Colposcopy of patients with cytologic inflammatory epithelial changes

Of 3,308 cervical cytologies performed at a university health service between September 1986 and September 1987, 371 were reported as showing inflammatory epithelial changes (IECs). Colposcopy was offered to all patients with this diagnosis and was actually performed on 200 (54%). Of these women, 44 had an atypical transformation zone; of the 33 who were biopsied, 23 had histologic diagnoses ranging from human papillomavirus (HPV) infection (4 cases) to grade III cervical intraepithelial neoplasia (CIN; 4 cases). Most biopsies showed CIN I. In our clinic, the 95% confidence limits for the histologic diagnosis of HPV or CIN in women with a cytologic diagnosis of IEC are 8.5% to 23.5%. Colposcopic examination of women with IEC may be able to detect patients with CIN who are missed by standard cytologic screening. Concerns about a potential bias from false-positive histology reports must be resolved before such an approach can be recommended.     

Investigation of 208 consecutive cases of cervical cone biopsies with regard to indication, negative samples and quality control

OBJECTIVE: To analyze factors in preoperative management and cytologic screening leading to a conization specimen free of neoplasia. STUDY DESIGN: From January 2001 through December 2003, cervical conization was performed on 208 consecutive cases at the Gynecologic Department, Krankenhaus Lainz, Vienna. Indications for cone biopsy were based on suspicious internal and/or external conventional cytologic screening results followed by punch biopsies in selected cases. RESULTS: Benign cervical lesions were diagnosed in 22 women (10.6%). Histologic results in negative cone biopsies were cervicitis (n = 12), infection with HPV without cervical intraepithelial neoplasia (n = 1), tubal metaplasia (n = 4) and combined diagnoses indicating no neoplasia (n = 5). Regarding cytologic screening results prior to conization, long-lasting infections with HPV can cause repeated findings of cells of unknown origin or reversible mild to moderate dysplasia eventually leading to conization specimens free of neoplasia. Furthermore, tubal metaplasia is a frequent pitfall in misinterpretation of cytologic smears. CONCLUSION: Reevaluation of cytologic screening results after the final histologic diagnosis becomes available following cone biopsy is a key issue in continuous quality assurance for the diagnostic procedure. In this article we also present a method of stratifying screening results according to the correctness of the results. Along with other established measures of diagnostic performance, this may support benchmarking and interpretation of the overall cytologic screening quality.     

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.     

Fine needle aspiration of breast lesions in women aged 30 and under

Fine needle aspiration (FNA) biopsies of 1,598 breast masses were performed between 1983 and 1989, and of them, 48 were from women aged 30 and under for whom a cytologic diagnosis was made by FNA and histologic follow-up was available. In 37 (77%) of the cases, both the cytologic and histologic diagnoses were benign. Fibroadenoma (20/37) and fibrocystic changes (14/37) were the most common benign lesions aspirated. Eight (17%) FNAs showed cytologic atypia. Four of these atypical lesions proved to be benign (two fibroadenomas, two fibrocystic changes). Epithelial proliferation in fibroadenomas and fibrocystic changes and cellular stroma in a fibroadenoma mimicking phylloides tumor were the causes of atypia in these biopsies. Four of the eight atypical lesions were shown to be carcinoma at biopsy (three infiltrating duct, one atypical medullary). Low cellularity, epithelial cohesiveness mimicking a fibroadenoma and background lactational changes in a pregnant patient were the causes of the atypical, rather than unequivocally malignant, diagnoses in these cases. In three patients (6%), a diagnosis of carcinoma was made by FNA and confirmed histologically (all were infiltrating duct carcinoma). Although most breast masses in women aged 30 and under are benign, cytologic atypia in a breast fine needle aspirate in this age group warrants a surgical biopsy. Clinical follow-up alone may be appropriate for young women with clinically nonsuspicious breast masses without cytologic atypia.     

