Nodular Goiter - an overview (original) (raw)
Chapters and Articles
You might find these chapters and articles relevant to this topic.
Thyroid
Katherine Berezowski, ... Mary K Sidawy, in Fine Needle Aspiration Cytology, 2007
NODULAR GOITER
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.
URL:
https://www.sciencedirect.com/science/article/pii/B9780443067310500069
Thyroid and Parathyroid Glands: Imaging, Treatment, and Beyond
Laurie A. Loevner MD, ... Gul Moonis MD, in Neuroimaging Clinics of North America, 2008
Nodular Diseases of the Thyroid Gland
Thyroid Goiter
Goiter refers to any enlargement of the thyroid gland. Nodular goiter is characterized by excessive growth with structural or functional transformation of one or several areas within an otherwise normal gland. In the absence of autoimmune thyroid disease, thyroiditis, thyroid dysfunction, and thyroid malignancy, this condition is termed simple nodular goiter.32 The pathogenesis of simple nodular goiter is related to genetic and environmental factors, most importantly iodine deficiency. To compensate for inadequate thyroid hormone output, follicular epithelium undergoes compensatory hypertrophy to achieve a euthyroid state. Hypo- or hyperthyroidism may develop. Initially, the goiterous enlargement is diffuse. However, with time it usually becomes nodular. If the impediment to thyroid hormone output abates, the thyroid gland may revert to normal during the diffuse state.
Diffuse nontoxic goiter represents diffuse, nonnodular enlargement of the thyroid associated with a euthyroid state. There are two stages. The first is hyperplasia (follicular cell growth) characterized by diffuse glandular enlargement and hyperemia. The second stage is colloid involution, which occurs when a euthyroid state is maintained. Endemic goiters are prevalent in iodine-deficient areas. There is a female predominance and a peak incidence at puberty.14 Most simple goiters progress to multinodular goiter that may remain nontoxic and are characterized by nodularity, focal hemorrhage, focal calcifications, and cyst formation. Glandular enlargement may be asymmetric, involving one lobe more than the other, or the isthmus. Thyroid goiters may extend substernally into the anterior mediastinum. A solitary cold nodule in a multinodular gland has similar cancer rates as those of a solitary cold nodule in a normal gland.33–35 Therefore, a dominant or enlarging mass within a goiterous thyroid raises concern for a malignancy and should be histologically sampled.36
Sonography is often able to differentiate among the various causes of an enlarged thyroid gland. On ultrasound, CT, or MR imaging, multinodular goiter has multiple nodules of varying size. These nodules commonly contain complex cystic areas, representing colloid often mixed with areas of hemorrhage and necrosis. Dystrophic calcifications are common and typically are coarse and large. On T1-W MR images, foci of high signal intensity may represent cysts with colloid or hemorrhage. On T2-W MR images, diffuse heterogeneity may be present,37 and nodules as small as 3 to 5 mm can be visualized.27 Unlike ultrasound and CT, calcifications may be difficult to detect on MR imaging.
CT and MR imaging are the most valuable imaging modalities in assessing secondary manifestations of goiter, including compression and displacement of the trachea, esophagus, and adjacent vessels (Fig. 4). Substernal and mediastinal extension are readily detected. When symptoms related to compression of the aerodigestive tract or vessels occur in elderly patients, nonsurgical candidates, or those refusing surgery, therapy with I-131 may be effective in reducing thyroid volume.32,38
Fig. 4. Thirty-five-year-old woman with palpable left thyroid enlargement. Axial T1-W MR image shows a large mass (M) in the left lobe of the thyroid gland, which compresses the trachea (T), which is displaced from left to right. Also note there is about 30% luminal narrowing of the trachea.
