INTRODUCTION

Fine-needle aspiration cytology (FNAC) is a widely known and cost-effective diagnostic tool that is simple to perform and carries a low complication rate. Having no absolute contraindications, FNAC has a high diagnostic accuracy and was once commonly used in clinical practice [1-3]. Before the development of breast screening programs, the primary reason for patients visiting breast clinics was palpable breast lesions, and FNAC was the primary diagnostic method [4]. When a malignancy was diagnosed on FNAC, the diagnosis was confirmed by incisional biopsy and frozen section in the operating field, followed by surgical excision.

However, with advances in breast screening programs, a significant increase has been observed in the detection of non-palpable breast lesions [5,6]. In conjunction with the development of radiology and the need to evaluate biomarkers for determining the feasibility of preoperative targeted therapies, core-needle biopsy (CNB) has become the preferred method [7,8]. As a result, the role of FNAC in diagnosing breast lesions has diminished, with its diagnostic use decreasing dramatically in clinical settings. Only in low- and middle-income countries, does FNAC remain the primary diagnostic tool for breast pathology [9-11].

While the use of FNAC in the diagnosis of breast lesions has decreased, it remains relevant in situations requiring a rapid and minimally invasive diagnostic test. FNAC is still used when CNB is challenging due to the location of the lesion, or when assessing small axillary lymph nodes or distant metastatic lesions. Ancillary tests such as immunocytochemical staining can also be performed on cytology samples. Imprint cytology continues to be used for frozen-section diagnoses. It has been reported that mRNA and DNA extracted from FNAC samples are of a higher quality compared with those from formalin-fixed paraffin-embedded (FFPE) tissue, making them suitable for molecular pathology analysis [12,13]. Recent reports suggest that FNAC may have advantages over CNB in digital pathology systems using artificial intelligence (AI) [14].

Given that CNB is now the primary diagnostic tool for breast lesions in developed countries, we aim to review the evolving role of FNAC in breast lesion diagnosis.

TRENDS IN DIAGNOSIS OF BREAST LESIONS

The decline in breast FNAC

After its introduction by Martin and Ellis [15] in New York in the 1930s, breast FNAC evolved significantly at the Karolinska Institute in Sweden over the 1950s and became a primary diagnostic tool for palpable breast lesions, particularly in the United States [16-18]. From the 1980s onward, the techniques and diagnostic applications of breast FNAC continued to improve, making it a safe, economical, and accurate diagnostic method [19,20]. FNAC offers particular advantages in cases involving small lesions and those just beneath the skin or above the chest wall, as well as in patients with breast implants and those taking anticoagulants [21,22].

However, the effectiveness of FNAC depends on the skill and experience of the physician performing the aspiration and the cytopathologist interpreting the results. As breast screening mammography became more popular with the development of innovative localization devices and advances in radiology, the demand for FNAC changed. The high rate of inadequate specimens, difficulties distinguishing in situ from invasive lesions, challenges diagnosing certain lesion categories (e.g., papillary breast lesions, atypical hyperplasia, and lobular carcinoma), and lower diagnostic accuracy for non-palpable lesions and those smaller than 10 mm contributed to the global decline in FNAC use. The rising incidence of false-positive cases and resulting legal actions also contributed to its reduced use [7,8]. Although attempts have been made to address these challenges through image-guided aspiration and the implementation of the triple test (cytology combined with clinical and radiological imaging), the trend in developed countries, including Korea, has shifted toward CNB as the preferred diagnostic method. However, FNAC remains in use in low- and middle-income countries [9-11].

With CNB now the preferred diagnostic method for breast lesions, clinicians have fewer opportunities to practice FNAC skills, and cytopathologists have fewer chances to interpret FNAC results [23]. This has led to a vicious cycle in which the number of poor-quality smears increases, reducing diagnostic accuracy and prompting more clinicians to choose CNB, ultimately resulting in the abandonment of FNAC [24,25].

The role of CNB

Since its introduction in the late 1990s, the use of CNB has increased significantly, and it is now the primary diagnostic method for evaluating palpable breast lesions and category 4 lesions under the Breast Imaging Reporting and Data System (BI-RADS) [8]. Compared with FNAC, CNB is more expensive, complex, and invasive. It is associated with a higher risk of complications, such as bleeding and hematoma formation, localized infections (up to 2.0% in CNB vs. up to 0.2% in FNAC), skin tethering due to malignant cell seeding along the needle tract (up to 50.0% of CNB cases), and penetration of the pneumothorax or chest wall (1 in 10,000 for FNAC vs. 5 in 10,000 for CNB) [26,27]. Patients often report more pain during or after CNB procedures, a response that can be attributed to the large gauge of needle used. CNB typically involves needles ranging from 14- to 20-gauge, with external diameters of 2.1 to 0.9 mm, compared with FNAC, which uses smaller 22- to 25-gauge needles with an external diameter of 0.7 mm. Despite these drawbacks, CNB offers greater diagnostic accuracy, particularly in cases of non-palpable or calcified lesions, and can more reliably differentiate between in situ and invasive carcinomas. CNB also yields a larger sample volume, which makes possible additional assessments, such as tumor grading, and the evaluation of predictive markers, such as hormone receptors and human epidermal growth factor receptor 2 (HER2) status [28]

NEW APPROACHES TO OVERCOME FINE-NEEDLE ASPIRATION CYTOLOGY LIMITATIONS

Despite the increasing use of CNB, FNAC remains a cost-effective method for diagnosing breast lesions. Numerous studies have compared the diagnostic accuracy of CNB and FNAC, with FNAC sensitivity reportedly ranging from 43.8% to 97.5%—higher when performed by experienced cytopathologists, although sensitivity tends to be lower for atypical or suspicious lesions. Specificity of FNAC ranges from 89.8% to 100%, with a positive predictive value (PPV) as high as 99.3% and a negative predictive value (NPV) of 96.2%. In comparison, CNB typically achieves a sensitivity of 85.0% to 100% and a specificity between 86.0% and 100%, generally showing higher sensitivity and specificity than FNAC, particularly in the evaluation of non-invasive and suspicious lesions. CNB is often preferred over FNAC in cases of suspected malignancy due to its superior diagnostic accuracy and predictive values [7,8]. However, recent comparative studies suggest that the diagnostic outcomes between the two methods do not differ significantly. One study reported that FNAC achieves similar sensitivity (97.0% vs. 97.0%), specificity (94.0% vs. 96.0%), diagnostic accuracy (95.0% vs. 96.0%), and NPV (98.0% vs. 96.0%) when compared with CNB, while offering fewer complications [21].

A new reporting system, the International Academy of Cytology Yokohama System

Introduction of International Academy of Cytology Yokohama System

Since 2016, the International Academy of Cytology (IAC) Yokohama System has been recommended for breast cytology diagnosis. The system involves reporting breast cytology in five categories based on the risk of malignancy (ROM): “insufficient/inadequate,” “benign,” “atypical,” “auspicious of malignancy,” and “malignant.” Each category uses clear descriptive terms and provides definitions, ROM, and a management algorithm. The system outlines key diagnostic cytological features for lesions within each category, supported by illustrations [29].

