A parasitic nodule is a thyroid nodule in the neck that is anatomically separate from the main thyroid gland. The background thyroid gland is often a multinodular goiter. The parasitic nodule probably results from a colloid or hyperplastic nodule located outside of the thyroid gland, which becomes enlarged and migrates laterally in the neck

Parasitic nodules range in size from 1 to 4 cm and may be connected to the thyroid gland by a thin strand of fibrovascular tissue or may be completely separate, with a blood supply from the surrounding tissues

The histologic appearance is similar to normal thyroid tissue with hyperplastic or colloid-filled follicles

Metastatic thyroid carcinoma

Thyroglossal duct cyst is a cystic dilation of thyroglossal duct remnant, found along the course of thyroglossal duct (from the posterior tongue down along the anterior midline to below cricoid cartilage). The duct may run anterior to, within, or posterior to the hyoid bone

Thyroglossal duct cysts are usually present in childhood with a midline nodule that may be tender and can be associated with the sinus tract. Fistulas may develop secondary to infection and may open into the pharynx or skin

Heterotopic thyroid tissue associated with the cyst may give rise to thyroid malignancies (papillary carcinoma)

Thyroglossal duct cyst is filled with mucin and measures up to 3 cm in diameter. Normal thyroid tissue may be seen in the wall of the cyst

Thyroglossal duct cysts are usually lined by pseudostratified ciliated or squamous epithelium. The epithelial lining may not be identified if inflammation is prominent. The surrounding stroma shows thyroid follicles and inflammation

Heterotopic thyroid

Branchial cleft cyst

Thyroid neoplasm with cystic degeneration

Acute thyroiditis is usually caused by bacteria, although fungi and viruses have also been implicated. Usually, the thyroid is secondarily involved by a systemic infection or local infection in the neck

Patients often present with chills, fever, and malaise and an enlarged and painful thyroid. Gram-positive organisms such as Staphylococcus aureus, Streptococcus pyogenes, Streptococcus epidermidis, and Streptococcus pneumoniae are most common, but Gram-negative bacilli can also be isolated

The thyroid may be enlarged, with areas of necrosis and abscesses

Acute thyroiditis is characterized by acute inflammation of the thyroid gland with neutrophils and microabscess formation as well as foci of necrosis. Special stains for bacteria and fungal organisms can help identify the organism

Other types of thyroiditis (granulomatous or lymphocytic)

Trauma and ischemic necrosis

Granulomatous inflammation occurs in the thyroid in a variety of conditions including infection, sarcoidosis, foreign body reaction, and reaction to hemorrhage, among others

Granulomatous thyroiditis includes nonsuppurative thyroiditis, subacute thyroiditis, and De Quervain thyroiditis

Women are more commonly affected than men

Granulomatous thyroiditis is usually associated with pain and systemic symptoms such as fever, malaise, and weakness. The clinical course of granulomatous thyroiditis has been divided into hyperthyroid phase, hypothyroid phase, and recovery phase

The etiology is unknown, but some cases of granulomatous thyroiditis are thought to be caused by a viral infection, either systemic or an infection of the thyroid itself. Many patients have recently had an upper respiratory infection, and epidemiology studies have shown association with numerous viruses (mumps, Coxsackie, adenovirus, influenza, Epstein Barr, measles, and mononucleosis, among others)

The overwhelming majority of patients recover in a few months. Mild cases are treated with aspirin, while prednisone is used in severe cases

The thyroid is enlarged (usually asymmetrical) up to twice the normal size. The cut surface shows areas of irregular firm tan tissue among more normal-appearing thyroid tissue

Granulomatous thyroiditis is characterized by patchy uneven involvement of the thyroid by neutrophils and microabscesses early to mixed lymphohistiocytic inflammation and vague, noncaseating granulomata with foreign body-type giant cells centered on and destroying follicles and engulfing free colloid. Patchy areas of fibrosis and regenerating follicles may be seen later in the disease

