Nodular Goiter

The pathogenesis of nodule formation in these patients is iodine deficiency-induced hyperplasia followed by the formation of functioning nodules that undergo hemorrhage and necrosis replaced by lakes of colloid.

From: Nuclear Medicine (Third Edition), 2006

Chapters and Articles

Thyroid

Katherine Berezowski, ... Mary K Sidawy, in Fine Needle Aspiration Cytology, 2007

CLINICAL FEATURES

Goiter is a clinical term that denotes enlargement of the thyroid, which occurs due to impaired synthesis of thyroid hormones. Clinically, goiter presents in a nodular or diffuse form, and is divided by the functional activity of the thyroid into the non-toxic and toxic variants. Non-toxic nodular goiter is the most common form in the United States, affecting approximately 5% of the population. In essence, it is a compensatory response of the gland for a decrease in hormone secretion. The specific cause of this form of goiter is usually unknown. The basic mechanism involves stimulation of the thyroid by TSH due to low levels of the thyroid hormones, which leads to follicular cell hyperplasia and involution. Nodular goiter is the end-stage of a diffuse goiter and is caused by the cyclic changes taking place during hyperplasia and involution.

NODULAR GOITER (ADENOMATOID NODULE) – DISEASE FACT SHEET

Incidence

Affects 5% of population

Gender and Age Distribution

Female predominance

Occurs in adults

Clinical Features

Asymptomatic, euthyroid

Slow growing

Sudden growth as result of hemorrhage

Compressive symptoms

Nodular goiter is a disease of adults and shows a female predominance. Most patients are asymptomatic and, by definition, euthyroid. Multinodular goiter develops over many years and is detected on routine physical examination or by the patient noticing an enlargement in the neck. If the goiter is large enough, it can lead to compressive symptoms. Patients may complain of sudden pain caused by hemorrhage into a nodule.

CYTOPATHOLOGIC FEATURES

Cytologic nomenclature of nodular goiter includes adenomatoid, cellular adenomatoid, adenomatous, hyperplastic, and non-neoplastic nodule. The aspirates from nodular goiter are of low to moderate cellularity. They demonstrate an admixture of colloid and follicular cells in variable proportion, reflecting the different phases of evolution of the disease. During the hyperplastic stage, follicular cells are abundant and colloid is scant. As the disease progresses to the involutional stage, follicular cells become fewer and colloid becomes abundant.

The presence of abundant colloid and a high colloid to cell ratio are extremely helpful in the cytologic diagnosis of goiter. Macroscopically, smeared unstained colloid resembles varnish. Microscopically, colloid can appear as thick amorphous material with sharply circumscribed edges or as a thin translucent film in the background, often with folds and cracks. When diluted by blood, its appearance overlaps with serum. Colloid may be lost during processing, particularly with liquid-based preparations (see Fig. 2-1).

NODULAR GOITER (ADENOMATOID NODULE)–PATHOLOGIC FEATURES

Cytopathologic Findings

High colloid to cell ratio

Follicular cells arranged in honeycomb sheets, spherules, tissue fragments, or singly

Small round nuclei, naked nuclei, delicate cytoplasm

Hürthle cells

Cystic change: macrophages (pigmented, multinucleated), cyst-lining cells

Differential Diagnosis and Pitfalls

Cystic papillary carcinoma

Follicular neoplasm

Follicular variant of papillary carcinoma

Parathyroid cyst

Follicular cell nuclei are 1.5–2 times the size of mature lymphocytes. The chromatin is finely granular and uniformly dispersed, with inconspicuous nucleoli. The nuclei are round and may show enlargement and variability in size. The cytoplasm is delicate with indistinct borders (Fig. 2-7). The follicular cells are arranged in groups, honeycomb sheets, spherules, and tissue fragments. A spherule represents an intact non-neoplastic macrofollicle with its basement membrane. It appears as a round structure, with smooth borders and evenly spaced nuclei. A spherule may mimic a giant cell, but the latter can be differentiated by its irregular outline and unevenly spaced, elongated nuclei (Fig. 2-8). Tissue fragments with supporting vascular stroma may be mistaken for papillary structures and suggest papillary carcinoma. However, attention to the arrangement of the follicular cells within the tissue fragments (spherules and honeycomb sheets with maintained nuclear polarity) should prevent such a pitfall (Fig. 2-9). The follicular cells may also be found dispersed singly and stripped of their cytoplasm (Fig. 2-10). Hürthle cells with enlarged nuclei showing variable degrees of pleomorphism are seen in nodular goiter.