Categories, ROM, and summary of recommended managements

The “insufficient/inadequate” category is characterized by a paucity of cells, poor smearing, or suboptimal fixation, rendering cytomorphological diagnosis unfeasible. The recommended ROM for this category ranges from 2.6% to 4.8%. When clinical and imaging findings are uncertain or suspicious, a repeat FNAC or CNB is recommended. In cases of imaging findings that appear benign, a repeat FNAC is advised. The “benign” category only applies when cytological findings are unequivocal, and a specific benign diagnosis may be given. With a recommended ROM of 1.4% to 2.3%, further tissue biopsy is unnecessary if the clinical and imaging findings are benign (i.e., the “triple test” is concordant). If clinical or imaging findings are ambiguous or suspicious, a repeat FNAC or CNB should be performed. “Atypical” is defined by cytological features that are predominantly benign but include rare findings potentially associated with malignancies. The recommended ROM for this category is 13.0% to 15.7%. If atypia can be attributed to technical issues, repeat FNAC is warranted. If the smear quality is adequate but atypia persists, a repeat FNAC or CNB is recommended. The “suspicious of malignancy” category includes lesions with definitive malignant cellular features, although insufficient in quantity or quality for a malignant diagnosis. Describing the suspected malignancy is encouraged. The recommended ROM for this category ranges from 84.6% to 97.1%, and CNB is mandatory after reviewing clinical and imaging findings. The “malignant” category includes smears with clear malignant cytological features, and the type of malignancy should be described if possible. The recommended ROM for this category is 99.0% to 100%. Discrepancies between clinical/imaging findings and cytology necessitate a CNB. If the “triple test” indicates malignancy, definitive treatment should proceed [20,29].

Published data of diagnostic accuracy of IAC Yokohama System

Many studies of the use of the IAC Yokohama System’s five-tier reporting framework and its application across institutions have been conducted. Based on those published between 2019 and 2021, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy of each category were analyzed (Table 1) [30-44]. Diagnostic accuracy varied depending on the exclusion of categories such as “insufficient,” “atypical,” or “suspicious for malignancy.” Studies published in 2019 showed considerable heterogeneity, with diagnostic accuracies ranging from 68.2% to 95.0%, whereas studies published after 2020 demonstrated accuracies that had improved to between 82.7% and 99.4%. This may be likely attributable to accumulated experience with the IAC Yokohama System [45]. Agrawal et al. [39] retrospectively analyzed all cases of breast masses evaluated using FNAC and their histologic correlations in 321 cases. Sensitivities for the “atypical,” “suspicious for malignancy,” and “malignant” categories were 98.2%, 96.0%, and 86.7%, respectively. Specificities for the same categories were 59.5%, 91.9%, and 100%, respectively. The ROMs for the “benign,” “atypical,” “suspicious for malignancy," and “malignant” categories were estimated at 8.3% (range, 2.3% to 20.0%), 17.2% (range, 5.8% to 35.8%), 77.8% (range, 57.7% to 91.4%), and 100% (range, 98.1% to 100%), respectively, demonstrating a favorable cytological-histologic correlation. The IAC Yokohama System primarily recommends basing reports on direct smears, and studies have found strong interobserver agreement [46]. Folarin et al. [47] also reported excellent interobserver agreement in liquid-based cytology (LBC) evaluations.

The “atypical” category

In the absence of a standardized cytology reporting system, the clinical decision-making impact of “atypical” diagnoses varies, but has yet to be clearly analyzed. Without standardized guidelines, clinicians tend to base “atypical” diagnoses on sample type and individual judgment. A standardized reporting system allows cytopathologists, clinicians, and patients to mutually understand what an “atypical” diagnosis entails, reducing the unnecessary use of this category, minimizing confusion or patient anxiety, and fostering effective communication between cytopathologists and clinicians. The five-tier IAC Yokohama System is considered an appropriate standardized reporting system for breast-lesion FNAC. However, much discussion has occurred regarding the “atypical” category, which continues to pose challenges [20,44,48]. How clinicians within each institution interpret and respond to the “atypical” category is a critical factor. Additional explanations, such as “favor benign” or “cannot exclude malignancy,” can help convey the level of concern and limitations regarding an “atypical” diagnosis, drawing on the relationship between pathologists and clinicians. Multidisciplinary discussions can initiate these conversations, although it may take time for clinicians to become familiar with a new reporting system [49]. It is particularly important for institutions to use prospective ROM categories in a manner consistent with their chosen reporting system to ensure structured management (Table 2) [30-44,50,51].

Limitations of the IAC Yokohama System

This new structured standardized reporting system, which is based on the ROM, would improve the performance, interpretation, and reporting of breast FNAC and clarify communication between cytopathologists and clinicians. The suggested management algorithm will benefit patient and provide diagnostic options. Nevertheless, diagnostic pitfalls persist. Pauci-cellular smears can lead to false-negative diagnoses, particularly for lobular carcinoma. Complex sclerosing lesions, fibroadenomas, and papillomas can exhibit worrisome features, resulting in false-positive diagnoses. Benign inflammatory lesions such as fat necrosis, and rare entities such as collagenous spherulosis, may also cause diagnostic challenges. Ductal carcinoma in situ may lead to both false-negative and false-positive diagnoses, particularly in distinguishing high-grade lesions from invasive carcinoma, highlighting the limitations of cytology in certain cases [52].

FNAC with rapid on-site evaluation

In cytology, rapid on-site evaluation (ROSE) assists in evaluating the cytomorphological features of fine-needle aspiration (FNA) smears or biopsy touch preparations [53]. ROSE reduces the number of “insufficient/inadequate” samples in breast cytology to less than 1%, and concordance between on-site diagnoses and final diagnoses is high [54]. ROSE also helps determine whether additional FNAC attempts are necessary, and after assessing the ROSE results, further sampling from the lesion can be performed for ancillary tests [54]. During ROSE, the consistency of the lesion/mass (soft, firm, or hard), changes in lesion size after aspiration, color of the aspirated fluid (bloody, clear, or green, etc.), consistency of the aspirated fluid (viscous, watery, or mucinous, etc.), and cellularity are evaluated [54]. Schoellnast et al. [55] emphasized the importance of having a cytopathologist evaluate the quality of the specimen on-site. They reported that FNAC without on-site cytopathological evaluation does not yield superior sensitivity and specificity compared with CNB. When on-site evaluations were performed, the average non-diagnostic rate of FNAC decreased from 20.0% to 0.1%, and diagnostic accuracy increased to 96.0% [53,56,57].