Evaluation of proposed cytomorphologic criteria for the diagnosis of Chlamydia trachomatis in Papanicolaou smears

To evaluate the proposed cytomorphologic criteria for the cervical cytologic diagnosis of Chlamydia trachomatis infection, a study was made of 171 endocervical smears. All cytomorphologic elements that could be ascribed to Chlamydia trachomatis infection were correlated with the diagnostic confirmation of this microorganism by monoclonal antibody (MAb) staining. The presence of Chlamydia trachomatis was detected in 21 samples (12.28%) by MAb staining. Comparing the cytomorphologic results with the MAb results, the sensitivities and specificities of the Papanicolaou smear diagnoses were 19% and 86% using the cytologic criteria proposed by Gupta and coworkers, 38% and 87% using the criteria proposed by Kiviat and coworkers and 23% and 91% using the criteria proposed by Shiina. In view of (1) its low sensitivity, (2) the subjective elements and individual variations in the proposed cytologic criteria, (3) the similarity with Trichomonas vaginalis-produced exudates and (4) the implications of a misdiagnosis of a sexually transmitted disease, it is concluded that cervical cytology is not useful for ascertaining the presence of Chlamydia trachomatis.     

Association of human papillomavirus and Chlamydia infections with incidence cervical neoplasia

Incidence cervical neoplasia is defined as disease that becomes manifest during a given period of observation. Association with preceding genital infections having characteristic cytologic findings would seem to be more likely for incidence than for prevalence cases since the usual long latency period of carcinoma in situ (CIS) could allow resolution of infectious processes. For this reason, it was elected to examine the preceding Papanicolaou smears from patients with tissue-confirmed incidence CIS or invasive epidermoid carcinoma. There were 67 women with biopsy-proven CIS or invasive carcinoma of the uterine cervix identified in the files of the University of New Mexico Cytopathology Laboratory from 1966 to 1982 who had two initial negative smears as well as smears at intervals of three years or less. All cytologic smears prior to tissue diagnosis were rescreened for confirmation of cytologic atypia or its absence as well as for morphologic evidence of human papillomavirus (HPV) or chlamydial infections. Control cases matched for age, gravidity, ethnicity and number of smears were reviewed in an identical manner. Koilocytes indicative of HPV infection were found in 17 index cases (25%) and 5 controls (7%) (p = 0.005). Chlamydial infections were identified in 18 index cases (27%) and in 4 controls (6%) (p = 0.001). The times required for conversion from smear negativity to malignancy were determined for each incidence case. The results showed great variability but suggest that the progression to malignancy is not hastened in women with antecedent HPV or chlamydial infections. Our results indicate that the presence of koilocytes and/or chlamydial inclusions in cervical smears serves to identify a group of women with a significantly increased risk of developing cervical carcinoma, even in the absence of concurrent dysplasia.     

Feasibility of cytology-based cervical cancer screening in rural Cameroon

OBJECTIVE: To determine the prevalence of cervical cancer and its precursors in a rural population in Cameroon and to evaluate the feasibility of a cytology-based screening program in such areas. STUDY DESIGN: A prospective study was conducted in the rural town of Bafang. Following an advocacy campaign, 750 women were recruited. After a clinical examination, all women had a Pap smear with the Cervex Brush. Each sample had two preparations, conventional and liquid based. The conventional smears were interpreted in Bafang. Cytologically abnormal cases, those with clinical inflammation and/or macroscopic cervical lesions, had a colposcopic examination and directed biopsy. HSIL and colposcopically abnormal cases were treated with large loop excision of the transformation zone (LLETZ). The liquid-based preparations and histopathology were performed in Geneva and the results sent to Cameroon for patient follow-up. RESULTS: Mean age and parity of the women screened were 43.7 years and 7.8, respectively. The conventional smears showed 3.6% cervical abnormalities: 2% (15/740) ASCUS/LSIL and 1.6% (12/740) HSIL. The liquid-based preparations showed 12.6% (91/722) cervical abnormalities: 10.1% (73/722) ASCUS/LSIL and 2.5% (18/722) HSIL. Fifty percent of samples in both preparations showed evidence of inflammation. Histology was performed on 64 colposcopically directed punch biopsies and LLETZ specimens. The histologic diagnoses agreed with the cytologic findings in 60% (14/23) of conventional smears and 85% (12/14) of liquid-based preparations. CONCLUSION: There is a high rate of cervical intraepithelial neoplasia in the unscreened rural population of Cameroon. The situation is complicated by a high rate of cervical infection. A population-based cytologic screening program for cervical cancer would not be feasible in rural Cameroon because of high cost, low quality and limited technical facilities. Rural Africa requires an algorithm using a simple, low-cost technique of mass screening and an improved cytology service only to triage selected patients.     

