{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:15:04Z","timestamp":1788430504897,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Axillary lymph node (ALN) fine-needle aspirations (FNAs) can guide the next steps in the management of patients with invasive breast carcinoma (BC). The objective is to evaluate the diagnostic performance of ALN FNA in the detection of metastatic breast carcinoma. Methods: We evaluated ALN FNAs from 2020 to 2024 to determine the risk of malignancy (ROM) of different cytologic diagnostic categories using a general WHO cytology reporting system framework (insufficient, benign, atypical, suspicious, and malignant). Results: A total of 290 axillary lymph node FNAs from patients with newly diagnosed invasive breast carcinoma were identified, of which 226 (78%) had histologic and\/or adequate clinical follow-up. Cytologic diagnoses included six (2.1%) non-diagnostic, 99 (34.1%) benign, two (0.7%) atypical, seven (2.4%) suspicious for malignancy, and 176 (60.7%) malignant cases. The risk of malignancy (ROM) was 50.0% for non-diagnostic, 17.0% for benign, 100% for atypical, 85.7% for suspicious, and 99.2% for malignant diagnoses. Most false-negative benign cases were attributed to sampling limitations rather than interpretive error, with five cases showing only a single sentinel lymph node metastasis measuring &lt;5 mm. Indeterminate diagnoses were most commonly associated with scant cellularity, acellular cell blocks, obscuring blood or fibrin, and equivocal immunohistochemistry. Excluding cases without histologic follow-up, ALN FNA demonstrated a sensitivity of 86.5%, specificity of 97.4%, positive predictive value of 98.5%, negative predictive value of 79.2%, and overall accuracy of 90.3% for the detection of metastatic breast carcinoma (OR = 243.2, Fisher\u2019s exact test, p &lt; 0.0001). Conclusion: ALN FNA is a highly reliable method for confirming axillary lymph node metastasis in invasive breast carcinoma when malignant cells are identified, with a ROM of 99% for the malignant category. The suspicious category was also strongly associated with malignancy (ROM 86%). However, the 17% ROM observed in the benign category indicates that a negative FNA does not reliably exclude metastatic disease, and surgical nodal staging may still be warranted in clinically or radiologically suspicious cases. These findings support the clinical applicability of the WHO System for Reporting Lymph Node Cytopathology and provide breast carcinoma-specific ROM estimates for this clinical setting.<\/jats:p>","DOI":"10.3390\/cancers18172847","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Applicability of the WHO Reporting System for Axillary Lymph Node Fine-Needle Aspiration in Invasive Breast Carcinoma"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6555-0167","authenticated-orcid":false,"given":"Mariana","family":"Canepa","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Allison","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-1722","authenticated-orcid":false,"given":"Stephanie L.","family":"Graff","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Brown University Health, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10549-018-4796-9","article-title":"The relationship between tumour size, nodal status and distant metastases: On the origins of breast cancer","volume":"170","author":"Sopik","year":"2018","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3390\/jmp3040020","article-title":"The Value of Fine Needle Aspiration Biopsy in the Pre-Operative Assessment of the Axilla in Breast Cancer Patients","volume":"3","author":"Raymond","year":"2022","journal-title":"J. Mol. Pathol."},{"key":"ref_4","first-page":"1860","article-title":"Impact of sentinel lymph node biopsy in newly diagnosed invasive breast cancer patients with suspicious node: A comparative accuracy survey of fine-needle aspiration biopsy versus core-needle biopsy","volume":"10","author":"Bhandari","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"554","DOI":"10.4048\/jbc.2021.24.e47","article-title":"Imaging Protocol and Criteria for Evaluation of Axillary Lymph Nodes in the NAUTILUS Trial","volume":"24","author":"Chang","year":"2021","journal-title":"J. Breast Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"696","DOI":"10.2214\/AJR.12.9036","article-title":"Utility of Preoperative Ultrasound for Predicting pN2 or Higher Stage Axillary Lymph Node Involvement in Patients with Newly Diagnosed Breast Cancer","volume":"200","author":"Abe","year":"2013","journal-title":"Am. J. Roentgenol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.2214\/AJR.05.0936","article-title":"Role of Sonography in the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review","volume":"186","author":"Alvarez","year":"2006","journal-title":"Am. J. Roentgenol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1148\/radiol.13122637","article-title":"Axillary Lymph Node Biopsy in Newly Diagnosed Invasive Breast Cancer: Comparative Accuracy of Fine-Needle Aspiration Biopsy versus Core-Needle Biopsy","volume":"269","author":"Rautiainen","year":"2013","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pyo, J.-S., Jung, J., Lee, S.G., Kim, N.-Y., and Kang, D.