False negative cytology in large thyroid nodules

Ann Surg Oncol. 2015 Jan;22(1):152-7. doi: 10.1245/s10434-014-3952-7. Epub 2014 Jul 30.


Background: Controversy exists regarding the accuracy of fine-needle aspiration (FNA) in large thyroid nodules. Recent surgical series have documented false-negative rates ranging from 0.7 to 13 %. We examined the accuracy of benign FNA cytology in patients with thyroid nodules ≥3 cm who underwent surgical resection and identified features characteristic of false-negative results.

Methods: We retrospectively studied all thyroidectomy specimens between January 2009 and October 2011 and identified nodules ≥3 cm with corresponding benign preoperative FNA cytology. We collected clinical information regarding patient demographics, nodule size, symptoms, sonographic features, FNA results, and final surgical pathology. For comparison, we analyzed nodules <3 cm from this cohort also with benign FNA cytology.

Results: A total of 323 nodules with benign preoperative cytology were identified. Eighty-three nodules were <3 cm, 94 nodules were 3-3.9 cm, and 146 nodules were ≥4 cm in size. The false-negative rate was 11.7 % for all nodules ≥3 cm and 4.8 % for nodules <3 cm (p = 0.03). Subgroup analysis of nodules ≥3 cm revealed a false-negative rate of 12.8 % for nodules 3-3.9 cm and 11 % for nodules ≥4 cm. Age ≥55 years and asymptomatic clinical status were the only patient characteristics that reached statistical significance as risk factors. Final pathology of the false-negative specimens consisted mainly of follicular variant of papillary thyroid cancer and follicular thyroid cancer.

Conclusions: When referred for thyroidectomy, patients with large thyroid nodules demonstrate a modest, yet significant, false-negative rate despite initial benign aspiration cytology. Therefore, thyroid nodules ≥3 cm may be considered for removal even when referred with benign preoperative cytology.

MeSH terms

  • Adenocarcinoma, Follicular / diagnosis*
  • Adenocarcinoma, Follicular / surgery
  • Biopsy, Fine-Needle
  • Carcinoma, Papillary / diagnosis*
  • Carcinoma, Papillary / surgery
  • Cytodiagnosis*
  • False Negative Reactions
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / surgery
  • Thyroid Nodule / diagnosis*
  • Thyroid Nodule / surgery
  • Thyroidectomy

Supplementary concepts

  • Thyroid cancer, follicular