Non-Neoplastic Lesions of the Thyroid Gland

Clinical Features

Thyroglossal duct cysts represent the most common midline mass in children but may also be found in adults and in the elderly. At least one-third occur after the age of 30 years. There is no sex predilection. The classic presentation is of a midline, mobile neck mass located either at or immediately below the hyoid bone (75%) ( Fig. 23.1 ). Less commonly, such cysts may be suprahyoid, submental, intrathyroidal, and rarely intralingual. Slightly off-midline examples may be seen; in such cases, the presence of a fibrous tract or cord emanating from the hyoid bone is a helpful finding. Cysts can be linked to the skin or foramen cecum by a sinus tract.

In most cases, the patient is asymptomatic but may have pain, a draining sinus, a fistula (10% to 20%), dysphagia, or rarely airway obstruction. Infection occurs in one-third of cysts. The cysts may fluctuate in size, especially if infected. Thyroglossal duct cysts move vertically with swallowing or protrusion of the tongue.

Radiographic Features

Radiographic studies usually show a cystic mass, often with bright signal on magnetic resonance imaging (MRI) studies. These cysts are usually found at midline, with the point of origin frequently identified.

Pathologic Features

Gross Findings

The surgical specimen usually consists of the thyroglossal duct cyst as well as the fibrous tract/duct extending to the foramen cecum and the central 1 to 2 cm of the hyoid bone ( Fig. 23.2 ). The mean cyst size is around 2.5 cm, although cysts up to 8.5 cm have been reported. The cyst may contain clear mucoid fluid or, if infected, purulent material. Solid or firm areas should be carefully sampled to exclude an associated neoplasm.

Thyroglossal Duct Cyst—Pathologic Features

Gross Findings

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  Cyst filled with mucoid or purulent material

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  Fibrous tract from area of foramen cecum to hyoid bone

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  One-third present as fistulas, usually due to infection

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  Solid areas sampled to exclude neoplasm

Microscopic Findings

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  Cyst lined by respiratory and/or squamous epithelium

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  If the cyst is infected, granulation tissue may replace epithelium

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  Fibrosis and chronic inflammation in cyst wall

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  Thyroid tissue identified in at least two-thirds of cases

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  If carcinoma is present, at least 90% are of the papillary type

Fine Needle Aspiration

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  Thick mucoid or purulent material, sparsely cellular and with inflammatory material

Pathologic Differential Diagnosis

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  Epidermoid and dermoid cysts, plunging ranula, degenerated adenomatoid nodules

Microscopic Findings

The thyroglossal duct cyst is normally lined by respiratory epithelium, but squamous metaplasia is quite common and most cysts contain a mixture of squamous and respiratory epithelium ( Figs. 23.3 and 23.4 ). About 10% are purely squamous-lined. If the cyst has been infected, the lining epithelium may be replaced by granulation tissue, sometimes with granulomatous elements such as foamy histiocytes and multinucleated giant cells ( Fig. 23.4 ). Fibrosis and chronic inflammation are often found in the cyst wall. Thyroid tissue is not invariably present but is quite common, found in up to 71% of cases with careful examination ( Fig. 23.5 ). Seromucinous glands and cartilage may also be found in the wall.

The associated thyroid tissue may harbor any inflammatory, hyperplastic, or neoplastic alteration that can be seen in the normal follicular epithelial component of the thyroid gland. Up to 3% of thyroglossal duct cysts will have an associated carcinoma, with papillary thyroid carcinoma (PTC) representing at least 90% of cases. Thyroglossal duct cysts in elderly patients are much more likely to harbor malignancies. No examples of medullary carcinoma have been documented, presumably due to the different embryologic origin of the C cells from the ultimobranchial body.

Ancillary Studies

Differential Diagnosis

Epidermoid cysts of the thyroid, plunging ranula of salivary origin, or degenerated cystic adenomatoid nodules may be considered in the differential diagnosis; but the midline location and respiratory and/or squamous epithelial lining are key elements in making the diagnosis of thyroglossal duct cyst. When a thyroid carcinoma arising in a thyroglossal duct cyst is under consideration, the possibility of a metastatic tumor from the thyroid proper should be excluded.

