Collagen balls in cervical smears. A previously undescribed finding

OBJECTIVE: To evaluate several conventional cervical smears obtained from women undergoing routine screening for cervical dysplasia or carcinoma and whose smears contained structures resembling collagen balls. STUDY DESIGN: Between 1995 and 1998, cervical smears containing collagen balls were analyzed. The clinical histories of the patients whose smears contained collagen balls, including the gestational history, were reviewed. Histopathologic material from any related surgical specimens was reviewed, with special attention to mesothelial surfaces. RESULTS: Collagen balls were found in 5 of 77,891 Pap smears examined (0.006%). None of the patients had evidence of neoplasms of the genital tract. One of the patients was in the first trimester of pregnancy. CONCLUSION: We suggest that collagen balls in cervical smear originate in mesothelium-covered organs, from where they are transported via the fallopian tubes into the uterine cavity. Their significance lies in their being mistaken for mucin-distended cells exfoliated from a neoplasm or from detached fragments of a papillary ovarian neoplasm.     

Screening for cervical cancer: a new scope for general practitioners? Results of the first year of colposcopy in general practice.

A survey was carried out over one year of all the women who attended a colposcopy clinic in a general practice. During the year 1254 women underwent cytological screening in the practice and 197 of these underwent colposcopy. Of 79 women with abnormal smears that suggested cervical intraepithelial neoplasia, 62 (79%) were confirmed by biopsy to have cervical premalignancy. In addition, the remaining 118 women with normal or inflammatory smears underwent colposcopy either because of their history or because they requested the investigation. A general underestimate of cervical intraepithelial neoplasia when cytology alone was used was discovered. Seven out of 28 women with inflammatory smears were found to have important cervical premalignancy. Mildly dyskaryotic smears led to a falsely reassuring estimate of the degree of severity of cervical lesions. Seven out of 13 patients who underwent colposcopy because they were thought to be at high risk of neoplasia because of a history of genital warts, unexplained recurrent cystitis, heroin abuse, or immunosuppression had cervical intraepithelial neoplasia proved at biopsy. This report shows that both in screening for and in the follow up of known cervical disease a normal smear cannot guarantee normal pathology. Diagnostic colposcopy is a valuable complementary investigation that could be carried out in a general practice.     

Quinquennial cervical smears: every woman's right and every general practitioner's responsibility.

Out of 558 women aged 16 to 64 who were registered with one general practitioner, 459 were eligible to be screened for cervical cancer. Even though the practice had been taking cervical smears for many years, they were predominantly from women under 35. Of the eligible women between 35 and 64, 111 (37%) had never had a smear. After short term intensive screening the uptake rates, defined by a smear done within the past five years, rose to 100% for women under 35, 94% for those aged 35 to 64, and 96% for all eligible women. Screening was rewarding both in its clinical yield and in the income generated by item of service payment. The success of screening was largely due to the participation of practice nurses in taking smears, and to a new method of recording smear results and claims for them. Some women, however, refused to have cervical smears.     

The Irrigation Smear—A New Cytodiagnostic Technique for the Detection of Cancer of the Uterine Cervix

Using the Davis cytopipette, cytologic smears were prepared from 2014 patients; 1367 of these specimens were obtained by the patients themselves. The series included 57 cases of carcinoma or atypia of the cervix, and 50 (88%) of these cases were found to have abnormal cells in the irrigation smear.Cytopipette samples were obtained by a nurse from 647 Eskimos, but cell preservation in this group was not satisfactory because of a delay of several weeks in preparing the smears. Accurate results depend also on specific training of the personnel reading the smears because fewer cells may be present in these smears than in cervical scrape smears.The irrigation smear is recommended as a reasonably accurate method of screening women for cancer of the cervix if they are not being examined regularly by the cervical scrape method. Hospital admissions of females may be a fruitful source of such cases.     

