Bone tumor radiograph review by pathologists prior to pathologic diagnosis: a receiver operator curve analysis of diagnostic utility

OBJECTIVE: To assess the performance of quick rescreening as an internal quality control for cervical smears previously screened as negative and to compare this method with clinically indicated rescreening of negative smears and with further 10% random rescreening. STUDY DESIGN: In a small-workload laboratory with many different types of indications for cytology, during a three-month period, all gynecologic cytology smears considered negative for significant findings (anything above atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance (AGUS) in the Bethesda System) or inadequate were quickly rescreened using a 10 x objective. RESULTS: Of the total 2,188 smears processed, 164 (7.5%) were excluded from rapid review because they were positive on routine screening, and 2,024 cases were subjected to rapid rescreening: 1,925 (95.1%) cases were considered negative and 99 (4.9%) positive for significant findings; 58 of the latter were confirmed and 41 not confirmed by the cytopathologist's detailed examination. The 58 confirmed cases were classified as: 43 ASCUS/AGUS, 14 of low grade squamous intraepithelial lesion and 1 of invasive cancer. No cases of high grade squamous intraepithelial lesion were detected. CONCLUSION: Considering that the routine screening and internal quality control of the laboratory had detected 117 positive cases, the additional 58 represent a definite increase in the efficiency of a small-workload laboratory. In such a clinical setting, no additional case of a high grade lesion was detected by rapid rescreening. The increase in cost and time was considered very reasonable, and the method was incorporated as quality control for the laboratory. Clinically indicated rescreening of negative smears and random 10% rescreening after random rescreening did not add significantly to quality assurance.     

Atypical squamous cells of undetermined significance. Stratification of the risk of association with, or progression to, squamous intraepithelial lesions based on morphologic subcategorization

OBJECTIVE: To analyze follow-up data on atypical squamous cells of undetermined significance (ASCUS) based on morphologic characteristics. STUDY DESIGN: Five years of follow-up was obtained on a cohort of 437 consecutive patients from 1986 who had initial diagnoses of ASCUS, with a further categorization of type based on the maturity of the atypical cells. All such categorizations were made on the basis of specific cytologic criteria. Follow-up cytology and/or biopsy was available on 366 patients. RESULTS: During the follow-up period, 40 patients (13.5%) with ASCUS were diagnosed as having a squamous intraepithelial lesion (SIL); 15 (5%) were interpreted as high grade. When stratified by type of ASCUS based on cellular maturity, the following association/progression rates were noted: mature ASCUS, 10%; metaplastic ASCUS, 24%; and immature metaplastic ASCUS, 42%. In metaplastic and immature metaplastic ASCUS cases, high grade SIL accounted for 42% and 60% of those subsequently diagnosed with a squamous intraepithelial lesion, respectively, versus 30% for mature ASCUS. CONCLUSION: With well-defined and consistent criteria for the diagnosis of the variety of "squamous atypias," a stratification of risk of progression to or association with SIL can be made. When features of metaplasia and immature metaplasia are noted in the cells of ASCUS, patients were observed to be at increasingly greater risk for the detection of SIL; those cases were proportionately more likely to be high grade.     

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.     

Detecting structural changes at the molecular level with Fourier transform infrared spectroscopy. A potential tool for prescreening preinvasive lesions of the cervix

OBJECTIVE: To study cervical exfoliated cells with Fourier transform infrared spectroscopy (FTIR). STUDY DESIGN: Consecutive samples from 133 women attending the Dysplasia Clinic, Ottawa Civic Hospital, were collected in balanced electrolyte solution. After centrifugation, two smears were prepared for routine screening. The remainder of the pellet was frozen for FTIR spectroscopic study. RESULTS: In 120 samples, adequate material was available for spectroscopic study. All smears from 17 women with normal spectra were within normal limits (WNL). One hundred three spectra were abnormal. The corresponding smears were interpreted as: 41 low grade squamous intraepithelial lesions, 20 high grade squamous intraepithelial lesions, 6 atypical squamous cells of undetermined significance, 17 cases with benign cellular changes, and 19 WNL. Ten of 17 cases with benign cellular changes had characteristic spectra consistent with inflammatory changes. CONCLUSION: FTIR spectroscopy is a highly sensitive technique for detecting cervical abnormalities and a potential tool for prescreening preinvasive lesions of the cervix.     