In Diff-Quik-stained smears, the follicular cells may reveal abundant intracytoplasmic blue granules, which can obscure the nuclei. These granules are seen in cystic and hemorrhagic lesions, and represent hemosiderin pigments. They are not specific and may be seen in goiter, as well as in benign and malignant neoplasms (Fig. 2-11). These non-specific granules should be distinguished from a different type of granules, ‘paravacuolar granules’ (Fig. 2-12). The latter consist of small blue granules grouped within a vacuole close to the nucleus. They are frequently observed in non-lesional thyroid tissue and occasionally in Hashimoto's thyroiditis. When the majority of aspirated follicular cells display paravacuolar granules, the cytopathologist needs to consider that the targeted lesion (especially when small) was missed and only adjacent non-lesional thyroid tissue was sampled.

Hemorrhage and cystic change are quite common in aspirates from nodular goiters. Cytologically, they manifest by the presence of histiocytes and hemosiderin-laden macrophages (many multinucleated), cholesterol crystals, and cyst-lining cells (Fig. 2-13 & Fig. 2-14). Cyst-lining cells appear as flat sheets of spindled to polygonal (squamoid) cells with abundant, dense cytoplasm, enlarged pleomorphic nuclei, and prominent nucleoli (Fig. 2-15). Bi- and multinucleation are common.

ANCILLARY STUDIES

Ancillary techniques including morphometry, image analysis, DNA measurements by flow cytometry, telomerase activity (by polymerase chain reaction [PCR]), and immunocytochemistry for a variety of antigens have been advocated for discriminating between benign and malignant nodules; however, none of these methods is sufficiently reliable.

DIFFERENTIAL DIAGNOSIS AND PITFALLS

The differential diagnosis of nodular goiter depends on the stage of the disease. Cystic nodules must be differentiated from cystic papillary carcinomas, while the differential diagnosis of cellular adenomatoid (hyperplastic) nodules includes follicular neoplasms and follicular variant of papillary carcinomas.

CYSTIC PAPILLARY CARCINOMA

Thirty per cent of thyroid nodules are cystic, most of which are nodular goiter. It is also important to point out that a third of papillary carcinomas are cystic, while cystic degeneration is rare in follicular, medullary, and anaplastic carcinomas. The gross appearance of the fluid (yellow or hemorrhagic) is not reliable in distinguishing goiter from papillary carcinoma. To the uninitiated, the prominent cytologic atypia and squamoid appearance of the cyst-lining cells of nodular goiter may lead to the erroneous diagnosis of papillary carcinoma.

FOLLICULAR NEOPLASMS

The cytologic features of cellular adenomatoid nodules overlap with those of follicular neoplasms, making the distinction between the two entities unreliable. High cellularity, scant colloid, and follicular cells arranged in acini and occasional microfollicles are shared features of both entities. When the distinction is difficult, the aspirates fall in the indeterminate category and are classified as ‘cellular follicular lesions’. The risk of malignancy with indeterminate thyroid cytology is reported as 15–20%.

FOLLICULAR VARIANT OF PAPILLARY CARCINOMA

This is a well-known pitfall, and one of the major sources of false negative diagnoses in thyroid FNA. This variant of papillary carcinoma reveals neoplastic cells arranged in syncytial clusters and microfollicles, and should be considered in the differential diagnosis of cellular follicular lesions. Attention to the nuclear features may help in establishing the correct diagnosis, or at least including papillary carcinoma in the differential diagnosis.

PARATHYROID CYST

When crystal-clear fluid is aspirated, the possibility of a parathyroid cyst should be considered. Measuring the level of C-terminal/midmolecule parathyroid hormone in the fluid helps in confirming the diagnosis.

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Endocrine System

Harvey A. Ziessman MD, ... James H. Thrall MD, in Nuclear Medicine (Third Edition), 2006

Hot and Warm Nodules

Radioiodine uptake within a nodule denotes function. A functioning nodule is very unlikely to be malignant. Less than 1% of hot nodules harbor malignancy. The term hot nodule should be reserved for those that not only have high uptake in the nodule scintigraphically, but also have suppression of extranodular tissue (see Fig. 5-17). If extranodular tissue is not suppressed, it should be referred to as a warm nodule.