Autoimmune thyroiditis

Acute thyroiditis

Tuberculosis or mycosis

Sarcoidosis

Palpation thyroiditis

Riedel fibrous thyroiditis is a rare, idiopathic inflammatory process manifested by extensive fibrosis of the thyroid gland, extending beyond the gland into the surrounding tissue and usually involving the cervical musculature

Fibrous thyroiditis may be related to fibrosing mediastinitis and retroperitoneal fibrosis (idiopathic fibrosclerosis)

Patients tend to be adult or elderly (average age = 50 years), with slight female predilection. Patients present with painless, poorly defined thyroid enlargement that is often firm to rock hard

The thyroid gland is enlarged and hard with white fibrous tissue replacing parenchyma and extending into surrounding tissue, obliterating normal anatomic boundaries and extending into adjacent muscles, nerves, and vessels, making excision difficult or impossible

The thyroid shows extensive fibrosis, infiltrating beyond the thyroid into the muscle and other tissue, with keloid-like hyalinized collagen. Areas of more normal uninvolved thyroid are seen. There is a patchy lymphoid and plasmacytic infiltrate

Involved vessels may show mural inflammation and occlusive phlebitis

Giant cells are not prominent, which helps to differentiate Riedel thyroiditis from granulomatous thyroiditis, although granulomatous thyroiditis lacks that extensive fibrosis seen in Riedel thyroiditis

Fibrosing Hashimoto thyroiditis

Granulomatous thyroiditis

Lymphocytic thyroiditis is an autoimmune thyroiditis caused by autoantibodies directed against thyroglobulin and other follicular cell antigens

Lymphocytic thyroiditis is usually seen in children and adults and is more common in women (F:M = 2:1). Patients present with asymptomatic goiter and may have transient hyperthyroidism. The process usually resolves within 1 year

The thyroid shows mild to moderate enlargement and has a slightly nodular appearance

The thyroid shows scattered interstitial lymphoid follicles with germinal centers. The follicles typically show minimal reaction to inflammation, but there may be some mild atrophy or Hürthle cell change

Hashimoto thyroiditis

Graves disease

Hashimoto thyroiditis is an autoimmune thyroiditis characterized by a goiter and circulating antithyroglobulin and antithyroid peroxidase (antimicrosomal) antibodies

Classically, Hashimoto thyroiditis occurs in young to middle-aged females (30–50 years old; F:M = 10:1). Hashimoto thyroiditis is the most common thyroid disease in children and adolescents. Different HLA haplotypes have been associated with Hashimoto disease. Hashimoto thyroiditis is associated with other autoimmune diseases. Hashimoto thyroiditis may be associated with autoimmune disease of adrenals (Addison disease), pancreas (diabetes), or stomach (pernicious anemia). Individuals with Down syndrome have an increased susceptibility to autoimmune thyroid diseases, including Hashimoto thyroiditis

Patients present with diffuse firm goiter, tenderness, and hyperthyroidism. As the disease progresses, thyroid function decreases, eventually resulting in hypothyroidism

There is an increased risk of lymphoma, leukemia, and thyroid carcinoma

The thyroid gland shows diffuse, firm enlargement. The cut surface may show areas of fibrosis and pale tan color due to the chronic inflammatory infiltrate, unlike the beefy red diffuse appearance of the thyroid in Graves disease. Increasing fibrosis is noted with increasing age

The thyroid shows marked interstitial lymphocytic inflammation with prominent lymphoid follicles with germinal centers. The thyroid follicles are small and atrophic lined by oxyphilic epithelium (Hürthle cells). Interstitial fibrosis may accentuate lobular architecture. Regenerative hyperplasia and squamous metaplasia may be seen

Fibrosing Hashimoto thyroiditis

Lymphocytic thyroiditis

Graves disease

Postpartum thyroiditis is an autoimmune disorder, associated with microsomal antibodies, which affects women in the first postpartum year. Postpartum thyroiditis has an early thyrotoxic phase and a longer hypothyroid phase. Histologically, postpartum thyroiditis is shown by focal or diffuse chronic thyroiditis and resembles spontaneous silent thyroiditis. The hypothyroid phase is characterized by follicular disruption and hyperplasia, while focal lymphocytic thyroiditis is seen in the recovery phase

