INTRODUCTION

Main sonographic criteria in the evaluation of thyroid nodules:

1. Margins
2. Echogenicity
3. Composition (cystic or solid)
4. Internal punctuate echogenicities
5. Shape
6. Vascularity

The sensitivities, specificities, and negative and positive predictive values for these criteria are extremely variable from study to study, and no US feature has both a high sensitivity and positive predictive value for thyroid cancer.

Nodule size, homogeneity or heterogeneity of echotexture, and rim calcification are NOT a predictor of malignancy.

The incidence of malignancy in multinodular goitre is 1-3%, and malignancy is more likely in a solitary nodule.  On the other hand, malignant and benign nodules present simultaneously in 10-20% of cases; and up to 10-20% of papillary carcinomas can be multi-centric.

PART 1: SONOGRAPHIC EVALUATION OF THYROID NODULES

Criterion No. 1: Margins

BENIGN: Well-defined smooth margins (76% of benign), thin hypoechoic halo around the entire nodule (if complete halo is present, 12x more chance that the nodule is benign).  An incomplete halo around the nodule also indicates a benign lesion (4x more chance of nodule being benign). 

A halo may be seen in 15-30% of malignancies.

Fig. 1: Isoechoic nodule within the left thyroid lobe with a complete hypoechoic halo. FNA showed no malignant cells.

Fig. 2: Isoechoic nodule within the left thyroid lobe with an incomplete hypoechoic halo. FNA showed no malignant cells.

MALIGNANT: Irregular or well-defined spiculated margins (81% of malignant), no halo. 

Fig. 3: Hypoechoic nodule at the junction of the left thyroid lobe and isthmus expanding the thyroid contour. Margins are ill defined. FNA showed a papillary thyroid carcinoma.

Ill defined margins are seen in 19% of malignant and 15% of benign!

Criterion No. 2: Echogenicity

BENIGN: Hyperechoic (96% of hyperechoic are benign, compared to 74% of isoechoic and 39% of hypoechoic).

Fig. 4: Incidental finding during nuchal ultrasound. A well delineated hyperechoic nodule is seen within the right thyroid lobe. Doppler analysis revealed no increased flow within this nodule (not shown). 96% of all hyperechoic nodules are benign.

Fig. 5: Right sided hypoechoic nodule - this was sampled through FNA and shown to be benign. Around 63% of hypoechoic nodules are malignant.

MALIGNANT: Hypoechoic (63% of hypoechoic, 26% of isoechoic, and 4% of hyperechoic are malignant).

Fig. 6: Multifocal papillary carcinoma. Two hypoechoic nodules with internal punctate calcifications are seen - one at the junction of the thyroid isthmus and right thyroid lobe, the other within the left thyroid lobe.

Criterion No. 3: Consistency

Cystic thyroid nodules are usually benign but up to a third of papillary NGs have a cystic component.

BENIGN: Most (87%) are predominantly solid.  13% are predominantly cystic, with hyperechoic solid components.

Fig. 7: Benign 4.3 cm nodule within the right thyroid lobe, with retrosternal extension. This nodule is heterogeneous and mostly isoechoic to the normal thyroid parenchyma. Cystic components are also seen. The patient had similar, albeit smaller, nodules within the isthmus and left thyroid lobe, in keeping with a multinodular goitre.

Fig. 8: Benign, predominantly cystic, thyroid nodule. A complete hypoechoic halo is seen. No internal Doppler flow was present in the solid components.

MALIGNANT: 98% NGs are predominantly solid, but one third of papillary carcinomas exhibit cystic degeneration with a cystic component.

Fig. 9: Large heterogenous, predominantly hyperechoic, nodule with a minor cystic component and with retrosternal extension. This patient had presented with a lump in the occipital region (Figure 16), which was biopsied. Histopathological analysis from the latter revealed a metastatic follicular neoplasm. A FNA of this thyroid nodule was therefore performed, and it was confirmed as being the primary lesion.

Criterion No. 4: Internal punctate echogenicities

Punctate echogenicities with comet-tail artefacts are features of benign colloid cysts.  The comet tail sign is the only highly specific sign of benignity and its presence almost invariably signifies a benign colloid cyst.

Fig. 10: Comet-tail artefacts within two colloid cysts in two different patients. An anechoic 3.5 cm colloid cyst with peripheral comet tail artefacts is seen on the left. A small colloid cyst is seen in the midportion of the left thyroid lobe (right), with a central comet tail artefact.

Fine punctate echogenicities with NO comet-tail artefacts represent punctate microcalcifications usually associated with papillary carcinoma. These are too small to produce posterior acoustic shadowing.

Fig. 11: Punctate echogenicities within an isoechoic thyroid nodule, in keeping with punctate calcifications. Posterior acoustic shadowing is seen due to clumping of these punctate calcifications. FNA revealed a papillary thyroid carcinoma.

Microcalcifications are associated with a 3x increased risk of malignancy, while coarse calcifications are associated with a 2x increased risk.  A peripheral/rim type of calcification indicates benignity.