Benign Adenomas
Thyroid adenomas are true benign neoplasms distinct from adjacent thyroid tissue and encased by a fibrous capsule. They are usually solitary and nonfunctioning, often detected in young and middle-aged adults. Autonomously functioning adenomas less than 3 mm in diameter are usually not associated with hyperthyroidism.39 Toxicity is usually associated with large lesions and advanced age. Follicular adenomas slowly increase in size, usually not exceeding 4 cm in diameter.14 Sudden enlargement of a follicular adenoma is usually related to spontaneous hemorrhage within the lesion.40 Most thyroid cysts represent spontaneous degeneration of adenomas. Carcinoma within an adenoma is exceedingly rare.40
If an adenoma is autonomous (independent of thyrotropin), ablation with I-131 may be performed, as the short-acting beta-radiation will deposit preferentially in the nodule. Alternatively, the nodule may be surgically removed. The previously suppressed normal thyroid tissue resumes normal function following treatment. The risk of postprocedural hypothyroidism is small. Ethanol injection, including with ultrasound guidance, has been reported. However, it has not gained wide acceptance.41–49
Evaluation of Thyroid Nodules that are Cancer
Thyroid nodules are common, with palpable nodules occurring in 4% to 7% of the adult population in the United States.50 Fine needle aspiration of all palpable nodules to assess for cancer in euthyroid patients is the accepted standard of care. In the hands of experienced cytologists, fine needle aspiration has a high accuracy rate.50 Several factors influence the likelihood that a nodule is cancer. Malignancy is more common in patients under 20 or over 60 years of age, and is more common in men. Findings on physical examination associated with an increased risk of malignancy include firmness of the nodule, rapid growth, fixation to adjacent structures, vocal cord paralysis, and enlarged cervical lymph nodes. A history of neck irradiation or a family history of thyroid cancer also increases the risk that a nodule is cancer.17,43,44
The purpose of CT and MR imaging in assessing patients with a suspected thyroid malignancy is to evaluate for extension of tumor outside the thyroid capsule and into adjacent soft tissues of the neck. This should be suspected in patients with complicated clinical presentations (see below). In certain circumstances, CT and MR imaging are also important in assessing for cervical and mediastinal lymph nodal metastases, especially when there is adenopathy on clinical examination as imaging will help determine the extent and type of neck dissection.
URL:
https://www.sciencedirect.com/science/article/pii/S1052514908000518
Iodine Efficiency
Massimo Tonacchera, ... Paolo Vitti, in Best Practice & Research Clinical Endocrinology & Metabolism, 2010
Nodular goitres are enlargements of the thyroid gland. In the absence of thyroid dysfunction, autoimmune thyroid disease, thyroiditis and thyroid malignancy, they constitute an entity described as non-toxic nodular goitre, which occurs both endemically and sporadically. In the early phase of goitrogenesis, goitres are diffuse and, with time, such goitres tend to become nodular. Concomitantly, thyroid function often becomes autonomous, and therefore the patients gradually develop hyperthyroidism. Some non-toxic goitre patients have no symptoms at all, or just complaints of cosmetic disfigurement. In the diagnostic evaluation protocol, neck palpation and several imaging methods are available: ultrasonography (US), the new developed US elastography, scintigraphy, computed tomography (CT) scan and magnetic resonance imaging (MRI). Fine-needle aspiration biopsy (FNAB) provides the most direct and specific information about a thyroid nodule. Recently, a combination of cytology and molecular testing has shown significant improvement in the diagnostic accuracy and allowed for better prediction of malignancy in thyroid nodular disease.
URL:
https://www.sciencedirect.com/science/article/pii/S1521690X09000992
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.
URL:
https://www.sciencedirect.com/science/article/pii/B9780443067310500069
Endocrine System
Harvey A. Ziessman MD, ... James H. Thrall MD, in Nuclear Medicine (Third Edition), 2006
Colloid Nodular Goiter
Before the addition of iodine supplements to salt and food, goiter was endemic in the northern United States around the Great Lakes, and still occurs in some parts of the world. These endemic goiters were typically composed of colloid nodules (colloid nodular goiters) and most were benign.
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. Repetition of this process over time leads to glandular enlargement, with nonfunctioning colloid nodules as the dominant histopathological feature. The typical scintigraphic appearance of benign multinodular colloid goiters is inhomogeneous uptake of tracer with cold areas of various sizes (Fig. 5-23).
URL:
https://www.sciencedirect.com/science/article/pii/B9780323029469500106
Thyroid and Parathyroid Glands
Rebecca Chernock, Michelle D. Williams, in Gnepp's Diagnostic Surgical Pathology of the Head and Neck (Third Edition), 2021
Nontoxic Nodular Goiter
Clinical Features and Pathogenesis
The term nontoxic goiter, also known as multinodular, simple, or colloid goiter, refers to nodular enlargement of the thyroid gland in the absence of hyperthyroidism or hypothyroidism, inflammatory processes, or neoplasms.21 Nontoxic nodular goiter is the most common form of goiter in the United States. With large goiters, displacement or compression of the esophagus and trachea may give rise to dysphagia or dyspnea. Pain may be associated with hemorrhage into one of the nodules. Clinically, the incidence of nontoxic nodular goiter is 3% to 5%.113 At autopsy, the prevalence of this disorder is substantially higher and is in the range of 30% to 50%.