Focal lymphocytic thyroiditis (nonspecific thyroiditis, focal autoimmune thyroiditis) is thought to be an incidental finding, which usually affects elderly, is more common in women than in men, and is relatively common with autopsy studies showing that 20% of thyroids are involved. The thyroid shows dense lymphoid aggregates with or without germinal centers

Graves disease (diffuse hyperplasia) is an autoimmune thyroiditis caused by autoantibodies directed against thyroid-stimulating hormone receptors, resulting in chronic follicular stimulation and hyperthyroidism (diffuse toxic goiter)

Graves disease is most commonly seen in young females (20–40 years old; F:M = 4:1) and may occur in children. In the United States, Graves disease affects about one of every 2,000 people

Patients present with diffuse goiter and hyperthyroidism. Patients often have a family history of autoimmune diseases. Graves disease is diagnosed clinically by physical examination and laboratory testing including elevated serum thyroxine with low TSH and high radioactive iodine uptake

Untreated, Graves disease can cause severe thyrotoxicosis, osteoporosis, and catabolism of muscle and bone with myopathy, among other complication s

The thyroid shows mild to moderate diffuse enlargement and has soft consistency and pink tan color

The thyroid shows markedly hyperplastic follicles lined by active tall columnar cells showing clear, sometimes vacuolated, cytoplasm. Colloid appears pale and depleted, with scalloped edges at the epithelial border. Epithelial hyperplasia resulting in papillae with fibrovascular cores, resembling papillary carcinoma, is characteristically seen

Interstitial lymphoid aggregates with germinal centers may be present

The classic appearance is usually altered by preoperative medication. Iodine therapy can greatly diminish hyperplasia, resulting in an almost normal-appearing gland with involution of the epithelium with cuboidal rather than columnar cells, increased colloid, and decreased vascularity, while propylthiouracil and methimazole therapy are associated with hyperplastic changes

Papillary thyroid carcinoma

Lymphocytic thyroiditis

Hashimoto thyroiditis

Toxic nodular goiters

Goiter means enlarged thyroid gland. Simple nontoxic goiters can be sporadic or endemic. Sporadic nontoxic goiter is the most common nontoxic goiter. Sporadic goiters are identified in approximately 5% of the population, are more common in women, and are uncommon in children. The cause of sporadic goiters is generally unknown, but they can be associated with some medications and may have a hereditary component. When the thyroid cannot produce sufficient thyroid hormone, the gland enlarges to overcome this deficiency. Endemic goiters are seen in areas of iodine deficiency and have become relatively uncommon due to iodized table salt

Most patients are euthyroid, presenting with symptoms of simple or multinodular thyroid enlargement, which may be generalized or have dominant nodule. Goiters may cause obstructive symptoms due to tracheal or esophageal compression and voice change due to laryngeal nerve compression. Goiters are usually slow growing and painless. A sudden increase in growth, a new nodule, or a dominant nodule in a multinodular goiter are concerning for malignancy. Goiters are treated with thyroxine, radioactive iodine, and surgery and can recur

The thyroid gland is enlarged in both simple and multinodular goiters. Simple goiters are diffusely enlarged, while multinodular goiters show multiple nodules grossly. The normal thyroid gland weighs 15–25 g, while goiterous thyroid glands can weigh over a 100 g

The histologic features of goiters can be varied. Goiters are generally composed of a mixture of small follicles with cuboid lining cells and large follicles with flattened lining cells. Large cystic structures showing hyperplastic areas of follicles or papillary structures (foci of secondary proliferation) are often seen

Endemic and sporadic multinodular goiters show similar histologic features

Multinodular goiters show many nodules of different sizes, some encapsulated, compress the adjacent thyroid parenchyma . An individual nodule, particularly a dominant nodule, in a multinodular goiter can be difficult to be distinguished from a follicular adenoma