Percentages of cervical cytologic diagnoses as a quality assurance method

OBJECTIVE: To demonstrate empirically that the efficiency of rescreening to discover false negative cytologic diagnoses is greatly enhanced by prospectively stratifying accessions according to risk level. STUDY DESIGN: We stratified accessions from 11 clinical sources and established the rate of diagnoses according to three categories: (1) "within normal limits"/"benign cellular changes" (WNL/BCC), (2) "atypical squamous/glandular cells of undetermined significance" (ASCUS/AGCUS) and (3) "squamous intraepithelial lesion/invasive carcinoma" (SIL/CA). We then prospectively rescreened all negative smears from sources with rates of positive diagnoses (ASCUS/AGCUS and SIL/CA) in excess of 20% and 5% of negative smears from sources with rates of positive diagnoses < 20%. We compared the detection rates of false negatives on rescreening target groups with random rescreening of 10% of all negative smears. RESULTS: The rates of SIL/CA, ASCUS/AGCUS and WNL/BCC varied from 0 to 43%, 4% to 14% and 46% to 94%, respectively. Rescreening 10% of all negative smears revealed a false negative fraction of 3%; rescreening target groups revealed a false negative fraction of 5.9%. CONCLUSION: The yield of prospectively detected false negative diagnoses was significantly increased by targeting high-risk accession groups. When cytology laboratories serve diverse populations, stratifying accessions by risk to permit increased sampling from the proportionately higher risk categories is a simple and effective device to maximize the yield and benefit from rescreening.     

Serum leptin concentration and insulin sensitivity in men with abdominal obesity

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.     

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.     

Immunological identification of a basic homologue to acidic virus-inducible cucumber peroxidase

BACKGROUND: The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established. METHODS: Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined. RESULTS: Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed. CONCLUSIONS: The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears.     

The effect of route of delivery on regression of abnormal cervical cytologic findings in the postpartum period

OBJECTIVES: We sought to determine whether pregnant women with abnormal antepartum cervical cytologic findings differ in their postpartum rates of regression with respect to mode of delivery. STUDY DESIGN: Between 1990 and 1997, 446 pregnant women with antepartum abnormal cervical cytologic findings were identified. Complete demographic, clinical, and cytologic reports were available for 138 women. Papanicolaou smear data were collected and separated into three groups by use of the Bethesda classification system (atypical squamous cells of undetermined significance, low-grade squamous intraepithelial cells, and high-grade intraepithelial cells). Postpartum regression rates of antepartum Papanicolaou smears, with respect to degree of squamous epithelial cell abnormality and mode of delivery, were analyzed by Fisher's exact and Wilcoxon rank sum tests. RESULTS: Of the 138 women, 109 (79%) were delivered vaginally and 29 (21%) by cesarean section. No statistically significant difference was found between women delivered vaginally and those delivered by cesarean section with respect to age, parity, and smoking history within the three groups (atypical squamous cells of undetermined significance, low-grade squamous intraepithelial cells, and high-grade squamous intraepithelial cells). The overall postpartum regression rate for the 59 women with antepartum high-grade squamous intraepithelial cells was 48%. Of the 47 women with high-grade squamous intraepithelial cells who were delivered vaginally, 28 showed regression in the postpartum period versus none of the 12 women delivered by cesarean section (60% vs 0%, p < 0.0002). CONCLUSION: Postpartum spontaneous regression of Papanicolaou smears consistent with high-grade squamous intraepithelial cells occurs with increased frequency among women who are delivered vaginally versus by cesarean section.     

Bactericidal activity of a fermented hot-water extract from Stevia rebaudiana Bertoni towards enterohemorrhagic Escherichia coli O157:H7 and other food-borne pathogenic bacteria

AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical records of 662 patients who underwent FNA cytology of the thyroid and thyroid surgery were analysed. Frozen section biopsies were taken from 586 of the 662 patients. The diagnostic correlations of FNA cytology, frozen section, and both FNA cytology and frozen section with definitive histological assessment were evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were 356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive predictive value for the detection of malignancy by FNA cytology was 92.1% and the negative predictive value was 95.2%. The incidence of malignancy in the indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in 7 cases (1.2%). By frozen section, the positive and negative predictive values were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when FNA cytology and frozen section diagnoses were in agreement. No false positives were observed when FNA cytology and frozen sections were both positive for malignancy. When FNA cytology and frozen section diagnoses were discordant, frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that FNA cytology is a useful tool in the initial evaluation of thyroid nodules. Intraoperative frozen section is a valuable procedure to confirm the cytological diagnosis and identify malignancy in patients with indeterminate or unsatisfactory cytological diagnosis. With reliance on frozen sections as an intraoperative guide of thyroid surgery, the possibility of unnecessary extensive surgery and the need for the second operation are considerably lower.     