"Nonclassic" cytologic signs of cervical condyloma. A case-control study

The association between "nonclassic" cytologic signs of condyloma and human papillomavirus (HPV) infection in women with negative Papanicolaou smears was analyzed via a case-control study. The cytologic signs considered were mild koilocytosis, mild dyskeratosis, binucleation or multinucleation, cleared cytoplasm and nuclear hyperchromatism. The Papanicolaou smears of 166 cases that showed colposcopic and histologic evidence of HPV infection (but whose smears lacked the classic cytologic signs of condyloma) and 166 controls that were negative colposcopically were randomly admixed and blindly reviewed by a panel of cytologists. A significant association to HPV infection was observed for all of the nonclassic signs studied, but multivariate analysis showed a weakly independent association only for mild koilocytosis. The sensitivity (0.46) and the specificity (0.87) of these nonclassic signs were not satisfactory. The utility of selecting women with negative Papanicolaou smears for colposcopy on the basis of these signs is discussed.     

Fine needle aspiration cytology of neoplasms metastatic to the breast

The fine needle aspiration (FNA) cytologic findings in 18 cases of metastatic neoplasms of the breast are reported. The cases were encountered in a combined series of 2,529 FNA breast biopsies, of which 666 were malignant; the metastatic neoplasms of the breast thus constituted 2.7% of all the malignant breast tumors. The series consists of 15 women and 3 men, with a mean age of 48 years (range of 11 to 73 years). Sixteen biopsies confirmed metastatic malignancy in patients with known extramammary primaries; the prebiopsy clinical diagnoses in six of the patients were benign breast lesions. In eight patients, the clinical differential diagnosis was either a benign or malignant primary breast lesion versus a metastatic malignancy. In two additional patients, the FNA biopsy identified metastatic neoplasms from unsuspected extramammary primaries. The metastatic neoplasms included three small-cell carcinomas of the lung, one squamous-cell carcinoma of the lung, two malignant melanomas, three ovarian malignancies, including a dysgerminoma, and one each of carcinoma of the fallopian tube, endometrial carcinoma, transitional-cell carcinoma of the urinary bladder, prostatic carcinoma, acute granulocytic leukemia, lymphoma, mycosis fungoides, hepatoma and neuroblastoma of the retroperitoneum. Recognition of unusual cytologic patterns raised the suspicion of, or confirmed the diagnosis of, malignancy in all cases, with no false-negative diagnoses. None of the cases were cytologically interpreted as a primary breast malignancy. Ancillary studies performed on the FNA material, including immunocytochemistry, contributed to a definitive diagnosis in three cases. FNA diagnosis of metastatic malignancy of the breast is essential in order to avoid unnecessary mastectomy and to ensure appropriate chemotherapy and/or irradiation treatment.     

Cervical smear abnormalities in the United Arab Emirates: a pilot study in the Arabian Gulf

