PAPILLON COURSE on THYROID ULTRASOUND

Section 2 The nodular goiter

Part 8 The halo sign and vascular pattern of nodules

Manual

 

OPENING

Halo sign means a hypoechoic rim that surrounds a portion of thyroid tissue and thus separates it from the rest of the thyroid gland. Different histological entities may correspond to halo, i.e. a capsule or pseudocapsule or surrounding capsular vessels or compressed thyroid tissue (1-4). Baskin et al. suggested that in most instances, the peripheral halo corresponds to a pericapsular arrangement of nodule vascularity, as demonstrated by Doppler or power flow mapping (5).

Color and power Doppler examinations provide careful visualization of the

vascular architecture of thyroid nodules (5-6). The vascularization of the nodules has long been examined. After the initial enthusiasm, it has now become clear that the value of nodule vascularization in the assessment of the risk of thyroid carcinoma is limited because of the absence of clear-cut differences between benign and malignant lesions. Nevertheless, as a minor sign, it has some role in differential diagnostic. Thus, the use of color and power Doppler in thyroid nodule examination only provides complementary information (7).

 

THE IMPORTANCE OF HALO SIGN IN THE DIFFERENTIAL DIAGNOSTICS OF THYROID NODULES

Although the halo sign is more frequently found in the benign nodules, it is not highly specific for the benignity (8-9) and frequently found in follicular neoplasm (10-11), and the absence of the halo is less specific for malignancy (12-13). Moreover, a follicular tumor including the malignant counterpart, the follicular cancer is, by definition surrounded by capsule, and the ultrasound (US) equivalent of this capsule is the halo. This means that if the halo is clearly considered a benign signal, we are unaware of the possibility of follicular cancer.

Campanella et al have found that the highest risk of malignancy was associated with the 'taller-than-wide' shape (DOR of 10.2; 95% CI: 6.7-15.3), an absent halo sign (7.1; 95% CI: 3.7-13.7), microcalcifications (6.8; 95% CI: 4.7-9.7), and irregular margins (6.1; 95% CI: 3.1-12.0) (14).

Apparently, there is a contradiction here: on the one hand, the absence of the halo signal is one of the most important suspicious signs, at the same time, the presence of the halo is the most common sign of follicular cancer. This can be explained by the fact that papillary cancer is by far the most common cancer in the thyroid gland (about 10 times more common than follicular cancer), so the signs that characterize papillary cancer are statistically characteristic of all thyroid cancers. A thin halo was found to decrease the malignancy risk (DOR 0.3) while the absence or thick halo was reported to increase the risk of malignancy (DOR 3.4) (15). Zhang et al.

reported that the absent or thick halo increased the risk of FTC (16). We found that the halo signal has a different meaning depending on the echogenicity of the nodule: the risk of malignancy was decreased in all nodules except for moderately hypoechoic ones if they presented halo sign while the absence of halo increased the risk of cancer in all but moderately hypoechoic lesions (17).

In moderately hypoechoic lesions the situation was just the opposite, the presence of halo significantly increased the risk of cancer while the lack of significantly decreased the risk of cancer. The difference between deeply and moderately hypoechoic nodule was explained by the difference in visualization of halo on US: The absence of a halo decreases the risk of malignancy only because this sign cannot be demonstrated in the most frequently occurring malignant nodules, in hypoechogenic ones. The demonstration of a halo sign is very difficult or even impossible in most hypoechogenic nodules because the US appearance of the capsule in such lesions is identical with the nodule. This is clearly proved by the fact, that for follicular adenomas, which are encapsulated in 100% of the cases, only 8.8% of the hypoechogenic nodules exhibit a halo sign, whereas this feature can be demonstrated by US in 64.1% of all other types of nodules. It is not surprising therefore, that the presence of a halo sign significantly increases the risk of malignancy in cases of moderately hypoechogenic nodules, while in hyperechogenic nodules the presence or absence of a halo sign does not influence the likelihood of malignancy.

 

THE HALO SIGN IN VARIOUS GUIDELINES AND TIRADS

In the guideline of the American Thyroid Association (ATA) and the American College of Radiologist (ACR) the halo sign is not mentioned or omitted, ATA or ACR, respectively (18-19). The latter mentions that the halo has no discriminatory effect.

The other three guidelines summarize the above-discussed findings in the literature (20-22).