The development of goiter most likely results from a variety of mechanisms that lead to impairment of T3 and T4 production.16 This leads to increased production of TSH and subsequent stimulation of the thyroid gland. One hypothesis is that the inability to form sufficient T3 and T4 represents an inborn error of metabolism that is related to, but not as severe as, that present in patients with dyshormonogenetic goiter. The levels of TSH are not substantially increased in individuals with nodular goiter, however. This suggests that levels of TSH may be only minimally or sporadically increased in affected patients. An alternative possibility is that subsets of thyroid follicular cells may be more susceptible to the stimulatory actions of normal levels of TSH. It has also been suggested that there may be a class of thyroid growth–stimulating immunoglobulins that stimulate growth but do not stimulate adenylase activity in patients with nontoxic nodular goiter. A recent association with germline mutations in DICER1 and multinodular hyperplasia has been identified in young adults particularly women.114,115 DICER1 is a ribonuclease that processes miRNA involved in regulating thyroid function.
Pathologic Features and Differential Diagnosis
The initial phase of the development of this type of goiter is characterized by diffuse glandular enlargement. There is nodular hyperplasia of follicular cells with the formation of papillary infoldings of the epithelium and scant amounts of colloid. In the phase of involution, the follicles become filled with colloid. Rupture of follicles may lead to inflammation with histiocytes, lymphocytes, and multinucleate giant cells. The disease process is, therefore, characterized by alternating phases of hyperplasia and involution.
Nodular thyroids are typically enlarged, with weights of up to 500 g (Fig. 7.22). Usually, the gland is markedly distorted by multiple nodules that measure from less than 1 cm to many centimeters in diameter. In some instances, the growth may extend beneath the sternum (substernal goiter). Individual nodules have a remarkable array of histologic appearances. Some may be composed of markedly enlarged follicles that are distended with colloid (Fig. 7.23), whereas others may have a microfollicular appearance. Other nodules may appear hyperplastic, with papillary formations extending into the follicular spaces (Fig. 7.24). Nodules composed of oncocytes may also occur. Individual nodules may be partially demarcated from the adjacent thyroid parenchyma by an incomplete fibrous capsule. In contrast to adenomas, which typically have a uniform follicular architecture, hyperplastic nodules are characterized by variation in follicular size. The adjacent thyroid parenchyma is not usually compressed adjacent to hyperplastic nodules, in contrast to the compressive effects of adenomas. Degenerative changes including hemorrhage, calcification, and ossification are frequent. Some follicular nodules may undergo complete cystic degeneration. In some cases, a single nodule may be present, with the remainder of the gland showing either normal or mild hyperplastic change. The nodules may be partially encapsulated and have a relatively uniform microfollicular growth pattern. In such cases, the distinction between a hyperplastic nodule and a follicular adenoma is particularly difficult. The term adenomatoid nodule or adenomatous change is sometimes used for those nodules, acknowledging a similarity of their appearance to follicular adenomas.
Studies employing molecular techniques have revealed that, although most of the nodules in multinodular goiters are polyclonal and therefore non-neoplastic, some of them may represent clonal proliferations.116 In some series, as many as 70% of hyperplastic nodules in multinodular goiter were monoclonal, whereas the adjacent thyroid parenchyma was polyclonal.117 Moreover, there were no morphologic differences with respect to cellularity or encapsulation in nodules that were monoclonal or polyclonal.
Treatment and Prognosis
Patients with large multinodular goiters with evidence of compressive symptoms are generally treated by thyroidectomy. In patients with normal or elevated levels of TSH, administration of thyroid hormone may lead to a decrease in the size of the goiter. Radioactive iodine has also been used in some instances.
URL:
https://www.sciencedirect.com/science/article/pii/B9780323531146000079
Endocrine
Anne Marie McNicol, in Surgery (Oxford), 2007
The pathological features are a combination of hyperplastic and involutional change and nodule formation. Some nodules may appear larger—‘dominant nodules’. These may be nodules with extensive colloid accumulation and degeneration that are easily recognized on FNA, or hyperplastic nodules that histologically resemble follicular neoplasms. Some may be encapsulated. It may be difficult to distinguish histologically between a follicular adenoma and a hyperplastic nodule in a nodular goitre. The term ‘adenomatoid nodule’ is often used in the context of overall nodularity. The specific classification is unimportant as long as there are no features to indicate malignancy after adequate histological examination.