Wong et al. [42] reported statistically significant differences in the “inadequate” and “malignant” categories when comparing FNAC with ROSE. IAC Yokohama System also recommends the use of ROSE where possible to reduce the rate of insufficient and/or inadequate samples in FNAC. They found that ROSE reduced the proportion of inadequate samples from 17.1% to 4.0% and increased the proportion of malignant samples from 17.9% to 39.0%, with statistically significant differences. ROSE is recommended to reduce the proportion of “inadequate” and “atypical” categories and increase the diagnoses of “suspicious of malignancy” and “malignant,” allowing for immediate classification for additional biopsy when necessary [25,42]. Suciu et al. [58] analyzed the diagnostic accuracy of the on-site cytopathology advance report (OSCAR) for breast masses classified by the American College of Radiology BI-RADS. Their findings demonstrated a sensitivity of 97.4%, specificity of 95.0%, and diagnostic accuracy of 96.5%. The OSCAR procedure proved to be a reliable diagnostic approach, particularly in multidisciplinary, integrated, one-stop clinics where an interventional cytopathologist can efficiently identify patients who require CNB [58].

Agrawal et al. [31], who classified breast lesions using the IAC categories, reported overall sensitivity and specificity of 99.1% and 99.3%, respectively, with ROSE significantly enhancing the diagnostic outcomes. ROSE reduced the rate of “insufficient” cases (p < .001) and improved the concordance between cytopathology and histopathology from 76.9% to 90.2%. The ROM progressively increased from the “insufficient” to the “malignant” categories, with this trend becoming more pronounced when ROSE was applied. Studies have found that, with ROSE, the ROM in the “insufficient” category was reduced from 0%–60.9% to 0%–11.0% [42]. Bharti et al. [59] suggested that standardized guidelines for ROSE are essential for its broader implementation and to reduce the rate of the “insufficient/inadequate” category. However, under the current healthcare system in Korea, inadequate reimbursements and the labor-intensive nature of the procedure have prevented the widespread adoption and made it difficult to implement in secondary and tertiary hospitals.

Combined approach of FNAC followed by CNB

FNAC and CNB are both useful diagnostic methods, each with distinct advantages and limitations. Several studies have suggested that these two techniques can be used complementarily rather than separately. One study reported that the sensitivity for breast cancer diagnosis was 80% when FNAC was used alone, 88.0% when CNB was used alone, but 100% when both techniques were applied [60]. While the use of FNAC has gradually declined and been replaced by CNB in many institutions, Nassar [8] emphasized the importance of FNAC and the utility of newer techniques that could help overcome its limitations compared with CNB. One of the major disadvantages of FNAC is the relatively high rate of inadequate samples compared with CNB. In studies of non-palpable breast lesions, Salami et al. [61] reported that 22.0% of FNAC samples were inadequate, while Ibrahim et al. [62] found an even higher rate of 58.7%. To address these limitations, Joudeh et al. [63] proposed performing CNB immediately after ensuring an adequate FNAC sample in the same setting. This approach allows both tests to be completed in a single visit, making it convenient for the patient, and the combined samples from FNAC and CNB enable a more accurate diagnosis, reducing the need for additional invasive procedures and improving cost efficiency. They also suggested that, when CNB is performed in the same setting as FNAC, adding a touch imprint would provide even more diagnostic information.

The combination of FNAC and CNB can increase overall diagnostic accuracy, particularly in small lesions, and provide more material for additional ancillary studies. FNAC and CNB together allow for better interpretation of morphology and structure, increase sensitivity and specificity compared with either method alone, and offer greater convenience to patients. This approach can provide greater satisfaction to clinicians who may hesitate to rely solely on cytological data. It also gives pathologists who rely on histological diagnoses the opportunity to build more experience with cytology, making it a valuable approach to handling complex malignancies such as composite malignancies.

Sustova and Klijanienko [64] evaluated the diagnostic accuracy of FNAC and CNB in palpable breast tumors. While CNB had greater diagnostic accuracy for benign tumors (94.7% for FNAC vs. 100% for CNB), FNAC was more accurate when dealing with malignant tumors (95.6% for FNAC vs. 94.7% for CNB). The diagnostic correlation between FNAC and CNB for malignant tumors was strong, and the unsatisfactory category was lower for FNAC (2.7% for FNAC vs. 4.9% for CNB). Only 0.4% of cases had unsatisfactory results from both FNAC and CNB, and when the two methods were combined, sensitivity reached 99.8%. Based on these findings, Sustova and Klijanienko [64] concluded that combining FNAC and CNB is the optimal approach to diagnosing palpable breast tumors, and they recommended it as a standard diagnostic method.

FNA using LBC

According to the College of American Pathologists’ National Breast FNA Biopsy Practice Survey, approximately 40% of laboratories reported using LBC for breast FNA [65]. Multiple studies have reported that FNA using conventional smears and LBC are comparably accurate in detecting malignant tumors [45,66,67]. Folarin et al. [47] emphasized the utility of LBC, particularly given the relative decline in breast FNAC and the lack of ROSE for assessments. They evaluated the reproducibility of the IAC Yokohama System for reporting breast FNA using LBC, reporting substantial to almost perfect agreement among reviewers (κ = 0.73–0.91) and concordance with histopathologic follow-up (κ = 0.66–0.85). The use of LBC reduced the rate of inadequate samples compared with conventional cytology, although the categories with the lowest agreement were “inadequate” and “atypical.” The lower concordance in the atypical category was attributed primarily to low cellularity or incomplete structural features.

Proposed diagnostic algorithm

Silva et al. [68] recommended a stepwise diagnostic approach in a multidisciplinary setting. The first step involves mammography and ultrasound imaging, followed by FNAC. In rare cases, cytologically benign but highly cellular lesions undergo further evaluation with CNB. If malignant cells are detected in FNAC, CNB of the breast tumor is performed along with FNAC of the axillary lymph nodes, and treatment planning is based on staging.

A diagnostic algorithm that combines FNAC with CNB has been recognized as an effective approach to improved diagnostic accuracy in breast lesions and providing better information in uncertain cases. This approach starts with an initial evaluation using FNAC to rapidly assess malignant, benign, or atypical cells. If the FNAC results are atypical or suspicious, or if the patient or physician desires a definitive diagnosis, CNB is performed for further tissue sampling. This method improves the accuracy of breast lesion diagnosis while minimizing patient discomfort [7,8,69]. This diagnostic algorithm can be an effective strategy to reduce unnecessary surgeries or additional tests, while ensuring rapid and accurate diagnosis of malignant lesions.

BEYOND THE CYTOLOGY IN BREAST FINE-NEEDLE ASPIRATION

Immunocytochemical stains in breast FNAC

While it was known that receptor expression could not be reliably assessed in cytological specimens, several studies published since the 2000s have demonstrated the successful evaluation of receptor expression in FNAC samples [70,71]. Studies have confirmed that estrogen receptor (ER) and progesterone receptor (PR) analyses can be accurately performed on FNAC smears. Durgapal et al. [72] reported a 99.0% diagnostic accuracy for immunocytochemical analysis performed on FNAC samples compared to immunohistochemistry, with 100% concordance between immunocytochemistry and fluorescence in situ hybridization (FISH) techniques. Vohra et al. [73] analyzed the correlation between expression of these markers in cell blocks obtained from FNAC and tissue blocks, showing excellent agreement for ER and HER2 and “moderate agreement” for PR. Cytological preparations differ from tissue fixed in formalin in that they are alcohol-fixed, which can lead to differences in tissue structure and cellular composition [74]. Additionally, the lack of tissue architecture in cytological specimens can affect the interpretation of immunocytochemical staining [75]. Extensive validation studies have been conducted for immunocytochemical staining, including comparisons with paired surgical or core biopsy specimens and/or clinical data, to account for factors that could affect interpretation [76].