Hot nodules are caused by toxic adenomatous nodules. Warm nodules may be caused by autonomous hyperfunctioning adenomas. However, they are not toxic, that is, they are not producing enough thyroid hormone to cause thyrotoxicosis and thus TSH is not suppressed. A warm nodule may also be due to nonautonomous hyperplastic tissue or even normal functioning tissue surrounded by poorly functioning thyroid. Differentiation can be made by administration of thyroid hormone (thyroid suppression test). Autonomous nodules cannot be suppressed (see T-3 Suppression Test). However, the suppression test is rarely needed in current practice.

Large hot nodules greater than 2.5–3.0 cm usually produce overt hyperthyroidism. Some patients with smaller nodules have subclinical hyperthyroidism, which can be confirmed by a suppressed serum TSH but normal T4. In the past, a small autonomous nodule might be followed clinically because some stabilize, whereas others regress or undergo involution (Fig. 5-20). Increasingly, nodules are treated at an early stage because of the low incidence of regression and increased awareness of adverse consequences associated with subclinical hyperthyroidism (e.g., bone mineral loss).

Radioiodine I-131 is the usual therapeutic method of choice for toxic nodules. Radiation is delivered selectively to the hyperfunctioning tissue while sparing suppressed extranodular tissues. The suppression of normal tissue results in a low incidence of posttherapy hypothyroidism. After successful treatment of the nodule, the suppressed tissue regains function. Surgery, usually lobectomy, may be indicated if there are local symptoms or cosmetic concerns.

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Oncology Imaging

Stefan Delorme, Michael Baumann, in Encyclopedia of Cancer (Third Edition), 2019

Thyroid Tumors

Nodular goiters are common and endemic in areas with low iodine concentration in drinking water, and most nodules are benign. In fact, the annual incidence of thyroid carcinoma in 2014 was 3.7/100,000 in men, and 8.9/100,000 in women (Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. (GEKID), 2014), whereas the mortality in 2012 was 0.35/100,000 in men and 0.29/100,000 in women (Becker and Wahrendorf, 1998), which indicates that the cure rate is in the range of 90% or higher. This results from the fact that after thyroidectomy and modified neck dissection, the standard surgical procedure, radioiodine ablation using 131-J is highly effective in eradicating not only local remnants but also distant metastatic disease of follicular and papillary thyroid carcinoma. It will not work, however, if iodine is not (primarily in anaplastic or medullary thyroid carcinoma, MTC) or no longer be taken up, as may occur by dedifferentiation. Hence, the prognosis of anaplastic or secondarily dedifferentiated carcinoma is poor. For the same reason, distantly metastatic MTC is impossible to control definitely, but apart from highly aggressive variants, MTC will progress only slowly, over decades rather than years.

The primary task in the workup of thyroid nodules is to spare as many patients as possible invasive measures without missing the relatively few ones who have thyroid carcinoma, with the diagnostic tools ultrasound, 99-m-pertechnetate scintigraphy, cytology from fine needle aspiration, accompanied by serum levels for T3, T4, TSH, and calcitonin for the rare cases of medullary thyroid carcinoma. The tumor marker thyroglobulin is used only to screen for recurrences in patients post thyroidectomy and radioiodine ablation; in all other patients, its serum levels are of no diagnostic use. As a rule, hypoechogenic and scintigraphically cold nodules more than 10 mm in diameter should undergo fine needle aspiration, be followed up with ultrasound if the biopsy is benign, and rebiopsied in case of further growth. Recently, Tc-99m-MIBI scintigraphy has been used for nodules that are cold in pertechnetate scintigraphy, and a persisting MIBI uptake after 120 min may be an additional indicator of malignancy. Still, under which circumstances MIBI scintigraphy should be performed remains to be determined. For preoperative nodal staging, additional ultrasound is the method of choice. Computed tomography plays almost no role for locoregional staging, since iodine-containing contrast agents are contraindicated. After thyroidectomy, radioiodine scintigraphy is the primary method for restaging, in combination with ultrasound. As long as any metastases continue to take up iodine, additional imaging studies will serve for morphologic workup of suspicious scintigraphic findings. Tumors that do not or no longer take up iodine (in case of secondary dedifferentiation, anaplastic, or medullary carcinoma), contrast-enhanced CT or MRI will be used in addition to ultrasound. FDG PET/CT is reserved for secondarily dedifferentiated carcinoma or anaplastic carcinoma.