-W. (2020). Diagnostic Accuracy of Fine-Needle Aspiration Cytology and Core-Needle Biopsy in the Assessment of the Axillary Lymph Nodes in Breast Cancer\u2014A Meta-Analysis. Diagnostics, 10.","DOI":"10.3390\/diagnostics10090717"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/cncr.23344","article-title":"Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients","volume":"114","author":"Alkuwari","year":"2008","journal-title":"Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1002\/cncr.10786","article-title":"Role of ultrasound-guided fine-needle aspiration of indeterminate and suspicious axillary lymph nodes in the initial staging of breast carcinoma","volume":"95","author":"Krishnamurthy","year":"2002","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/cncy.22770","article-title":"Fine-needle aspiration biopsy of axillary lymph nodes: A reliable diagnostic tool for breast cancer staging","volume":"132","author":"Sallout","year":"2023","journal-title":"Cancer Cytopathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.2214\/AJR.10.4414","article-title":"Axillary Ultrasound and Fine-Needle Aspiration in the Preoperative Evaluation of the Breast Cancer Patient: An Algorithm Based on Tumor Size and Lymph Node Appearance","volume":"195","author":"Mainiero","year":"2010","journal-title":"Am. J. Roentgenol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1159\/000548199","article-title":"The World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Part 1\u2014Lymph Node","volume":"70","author":"Cozzolino","year":"2025","journal-title":"Acta Cytol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000548853","article-title":"The World Health Organization Reporting System for Lymph Node, Spleen, and Thymus Cytopathology: Part 2\u2014Spleen and Thymus","volume":"70","author":"Cozzolino","year":"2025","journal-title":"Acta Cytol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.14218\/JCTP.2023.00044","article-title":"Introduction of the WHO Reporting System for Lymph Node Cytopathology","volume":"4","author":"Gao","year":"2023","journal-title":"J. Clin. Transl. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1159\/000527580","article-title":"The World Health Organization Reporting System for Lung Cytopathology","volume":"67","author":"Schmitt","year":"2022","journal-title":"Acta Cytol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1159\/000499509","article-title":"The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology","volume":"63","author":"Field","year":"2019","journal-title":"Acta Cytol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1159\/000527912","article-title":"The World Health Organization Reporting System for Pancreaticobiliary Cytopathology","volume":"67","author":"Pitman","year":"2022","journal-title":"Acta Cytol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1089\/thy.2017.0500","article-title":"The 2017 Bethesda System for Reporting Thyroid Cytopathology","volume":"27","author":"Cibas","year":"2017","journal-title":"Thyroid"},{"key":"ref_21","first-page":"72","article-title":"World Health Organization Reporting System for Soft Tissue Cytopathology: A Concise Review with a Practical Diagnostic Approach","volume":"5","author":"Bui","year":"2025","journal-title":"J. Clin. Transl. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/ajcp\/aqac132","article-title":"The Use of the International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy","volume":"159","author":"Nikas","year":"2022","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1590\/0100-3984.2014.0121","article-title":"Axillary ultrasound and fine-needle aspiration in preoperative staging of axillary lymph nodes in patients with invasive breast cancer","volume":"48","author":"Rocha","year":"2015","journal-title":"Radiol. Bras."},{"key":"ref_24","first-page":"69","article-title":"Staging the axilla in women with breast cancer: The utility of preoperative ultrasound-guided needle biopsy","volume":"11","author":"Houssami","year":"2014","journal-title":"Cancer Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4048\/jbc.2023.26.e13","article-title":"Evaluation of the Role of Axillary Lymph Node Fine-Needle Aspiration Cytology in Early Breast Cancer with or Without Neoadjuvant Chemotherapy","volume":"26","author":"Takatsuka","year":"2023","journal-title":"J. Breast Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s43046-025-00318-7","article-title":"De-escalating axillary surgery in node-positive early breast cancer patients undergoing primary surgery: Current evidence and recommendations","volume":"37","author":"Abdulla","year":"2025","journal-title":"J. Egypt. Natl. Cancer Inst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1001\/jama.2013.278932","article-title":"Sentinel Lymph Node Surgery After Neoadjuvant Chemotherapy in Patients with Node-Positive Breast Cancer","volume":"310","author":"Boughey","year":"2013","journal-title":"JAMA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111304","DOI":"10.1016\/j.ejso.2025.111304","article-title":"Patients with positive axillary nodes undergoing upfront surgery: Can axillary dissection be safely omitted?","volume":"52","author":"Addie","year":"2025","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1001\/jama.2017.11470","article-title":"Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women with Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial","volume":"318","author":"Giuliano","year":"2017","journal-title":"JAMA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"26","DOI":"10.4103\/1742-6413.141820","article-title":"The value of preoperative ultrasound guided fine-needle aspiration cytology of radiologically suspicious axillary lymph nodes in breast cancer","volume":"11","author":"Sauer","year":"2014","journal-title":"Cytojournal"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/cncr.23347","article-title":"Cytologic diagnosis of lobular carcinoma of the breast","volume":"114","author":"Menet","year":"2008","journal-title":"Cancer"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2847\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:27:12Z","timestamp":1788427632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/17\/2847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cancers18172847"],"URL":"https:\/\/doi.org\/10.3390\/cancers18172847","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}