Pinto and Schmitt [77] conducted extensive validation of four immunostains (ER, PR, HER2/neu, and Ki-67) on primary breast lesions and cytological specimens. Studies applying a 1% cutoff for ER- and PR-positivity have shown concordance rates ranging from 80% to 99% [73,78,79]. Vohra et al. [73] reported more than 98% concordance between HER2 immunocytochemistry and HER2 FISH performed on cell blocks. Studies using Ki-67 immunostaining with a 20% cutoff reported concordance rates of 85%–90% [80,81].

For axillary metastases, studies of tissue sections from FFPE samples have shown high (greater than 95%) concordance rates for hormone receptor status between primary tumors and axillary lymph node metastases. For HER2, concordance was slightly lower but still above 85% [82,83]. Although few studies have examined receptor expression in metastatic breast cancer, Pareja et al. [84] reported finding similar concordance between primary breast lesions and metastatic sites. However, some discordance was observed, with most cases involving loss of hormone receptor positivity in axillary lymph node FNACs from initially hormone receptor–positive primary tumors. This phenomenon, known as receptor loss, is often seen following endocrine therapy and could explain discrepancies in studies in which biopsy data from both primary and metastatic sites are separated by treatment intervals [85], Nevertheless, it is essential to consider potential sampling errors or low cellularity before prematurely attributing negative results to treatment effects [86]. With the approval of trastuzumab-deruxtecan for HER2-low metastatic breast cancer, the interobserver variability in HER2 immunostaining interpretation of cytological specimens from metastatic sites has been evaluated. Discrepancies were observed in approximately 30% of cases, highlighting the need for standardization in interpretation [87].

Molecular study using cytology samples

Generally, non-formalin-fixed cytological material is more suitable for molecular testing than formalin-fixed tissue or cell blocks. This is because such samples tend to preserve high-quality nucleic acids that are stable and easy to extract [88]. Most molecular tests are now conducted on FFPE samples, largely because these tests have been validated on FFPE samples. Although cytological samples are underutilized in molecular pathology [88,89], several studies have shown that cytological preparations, such as smears and LBC, perform equally well or better than FFPE samples in molecular testing [89,90]. With proper sample collection and careful validation of molecular tests, cytological samples can be a valuable resource for molecular diagnostics.

FNAC samples can be particularly useful for biomarker evaluation or discovery, as they often contain a higher proportion of tumor cells compared with CNB or surgically excised tissue [91]. FNAC samples have been used successfully for genomic testing across a variety of tumor types, yielding reliable results [92]. Park et al. [93] identified novel cancer biomarkers using high-throughput proteomic analysis of FNAC samples from breast cancer, demonstrating results comparable to those obtained from tissue.

LBC improves sample quality by reducing contamination and artifact formation and can preserve residual material for additional molecular analyses. LBC reportedly provides high-quality DNA suitable for genetic testing and plays a key role in identifying actionable mutations in breast cancer [94]. Akahane et al. [95] reported that high-quality DNA and RNA were obtained from cells preserved in various LBC fixatives, detecting expected genetic mutations and fusion genes. The use of residual LBC specimens for genomic analysis, including gene fusion analysis, is especially useful for obtaining preoperative genomic information.

Although cytomorphologic evaluations using tissue-touch imprints during ROSE or intraoperative consultation are valuable, few studies have explored their use in molecular testing, and next-generation sequencing in particular. Aydin Mericoz et al. [96] suggested that touch imprint slides could serve as an alternative when neoplastic cells are scarce or when nucleic acid quality is compromised by decalcification in permanent biopsy specimens. They recommended routine use of touch imprints in all bone biopsies, with digital scans made for reference and original slides reserved for DNA/RNA-based molecular research.

Cell block (and blood clot) preparations are reliable sources of stored material for molecular testing. FISH is one of the most commonly performed tests in routine practice. In breast cancer, FISH can be used to detect specific gene fusions, such as MYB-NFIB, or to assess the level of HER2 amplification [97,98].

Although most molecular tests are performed on FFPE tissue samples, several well-established molecular diagnostic tests and both commercial and laboratory-developed tests can be performed on cytological samples [88].

Digital pathology and AI

Modern whole-slide scanners, capable of capturing high-resolution and stacked images, have enabled the development of digital tools for cytopathology and AI models [99]. The use of whole-slide imaging (WSI) in cytopathology has lagged behind that in histopathology. Ren et al. [100] scanned glass slides of intraoperative touch imprint cytology from the axillary sentinel lymph nodes of patients with breast cancer using two different WSI scanners. They compared intraobserver and interobserver agreement, accuracy, potential causes of diagnostic errors, scanning times, and review times between WSI and light microscopy (LM). When comparing LM slides with WSI digital slides, intraobserver and interobserver agreement was high. LM accuracy averaged 98.06%, slightly higher than that of WSI (96.8%–97.8%). Most diagnostic errors were due to false negatives, typically arising from cases with few cancer cells or confusion between cancer cells and histiocytes or lymphocytes. The Ren et al.’s study [100] suggested that WSI may serve as a practical option for intraoperative touch imprint cytological diagnosis of sentinel lymph nodes when experienced pathologists are unavailable.

Deep learning algorithms for detecting lymph node metastases from tissue sections have shown promising results [101]. As digital cytopathology and AI continue to evolve, future capabilities may include not only cytological diagnosis but integrated structural reporting, possibly even replacing certain molecular tests [102,103].

CONCLUSION

We reviewed the role of breast FNAC in the diagnosis of breast lesion. Despite the increasing use of CNB, FNAC remains a cost-effective, minimally invasive, and safe diagnostic method of evaluating breast lesions with a significant degree of accuracy, particularly when performed by experienced practitioners.

To overcome the limitations and declining use of breast FNAC, new approaches have been attempted. A new standardized reporting system, the IAC Yokohama System, based on the ROM can improve the diagnostic skill and interpretation of breast FNAC, as well as communication between cytopathologists and clinicians. The introduction of ROSE has substantially reduced the number of inadequate samples, further enhancing FNAC’s diagnostic value. A combination of FNAC and CNB can significantly enhance diagnostic accuracy. Together, these techniques allow for more comprehensive evaluation, particularly when the initial FNAC result is “indeterminate” or “atypical.”