URL:
https://www.sciencedirect.com/science/article/pii/S0263931907002499
Head and Neck Ultrasound
Robert A. Sofferman MD, in Otolaryngologic Clinics of North America, 2010
Multinodular Goiter
There are many sonographic variations of nodular goiter. Nodules may be hypoechoic, hyperechoic, or anechoic and vary in size and position. Coarse calcifications are common. Occasionally, the inferior extent of the thyroid cannot be determined on ultrasound, requiring CT scan to determine the degree of substernal extension. The isthmus must be carefully assessed, as it is easy to forget that it can harbor large nodules or significant pathology. One of the most difficult concepts in assessment of multinodular goiter is to determine which nodules to biopsy. The “dominant” nodule is the largest of multiple nodules and traditionally the one most likely to be biopsied; however, there are other nodule characteristics that may require biopsy. Irregularity, infiltration of strap muscles, hypervascularity, and microcalcifications are some of the features that demand biopsy.
URL:
https://www.sciencedirect.com/science/article/pii/S0030666510001866
Non-neoplastic lesions of the thyroid gland
Carol F. Adair, in Head and Neck Pathology (Second Edition), 2013
■ Adenomatoid nodule (nodular goiter)
The common multinodular goiter represents diffuse enlargement of the thyroid with varying degrees of nodularity. The “building block” of multinodular goiter is the adenomatoid nodule. Similar nodules may be seen in long-standing or treated Graves disease and in Hashimoto thyroiditis.
A variety of factors are involved in the development of multinodular goiters; most are associated with some impairment of thyroid hormone production. The response is increased secretion of TSH, which stimulates proliferation of the follicular epithelium and increased thyroglobulin production in a compensatory process, with increased thyroid mass and hormone-producing capacity. In iodine-deficient areas of the world, multinodular goiters at one time affected over half of adolescent girls; this was essentially reversed by iodine supplementation. Excess iodine intake, including iodine-containing medications, or other goitrogens, can also induce multinodular goiter by interfering with efficient organification of iodine in the production of thyroid hormone. A genetic component may play a role in multinodular goiter development.
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.”
Prognosis and therapy
Multinodular goiters are not life threatening, and treatment is usually sought for cosmetic or comfort issues. There is no increased incidence of thyroid carcinomas in patients with multinodular goiters. The therapeutic approach to multinodular goiter includes medical therapy (thyroxin administration for suppression of the gland), radioactive iodine ablation, and thyroidectomy. Radioactive iodine ablation is not widely used in the United States for treatment of multinodular goiter, but may be useful in patients who are not surgical candidates or for those with toxic multinodular goiter. Hypothyroidism is a risk in any patient treated surgically for multinodular goiter.
URL:
https://www.sciencedirect.com/science/article/pii/B9781437726077000312
Goiter in the Elderly
Shakaib U. Rehman, ... Florence N. Hutchison, in Comprehensive Handbook of Iodine, 2009
Publisher Summary
The term goiter means thyroid enlargement, either diffuse or nodular. The incidence of goiter increases with age. The most common type of goiter in the elderly is multinodular goiter. Graves' disease is very rare in older adults. The most common cause of goiter worldwide is iodine deficiency. It is becoming less of a problem in developed countries, due to the addition of iodine to salt and bread. Goiter commonly presents as neck mass. Although most patients with goiter do not have any symptom other than neck swelling, occasionally patients complain of dysphagia, dysphonia, or pain. Many goiters do not cause any thyroidal hormonal abnormality (euthyroid status). Graves' disease, uncommon in the elderly, usually presents with a diffusely enlarged goiter with a bruit. The common symptoms of heat intolerance, tremor, tachycardia, and so on, may be erroneously attributed to normal aging or commonly present coexisting diseases in the elderly. Goiters associated with hypothyroidism can be regressed with thyroxine replacement therapy. Low doses of thyroxine should be used first and titrated in the elderly to avoid cardiac toxicity. Proper work-up for elderly patients with goiter includes a thorough history, detailed clinical examination, thyroid hormone assays, e.g., TSH, T4, T3, and an ultrasound or CT scan. Most goiters are benign in nature and may not require tissue diagnosis. In some elderly patients, fine needle aspiration and biopsy may be considered to rule out malignancy. Most elderly patients with nodular goiter are treated best by surgical removal, while radioiodine therapy and/or antithyroid drugs are the most effective therapy for non-nodular goiter.
URL:
https://www.sciencedirect.com/science/article/pii/B9780123741356000340