Diagnostic value of Gram stain for assessment of vaginal smears during pregnancy

The main aim of this study was to compare the diagnostic value of Giemsa stained method with Gram stained method for the evaluation of vaginal smears among pregnant women. A study population comprised 111 pregnant between 6 and 30 weeks of gestation. The vaginal smears from every subject was diagnosed according to Giemsa and Gram stained method and micro-organisms were isolated by culture. In 29.3% cases diagnosed as normal flora (2a) on the basis of Giemsa method bacterial vaginosis was detected in Gram stains according to Spiegel's criteria and pathological microflora in concentration > or = 10(5) CFU/ml was cultured among 75.9% of them. Among 31.7% women who had grade 3a (abnormal) in Giemsa stains method normal flora was diagnosed on the basis on Gram's method and from 17.1% pregnant women from this group we did not isolated any pathogens. For evaluation of vaginal smears during pregnancy the Giemsa method should be replaced by Gram stained method.     

Cytological Changes Associated With Tubo-Endometrioid Metaplasia of the Uterine Cervix

Two women who had undergone previous cervical surgery for the treatment of glandular intraepithelial neoplasia (GIN) and cervical intraepithelial neoplasia (CIN), were found to have severely dyskaryotic cells of glandular and metaplastic type in follow-up cervical smears. A third patient was found to have similar abnormal cells in a routine screening smear. All of the patients were subjected to either hysterectomy or cervical conization and in all cases histological examination showed tubo-endometrioid glands in the endocervix, well away from the uterine isthmus, with no associated endometrial stromal tissue. All of the cervical smears were reviewed and cytological features that facilitate the distinction between tubo-endometrioid metaplasia and squamous or glandular dyskaryosis were identified. These features include the smaller size of affected cells, more marked nuclear hyperchromasia, inconspicuous nucleoli, the formation of glandular structures, the lack of discrete squamous dyskaryosis and the absence of the typical 'feathering' noted with GIN. the possibility of tubo-endometrioid metaplasia should be considered when atypical glandular or metaplastic cells are noted in cervical smears, particularly, but not exclusively, in women who have been treated for CIN or GIN. In the presence of these changes clinicians should rebiopsy the cervix before embarking on further unnecessary surgery which may adversely affect fertility and pregnancy, particularly in younger patients.     

P bodies promote stress granule assembly in Saccharomyces cerevisiae

Recent results indicate that nontranslating mRNAs in eukaryotic cells exist in distinct biochemical states that accumulate in P bodies and stress granules, although the nature of interactions between these particles is unknown. We demonstrate in Saccharomyces cerevisiae that RNA granules with similar protein composition and assembly mechanisms as mammalian stress granules form during glucose deprivation. Stress granule assembly is dependent on P-body formation, whereas P-body assembly is independent of stress granule formation. This suggests that stress granules primarily form from mRNPs in preexisting P bodies, which is also supported by the kinetics of P-body and stress granule formation both in yeast and mammalian cells. These observations argue that P bodies are important sites for decisions of mRNA fate and that stress granules, at least in yeast, primarily represent pools of mRNAs stalled in the process of reentry into translation from P bodies.     

The preparation of additional smears from a cervical scrape: impact on the rate of detection of cervical neoplasia

The preparation of additional smears from a cervical scrape: impact on the rate of detection of cervical neoplasia It has been known for some time that only a proportion of the cells on the smear-taking device is transferred to the slide. This can give rise to errors in reporting although the smear may have been taken correctly. This study was undertaken to identify a quick and simple method of improving the accuracy of the Papanicolaou test. A conventional smear and five additional smears were obtained from 62 women attending a Genito-Urinary Medicine clinic. The cell content of the conventional smears and the additional smears was compared. Dyskaryotic cells were detected both in the conventional smear and in the first and second additional smears from 22 women. Dyskaryotic cells were detected in the first and second additional smears only in five women. Thus, the conventional smear failed to detect biopsy-confirmed cervical abnormality in these women. A cell count of the first additional smear in the five cases where the conventional smear was negative showed that they contained, on average, 310 dyskaryotic cells. The preparation of one additional cervical smear per cervical scrape could significantly increase the accuracy of the cervical smear test by 11% (P=0.025, McNemar's test).     

