THE PAPANICOLAOU-TRAUT METHOD OF CANCER DIAGNOSIS,Its Use as a Routine Pathologic Laboratory Procedure

In a series of 450 examinations by the smear technique in the pathologic laboratory of a small private hospital, the total diagnostic error on all smears was 6.6 per cent. The error on vaginal smears was 4.7 per cent. These figures include false positives, false negatives, and all those smears classified as suspicious even though positive or negative diagnoses were made on subsequent examinations.The Papanicolaou-Traut method of cancer diagnosis can easily be made one of the routine pathologic procedures in the small hospital laboratory. Technicians with little previous cytologic experience can be trained to screen vaginal and other smears accurately after a short training period. This cytologic method is proving to be of value in the early detection of some neoplasms, and if its application is to be extended, the practicing pathologist should add the test to his diagnostic routine.     

Vaginal intraepithelial neoplasia and the Pap smear

OBJECTIVE: To assess the sensitivity of the vaginal smear cytologic examination in detecting vaginal intraepithelial neoplasia (VAIN) and to evaluate the cytologic findings of cases of VAIN. STUDY DESIGN: Cases with a histologic diagnosis of VAIN were identified from the Barnes-Jewish Hospital South and North Campus over a period of five and nine years, respectively. Only posthysterectomy patients with a tissue biopsy diagnosis of VAIN and with a vaginal smear obtained within three months of the biopsy were included in the study. Pertinent clinical information was obtained by reviewing the medical records. Two pathologists reviewed the pathologic samples. RESULTS: Thirty-five vaginal smears from 31 posthysterectomy patients were included in the study. The mean age was 57 years (range, 29-84). The cytologic diagnoses of smears from patients with VAIN included: high grade squamous intraepithelial lesion (19 cases), low grade squamous intraepithelial lesion (10 cases), atypical squamous cells of uncertain significance (5 cases) and negative for malignancy (1 case). CONCLUSION: The sensitivity of the vaginal smear cytologic examination in detecting VAIN is 83%. Obscuring inflammation contributed to false negative diagnoses in two cases.     

Cytologic Diagnosis of Gastric Cancer

Follow-up of cytologic examinations of specimens obtained from 187 patients by gastric lavage with saline solution, without the use of enzymes or abrasive devices, showed a false positive rate of 0.6 per cent and a false negative rate of 17 per cent.To achieve satisfactory results with such examinations, great attention to detail in obtaining, preparing and examining the specimens is essential. Cytologic examination should be done in any case in which gastric cancer is suspected clinically or roentgenographic or gastroscopic findings arouse suspicion.     

Microscopic diagnosis of vulvovaginal candidiasis in stained vaginal smears by Dutch general practitioners

OBJECTIVE: To determine the accuracy of the microscopic diagnosis of vulvovaginal candidiasis (presence of [pseudo] hyphae and blastospores) in stained vaginal smears in clinical practice. STUDY DESIGN: General practitioners trained in diagnosing vulvovaginal candidiasis performed microscopy of 324 stained vaginal smears. These smears were sent to the pathologist for confirmation of the microscopic diagnosis of the clinician; cytologic diagnosis by the pathologist was considered the gold standard. RESULTS: In 104 of the 342 cases Candida was established by the pathologist. The clinicians made 24 false positive and 50 false negative diagnoses of Candida. Sensitivity and specificity of the microscopic diagnoses of the clinicians were 52% and 89%, respectively. The most frequent reason for a false positive diagnosis was presence of hairs, whereas the most frequent reason for a false negative diagnosis was understaining of the smear. CONCLUSION: This study shows that even in stained smears it is difficult for clinicians to recognize blastospores and (pseudo)hyphae. Efforts are clearly needed to improve the quality of the clinical diagnosis of vulvovaginal candidiasis.     

