Significance of atypia in conventional Papanicolaou smears and liquid-based cytology: a follow-up study

The diagnosis of atypical squamous epithelial cells, borderline nuclear changes, is associated with some controversy, as it encompasses benign, reactive, as well as possible neoplastic conditions. The aim of this study was to evaluate the follow-up diagnoses of cytological atypia in conventional Papanicolaou smears (CP) and liquid-based samples by the ThinPrep Pap Test (TP). A total of 1607 CP smears from 1 January 2000 to 31 December 2000 and 798 TP samples from 1 January 2002 to 31 December 2002 diagnosed as atypia were included. The results show that the detection rate of atypia in cervical cytological samples was reduced by 41.3% (P < 0.001) in TP compared with CP. Cytological and histological follow-up data showed the presence of neoplastic lesions in 34.7% of patients screened by TP versus 22.3% of patients screened by CP, corresponding to a 55.6% increase in TP (P < 0.001). Follow-up diagnosis of mild dysplasia was seen more than twice as often in TP than in CP (12.8% versus 5.0%, P < 0.001). The prevalence of moderate and severe dysplasia was significantly increased with 26.7% in TP compared with CP (21.9% versus 17.2%, P < 0.01). In conclusion, the ThinPrep Pap Test yielded a significant decrease in atypia rates compared with the conventional Papanicolaou test. In subsequent follow-up the percentage of neoplastic lesions was significantly increased in the ThinPrep Pap Test samples.     

Distinct ultrastructural aspects in different biopsies of a single patient with diffuse cutaneous leishmaniasis

The authors investigated the relation between parasites and host-cells in active and regressed lesions of a patient with diffuse cutaneous leishmaniasis, evaluating the frequency of different cell types, and the location and integrity of amastigotes. No correlation was found between parasite integrity and size of parasitophorous vacuoles. They observed ultrastructural findings characterizing a cell mediated immune response: macrophages lysis, parasitic destruction inside macrophages, close contact between parasitized macrophages and lymphocytes and between parasites and lymphocytes, lymphocytic infiltration and fibrosis. They suggest that in DCL there is a limited cellular immune response, although insufficient to control infection.     

Cytologic findings in primary malignant carcinoid tumor of the cervix. Including immunohistochemistry and electron microscopy performed on cervical smears

The cytologic findings in a primary malignant carcinoid tumor of the cervix are presented. In addition to the presence in the smears of cells suggestive of squamous carcinoma and adenocarcinoma, which led to an initial diagnosis of adenosquamous carcinoma, there were multinucleated giant cells with prominent, reddish nucleoli, finely granular chromatin and grayish-blue to eosinophilic cytoplasm, as well as smaller pleomorphic cells, against a tumor-diathesis type of background. Immunocytochemistry performed on the cervical smears showed the presence of serotonin, and ultrastructural analysis revealed abundant intracytoplasmic, membrane-bound granules in malignant cells, thus confirming the diagnosis of a carcinoid tumor.     

Comparing the accuracy of ThinPrep Pap tests and conventional Papanicolaou smears on the basis of the histologic diagnosis: a clinical study of women with cervical abnormalities

OBJECTIVE: To confirm that the ThinPrep Pap test (TP) is as effective as or more effective than the conventional Papanicolaou smear (CS) in detecting epithelial cell abnormalities in a population with cervical abnormalities. STUDY DESIGN: In a blinded, split-sample, matched-pair study, a CS was prepared using a cytobrush, and then TP slides were prepared from the remainder of the sample. All slides were evaluated as defined and classified by the Bethesda System. The results of the two cytologic tests were compared in 483 women relative to the histologic diagnoses of subsequent colposcopically directed cervical biopsies in 158 cases. RESULTS: The cytologic diagnoses from the two methods agreed exactly in 91.4% of cases. The comparison between the two cytologic diagnoses with reference to the histologic diagnosis of subsequent colposcopically directed cervical biopsies showed that TP was significantly more specific for diagnosing lesions than was CS. The sensitivity of the two methods was equivalent. CONCLUSION: In a population with cervical abnormalities, TP is more specific than and as effective as CS in detecting cervical epithelial cell abnormalities. TP improved the specificity of disease detection by reducing the atypical squamous cells of undetermined significance category and/or false positive cases.     