Degenerative changes with hemorrhage, fibrosis, and calcification are common

Follicular neoplasms

Dyshormonogenetic goiters are usually due to an autosomal recessive genetic defect in the synthesis of thyroid hormone. Although most dyshormonogenetic goiters develop in childhood, they can be identified over a wide age range. Patients present with hypothyroidism, goiter, or growth deficiencies. Patients with congenital goiter and congenital sensorineural deafness have a defect in the Pendred syndrome gene, 7q22–31.1, which encodes pendrin, an iodide/chloride transporter

Dyshormonogenetic goiters are large and multinodular

The nodules are diffusely hypercellular and show an irregular growth pattern. The follicular cells show nuclear atypia and mitotic activity and can be confused with malignancy. Thyroid carcinomas, particularly follicular, can occur in these goiters

Toxic multinodular goiters are multinodular goiters associated with thyrotoxicosis, although these patients lack the ophthalmic changes seen in Graves disease. Multinodular goiters may be present for years and may insidiously become toxic goiters

Grossly toxic multinodular goiters appear similar to nontoxic multinodular goiters. Both are enlarged thyroids composed of multiple nodules with fibrosis

Toxic multinodular goiters are composed of a mixture of hypercellular nodules with tall columnar cells, papillary hyperplasia, and inactive appearing nodules with flat epithelium

The pattern of hypercellular nodules of toxic multinodular goiter differs from that of dyshormonogenetic goiters, which show more diffuse hyperplasia throughout the gland

Papillary thyroid carcinoma (PTC) is the most common thyroid carcinoma, accounting for approximately 80% of thyroid carcinomas. They occur in adults and children, with females being affected more commonly than males. Rare familial PTC can occur

A variety of thyroid disorders including Graves, Hashimoto thyroiditis, and hyperplastic nodules have been identified with PTC. PTCs are associated with a history of radiation exposure, and radiation-associated tumors have been associated with aggressive behavior and solid growth pattern

Papillary thyroid carcinomas are often irregular or well-demarcated masses on ultrasound and cold nodules on radioactive iodine scan

The prognosis of PTC is generally excellent, with overall survival greater than 90%. Poor prognostic factors include increased age (>40 years), male sex, large tumor size, multicentricity, vascular invasion, extrathyroid extension, distant metastases, and dedifferentiation to poorly differentiated and anaplastic thyroid carcinoma. Variants of PTC with more aggressive behavior include tall cell, columnar cell, and solid variant

Papillary thyroid carcinomas are often treated by complete thyroidectomy and ipsilateral lymph node dissection, and radioactive iodine can be used to ablate any remaining tumor

Papillary thyroid carcinomas are variably sized, from microscopic to >10 cm, usually 2–3 cm, solid, white, infiltrating masses, often with a granular cut surface and calcifications. These tumors may be single or multiple and may undergo cystic change

Papillary thyroid carcinomas are composed of complex papillae with single layer or stratified epithelial cells supported by branching fibrovascular cores lined by follicular cells with characteristic cytologic features. Classic cases usually show a predominance of papillary structures, although this feature can be extremely variable. Foci of more follicular areas and solid areas as well as squamous metaplasia can be seen

Diagnostic nuclear features include nuclear enlargement, nuclear irregularity, ground glass nuclei (large optically clear “Orphan Annie” nuclei that tend to overlap), nuclear grooves (due to folded nuclear membrane), and nuclear pseudoinclusions (due to intranuclear cytoplasmic invagination)

Psammoma bodies (laminated basophilic bodies) occur in 50% of cases and are more common in tumors with prominent papillary growth

The colloid in PTC is often darker than that of the surrounding normal thyroid

The stroma is often abundant, fibrous, and sclerotic. A lymphocytic infiltrate can be seen at the periphery of the tumor lobules. Cystic change is common. Mitotic figures and necrosis are uncommon. A significant number of cases (25–75% depending on sampling) show multiple tumor foci