Ten percentage of thyroid cancers are medullary carcinomas. Here, contrast-enhanced CT and ultrasound of the neck and abdomen are usual methods for staging as well as follow-up for patients who continue to have elevated serum levels for calcitonin or CEA. FDG PET/CT may be used in aggressive variants of the disease; slowly progressing tumors, the majority of cases, rather take up 18-F-DOPA, and PET/CT may be used to detect distant metastases. However, PET/CT studies for medullary carcinomas should be reserved for patients in whom positive findings would result in surgical resection. In late stages, this is only rarely the case.

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Non-neoplastic lesions of the thyroid gland

Carol F. Adair, in Head and Neck Pathology (Second Edition), 2013

Clinical features

ADENOMATOID NODULE (NODULAR GOITER)—DISEASE FACT SHEET

Definition

Diffuse enlargement of the thyroid with varying degrees of nodularity, usually associated with some impairment of thyroid hormone production and increased thyroid-stimulating hormone secretion

Incidence and location

Clinically detectable nodules found in <5% of patients

Highest incidence in areas with iodine-deficient diets; may also occur with excess iodine intake

Gender and age distribution

Female >> male (8:1)

Wide age range, although usually adults

Clinical features

One or more thyroid nodules usually discovered by patient or health care provider

Most patients are euthyroid

A dominant nodule may be mistaken clinically as a thyroid neoplasm

Tracheal compression or dysphagia may develop with large nodules

Prognosis and treatment

Multinodular goiters are usually treated for cosmetic or comfort reasons

Thyroxin therapy is often used to suppress nodules

Surgery is typically chosen for cosmetic reasons, or for a dominant nodule that may be suspicious for neoplasm

Radioactive iodine ablation for poor surgical candidates, toxic nodules

Hypothyroidism may develop, especially after surgical or radioactive iodine therapy

Adenomatoid nodules are common, found in ∼10% of autopsies (up to 50% if microscopic nodules are included), but clinically detectable nodules are found in <5% of individuals. Most patients are euthyroid; however, a few patients develop hyperthyroidism, a condition known as “toxic nodular goiter,” or Plummer disease.

Adenomatoid nodules are more common in women than in men (8:1) and occur over a very wide age range but tend to come to attention in adulthood. Nodules often become noticeable during pregnancy. Patients present with one or more nodules, or the nodule is discovered by a health care provider. The nodules are usually multiple, but one may be dominant and suggest a solitary nodule. Nodules that attain a large size may produce symptoms due to compression of adjacent structures (dysphagia, hoarseness, stridor). Radiologic studies are not usually necessary, although ultrasound may demonstrate the multiplicity and heterogeneous appearance of nodules (Figure 22-45).

Pathologic features

ADENOMATOID NODULE (NODULAR GOITER)—PATHOLOGIC FEATURES

Gross findings

Enlarged gland with multiple nodules of variable size

May be gelatinous with colloid exuding from cut surface

Degenerative changes include hemorrhage, central scars, fibrous pseudocapsules, cystic change, calcification, and metaplastic bone formation

Sample periphery for histologic sections

Microscopic findings

Nodules lack a capsule, but have a pushing border that merges with the surrounding follicles or may have a “pseudocapsule”

Hemorrhage common, with hemosiderin-laden macrophages and cystic change

Most nodules contain large follicles distended with colloid; the lining epithelium is flattened and inconspicuous.

Epithelial cells may demonstrate prominent oxyphilic change

Cellular nodules have increased cellularity (solid, microfollicular) with little colloid

Papillary fronds may be dominant, but with round, basally oriented nuclei

Fine needle aspiration

Usually low cellularity and abundant, thin colloid, often with scratches, waves, or cracks

Sheets of follicular epithelium with small, round, dense nuclei arranged in a “honeycomb pattern”

Hemosiderin-laden macrophages if degeneration is present

Cellular nodules have high cellularity and scant colloid, difficult to distinguish from follicular neoplasm

Pathologic differential diagnosis

Papillary carcinoma, follicular neoplasm, metastatic thyroid carcinoma versus parasitic nodule