Evolution of atypical gynecological cervical smears in a captive population

BACKGROUND: An atypical cervical smear may represent a wide variety of lesions, from banal diseases to invasive neoplastic lesions. AIM: To study the evolution of atypical cervical smears in a highly controlled women population. MATERIAL AND METHODS: A retrospective analysis of 117 women with atypical cervical smears, diagnosed between 1985 and 1994, was performed at the institutional hospital of a mining corporation in Chile. RESULTS: Patients age ranged from 25 to 65 years. Six percent of atypical cervical smears were associated to Papillomavirus infection and 25% to unspecific infectious agents. In the second smear, during follow up, 22.2% of women had some degree of squamous intraepithelial lesion or signs of Papillomavirus infection. A cervical biopsy was performed to 69 women, confirming the presence of a squamous intraepithelial neoplasia or signs of Papillomavirus infection in 38.4% of them. Only one patient had microinvasion. CONCLUSIONS: All patients with atypical gynecological cervical smears should be closely followed to ascertain the diagnosis.     

Fine needle aspiration cytology of oral and pharyngeal lesions. A study of 45 cases

Forty-five patients with oral or pharyngeal swellings were subjected to fine needle aspiration cytology (FNAC) of the mucosal surface over eight years. The age of the patients ranged from 2 to 85 years. The male:female ratio was 25:20. The common sites of involvement were palate (16 cases), cheek (9), pharynx (7) and tonsillar/peritonsillar area (6). Tongue, maxilla, alveolus and lips were less frequently involved. FNAC played an important role in differentiating inflammatory from neoplastic lesions and also benign from malignant neoplasms. Fifteen cases were cytologically diagnosed as benign neoplasms and included pleomorphic adenoma (11 cases), schwannoma (2), odontogenic tumor (1) and benign neoplasm not otherwise specified (1). Sixteen cases were diagnosed as malignancies. There were seven cases of malignant salivary gland tumors and 6 of squamous cell carcinoma. Two cases were high grade non-Hodgkin's lymphomas, and one was malignant odontogenic tumor. Of the 11 inflammatory or reactive lesions, 4 were found to be harboring Actinomyces. The rate of inadequate sampling was 6.7%. Histopathology reports on excised tissue were available for 10 cases only. Seven of nine cases with adequate cytology (77.88%) showed complete agreement with histology.     

Social support among African-American adults with diabetes. Part 1: Theoretical framework

BACKGROUND: Atypical squamous cells of undetermined significance (ASCUS) is a cytopathologic term used to describe cases without specific pathologic substratum. Between 10-60% of ASCUS cases correspond to squamous intraepithelial lesions (SIL). METHODS: The objectives of this study were: 1) to detect the pathologic significance of ASCUS in study patients, 2) to determine whether PAPNET identifies these cases, and 3) to compare the results of PAPNET with those of a second conventional screening. One hundred and sixty-three consecutive patients with the cytologic diagnosis of ASCUS and adequate follow-up were selected. Of these, 111 patients had colposcopic lesions and biopsies were performed; in the remaining 52 cases colposcopy was negative, as were 3 consecutive annual Papanicolaou smears. In a blind review, all 163 cases were rescreened using PAPNET. A second manual screening was performed for comparison. RESULTS: One hundred and twenty-six of the 163 cases (77.3%) showed no SIL on biopsy or follow-up. Of the 37 pathologic cases, the diagnosis was koilocytosis (flat condyloma) in 13 cases (8%), cervical intraepithelial neoplasia (CIN) type I in 11 cases (6.8%) low grade SIL [LSIL] in a total of 24 cases [14.8%]), and CIN II-III or high grade SIL (HSIL) in 11 cases (6.8%). In the review using PAPNET, 57 previous ASCUS cases were classified correctly as negative, and 7 of 13 koilocytosis cases (54%), 9 of 11 CIN I cases (82%), and 7 of 11 CIN II-III cases (64%) were diagnosed correctly. In the second conventional screening, 74 cases were negative and 77 cases were ASCUS; only 3 of 13 koilocytosis cases (23%), 4 of 11 CIN I cases (36.4%) and 5 of 11 CIN II-III cases (45.5%) were reclassified correctly. CONCLUSIONS: Among 163 patients with ASCUS, 77.3% had no precancerous squamous lesions. Concordance with definitive diagnosis was more accurate in our study using PAPNET analysis (Kappa index [K] = 0.7158) than by second conventional screening (K = 0.4537). Furthermore, we reclassified 35% of smears as negative and 15% as SIL.     

