Paolo Bulgaresi

Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a triage test in breast cancer staging

IntroductionAxillary node fine needle aspiration cytology (FNAC) has the potential to triage women with operable breast cancer to initial nodal surgical procedure. Because of variability in the reported accuracy of this test its role and clinical utility in pre-operative staging remains controversial.MethodsWe retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all consecutive clinically T1–2 N0–1 breast cancers that had undergone this test (491 biopsies). We included subjects with clinically or sonographically indeterminate or suspicious nodes. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy).ResultsSensitivity of node FNAC was 72.6% (67.3–77.9) and specificity was 95.7% (92.5–98.8) for all cases, sensitivity was lower at 64.6% (59.3–70.0) if inadequate cytology was included as a negative result. FNAC sensitivity was highest in women with clinically suspicious nodes [92.5% (88.2–96.7)] and lowest in women with sonographically abnormal and clinically negative nodes [50.0% (41.3–58.7)]. Specificity was high in both groups, 81.2% (54.5–96.0) and 97.2% (94.6–99.9), respectively. The false-negative rate was 15.3% (12.1–18.5), the false-positive rate was 1.4% (0.4–2.5), and the inadequacy rate was 10.8% (8.0–13.5). The likelihood of node FNAC being positive was significantly associated with tumour grade and stage, and the number of nodes involved with metastases.DiscussionOur data show that axillary FNAC has moderate sensitivity (which varies according to selection criteria for the test) and consistently high specificity, is associated with low inadequacy and very few false positives. We estimate that its use would have improved triage to initial nodal procedure in about one quarter of our cases. If one accepts the premise that initial surgical staging of the axilla should be based on all information available through pre-operative diagnosis, then axillary FNAC should be adopted routinely into clinical practice.

Fine needle aspiration cytology of the breast: review of 9533 consecutive cases

Abstract A consecutive series of 9533 breast lesions (1828 malignant, 7705 benign) undergoing fine needle aspiration cytology (FNAC) is reported. The FNAC inadequacy rate was 6.9% for cancers and 24.1% for benign lesions. FNAC sensitivity was 89.5% and was dependent of histological type (invasive 90.1%, in situ 79.6%, infiltrating lobular 84.5%, infiltrating ductal (no special type) 92.4%, other invasive carcinoma of special type 90.6%). The specificity was 98.5%. The positive predictive value of an equivocal and malignant FNAC report was 66.0% and 98.5% respectively. FNAC was abnormal and responsible for an unnecessary biopsy in 42 benign lesions but was the only abnormal test in 116 cancers. Reaspiration corrected most of inadequate or false negative samples suggesting repeat FNAC in such instances might be a useful routine policy. FNAC is fundamental for breast cancer diagnosis and should be available in all breast clinics.

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

SummaryWe 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 2334 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.

Accuracy of needle biopsy of breast lesions visible on ultrasound: audit of fine needle versus core needle biopsy in 3233 consecutive samplings with ascertained outcomes.

INTRODUCTION Core needle biopsy (CNB) has progressively replaced fine needle aspiration cytology (FNAC) in the diagnosis of breast lesions. Less information is available on how these tests perform for biopsy of ultrasound (US) visible breast lesions. This study examines the outcomes of CNB and FNAC in a large series ascertained with surgical histology or clinical-imaging follow-up. MATERIALS AND METHODS Retrospective five-year audit of 3233 consecutive US-guided needle samplings of solid breast lesions, from self-referred symptomatic or asymptomatic subjects, performed by six radiologists in the same time-frame (2003-2006): 1950 FNAC and 1283 CNB. The probability of undergoing CNB as a first test instead of FNAC was evaluated using logistic regression. Accuracy and inadequacy were calculated for each of CNB and FNAC performed as first test. Accuracy measures included equivocal or borderline/atypical lesions as positive results. RESULTS The probability of CNB as a first test instead of FNAC increased significantly over time, when there was a pre-test higher level of suspicion, in younger (relative to older) women, with increasing lesion size on imaging, and for palpable (relative to impalpable) lesions. Inadequacy rate was lower for CNB (B1 = 6.9%) than for FNAC (C1 = 17.7%), p < 0.001, and specifically in malignant lesions (B1 = 0.9% vs. C1 = 4.5%; p < 0.001). False negative rate was equally low for both CNB and FNAC (1.7% each test). CNB performed significantly better than FNAC for absolute sensitivity (93.1% vs. 74.4%; p < 0.001) and complete sensitivity (97.4% vs. 93.8%; p = 0.001), however specificity was lower for CNB than FNAC (88.3% vs. 96.4%; p < 0.001). Absolute diagnostic accuracy was higher for CNB than FNAC (84.5% vs. 71.9; p < 0.001) while FNAC performed better than CNB for complete diagnostic accuracy (95.4% vs. 93.2; p < 0.008). In the small subgroup assessed with CNB after an inconclusive initial FNAC (231 cases) there was improved complete sensitivity (from 93.8% to 97.0%) however this also increased costs. CONCLUSION FNAC and CNB were generally performed in different patients, thus our study reported indirect comparisons of these tests. Although FNAC performed well (except for relatively high inadequacy), CNB had significantly better performance based on measures of sensitivity, but this was associated with lower specificity for CNB relative to FNAC. Overall, CNB is the more reliable biopsy method for sonographically-visible lesions; where FNAC is used as the first-line test, inadequate or inconclusive FNAC can be largely resolved by using repeat sampling with CNB.