Gross findings

The thyroid is diffusely enlarged and nodular (Figures 22-45, 22-46, and 22-47). The weight of the gland is quite variable, up to several hundred grams or more. Sectioning may reveal nodules that are similar in texture, with a fleshy gelatinous surface; colloid may exude from the cut surface on scraping with a scalpel blade (Figure 22-45), while other nodules are characterized by their heterogeneity (Figure 22-46). Nodules may demonstrate hemorrhage in the form of central hematomas or areas of organization with brown patches representing hemosiderin deposits. Cystic degeneration is common, particularly in larger nodules or following FNA, and may go on to develop thick fibrous pseudocapsules. Fibrous scars may be seen in some nodules; degenerated nodules are often calcified, and may require decalcification prior to histologic processing. Necrosis, if present, is usually central and confluent due to vascular insufficiency. Sections from the periphery of nodules are more useful than those from the center of the lesion (Figure 22-47). It is always prudent to remember that a multinodular goiter can easily harbor a thyroid neoplasm among its nodules. Therefore, nodules with capsules or pseudocapsules should be generously sampled, concentrating on the periphery or “capsule” of the lesion to exclude carcinoma (papillary carcinoma specifically).

Microscopic findings

In addition to the large macroscopic nodules selected for histologic assessment, one usually finds small areas of incipient nodularity scattered through the grossly unremarkable portions of the thyroid (Figure 22-48). They are seen as small groupings of enlarged follicles, which stand out among the normal background follicles.

The histologic features of adenomatoid nodules are as heterogeneous as the gross findings. Most adenomatoid nodules are composed of enlarged follicles distended with colloid, lined by flattened follicular epithelial cells (Figure 22-49). Some adenomatoid nodules are more cellular, sometimes appearing solid, with minimal colloid. The cytologic appearance varies, including oxyphilic cells (common) (Figure 22-50) and clear cells (occasionally) (Figure 22-50). It is important to realize that oxyphilic cells may exhibit some of the nuclear features of papillary carcinoma, including nuclear enlargement, vesicular chromatin, and irregular nuclear contours, but these are set in the architecture of a nodule (Figure 22-51).

Some adenomatoid nodules, usually those with cystic change, develop papillary structures (Figure 22-52). The cells lining these papillae, unlike papillary carcinoma, usually have small round nuclei with dense chromatin; the polarity of the cells is maintained, with the nuclei aligned evenly at the base of the epithelium.

Hemorrhage and cystic degeneration often go hand in hand (Figure 22-53). Hemosiderin may be seen deposited in granulation tissue or fibrous scar tissue in areas of degeneration. Hemosiderin-laden macrophages are often seen in the cystic areas and in adjacent parenchyma. In areas of marked hemorrhage, small granules of hemosiderin may be present in the cytoplasm of follicular cells, giving them a red-brown appearance (Figure 22-54). A chronic inflammatory infiltrate may be present. A variety of metaplastic changes may be seen, including fatty, squamous, cartilaginous, and osseous metaplasia.

A phenomenon that occasionally causes confusion, particularly during frozen section examination, is the parasitic nodule (Figure 22-55). This represents a nodule of thyroid tissue which has become separated from the thyroid gland, often demonstrating either adenomatoid nodules or nodular Hashimoto thyroiditis. The attachment to the thyroid is by an inconspicuous cord of fibrous tissue, often overlooked intraoperatively. The histologic appearance is usually that of an adenomatoid nodule; however, in cases associated with a dense lymphocytic infiltrate, they may resemble lymph node, especially when submitted as such during intraoperative assessment. As parasitic nodules lack the structures of a lymph node (subcapsular sinus, sinusoids, etc.), the misdiagnosis of metastatic papillary carcinoma in a lymph node can be averted.

Ancillary studies

Fine needle aspiration

The cytologic features of the usual adenomatoid nodule include abundant, usually thin, colloid and relatively low cellularity with hemosiderin-laden macrophages (Figure 22-56). The follicular epithelial cells from the large follicles ruptured by the aspiration process are usually found as large flat sheets, with evenly spaced, round nuclei, in a honeycomb pattern. The nuclei of the follicular cells have dense chromatin and are not crowded or overlapping (Figure 22-57). In lesions with degenerative changes, the follicular cells may be somewhat oxyphilic. Reactive or reparative follicular cells may be present; they are elongated, and may demonstrate nuclear enlargement and prominent nucleoli. Occasionally, aspirates of cellular adenomatoid nodules that have little colloid are indistinguishable from those of follicular neoplasms, based on cytologic examination alone. These are considered to be indeterminate or “suggestive of neoplasm”; surgical removal of the nodule is usually required in such cases.