Evaluation of p16INK4a in cervical lesion of premenopausal and postmenopausal women

Pap smears of postmenopausal women are often misdiagnosed because of the difficulty in distinguishing atrophic epithelial cells groups only by morphological criteria. In this study we investigated the diagnostic application of immunocytochemical staining of p16INK4a on conventional Pap smear. A total of 137 cervical specimens were enrolled in this study, of which 77 and 60 cervical smears were taken from premenopausal and postmenopausal women, respectively. Two cervical smears were taken simultaneously in 68 women, one for conventional cytology and the other for immunostaining. Additional 69 cervical smears were taken from the archive, decolorized and then used for immunostaining. In premenopausal women 1 out of 14 (7.1%) with negative cytology, 7 out of 24 (29.2%) with low grade squamous intra-epithelial lesion (LSIL), all 35 (100%) with high grade squamous intraepithelial lesion (HSIL) and all 4 (100%) with squamous cell carcinoma (confirmed by histopathology) had positive staining to p16INK4a. In postmenopausal women p16INK4a positivity was observed in 4 out of 7 (57.1%) cases of LSIL, 12 out of 14 (85.7%) cases of HSIL and all 4 out of 5 (80%) different cases of carcinoma (1 cervical adenosquamous carcinoma and 3 cervical squamous cell carcinoma in situ confirmed by histopathology), but none of 34 smears with normal cytology. Twenty smears with normal cytology chosen for the negative control in this study were from the group of postmenopausal women and were as expected negative for p16INK4a immunostaining. In the group of postmenopausal women, 16 out of 60 (26.7%) cases the cytological diagnosis was established on the basis of pl6lNK4a immunostaining as being HSIL. From our preliminary study on a limited number of samples, we can however conclude that pl6INK4a immunostaining is a very useful tool for cytological diagnosis enabling to distinguish HSIL from normal, reactive or inflammatory changes.     

Acellular bodies in sputum

From 70 patients 68.3 +/- 10.1 years of age, 260 sputum specimens containing various acellular bodies were evaluated. This corresponded to 1% of all sputum specimens examined. The round to oval bodies were mostly concentrically structured and displayed different, partly amorphous, partly crystalline components. The periodic acid-Schiff stain was usually positive in these smears, 52% of which contained birefringent bodies. The average diameter was 25 +/- 10.9 micron. While intersample and intrasample frequencies of such bodies were extremely variable, a correlation with an increased number of Curschmann spirals and the degree of inflammation was observed (P less than 0.02). There was a correlation with neither sex, smoking habits nor most types of cancer. A positive correlation existed with chronic obstructive bronchitis, cor pulmonale, obstructive pulmonary diseases and one case of adenocarcinoma of the lung. This finding was confirmed by eight of ten new cases. The formation of the bodies can be intraalveolar, comparable to microliths, in the bronchial glands, corresponding to sialiths, and by intrabronchial mucus condensation, eventually around structures serving as cores. Changing frequencies in repeat investigations demonstrated a presumably rapid formation.     

