The role of fine-needle aspiration biopsy (FNAB) has been under debate worldwide in recent years (1–5). Needle biopsy has gained popularity and is now considered the standard biopsy method (1,2). On the other hand, it has been discussed that the increase in the number of needle biopsies is not entirely the result of evidence-based reasons (3). There are some advantages of FNAB over needle biopsy for breast lesions: i) it is widely available, easy, quick and inexpensive; ii) it is associated with a lower risk of complications; and iii) it may be appropriate for small lesions, symptomatic (palpable) lesions and for confirming benign lesions (1,3,6–8). Although there is an increasing need for preoperative evaluation of hormone receptors and human epidermal growth factor receptor 2 (HER2/neu) status (1), a number of physicians select needle biopsy in order to avoid obtaining inadequate and/or indeterminate results from cytological analyses (3–5). As a result, the cytological examination has been omitted.

Although FNAB is highly accurate, it is not 100% accurate (9–15). This point has not been well understood, especially by the general public. However, breast cancer screening is becoming more widespread, and the number of people receiving breast examinations has been increasing. Under these recent circumstances, it is considered that FNAB is an appropriate diagnostic tool (6,7).

The Working Group on the Accuracy of Breast Fine-Needle Aspiration Cytology of the Japanese Society of Clinical Cytology was assembled to assess the current status of breast cytology in Japan by conducting a large-scale survey on the accuracy of breast FNAB in 12 cooperating facilities in Japan. Data on 1,250 of the 10,890 subjects in the present study were presented in our previous study as a pilot project (15). However, they were included in this current study to provide a larger sample size, and the data were re-analyzed as part of the larger sample. In the present study, we analyzed and compared the data for cytological diagnosis and individual variables at these 12 facilities, and further investigated the discrepant cases between the cytological and histological diagnoses (false-negative and false-positive cases). It is considered that these data are important for doctors, patients and those in medicolegal circles.

We conducted a survey in 12 facilities in order to determine the accuracy of breast FNAB. After reviewing the data from 2009 and the preceding years, we conducted a survey over several years (1–7 years, average 4.3 years) at 12 facilities that dealt with a large number patients. Data were collected from each institution or region, and cytological data confirmed by histological findings obtained after surgery or needle biopsy were included in the study. The manner of data collection is shown in Table I (modified from our previous report with permission) (15).

To the best of our knowledge, this survey collected data from the largest number of cases for breast FNAB. The role of FNAB has been debated recently, as to whether FNAB has been replaced with the core needle (or vacuum) biopsy (2). Consequently, many reports concerning the accuracy of breast cytology have already been discussed, mainly in the 1990s (9–12,18). Although there are a number of advantages and disadvantages for both needle biopsy and FNAB (1), usage of FNAB has been decreasing in many countries over the last decade. Based on our preliminary survey, a number of hospitals and clinics in Japan primarily use FNAB (unpublished data). Therefore, the current accuracy rate of FNAB must be determined and doctors, paramedics, patients as well as medical lawyers must be informed. A cytological examination for cancer screening in Japan and in several other countries continues to play an important role. For example, cytological examination plays a major role in the diagnosis of both palpable and non-palpable breast masses in Egypt because it is cost-effective (7).

We compared the combined data from the present study with previously reported data (9–14). The data from the present study were compared with the goals of assessment of diagnostic accuracy reported in the UK (9,10) (absolute sensitivity, >60%; complete sensitivity, >80%; specificity, >60%; positive predictive value, >95%; false-negative rate, <5%; false-positive rate, <1%; inadequate rate, <25%; suspicious rate, <20%), and were also compared with studies from several other countries, including a large-scale study (10,571 cases) in North America (the values had ranges of 75.8–98.7% for sensitivity, 92–100% for specificity, 0.6–2.5% for false-positive rate and 2.5–17.9% for false-negative rate) (11,14). The combined data in our survey were within these ranges, except for the specificity (84.3%) and the inadequate rate (17.7%) which were >10% (the goal of the Japanese criteria) (16). Therefore, the accuracy of a cytological examination in our survey is considered to be generally useful during clinical practice. However, we previously reported several differences among the institutions in our regions (15), discussed some of the reasons for this situation and speculated on the poor communication between the clinical and pathological sides (15). The present study provided improved results in many categories compared to the previous pilot study. Likely reasons for this are that the previous study included general hospitals and a reference laboratory (15), whereas the present study included mainly larger university-level hospitals with specialized breast disease departments.