The ongoing integration of advanced technologies, such as LBC, molecular testing using FNAC samples, and digital pathology supported by WSI and AI, is transforming the landscape of cytological diagnostics. These innovations allow for more precise molecular profiling, superior sample preservation, and enhanced diagnostic accuracy, making FNAC a relevant and valuable tool, even in the modern era of breast pathology. As these technologies continue to evolve, FNAC’s role may expand, providing a cost-effective, efficient, and less-invasive option for breast cancer diagnosis, particularly in multidisciplinary settings where rapid, reliable diagnoses are critical for treatment planning.

REFERENCES

• 1. Gupta DK, Mooney EE, Layfield LJ. Fine-needle aspiration cytology: a survey of current utilization in relationship to hospital size, surgical pathology volume, and institution type. Diagn Cytopathol 2000; 23: 59-65. ArticlePubMed
• 2. Ly A, Ono JC, Hughes KS, Pitman MB, Balassanian R. Fine-needle aspiration biopsy of palpable breast masses: patterns of clinical use and patient experience. J Natl Compr Canc Netw 2016; 14: 527-36. ArticlePubMed
• 3. Farras Roca JA, Tardivon A, Thibault F, et al. Diagnostic performance of ultrasound-guided fine-needle aspiration of nonpalpable breast lesions in a multidisciplinary setting: the Institut Curie's experience. Am J Clin Pathol 2017; 147: 571-9. ArticlePubMed
• 4. Ciatto S, Cariaggi P, Bulgaresi P, Confortini M, Bonardi R. Fine needle aspiration cytology of the breast: review of 9533 consecutive cases. Breast 1993; 2: 87-90. Article
• 5. Elmore JG, Barton MB, Moceri VM, Polk S, Arena PJ, Fletcher SW. Ten-year risk of false positive screening mammograms and clinical breast examinations. N Engl J Med 1998; 338: 1089-96. ArticlePubMed
• 6. Fornage BD, Faroux MJ, Simatos A. Breast masses: US-guided fine-needle aspiration biopsy. Radiology 1987; 162: 409-14. ArticlePubMed
• 7. Willems SM, van Deurzen CH, van Diest PJ. Diagnosis of breast lesions: fine-needle aspiration cytology or core needle biopsy? A review. J Clin Pathol 2012; 65: 287-92. ArticlePubMed
• 8. Nassar A. Core needle biopsy versus fine needle aspiration biopsy in breast: a historical perspective and opportunities in the modern era. Diagn Cytopathol 2011; 39: 380-8. ArticlePubMed
• 9. Tikku G, Umap P. Comparative study of core needle biopsy and fine needle aspiration cytology in palpable breast lumps: scenario in developing nations. Turk Patoloji Derg 2016; 32: 1-7. ArticlePubMed
• 10. Mremi A, Pallangyo A, Mshana T, et al. The role of clinical breast examination and fine needle aspiration cytology in early detection of breast cancer: a cross-sectional study nested in a cohort in a low-resource setting. Womens Health (Lond) 2024; 20: 17455057241250131.ArticlePubMedPMCPDF
• 11. Khorsandi N, Balassanian R, Vohra P. Fine needle aspiration biopsy in low- and middle-income countries. Diagn Cytopathol 2024; 52: 426-32. ArticlePubMed
• 12. Uzan C, Andre F, Scott V, et al. Fine-needle aspiration for nucleic acid-ased molecular analyses in breast cancer. Cancer 2009; 117: 32-9. ArticlePubMed
• 13. Lee HB, Joung JG, Kim J, et al. The use of FNA samples for whole-exome sequencing and detection of somatic mutations in breast cancer surgical specimens. Cancer Cytopathol 2015; 123: 669-77. ArticlePubMed
• 14. Islam R, Tarique M. Artificial intelligence (AI) and nuclear features from the fine needle aspirated (FNA) tissue samples to recognize breast cancer. J Imaging 2024; 10: 201.ArticlePubMedPMC
• 15. Martin HE, Ellis EB. Aspiration biopsy. Surg Gyn Obst 1934; 59: 578-89.
• 16. Bauermeister DE. The role and limitations of frozen section and needle aspiration biopsy in breast cancer diagnosis. Cancer 1980; 46: 947-9. ArticlePubMed
• 17. Masood S. Core needle biopsy versus fine-needle aspiration biopsy: are there similar sampling and diagnostic issues? Breast J 2003; 9: 145-6. ArticlePubMed
• 18. Cobb CJ, Raza AS. Obituary: "alas poor FNA of breast: we knew thee well!". Diagn Cytopathol 2005; 32: 1-4. ArticlePubMed
• 19. Pinto DG, Tse G, Tan PH, Schmitt F. Aspiration techniques. In: Tse G, Tan PH, Schmitt F, eds. Fine needle aspiration cytology of the breast: atlas of cyto-histologic correlates. Berlin: Springer, 2023; 21-31.
• 20. Field AS, Raymond WA, Richard MT, et al. Introduction and overview. In: Field AS, Raymond WA, Schmitt F, eds. The International Academy of Cytology Yokohama System for reporting breast fine needle aspiration biopsy cytopathology, Berlin: Springer, 2020; 1-9.
• 21. Moschetta M, Telegrafo M, Carluccio DA, et al. Comparison between fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) in the diagnosis of breast lesions. G Chir 2014; 35: 171-6. ArticlePubMedPMC
• 22. Ballo MS, Sneige N. Can core needle biopsy replace fine-needle aspiration cytology in the diagnosis of palpable breast carcinoma: a comparative study of 124 women. Cancer 1996; 78: 773-7. ArticlePubMed
• 23. Berner A, Sauer T. Fine-needle aspiration cytology of the breast. Ultrastruct Pathol 2011; 35: 162-7. ArticlePubMed
• 24. El Chamieh C, Vielh P, Chevret S. Statistical methods for evaluating the fine needle aspiration cytology procedure in breast cancer diagnosis. BMC Med Res Methodol 2022; 22: 40.ArticlePubMedPMC
• 25. Field AS, Raymond WA, Rickard M, Schmitt F. Breast fine needle aspiration biopsy cytology: the potential impact of the International Academy of Cytology Yokohama System for reporting breast fine needle aspiration biopsy cytopathology and the use of rapid on-site evaluation. J Am Soc Cytopathol 2020; 9: 103-11. ArticlePubMed
• 26. Hoorntje LE, Schipper ME, Kaya A, Verkooijen HM, Klinkenbijl JG, Borel Rinkes IH. Tumour cell displacement after 14G breast biopsy. Eur J Surg Oncol 2004; 30: 520-5. ArticlePubMed
• 27. Kazi M, Parshad R, Seenu V, Mathur S, Haresh KP. Fine-needle aspiration cytology (FNAC) in breast cancer: a reappraisal based on retrospective review of 698 cases. World J Surg 2017; 41: 1528-33. ArticlePubMedPDF
• 28. Litherland JC. Should fine needle aspiration cytology in breast assessment be abandoned? Clin Radiol 2002; 57: 81-4. ArticlePubMed
• 29. Field AS, Raymond WA, Rickard M, et al. The International Academy of Cytology Yokohama System for reporting breast fine-needle aspiration biopsy cytopathology. Acta Cytol 2019; 63: 257-73. ArticlePubMedPDF
• 30. Nigam JS, Kumar T, Bharti S, Sinha R, Bhadani PP. The International Academy of Cytology standardized reporting of breast fine-needle aspiration biopsy cytology: a 2 year's retrospective study with application of categories and their assessment for risk of malignancy. Cytojournal 2021; 18: 27.ArticlePubMedPMC
• 31. Agrawal N, Kothari K, Tummidi S, Sood P, Agnihotri M, Shah V. Fine-needle aspiration biopsy cytopathology of breast lesions using the International Academy of Cytology Yokohama System and rapid on-site evaluation: a single-institute experience. Acta Cytol 2021; 65: 463-77. ArticlePubMedPDF
• 32. Sundar PM, Shanmugasundaram S, Nagappan E. The role of the IAC Yokohama System for reporting breast fine needle aspiration biopsy and the ACR Breast Imaging-Reporting and Data System in the evaluation of breast lesions. Cytopathology 2022; 33: 185-95. ArticlePubMedPDF
• 33. Agrawal S, Anthony ML, Paul P, et al. Prospective evaluation of accuracy of fine-needle aspiration biopsy for breast lesions using the International Academy of Cytology Yokohama System for reporting breast cytopathology. Diagn Cytopathol 2021; 49: 805-10. ArticlePubMedPDF