Neither of the TIRADS involves halo sign in the classification of thyroid nodules. The AACE is the only TIRADS which mentions the 'regular halo' among features characteristic of benign lesions (20). However, the presence of halo is not a prerequisite to categorize a lesion among the benign subgroup which means that even in this system, neither the lack or the absence of halo influences the classification of a nodule.

 

THE HALO SIGN IN THE MOST FREQUENT SUBTYPES OF THYROID CANCER

Except for the follicular variant (FVPC, papillary cancer is characterized by the absence of halo. Halo sign was found in 25% of FVPCs while in only 3% of non-FVPC cases (23). Follicular cancer behaves just the opposite, here the most common ultrasound feature is the halo, halo sign was detected in 26% of PTC while in 87% of FTC in the study of Jeh et al (10).

Medullary cancer has been much less studied in this regard, but MTC seems to behave similarly to PTC. Lai et al have found that6.3% of MTCs and 4.5% of PTCs present with halo (24).

 

CLASSIFICATION OF VASCULAR PATTERNS

Three different classifications for nodule' vascularization are suggested in the professional guidelines (see Table 1). We should not memorize these

but reading the literature, it is worth noting that not the same patterns are represented by categories of different guidelines of the same name.

Table 1 The classification of vascularity of thyroid nodules in three guidelines.

 

ETA

KSTR

 

AACE

Type 1

Absence of intranodular and perinodular vascularity

Absence of intranodular and perinodular vascularity

 

Peripheral pattern

Type 2

Presence of perinodular and/or slight intranodular flow

Presence of circumferential vascularity at margin of nodule

 

Intranodular pattern

Type 3

Marked intranodular and slight perinodular flow

Intranodular vascularity with or without peripheral vascularity (< 50%)

 

Absence of blood flow

Type 4

-

Marked intranodular vascularity with or without peripheral vascularity (> 50%)

 

-

In everyday practice, in order to avoid misunderstandings, it is worth specifically describing what we see (perinodular and or central flow). If we see internal flow, it is worth describing its extent: minimal, increased, or chaotic. The Doppler criteria remain controversial (7), mainly because the performance of Doppler examination is highly dependent on the US equipment and settings. Hoang defined perinodular vascularity as the presence of blood flow around at least 25% of the circumference of a

nodule (25).

Regarding intranodular vascularity, we lack clear definitions and the interobserver agreement is low (20). The quantitative analysis of the vascular patterns is not well established and is time-consuming (26).
Nor is it clear whether the vascularity of the nodule should be examined on its own or compared to the surrounding tissue.  

 

THE ROLE OF VASCULAR PATTERNS IN DIFFERENTIAL DIAGNOSTICS OF NODULAR GOITER

Basically, the most common pattern of vascularity in thyroid malignancy is marked intrinsic hypervascularity, which is defined as flow in the central part of the tumor that is greater than that in the surrounding thyroid parenchyma (25). Perinodular pattern is more characteristic of benign thyroid lesions but also has been found in 22% of thyroid malignancies (9). In contrast, complete avascularity is a more useful sign: Chan et al (9) reported that all papillary thyroid carcinomas had intrinsic blood flow, and they concluded that a completely avascular nodule is very unlikely to be malignant. Although, there is statistically significant difference in the vascular presentations between benign and malignant nodules, the usefulness of Color examination is very limited in the everyday practice. Perhaps, it depends on the fact that there is not good enough technology to detect it. However, this point remains a matter of debate among specialists worldwide (27).

The presence of intranodular vascularity ranges from 16.7% to 91.7% in malignant tumors (7, 9, 28-32) and from 30.7% to 65.3% in benign lesions (7, 29-32). Although the presence of intranodular vascularity might increase the risk of malignancy (28, 30), there are no consistent results regarding the association of an intranodular vascularity pattern with the risk of malignancy (7, 29, 32, 33). Recent studies suggested that the presence of intranodular flow was not predictive of the malignancy (7, 34), and that it could not provide an added value over that of the information gained by gray-scale US for the prediction of the malignancies (7).

In a recent meta-analysis, a higher risk of malignancy was associated

with the following features: nonparallel orientation (odds ratio (OR) 10.15), absence of halo (OR 7.14), microcalcifications (OR 6.76), irregular margins (OR 6.12), hypoechogenicity (OR 5.07), solid nodule structure (OR 4.69), and intranodular vascularization (OR 3.76) (14). Chaotic intranodular vascular images, mild hypoechogenicity, and rounded appearance also have a predictive value, albeit a low one (5, 6, 35).

