The aim of this study was to evaluate whether malignant-looking thyroid nodules with size reduction were malignant or not.
From November 2010 to July 2011, we retrospectively enrolled 16 patients with 16 nodules (11 females and five males; mean age, 55 years) who underwent core needle biopsy (CNB), and whose thyroid nodules had malignant ultrasonographic (US) features, although they showed size reduction (>20% decrease in maximum diameter) during the follow-up period (mean, 37±27 months). The histologic findings of the CNB specimen were reviewed and correlated with the US findings. US studies were analyzed for their internal content, shape, margin, echogenicity, the presence of microcalcification and macrocalcification, inner isoechoic rim, and low-echoic halo.
All nodules were confirmed as benign by CNB. Pathologic analysis was available for 12 CNB specimens. US imaging showed central hypoechogenicity or marked hypoechogenicity in all cases and a peripheral isoechoic rim in 15 nodules. US-pathologic correlation showed that the central hypoechoic area was primarily composed of fibrosis (12/12) and hemorrhage (8/12) and that the isoechoic rim was composed of follicular cells.
In our study, the CNB results of all of the malignant-looking thyroid nodules with size reduction were benign and were primarily composed of internal fibrosis and hemorrhage. Understanding these US and pathologic features could prevent repeated fine-needle aspiration or unnecessary diagnostic surgery.
The criteria for differentiating benign from malignant nodules in ultrasonographic (US) imaging are well-established, and the major guidelines recommend fine-needle aspiration (FNA) under US guidance for nodules with malignant US features [
Regarding the management of these nodules, if investigators encounter thyroid nodules with malignant US features but without definite, previous information, that is, known history of ethanol or radiofrequency ablation and/or previous sonograms, they should biopsy the nodules. Even if the biopsy results are benign, repeat FNA or diagnostic surgery will still be necessary due to their malignant US features [
Therefore, our study was performed to test the hypothesis that thyroid nodules with size reduction, although with malignant US features, are benign, degenerating nodules rather than malignancies. To test this hypothesis, we evaluated the follow-up results regarding these nodules as well as the histological analysis of their core needle biopsy (CNB) specimens.
This retrospective study was approved by our Institutional Review Board, and informed consent was waived for use of the data in the research study; however, informed consent for all procedures had already been obtained from each patient before procedures were performed.
Computerized medical records and sonograms of 3,114 patients who had undergone US-guided FNA for thyroid nodules at our institution between November 2010 and July 2011 were reviewed. Among these patients, those with thyroid nodules showing all of the following criteria were enrolled: (1) thyroid nodules showing malignant US features, (2) size reduction seen on follow-up US (size reduction was defined as >20% decrease in the longest diameter), (3) follow-up of more than 1 year, and (4) undergoing CNB. The final diagnosis was based on the results of CNB and surgical pathologic examination.
The criteria for classifying a case as having malignant features on US imaging included at least one of the following: (1) marked hypoechogenicity, (2) the presence of microcalcification or macrocalcification, (3) taller-than-wide shape, and (4) a spiculated margin [
US was performed using one of two US systems, an iU22 unit (Philips Healthcare, Bothell, WA, USA) or an EUB-7500 unit (Hitachi Medical Systems, Tokyo, Japan) equipped with a linear high-frequency probe (5-14 MHz). All US and US-guided procedures were performed by clinically experienced radiologists with 7-17 years of clinical experience performing and evaluating thyroid sonograms.
