Objective: We evaluated the diagnostic role of ultrasonography-guided core needle biopsy (CNB) according to ultrasonography features of thyroid nodules that had inconclusive ultrasonography-guided fine-needle aspiration (FNA) results.
Methods: A total of 88 thyroid nodules in 88 patients who underwent ultrasonography-guided CNB because of previous inconclusive FNA results were evaluated. The patients were classified into three groups based on ultrasonography findings: Group A, which was suspicious for papillary thyroid carcinoma (PTC); Group B, which was suspicious for follicular (Hurthle cell) neoplasm; and Group C, which was suspicious for lymphoma. The final diagnoses of the thyroid nodules were determined by surgical confirmation or follow-up after ultrasonography-guided CNB.
Results: Of the 88 nodules, the malignant rate was 49.1% in Group A, 12.0% in Group B and 90.0% in Group C. The rates of conclusive ultrasonography-guided CNB results after previous incomplete ultrasonography-guided FNA results were 96.2% in Group A, 64.0% in Group B and 90.0% in Group C (p=0.001). 12 cases with inconclusive ultrasonography-guided CNB results were finally diagnosed as 8 benign lesions, 3 PTCs and 1 lymphoma. The number of previous ultrasonography-guided FNA biopsies was not significantly different between the conclusive and the inconclusive result groups of ultrasonography-guided CNB (p=0.205).
Conclusion: Ultrasonography-guided CNB has benefit for the diagnosis of thyroid nodules with inconclusive ultrasonography-guided FNA results. However, it is still not helpful for the differential diagnosis in 36% of nodules that are suspicious for follicular neoplasm seen on ultrasonography. Advances in knowledge: This study shows the diagnostic contribution of ultrasonography-guided CNB as an alternative to repeat ultrasonography-guided FNA or surgery.
DISCUSSION The ultrasonography-guided FNA analysis of the thyroid gland will continue to have a central role in the investigation of patients with nodular disease of the thyroid gland. However, there remains the question of how to approach the 5–20% of patients with non-diagnostic results  and the 1–11% of patients with false-negative results [16,17]. Repeat ultrasonography-guided FNA is recommended for thyroid nodules with initially non-diagnostic cytology results to avoid unnecessary surgery [15,18,19]. Nevertheless, the persistently non-diagnostic rates for nodules with initially non-diagnostic results on FNA are reported to be 20–38% [15,20,21]. In addition, the third FNA for thyroid nodules with two consecutive non-diagnostic cytology results is less likely to be diagnostic . Although the guidelines of the American Thyroid Association and the American Association of Clinical Endocrinologists recommend surgery for thyroid nodules with persistently non-diagnostic cytology results, it is true that surgery for all thyroid nodules with persistently non-diagnostic cytology results is not cost-effective, not to mention the increased morbidity and unnecessary post-operative medication for patients. However, the malignancy rate for thyroid nodules with one or two consecutive non-diagnostic results on FNA is reported to be 12–14% [16,20,22,23]. Thus, besides repeat ultrasonography-guided FNA or surgery, there is a need for further guidelines for thyroid nodules with persistently inconclusive cytology results. Several studies have demonstrated that ultrasonography-guided CNB of the thyroid gland is a safe technique with high yield and accuracy [24–26] and can effectively reduce non-diagnostic readings when compared with repeat ultrasonography-guided FNA of thyroid nodules with non-diagnostic cytology results [10,11,27].