Wisconsin Cytology Proficiency Testing Program. Results of voluntary testing in 1994

OBJECTIVE: The Wisconsin Cytology Proficiency Testing Program (WCPTP) was developed cooperatively by the Wisconsin State Laboratory of Hygiene, the Wisconsin Society of Pathologists and the Wisconsin Society of Cytology to enable pathologists and cytotechnologists in Wisconsin to meet Clinical Laboratory Improvement Act of 1988 (CLIA '88) requirements for proficiency testing (PT). STUDY DESIGN: A joint steering committee designed the WCPTP to comply with all CLIA '88 regulations. The WCPTP application to the Health Care Financing Administration received tentative approval in May 1994. In 1994, mock PT was conducted at meetings of both state societies, and voluntary, on-site PT was conducted at 19 laboratories. RESULTS: Each of the 119 participants (49 pathologists, 70 cytotechnologists) was tested with sets of 10 glass slides, each representing one of four specified categories: A, unsatisfactory; B, normal/benign; C, low grade squamous intraepithelial lesion; and D, high grade squamous intraepithelial lesion and cancer. The failure rate for pathologists was 22.5% (11/49) and for cytotechnologists, 1.4% (1/70). The CLIA '88 scoring system for pathologists is more stringent. If cytotechnologists were scored as pathologists, 10% (7/70) would have failed. Using the cytotechnologist grid, 14.5% (7/49) of the pathologists would have failed. CONCLUSION: This voluntary program provided some preliminary insights into the issues related to PT evaluation of personnel competence and diagnostic criteria.     

Negative predictive value of imaging-guided abdominal biopsy results: cytologic classification and implications for patient management

OBJECTIVE: Our purpose was to assess the negative predictive value of imaging-guided abdominal biopsy results and correlate it with cytology classification, lesion size, needle gauge, and cancer history. MATERIALS AND METHODS: A retrospective study was performed of 100 patients with proven diagnoses who had undergone imaging-guided abdominal biopsies showing no cells that were malignant or suspicious for malignancy. Specimens were classified as normal or benign, nondiagnostic, or atypical. Negative predictive value was calculated for each cytologic category, lesion size, needle gauge, and cancer history. Logistic regression analysis was performed to allow us to identify predictors of false-negative results. RESULTS: Overall negative predictive value was 67%. Other negative predictive values were normal or benign result, 78%; nondiagnostic result, 66%; and atypical result, 29%. Negative predictive value was greater when the lesion was large (> or =3 cm) (p = .031). Logistic regression analysis allowed us to predict a 9.3% chance of a false-negative result for a specimen of normal or benign cytology that was taken from a large lesion in a patient with no cancer history but an 87% chance of a false-negative when a specimen of atypical cytology was taken from a small (<3 cm) lesion in a patient with a cancer history. CONCLUSION: Imaging-guided abdominal biopsy specimens containing atypical cells should be viewed with caution. In patients without cancer, if a lesion is large and the specimen contains normal target organ or benign cells, the likelihood of a false-negative result may be low enough that imaging surveillance at appropriate intervals may be sufficient.     

Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings

OBJECTIVE: To determine the clinical implications of atypical glandular cells of uncertain significance (AGCUS) in cervical cytologic smears. STUDY DESIGN: Retrospective analysis. RESULTS: Eighty-eight of 32,181 (0.27%) cervical smears obtained during the study period contained AGCUS. Of the 47 women with AGCUS, 16 had intraepithelial or invasive neoplasms (34%; 95% confidence interval, 21-49%), including 9 low or high grade squamous intraepithelial lesions, 1 adenocarcinoma in situ of the cervix, 3 adenocarcinomas of the cervix, 2 adenocarcinomas of the endometrium and 1 adenoid basal cell carcinoma of the cervix. CONCLUSION: The high prevalence of cervical and endometrial neoplasia among women with the isolated finding of AGCUS on cervical cytologic smears warrants a thorough diagnostic evaluation.     

