Rapid intraoperative cytokeratin immunohistochemistry improves diagnostic accuracy of sentinel lymph nodes in post-neoadjuvant breast cancer.

Intraoperative evaluation of sentinel lymph nodes (SLNs) in breast cancer patients after neoadjuvant therapy (NAT) is challenged by treatment-related fibrosis and scarring, leading to high false-negative rates with conventional frozen-section hematoxylin-eosin (FS-HE) analysis. We prospectively validated whether cytokeratin rapid immunohistochemistry (CK-RIHC) could improve the accuracy of intraoperative SLN diagnosis in this setting. This prospective study included 204 breast cancer patients undergoing SLN biopsy after NAT. The SLN was the unit of analysis. Intraoperatively, paired adjacent frozen sections were evaluated by FS-HE and CK-RIHC (FS-HE first, followed by CK-RIHC), and results were compared with definitive postoperative paraffin histopathology as the reference standard. The primary endpoint was per-node sensitivity for residual nodal involvement. Definitive pathology confirmed nodal involvement in 140 of 693 evaluable SLNs (20.2%). One additional SLN was uncertain (non-verifiable) and excluded from the primary performance analyses. CK-RIHC demonstrated higher sensitivity than FS-HE (98.6% vs 84.3%, p < 0.05) and increased per-node diagnostic accuracy from 96.8% to 99.7%. FS-HE missed 22 involved SLNs, including 1 macrometastasis and 13 micrometastases. CK-RIHC detected all macrometastases and micrometastases in the evaluable cohort, whereas detection of ITCs remained less complete. Intraoperative CK-RIHC is significantly superior to FS-HE in the evaluation of intraoperative SLNs. By enhancing the detection of epithelial cells within therapy-modified tissue, this method reduces false-negative diagnoses of clinically relevant metastatic SLNs. CK-RIHC represents a valuable pathological tool for optimizing intraoperative diagnostic accuracy in post-NAT breast cancer specimens.