OBJECTIVE: To gather epidemiologic data on cervical abnormalities and make recommendations pertaining to a national cervical screening policy in the United Arab Emirates (UAE). STUDY DESIGN: A cross-sectional survey of patients and physicians in the UAE with regard to cervical cytology was carried out. Knowledge, attitudes and practices (KAP) of a group of female primary care physicians on cervical cytology were assessed by a self-administered questionnaire. Pap smears and Chlamydia testing were offered to women attending selected primary care centers and secondary health care facilities. RESULTS: Results of Chlamydia prevalence and KAP were published elsewhere; this report addresses the cytologic aspects of this study. There were 2,013 smears collected from primary health centers and 2,042 from secondary care. The overall rate of cervical screening among women in this survey was 85.5% in primary care and 77% in secondary care. The proportion of unsatisfactory smears was < 5%. The prevalence of cervical abnormalities according to the Bethesda System 2001 was 3.6%. There were 9 (primary care) and 21 (secondary care) cases of low grade squamous intraepithelial lesion (LSILs), for a prevalence of 0.77%. There were 4 primary care and 17 secondary care cases of high grade squamous intraepithelial lesion (HSIL), for a prevalence of 0.54%. The combined prevalence for LSIL and HSIL is 1.32%. There were 3 cases of glandular abnormalities. The atypical squamous cells of undetermined significance/SIL ratio was 1.71. No cases of squamous cell carcinoma were detected. No tissue follow-up information is available. The prevalence of cervical abnormalities is low in the UAE. We first recommend the institution of a more organized approach to opportunistic screening in the UAE with appropriate clinical follow-up rather than the immediate launch of a cervical mass screening program.     

Detection of Chlamydia trachomatis in Papanicolaou-stained cervical smears by an indirect immunoperoxidase method

A two-step (indirect) immunoperoxidase method directed against Chlamydia trachomatis was developed. The method was then used to evaluate the specificity of cytologic changes suggestive of C. trachomatis in Papanicolaou smears of cervical specimens from women who were culture-negative for the organism. Positive immunoperoxidase staining was detected in 9 of 21 cases (43%) tested. Technical problems, especially background staining, precluded interpretation in the remainder of the cases. Cervical cytology, as demonstrated by immunoperoxidase staining, may, in some instances, be more sensitive than the culture. However, because the etiology of cytologic changes not specifically identified by immunoperoxidase staining may be due to other organisms or factors, immunoperoxidase procedures, as described, should not replace culture for confirmation of cytologic findings suggestive of C. trachomatis.     

Urethral cytology of Cytobrush specimens. A new technique for detecting subclinical human papillomavirus infection in men

Cytologic examination of urethral smears prepared with the Cytobrush and colposcopic examination of the penis were performed in 53 male partners of women with cervical human papillomavirus (HPV) infections and in 14 healthy controls. A diagnosis of HPV infection was recorded in 28 subjects (52.8%). Cytology was positive in 26 cases (49%) and colposcopy was positive in 5 cases, with both tests positive in 3 cases. No controls were positive by cytology or colposcopy. These findings suggest that urethral cytology and colposcopic examination should be routinely performed in partners of women with HPV infections to detect inapparent infections. The Cytobrush should be employed for the urethral cytologic sampling; smears prepared by other techniques (urine collection or urethral swabbing) yield lower detection rates.     

Interobserver variability in the fine needle aspiration biopsy diagnosis of follicular lesions of the thyroid gland

OBJECTIVE: To study the degree of interobserver variability in the interpretation of fine needle aspiration (FNA) biopsies of the thyroid, specifically in the categorization of follicular lesions (FLs), and to examine the accuracy of FNA diagnosis of FLs with surgical follow-up. STUDY DESIGN: Fifty cases were chosen with surgical follow-up and a cytologic diagnosis of either FL (21) or follicular neoplasms (29). Representative slides were selected for each case and circulated to 4 pathologists for review. Interobserver variability was assessed using pairwise K statistics. Accuracy of the cytologic diagnoses in predicting a nonneoplastic or neoplastic outcome was determined by measuring sensitivity and specificity. Likelihood ratios and receiver operator characteristic curves were calculated for each reviewer. RESULTS: Interobserver agreement between the 4 pathologists was fair to substantial (K scores, 0.199-0.617). The accuracy of the 4 pathologists' cytologic diagnoses in predicting the surgical outcome was 77-90% for follicular neoplasms and 53-74% for nonneoplastic diagnoses. CONCLUSION: FLs present diagnostic difficulties as to cytologic categorization. A wide range of interobserver agreement was found in this study of 4 pathologists from the same institution. Some pathologists make greater use of intermediate categories, such as FL, favor nonneoplastic, or FL, favor neoplastic, whereas others show more definitive categorization into benign and neoplastic groups.     