Oncogenic human papillomaviruses and ploidy in cervical lesions

AIM: To compare ploidy measurements obtained on tissue sections of selected low and high grade squamous intraepithelial lesions containing oncogenic HPV (types 16, 18 or 33) detected by in situ hybridisation (ISH) or PCR. METHODS: DNA ploidy was assessed by image cytometry after Feulgen staining of contiguous serial sections of eight lesions exhibiting atypical squamous cells or squamous atypia and 53 low and 63 high grade squamous intraepithelial lesions in which HPV had been detected by ISH or PCR. RESULTS: Aneuploidy was strongly associated with the presence of oncogenic HPV, being detected in 50% of lesions with squamous atypia and 75.5% of the low and 95.2% of the high grade squamous intraepithelial lesions. The multiploid profile was highly associated with high grade lesions and with the pattern of HPV DNA integration. CONCLUSIONS: The presence of aneuploidy is strongly suggestive of the presence of oncogenic HPV types. Combining the detection of HPV by ISH and PCR with DNA image cytometry may provide the pathologist and the physician with important prognostic information about low grade lesions, especially when these lesions have a multiploid DNA profile and contain oncogenic HPV.     

Comparing two modalities of management of women with cytologic evidence of squamous or glandular atypia: early repeat cytology or colposcopy

Early repeat cytology is recommended in most screening programs for cervical cancer in subjects with squamous or glandular abnormalities not amounting to neoplasia (atypical squamous cells of undetermined significance, ASCUS), but immediate colposcopy is also recommended in some countries, especially those where there is easy access to colposcopic facilities. We evaluated the cost-effectiveness of the two procedures in a prospective study of women with cytologic ASCUS, invited to cytocolposcopic assessment after 6 months. Colposcopy-directed biopsy was assumed as the gold standard, and the accuracy of colposcopy at 6 months was assumed to be equal to that of immediate colposcopy. Out of 874 compliers, punch biopsy was performed in 303 cases (34.7%), and 19 CIN2+ lesions were detected (CIN2 = 12, CIN3 = 6, microinvasive carcinoma = 1). Detecting 13 CIN2+ lesions at colposcopy required 874 colposcopies and 303 directed biopsies: the cost per CIN2+ lesion detected with the procedure was 2,749 US$. Detecting 15 CIN2+ lesions at repeat cytology required 874 cytologic examinations, 137 colposcopies, 64 directed biopsies, and 6 diagnostic large-loop resections, the latter being performed in subjects with high-grade squamous intraepithelial lesion and less severe lesions at punch biopsy: the cost per CIN2+ lesion detected with the procedure was 1,961 US$. The policy of repeat smear was more cost-effective than immediate colposcopy. According to such results, the protocol of the Florence screening program has been modified since October 1996.     

Quality of life of women with stress urinary incontinence with or without pollakiuria]

BACKGROUND: The optimal management of low grade Papanicolaou (Pap) smear abnormalities remains controversial. This center's experience with recommending cytologic follow-up for women with atypical cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL) was reviewed to determine outcome and patient/physician compliance. METHODS: The records were reviewed on women with Pap smears reported as either ASCUS (320) or LSIL (112) who did not have a history of dysplasia. The cytologic and colposcopic follow-up for a 2-year period was obtained from the laboratory data base that includes the colposcopy and cancer referrals for this region. Repeat Pap smear in 6 months was recommended. If patients subsequently demonstrated high grade SIL (HSIL) or persistent ASCUS or LSIL over three time intervals, colposcopic evaluation was recommended. RESULTS: The outcome was determined by the most significant diagnosis among the follow-up Pap smears or colposcopic biopsies. 29% of patients were lost to follow-up. Of the remaining patients, 70.5% reverted to normal or benign cellular changes, 25.3% persisted as ASCUS or LSIL, and 5.2% progressed to HSIL. The majority of patients (68%) were referred for colposcopy for persistent mildly abnormal Pap smears. The timing of referral ranged from 3-30 months. CONCLUSIONS: These results suggest that cytologic follow-up of women with low grade Pap smear abnormalities will identify a large number whose smears will regress to normal. A small but significant proportion of women showed subsequent HSIL. Most HSIL was detected within 1 year of the initial abnormal Pap smear and the majority of intervening Pap smears also were abnormal. Approximately one third of patients did not have follow-up within the study system and their outcome was uncertain. Although the recommendations are standard, patterns of follow-up and referral to colposcopy varied widely, suggesting that the guidelines need to be reinforced to both patients and physicians. [See editorial on pages 1-4, this issue.]