What thyroid nodules not to biopsy according to ultrasound criteria: do we need more uncertainty?

TOPIC: S onographic appearance of cystic thyroid nodules

Title: Partially cystic thyroid nodules on ultrasound: probability of malignancy and sonographic differentiation.

Authors: Lee M-J, Kim E-K, Kwak JY, & Kim MJ.

Reference: Thyroid 19: 341-346, 2009



Thyroid nodules are very common and a large portion of them are mixed echoic, with both solid and cystic areas.


To evaluate the frequency of malignancy in mixed echoic thyroid nodules and ascertain the ultrasound findings that help distinguish benign from malignant nodules.


Among 1.056 thyroid nodules undergoing ultrasound with FNAB, 392 nodules (37.1%) were mixed echoic. From this group, the nodules that were read as benign or malignant on histopathology examination after surgery and the nodules that were not resected but were considered benign or malignant on cytology were analyzed retrospectively for their ultrasonographic features. The nodules were divided into 3 groups. Group 1 ( n = 93) included nodules in which the solid portion was <50%; group 2 ( n = 216) comprised nodules in which the solid portion was 50%; and group 3 ( n = 26) included mixed echoic (spongy) nodules. The solid portion of the nodule, namely its position (eccentric or not), shape, margin, and echogenicity, and whether there were micro/macro-calcifications were also analyzed.


In the FNA sample, 52 nodules were inadequate for cytological diagnosis and the remaining 340 (86.7%) were adequate. Eighteen nodules were malignant and 317 benign, yielding a malignancy rate of 5.4%. By group, the malignancy rate was 2.2% in group 1, 7.4% in group 2, and 0% in group 3. There were more malignancies in group 2 than in the other groups (P = 0.04). Among the sonographic findings, eccentric placement (P = 0.007) and presence of micro-calcifications (P <0.001) were significantly correlated with malignancy.


About 5% of partially cystic nodules in this series were malignant. When more than 50% of the nodule is solid and the solid portion of the nodule is eccentric, the risk of malignancy is higher. As has been noted for completely solid nodules, micro-calcifications were associated with increased risk of malignancy.


This investigation provides another ultrasonographic (US) clue that enhances assessing the risk of cancer among thyroid nodules and may improve needle biopsy by revealing where to puncture a complex nodule. The authors examined retrospectively US features of 392 thyroid nodules that had solid and cystic components for characteristics that were predictive of malignancy and assessed the prevalence of thyroid cancer in that population. They report that there is an increased risk of cancer in a complex nodule when US reveals that more than 50% of the nodule is solid and the solid portion of the nodule is eccentric.

The article can also be interpreted as showing where and possibly when not to biopsy and this aspect is the particular focus of present comment. The difference between these two approaches results in a big difference in the risk of missing a cancer. The difference is similar to misjudging that a dog will bite, and giving it wide berth to avoid getting bitten, and mistaking that a dog does not bite and getting mauled. Using US as a reason not to biopsy may result in missing an unusual cancer and can complicate patient’s management, informed consent, third party decisions of medical necessity, and tort.

Physicians and patients have been educated that ultrasound-guided FNAB of thyroid nodules is the gold-standard of triage for cancer and thyroid surgery. However, some specialists in imaging are now advocating that, based on US criteria, there are “ leave me alone nodules ” that do not require biopsy or further treatment (see Moon WJ et al. in Acta Radiologica 25:1-6, 2009). Their opinion derives from US characteristics associated with low cancer-risk that include hyper-echogenicity, spongiform appearance, Napoleon pastry-like layering of sheets of increased and decreased echoes, and comet tail appearance of a bright spot. Lesions that meet these criteria probably are a colloid nodule or nodular hyperplasia and that is useful to know. The associations for the population that has been investigated are reasonably robust but the supporting data were mainly retrospective and drawn from low-powered statistics: they are therefore imperfect, especially when applied to a single patient. The rationale behind not biopsying such nodules is that fewer biopsies will lead to less delay of the ‘truly necessary’ biopsies, less false-positives, fewer surgical operations, and reduced costs. These goals are understandable but the predicament is that cancer in a goiter or thyroiditis or in a small portion of a degenerated, hemorrhagic complex nodule is difficult to identify and constitutes a well-known clinical trap.

Creating an ultrasound image is an art, interpreting it is subjective, and making it relevant for specific patient-encounter remains a clinician’s challenge. Well structured, properly powered, and prospective investigation of the specificity and accuracy of US features that permit de-selection for biopsy are required before observations can be extrapolated into management. Such triage of thyroid cancer-non-risk is premature and is an entirely different philosophy from using US to support performing a biopsy of nodules that exhibit features that correlate more highly with malignancy. Complex nodules remain a conundrum and this writer believes that as much of the solid portion as possible should be sampled, especially the parts that meet Lee’s criteria.

In summary, we should not use tentative data from limited investigation to make a pivotal decision not to biopsy certain thyroid nodules and selection against surgery. There is a relatively simple, reasonably safe, inexpensive, and more reliable protocol: use the US to enhance the efficiency and accuracy of biopsying nodules, especially the suspicious ones.

Summary and Commentary prepared by Manfred Blum (Related to Chapter 6 [sections c & d] of TDM)

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