US-guided FNA was performed using a 23-gauge needle attached to a 10-mL, disposable, plastic syringe. US-guided CNBs were performed using a disposable, 18-gauge, double-action, spring-activated needle (1.1- or 1.6-cm excursion, TSK Ace-cut, Create Medic, Yokohama, Japan). After local anesthesia with 1% lidocaine, the end of the biopsy needle was advanced into the edge of or within the nodule using a free-hand technique, and after which the stylet and cutting cannula of the needle were fired sequentially. After FNA or CNB, each patient was observed, and a firm, local compression of the biopsy site was applied for 10-20 minutes [
Sonograms were retrospectively reviewed independently by two clinically experienced radiologists (H.Y.L. and J.H.B., with 8 and 17 years, respectively, of clinical experience performing and evaluating thyroid US). Any diagnostic discrepancies between the two reviewers were resolved by consensus. Individual sonograms were analyzed for the internal content (solid, predominantly solid, predominantly cystic, or cystic), shape (oval-to-round, irregular, or taller-than-wide), margin (smooth, ill-defined, or spiculated), echogenicity (markedly hypoechoic, hypoechoic, isoechoic, or hyperechoic), the presence of microcalcification and macrocalcification, an inner isoechoic rim, and a low-echoic halo [
Histopathologic analysis of the CNB and the surgical specimens was available in 12 and two patients, respectively, and which were retrospectively reviewed by one clinically experienced cytopathologist (D.E.S., with 9 years of clinical experience in thyroid cytopathology). As the diagnostic criteria of CNB have not been standardized for thyroid nodules, diagnoses based on CNB histology were categorized into the six categories of the Bethesda System as follows [
The demographic data, histologic diagnosis, and US features are presented in
CNB specimens of 12 nodules were retrieved for histological analysis from the Department of Pathology of our institution. CNB specimens of four patients were not available to review because they were not retrievable from our pathology department. Among the 12 nodules, the central portions were mainly composed of fibrosis (n=12, 100%), hemorrhage (n=8, 67%), atypia (n=1, 8%), and relatively few follicular cells in all cases, and which corresponded to the hypo- or marked hypoechogenicity seen on US (
Our study demonstrated that all 16 thyroid nodules with malignant US features and with reduction in size during the follow-up period were found to be benign rather than malignant. On histological review of the CNB specimens of 12 nodules, the nodules consisted primarily of fibrosis (100%) and hemorrhage (67%). In terms of the histologic features of these degenerating nodules, the malignant US features were derived from fibrosis and hemorrhage. There were relatively few follicular cells in the center of the nodules, although there was a substantial number in the periphery in 91.7% (11/12) of the nodules. Targeting the central portion of a nodule may pose a higher risk of a non-diagnostic rate on FNA. CNB including the center and periphery of the nodules could minimize non-diagnostic results as well as provide histologic information regarding the degenerative changes.
It is well known that degeneration of cystic or partly cystic thyroid nodules shows malignant US features with reduction in the nodule size [
Ko et al. [
The cause of malignant US features in benign thyroid nodules is not well established. Several studies have reported that low echogenicity, one of the malignant US features, is related to the fibrotic component of thyroid nodules [
Several studies have reported the natural history of thyroid nodules [
In our study, two patients underwent diagnostic surgery due to malignant US features, although the CNB results were benign. Recently, CNB has been reported to be a valuable diagnostic tool that can be used to reduce the incidence of diagnostic surgery and/or repeated FNA in patients with previously non-diagnostic [
Our study has some limitations, including its retrospective study design and small number of patients, which may have caused a selection bias. However, our study has a definite clinical impact when considering that the incidence of solid or predominantly solid nodules showing gradual size reduction is relatively rare, and the number of cases with histologic confirmation using CNB or surgical excision is limited. Nevertheless, our results require additional, prospective studies with larger patient populations. Specific statistical analysis was not performed because the purpose of our study was to identify the benignancy of degenerating nodules according to the pathology correlation.
To conclude, we found that all of the 16 nodules with malignant US features that showed gradual size reduction on follow-up were confirmed to be benign. Our study results could help CNB prevent further diagnostic surgery or repeated FNA for thyroid nodules with malignant US features but with reduction in size, by providing an understanding of the histologic changes of degeneration.
No potential conflict of interest relevant to this article was reported.
A. Transverse sonogram shows a 1.2-cm, hypoechoic solid nodule with an inner isoechoic rim (arrowhead) and a peripheral, low-echoic halo (arrows) in the left thyroid lobe. Subsequent core needle biopsy (CNB) confirmed it as degenerating nodular hyperplasia. B. A CNB specimen shows tissue consisting of a central portion of severe fibrosis and a periphery of a few follicular cells at the corresponding areas seen on sonogram (H&E, ×40).