Differential diagnosis

The chief differential diagnostic problems arise when adenomatoid nodules are cellular or when papillary hyperplasia is present, requiring separation from follicular neoplasms and papillary carcinoma. Cellular adenomatoid nodules may have a pseudocapsule associated with degenerative changes; prominent cystic degeneration is more often found in adenomatoid nodules than in follicular neoplasms, although FNA may induce such changes in neoplasms. Examination of the nodule’s periphery for capsular or vascular invasion is necessary to exclude a minimally invasive follicular carcinoma. Once invasion is excluded, the distinction between an adenomatoid nodule and a follicular adenoma is of no clinical significance, and may, in fact, be impossible. A true neoplasm usually has smooth muscle–walled vessels in the fibrosis, but this is not always identifiable. Adenomatoid nodules with extensive papillae lack the nuclear features of papillary carcinoma and have an orderly, polarized arrangement of their cells and are called “adenomatoid nodules, cystic with papillae.”

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Mediastinum

Saul Suster MD, Cesar A. Moran MD, in Diagnostic Pathology: Thoracic (Second Edition), 2017

Histologic Features

Thyroid tumors

Thyroid nodular hyperplasia

Ill-defined, unencapsulated nodules composed of normal follicular structures

May show abundant regressive changes, including fibrous pseudocapsule, hemorrhage, and cystic degeneration

May contain focal papillary structures, calcifications, and intraluminal follicular proliferations (Sanderson polsters)

Rare cases may show local recurrence and infiltration of surrounding soft tissues

Thyroid carcinoma

Rarely, follicular or papillary carcinoma may arise from displaced thyroid elements

Follicular carcinoma shows follicles with invasion of capsule and blood vessels

Papillary carcinoma is characterized by usual nuclear features of this tumor in thyroid

Medullary carcinoma, anaplastic carcinoma, and poorly differentiated (“insular”) carcinoma can also arise in mediastinum

Well-differentiated thyroid follicular and papillary neoplasms are positive for thyroglobulin and TTF-1

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Nontoxic Diffuse and Nodular Goiter and Thyroid Neoplasia

Martin-Jean Schlumberger, ... Ian D. Hay, in Williams Textbook of Endocrinology (Twelfth Edition), 2011

Imaging in Nodular Goiter Evaluation

Today, when a nodular goiter is clinically present, ultrasonography represents by far the most useful thyroid imaging technique for providing helpful information for disease management and treatment. Ultrasonography should be used to assess both the morphology and the size of the goiter and may assist in screening and in follow-up of thyroid nodules.1,2,10,35 Ultrasonography is capable of detecting even minute thyroid nodules. Of 1000 normal control subjects, 65% had detectable nodularity on high-resolution scanning.34

Attempts have been made to develop criteria for distinguishing benign and malignant nodules (see Table 14-3). Echo-free (cystic), spongiform, and homogeneously hyperechoic lesions are reputed to carry a low risk of malignancy.10,35 Positive predictive criteria of malignancy include predominantly solid nodules and absence of cystic elements, hypoechoic nodules, presence of microcalcifications, irregular margins and absence of halo, and a taller rather than a wide shape measured in the transverse dimension.59 Nodules that can be clearly identified as benign by sonography are uncommon. The color Doppler finding of predominantly internal or central blood flow appears to increase the risk that a nodule is malignant. However, like other sonographic features, color Doppler cannot be used to diagnose or exclude malignancy with a high degree of confidence.10,35 Elastography is a promising technique that requires further evaluation to determine its usefulness in clinical practice.15

Recently, an equation was devised to predict the probability of malignancy in thyroid nodules, based on 12 ultrasound parameters. It was suggested that such a thyroid imaging reporting and data system could decide optimal strategies for managing thyroid nodules.60

Ultrasonography is useful in identifying hypoechoic solid nodules that should be submitted to FNAB, particularly in the presence of microcalcifications, and also in examining the rest of the thyroid gland and lymph node areas (Fig. 14-3).2,10 It may also be used to direct the needle during FNAB—into the nodule in routine practice, or into solid portions in the case of partially cystic nodules—and in the setting of nonpalpable nodules, especially when the diameter of the nodule is 1 cm or more.10 Cystic lesions may be treated by aspiration of the fluid and ethanol injection to avoid recurrence; this is optimally performed under ultrasonographic guidance.61

In patients with large goiters, CT or MRI is indicated to define the relationships with surrounding structures.