Aylesbury and cervitula spatulas: a comparative study to assess the adequacy of cervical smears

OBJECTIVE: To assess whether the Aylesbury (Pharmaceutical Enterprises Ltd., Pinelands, Capetown, South Africa) or Cervitula spatula (Harwill Medical, Capetown, South Africa) is more effective for adequate cervical smears in obstetric and gynecology patients. STUDY DESIGN: The Cervitula spatula was compared with the Aylesbury spatula by taking a total of 160 smears, which were examined cytologically. This consisted of 40 obstetric and 40 gynecology patients. The sequence in which the spatiulas were used was determined by computer randomization. Our main outcome criterion was whether both ectocervical and endocervical cells were present, thus making the smear adequate. Our numbers were too small to draw conclusions on the cytologic abnormalities detected between the two spatulas. RESULTS: The Cervitula was more effective for the identification of endocervical cells in obstetric patients (P = .0008). When combining the obstetric and gynecology groups, the Cervitula was also better in obtaining endocervical cells, but this did not reach statistical significance (P = .016). CONCLUSION: Pap smear sampling with the Cervitula reduces the number of cases without endocervical cells, which would constitute an inadequate smear, requiring unnecessary recall of patients for repeat smears.     

Evaluation of proficiency testing as a method of assessing competence to screen cervical smears

Evaluation of proficiency testing as a method of assessing competence to screen cervical smears Regular proficiency testing of pathologists and cytotechnologists who undertake the analysis of cervical smears has been carried out in cytology laboratories in the North Thames (West) Region since 1989. The protocol followed is one that has been adopted nationally. Since the scheme started, laboratory personnel from 17 cytology laboratories in the Region have participated and seven rounds of testing have been completed. Nine hundred and seventy-one tests were carried out and a pass rate of 96.4% was recorded. Two hundred and forty-seven cytologists took the test on at least one occasion and 63 cytologists took part in all seven rounds. Our results indicate that proficiency testing is capable of detecting cytologists who consistently perform below an acceptable standard and require retraining. They also show that even the most competent screeners can miss an abnormal smear. Seven cytologists who had proved their competence to screen on six occasions, missed an abnormal smear on the seventh, despite the fact that they were screening under test conditions when their vigilance should have been at its peak. Our findings indicate that false-negative reporting will inevitably occur during manual screening, and emphasize the need for further research into the causes and prevention of screening error. Evaluation des tests d'aptitude comme méthode d'appréciation de la compétence à lire les frottis cervico-utérins de dépistage Le passage régulier de tests d'aptitude pour les pathologistes et les cytotechniciens qui prennent en charge l'analyse de frottis cervico-utérins est utilisé dans les laboratoires de cytologie de la région North Thames (West) depuis 1989. Le protocole choisi est l'un de ceux qui ont été adoptés au niveau national. Depuis le début de ce programme, 7 sessions de tests ont été organisées et le personnel de 17 laboratoires de cytologie de la région a participé. Neuf cent soixante et onze tests ont été pratiqués et le taux de participation enregistré est de 96,4%. Deux cent quarante sept cytologistes ont fait le test au moins une fois et 63 cytologistes ont passé les 7 sessions de tests. Nos résultats indiquent que les tests d'apitude sont capables d'identifier les cytologistes qui ont besoin d'une formation car leur résultats aux tests sont régulièrement en dessous des standards acceptables. Ils montrent également que même les “screeners” les plus compétents peuvent passer à côté d'un frottis anormal. Sept cytologistes ayant montré leur compétence pour la lecture des frottis de dépistage sur 6 tests n'ont pas été capable de détecter un frottis anormal sur le septième test, bien que cette lecture ait été faite dans des conditions de test où leur vigilance aurait dû être à son maximum. Ces résultats indiquent qu'il est impossible d‘éviter les faux négatifs au cours du “screening manuel” et confirment la n?essité de poursuivre les recherches sur les causes des erreurs de lecture et sur leur prévention. Die Ergebnisse der Laistungstests als Grundlage für die Fähigkeit gynäkologische Abstriche auszuwerten Regelmässige Leistungstests von Zytopathologen und Zytotechnikerinnen beim Auswerten gynäkologischer Abstriche wurden seit 1989 in den Labors der Nord-Themse Region durchgeführt. Das Testprotokoll entspricht dem landesweit angewandten. Inzwischen nahmen 17 Labors an insgesamt 7 Testrunden teil. Die Gesamtzahl der Tests beträgt 971 wobei 96,4% der Teilnehmer die Tests bestanden. 247 Teilnehmer nahmen an zumindest einem Test, 63 an allen sieben teil. Die Auswertungen ergaben, dass auf diese Weise Zytologen mit unterdurch schnittlicher Leistung identifiziert und einem Zusatztraining zugeführt werden können. Sie zeigen aber auch, dass selbst die Erfahrendsten gelegentlich positive Befunde übersehen. Sieben Teilnehmer begingen diesen Fehler nach sechs fehlerfreien Durchgängen beim siebten Test trotz der bekannten Testsituation. Dies bedeutet, dass Fehler bei nichtautomatischer Auswertung unvermeidbar sind. Die Ursachenforschung muss weitergeführt werden.     