Although the malignancy rate demonstrated the lowest value in Group B (Group A, 49.1%; Group B, 12.0%; and Group C, 90.0%), persistently inconclusive results after ultrasonography-guided CNB were most frequently obtained in Group B (36.0%). The reason for this is because a follicular adenoma cannot be differentiated from a low-grade follicular carcinoma without examination of the entire nodule for evidence of capsular or vascular invasion . Many studies have attempted to improve the pre-operative diagnosis of follicular neoplasm by FNA or imaging characteristics on ultrasonography, but there is still no accurate way for predicting the risk of malignancy [10,28–31]. In this study, we found that the use of CNB would have reduced the inconclusive rate for Group B by 36.0%. For these 36% of indeterminate nodules, surgery still plays an important role by allowing a confirmative diagnosis. We also found that ultrasonography-guided CNB could be useful for accurate diagnosis in cases suspicious for PTC (i.e. Group A) or thyroid lymphoma (i.e. Group C). These were consistent with other reports, suggesting that ultrasonography-guided CNB might be a suitable replacement for repeat FNA [10,11] or diagnostic thyroid surgery .
In our study, the numbers of thyroid nodules with persistently inconclusive results after ultrasonography-guided CNB were 2 (3.8%) in Group A, 9 (36.0%) in Group B and 1 (10.0%) in Group C (p=0.001), respectively. These 12 persistently inconclusive thyroid nodules were finally diagnosed as benign thyroid lesions, including nodular hyperplasia and chronic lymphocytic thyroiditis (n=8), PTC (n=3) and lymphoma (n=1). Although ultrasonography-guided CNB performed by experienced radiologists is a safe and well-tolerated procedure with advantages including larger tissue sample, less operator dependency if the needle successfully penetrates the nodule, capability of assessment of the histological architecture and relation to the adjacent thyroid tissue [6,7], there are still certain possible complications and technical difficulties. Compared with FNA, ultrasonography-guided CNB may be technically difficult in some cases (especially in small nodules located in the posterior portion of the thyroid gland or very close to the carotid artery or trachea).
In our 12 cases with persistently inconclusive results, 5 nodules were under 1 cm and 4 nodules were located in the posterior portion of the thyroid gland or very close to the main vascular structures. These small sizes and particular locations could lead to persistently inconclusive results owing to inaccurate targeting. The remaining three nodules showed mainly fibrosis and a few benign follicular cells in the specimen. The confirmation failure of core biopsy for the fibrotic portion within the relatively large nodule could also produce inconclusive results. When a large nodule shows heterogeneous components on ultrasonography, biopsies should be performed in different areas to avoid the inconclusive results .
In this study, the number of previous ultrasonography-guided FNA biopsies was not significantly different between the conclusive and the inconclusive result groups of ultrasonography-guided CNB (p=0.205). In other words, inconclusive results can be persistently obtained despite the repeat ultrasonography-guided FNAs for the definitive diagnosis. However, CNB produces a histological sample that retains its cytological appearances and its tissue architecture. The histological sample is familiar to most pathologists, and the larger amount of tissue permits the use of a range of immunohistochemical stains and may provide a more precise histological diagnosis [6,33,34].
There are some limitations in this study. First, our study was designed as a retrospective study. Thus, there could be selection bias owing to inclusion of only cytologically inconclusive cases because indications for ultrasonography-guided CNB had not been flexible at the time of study. This may cause underestimation of the ultrasonography-guided CNB performance. Second, we did not consider the differences in experience levels of the radiologists performing ultrasonography-guided CNB. Finally, surgical confirmation was not obtained in 39 patients with benign thyroid nodules and in 3 patients with inconclusive thyroid nodules. Even though we set a standard follow-up period of at least 1 year in these study populations, this follow-up period may not be long enough to exclude a slow-growing malignancy.
In conclusion, the rates of conclusive ultrasonography-guided CNB results after previous incomplete ultrasonography-guided FNA results were 96.2% in Group A (suspicious for PTC), 64.0% in Group B (suspicious for follicular neoplasm) and 90.0% in Group C (suspicious for lymphoma). Ultrasonography-guided CNB has benefit for the diagnosis of thyroid nodules with inconclusive ultrasonography-guided FNA results. However, it is still not helpful for the differential diagnosis in 36% of nodules that are suspicious for follicular neoplasm seen on ultrasonography.