• 34. Wong YP, Vincent James EP, Mohammad Azhar MA, et al. Implementation of the International Academy of Cytology Yokohama standardized reporting for breast cytopathology: an 8-year retrospective study. Diagn Cytopathol 2021; 49: 718-26. ArticlePubMedPDF
• 35. Dixit N, Trivedi S, Bansal VK. A retrospective analysis of 512 cases of breast fine needle aspiration cytology utilizing the recently proposed IAC Yokohama System for reporting breast cytopathology. Diagn Cytopathol 2021; 49: 1022-31. ArticlePubMed
• 36. Ahuja S, Malviya A. Categorization of breast fine needle aspirates using the International Academy of Cytology Yokohama System along with assessment of risk of malignancy and diagnostic accuracy in a tertiary care centre. J Cytol 2021; 38: 158-63. ArticlePubMedPMC
• 37. Marabi M, Aphivatanasiri C, Jamidi SK, et al. The International Academy of Cytology Yokohama System for Reporting Breast Cytopathology showed improved diagnostic accuracy. Cancer Cytopathol 2021; 129: 852-64. ArticlePubMedPDF
• 38. Oosthuizen M, Razack R, Edge J, Schubert PT. Classification of male breast lesions according to the IAC Yokohama System for reporting breast cytopathology. Acta Cytol 2021; 65: 132-9. ArticlePubMedPDF
• 39. Agarwal A, Singh D, Mehan A, et al. Accuracy of the International Academy of Cytology Yokohama System of breast cytology reporting for fine needle aspiration biopsy of the breast in a dedicated breast care setting. Diagn Cytopathol 2021; 49: 195-202. ArticlePubMedPDF
• 40. De Rosa F, Migliatico I, Vigliar E, et al. The continuing role of breast fine-needle aspiration biopsy after the introduction of the IAC Yokohama System for reporting breast fine needle aspiration biopsy cytopathology. Diagn Cytopathol 2020; 48: 1244-53. ArticlePubMedPDF
• 41. Apuroopa M, Chakravarthy VK, Rao DR. Application of Yokohama System for reporting breast fine needle aspiration cytology in correlation with histopathological and radiological findings. Ann Pathol Lab Med 2020; 7: A210-5. Article
• 42. Wong S, Rickard M, Earls P, Arnold L, Bako B, Field AS. The International Academy of Cytology Yokohama System for reporting breast fine needle aspiration biopsy cytopathology: a single institutional retrospective study of the application of the system categories and the impact of rapid onsite evaluation. Acta Cytol 2019; 63: 280-91. ArticlePubMedPDF
• 43. McHugh KE, Bird P, Sturgis CD. Concordance of breast fine needle aspiration cytology interpretation with subsequent surgical pathology: an 18-year review from a single sub-Saharan African institution. Cytopathology 2019; 30: 519-25. ArticlePubMedPDF
• 44. Montezuma D, Malheiros D, Schmitt FC. Breast fine needle aspiration biopsy cytology using the newly proposed IAC Yokohama System for reporting breast cytopathology: the experience of a single institution. Acta Cytol 2019; 63: 274-9. ArticlePDF
• 45. Nikas IP, Vey JA, Proctor T, et al. The use of the International Academy of Cytology Yokohama System for reporting breast fine-needle aspiration biopsy. Am J Clin Pathol 2023; 159: 138-45. ArticlePubMedPDF
• 46. Layfield LJ, Wang G, Yang ZJ, Gomez-Fernandez C, Esebua M, Schmidt RL. Interobserver agreement for the International Academy of Cytology Yokohama System for reporting breast fine-needle aspiration biopsy cytopathology. Acta Cytol 2020; 64: 413-9. ArticlePubMedPDF
• 47. Folarin O, Kim D, Gokozan HN, et al. Interobserver agreement and risk of malignancy using the International Academy of Cytology Yokohama System for reporting breast FNA biopsy in a liquid-based exclusive cohort. Cancer Cytopathol 2024; 132: 320-6. ArticlePubMed
• 48. Hoda RS, Brachtel EF. International Academy of Cytology Yokohama System for reporting breast fine-needle aspiration biopsy cytopathology: a review of predictive values and risks of malignancy. Acta Cytol 2019; 63: 292-301. ArticlePubMedPDF
• 49. VandenBussche CJ, Baloch ZW. The cytologic diagnosis of "atypical": criteria and controversies. Diagn Cytopathol 2022; 50: 143-5. ArticlePubMedPDF
• 50. Tejeswini V, Chaitra B, Renuka IV, Laxmi K, Ramya P, Sowjanya KKS. Effectuation of International Academy of Cytology Yokahama reporting system of breast cytology to assess malignancy risk and accuracy. J Cytol 2021; 38: 69-73. ArticlePubMedPMC
• 51. Sarangi S, Rao M, Elhence PA, et al. Risk stratification of breast fine-needle aspiration biopsy specimens performed without radiologic guidance by application of the International Academy of Cytology Yokohama System for reporting breast fine-needle aspiration cytopathology. Acta Cytol 2021; 65: 483-93. ArticlePubMedPDF
• 52. Gomes Pinto D, Schmitt FC. Overcoming pitfalls in breast fine-needle aspiration cytology: a practical review. Acta Cytol 2024; 68: 206-18. ArticlePubMedPDF
• 53. Cai G, Adeniran AJ. Overview. In: Cai G, Adeniran AJ, eds. Rapid on-site evaluation (ROSE). Berlin: Springer, 2019; 3-11.
• 54. Hernandez A, Brandler TC, Cangiarella JF. Breast. In: Cai G, Adeniran AJ, eds. Rapid on-site evaluation (ROSE). Berlin: Springer, 2019; 61-92.
• 55. Schoellnast H, Komatz G, Bisail H, et al. CT-guided biopsy of lesions of the lung, liver, pancreas or of enlarged lymph nodes: value of additional fine needle aspiration (FNA) to core needle biopsy (CNB) in an offsite pathologist setting. Acad Radiol 2010; 17: 1275-81. ArticlePubMed
• 56. Silverman JF, Finley JL, O'Brien KF, et al. Diagnostic accuracy and role of immediate interpretation of fine needle aspiration biopsy specimens from various sites. Acta Cytol 1989; 33: 791-6. PubMed
• 57. Nasuti JF, Gupta PK, Baloch ZW. Diagnostic value and cost-effectiveness of on-site evaluation of fine-needle aspiration specimens: review of 5,688 cases. Diagn Cytopathol 2002; 27: 1-4. ArticlePubMed
• 58. Suciu V, El Chamieh C, Soufan R, et al. Real-world diagnostic accuracy of the On-Site Cytopathology Advance Report (OSCAR) procedure performed in a multidisciplinary one-stop breast clinic. Cancers (Basel) 2023; 15: 4967.ArticlePubMedPMC
• 59. Bharti JN, Nigam JS, Rath A, Pradeep I. Insufficient/inadequate category in breast cytology: are the standardized guidelines of rapid on-site evaluation available to reduce its rate? Diagn Cytopathol 2023; 51: 321-4. ArticlePubMedPDF
• 60. Poole GH, Willsher PC, Pinder SE, Robertson JF, Elston CW, Blamey RW. Diagnosis of breast cancer with core-biopsy and fine needle aspiration cytology. Aust N Z J Surg 1996; 66: 592-4. ArticlePubMed
• 61. Salami N, Hirschowitz SL, Nieberg RK, Apple SK. Triple test approach to inadequate fine needle aspiration biopsies of palpable breast lesions. Acta Cytol 1999; 43: 339-43. ArticlePubMed
• 62. Ibrahim AE, Bateman AC, Theaker JM, et al. The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions. J Clin Pathol 2001; 54: 121-5. ArticlePubMedPMC
• 63. Joudeh AA, Shareef SQ, Al-Abbadi MA. Fine-needle aspiration followed by core-needle biopsy in the same setting: modifying our approach. Acta Cytol 2016; 60: 1-13. ArticlePDF
• 64. Sustova P, Klijanienko J. Value of combined use of fine-needle aspiration and core needle biopsy in palpable breast tumors performed by pathologist: Institut Curie experience. Diagn Cytopathol 2020; 48: 71-7. ArticlePubMedPDF
• 65. Li Z, Souers RJ, Tabbara SO, Natale KE, Nguyen LN, Booth CN. Breast fine-needle aspiration practice in 2019: results of a College of American Pathologists national survey. Arch Pathol Lab Med 2021; 145: 825-33. ArticlePubMedPDF
• 66. Gerhard R, Schmitt FC. Liquid-based cytology in fine-needle aspiration of breast lesions: a review. Acta Cytol 2014; 58: 533-42. ArticlePubMedPDF