Localization of mitochondrial ribosomal RNA on the chromatoid bodies of marine planarian polyclad embryos

Electron-dense cytoplasmic structures, referred to as chromatoid bodies, are observed in the somatic stem cells, called neoblasts, and germline cells in adult planarians. Although it has been revealed that the chromatoid bodies morphologically resemble germline granules in Drosophila and Xenopus embryos, what essential role it plays in the planarian has remained unclear. In the present study, to examine whether chromatoid bodies in planarian embryos are responsible for germline formation, the presence and behavior of chromatoid bodies during embryogenesis were examined. Mitochondrial large ribosomal RNA and mitochondrial small ribosomal RNA were used as candidate markers for components of the chromatoid body. Starting from the fertilized egg, extramitochondrial signals of both RNA (mtrRNA) were observed. At the ultrastructural level, mtrRNA were localized on the surface of the chromatoid bodies. At subsequent stages, the signals of mtrRNA were observed in certain restricted blastomeres that contribute to the formation of larval structures. The signals gradually decreased from the gastrula stage. These results suggest that the chromatoid bodies associated with mtrRNA in embryogenesis are not germline granules. The chromatoid bodies of blastomeres may be concerned with the toti- or pluripotency and cell differentiation as proposed in adult planarian neoblasts.     

The effect of delivery on regression of abnormal cervical cytologic findings

The purpose of this study was to determine whether abnormal antepartum cervical cytologic findings result in differing postpartum regression rates. Between 1993 and 2000, 107 pregnant women with antepartum abnormal cervical cytologic findings were identified. Papanicolaou smear data were separated into three groups by use of the CIN classification system. Postpartum regression rates of antepartum Papanicolaou smears were analyzed six months after delivery. Normalization of Papanicolaou smears in the postpartum period were observed in 50 of 107 women (46.7%). Regression of cervical cytologic findings was noted in 61 of 107 women (57%). Respectively, persistence of Papanicolaou smear was noted in 43 of 107 patients (40%). Only 3 of 107 (3%) antepartum findings progressed after delivery. Desquamation of the cervical epithelium or enhancement of a localized reparative immunologic response after vaginal delivery could play an important role in the spontaneous regression of cervical dysplasia in the postpartum period.     

Actinomyces in cervical smears of women using intrauterine contraceptive devices

Cervical smears from 1,784 women who attended the family planning clinics of the Institute for Research in Reproduction were examined for the presence of Actinomyces-like organisms. Among 815 intrauterine contraceptive device (IUD) users, the repeat smears from 57 women were positive for Actinomyces-like organisms, giving a prevalence rate of 6.99%. Immunofluorescent staining using specific antisera confirmed the presence of A. israelii in all 57 women. Forty IUD users whose smears were positive for Actinomyces-like organisms underwent bacteriologic culture studies; A. israelii was isolated in 23 of these cases. The clinical findings at the time of smear collection in the 57 IUD users were within normal limits. The initial cervical smears of all IUD users and both the initial and repeat smears of all nonusers were negative for Actinomyces-like organisms. The data indicate that prolonged use (greater than 2 years) of an inert or copper intrauterine device promotes the overgrowth of Actinomyces in the vagina and that this can be detected by routine cervical cytology.     

Review of cervical smears from 76 women with invasive cervical cancer: cytological findings and medicolegal implications