Inflammatory atypia and the false-negative smear in cervical intraepithelial neoplasia

The effectiveness of cervical cytologic screening is compromised by the increasingly recognized prevalence of false-negative smears. Our previous studies suggested that some false-negative cytologies can be accounted for by smears showing cervical intraepithelial neoplasia (CIN) reported as inflammatory atypia; we found that at least 4% of 5,752 consecutive smears had been underreported in this manner. In the present study, that data was reanalyzed to derive 95% confidence limits for the number of CIN smears reported as inflammatory atypia. Using several differing estimates of cytologic screening sensitivity, it is speculated that, under certain testable assumptions, colposcopy of patients with cytologic diagnoses of inflammatory atypia may be one cost-effective approach to finding CIN cases missed by screening. If confirmed, these findings imply that laboratory quality assurance efforts, traditionally directed to the most serious cytologic diagnoses, should also focus in part on nondysplastic atypia.     

Positive predictive value of fine needle aspiration cytology of breast lesions

The predictive value of fine needle aspiration (FNA) was assessed in 1,181 consecutive cases of breast lesions in which cytologic abnormalities were reported. The positive predictive value (PPV) of an FNA cytologic report of atypia, suspicious or positive was 0.49, 0.95 or 0.996, respectively. In the presence of a suspicious/positive report by both physical examination and mammography, the PPV of a cytologic report of suspicious was 0.99. The PPV was directly correlated with age, partly due to the incidence of fibroadenomas among younger patients; fibroadenomas were present in 53 of 146 cases with a false FNA report of atypia, in 10 of 19 cases with a false FNA report of suspicious and in 2 of 2 cases with a false FNA report of positive. Overall, 93 cases reported as benign by physical examination and mammography were biopsied on the basis of the FNA cytologic report; cancers were diagnosed in 33 of these 93 cases (6 cancers among 42 women less than 40 years old and 27 cancers among 51 women greater than 39 years old). The widespread use of FNA cytology to study breast lesions is thus recommended, without regard to patient age and even in the presence of clinically benign findings, since the increase in the rate of cancer detection is worth the excess of unnecessary biopsies. The predictive value of a positive report of FNA cytology, or even of a suspicious report in the presence of clinical suspicion, is so high that an intraoperative frozen section biopsy might be spared in such cases.     

Prevalence of chlamydial genital infection and associated risk factors in adolescent females at an urban reproductive health care center in Croatia

The study was undertaken to determine the prevalence of chlamydial genital infection in sexually active, urban adolescent females 15-19 years; to identify behavioral, demographic, and clinical factors associated with chlamydial infections; and to develop criteria for potential screening strategies. 500 adolescent women, median age 17.7 years, who visited gynecological outpatient clinic in Children's Hospital Zagreb for different reasons were enrolled in this study. Gynecological exam, colposcopy, detection of chlamydial infection by the rapid direct immunoassay of endocervical swab (Clearview Chlamydia-Unipath), endocervical cytological examination--Papanicolaou smear, and questionnaire to obtain demographic, social, behavioral and presence of symptoms data were performed. Positive Chlamydia trachomatis test were found in 16.4% of participants, cytologic cervical abnormalities--cervical intraepithelial neoplasia (CIN I-CIN III) were found in 25.2% and cytological signs of Human papilloma virus were found in 11.4%. Stepwise multivariate logistic regression analysis identified five factors associated with infection: the age of menarche < or =13 years, > or =4 lifetime sexual partners, non-use of contraception (rare or never), cervical friability, and abnormal Papanicolaou test. Urban adolescent sexually active women are at high risk for chlamydial infection and other sexually transmitted diseases including HIV infection. Association between chlamydial genital infection and risk-taking sexual and contraceptive behavior was found. Routine Chlamydia trachomatis testing for this population is recommended as well as implementation of school based sexual health education because of their risk-taking sexual behavior.     

Is screening for bacteriuria in pregnancy worth while?

