Thyroid Gland

Diffuse Changes

Enlarged Thyroid Gland

Small Thyroid Gland

Hypoechoic Structure

Hyperechoic Structure

Circumscribed Changes

Differential Diagnosis of Hyperthyroidism

Radiation-Induced Hypothyroidism

Cysts

Cystic masses, along with thyroid nodules, are the most common focal changes that are found in the thyroid. Thyroid cysts are not true cysts and therefore do not contain cystic epithelium. Solitary cysts in an otherwise normal thyroid generally result from central hemorrhage in adenomas.

Cyst contents. Depending on their contents, cysts may appear sonographically as anechoic masses or may show a hypoechoic, hyperechoic, or irregular internal echo pattern ( 14.2). Further diagnostic tests consist of color duplex sonography and fine-needle aspiration cytology. In many cases the cyst contents are

unknown until fine-needle aspiration is performed. Cysts may contain various fluids:

●Fresh hemorrhage ( 14.2 d,e)

●Older hemorrhage (chocolate cysts,

Fig.14.49)

●Old hemorrhage (yellow cysts)

●Colloid (colloid cysts, 14.2f)

●Lymph (lymph cysts)

Fresh hemorrhages and colloid cysts generally have a distinctive internal echo pattern and appear hypoechoic or hyperechoic, not anechoic ( 14.2 d,e). With color duplex, cystic tumors show a vascularity that is never seen in cysts or hemorrhages. Other cysts extrinsic to

the thyroid, such as neck cysts, should also be included in the differential diagnosis.

Solitary cysts. Uncomplicated serous cysts appear sonographically as anechoic, rounded or polygonal, sometimes lobulated, scalloped or patchy lesions with smooth margins. Like cysts in other organs, they display several typical cystic features such as absence of internal echoes, smooth borders, and distal acoustic enhancement, while a circular shape is somewhat unusual. Edge shadows are not present because of the absence of a cyst wall. There is an additional sign, however: definite compressibility of the cysts by external transducer pressure.

Hemorrhagic, colloid cysts

Cysts in nodular goiters

c Anechoic cystic mass in a hyperplastic thyroid nodule surrounded by a vascular rim; no internal blood flow. VJ = jugular vein.

f Two cystic areas (C), one with internal echoes. Fine-needle aspiration yielded a creamy colloidal fluid (confirmed cytologically as colloid). M = musculature, TR = trachea.

Prevalence. Thyroid nodules are found in 35–50% of people living in iodine-deficient areas.

A thyroid nodule is a discrete lesion within the thyroid gland that is palpable and/or ultrasonographically distinct from the surrounding thyroid parenchyma. Nonpalpable nodules detected incidentally with high-resolution technique in ultrasound or other imaging studies are termed “incidentalomas” (in 17–67%, varying regionally11). The exclusion of carcinomas is of clinical significance (depending on several factors up to 5–10%). Nonpalpable nodules have the same risk of malignancy as palpable nodules of the same size.

It is estimated that autonomous nodules are present in 2–6% of the general population12 and in 10–20% of patients with a preexisting goiter.

Pathogenesis. The normal thyroid gland already contains a number of thyrocytes with an autonomous growth tendency that may give rise to adenomas, regardless of the iodine supply. A similar mechanism underlies the development of the predominantly autonomous nodules in a nodular goiter.

Morphology. True adenomas are benign neoplasms. Aside from very rare leiomyomas, they account for virtually all benign neoplasms in the thyroid. Follicular adenomas are the most common type of adenoma. Other variants are papillary adenoma and oncocytoma. Adenomas, unlike the adenomatous nodules in a nodular goiter, do not take part in autoimmune changes. Functionally, microfollicular adenomas consist mainly of autonomously functioning adenomas that appear as hot nodules at scintigraphy, whereas macrofollicular adenomas usually appear as cold nodules.

adenomas are the most common types of adenoma, while hyperechoic adenomas are the least common.