Papillary thyroid carcinomas are positive for thyroglobulin, thyroid transcription factor (TTF1), and keratin (see Table 20.1). Papillary thyroid carcinomas are negative for chromogranin, synaptophysin, and calcitonin. Immunohistochemical markers that may be helpful confirming a diagnosis of PTC include HBME-1, galectin-3, cytokeratin 19, and CITED-1

BRAF mutations and RET/PTC rearrangements are alternative events in the pathogenesis of PTC

BRAF mutations , especially BRAF(V600E), is detected in 36–69% of PTC. BRAF mutations are frequent in PTC with papillary or mixed papillary–follicular growth pattern, Warthin-like PTC, micropapillary PTC, and oncocytic/oxyphilic (Hürthle cell) variant of PTC. BRAF mutations are rarely detected in pediatric or radiation-associated PTC. BRAF mutations are also present in poorly differentiated and anaplastic carcinomas arising from PTC

RET/PTC rearrangement is identified in approximately 20–30% of PTC, although the prevalence varies among geographical sites and tumor subtypes. This rearrangement is particularly common in radiation-associated PTC. RET/PTC1 and RET/PTC3 account for greater than 90% of the rearrangements. RET/PTC1 is more common in papillary microcarcinomas, tumors with classic papillary growth, and a more benign clinical course, while RET/PTC3 is more common in the solid variant of PTC and aggressive behavior

Papillary microcarcinoma

Follicular variant of PTC

Tall cell variant of PTC

Columnar variant of PTC

Solid variant of PTC

Diffuse sclerosing variant of PTC

Oxyphilic (oncocytic/Hürthle cell variant of PTC)

Warthin-like variant of PTC

Cribriform-morular variant of PTC

Clear cell variant of PTC

Papillary thyroid carcinoma with nodular fasciitis-like stroma

Papillary thyroid carcinoma with lipomatous stroma

Hobnail variant of PTC

Graves disease

Hyalinizing trabecular tumor (Figs. 20.21 and 20.22)

Follicular carcinoma

Follicular adenoma

Hürthle cell tumors

Hyalinizing trabecular tumors are unique and can mimic PTC and medullary thyroid carcinoma . The biologic potential has been controversial, but the overwhelming majority of these tumors behave in an indolent fashion. They should probably only be treated as a malignancy when there is obvious capsular or vascular invasion or metastasis

Hyalinizing trabecular tumors are circumscribed, yellow-tan, encapsulated nodules that measuring 0.3–4 cm in diameter

Hyalinizing trabecular tumors are circumscribed or encapsulated solid tumors that show a trabecular growth pattern with prominent extracellular eosinophilic hyaline fibrosis that is reminiscent of amyloid but negative for Congo red

The trabeculae and nests of cells are composed of polygonal and elongated cells with oval nuclei with perinuclolar vacuoles, nuclear inclusions, nuclear grooves, and fine granular cytoplasm. The prominent intranuclear cytoplasmic inclusions can cause confusion with PTC

Cytoplasmic yellow bodies are frequently noted in hyalinizing trabecular tumors, but these are not specific as they can be seen in other tumors

Hyalinizing trabecular tumors are positive for thyroglobulin and TTF1 and negative for calcitonin, chromogranin, and CEA. These tumors also show characteristic cytoplasmic and cell membrane staining for MIB1 (Ki67)

Galectin-3 shows variable staining. HBME-1, a marker that is usually positive in PTC, is negative in hyalinizing trabecular tumors

RET proto-oncogene rearrangements are a common finding in PTC and have been detected by RT-PCR and immunohistochemistry in some cases. However, some of the cases also harbored PTC; thus this finding is difficult to interpret

BRAF mutations are generally not detected in hyalinizing trabecular tumors

Medullary thyroid carcinoma

Papillary thyroid carcinoma

Follicular adenomas are benign, encapsulated tumors showing follicular differentiation