Prognosis and Therapy

The preferred treatment for a thyroglossal duct cyst is the Sistrunk procedure, which requires resection of the entire tract of the thyroglossal duct along with the cyst or fistula and the central 1 to 2 cm of the hyoid bone. The recurrence rate after this procedure is 4% to 6%; if the hyoid bone segment is not removed, the recurrence rate increases to above 25%. Well-differentiated thyroid carcinoma arising in a thyroglossal duct cyst has an excellent prognosis with the Sistrunk procedure. Total thyroidectomy is not usually required for benign cysts except in high-risk patients or in the instance of carcinoma arising in the thyroglossal duct cyst.

Clinical Features

Most thyroid ectopia is clinically occult and discovered incidentally in patients undergoing surgery for another indication. Lingual thyroid is the most common type of clinically detected thyroid ectopia (90% of cases). In addition, most patients have no other thyroid tissue in the neck (complete thyroid ectopia). It can present at any age and is more common in women. The male-to-female ratio is 1 : 5.

Patients with lingual thyroid may present with symptoms including cough, hoarseness, and sleep apnea, but most are asymptomatic. Airway obstruction is rare. Over half of patients are hypothyroid. Clinically visible lingual thyroids appear as a submucosal, smooth mass at the base of the tongue.

Radiographic Features

Radionucleotide scanning either with ^99m Tc pertechnetate, ¹²³ I, or ¹³¹ I is virtually diagnostic of thyroid ectopia.

Pathologic Features

Microscopic Findings

Thyroid ectopia is histologically identical to normal thyroid ( Fig. 23.7 ). Lingual thyroids often have intervening skeletal muscle. Changes typical of nodular hyperplasia, variability in follicle size, cyst formation, fibrosis, and calcification may be present. Thyroid carcinoma is rare (1%).

Ancillary Studies

Differential Diagnosis

Metastatic well-differentiated PTC is the main consideration in the differential diagnosis of thyroid ectopia. Thyroid ectopia lacks nuclear features of PTC, but metastases of papillary thyroid carcinoma can be deceptively bland; therefore, careful examination is important. In the lateral neck, thyroid tissue usually represents metastatic disease rather than ectopia, especially in a lymph node.

Prognosis and Therapy

No treatment is required for asymptomatic thyroid ectopia/lingual thyroid. If symptomatic, thyroid hormone replacement may be used to shrink the thyroid tissue. Surgery or radioactive iodine ablation can be used to treat more severe symptoms in patients who are not surgical candidates. Associated hypothyroidism is treated by hormone replacement. Death from airway obstruction is very rare.

Clinical Features

Solid cell nests, which are fairly common, are of no clinical significance. They are identified in some 25% of thyroid resection specimens; their discovery is largely related to the generosity of sampling of “normal” thyroid tissue.

Pathologic Features

Ultimobranchial remnants (solid cell nests) are quite small, most measuring no more than 0.1 mm. They are represented by a cluster of small, round, or lobulated epithelial nests and may be solid or partially cystic ( Fig. 23.8 ). Occasionally, several foci may be found in a gland. The epithelial cells are small and ovoid to polygonal, with slightly elongated nuclei; they are called “main cells.” The chromatin is finely granular and evenly dispersed. A longitudinal nuclear groove is often present ( Fig. 23.9 ). The overall histologic pattern is very similar to that of immature squamous metaplasia, but keratinization and intercellular bridges are not visible. A minor population of cells with clear cytoplasm comprises C-cells. Degenerative changes are thought to account for the occasional presence of mucicarmine-positive material in ultimobranchial remnants.

Ancillary Studies

Differential Diagnosis

Ultimobranchial remnants are sometimes mistaken for squamous metaplasia, incidental microscopic PTC , or a small medullary carcinoma/C-cell hyperplasia . Although nuclear grooves are frequent in ultimobranchial remnants, these lesions lack the other nuclear features of PTC (overlapping nuclei, ground-glass chromatin pattern, intranuclear inclusions) as well as an adjacent stromal desmoplastic reaction.

C-cell hyperplasia or a small medullary carcinoma may have similar nodular growth. However, C-cells (which give rise to both hyperplasia and medullary carcinoma) are plasmacytoid; they have granular chromatin and more abundant pale pink to clear cytoplasm than solid cell nests. Small medullary carcinomas show expansile growth, stromal fibrosis, and/or amyloid deposition as well. Scattered calcitonin or neuroendocrine marker staining should not be mistaken for C-cell neoplasia, as C-cells are normally present in solid cell nests.

