Term
| what are solitary thyroid nodules more likely to be? |
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Definition
| neoplastic (but may not be malignant) |
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Term
| what are thyroid nodules more likely to be in younger pts? |
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Definition
| neoplastic (but may not be malignant) |
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Term
| what are thyroid nodules in male pts more likely to be? |
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Definition
| neoplastic (but may not be malignant) |
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Term
| hx of what is associated with a greater incidence of thyroid CA? |
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Definition
| radiation of the head/neck |
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Term
| if a nodule is hot and takes up radioactive iodine, what is it likely to be? |
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Definition
| benign - b/c they are still functional |
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Term
| what characterizes adenomas found in the thyroid? |
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Definition
| thyroid adenomas are discrete, solitary masses derived from follicular epithelium (also called follicular adenomas). these may mimic follicular hyperplasia or CA, but can be differentiated via fine needle aspiration. thyroid adenomas generally *don't give rise to CA, most are non-functional but still produce some thyroid hormone. |
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Term
| what genetic mutations are found in thyroid adenomas? |
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Definition
| mutations in RAS, PIK3CA, PAX-PPARG, TSHR, and GNAS |
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Term
| how do thyroid adenomas appear grossly? |
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Definition
| *encapsulated (helps differentiate from CA), well demarcated, avg 3 cm (can be much larger), gray-white to red brown, and often encroaching on adjacent thyroid |
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Term
| what kind of change can thyroid adenomas go through? |
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Definition
| fibrotic, hemorrhagic, calcific, and cystic change (doesn't automatically indicate malignancy). thyroid adenomas tend to form *uniform follicles that produce colloid* and their growth patterns are usually distinct from the non-neoplastic thyroid. little pleomorphism is found in thyroid adenomas. |
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Term
| what is a hurthle cell adenoma? how does it appear histologically? |
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Definition
| a thyroid adenoma w/cells containing *eosinophilic granular cytoplasm. histologically: crowded sheets of eosinophilic, granular cells |
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Term
| how do thyroid adenomas appear histologically in general? |
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Definition
| uniform follicles in size/shape (monomorphic w/little pleomorphism or mitotic figures) w/a slightly more crowded growth pattern. |
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Term
| what is the pathogenesis of thyroid neoplasms? |
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Definition
| genetic alterations along w/environmental factors |
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Term
| what are the genetic associations w/papillary thyroid CA? |
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Definition
| either RET or NTRK1 (neutrophilic tyrosine kinase receptor) rearrangements, both of which lead to formation of *RET/PTC proteins* which activate the MAP kinase pathway. point mutations in *BRAF can also activate the MAP kinase pathway. these mutations are especially common in pts who have been exposed to radiation. typically, only one of these pathways will be demonstrated in papillary thyroid CA. |
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Term
| what are the genetic associations w/follicular thyroid CA? |
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Definition
| 1/3 have oncogenic mutations in the *PI-3K/AKT signaling pathways. gain of function mutations are seen in RAS and PIK3CA. loss of function mutations are found in the tumor suppressor gene *PTEN. some cases have a fusion gene composed of *PAX8 and PPARG* (peroxisome proliferation-activated receptor gene), which results in cell growth/proliferation. |
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Term
| what are the genetic associations w/anaplastic thyroid CA? |
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Definition
| anaplastic thyroid CA may form de novo or from a well differentiated papillary/follicular CA. there may be genetic changes in RAS, PIK3CA, inactivation of p53, and activation of beta-catenin. |
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Term
| what are the genetic associations w/medullary thyroid CA? |
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Definition
| familial: MEN2 or germline mutations of the RET proto-oncogene |
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Term
| what environmental factors are associated w/thyroid CA formation? |
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Definition
| ionizing radiation esp during the first 2 decades of life (which is linked particularly to papillary CA) and deficiency of dietary iodine (which is linked specifically to follicular CA) |
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Term
| what characterizes papillary thyroid CA? |
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Definition
| this is the *most common form of thyroid CA and usually occurs in pts between 25-50 y/o. papillary thyroid CA accounts for most thyroid CA linked to ionizing radiation (get good occupational hx). |
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Term
| how does papillary thyroid CA appear grossly? |
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Definition
| solitary or multifocal, may be well circumscribed and encapsulated (may mimic adenoma) - some may infiltrate the parenchyma w/ill-defined margins and papillary thyroid CA may contain fibrosis+calcifications. |
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Term
| how does papillary thyroid CA appear histologically? |
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Definition
| papillary thyroid CA may be cystic (like adenomas) and often there is *branching papillae w/a fibrovascular stalk covered by multiple layers of cuboidal epithelial cells. there may be varying degrees of pleomorphism and well differentiated cells. the cells have *optically clear nuclei* (orphan annie eyes), *nuclear grooves (invaginations of cytoplasm), and *psammoma bodies (layered concretions, seen more in the cores of the papillae) |
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Term
| what characterizes patterns of spread with papillary CA? |
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Definition