Follicular adenomas occur in 5–10% of the population, predominantly in adults, and are more common in women. Patients present with a palpable nodule showing little to no I131 uptake or as asymmetrical thyroid enlargement

Follicular adenoma is a single encapsulated nodule, 1–3 cm in size. The cut surface varies from gray-tan to pink and fleshy, depending on cellularity and colloid. Larger adenomas may show hemorrhage, cyst formation, fibrosis, and calcification

Follicular adenomas have a complete, usually thin, capsule with compression of surrounding thyroid tissue. No invasion of the capsule or vessels is present

A variety of growth patterns may be seen within the nodule including microfollicular, macrofollicular, trabecular, solid, and focal pseudopapillary architecture, which can be seen occasionally (Figs. 20.23 and 20.24). The growth pattern of cells within nodule classically stands in sharp contrast to appearance of normal thyroid parenchyma outside capsule

Many histologic variants of follicular adenoma have been described as follicular adenoma with bizarre nuclei, adenolipomas, adenochondromas, mucinous follicular adenomas, toxic adenomas, follicular adenomas with clear cell change, follicular adenoma with papillary hyperplasia, and signet ring cell adenomas

Atypical follicular adenomas are cellular tumors, which may show nuclear atypia or irregular growth, but lack definitive vascular or capsular invasion. Atypical adenomas usually behave in an indolent fashion

Follicular adenomas are immunoreactive for thyroglobulin, keratin, and TTF1

Follicular adenomas generally do not show prominent staining for HBME-1, CK19, galectin 3, and CITED as is often seen in PTC

Specific genetic markers diagnostic of follicular adenoma have not been identified. Follicular adenomas frequently show RAS mutations, and a small percentage of tumors may show PAX8 to PPAR gamma (peroxisome proliferator-activated receptor gamma) rearrangements

Follicular thyroid carcinoma

Follicular variant of PTC

Adenomatous nodule

Hyalinizing trabecular tumor (Figs. 20.21 and 20.22)

Follicular c arcinoma is a malignant epithelial tumor showing follicular differentiation and lacking the diagnostic nuclear features of PTC

Follicular carcinomas account for 10–15% of thyroid carcinomas, present as a single palpable neck mass, affect females more commonly than males, and occur at an average age of 50 years. A higher incidence of follicular carcinomas is identified in iodine-deficient regions. These tumors show little or no I131 uptake

Unlike PTC, follicular carcinomas show infrequent regional lymph node metastases

Patients with follicular thyroid carcinomas usually undergo total thyroidectomy. Minimally, invasive follicular carcinomas have an excellent prognosis with a mortality of 5%, while widely invasive carcinomas have a mortality of 50%

Follicular carcinomas are solid, round to oval tumors, tan to brown in color. These tumors may grossly appear encapsulated or may form a poorly circumscribed mass. The capsule is often thicker and more irregular than in follicular adenoma

Widely invasive tumors may show gross capsular or vascular invasion. The cut surface usually appears similar to follicular adenoma (gray-tan to pink and fleshy)

Histologically, follicular carcinoma can be difficult to distinguish from follicular adenoma. Follicular carcinomas are cellular, show a follicular or solid growth pattern, and lack cytologic features of PTC

Vascular invasion or capsular invasion is required for the diagnosis of follicular carcinoma. Capsular invasion often shows a mushroom-type of growth through the capsule. This pattern is different from the linear pattern of tumor associated with hemorrhage, inflammation, and young collagen that is seen in fine-needle aspiration sites

Follicular carcinomas have been classified as minimally and widely invasive based on the amount and type of invasion. Minimally invasive tumors show focal capsular and/or vascular invasion, while widely invasive carcinomas show many areas of invasion. Tumors with capsular invasion only (no vascular invasion) may behave less aggressively than those with vascular invasion. Tumors with prominent vascular invasion may also be referred to as angioinvasive follicular carcinomas

Follicular carcinomas are positive for thyroglobulin, TTF1, and low molecular weight cytokeratin (CAM 5.2) (Table 20.1)

