium and glandular epithelium disappeared on day 12. beta4 integrin expression increasing on day 12 of pregnancy leads us to think a possible functional role supporting pregnancy.     

Cytology of peritoneal washings in gynecologic patients. Diagnostic criteria and pitfalls

A total of 226 peritoneal washing specimens obtained from gynecologic patients over a three-year period was reviewed. The diagnostic problems encountered were: differentiating reactive mesothelium from low-grade malignancies; distinguishing between benign ovarian tumors, ovarian tumors of borderline malignancy and low-grade ovarian malignancies; and potential false-positive diagnoses in endometriosis. Low-grade malignancies could be distinguished from reactive mesothelium by evaluating subtle cytologic criteria and by comparing the cells to those of the tumor on histologic section. The differentiation of low-grade epithelial malignancies from benign epithelial lesions caused difficulties that could only be resolved by evaluating the histologic material. Positive peritoneal washings increased the stage in 8 of 110 patients undergoing initial surgery for gynecologic malignancy. Two of 76 patients undergoing a second-look laparotomy had positive washings without histologic evidence of tumor. These ten patients did less well than did those with similar histology but negative washing cytology, despite receiving additional therapy because of the cytologic findings.     

Immunohistochemical assessment of prostaglandin H-synthase in bovine endometrial biopsy samples collected throughout the oestrous cycle

The study was designed to determine the distribution of prostaglandin H-synthase (PGS) also known as cyclooxygenase in specific uterine cell populations during the oestrous cycle. Endometrial biopsy samples were obtained from a total of 10 clinically healthy cows at days 1 (initiation of behavioural oestrus), 8, 15, and 19 of the oestrous cycle. All animals conceived after biopsy regimen. Data of semiquantitatively scored immunoreactivities were analysed using analyses of variance, t-tests for paired data and correlation analyses. Biotin-streptavidin-peroxidase immunostaining technique was employed to localise PGS. Specific staining was consistently present in endothelial cells of arteries but not capillaries and venules. A gradient of staining intensity was clearly apparent within the endometrium: surface epithelial cells and stromal cells located near the endometrial surface are consistently stained more intensely than glandular epithelial cells and stromal cells lying deeper in the endometrium. Days of oestrous cycle also influenced PGS immunoreactivities. Generally, higher immunoreactivities were recorded in surface epithelium, uterine glands and endometrial stromal cells at cycle days 1 and 19 as compared to cycle days 8 and 15. Minimal scoring values were mainly found at cycle day 8. The results of the present study suggest that the amount of bovine endometrial PGS varies considerably with the day of cycle in the above mentioned cell-type- and location-restricted manner. Therefore, the capacity of the bovine uterine mucosa for prostaglandin production may—amongst other factors—depend on the cycle-restricted availability of the respective enzyme systems.     

False "false-positive" results in diagnostic cytology

With the introduction of transbronchial brushings and fine needle aspiration biopsy, which enable us to obtain samples directly from lesions, the diagnostic potential of cytology for the detection of malignancy, including early cancer, has been greatly enhanced. From 1976 to 1982, five positive cytology reports were initially considered to be "false positives" on the basis of negative gross findings, benign operative biopsies or negative histologic findings in the resected surgical specimens. However, these proved to be false "false positives," based upon the clinical follow-up or further examination of the surgical specimens. Presentation is made of three of these cases with positive cytologic findings and initially negative histologic diagnoses, with an analysis of the causes of the latter. From our experience, four types of cancerous lesions seem prone to being missed during gross examination, namely: any small cancer with a consistency similar to that of the parenchyma of the organ in which the tumor is located, superficially invasive carcinoma, scar cancer and a radiologically occult lung cancer in the presence of a coexisting radiologically demonstrable lesion. With more clinical application of these cytologic methods, false "false positives" are expected to occur more often.