Sub-Centimeter Thyroid Nodule Size May Not Offer Good Prognostic Indicator for Biopsy

The rising overall risk of all sizes of malignant thyroid cancer has made clinicians question whether or not sub-centimeter thyroid nodules should also be biopsied. Recent American Thyroid Association (ATA) guidelines have stated that cytological biopsy should not be performed for anyone with thyroid nodules that are ≤1 cm in size. However, analysis of evidence-based data examining whether or not >1-cm thyroid nodules indicate a higher risk of recurrence and malignancy is lacking.

To address this question, investigators at the University of Tulane, New Orleans, LA, performed a retrospective analysis, spanning 6 years, of patients with thyroid nodules of various sizes. They identified 912 nodules for analysis. Roughly 17% (n = 154) were malignant and 83% (n = 758) benign. Based on the ATA risk score criteria, there were 5% (n = 8) in the high-risk, 20% (n = 31) in the intermediate-risk, and 74% (n = 114) in the ATA low-risk categories. For prognostic outcomes, each patient was also stratified to three categories based on MACIS scores (distantMetastasis, patientAge,Completeness of resection, localInvasion, and tumorSize), which are used to predict mortality for papillary thyroid carcinoma (PTC) in adults. The rate of cancer recurrence and outcome for patients was analyzed with respect to whether the thyroid nodule is ≤1 cm compared with >1 cm and evaluated with respect to malignant potential and outcome.

Muhammad Ahmed Farooq Anwar, MBBS, presented the results of the retrospective study. Surprisingly, there was no significant difference in the ATA risk of recurrence for patients initially presenting with ≤1-cm lesions compared with >1 cm (P= .72). Similarly, the size of the initial presenting thyroid nodule was not predictive of MACIS probability outcome (P=.76). There was no significant difference between initial presentations of ≤1-cm compared to >1-cm nodules. This suggests that larger thyroid nodule size is not suggestive of a poor prognosis.

Analysis of the other prognostic tests confirmed that calcifications detected by ultrasound, extrathyroid extensions, capsular invasion, lymphovascular invasion, aggressive histology,BRAFmutation, and positive surgical margins were all directly associated with higher risk of disease recurrence and of poorer prognosis. Of the 13 malignant cases with nodule size ≤1 cm, there were two that had extrathyroid extension. Two more had capsular invasion. Five had lymphovascular invasion and six had positiveBRAFmutation (P>.05).

Based on this analysis, Anwar emphasized that the recent ATA guidelines to abstain from cytological evaluation by biopsy for patients solely on the basis of having thyroid nodules ≤ 1cm is not advisable:

Based on our data we conclude that the risk for occurrence in the sub-centimeter nodules is the same as for larger nodules. The current question is to identify another tool that can be used to better determine the future prognosis for any size nodule. Until we can identify a tool that can be used to better determine the true malignancy risk, we believe we should continue to biopsy sub-centimeter nodules under the 2009 guidelines.

Anwar et al have concluded that thyroid nodule size alone is insufficient information for making a biopsy decision, because this retrospective analysis revealed that the prognosis and risk of cancer recurrence are independent of thyroid nodule size at presentation. The investigators expressed that prospective studies are needed to obtain higher quality data. Prognostic indicators that are better than gross 1-cm thyroid nodule size need to be identified to provide higher quality biopsy decision-influencing information.

Anwar M. Do the recent American thyroid association guidelines accurately guide the biopsy according to nodule size? A retrospective review. Presented at the 15th International Thyroid Congress: Lake Buena Vista, Florida; October 21, 2015. Abstract #470.