Section 2 The nodular goiter

Part 5 The borders of the nodule





In this section we discuss a feature, the presence of which significantly increases the likelihood of thyroid carcinoma, namely the papillary cancer. All types of abnormal increases the likelihood of thyroid malignancy but the different subtypes differ in sensitivity, specificity and interobserver agreement. The issue is that this phenomenon is quite difficult to judge, and the interobserver variation is the highest (1-4) or the highest but one among suspicious features (5). Small irregularities are frequently observed in nodular goiters. The distinction between a non-specific irregularity and a really irregular margin depends highly on the judgement of the investigator. We have no exact number of ratios or angles based on

which we can differentiate between normal and irregular margins.

Beside blurred (ill-defined) and lobulated/spiculated margins we present a third type of abnormal borders, the so-called invasive margins which is less frequently mentioned in the literature.

We give a brief overview, discuss their role in the diagnosis of various subtypes of thyroid malignancies. We describe the pitfalls, the differentiation of pathological and non-pathological causes of abnormal borders.



A normal nodule' margin is characterized by sharp and smooth surf ace. Basically, there are two well-known, abnormal types of the nodule' borders, these are the blurred or ill-defined margins and the lobulated/spiculated borders. There is a third type less frequently mentioned in the literature, we call this type as invasive.
The term 'macrolobulated' margin cause a further possible discrepancy.

This term was applied to describe large undulations on the solid part of a mixed nodule (6, 7). However, the margins of a nodule should refer to the external surface of a lesion and not to irregularities of the borders between different parts of the lesion. Macrolobulation was also used to describe larger undulations in the external margins of the nodule (5). To hinder further deepening of the already high confusion in terminology, the use of macrolobulation is best to avoided.

Blurred or ill-defined borders

In the event of blurred borders, it is difficult to judge where the lesion ends. There is no overall agreement regarding the degree/extent of blur which should be counted abnormal. The suggestion of Hoang et al. seems to be reasonable: a thyroid nodule is considered ill-defined if more than 50% of its border is not clearly demarcated (8). The blurred border is a less specific sign which can be found even in various forms of thyroiditis (4, 9). Although none of the TIRADS includes blurred borders among suspicious signs, disregarding this feature would be a failure.

In the everyday practice an experienced investigator finally gets an overall impression about the thyroid and although the presence of blurred borders is not the most important factor but an essential part of a final judgement.
Kwak et al. have found that blurred borders are associated with a significant increase of malignancy risk, but the odds ratio was relatively low, 1.63 (10).

Lobulated/spiculated margins

The US terminology for the nodule margin is controversial (11-16), and many different terminologies have been used to describe the margins of the malignant tumors. Most papers in the literature involve lobulated or microlobulated and spiculated margins among irregular types of borders. The term infiltrative is also frequently used as a synonym (17, 18).

In the second type of abnormal borders, we can see sharp but irregular surface which can be either spiculated and angled or lobulated and curved. EU-TIRADS uses the term microlobulated margin if the nodule presents of one or more smooth, focal, round protrusion on the margin, while defines spiculated margin as the presence of 1 or more sharp angles or spiculations (19). These types of margins are counted as irregular in all TIRADS system. These types of margins, particularly the spiculated one, are frequently observed in discrete lesions of Hashimoto's thyroiditis, and this is not a great surprise. Both papillary carcinoma and thyroiditis are infiltrative disorders and spread with projections toward the normal parenchyma. In a recently published meta-analysis the presence of irregular margins had a 6.12 odds ratio for malignancy (20), others have found a 6.0 odds ratio (10).

Benign nodules might also present irregular margins. The borders can be lobulated because normal structures with different resistance influence the growth of a benign lesion. The distinction between a microlobulated and a macrolobulated margin makes the judgement even more complicated and this distinction is prone to an even higher interobserver variation. Nevertheless, a macrolobulated margin is of greater importance compared with microlobulated presentation.

Most nodules present slight irregularities. The issue is that there is no exact measure of protrusion, on which we can clearly decide whether this is abnormal or only normal variant. The other problem is that Notably, in large nodules (diameter >4 cm), accurate assessment of the profile and regularity of margins may be difficult (21). The finding that around 60% of benign lesions presents lobulated margins (5) underlines the uncertainty about the usefulness of this sign and reflects the lack of common interpretation among various authors.

For those who will more deeply immerse in the ocean of published data, we offer the publication of Remonti et al. as a starting (or ending) point (22).

Invasive margins

There is a third type of abnormal borders, the presence of which is very specific for papillary carcinoma. This is characterized by a core of tumor having numerous microcalcifications and areas in a distance from this core presenting microcalcifications.



Non-pathological causes of ill-defined borders
The possible causes are listed in Table 1. We face the most common cause in the event of nodules which echogenicity is identical or almost identical to the neighboring tissue (23). The second group of non-pathological blur is caused by technical problems. Lesions located in the dorsal part are less adequate to project in ultrasound. Similar technical problems might arise if we set the focus improperly, i.e. ventral compared to the dorsal surface of the nodule. Another frequent technical cause comes from the difficulty of proper positioning of the transducer: the anatomy of the neck not infrequently hinders the adequate fitting of the probe to the neck structures. Anatomical structures ventral to the lesion might also modify the way of the ultrasound wave to and back to the border of a lesion.

Table 1 Non-pathological causes of blurred margins.

The nodule and the surrounding parenchyma have very similar echo pattern.