OBJECTIVE: To review cervical smears from 76 women which were taken prior to the diagnosis of invasive cervical cancer and to determine the appropriateness of the cytology reports issued on the smears. METHODS: Cervical smears, clinical records, cervical smear history and cytology reports from 76 women with invasive cervical cancer were reviewed. After microscopic review of the cervical smears, the cases were divided into two groups: Group 1 comprised 50 women who were found to have had at least one false-negative (F/N) smear report prior to the diagnosis of invasive cervical cancer. Group 2 comprised 26 women for whom no evidence of F/N reporting was found. RESULTS: A total of 209 cervical smears from the 50 women in group 1 were available for review (range 2-12 smears per woman); 100 of the 209 smears were considered to have been reported appropriately. Ninety-seven smears which had been reported originally as negative or inadequate were found, on review, to contain numerous severely dyskaryotic cells and were reclassified as F/N smears. All of the 50 women had at least one F/N smear and 29 had two or more. Twelve smears from eight women contained only a few (<200 severely dyskaryotic cells). Forty women developed invasive squamous carcinoma and 10 developed invasive adenocarcinoma. The stage at diagnosis ranged from 1A to stage 4. Seventy-one smears from the 24 women in group 2 were available for review (range 1-15 smears per woman). In two cases included in group 2, no smears were provided for review as the smears had been lost or mislaid. Review of the 71 smears confirmed the accuracy of the original cytological classification of the smear. Nineteen women were diagnosed with squamous cancer, two microinvasive cancer, one glassy cell, two adenocarcinomas, and one with adenosquamous carcinoma. One women was found to have an embryonal rhabdomyosarcoma of the corpus uteri involving the cervix. DISCUSSION/CONCLUSION: The medicolegal implications are discussed in the light of the above findings. Evidence of breach of duty of care was presented in all 50 cases in group I although causation was not established in every case. There was no evidence of failure of duty of care in terms of the standard of the cervical cytology reports issued or standard of clinical management in 17 of the 26 cases in group 2. However, in seven of the 26 cases in group 2, clinical management of the case was substandard due to failure to investigate symptoms of irregular bleeding regardless of a negative cytology report (two cases), failure to act upon a suspicious smear report or consecutive inadequate smear reports (two cases), failure of follow-up after treatment of CIN3 (two cases) and histological misdiagnosis (one case).     

Human papillomavirus infection in the cervix of pregnant females in Hong Kong

Routine cytological examination and HPV-DNA probing were performed on cervical cells obtained from 215 pregnant Chinese females. The procedure utilized the specific binding of a mixture of complementary [32P]-labelled RNA probes to membrane-bound target HPV DNA types 6, 11, 16, 18, 31, 33 and 35. Positive results for HPV-DNA were obtained in 11/215 (5%) of the cases. The cervical smears were routinely processed and in 3/215 (1.5%) cases a cytological diagnosis of wart virus infection was made. All three were included in the 11 probe-positive cases. Using similar molecular biological techniques, pregnant Western females have an incidence of HPV infection of the cervix which is up to five times that of the present series. This is an unexpected finding in view of the fact that the incidence of cervical cancer is higher in Chinese women than American women.     

The presence of endometrial cells in cervical smears in relation to the day of the menstrual cycle and the method of contraception

The presence of endometrial cells in cervical smears was studied in a large series of women participating in a population screening program for cervical cancer, in relation to different time periods of the menstrual cycle and to the method of contraception practiced. In the total group of women studied, endometrial cells were present in an average of 12% of the cervical smears. In women who were menstruating cyclically, the percentage of cervical smears containing endometrial cells was not age dependent. Only in women over 52 years was a lower number of endometrium-positive cervical smears found: in postmenopausal women, 0.6% of smears were found to contain endometrial cells. In menstruating women, the frequency of endometrial cells in cervical smears was highest during the menses. After day four, through the proliferative phase, the percentages of cervical smears containing endometrial cells markedly decreased. During the secretory phase, an average of 2% of the smears contained endometrial cells; in the premenstrual phase (after day 25), the percentages of endometrial cell-positive smears rose again. When related to the method of contraception practiced, significant differences in the percentages of cervical smears with endometrial cells appeared. In women using oral hormonal contraceptives, the average numbers of smears containing endometrial cells for the whole cycle as well as for each period of the cycle were significantly lower. This phenomenon might be due to endometrial atrophy on the basis of prolonged use of oral hormonal contraceptives. In women wearing an intrauterine device, at any moment the frequencies of smears with endometrial cells present were significantly higher than the values found in women using any other method of contraception or not using contraceptives. The evaluation of cells originating from the endometrium requires considerable experience. The identification of endometrial cells can be made with greater confidence when the cytologist is aware of the exact date of the menstrual cycle and of the impact on the presence of endometrial cells in cervical smears caused by different methods of contraception.     

Cervical cancer screening programs: summary of the 1982. Canadian task force report.