Is Conventional Urinary Cytology Still Reliable for Diagnosis of Primary Bladder Carcinoma? Accuracy Based on Data Linkage of a Consecutive Clinical Series and Cancer Registry

Objective: Reported urine cytology accuracy, particular sensitivity, is highly variable. We evaluated the accuracy of urinary cytology for primary bladder cancer using population data linkage to provide valid estimates. Study Design: Consecutive cytology tests processed through a major service between January 2000 and December 2004 were linked to a regional population cancer registry (allowing outcome ascertainment). Sensitivity and specificity were calculated using different thresholds, based on standardized reporting categories (C1 = negative, C2 = reactive, C3 = atypical, C4 = suspicious, C5 = malignant, Cx = inadequate). Results: Cancer registry matching of 2,594 tests revealed 130 incident bladder cancers, of which 97 occurred within 12 months of cytology and were included in calculating accuracy. Sensitivity (C3–C5 considered positive) ranged between 40.2 and 42.3%, and specificity was 93.7–94.1%. If C3 results are counted as negative, sensitivity estimates reduced to 24.7–26.0%. The positive predictive value of a C3, C4 or C5 report was 11.7, 39.2, and 66.6%, respectively. High tumor grade was associated with significantly higher sensitivity compared to low and intermediate grades combined (p = 0.02). Conclusion: Urine cytology is highly specific but has intermediate sensitivity, indicating that it has a role in adjunct diagnosis, but not in screening for primary bladder cancer. C3 results should be considered ‘positive’ and further investigated, and all positive results should prompt further intervention.

Analysis of morphologic patterns of fine-needle aspiration of the breast to reduce false-negative results in breast cytology.

The identification of specific morphologic diagnostic criteria is of paramount importance to optimize the accuracy of fine‐needle aspiration cytology (FNAC) and to reduce the rate of false‐negative results. In the current study, the authors reviewed a consecutive series of false‐negative findings observed in the study center to define the presence and degree of cytologic abnormalities. False‐negative cases were randomly mixed with true‐negative cases and were reviewed by a panel of expert readers in a blinded fashion. The main objective of the current study was to identify a morphologic pattern that may permit the reduction of false‐negative findings while maintaining the specificity of FNAC.

Reliability of sparing Papanicolaou test conventional reading in cases reported as No Further Review at AutoPap-assisted cytological screening: survey of 30,658 cases with follow-up cytological screening.

AutoPap‐assisted smear reading has been proposed prior to conventional manual reading; the latter may be unnecessary for cases reported as No Further Review (NFR) and would be required for cases reported as Review (REV).

Conventional pap smear and liquid-based cervical cytology smear: comparison from the same patient.

Background The results of blind reading of smears obtained with liquid-based cytology in patients previously screened by conventional cytology were compared. Material and methods Cases selected for the study were a consecutive series of 99 subjects undergoing colposcopy within the screening program of the Florence District. The Pap test samples were processed utilizing the Thin Prep 2000 (Cytyc Corporation, Boxborough, MA). The liquid-base cytology smears were randomly admixed and read by seven expert cytologists with more than 15 years of experience in Pap smear reading. For each case, a consensus diagnosis was created and considered as the definitive diagnosis. Cytologic reports in conventional and liquid-based cytology smears were compared by the κ statistic to evaluate diagnostic agreement. Results The study showed that the conventional and liquid-based cytology provide comparable cytologic reports and that the latter is not less sensitive than the former in detecting CIN2+ lesions of the cervix. Discussion Such evidence suggests the feasibility of randomized studies comparing the two methods, which are needed before adopting liquid-based cytology as the current method when screening for cervical cancer.

Analysis of false-negative and underreported smears in the Florence district screening program for cervical carcinoma.

Aims and background To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25–60 years screened per year. Methods 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. Results Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to mis-perception of cellular abnormalities. Conclusions Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.

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.