Technical causes

•  lesions in the dorsal part of the lobe

•  improper focusing

•  improper positioning of the transducer

The influence of anatomical structures ventral or within to the lesion

•  macrocalcifications in the subcutis or within the lesion

The presence of the acoustic shadow caused by a macrocalcification might lead to misinterpretation: the acoustic shadow can interfere with the nodule' borders. The problem arises if the primary focus of macrocalcification cannot be visualized.
Non-pathological causes of lobulated/spiculated margins

Beside the difficult-to-solve issue of interobserver disagreement there are certain conditions which might cause misinterpretation which could be avoid by thorough analysis of the ultrasound pattern. These conditions are listed in Table 2.

From a practical point-of-view the most important problem is the multinodularity, the cluster of grapes-like presentation of multiple small lesions next to each other (24). This pattern should be differentiated from that of a nodule having parts with different echo patterns. Although the repeated analysis of the mass in multiple different angles might solve the problem, the distinction is not always possible. If the lesion has parts with (slightly) different echogenicity or with different patterns of intranodular echogenic figures or vascularization, than the probability of a multinodular goiter increases.

We are faced with the second, more distressing cause in cystic nodules after the aspiration of cystic fluid. Although just after the aspiration we are aware that the irregular margins of a nodule is simply caused by the removal of the fluid. However, in the case of non-recurring cysts the investigator is not aware of the original shape of the lesion months or years later. Therefore, it seems to be important to describe on the report, if the shape or the border of a lesion becomes abnormal after aspiration of the cystic content.

The underlying normal anatomical situation has a deep impact on the shape of large nodules or on those which extend toward the isthmus where the thyroid normally gets narrowed. The situation which arises after surgery might have a similar impact on the borders of the nodule: a fibrotic scar might cause impression on the thyroid and on the nodule within an operated thyroid, as well.

Table 2 Non-pathological causes of lobulated margins.

The influence of the anatomy

A mass composed of multiple nodules

Cystic nodule after the aspiration of cystic fluid

The operated thyroid



Table 3 summarizes the occurrence of abnormal margins in the 3 most common subtype of thyroid carcinomas. Similarly to other characteristics, the irregular border occurs significantly more frequently in papillary cancer compared with follicular carcinoma. Medullary cancer presents irregular margins in a similar proportion as do papillary carcinomas. The very broad range of the observed frequencies of irregular margins is explained by the unusually high interobserver disagreement in the judgement of nodule borders.
Table 3 Occurrence of irregular margins in the three most common subtypes of thyroid carcinomas
Occurrence - range (%)
Occurrence - median (%)
Follicular carcinoma
2.5 - 60.9
Medullary carcinoma
25.6 - 63.6
Papillary carcinoma
22.3 - 83.6



No TIRADS involves blurred borders among suspicious signs, while lobulated/spiculated margins belongs to the most suspicious features in all TIRADS (19, 21, 24-26). The presence of lobulated/spiculated margins automatically groups the lesion among the most suspicious subgroup in the AACE and in the European TIRADS, while to group a lesion presenting irregular margins into the most suspicious category in the event of hypoechoic nodules in the ATA and Korean TIRADS.

Regarding the ACR TIRADS, the presence of irregular margins worth two points. Following the logic of this system, it means that such lesions should be categorized into category 4 or 5 depending on the presence of other suspicious signs. (See Table 4.)

Table 4 The role of irregular margins in the most important TIRADS systems.

Type of TIRADS
Echogenicity of the nodule
Lobulated/spiculated margins present
4 or 5



There are at least two mechanisms in thyroiditis which might have relevance in this topic. First, thyroiditis usually appears in the form of discrete hypoechogenic lesions. Because thyroiditis is an infiltrative process, it is not surprising that the shape and borders of these discrete lesions are not regular. Except for the invasive pattern all other abnormal patterns can occur in the event of thyroiditis; irregular patterns are not the exceptions but the rule. Anderson et al. have found that 40% of Hashimoto's cases present blurred borders and 9% of all Hashimoto's cases are characterized by lobulated margins (27). There is no question that great proportion of the discrete lesions in Hashimoto's thyroiditis and even in de Quervain's thyroiditis have irregular surface, the issue is whether these lesions are nodules or not. A distinct chapter focuses on this problem, we only mention here that there is no general agreement on the ultrasound definition on nodules, in our opinion the term nodule should be used in pathological term and a discrete lesion seen on ultrasound is not equal to nodule.

There is another situation in which Hashimoto's thyroiditis might cause difficulties. This situation arises in the coexistence of thyroiditis and nodular goiter. If the underlying thyroiditis infiltrates the nodule, the latter can have irregular margins. However, the lobulation of the nodule in this event is caused not by the infiltrative nature of the nodule but by the infiltrative nature of the thyroiditis.


The most important condition to be mentioned here is previous thyroid surgery. The procedure causes deep changes in the parenchyma; scars, adhesions, the remnant of surgical thread, all have a deep impact on the resected thyroid. Most thyroids become hypoechogenic after an operation which makes even more important to avoid overestimating irregular borders of a normal remnant. The clue is the patient' history and the thorough analysis of the remnant. Regarding the former, the histopathology of the previous surgery might itself decides the issue if the patient was operated on diffuse Graves' disease. Non-surgical US-guided procedures might also cause irregular margins because they lead to shrinkage of the lesion. From a practical point-of-view, this has less importance, if we are aware of the previous intervention. (In such nodules the malignancy had to be excluded before the intervention.)

The most frequent procedure, the aspiration of cystic fluid has been already mentioned earlier.


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