Hypoechoic adenomas. The great majority of hypoechoic adenomas are autonomous adenomas, two-thirds of which are associated with latent hyperthyroidism (suppressed basal TSH with normal fT3/fT4 levels) and only one-third with overt hyperthyroidism.13 The most common microfollicular adenomas are conspicuous by their hypoechoic structure and round shape. The anechoic rim described above is also a general characteristic of adenomas, although it is not seen with every adenoma (see Table 14.2).

Another characteristic of hypoechoic adenomas is their internal vascularity, which signifies autonomy in a high percentage of cases (73%).14 The absence of internal vascularity rules out autonomy with a negative predictive value of 94%.13

A hypoechoic structure is in itself insufficient for evaluating functional autonomy (

14.3a,d,i).

Meanwhile, peripheral and internal vascularity is also found in a high percentage of malignancies, raising problems of differentiation based on ultrasound appearance.

Thyroid adenomas are also subject to regressive changes with intralesional hemorrhage and calcification, resulting in anechoic or hyperechoic internal structures ( 14.3 g–i; see also Fig.14.50). The above points can be summarized as follows:

●The color Doppler examination of thyroid nodules is a useful screening method for autonomous adenomas,12 especially in patients with known hyperthyroidism.

●True adenomas cannot be distinguished from adenomatous nodules by their sonographic features (this cannot even be done histologically in some cases). The sonographic findings can, however, provide clues for differentiation.

d Hypoechoic mass (T). Di erential diagnosis: adenoma, malignant tumor, hemorrhagic cyst.

g Isoechoic adenoma with hypoechoic areas devoid of internal vascularity: adenoma with fresh intralesional hemorrhage (painful swelling; treated surgically).

Functioning and nonfunctioning nodules in radionuclide scan

j Subclinical hyperthyroidism, radionuclide scan: Functioning nodule left lobe (1), nonfunctioning nodule of the right lobe

(2).

e Further examination with color Doppler shows intense peripheral vascularity as well as internal vessels.

h Hyperechoic adenoma with an old hemorrhagic area and cystic transformation

(C).

k Left thyroid lobe: two large hypoechoic adenomas.

f Several adenomas (A) of varying echogenicity in an otherwise normal thyroid, outlined by peripheral vascularity.

i Thyroid nodule, radionuclide thyroid scan shows a nonfunctioning (“cold”) nodule (see below, j), small calcification with shadow (S), small cystic lesion. This nodule must be examined by FNA and cytology.

l Right lobe, CDS: marked vascularized rim in the caudal nodule; rare internal vascularization, lack of peripheral vascularization in the upper nodule: FNA is required.

Oncocytic Adenoma

Differentiation is required from other hypoechoic tumors such as lipoma, malignant lymphoma, carcinoma, and metastases as well as rare abscesses or focal thyroiditis.

Abscess

Rare abscesses of the thyroid gland have a similar hypoechoic appearance to adenomas, cysts, and lymphomas. Their presence signifies an acute purulent thyroiditis.

Thyroid abscess appears sonographically as a mostly anechoic or hypoechoic mass with irregular internal echoes. Color duplex examination shows an absence of vascularity (Fig.14.37).

Fig. 14.37 Thyroid abscess (A) next to a thyroid adenoma with a regressive cyst (C): very hypoechoic mass opposite the cyst with faint internal echoes and blocky contours. Patient presented clinically with marked signs of inflammation and a reddish, tender neck mass.

De Quervain thyroiditis is usually a diffuse thyroid disease, but infrequent unilateral cases occur. The diagnosis is established by clinical examination and fine-needle aspiration cytology.

Typical ultrasound findings consist of wellcircumscribed or irregular hypoechoic areas that either are hypovascular or, in some reports, show moderate vascularity (Fig.14.38,

Fig.14.39).