• 67. Ryu HS, Park IA, Park SY, Jung YY, Park SH, Shin HC. A pilot study evaluating liquid-based fine needle aspiration cytology of breast lesions: a cytomorphological comparison of SurePath(R) liquid-based preparations and conventional smears. Acta Cytol 2013; 57: 391-9. ArticlePubMed
• 68. Silva E, Meschter S, Tan MP. Breast biopsy techniques in a global setting-clinical practice review. Transl Breast Cancer Res 2023; 4: 14.ArticlePubMedPMC
• 69. Chauhan D, Sahu N, Sahoo SR, Senapati U. Accuracy of cytological grading in the carcinoma breast and its correlation with pathological prognostic parameters. J Cancer Res Ther 2023; 19: 1956-61. ArticlePubMed
• 70. Bozzetti C, Nizzoli R, Guazzi A, et al. HER-2/neu amplification detected by fluorescence in situ hybridization in fine needle aspirates from primary breast cancer. Ann Oncol 2002; 13: 1398-403. ArticlePubMed
• 71. Konofaos P, Kontzoglou K, Georgoulakis J, et al. The role of ThinPrep cytology in the evaluation of estrogen and progesterone receptor content of breast tumors. Surg Oncol 2006; 15: 257-66. ArticlePubMed
• 72. Durgapal P, Mathur SR, Kalamuddin M, et al. Assessment of Her-2/neu status using immunocytochemistry and fluorescence in situ hybridization on fine-needle aspiration cytology smears: experience from a tertiary care centre in India. Diagn Cytopathol 2014; 42: 726-31. ArticlePubMed
• 73. Vohra P, Buelow B, Chen YY, et al. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression in breast cancer FNA cell blocks and paired histologic specimens: a large retrospective study. Cancer Cytopathol 2016; 124: 828-35. ArticlePubMedPDF
• 74. Torous VF, Cuda JM, Manucha V, et al. Cell blocks in cytology: review of preparation methods, advantages, and limitations. J Am Soc Cytopathol 2023; 12: 77-88. ArticlePubMed
• 75. Jamidi SK, Li JJX, Aphivatanasiri C, et al. Papillary lesions of the breast: a systematic evaluation of cytologic parameters. Cancer Cytopathol 2021; 129: 649-61. ArticlePubMedPDF
• 76. van Essen HF, Verdaasdonk MA, Elshof SM, de Weger RA, van Diest PJ. Alcohol based tissue fixation as an alternative for formaldehyde: influence on immunohistochemistry. J Clin Pathol 2010; 63: 1090-4. ArticlePubMed
• 77. Pinto D, Schmitt FC. Immunohistochemistry applied to breast cytological material. Pathobiology 2022; 89: 343-58. ArticlePubMedPDF
• 78. Dong J, Ly A, Arpin R, Ahmed Q, Brachtel E. Breast fine needle aspiration continues to be relevant in a large academic medical center: experience from Massachusetts General Hospital. Breast Cancer Res Treat 2016; 158: 297-305. ArticlePubMedPDF
• 79. Kumar SK, Gupta N, Rajwanshi A, Joshi K, Singh G. Immunochemistry for oestrogen receptor, progesterone receptor and HER2 on cell blocks in primary breast carcinoma. Cytopathology 2012; 23: 181-6. ArticlePubMed
• 80. Puccetti M, Ravaioli S, Tumedei MM, et al. Are fine-needle aspiration biopsy-derived cell blocks a useful surrogate for tissue samples in breast cancer? Histopathology 2018; 73: 801-8. ArticlePubMedPDF
• 81. Briffod M, Hacene K, Le Doussal V. Immunohistochemistry on cell blocks from fine-needle cytopunctures of primary breast carcinomas and lymph node metastases. Mod Pathol 2000; 13: 841-50. ArticlePubMedPDF
• 82. Singh S, Shukla S, Singh A, Acharya S, Kadu RP, Bhake A. Comparison of estrogen and progesterone receptor status in tumor mass and axillary lymph node metastasis in patients with carcinoma breast. Int J Appl Basic Med Res 2020; 10: 117-21. PubMedPMC
• 83. Baros IV, Tanaskovic N, Pellas U, Eri Z, Tadic Latinovic L, Tot T. Internodal HER2 heterogeneity of axillary lymph node metastases in breast cancer patients. Bosn J Basic Med Sci 2019; 19: 242-8. PubMedPMC
• 84. Pareja F, Murray MP, Jean RD, et al. Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma. J Am Soc Cytopathol 2017; 6: 33-40. ArticlePubMedPMC
• 85. Kuukasjarvi T, Kononen J, Helin H, Holli K, Isola J. Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. J Clin Oncol 1996; 14: 2584-9. ArticlePubMed
• 86. Kane G, Fleming C, Heneghan H, et al. False-negative rate of ultrasound-guided fine-needle aspiration cytology for identifying axillary lymph node metastasis in breast cancer patients. Breast J 2019; 25: 848-52. ArticlePubMedPDF
• 87. Desai N, Connelly CF, Sung S, Cimic A, Baskota SU. Interobserver variability in HER-2 immunostaining interpretation of metastatic HER2 low breast cancers in cytology specimens. Diagn Cytopathol 2024; 52: 722-30. ArticlePubMed
• 88. Pisapia P, Pepe F, Sgariglia R, et al. Next generation sequencing in cytology. Cytopathology 2021; 32: 588-95. ArticlePubMedPMCPDF
• 89. Rekhtman N, Roy-Chowdhuri S. Cytology specimens: a goldmine for molecular testing. Arch Pathol Lab Med 2016; 140: 1189-90. ArticlePubMedPDF
• 90. Vishnubhotla PS. Molecular testing of cytology specimens: are we ready for the new era? Cancer Cytopathol 2016; 124: 9-10. ArticlePubMed
• 91. Symmans WF, Ayers M, Clark EA, et al. Total RNA yield and microarray gene expression profiles from fine-needle aspiration biopsy and core-needle biopsy samples of breast carcinoma. Cancer 2003; 97: 2960-71. ArticlePubMed
• 92. Roy-Chowdhuri S, Chen H, Singh RR, et al. Concurrent fine needle aspirations and core needle biopsies: a comparative study of substrates for next-generation sequencing in solid organ malignancies. Mod Pathol 2017; 30: 499-508. ArticlePubMedPDF
• 93. Park HE, Han D, Lee JS, et al. Comparison of breast fine-needle aspiration cytology and tissue sampling for high-throughput proteomic analysis and cancer biomarker detection. Pathobiology 2024; 91: 359-69. ArticlePubMedPDF
• 94. Hoshino A, Oana Y, Ohi Y, et al. Using the DNA integrity number to analyze DNA quality in specimens collected from liquid-based cytology after fine-needle aspiration of breast tumors and lesions. Acta Cytol 2024; 68: 145-52. ArticlePubMedPDF
• 95. Akahane T, Isochi-Yamaguchi T, Hashiba-Ohnuki N, et al. Cancer gene analysis of liquid-based cytology specimens using next-generation sequencing: a technical report of bimodal DNA- and RNA-based panel application. Diagn Cytopathol 2023; 51: 493-500. ArticlePubMed
• 96. Aydin Mericoz C, Eren OC, Kulac I, Firat P. Fusion of old and new: employing touch imprint slides for next generation sequencing in solid tumors. Diagn Cytopathol 2024; 52: 264-70. ArticlePubMed
• 97. Martelotto LG, De Filippo MR, Ng CK, et al. Genomic landscape of adenoid cystic carcinoma of the breast. J Pathol 2015; 237: 179-89. ArticlePubMedPMCPDF
• 98. D'Alfonso TM, Mosquera JM, MacDonald TY, et al. MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Hum Pathol 2014; 45: 2270-80. ArticlePubMed
• 99. Farahani N, Parwani AV, Pantanowitz L. Whole slide imaging in pathology: advantages, limitations, and emerging perspectives. Pathol Lab Med Int 2015; 7: 23-33. Article
• 100. Ren F, Li H, Yang W, et al. Viability of whole-slide imaging for intraoperative touch imprint cytological diagnosis of axillary sentinel lymph nodes in breast cancer patients. Diagn Cytopathol 2024; 53: 18-26. ArticlePubMedPMC
• 101. Liu Y, Kohlberger T, Norouzi M, et al. Artificial intelligence-based breast cancer nodal metastasis detection: insights into the black box for pathologists. Arch Pathol Lab Med 2019; 143: 859-68. ArticlePubMedPDF
• 102. Sandbank J, Bataillon G, Nudelman A, et al. Validation and real-world clinical application of an artificial intelligence algorithm for breast cancer detection in biopsies. NPJ Breast Cancer 2022; 8: 129.ArticlePubMedPMCPDF
• 103. Binder A, Bockmayr M, Hagele M, et al. Morphological and molecular breast cancer profiling through explainable machine learning. Nat Mach Intell 2021; 3: 355-66. ArticlePDF