Accuracy of liquid-based Pap tests: comparison of concurrent liquid-based tests and cervical biopsies on 782 women with previously abnormal Pap smears

OBJECTIVE: To evaluate the diagnostic performance of a liquid-based Pap test, the ThinPrep Pap test (TP) (Cytyc Corp., Boxborough, Massachusetts, U.S.A.), by comparing concurrent TP and cervical biopsy results on 782 patients who were referred for colposcopy because of previously abnormal conventional Pap smears (CPs). STUDY DESIGN: The ability of TP diagnoses of atypical cells of undetermined significance (ASC-US) and squamous intraepithelial lesions (SILs) to predict biopsy diagnoses of cervical intraepithelial neoplasia (CIN) was analyzed using chi2 and McNemar tests. RESULTS: The rate of agreement between diagnoses of SIL by TP and CIN by biopsy was 74.7%. ASC-US accounted for 16.0% of TP diagnoses. ASC-US had biopsy diagnoses of CIN 1 in 60% and CIN 2/3 in 12.8% of cases. For TP diagnosis of low grade SIL, biopsy diagnoses of CIN 2/3 were found in 13.5% of cases. For TP diagnoses of ASC-US and higher, the proportions of TP and cervical biopsies in comparable diagnostic categories were statistically significant (p < 0.001), with TP having sensitivity of 89.4% and positive predictive value of 89.7% for the detection of CIN. The false positive rate for TP was 8.1%, but rescreening confirmed the presence of abnormal cells in 51 of 63 (81.0%) cases of ASC-US or higher having negative biopsies. TP had a false negative rate of 8.3% and negative predictive value of 61.3%. Rescreening showed that most (77.6%) of the false negative TP specimens failed to have abnormal cells on the slides. CONCLUSION: For patients having previously detected cervical abnormalities by CP, concurrent TP demonstrated the following: (1) that it has high diagnostic accuracy for SIL, (2) that ASC-US was diagnostically equivalent to LSIL, and (3) that false negative TP for SIL can be attributed primarily to sampling rather than cytotechnologists' screening errors.     