PAX8-PPAR gamma translocation t(2;3)(q13;p25) resulting in a fusion oncoprotein has been identified in a proportion of follicular carcinomas and occasionally in follicular adenomas. Follicular carcinomas with PAX8-PPAR gamma occur in younger patients with smaller, but overtly invasive, tumors, which are usually positive for galectin-3 and negative for HBME-1

RAS mutations appear separate from PAX8-PPAR gamma translocations. Follicular carcinomas with RAS mutations are often positive for HBME-1 and negative for galectin-3

Follicular adenoma

Papillary carcinoma, follicular variant

Hürthle cell adenomas are benign thyroid neoplasms composed exclusively or predominantly of Hürthle cells (oxyphil cells, oncocytes). Women are affected more commonly than men. The mean age at diagnosis is 55 years. These tumors are solitary nodules on ultrasound and show little or no I131 uptake

Hürthle cell adenomas are solid tumors, round to oval in shape, encapsulated, and have a brown cut surface typical of oncocytic tumors. Areas of hemorrhage, cyst formation, or calcification may be seen in larger tumors. Infarction can be seen in tumors that have undergone fine-needle aspiration biopsy

Hürthle cell adenomas are encapsulated and lack capsular or vascular invasion

The tumors can show a variety of growth patterns including follicles, solid areas, trabecular growth, and papillary growth. They are composed of at least 75% Hürthle cells, which are polygonal cells with abundant granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Areas of nuclear pleomorphism (“endocrine atypia”) may be identified

Hürthle cell adenomas are positive for thyroglobulin and TTF1 and are negative for chromogranin, synaptophysin, and calcitonin

Hürthle cell carcinoma

Hyperplastic Hürthle cell adenomatous nodule in Hashimoto thyroiditis

Adenomatous Hürthle cell nodules are multiple, lack a well-defined capsule, and are associated with a prominent lymphoplasmacytic infiltrate

Hürthle cell/oxyphil/oncocytic variant of PTC

Hürthle cell adenomas lack cytologic features classic of PTC

Hürthle cell carcinomas are malignant neoplasms composed predominantly or exclusively of Hürthle (oncocytic/oxyphilic) cells

Hürthle cell carcinoma accounts for 2–3% of thyroid carcinomas. Women are more commonly affected than men. The mean age at diagnosis is 55 years. Hürthle cell carcinoma is a well-demarcated nodule on ultrasound and shows little or no I131 uptake

Hürthle cell carcinomas are slightly more aggressive than follicular carcinomas and have an overall 5-year survival of 50–60%. Hürthle cell carcinomas show extrathyroidal invasion more frequently than follicular carcinomas and show lymph node metastases more often than follicular carcinomas. However, the most common sites of metastases are lung and bone, followed by regional lymph nodes. Poor prognostic factors include large tumor size and vascular invasion

Hürthle cell carcinomas are solid, encapsulated, round to oval tumors, with a brown cut surface. They are generally larger than adenomas and have a thicker more irregular capsule. Widely invasive tumors may show gross invasion of the capsule or vessels

Hürthle cell carcinomas are cellular tumors, composed of at least 75% Hürthle cells, and show a follicular, solid, or trabecular growth pattern. Hürthle cells are large polygonal cells with round nuclei and nucleoli and abundant granular eosinophilic cytoplasm and lack cytologic features of papillary thyroid carcinoma

Vascular or capsular invasion is required for the diagnosis of Hürthle cell carcinoma. Capsular invasion often shows a mushroom type of growth through the capsule. This pattern is different from the linear pattern of tumor associated with hemorrhage, inflammation, and young collagen that is seen in fine-needle aspiration sites. Hürthle cell carcinomas have been classified as minimally or widely invasive based on the amount and type of invasion. Minimally invasive tumors show focal capsular and/or vascular invasion, while widely invasive follicular carcinomas show many areas of invasion