The Canadian Task Force on Cervical Cancer Screening Programs, which produced its first report in 1976, was reconvened by the Department of National Health and Welfare in 1980 in response to concerns expressed about the significance of new data, changing sociosexual patterns and wide variations in the implementation of the 1976 recommendations. This article is a summary of the 1982 task force report. In addition to updates of the 1976 material new sections appear on groups at risk, mathematical models of screening, quality control in screening programs, cytologic screening coverage of the Canadian population and management of patients with abnormal smears. The 1982 recommendations deal with frequency of screening, laboratory quality control and follow-up mechanisms. The task force concludes that measures to improve the quality and sensitivity of screening programs and to include women who have never been screened will be more effective in reducing mortality from carcinoma of the cervix than will attempts to increase the frequency of screening. The task force views as unnecessary the annual screening of women over 35 years of age whose previous smears have been normal. Since younger women are sexually more active and tend to have more than one sexual partner they are at high risk. Therefore, the task force recommends annual screening for sexually active women aged 18 to 35 years. Physicians, health care professionals and government health agencies have a role to play in informing women about the recommended intervals for cervical smears and ensuring that screening programs of adequate quality are available. Although women are primarily responsible for entering and continuing in such a program, government-sponsored registries are essential if the full potential of cervical smear programs is to be realized.     

Micronuclei as biomarkers for evaluating the risk of malignant transformation in the uterine cervix

We evaluated micronucleus and apoptosis occurrence among women with normal smears and women with different kinds of cervical abnormalities, i.e., inflammatory processes and low- and high-grade squamous intraepithelial lesions (N = 12, N = 10 and N = 27, respectively). The sample included 59 women who were seen at a public medical service for cervical cancer prevention in Feira de Santana, Bahia, Brazil. The diagnosis was established by means of cytological, colposcopic, and histopathological examination. Cytogenetic analysis was performed on 2000 cells from each woman and included assessment of micronuclei and nuclear degenerative abnormalities indicative of apoptosis (karyorrhexis, pyknosis and condensed chromatin). Micronucleus frequency was significantly higher in the women with high-grade squamous intraepithelial lesions than in the women without cervical abnormalities or inflammatory processes (P< 0.001) or in the women with low-grade squamous intraepithelial lesions (P < 0.005). The frequency of apoptosis was similar in women without cervical abnormalities and women showing high-grade squamous intraepithelial lesions (P > 0.50), and significantly lower in women without cervical abnormalities and in women showing high-grade squamous intraepithelial lesions than in women showing inflammatory processes or low-grade squamous intraepithelial lesions (P < 0.0001). These results indicate that, in addition to Papanicolaou cervical cytological analysis, it would be useful to use micronucleus analysis to screen women who are at risk of developing cervical cancer. The assessment of nuclear degenerative abnormalities indicative of apoptosis increased the sensitivity of this test.     

Prevalence of Chlamydia trachomatis infections in Karachi, Pakistan.

An epidemiological study was carried out to determine the prevalence of Chlamydia infections in adult females by enzyme immunoassay and microscopic examination of Giemsa-stained smears. Endocervical swabs were collected from 126 females attending OB/GYN ward at Abbasi Shaheed Hospital, Karachi. 13.5% of 126 females tested were positive by enzyme immunoassay and only 5.6% were positive by the Giemsa-staining method. The infection rate among pregnant and nonpregnant women with urinogenital problems were 11.8% and 14.7%, respectively. The majority of females complained of excessive cervical discharge and pain in the lower abdomen. A high prevalence of infection in normal pregnant women (18.2%) indicates the asymptomatic nature of this infection.     

Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing.

OBJECTIVE--To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens. DESIGN--Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae. SETTING--Family practice teaching clinic in a university hospital. PATIENTS--411 women presenting for a smear test. MAIN OUTCOME MEASURES--Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear. RESULTS--Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups. CONCLUSION--Reports of inflammatory changes on cervical smear testing are a poor indicator of infection.