Criterion No. 5: Shape

91% of benign are ovoid to round.

A ‘taller than wide’ shape is very specific for malignancy, BUT poorly sensitive since 58% of malignant nodules are ovoid to round!

‘Taller than wide’ = anteroposterior diameter of a nodule longer than its transverse diameter on a transverse or longitudinal plane.

Criterion No. 6: Vascularity

A hypervascular nodule is one in which the flow inside the nodule is more than that in the surrounding parenchyma.  Most often, colour Doppler gain settings have to be maximised for slow flow

BENIGN: Hypervascular at the periphery and internally hypovascular (‘ring of fire’).

Fig. 12: Isoechoic nodule with a complete hypoechoic halo, and with no detectable internal Doppler flow. These findings are all in keeping with benignity and were confirmed by FNA.

MALIGNANT: Marked intranodule vascularity increases the risk of malignancy.  This is defined as flow inside the nodule being more than in the surrounding parenchyma.  On the other hand, papillary carcinoma can be hypovascular.

Criterion No. 7: Regional lymph nodes

The presence of abnormal cervical lymph nodes should prompt biopsy of the abnormal lymph nodes and/or an ipsilateral thyroid nodule of any size. 15-30% of thyroid carcinomas present as palpable cervical lymph nodes.

Metastatic nodes from papillary carcinoma show cystic necrosis in 25% of cases and punctate calcification in 50%; they are hypoechoic relative to muscle in 80%.

Fig. 13: Pathological lymph nodes (different patients). Increase in the short to long axis ratio is seen on the left, with the enlarged lymph node assuming an oval shape. A peripheral pattern of flow (as opposed to the physiological hilar pattern) is seen. A disorganised interrupted peripheral pattern of flow is also seen on the left, together with internal nodal punctate calcifications. Both patients had a papillary thyroid carcinoma.

Metastatic lymph nodes from medullary carcinoma show echogenic foci; they are invariably hypoechoic relative to adjacent muscles.

Other sonographic features of malignant lymph nodes include:

1. Iincreased short to long axis ratio (i.e. round shape)
2. Absence of the echogenic fatty hilum
3. Heterogeneous cortex
4. Ill defined margins in keeping with invasion of the adjacent anatomical structures
5. Disorganised peripheral pattern of flow with areas of relative avascularity (in keeping with areas of necrosis)

PART 2: TYPES OF THYROID CARCINOMA

Can be subdivided into:

1. Papillary carcinoma (approx. 71%)
2. Follicular neoplasms (approx. 14%)
3. Medullary carcinoma (approx. 4%)
4. Anaplastic carcinoma (approx. 4%)
5. Lymphoma (approx 3%)
6. Other aetiologies including metastases (approx 4%)

Papillary carcinoma

This is the most common type of thyroid cancer, with most patients being female.  Prognosis is excellent, with a 20 year survival rate above 90%.

Poor prognostic signs include male sex, old age at presentation, large size, and extra-capsular or vascular invasion.

Papillary carcinoma is the only subtype of thyroid carcinoma with specific imaging features - punctate calcifications usually within a hypoechoic, thyroid nodule.  Papillary carcinomas have a propensity for lymphatic spread.  Lymph node metastasis often contain identical punctate microcalcifications. 

Up to one third of papillary carcinomas exhibit cystic degeneration with a cystic component.

Fig. 3: Hypoechoic nodule at the junction of the left thyroid lobe and isthmus expanding the thyroid contour. Margins are ill defined. FNA showed a papillary thyroid carcinoma.

Fig. 6: Multifocal papillary carcinoma. Two hypoechoic nodules with internal punctate calcifications are seen - one at the junction of the thyroid isthmus and right thyroid lobe, the other within the left thyroid lobe.

Fig. 11: Punctate echogenicities within an isoechoic thyroid nodule, in keeping with punctate calcifications. Posterior acoustic shadowing is seen due to clumping of these punctate calcifications. FNA revealed a papillary thyroid carcinoma.

Fig. 13: Pathological lymph nodes (different patients). Increase in the short to long axis ratio is seen on the left, with the enlarged lymph node assuming an oval shape. A peripheral pattern of flow (as opposed to the physiological hilar pattern) is seen. A disorganised interrupted peripheral pattern of flow is also seen on the left, together with internal nodal punctate calcifications. Both patients had a papillary thyroid carcinoma.

Fig. 14: Multifocal papillary carincoma in a 35 year old male (two views of the same nodule are shown). A cystic component is evident. The internal punctate echogenicities were difficult to differentiate from comet tail artefacts, and FNA was performed on the basis that this nodule was 3.5 cm in diameter, and showed increased internal Doppler flow (not shown). Pathological ipsilateral lymph nodes were also seen (refer to Figure 15).

Fig. 15: Lymph node metastases with cystic degeneration from the same patient as in Figure 14. Complete absence of the central fatty hilum is seen, together with widespread punctate calcifications.