Hürthle cell carcinomas are immunoreactive for thyroglobulin, although staining is not as strong as other thyroid follicular neoplasms (Table 20.1). Hürthle cell carcinomas are also positive for TTF1 and are negative for chromogranin, synaptophysin, and calcitonin

Numeric chromosomal abnormalities include changes in p53 and cyclin D1 and chromosomal gains and have been identified in Hürthle cell carcinomas. These tumors tend to show more chromosomal losses than adenomas. PAX8-PPAR gamma rearrangements and RAS mutations are not frequent in Hürthle cell carcinomas. GRIM-19 point mutations were the first mutation relatively specific to Hürthle cell tumors

Hürthle cell adenoma

Hürthle cell/oxyphilic variant of PTC

Oxyphilic variant of medullary thyroid carcinoma

Poorly differentiated carcinomas are follicular cell neoplasms that are in between well-differentiated follicular and papillary carcinomas and undifferentiated or anaplastic carcinomas

Patients usually present with a large solitary thyroid mass . They often have a history of recent thyroid enlargement or enlargement of a tumor that has been present for a number of years. Patients are usually >50 years of age, and women are affected more commonly than men. Poorly differentiated thyroid carcinomas appear to be more common in Italy and Latin America

Treatment is total thyroidectomy with resection of any involved lymph nodes and radioactive iodine therapy. The prognosis is relatively poor with lymph node, with distant metastases being relatively common. The 5-year survival rate is approximately 50%

Poorly differentiated tumors are large, have a pale, gray-white cut surface with areas of necrosis and may have a pushing border, extrathyroid extension, and satellite nodules

These tumors can show a variety of growth patterns including insular, trabecular, and solid. Some authors refer to tumors showing an insular or trabecular growth pattern growth as “insular carcinomas.” Tumors may also show a characteristic “peritheliomatous” pattern of growth with extensive necrosis with preservation of viable cells around vessels. The tumor cells may show nesting or sheetlike growth with necrosis and vascular invasion frequently identified. The tumor cells are small and uniform with vesicular or hyperchromatic nuclei, small nucleoli, and prominent mitotic activity. Areas resembling papillary or follicular carcinomas are identified in association with some tumors, raising the possibility that these tumors may have dedifferentiated. Recent studies have suggested diagnostic criteria of solid/trabecular/insular growth, absence of papillary thyroid carcinoma cytologic features, and the presence of one of the following criteria (convoluted nuclei or 3 or more mitoses per 10 high power fields or tumor necrosis). Others find high-grade features, mitotic index, and necrosis to be most helpful diagnostically regardless of growth pattern

These tumors are positive for thyroglobulin, low molecular weight kininogen, and TTF (see Table 20.1). If present, TP53 nuclear staining is usually focal and high Ki67 index is common

Mutations of H-, K-, and N-RAS are identified in 50% of poorly differentiated carcinomas. Mutations of TP53 mutations are present in 20–30%, and p53 overexpression is present in 40–50%. A small percentage of tumors may show BRAF mutation, RET/PTC, or NTRK1 rearrangements

Medullary thyroid carcinoma

Follicular carcinoma

Solid variant of PTC

Metastatic carcinomas to the thyroid

Anaplastic (undifferentiated) thyroid carcinoma is a highly malignant tumor composed in part or entirely of undifferentiated cells with immunohistochemical and ultrastructural features supporting epithelial differentiation

These tumors usually present as a rapidly expanding mass with symptoms of regional invasion (dysphagia, dyspnea, or dysphonia) in elderly patients. Females are affected more commonly than males (1.5:1)

At surgery, invasion of adjacent structures including the neck muscles, trachea, esophagus, laryngeal nerve, and larynx is common. Almost half of all patients have distant metastases at diagnosis. The most common metastatic sites include the lung, bone, and brain. These are highly aggressive tumors with a mortality rate of greater than 90% and a mean survival of 6 months

The tumors are grossly invasive, replace the thyroid, and extensively involve regional neck structures. The tumors have a white to tan cut surface and are firm to hard. Hemorrhage and necrosis are common