Fig. 14.38 Focal de Quervain thyroiditis of the right thyroid lobe, transverse scan through both lobes (cursors). The right lobe contains a central, ill-defined, hypoechoic mass causing an elliptical contour bulge; the left lobe appears normal. Patient had a 3-month history of viral infection, high inflammatory parameters, and a circumscribed bulge with pain radiating to the right side of the neck.

Fig. 14.39 Focal de Quervain thyroiditis. Color Doppler image shows scant peripheral vascularity and no internal vessels. Scintigraphy revealed a cold spot on the right side. Fine-needle aspiration cytology showed no evidence of an abscess or malignancy. Weeks later the left thyroid lobe was also involved. TH = thyroid; M = muscle.

Malignant Lymphoma

Malignant lymphomas of the thyroid gland usually occur in the setting of generalized lymphomatous disease. Tumor clusters in the neck may be distributed about the thyroid gland. They can be difficult to delineate from the normal thyroid structure even when thyroid nodules are present.

Malignant lymphomas are characterized by a very low echogenicity. They show a variable degree of vascularity (Fig.14.40).

Fig. 14.40 Stage IIb Hodgkin lymphoma, nodular sclerosis.

a Highly malignant non-Hodgkin lymphoma on the left side after strumectomy: nodular hypoechoic mass, colorflow Doppler scan: marked vascularization.

b Primary non-Hodgkin lymphoma of the thyroid; the findings are not distinguishable from other tumors/metastases; intense vascularization.

Carcinoma

Thyroid carcinomas present as a clinically palpable neck mass that produces a cold nodule at scintigraphy. Ultrasound can be an effective adjunct to radionuclide scanning by showing that many cold nodules are not suspicious for cancer (cysts, calcified or hyperechoic nodules). Malignancies always have a hypoechoic or nonhomogeneous hypoechoic structure.

Histology. The following malignant thyroid tumors are listed in the World Health Organization (WHO 2004) classification:

●Carcinoma

–Follicular carcinoma

–Papillary carcinoma

–Medullary thyroid carcinoma

–Poorly differentiated (anaplastic) carcinoma

–Special form: squamous cell carcinoma (Lindsay tumor)

●Nonepithelial tumors

●Primary lymphoma and plasmacytoma

●Secondary tumors of the thyroid

Papillary and follicular carcinoma are more common in the thyroid gland than medullary C-cell carcinoma, while anaplastic and squamous cell carcinoma are rare. Distant metastases are more common with follicular and medullary C-cell carcinoma, while locoregional metastases are more typical of papillary carcinoma. Positions of lymph nodes are the cer- vico-central and parathyroidal region, the cer- vico-lateral and upper mediastinal region.

Medullary C-cell carcinoma grows slowly but often has already metastasized after reaching 10 mm. Undifferentiated anaplastic carcinoma is considered highly malignant because of its propensity for rapid invasive growth and early metastasis. Only about 3% of patients survive longer than 2 years.

Detection. A thyroid malignancy cannot be positively detected by ultrasonography, even when color Doppler is used. FNA cytology is still the most accurate method for cancer diagnosis. This pertains chiefly to papillary and medullary cancers. The diagnosis of follicular carcinoma must generally rely on surgical specimen histology. C-cell carcinoma is best diagnosed by FNA with a calcitonin assay or by direct histologic examination.

Medullary Thyroid Carcinoma

Multiple endocrine neoplasia (MEN) syndrome. Medullary thyroid carcinoma (MTC) is not a carcinoma of the thyroid tissue itself but an endocrine carcinoma located in the thyroid gland. It has a familial occurrence (FMTC) and may be isolated or may occur in the setting of MEN II syndrome: MTC, pheochromocytoma, parathyroid hyperplasia, cutaneous neurofibromatosis). Sporadic cases also occur.