Atypical glandular cells in cervical smears: histological correlation and a suggested plan of management based on age of the patient in a low-resource setting

Objectives:  To perform an audit of all smears reported as atypical glandular cells (AGC) using the Bethesda system (TBS) 2001.
Methods:  A total of 18 376 cervical smears were screened from January 2005 to June 2007, of which 65 cases were reported as AGC. Follow-up histology was available in 31 cases (47.7%), in whom a detailed cytological/histological correlation was carried out.
Results:  AGC constituted 0.35% of all Pap smears. Follow-up histology was normal or benign in 20 cases, whereas a squamous or glandular abnormality was seen in 11 cases. Squamous abnormalities included one case each of cervical intraepithelial neoplasia (CIN)1, CIN2 and CIN3 and five cases of squamous cell carcinoma. All glandular epithelial abnormalities were endometrial in origin and included two endometrial adenocarcinomas and one uterine serous carcinoma. Neither in situ nor invasive adenocarcinoma of the endocervix was observed. Review of smears and reclassification as AGC, not otherwise specified and favour neoplasia revealed a higher proportion of abnormality in the latter group, reaffirming the utility of subtyping. The median age of women with AGC was 41 years. The outcome was analysed with respect to the median age. In women aged equal or more than 40 years, AGC reflected a high-grade squamous or glandular epithelial abnormality in 50% of cases compared with none in those less than 40 years old ( P  = 0.010).
Conclusion:  The age of the woman as well as the subtype of atypical glandular cells influences outcome and hence must be taken into consideration while formulating an acceptable management strategy in these women in a low-resource setting.     

Experience in managing a large-scale rescreening of Papanicolaou smears and the pros and cons of measuring proficiency with visual and written examinations

Experiences in a large-scale interlaboratory rescreening of Papanicolaou smears are detailed, and the pros and cons of measuring proficiency in cytology are discussed. Despite the additional work of the rescreening project and some psychological and technical problems, it proved to be a useful measure of the laboratory's performance as a whole. One problem to be avoided in future similar studies is the creation of too many diagnostic categories. Individual testing and certification have been shown to be accurate predictors of proficiency. For cytology, such tests require a strong visual component to test interpretation and judgment skills, such as by the use of glass slides or photomicrographs. The potential of interactive videodisc technology for facilitating cytopathologic teaching and assessment is discussed.     

Clinical prognostic factors for pediatric extra-abdominal desmoid tumor: analyses of 66 patients at a single institution

Background and purpose

Pediatric desmoid tumor (PDT) is rare and has a high local recurrence rate. The purpose of the present study was to analyze clinical risk factors of local recurrence in PDT patients.

Materials and methods

We reviewed clinical data of 66 PDT patients from 2004 to 2015. All patients underwent macroscopically complete resection, and some recurrent tumors were prescribed radiotherapy. Factors such as sex, age at presentation, location, and proximity to nerves or vasculature were analyzed. The local recurrence rate and recurrence-free survival were analyzed with these factors.

Results

All patients in the present study were children and had extra-abdominal tumors. The median follow-up time was 6.6?years. Thirty-six (55%) patients had local recurrence. Age, sex, tumor site, tumor size, and proximity to nerves/vasculature had a significant impact on prognosis in univariate analysis. Radiotherapy decreased the local recurrence rate. In multivariate analysis, younger age, tumor location in buttocks, larger tumor, and proximity to important nerves/vasculature were independent risk factors for poor prognosis.

Conclusions

Favorable therapeutic strategies could be selected according to the preoperative prognostic risk factors. Radiotherapy should be considered for local recurrence of PDT.

     

Change in antimicrobial susceptibility of Escherichia coli urinary tract isolates at a single institution over a period of 10 years

Urinary tract infections are common. Few published studies have demonstrated the change in Escherichia coli urinary isolate antimicrobial susceptibility over time within a given area and (or) population. The purpose of this study was to evaluate the change in susceptibility of E. coli clinical isolates obtained from urine specimens at a single institution over a period of 10 years. The microbiology laboratory information system at St. Boniface Hospital (Winnipeg, Manitoba, Canada) was searched retrospectively from 1 January 2000 to 31 December 2009, for all E. coli isolates from either a midstream or catheter urine source that had susceptibility testing performed. Only one isolate per patient was included during the entire study period. Antimicrobial susceptibility testing was carried out with either a Microscan instrument (pre-April 2004) or a Vitek instrument (May 2004 onwards). In total, 7353 E. coli urinary isolates were included for evaluation. Ciprofloxacin susceptibility declined significantly, from 99% in 2000 to 85% in 2009 (p < 0.0001). A small but statistically significant decline in susceptibility was also observed for ampicillin, cefazolin, trimethoprim-sulfamethoxazole, gentamicin, and nitrofurantoin. These data suggest that certain antimicrobials recommended for the treatment of urinary tract infections (ciprofloxacin, trimethoprim-sulfamethoxazole) may no longer be optimal.     