Vaginal cytology in endocrinopathies

In order to evaluate the diagnostic significance of vaginal smears in endocrinopathies associated with menstrual disorders, the cytologic pattern of vaginal smears was examined in 703 patients who had a well-established diagnosis of the disorder's origin. The patients were classified into four groups according to their menstrual disorders: primary amenorrhea (159 patients), secondary amenorrhea (116 patients), primary oligomenorrhea (214 patients) and secondary oligomenorrhea (214 patients). Using the maturation index and the maturation value, three cytologic patterns of vaginal smears were distinguished: parabasal cell pattern, intermediate cell pattern and superficial cell pattern. The frequency with which the cytologic patterns occurred in the groups of patients and their subdivisions are presented. As a whole, the 703 patients showed 25.2% with a parabasal cell pattern, 58.3% with an intermediate cell pattern and 16.5% with a superficial cell pattern. Although the cytohormonal pattern of vaginal smears in endocrinopathies with associated menstrual disorders is not diagnostic of a specific endocrinopathy, the cellular patterns may prove helpful in suggesting a range of diagnoses or in excluding some possibilities.     

VAGINAL SMEARS—A Plea for More Critical Evaluation

To determine whether a conscious effort to reduce the incidence of equivocal (Class III) vaginal cytologic smear readings might have demonstrable clinical value, we have compared a previous study of our predictive efforts with a recent experience in screening a similar number of patients.It was possible to achieve an appreciable reduction in the incidence of Class III smears—from 2.4 per cent to 0.6 per cent. There was a modest increase in the reliability of the Class III smear as an indicator of cancer and a very notable increase in the reliability of the Class IV and V interpretations. While only 66 per cent of the earlier group with Class IV and V smears were shown to have cancer, 86 per cent of the present series with IV and V readings had malignant disease (97 per cent of the Class V group).The ultimate yield of malignancies was similar in the two series, but theoretically the overloading of Classes III, IV and V with women who do not actually have cancer necessarily leads to large numbers of diagnostic surgical procedures that might be avoided. Class III should be used to denote merely a temporary state of inconclusiveness rather than a real suspicion of cancer. With proper collaboration between physician and cytologist, most of the initially confusing situations can be either upgraded or downgraded to the proper rating, and eventually the bulk of patients standing to profit from conization will fall into Classes IV or V.     

Sensitivity and specificity of the Papanicolaou-stained cervical smear in the diagnosis of Chlamydia trachomatis infection

Two hundred young women had simultaneously prepared cultures for Chlamydia trachomatis and cervical smears; they also completed a questionnaire. Twelve of the chlamydial cultures were positive. There was poor correlation between the culture results and the cytologic morphology or symptoms. On initial blind reading, only 10% of the smears cytologically interpreted as positive were actually positive by culture. Under the most favorable (non-blind) interpretation, only 23% of the smears cytologically interpreted as positive for chlamydial infection were also culture positive. Because of the high incidence of false positives, we conclude that routine cytologic examination of Papanicolaou-stained smears is not an acceptable method for the diagnosis of chlamydial infections of the cervix. Immunoperoxidase staining of duplicate smears did not appear to be a successful replacement for culture.     

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.     

Retroperitoneal extramedullary anaplastic plasmacytoma masquerading as sarcoma: Report of a case with an unusual presentation and imprint smears

BACKGROUND: Extramedullary plasmacytoma of the retroperitoneum is rare. Furthermore, plasmacytoma with anaplastic features can be confused with high grade sarcoma clinically and histologically, particularly when the initial immunohistochemical tumor markers are negative. However, paying attention to cytologic imprint smears can give valuable clues to the correct diagnosis. CASE: A 73-year-old male was admitted to our hospital with a recent history of back pain. Abdominal computed tomography revealed a large retroperitoneal mass (6.8 x 5.1 cm). The initial pathologic evaluation revealed a high grade pleomorphic neoplasm that failed to express multiple epithelial, mesenchymal, lymphoid and melanoma immunohistochemical markers. Subsequent fresh tissue evaluation with touch imprints and immunophenotypic characterization confirmed the plasma cell origin of the tumor. Thorough retrospective review of the touch imprint smears clearly showed the plasmacytic cytologic features. Features of multiple myeloma were essentially absent. CONCLUSION: Performing cytologic imprint smears on fresh tissue material may help in making the correct diagnosis and is highly recommended.     

