False-Negative Frozen Section of Sentinel Nodes in Early Breast Cancer Patients

Abstract

Background: Sentinel lymph node biopsy (SLNB) is the standard approach of the axillary region for early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes of intraoperative frozen section (FNSNs) in real-world data.Methods: A case–control study with a 1:3 ratio was conducted. FNSN was diagnosed when sentinel nodes (SNs) are negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections.Results: A total of 20 FNSN cases and 60 matched controls were enrolled from 333 SLNB patients between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had larger tumor sizes in preoperative mammography (P = 0.033) and more lymphatic tumor emboli in core biopsy (P < 0.001). Four FNSN patients had metastasis in the non-relevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from the FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in non-relevant SNs were recognized in two patients. All FNSN patients received a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed recurrence of breast cancer. The disease-free survival, disease-specific survival, and overall survival in FNSN were not inferior to the controls.Conclusions: The patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, outcomes of FNSN patients after completing ALND were noninferior to those without metastasis in SNs. ALND provides a correct diagnosis of patients with metastasis in non-sentinel axillary lymph nodes.