While not necessarily within the differential diagnosis, endodermally derived tissues may be encountered in the thyroid gland, including cartilage, parathyroid gland ( Fig. 23.10 ), thymic tissue, and salivary gland tissue ( Fig. 23.11 ). These “inclusions” are usually of no clinical significance, typically representing incidental findings in surgical resection specimens. Thymic tissue retains its lobulated appearance, has small cystic islands of squamous epithelium (Hassall corpuscles) with an abundant lymphoid component that may be mistaken for lymphocytic thyroiditis or a lymph node ( Fig. 23.11 ). Parathyroid tissue , particularly if it is hyperplastic or neoplastic, can be difficult to distinguish from a cellular adenomatoid nodule or follicular thyroid neoplasm. Oxyphilic change makes separation a challenge. Parathyroid cells often have perinuclear clearing and the nuclei are very small, round, and hyperchromatic, with rather coarse chromatin that suggests a neuroendocrine cell type.

Prognosis and Therapy

No therapy is necessary as this is an incidental finding.

Clinical Features

Patients are usually febrile and complain of chills, malaise, and pain and swelling of the anterior neck. Dysphagia or hoarseness may also be noted. While most patients are euthyroid, occasional patients demonstrate clinical and laboratory evidence of hyperthyroidism or hypothyroidism.

Pathologic Features

Microscopic Findings

The key finding is the presence of polymorphonuclear leukocytes infiltrating the thyroid parenchyma. Microabscesses, foci of necrosis ( Fig. 23.12 ), and vasculitis may be seen. Identification of a causative organism may be possible with histochemical stains, such as tissue Gram stains, Gomori methenamine silver, or periodic acid–Schiff (PAS) stains for fungi or mycobacterial stains (Ziehl–Neelsen). Immunosuppressed patients may develop an acute infectious thyroiditis rather than the typical granulomatous type in response to fungal or mycobacterial organisms. Tissue cultures are invaluable in identifying the organism and in determining its sensitivity to antibiotic therapy.

Ancillary Studies

Differential Diagnosis

Subacute (granulomatous) thyroiditis also involves a neutrophilic infiltrate in its early phase, but it is folliculocentric with accompanying histiocytes, lymphocytes, and multinucleated giant cells. No infectious agent is identified. Secondary infection and acute inflammation can also accompany an underlying malignancy.

Prognosis and Therapy

The prognosis is favorable with treatment and in the absence of underlying predisposing factors such as immunosuppressive states or extensive neck trauma, which may carry their own risk of poor outcome. Appropriate treatment requires identification of the infectious agent, preferably by culture, and initiation of effective antibiotic therapy. If abscesses or areas of infarction are present, surgical incision and drainage or debridement may be necessary.

Clinical Features

The annual incidence in the United States is estimated at 5 per 100,000 population. Women are more commonly affected than men, with a female-to-male ratio of 3.5 : 1. The mean age of onset is in the 5th decade (range, 14 to 87 years). The most common presenting symptom is pain in the thyroid region, sometimes radiating to the jaw. Other complaints include dysphagia, sore throat, low-grade fever, arthralgia, myalgia, tremor, excessive sweating, and weight loss. Physical examination is notable for pain on palpation of the thyroid. The entire gland is usually involved; however, the changes may be localized to one lobe or to a distinct nodule. Thyroid function often varies with disease activity. In the early phase, patients may be hyperthyroid owing to destruction of follicles and release of thyroglobulin. Rarely, a life-threatening thyrotoxicosis or “thyroid storm” occurs early in the disease. With disease progression, thyroid epithelium is destroyed, resulting in hypothyroidism. However, most patients regain normal thyroid function after resolution of the disease.

Radiographic Features

Radioactive iodine (RAI) uptake is decreased.

Laboratory Studies

Serum thyroid-stimulating hormone (TSH) is suppressed and total and free T3 and T4 are elevated early in the course of disease. In the subsequent hypothyroid phase, TSH is elevated and total and free T3 and T4 are low.

Pathologic Features