The traditional imaging procedure of the thyroid in past years has been scintigraphy using 131I, 123I, or 99mTc. Most thyroid carcinomas are inefficient in trapping and organifying iodine and appear on scans as areas of diminished isotope uptake, so-called cool or cold nodules. This feature reflects the early decrease of NIS expression during tumorigenesis.62 However, most benign nodules also do not concentrate iodine and therefore are cold nodules. Furthermore, not all nodules with normal or slightly increased 99mTc uptake are benign, and some may appear cold on a thyroid scan with radioactive iodine.4,5

The only situation in which an iodine scan can exclude malignancy with reasonable certainty is in the case of a toxic adenoma, which is characterized by significantly increased uptake within the nodule (hot nodule) and markedly suppressed or absent uptake in the remainder of the gland. These lesions are suspected at clinical examination and are typically associated with a low or suppressed serum TSH level. They account for fewer than 10% of thyroid nodules and are almost invariably benign.35 Thyroid scintigraphy should be used as a second-line technique to detect hyperfunctioning nodules in patients with low or undetectable serum TSH levels.

CT scanning and MRI in the initial diagnosis of thyroid malignancy do not provide higher-quality images of the thyroid and cervical nodes than those obtained by ultrasonography. CT examination of the lower central neck is preferable if tracheal or mediastinal invasion is suspected.35

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Thyroid and Parathyroid

LORETTA L.Y. TSE, JOHN K.C. CHAN, in Modern Surgical Pathology (Second Edition), 2009

Thyroid Tissue in the Lateral Neck

Lateral Aberrant Thyroid

Thyroid tissue occurring in the lateral neck separate from the thyroid gland has often been referred to as lateral aberrant thyroid. This condition can occur in several circumstances58:

1.

Sequestered nodule in nodular goiter. The nodule may still be connected by a narrow strand of tissue to the main gland.

2.

Regrowth of thyroid tissue that has been implanted in the soft tissues of the neck from prior surgery.

3.

Sequestered thyroid tissue involved by Hashimoto's thyroiditis or Graves’ disease.

It is most important, however, to rule out the possibility of metastatic thyroid carcinoma (most commonly papillary carcinoma) in cervical lymph node.

Thyroid Inclusions in Cervical Lymph Node

Rarely, benign thyroid follicles can occur in cervical lymph nodes. Nonetheless, this belief is not universally accepted; some investigators consider all thyroid tissues within lymph nodes to represent metastasis from clinically undetected thyroid carcinoma.763 Because distinction between benign thyroid inclusions and metastasis from an occult thyroid carcinoma can be extremely difficult owing to the almost normal histologic appearances of some thyroid carcinomas, the following strict criteria must be used in the diagnosis of benign thyroid inclusions58,764,765:

1.

They consist only of a small conglomerate of thyroid follicles.

2.

They are limited to the periphery of one or two lymph nodes.

3.

Nuclear features of papillary carcinoma are lacking (i.e., nuclei are not enlarged, with fine chromatin and inconspicuous nucleoli).

4.

Psammoma bodies are absent.

5.

No desmoplastic reaction is present.

Metastatic Thyroid Carcinoma in Cervical Lymph Node

Papillary carcinoma commonly metastasizes to lymph node, whereas follicular carcinoma rarely does. Cervical lymph node metastasis is sometimes the first clinical manifestation of an occult papillary thyroid carcinoma—the thyroid primary tumor is almost always located on the ipsilateral side. The node can be cystic or can enlarge suddenly because of hemorrhage. On histologic examination, a diagnosis of metastatic papillary thyroid carcinoma can be obvious because of the presence of recognizable lymph node tissue and papillary carcinoma. However, in some cases, the cyst wall is formed by dense fibrous tissue with scant lymphoid tissue underneath, is lined by attenuated nondescript cells, and thus may be mistaken for a branchial cyst (Fig. 44-83). Careful search may be required to uncover small papillae projecting into the lumen or some elongated follicles in the wall, with the cells exhibiting the typical nuclear features of papillary carcinoma (see Fig. 44-83B and C). A diagnosis can be readily confirmed by positive immunostaining for thyroglobulin.

Mimicker of Metastatic Thyroid Carcinoma in Cervical Lymph Node

A sequestered thyroid nodule involved by florid Hashimoto's thyroiditis can potentially be mistaken for metastatic thyroid carcinoma in lymph node because the lymphoplasmacytic infiltrate with germinal center formation imparts a lymph node–like appearance and the thyroid follicles can exhibit nuclear atypia or pallor. However, subcapsular sinuses, a hallmark of lymph node, are lacking.