| lymphatic invasion is more common than vascular - metastasis to adjacent lymph nodes occurs in ~50% of cases. |
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Term
| what is the follicular variant of papillary CA? genetic associations? |
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Definition
| a type of papillary CA which has the characteristic optically clear nuclei, but has more follicular architecture. these tend to have a lower frequency of RET/PTC rearrangements, more RAS mutations, and a distinct BRAF mutation. the follicular variant also has a lower incidence of lymph node metastasis and extra-nodal invasion. |
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Term
| what is the tall cell variant of papillary CA? |
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Definition
| these have more tall columnar cells, occur in older pts, and have a higher incidence of metastasis and extension |
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Term
| what is the diffuse sclerosing variant of papillary CA? |
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Definition
| these occur in younger pts/children and feature extensive fibrosis w/a *prominent lymphocytic infiltration and frequent lymph node metastasis. the diffuse sclerosing variant of papillary CA lacks BRAF mutations but does have RET/PTC translocations. |
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Term
| what is a papillary microadenoma? |
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Definition
| these are less than 1 cm and are confined to the thyroid |
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Term
| how does papillary thyroid CA present clinically? |
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Definition
| initially asymptomatic, an enlarged cervical lymph node may be the first sign - as the tumor advances, signs include hoarseness, dysphagia, cough and dyspnea. if hematogenous spread does occur, the target is usually the lung. papillary thyroid CA produces cold nodules and pts w/this CA have an excellent 10 year prognosis. |
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Term
| what characterizes follicular thyroid CA? |
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Definition
| follicular CA is more common in women 40-60 y/o and is associated w/*iodine deficiency. follicular CA represents 5-15% of primary thyroid CA. |
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Term
| how does follicular thyroid CA appear grossly? |
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Definition
| follicular CA appears as single nodules (follicles) which may be well circumscribed or infiltrative and the more sharply demarcated lesions may look similar to a benign adenoma. on cut section, follicular thyroid CA is gray-tan and may be translucent due to large colloid-filled follicles. there may also be central fibrosis+calcification |
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Term
| how does follicular thyroid CA appear histologically? |
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Definition
| fairly uniform cells forming small follicles w/colloid closely resembling normal thyroid |
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Term
| what is the hurthle cell variant of follicular thyroid CA? |
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Definition
| in this, the cells have abundant granular eosinophilic cytoplasm but lack the nuclear features of papillary CA |
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Term
| what is a necessary precaution with minimally invasive follicular thyroid CA? |
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Definition
| extensive sampling to determine if *capsular or vascular invasion is present b/c *minimally invasive follicular thyroid CA may resemble an adenoma |
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Term
| is lymphatic spread common w/follicular thyroid CA? |
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Definition
| no, unlike papillary thyroid CA |
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Term
| how do follicular thyroid CA present clinically? |
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Definition
| as slowly enlarging painless nodules, most of which are "cold" and rarely involve lymphatics - but may involve vasculature to the bones, lungs, and liver. widely invasive lesions have a 50% 10 year survival, and the prognosis is improved greatly w/the minimally invasive variant. |
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Term
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Definition
| these undifferentiated tumors are composed of *highly anaplastic cells, *large giant cells, and *spindle cells w/sarcomatoid appearance. they account for less than 5% of thyroid tumors - but are very aggressive w/a mortality rate close to 100%. they may be positive for *cytokeratin, but are usually negative for thyroglobulin. |
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Term
| how does anaplastic CA present? |
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Definition
| as a rapidly growing large neck mass which usually spreads into the neck structures and often metastasizes to the lungs. symptoms: dyspnea, hoarseness, dysphagia, and cough. |
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Term
| what is medullary thyroid CA? |
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Definition
| these neuroendocrine tumors are derived from *parafollicular cells/C cells of the thyroid and account for 5% of thyroid tumors. medullary thyroid CA secretes *calcitonin as well as serotonin and ACTH. |
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Term
| what genetics are associated w/medullary CA? |
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Definition
| about 70% are sporadic but the remainder occur in the setting of MEN 2A-B. medullary thyroid CA has *activating point mutations in the RET proto-oncogene in both the sporadic and familial types. |
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Term
| how does medullary CA present grossly/histologically? |
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Definition
| the sporadic type presents as a solitary nodule while the familial type presents w/multicentricity and bilaterality. the larger lesions will have some hemorrhage+necrosis and the tissue appears firm pale gray to tan and infiltrative. histologically: polygonal to spindle-shaped cells may form nest, trabeculae and follicles. membrane-bound electron dense granules are seen in the cytoplasm. often amyloid deposits are seen and C-cell hyperplasia is seen in the familial type. |
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Term
| how does medullary thyroid CA present? |
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Definition
| sporadic cases present as a neck mass w/dysphagia and/or hoarseness (mass effects). familial cases often initially present w/endocrine neoplasms in other organs. medullary thyroid CA may manifest as paraneoplastic syndrome if hormones are secreted. |
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