In addition, we investigated the data with a focus on false-negative and false-positive cases. These values are important because if cases were omitted by the histological diagnosis, false-positive cases would proceed directly to breast cancer surgery, while many false-negative cases may not be re-evaluated. Such results may lead to legal issues. The present data showed that FNAB was not 100% accurate, and doctors, patients as well as lawyers should be informed. On the other hand, the accuracy of a cytological examination used in order for a diagnosis to be made, was relatively high.

Regarding the 297 false-negative cases, the histology of most cases was SIDC, followed by DCIS. These types of carcinoma are usually detected as small atypical cells in the cytological diagnosis (17,18). After re-evaluation of the 297 false-negative cases, the category of over 90% cases was changed to ‘inadequate’, ‘normal/benign’ or ‘indeterminate’. However, the category of 11 other cases was changed to ‘malignancy suspected’ and that of 5 cases was changed to ‘malignancy’. These histological types were mainly SIDC (data not shown; 5/11 cases and 2/5 cases, respectively) and the cells of small clusters showed mild atypia. SIDC showed a tendency toward inadequate and false-negative cytological findings based on their histological characteristics; that is, they are usually accompanied by thick fibrous tissues (18). Therefore, when this histological subtype which is simple to detect by imaging (i.e., mammography or ultrasound) is detected, needle biopsy rather than FNAB is recommended (17). Due to the lack of communication between the clinical and pathological sides, clinical information for 15% of the cases was not available (15). The rate of tumor size under 1 cm was approximately 15%; thus, the small tumor size was not the main reason for the false-negative cases.

Regarding false-positive cases, the histology of most cases was papilloma, fibroadenoma, fibrocystic disease (mastopathy) or adenomyoepithelioma. Papilloma is one of the most difficult histologic types for cytological diagnosis (19), while fibroadenoma is often misread for hyperplastic epithelial cells (20). Interestingly, adenomyoepithelioma showed the same rate of false-positive cases, for which the histological type has benign to malignant potential and is generally considered a benign lesion (21). This type is comparatively rare, and the frequency of encountering this type is low. However, we should be aware of the type, and of the characteristic cytological findings, including a loosely cohesive fragment of ductal epithelium surrounding fibrous and myxomatous cores (22). The clinical information was based mainly on the abnormal image findings and breast cancer (tumor), and therefore, most cases were suspected of malignancy on the clinical side. The pathological side may have been affected by this information. The rate of tumor size over 2 cm was more than one-third, and thus the tumor size was often larger. Even after re-evaluation, the category of 4 of 23 cases was still ‘malignancy suspected’, and these signs were similar to malignant findings. Knowledge of these findings (i.e., apocrine atypia) must be taken into consideration when making a diagnosis.

Although the present study did not always coincide with imaging data, a triple approach (clinical, pathological and radiological) is necessary for accuracy (1,3). Moreover, when the suspected histological type displays difficulties in cytological diagnosis using imaging analysis, which method to select (needle biopsy or cytological examination) depends on individual cases (1). In the future, FNAB should be used for non-palpable lesions with imaging guidance (especially ultrasound) (3).

In conclusion, the accuracy of a cytological examination in Japan is as high as those in other countries, such as the UK and US (9–11). On the other hand, the study demonstrated that there were some false-negative and false-positive cases. Japan may also need to establish a national quality assurance program, similar to the one in the UK (9,10). Furthermore, we must continue to improve accuracy based on the learning points in the present study, so that FNAB can become a more useful and reliable examination in clinical practice.