Follicular neoplasms

Benign follicular adenomas and malignant follicular carcinomas cannot be distinguished by imaging or by imaging guided fine needle aspiration (FNA) / biopsy.  Follicular neoplasms are therefore usually surgically excised and examined histologically.

No specific imaging features are seen in follicular neoplasms.  Follicular carcinomas can spread haematogeneously, and patients can present with symptoms and signs related to distant metastases.  Lymphatic spread is uncommon.

Fig. 9: Large heterogenous, predominantly hyperechoic, nodule with a minor cystic component and with retrosternal extension. This patient had presented with a lump in the occipital region (Figure 16), which was biopsied. Histopathological analysis from the latter revealed a metastatic follicular neoplasm. A FNA of this thyroid nodule was therefore performed, and it was confirmed as being the primary lesion.

Fig. 16: Metastatic follicular carcinoma in an elderly lady presenting with a large occipital lump (same patient as Figure 6). Selected image from an axial CT in bone window settings reveals a large osteolytic lesion replacing most of the occipital bone (left). Ultrasonography of this region shows that this lump is of an echogenicity distinct from the brain, and confirms its extra-axial location (middle). As seen on this selected colour Doppler image (top right), this lesion is highly vascular. Isotope bone scan (bottom right) showing a photopaenic defect in the occiptal region, corresponding to this lump, and two foci of increased uptake close to the vertex (which were also confirmed as being osteolytic metastastic deposits from the thyroid follicular carcinoma).

Fig. 17: Metastatic follicular carcinoma in a 38 year old female. This patient initially presented to her dental surgeon with mandibular pain. An ortho-panto-gram shows a lytic lesion located at the left sided portion of the mandibular bone. This lytic lesion has a wide zone of transition, and is in keeping with an aggressive bone lesion. Bone scintigraphy shows increased uptake of isotope in the corresponding region.

Fig. 18: Metastatic follicular carcinoma in a 38 year old female (same patient as in Figure 17). Further osteolytic metastatic deposits in the rib cage as seen on chest radiography (left), axial and reformatted CT (right upper and middle images) and bone scintigraphy (bottom right). Follicular carcinoma of the thyroid is a known cause of bone metastases with a large soft tissue component and florid bone destruction. Metastatic renal cell carcinoma is another tumour associated with this osteolytic pattern.

Hürthle cell carcinoma is a rare variant of follicular carcinoma, again with no specific sonographic features.  Imaging or image guided FNA cannot distinguish between an aggressive and a non-aggressive Hürthle cell neoplasm.

Fig. 19: Two different patients with a Hurthle cell neoplasm. A hypoechoic nodule is seen within the left thyroid lobe of the first patient (left) - this was confirmed to have no malignant potential following surgical excision. A larger hypoechoic nodule is seen within the right thyroid lobe of the second patient (right). Doppler analysis revealed increased flow within this nodule. Hemithyroidectomy confirmed a Hurthle cell carcinoma.

Medullary carcinoma

Medullary carcinomas arise from the parafollicular c-cells which secrete calcitonin.  10-20 % of cases are familial and are associated with Multiple Endocrine Neoplasia (MEN) syndrome II.  Nodal metastases are seen in 50% and distant metastases in 15-25% of patients.

Ultrasound features are non specific and include:

• Solid hypo-echoic nodule
• Focal (predominantly in the upper third of the gland) in the sporadic form or diffuse involvement of both lobes in the familial form
• Echogenic foci (representing dense deposits of amyloid and associated focal calcification)
• Disordered vascular pattern on colour flow imaging
• Associated characteristic lymphadenopathy with echogenic intra-nodal foci).

Fig. 20: Hypoechoic ellipsoidal nodule within the left thyroid lobe with internal punctuate echogenicities. FNA was performed since the findings were considered as being highly suspicious for papillary thyroid carcinoma. A mucinous carcinoma was subsequently diagnosed - the punctate echogenicities in this rare type of thyroid carcinoma are due to dense deposits of amyloid and associated calcifications.

Anaplastic carcinoma

Anaplastic thyroid carcinoma is rare, and is generally considered as one of the most aggressive head and neck cancers with survival rates of only a few months.  Patients usually present with a rapidly growing thyroid nodule which is causing pressure signs and symptoms.  Nodal or distant metastases are seen in 80% of patients.

Ultrasound features are again non-specific.  Invasion of the adjacent vessels and lymphadenopathy is a common feature.

Fig. 21: Patient presenting with a rapidly enlarging neck mass. Selected axial CT image shows infiltration of the platysma and prevertebral muscles. Encasement of the right common carotid artery is also seen. Apparent extension and direct invasion of the right side of the hypopharynx is also seen.
References: Dr Corinne Binns, Dr David Salvage. (2007, Mar 5). Anaplastic Thyroid Cancer, {Online}. URL: http://www.eurorad.org/case.php?id=5394 DOI: 10.1594/EURORAD/CASE.5394