In a recent work where 98% of the cancers were PTC, intranodular flow did not have independent predictive value for malignancy in multivariate logistic analysis (36). Overwhelming majority (98%) of cancers were PTC in this study. In three other publications in which the ratio of FTC was higher (10%-22%), the intranodular vascularity correlated with malignancy (37-39).

The above presented data characterize PTC. Similarly to other US characteristics, the presentation of FTC differs from PTC in vascularity (17). Much less data is available for FTC and MTC. Although the presence of a marked intranodular vascularity pattern might be predictive of malignancy in the follicular lesions or follicular neoplasm (40-44), the hypothesis remains controversial (45). MTC seems to behave similarly to PTC. Lai et al have found that increased vascularity was significantly more frequent in MTC (72.4%) than in PTC (47.7) (23). In a large study which 698 surgically treated patients, Yang et al. have found significantly higher intranodular vascularity in benign compared with malignant nodules (46). The occurrence of intranodular flow was significantly higher in encapsulated cancers compared with non-encapsulated ones (46).

 

 

THE VASCULAR PATTERNS IN TIRADS CLASSIFICATIONS
The guideline of the American College of Radiologist does not even mention Doppler examination (18). The other four important guidelines discuss the role of vascular patterns in the differential diagnostics, however the vascular pattern does not influence the categorization of nodules is any TIRADS (17, 19-21).
The AACE is the only TIRADS which mentions the 'intranodular vascularization' among may-be-present features characteristic of intermediate-risk lesions. However, the presence of intranodular blood flow is not a prerequisite to categorize a lesion among the intermediate-risk subgroup which means that even in this system, the vascular pattern has no role in the classification of a nodule (20).

 

OTHER ROLES OF DOPPLER EXAMINATION
We list some examples of when a circulation study may be of added benefit. The assessment of vascular flow may be useful for guidance of FNA. In multinodular goiters, nodules with intranodular blood flow are preferentially biopsied. (47, 48). The assessment of Color pattern may have role in mixed nodules, intensely vascularized portion should be carefully evaluated (9, 49).
The analysis of Doppler flow may be of help in discriminating thyroid nodules from strap muscles and to differentiate deeply hypoechoic lesions from intrathyroidal vessels. Examination of the vascularity can be a quick help in differentiating enlarged lymph nodes and cervical vessels. In the event of percutaneous ethanol injection therapy, the vascularity has a prognostic role in judging the success. If the solid part turns avascular, the success rate is higher compared to remaining vascularized (50).

 

DOPPLER EXAMINATIONS IN LYMPH NODES
In an enlarged lymph node, the presence of cystic changes, microcalcifications, or absence of hilum is highly suspicious (35, 51, 52), while rounded appearance and chaotic hypervascularity are also common but less specific signs of malignancy (20).
While a benign node is characterized by central vascularization, an indeterminate is with the absence of central flow. They speak of a suspicious lymph node if it shows cystic change or calcification (micro- or macrocalcification) or hyperechogenicity or abnormal vascularity (peripheral or diffuse) (51).

 

A POSSIBLE ROLE OF HALO SING AND NODULE'VASCULARITY IN FOLLICULAR LESIONS
There are different explanations for halo sign and for perinodular blood flow, but all include that at least in part of the cases, these US features correspond to thyroid capsule. E.g. Baskin et al suggested that in most instances, the peripheral halo corresponds to a pericapsular arrangement of nodule vascularity (5). All follicular tumors are surrounded with capsule and most of them present halo sign and/or perinodular blood flow. Taking these facts into account may be helpful in solving an important differential diagnostic problem. Follicular proliferation is the most important, most common and, with complete certainty, only histologically solvable problem in thyroid cytology.
In 30% of cases where cytology raises a suspicion of a follicular tumor, histological examination confirms a non-tumorous lesion, i.e. hyperplastic nodule. Although these may present halo sign, but with a significantly lower frequency compared with follicular tumors. This means that in cases where cytology raises a follicular tumor, the reconsideration of US presentation may help to avoid unnecessary surgery: the absence of halo substantially decreases the risk of follicular tumor including follicular cancer (53).

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