Fine needle aspiration of toxoplasmic (Piringer-Kuchinka) lymphadenitis: a cytohistologic correlation study

OBJECTIVE: To define the cytomorphologic features of toxoplasmic lymphadenitis (TL) and to establish the diagnostic sensitivity and specificity of the cytologic diagnosis. STUDY DESIGN: A cytohistologic correlation study of 11 patients in which a histologic diagnosis of TL was available. These cases were analyzed in a blind study among other cases of nonneoplastic lymphadenopathies. The results of the study are expressed in terms of diagnostic sensitivity and specificity. Although not included in the study, 3 other cases of TL with serologic confirmation were also reviewed. RESULTS: Microgranulomas were a characteristic finding in TL. They consisted of small clusters of epithelioid histiocytes, each with abundant cytoplasm and an eccentric, oval nucleus. Diff-Quik-stained smears had cytoplasm with particularly pale staining and a homogeneous appearance. Most microgranulomas had a monotonous appearance with a few, small lymphocytes accompanying the epithelioid cells. No necrosis, suppurative changes or giant cells were present. Blind examination by 4 reviewers led to a correct diagnosis of TL in 9 of the 11 cases. Eight of the 9 cases were recognized by each of the 4 reviewers. One false positive diagnosis was made by 1 of the reviewers. The sensitivity of the diagnosis was 72.7-81.8% and the specificity 98.8-100%. CONCLUSION: This study showed high sensitivity and specificity for the cytologic diagnosis of TL. Given the appropriate clinical context, the presence of characteristic epithelioid microgranulomas permits a diagnosis of TL. The cytologic diagnosis can be easily confirmed with serologic studies, thereby avoiding biopsy.     

Acceptability of the Cytopipette in General Hospitals

Altogether 2,798 cytopipette smears have been taken by patients entering the general medical and surgical wards of a hospital. Twelve unsuspected positive smears were found, a rate of 4 per 1,000. Biopsy of these patients has shown five pre-malignant lesions, one invasive carcinoma of cervix, and one carcinoma of corpus uteri. Five patients await biopsy.The cytopipette is both acceptable to the patient (62% acceptance) and a feasible laboratory technique and can produce good cytological smears. Only 30% of patients entering the hospital had already had the opportunity to obtain a smear before, and most of them welcomed the opportunity for the test.Though the self-pipette may be criticized for its inaccuracy we feel that any test, if it can detect cervical abnormality at the rate of 4 women per 1,000, is better than no test at all. It should have a place in routine cytological testing of women second only to the use of Ayre''s spatula.     

Cytology of pulmonary adenocarcinomas showing enteric differentiation

OBJECTIVE: To evaluate cytologic differences between primary pulmonary adenocarcinomas showing enteric differentiation (PAED) primary pulmonary adenocarcinomas of ordinary structure (PAC) and pulmonary metastases from colorectal carcinomas (MCR). STUDY DESIGN: During an 18-year period (1986-2003), cytologic materials were obtained from 5 PAEDs confirmed by pathologic examination of surgically resected specimens at the Cancer Institute Hospital. Aspiration cytologic and/or imprint smears of routine samples stained by the Papanicolaou method from the PAED cases were reviewed in comparison with 10 cases each of PAC showing a tubular pattern and MCR. RESULTS: The aspiration biopsy cytology and imprints showed similar features. Abundant necrotic debris in the background was recognized in a majority of all cases independent of the group. None to slight overlapping of tumor cells and less frequent palisading or glandular arrangements were characteristic features of PAED, significantly differing from MCR. Moreover, differences in nuclear features were evident as follows: in the MCR group, nuclear chromatin was hyperchromatic and coarsely condensed, and there were prominent nucleoli, whereas a slightly hyperchromatic pattern with some small to enlarged nucleoli was typical of PAED and PAC cases. CONCLUSION: Although diagnosis of PAED by routine cytology is difficult due to the features of the lesion, differential diagnosis between PAED, PAC and MCR is a possible using conventional cytologic criteria.     

Vaginal and oral cytology of the menopause. A comparative study

A comparative cytologic study was made of the hormonal content of the vaginal and oral mucosa of menopausal women. Twenty-three women between one and ten years (early menopause) and 33 patients more than ten years (late menopause) after cessation of menstruation had oral and vaginal smears taken. Comparable smears from 21 young women, and oral smears from 18 males served as controls. The smears were evaluated by the maturation value method, and averages were established for each group. The vaginal smears had low maturation values of 40 and 22 in the early and late menopausal groups, respectively. In these women, the buccal smears' maturation values were high, above 70. Similar high maturation values were found in buccal smears of the young women and men. It was concluded that the high maturation values found in the oral smears of the menopausal women are not the result of hormonal effect but that of local mechanisms or irritative factors.     

