Positive predictive value of breast fine needle aspiration cytology (FNAC) in combination with clinical and imaging findings: a series of 2334 subjects with abnormal cytology.

We calculate the positive predictive value (PPV) of abnormal (C3-5) FNAC, alone and in combination with clinical and imaging findings, based on a consecutive series of 2,334 subjects. The PPV of a C3, C4 or C5 report is 55.0%, 95.9% and 99.4%, respectively. C5 Cytology is highly predictive of malignancy (PPV=99.4-99.7%) except where imaging is negative or benign. When C4 cytology is associated with suspicious findings on imaging and/or palpation, its PPV increases to 98.5-98.7%. C3 is the least predictive of malignancy and even when associated with suspicious findings on imaging and/or palpation its PPV is 83.3% - C3 FNAC should therefore prompt pre-operative core biopsy. These data indicate that FNAB is still a useful test in breast diagnosis, and it may assist clinical decision-making as far as whether patients should progress to surgical management or should have further core biopsy before planning surgery.

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.

Prognostic value of breast cancer cytologic grading: a retrospective study of 213 cases.

The authors evaluate 213 consecutive breast cancer cases with positive fine-needle aspiration cytology. Cytologic smears were reviewed and classified according to a grading system. A correlation between cytologic grading and pathological stage (T and N category) was observed. Univariate analysis of 5-yr overall survival rate showed a significant negative association with prognosis only for G3 (90%) compared to G1 (72%) cases. Such prognostic correlation was no longer significant at multivariate (Cox) analysis adjusting for potential confounders such as T or N categories. The prognostic value of cytologic grading is limited and dependent on other classic prognostic indicators that are currently determined in breast cancer patients. Its practical value is negligible, as it does not improve the prognostic judgment.

A quality control system involving peer review of abnormal cervical smears.

An internal quality control system which is used in the centralized cytology laboratory of a population-based cervical cancer screening programme in Florence is described. It includes a peer review procedure. Abnormal cervical smears are circulated among all the cytologists and a consensus on the final diagnosis is reached. This daily procedure is designed to evaluate the performance of each cytologist and of the laboratory as a whole but can also be considered a valuable training opportunity. During an 18-month period 1197 smears were reviewed by 15 readers using a reporting form with six main categories of reporting (from 'negative' to 'invasive carcinoma'), plus an 'unsatisfactory' category. Overall the concordance between the 15 cytologists, assessed using the kappa statistic (range 0.46-0.71; median 0.60), was good. The level of agreement increased when a weighted kappa statistic (range 0.55-0.78; median 0.68) was used. Kappa values were also calculated for specific categories and suggested an increasing concordance with increasing severity of the lesions, the categories of 'severe dysplasia' and 'invasive carcinoma' showing the highest agreement. The poor results for the 'moderate dysplasia' confirmed the need for combining this group with the 'severe dysplasia', as proposed in the Bethesda system.

Fine-needle cytology of the breast: a controlled study of aspiration versus nonaspiration.

We report on 534 breast masses examined by fine-needle aspiration cytology. Two samples were obtained from each mass, one with aspiration and the other without. Aspiration, equivalent to that obtained by a 20-ml syringe on full aspiration, was obtained by an automatic aspirator. The two sampling modalities did not differ apart from aspiration and were compared in terms of inadequate sampling rates. The inadequacy rate was the same in 166 cancers (6.6%), whereas a significant difference was recorded in favor of aspiration (13.6 versus 24.4%) in 368 benign masses. When inadequate results were excluded, the accuracy of the two modalities was almost the same. Sensitivity was 97.4% and 96.7% and specificity was 99.4% and 99.3% for sampling with and without aspiration, respectively. Reducing the rate of inadequate sampling from benign masses seems to be the major advantage of aspiration. Double sampling, independent of the specific techniques, reduced inadequacy rates to very low levels (1.2% for cancers; 5.9% for benign masses) and may be useful as a routine policy.

The role of fine needle aspiration cytology in the differential diagnosis of suspected breast cancer local recurrences.

The authors report on 228 cases of suspected breast cancer local recurrences studied by fine needle aspiration cytology (FNAC). The nature (malignant = 133, benign = 95) of suspected lesions was assessed on histology (no. = 46) or according to unequivocal follow-up (no. = 182). Inadequacy rate was 0.20, 0.09 or 0.35 in total, cancer or benign cases, respectively, and was particularly high (0.50) for benign chest wall lesions. Accuracy was determined on adequate smears; dubious reports were assumed as positive. Sensitivity and specificity were 0.96 and 0.97, respectively. The routine use of FNAC is recommended since it helps in the differential diagnosis of suspicious cases and may bypass surgical biopsy of positive cases not eligible for surgical treatment.

The value of routine cytologic examination of breast cyst fluids.

The results of the cytologic examination of 6,782 consecutive breast cyst fluids aspirated from 4,105 women during the period 1976 to 1983 were reviewed to assess the value of the routine cytologic study of such specimens. Cases in which cancer had been suspected by physical examination and/or mammography before aspiration of the cyst were excluded from the evaluation. Five clinically and radiologically inapparent intracystic papillomas were detected overall (0.1%). All cases of intracystic papilloma produced a blood-stained fluid and showed an intracystic mass at pneumocystography. Cytology was negative in two of these cases and falsely positive in one case while correctly identifying the papilloma in two cases. One incidental case of occult in situ lobular carcinoma was also detected. Routine cytologic examination of all breast fluids is thus not recommended as a cost-effective practice. Cytology should be used only when a blood-stained fluid is obtained (2% in the present series) since its indiscriminate application to all cyst fluids does not affect the rate of detection of intracystic lesions, most of which are suspected before the aspiration.

Significance of nipple discharge clinical patterns in the selection of cases for cytologic examination.

The cytodiagnostic significance of the clinical patterns (types and sites) of nipple discharges was studied in 5,305 cytologically examined discharges from 3,687 women in a consecutive series of 50,181 self-referred women in whom 1,062 breast cancers were detected. The clinical patterns were correlated with cytologic and histologic results in both the whole series and in 119 biopsied cases, and the relative risk of association with breast cancer was calculated for each pattern. As a whole, aside from the pattern, cases with nipple discharges showed a higher relative risk (48.5) than did asymptomatic cases, but a bloody nipple discharge was by far more frequently associated with cancer than was any other pattern, being present in 70% of the cancer cases and in almost all cancer cases with suspicious cytologic findings in the discharge smear. The presence of a nipple discharge, being associated with a higher risk of breast cancer, is an indication for a careful physical examination; systematic cytologic examination should be limited only to bloody discharges. Since cancer is rare in cases with nonbloody discharges and is difficult to detect in cytologic smears of such discharges, systematic cytologic examination of all nipple discharges would not be cost-effective.

Behaviour of intestinal lactase after irradiation.

The behaviour of intestinal lactase has been studied in rats after irradiation. The significant increase of activity is not immediate, but slowly and progressively starting from 4 hrs after irradiation. The modifications of the activity are slow and gradual also during the reduction phase. This disaccharase does not show a return to normal values even after three weeks. We suggest that hypothesis that the increase could be due to a modification of the normal synthesis of enzymes caused by irradiation.