Figure & Data

References

Citations

Citations to this article as recorded by  

• Evaluation of Breast Lesions on Cytology Using International Academy of Cytology Yokohama Standardized Reporting System
  Manish Jaiswal, Anurag Gupta, Tripti Verma, Pradyumn Singh, Rita Yadav, Akash Agarwal, Ashish Singhal, Nuzhat Husain, Shamrendra Narayan, Neha Singh
  Diagnostic Cytopathology.2026; 54(3): 184.     CrossRef
• Personalizing therapies over the course of hormone receptor‐positive/HER2‐negative metastatic breast cancer
  Akshara Singareeka Raghavendra, Senthil Damodaran, Carlos H. Barcenas, Suzanne A. Fuqua, Rachel M. Layman, Debu Tripathy
  CA: A Cancer Journal for Clinicians.2026;[Epub]     CrossRef
• Transforming Breast Cancer Control in East Africa by Integrating Cytomorphology and Genetics Into National Policy
  Josephine N Rioki, Mwangi Joseph, Rency Lel, Marshal Mweu, Lucy Muchiri
  Cureus.2026;[Epub]     CrossRef
• Prélèvements mammaires percutanés
  A. Ribrag, R. Foucher
  EMC - Gynécologie.2026; 41(3): 1.     CrossRef
• Bulk-lysis protocols as a sensitive method for investigation of circulating CK19 cells in the peripheral blood of patients with breast cancer by flow cytometry
  Daniella Serafin Couto Vieira, Laura Otto Walter, Maria Eduarda Cunha da Silva, Lisandra de Oliveira Silva, Heloísa Zorzi Costa, Chandra Chiappin Cardoso, Fernando Carlos de Lander Schmitt, Maria Cláudia Santos-Silva
  Analytical Methods.2025; 17(23): 4771.     CrossRef