Examination of the λ equilibrium point hypothesis when applied to single degree of freedom movements performed with different inertial loads

 One of the theories of human motor control is the λ Equilibrium Point Hypothesis. It is an attractive theory since it offers an easy control scheme where the planned trajectory shifts monotionically from an initial to a final equilibrium state. The feasibility of this model was tested by reconstructing the virtual trajectory and the stiffness profiles for movements performed with different inertial loads and examining them. Three types of movements were tested: passive movements, targeted movements, and repetitive movements. Each of the movements was performed with five different inertial loads. Plausible virtual trajectories and stiffness profiles were reconstructed based on the λ Equilibrium Point Hypothesis for the three different types of movements performed with different inertial loads. However, the simple control strategy supported by the model, where the planned trajectory shifts monotonically from an initial to a final equilibrium state, could not be supported for targeted movements performed with added inertial load. To test the feasibility of the model further we must examine the probability that the human motor control system would choose a trajectory more complicated than the actual trajectory to control. Received: 20 June 1995 / Accepted in revised form: 6 August 1996     

Reporting endometrial cells in Papanicolaou smears of women age 40 and older: a qualifying educational note could prevent unnecessary follow-up biopsy

OBJECTIVE: To determine the impact of adding a qualifying educational note when exfoliated endometrial cells were present in the first half of the menstrual cycle. STUDY DESIGN: We identified all Pap smears that had endometrial cells in women > or = 40 years, between July and November, 2004. When endometrial cells were seen in the first half of menstrual cycle, it was stated that, "endometrial cells correlate with the menstrual history provided." We then attempted to determine if this qualifying comment had an impact on the decision to obtain a follow-up endometrial biopsy. RESULTS: A total of 325 women were identified. Of these, 51 (15.7%) had follow-up endometrial biopsy without clinical evidence of endometrial pathology, compared to a rate of 36.9% before implementation of the note (p < 0.0001). Biopsies were performed in 21 of 195 (10.8%) when the note indicated that endometrial cells correlated with menstrual history, compared to 30 of 130 (23%) in whom a different note was appended because endometrial cells were out of phase or patients were postmenopausal (p = 0.0032). Biopsies did not reveal significant endometrial pathology in any of the 51 patients. CONCLUSION: Adding an educational note when endometrial cells are reported in the first half of the menstrual cycle in women > or = 40 years may help reduce unnecessary biopsies.     

Follow up of women with a history of mildly abnormal cervical smears which have returned to normal without treatment

The progress of 124 women with at least two negative cervical smears following a history of mildly abnormal smears for which no treatment had been given was compared with 106 women with negative smears and a clinical history of genital warts or herpes virus infection and 460 age-matched controls. After 4 years, excluding those for whom there was no follow up, 5.8% of those with a history of abnormal smears, none of those with a clinical history of genital warts or herpes virus and 1.1% of controls had developed histological evidence of at least cervical intraepithelial neoplasia grade III (CINIII) when referred for investigation of subsequent abnormal smears; one woman, from the control group, had developed invasive cervical cancer. Women with two negative smears after a history of abnormal smears who subsequently developed CINIII were more likely to have had a previous smear reported as moderate or mild-moderate dyskaryosis (2/6) compared with those whose follow up was negative (2/89). the results suggest that two negative cervical smears may not necessarily indicate that a lesion has regressed, but that a clinical history of genital warts or herpes virus infection should not be an indication for increased surveillance.     