Performance of 3 methods for quality control for gynecologic cytology diagnoses

OBJECTIVE: To evaluate performance and viability of internal quality control (QC) strategies in a public health laboratory of the state of S?o Paulo. STUDY DESIGN: A retrospective study was performed with 3 QC strategies to improve internal cytologic diagnoses: morphologic guided-list criteria (MGLC), 100% rapid-rescreening (100% RR) of negative slides ("turret" method) and 10% rescreening (10% R) of negative slides. Cases were examined at Adolfo Lutz Institute, S?o Paulo, Brazil, from 2002 to 2004. Histopathologic results, when available, were considered gold standard; cytologic consensus diagnosis was by 2 pathologists when histologic results were unavailable. RESULTS: MGLC selected 20.7% samples with cytologic atypias, 10% R selected 0.6% and RR selected 2.5%. Cytologic/histologic initial concordance was 57.4%, low-grade squamous intra-epithelial lesion false negative rate was 34.9% and high-grade squamous intraepithelial lesion false negative rate was 12.2%. After diagnosis, consensus concordance was 97.2%. CONCLUSION: The 100% RR and 10% R QC strategies detected more false negative cases in liquid-based cytology than in conventional Pap smears. The 100% RR strategy reduced the false negative results and allowed evaluation of individual staff performance. The 10% R strategy did not offer significant results. We concluded that association of MGLC and 100% RR strategies might improve cytologic diagnostic quality.     

An approach to the problem of false negatives in gynecologic cytologic screening

A system of quality control for gynecologic cytologic screening designed to minimize the problem of false-negative cytologic reports is proposed. The system involves the harvesting of "quality control" smears, at the time of colposcopic examination, from patients referred to colposcopy because of previous abnormal smears that had been interpreted as representing dysplasia or neoplasia. These quality control smears are then submitted to the cytology laboratory, indistinguishable from bona fide cases, among the routine smears. This appears to be a more effective means of quality control than the current standard system used in the United States, which involves cytology laboratories routinely rescreening 10% of the slides reported out as "negative".     

Detection of false negative Pap smears by rapid reviewing. A metaanalysis

OBJECTIVE: To explore the diagnostic validity of rapid reviewing (RR) as a quality control method in cytologic laboratories. STUDY DESIGN: Fourteen studies dealing with the detection of false negative Pap smears by RR were included in a metaanalysis. RESULTS: The overall additional yield of positive slides, expressed as the percentage of all reviewed slides, is: 0.18% (95% confidence interval [CI]: .14-.21) for all cytologic abnormalities; 0.07% (CI: .05-.09) for squamous intraepithelial lesions (SIL) and 0.02% (CI: .01-.03) for high grade SIL. The false negative rate of primary screening, evaluated by RR, was 2.0% (CI: 1.5-2.6) for all cytologic abnormalities and 1.4% (CI: .8-2.1) for high grade SIL. The specificity of rapid rescreening was estimated as 97.2% (CI: 96.4-98.1). The positive predictive value of suspicion at RR is about 8.8%. Seven references contained historical data on full rescreening of a random sample of slides reported originally as negative. The results were also pooled and compared with RR. Complete rescreening is more sensitive, but if applied on only 10% of the negative workload, it would yield, on average, 4.7 times fewer extra positives, 5.6 times fewer SIL and 7.9 times fewer high grade SIL in comparison with RR of all sides. CONCLUSION: RR of all smears initially reported as nonpositive is a more effective and a fortiori a more cost effective quality control method in comparison with full rescreening of a 10% random sample.     

Rapid (partial) prescreening of cervical smears: the quality control method of choice?