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Multinodular Goiter

Laszlo Hegedüs, ... Steen J. Bonnema, in Endocrinology (Sixth Edition), 2010

ANTITHYROID DRUGS

Antithyroid drugs are indicated if the nodular goiter is complicated by coexisting hyperthyroidism. These drugs normalize thyroid function, but remission is very rare and lifelong treatment should be anticipated. Also, further goiter growth may be seen, possibly as a result of using these drugs. Antithyroid drugs are indicated before thyroid surgery to lower the operative risk and can be stopped during the immediate postoperative period.117 To reduce the risk for exacerbation of hyperthyroidism, it has been recommended to render the patient euthyroid with antithyroid drugs prior to 131I treatment. Usually, the antithyroid drug is discontinued at least 4 days before and is resumed no sooner than 3 days afterward.117 A meta-analysis, based mainly on studies of Graves' disease, found that the use of methimazole and propylthiouracil in conjunction with 131I therapy results in a decreased remission rate.118 Whether this applies also to toxic multinodular goiter patients is unknown. One study has shown attenuation of goiter reduction if methimazole is resumed after 131I therapy despite a neutral effect on thyroid function.119

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Toxic Nodular Goiter

Pamela R. Schroeder, Paul W. Ladenson, in Clinical Management of Thyroid Disease, 2009

RECOMBINANT THYROID-STIMULATING HORMONE–STIMULATED 131I Therapy

The relatively low fractional uptake of radioiodine by nodular goiters can limit the effectiveness of 131I therapy and increase the administered dose requirement. Consequently, in recent years, recombinant TSH (thyrotropin alfa, rTSH, Thyrogen) has been investigated as an off-label approach to increasing thyroidal radioiodine uptake for the treatment of hyperthyroidism and goiter size in patients with toxic nodular goiter. rTSH has also been used to facilitate goiter shrinkage with 131I in patients with nontoxic nodular goiter, in whom rTSH permits a 50% to 60% reduction in the administered 131I dose143,144 while producing a more substantial decrease in goiter volume. Studies in nontoxic nodular goiter patients have demonstrated the importance of using a rTSH dose less than that used for thyroid cancer testing (e.g., a single 0.01- to 0.45-mg rTSH dose).144-146 Larger rTSH doses have been reported to induce severe thyrotoxicosis or gland swelling with increased obstructive symptoms. rTSH-stimulated 131I therapy has also been used for older patients with clinical or subclinical hyperthyroidism caused by large multinodular goiters. In such patients, the relatively low fractional uptake of radioiodine by the thyroid reduces the cure rate after 131I. In one study of 41 patients with clinical or subclinical hyperthyroidism caused by large multinodular goiter, patients who were randomly assigned to receive 0.45 mg rTSH before 131I had a greater reduction in goiter volume at 1 year, 58% versus 40%. However, rTSH pre-treated patients also had a higher rate of postradioiodine hypothyroidism, 65% versus 21%,147 probably because rTSH enhanced uptake in previously suppressed regions of the gland. Because of its risk of exacerbating hyperthyroidism, rTSH is generally inadvisable when administering a larger 131I dose is an option, especially in older patients and those with underlying heart disease.

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URL: https://www.sciencedirect.com/science/article/pii/B9781416047452000146

Semiology of the Thyroid Gland

Dr. Manuela Stoicescu, in General Medical Semiology Guide Part I, 2020

Nodular Goiter

Lumps in the anterior cervical area of the neck—nodular goiter

19.

Do you have daily contact with radiation?

20.

Do you live in an area with radiation?

21.

Have you had several investigations such as CT and MRI performed? This can result in extensive radiance because the thyroid gland is very sensitive to radiation exposure.

22.

Do you live in a geographical area with deficient iodine?

23.

Do you have a family history of thyroid disease? hyperthyroidism? Graves’ disease? carcinoma of the thyroid gland?

24.

Are you constantly nervous, irritable, with a tremor of the hands and sweating palms, with intolerance to cold and excessively emotional?

The thyroid gland is shaped like a butterfly and located in front of the neck region. Normally, the thyroid gland is not palpable. The thyroid gland can be felt when there is an increase in volume and is called goiter.

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URL: https://www.sciencedirect.com/science/article/pii/B9780128196373000048