Predictors of malignancy in patients with cytologically suspicious thyroid nodules

Abstract

Background: Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology.

Methods: We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA.

Results: Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers.

Conclusion: In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown.

FIG. 1.

Study population. *Five patients without serum TSH values were on thyroid hormone replacement. TSH, thyroid-stimulating hormone.

FIG. 2.

Representative samples of the following cytological categories. (A) Suspicious for follicular neoplasm: Clusters of follicular cells arranged in microfollicles. (B) Suspicious for Hürthle cell neoplasm: Cluster of Hürthle cells arranged in a flat sheet with larger nuclei with prominent nucleoli. (C) Suspicious for papillary carcinoma: Cluster of follicular cells with round nuclei and minimal size variation and nuclear grooving. Note the presence of two distinct intranuclear inclusions that raise the possibility of papillary carcinoma (marked with arrows).

FIG. 3.

Prevalence of single nodules versus multinodular goiter by age group. Note increasing prevalence of multinodular goiter with advancing age.

FIG. 4.

Percent of patients with malignancy among thyroid hormone users and nonusers. A total of 166 thyroid malignancies were identified in the entire cohort. Their distribution is shown for all cohort and by suspicious category. Suspicious-neoplasm includes cytology suspicious for follicular or Hürthle cell neoplasm.