MEN I tumors are also derived from the peripheral endocrine (APUD) system. The diagnosis of this syndrome relies on intesti-

nal polypeptide screening. The age-depend- ent sequence of lesions occurring from early infancy to over age 50 is as follows: insulinomas, parathyroid adenomas, gastrinomas, prolactinomas (ACTH), glucagonomas, and finally VIPomas.

Laboratory values. MTC leads to a rise in basal or stimulated serum calcitonin levels, providing a marker for early diagnosis. Even if the tumor is not detectable, it can be inferred from elevated calcitonin levels. Car-

cinoembryonic antigen (CEA) is also elevated.

Growth characteristics. MTC grows slowly but metastasizes early to locoregional lymph nodes. Standard operative treatment should therefore include locoregional lymph node dissection in addition to total thyroidectomy. This operation is curative in 25% of cases even with positive cervical lymph nodes.15

nodules larger than 1–1.5 cm, those with a suspicious sonographic appearance should preferably be aspirated. A radioiodine scan should be performed in a low serum TSH. FNA should then be considered only for those isofunctioning or nonfunctioning nodules (see

Fig.14.62).17

Differential diagnosis. The most difficult lesion to distinguish sonographically from carcinoma is a hypoechoic adenoma. The former belief that adenoma could be distinguished from carcinoma by its peripheral rim is no longer supported by data in the literature.13 It remains unclear whether color duplex scanning can advance the differential diagnosis. The sonographic features of adenoma are contrasted with those of carcinoma in Table 14.4. Ultrasound is most accurate in diagnosing carcinoma only when multiple signs (absence of a

peripheral halo combined with microcalcifications and intranodal hypervascularity) are simultaneously present in a thyroid nodule (review: see Ref. 16). The presence of microcalcification increases the incidence of malignancy by a factor of three. Microcalcifications are calcified psammoma bodies producing comet-tail artifacts in ultrasound, but usually no shadowing. Sensitivity is low, but the specificity is considerable (see Table 14.3). The combination of several diagnostic signs improves the predictive value, but one criterion alone provides no reliable differentiation between benign and malignant.19 The combination of predominantly solid (< 25% cystic) and hypoechoic nodule with microcalcifications (31.6% malignant) is the most reliable criterion; the least useful criterion is the combination of cystic nodule (> 75% cystic) and absence of calcification (1% malignant).16

Further management.20 When a single nodule is found on thyroid ultrasonography, the presence of at least one of the following malignant findings necessitates FNA regardless of the size of the nodule (see Table 13.3):

●marked hypoechogenicity

●microcalcifications. The definition of a spongiform appearance is the aggregration of multiple microcystic components in more than 50% of the volume of the nodule and macrocalcifications

●a taller-than-wide shape

●a speculated margin

If a nodule has indeterminate findings on ultrasonography and it is larger than 1 cm in diameter, then FNA is recommended because the possibility of malignancy cannot be excluded. If a nodule has indeterminate findings and it is 1 cm or less in size, then a FNA biopsy is not

necessary and follow-up ultrasonography would suffice.

If a benign-appearing nodule is larger than 1 cm, thenwe recommend perfoming follow-up ultrasonography in 2 years and thereafter at 3–5 year intervals. If a benign-appearing nodule (e. g., a spongiform nodule) is larger than 2 cm, then selective FNA biopsy can be done (the definition of a spongiform appearance is the aggregation of multiple microcystic components in more than 50% of the volume of the nodule).

Table 14.5 shows the recommended diagnostic strategy for a scintigraphically cold nodule that is hypoechoic at ultrasound.

Table 14.5 Diagnosis and treatment of hypoechoic/isoechoic nodule (cold nodule in radioiodine scan)

FNAB = fine-needle aspiration biopsy.

Metastases. Metastases have the same ultrasound appearance as thyroid carcinoma. They may be microscopically small or may grow to a very large size, sometimes acquiring a scalloped shape. Their vascularity at color duplex examination ranges from hypovascular to very hypervascular (Fig.14.46, Fig.14.47).