A. Transverse sonogram shows a 0.8-cm, markedly hypoechoic, solid nodule with an inner isoechoic rim (arrowheads) and a low-echoic halo (arrows) in the right thyroid lobe. B. A core needle biopsy specimen confirmed nodular hyperplasia with fresh hemorrhage and severe fibrosis (H&E, ×40).
A. An isoechoic nodule is surrounded by a hypoechoic rim (arrow) in the thyroid gland. B. Internal hemorrhage (Hem) compresses the remaining isoechoic solid portion of the nodule (arrows). C. Nodule is gradually contracted with degenerative changes such as fibrosis, infarction, and calcifications.
Clinical data and histological diagnosis of nodules
Case No. | Age (yr) | Sex | F/U interval (mo) | Initial diameter (mm) | F/U diameter (mm) | Histological diagnosis |
---|---|---|---|---|---|---|
1 | 62 | F | 22 | 15 | 11 | Nodular hyperplasia |
2 | 37 | F | 14 | 11 | 8 | Benign fibrotic nodule |
3 | 63 | M | 15 | 11 | 8 | Nodular hyperplasia |
4 | 54 | F | 16 | 19 | 14 | Nodular hyperplasia |
5 | 54 | F | 12 | 17 | 10 | Nodular hyperplasia |
6 | 59 | F | 34 | 17 | 11 | Nodular hyperplasia |
7 | 62 | M | 51 | 13 | 4 | Nodular hyperplasia |
8 | 33 | F | 12 | 16 | 3 | Organizing hematoma |
9 | 61 | F | 99 | 65 | 7 | Nodular hyperplasia |
10 | 61 | F | 53 | 13 | 9 | Nodular hyperplasia |
11 | 59 | F | 67 | 16 | 6 | Nodular hyperplasia |
12 | 61 | M | 30 | 24 | 12 | Nodular hyperplasia |
13 | 63 | F | 77 | 41 | 26 | Nodular hyperplasia with hematoma |
14 | 39 | M | 44 | 30 | 13 | Nodular hyperplasia |
15 | 61 | F | 47 | 13 | 8 | Nodular hyperplasia |
16 | 51 | M | 15 | 19 | 6 | Hurthle cell adenoma |
F/U, follow-up; F, female; M, male.
US features of 16 thyroid nodules with benign histology that showed a gradual size decrease on follow-up US
US characteristic | Initial US feature | Follow-up US feature |
---|---|---|
Internal content | ||
Solid | 8 (50) | 16 (100) |
Predominantly solid | 4 (25) | - |
Predominantly cystic | 4 (25) | - |
Shape | ||
Ovoid-to-round | 16 (100) | 12 (75) |
Irregular | - | 4 (25) |
Margin | ||
Smooth | 9 (56) | 1 (6) |
Ill-defined | 6 (38) | 13 (81) |
Spiculated | 1 (6) | 2 (13) |
Echogenicity | ||
Markedly hypoechoic | 3 (19) | 6 (38) |
Hypoechoic | 8 (50) | 10 (62) |
Isoechoic | 5 (31) | - |
Calcification | ||
Microcalcification | 1 (6) | 2 (13) |
Macrocalcification | 2 (13) | 3 (19) |
Rim calcification | 1 (6) | 1 (6) |
Inner isoechoic rim | 0 | 15 (94) |
Low-echoic halo | 5 (31) | 13 (87) |
Values are presented as number (%).
Ultrasonographic (US) features at the time of core needle biopsy. The numbers in parentheses are percentages.
Histological results of 12 thyroid nodules found in core-needle biopsy specimens
Variable | No. (%) |
---|---|
Center | |
Hemorrhage | 8 (67) |
Fibrosis | 12 (100) |
Calcification | 3 (25) |
Granulation | 2 (17) |
Infarction | 0 |
Atypia | 1 (8) |
Periphery | |
Adequate follicular cells | 11 (92) |