A total of 4470 pregnant women were screened for bacteriuria by the dipslide method and significant growth found in 226 (5.1%). In 198 cases the urine was re-examined, in 119 by using suprapubic aspiration or catheterisation (62 (52%) samples contained bacteria) and in 79 by using midstream urine samples (26 (33%) samples contained greater than 10(8) colony forming units/1), showing the maximum prevalence of confirmed bacteriuria to be 2.6%. Overt urinary tract infection developed later in four of 80 patients with proved bacteriuria who had been given antibiotics, in one of eight untreated patients with bacteriuria, in one of 110 patients with unconfirmed bacteriuria, and in one of 226 non-bacteriuric controls. A history of urinary tract infection was given by 18% of controls and 42% of women with confirmed bacteriuria. Screening for bacteriuria and treatment with antibiotics to prevent later overt infection is expensive. Whether it is worth while and cost effective depends largely on the prevalence of bacteriuria in the local population and the proportion who develop overt infection. The screening and treatment programme reported here appeared to prevent only six cases of overt infection.     

Improving the sensitivity of cervical cytologic screening. A comparison of duplicate smears and colposcopic examination of patients with cytologic inflammatory epithelial changes

During a ten-month period, 264 cervical cytologic specimens were submitted in duplicate to two separate cytology laboratories. An attempt was made to perform colposcopy on all 45 patients reported as having an abnormality by either laboratory. All but one patient with a cytologic diagnosis of cervical intraepithelial neoplasia (CIN) underwent colposcopy, as did 68% of the patients with a diagnosis of nondysplastic atypia (inflammatory epithelial changes [IEC]). Five cases of histologically verified CIN were found by colposcopic study of patients with a cytologic diagnosis of CIN; two additional cases were found by colposcopic study of patients with a cytologic diagnosis of IEC. On the assumption that patients not colposcoped were not systematically different from the others with IEC, the screening sensitivities for both laboratories and for cytology followed by colposcopy of IEC cases were estimated. A statistically significant improvement in screening sensitivity was achieved by colposcopic examination of patients with IEC. This conclusion was tempered by a Bayesian analysis that suggested that some of the apparent improved sensitivity could be due to falsely positive biopsy reports. Despite potential benefits, it is premature to recommend universal colposcopic examination of patients with cytologic reports of inflammatory epithelial changes.     

The diagnostic reliability of cytologic typing in primary lung cancer with a review of the literature

To evaluate the growing tendency in recent years to attribute more diagnostic reliability to cytologic methods, we investigated the accuracy of cytologic typing in specimens obtained from bronchopulmonary material by five different clinical sampling methods, comparing the cytologic diagnoses with the known histologic diagnoses. The study consisted of 232 cytologic specimens from 157 cases of primary lung cancer. Of the 232 specimens, 173 (75%) were correctly typed and 59 (25%) incorrectly typed with respect to the appropriate histologic diagnoses. When all sampling methods were considered together, the study demonstrated that well-differentiated epidermoid carcinoma and "oat cell" and spindle-polygonal anaplastic carcinomas yielded high cytologic typing accuracies. In poorly differentiated tumors, bronchioloalveolar cell carcinoma and bronchogenic adenocarcinoma, the correct cytologic typing was much lower. The different tumor types and their degrees of differentiation seem to be the decisive factors in cytologic typing accuracy. The findings of this study were compared with those of others and were found to be consistent with the results of even larger series of cases. For some types the typing accuracy was higher than that reported in other series, whereas for other types, e.g., adenocarcinomas, it was lower.     

Cytologic detection of hepatic metastases

Cytologic preparations and histologic specimens from 404 liver biopsies were reviewed. The cytologic specimens were prepared from the saline rinsings of the Klatskin biopsy needle. Malignant neoplasms were detected by both methods in 50 cases. In seven cases, neoplasms were diagnosed by cytologic techniques alone; in nine cases neoplasms were present in the biopsy only. No false-positive cytologic diagnoses of malignancy occurred. The results of this study show that cytologic examination of the rinsings of the biopsy needle is a sensitive and highly specific adjunct to biopsy in the detection of hepatic metastases.