The cytology of vaginal, cervical and endometrial smears obtained at the time of embryo transfer during in vitro fertilization

Seventy-four women enrolled in an in vitro fertilization (IVF) program had cytologic smears of the vagina, cervix and endometrium obtained at the time of embryo transfer (ET). Of these, 68 vaginal, 46 cervical and 25 endometrial smears were available for cytologic examination. Of the 68 vaginal smears, 4% showed a proliferative pattern, 40% were early secretory and 56% were advanced secretory. The 46 cervical smears demonstrated a delayed hormonal effect, with 70% showing a proliferative pattern, 23% early secretory and 7% advanced secretory cytology. Endometrial cells were obtained only when the Jones catheter, which has a side opening, was used. Twenty-two patients had both vaginal smears and suitable endometrial smears. Of these, 8 of the 9 patients with early secretory vaginal cytology had secretory endometrium while 10 of the 12 patients with mid-secretory vaginal cytology had secretory endometrium. The value of endometrial cytology in predicting conception following IVF-ET is unknown. It seems, however, that a good correlation exists between endometrial and vaginal cytology and that the latter may be of value as an additional, noninvasive tool for the evaluation of endometrial development.     

Use of sulfonated primers to detect and type papillomavirus in cell cultures and cervical biopsies.

Human papillomavirus (HPV) was detected by using two sets of deoxyribonucleotide primers for differentiating between 'low-risk' types (HPV11 and HPV6) and 'high-risk' (hri) types (HPV16, HPV18 and HPV33). A new application of the Chemiprobe method for labeling DNA was used to detect products of the polymerase chain reaction (PCR) from 36 cervical biopsies. This method, first demonstrated by Uchimura et al. (submitted), is based on the sulfonation of a polycytidylic acid tail of 5-20 monomers attached to the 5' end of either one or both of the PCR primers. This procedure can increase the sensitivity of detection of PCR products more than 100-fold with respect to ethidium bromide (EtdBr) staining. Various methods were used to detect hri HPV DNA in the 36 clinical samples. The number of positive results obtained was as follows, two by Southern-blot hybridization; five by PCR amplification followed by electrophoresis and detection of products by EtdBr staining; six by PCR amplification using one or two sulfonated C-tailed primers followed by electroblotting and immunoenzymatic visualization; and five by hybridization of sulfonated genomic viral recombinant with a PCR product immobilized on a membrane. The yield of the PCR product was significantly greater when one of the primers was C-tailed than when both or neither of the primers were C-tailed. PCR employing sulfonated C-tailed oligo primers is very specific and sensitive, and the entire procedure can be employed as a nonradioactive substitute for radioactive dot-blot or Southern-blot hybridization procedures, routinely used for detection of HPV in clinical samples.     

Hydrilla tuber formation in response to single and sequential bensulfuron methyl exposures at different times

Hydrilla (Hydrilla verticillata (L.f.) Royle) grown in outdoor tanks was exposed to bensulfuron methyl concentrations of 25, 50, or 100 ppb on June 16, August 20 or October 15; 50 ppb June 16 and August 20, or 25 ppb on June 16, July 21, August 20, and October 15, 1990, with a 35-day contact time. Hydrilla was also exposed to the compound on August 9, 1991 at concentrations of 10, 20, 30, 40, or 50 ppb. In 1990, the August 20 exposure resulted in the greatest inhibition of tuber production for a single application. Exposure in June caused hydrilla to produce at least twice as many tubers as unexposed plants by April 10, 1991. Exposure in October arrested tuber production, which had already begun. Exposure in June and August delayed tuber formation until after February 9, 1991. Exposure in June, July, August, and October inhibited tuber formation for the entire growing season. Hydrilla treated with all concentrations of bensulfuron methyl on August 9, 1991 produced tubers only sporadically through March 16, 1992, compared to unexposed hydrilla, which produced an average of 48 tubers/531 sq cm by January 4, 1992. With the onset of warmer weather after March 16, tubers produced by unexposed hydrilla more than doubled, and comparable numbers of new tubers were produced by plants that were exposed to 10 or 20 ppb. Tuber production was inhibited for the entire growing season by exposure to 50 ppb on August 9, 1991. In spite of the promise that bensulfuron methyl showed for use in aquatic plant management, the Experimental Use Permit was not renewed in 1992 and efforts to register the compound were discontinued.