Rapid rescreening of all negative and inadequate smears is the quality control method of choice in the UK. The sensitivity of primary screening of laboratory and individual screeners are major indicators of screening quality and are dependent on the number of false negative smears found by rapid screening for their calculation. High sensitivity may indicate good quality primary screening or poor quality rapid review. Quantifiably high quality rapid rescreening is essential if these sensitivity figures are to be meaningful. A 12-month study was undertaken in routine practice using the prescreening mode to ascertain the sensitivity of rapid (partial) screening in our department. The final results of smears were compared with those of rapid prescreening. The calculated sensitivity ranged from 92-54% for high-grade abnormalities and 75-33% for all grades, revealing a wide range of performance between individual prescreeners. Rapid prescreening can identify individuals best suited to rapid screening in routine practice. By using these prescreeners only, the sensitivity of cervical screening could be raised. Rapid (partial) prescreening should be considered as the quality control method of choice.     

Adenoid cystic carcinoma of the uterine cervix. Cytologic features

A case of primary cervical adenoid cystic carcinoma in a 75-year-old woman is reported. Two cervical smears taken at the time of initial presentation for vaginal spotting were negative; a third smear, taken a year later prior to laparotomy, was diagnosed as positive. The cytologic findings in the positive cervical smear are described and illustrated. The differential diagnosis of the cytologic findings is discussed, and the literature on this lesion is briefly reviewed. The results in this case and others suggest that the diagnosis of cervical adenoid cystic carcinoma in an asymptomatic patient may be missed by routine smear examination.     

Monitoring laboratory performance by statistical analysis of rescreening cervical smears

The rescreening of cervical cytology smears, although inadequate both for checking the reliability of an individual screener and for the detection of false negatives, nonetheless represents an indispensable tool for assessing morphologic diagnostic criteria and monitoring laboratory performance. Interobserver and intraobserver concordance in a given laboratory determine the reliability of diagnostic criteria and disclose the possibility of improving diagnostic consistency. The various aspects of rescreening are discussed, and a simple statistical procedure for a quantitative comparison of screening reproducibility is described. This procedure, with calculation of phi-values and mean prevalence rates, was applied to screening and rescreening data from the Cyt-U-Universitair Cytology Laboratory from 1978 to 1983, in which the morphologic findings in each smear were recorded in detail using the QISO (Quality, Infection, Squamous epithelium and Other abnormalities) coding. The reproducibility of the reported presence of endocervical cells not only steadily improved over the years assessed, but also reached a sufficiently high level that diagnostic variability should not hamper its clinical utility. The same was true of the diagnosis of Trichomonas infection and moderate atypia of squamous cells. On the other hand, the reproducibility of the diagnosis of endometrial cells in smears did not significantly improve. However, since the intraobserver concordance on this criterion was good, it seems likely that the definitions of screeners in this area can still be brought into closer agreement. Conversely, the diagnosis of "abnormal endocervical cells" had such a high level of variability even at the intraobserver level as to question its use as a diagnostic criterion. Similar variability was seen in the distinction between atypical squamous metaplasia and mild dysplasia. Use of this statistical technique for the quality control of cytologic diagnoses frees that assessment from histopathologic control, which does not address the problem of variation within the cytologic or histologic diagnoses themselves.     

HER-2/neu evaluation by fluorescence in situ hybridization on destained cytologic smears from primary and metastatic breast cancer

OBJECTIVE: To evaluate HER-2/neu amplification by fluorescence in situ hybridization (FISH) (HER-2/neu by FISH) on archival cytologic smears stained with May-Grünwald-Giemsa (MGG) stain. STUDY DESIGN: Cytologic specimens from 69 breast cancer lesions (48 primary and 21 metastatic), stained with MGG stain for routine diagnostic cytology, were destained and subjected to HER-2/neu by FISH. Fifteen of the 69 samples were also evaluated by FISH on paired fresh smears. RESULTS: HER-2/neu by FISH was successfully assayed in 25 of the 48 primary tumors and in 15 of the 21 metastatic lesions, corresponding to an overall feasibility of 58%. These cases had been archived between 1 month and 10 years prior to FISH analysis. Eight of the 25 primary and 5 of the 15 metastatic tumors were amplified. In 15 of the 40 evaluable cases, HER-2/neu was also assessed on the corresponding fresh smears: 8 tumors were amplified and 7 unamplified on both destained MGG and fresh smears. CONCLUSION: HER-2/neu can be detected by FISH on routinely MGG-stained cytologic slides. This approach allows HER-2/neu evaluation whenever histologic sections or fresh cytologic material are not available. In these cases, HER-2/neu assessment on destained cytologic smears plays a role in the selection of targeted therapy.