Thyroid Neoplasms Flashcards
The majority of solitary nodules of the thyroid are what?
Either benign adenomas or localized neoplastic conditions
Carcinomas only account for <1% of solitary thyroid nodules
Clinical criteria for thyroid nodules
Solitary nodules are more commonly neoplastic than multiple
Nodules in very young or old (<20; >70) are more likely to be neoplastic
Nodules in males are more likely neoplastic
History of radiation exposure increases risk of thyroid malignancy
Nodules that uptake radioactive iodine in imaging studies are more likely to be benign
What is the most definitive way to determine thyroid nodules characteristics
Meddle aspiration and staining
Adenomas of the thyroid
Benign neoplasms that are derived from follicular epithelium
Usually are solitary and clinically are difficult to distinguish from dominant nodules
Most are nonfunctional however if they do, they always produce thyrotoxicosis via “toxic adenoma”
Adenoma pathogenesis
Results from driver mutations in the TSH Rc pathway (results in toxic adenomas)
Also mutations in either:
1) TSH receptor itself (more likely)
2) a-subunit of GNAS protein (less likely)
Minority of non functioning follicular adenomas also exhibit mutations in RAS proteins (20%)
Gross Morphology of benign and neoplastic adenomas
Often can look similar however usually
- benign = solitary spherical lesions with less capsule present
- neoplastic = ell-defined intact capsules
the hallmark morphological appearance of an adenoma is a well-formed capsule encircling the tumor
Clinical features of adenomas
Most are painless growths with large masses
Thyrotoxicosis is often present as well as dysphagia if the growth is large enough
Radioactive iodine and adenomas
Most adenomas take up iodine less than normal thyroid tissue
- termed “cold nodules”
- roughly 10% become malignant if untreated
However toxic adenomas take up iodine more than normal thyroid tissue
- termed “hot nodules”
- less than 1% become malignant if untreated
What techniques are used in preoperative evaluation of suspected adenomas?
Ultrasound and fine needle aspiration
Definitive diagnosis require microscopic evaluation for a capsule
- then is pathogenomic
Thyroid carcinomas (CA)
More common in females
All except medullary CAs are derived from the thyroid follicular epithelium and vast majority are well-differentiated lesions
Major subtypes:
- papillary carcinoma (>85% of cases)
- follicular carcinoma (5-15%)
- medullary carcinoma (5%)
- anaplastic carcinoma (<5%)
Broad Thyroid carcinoma pathogenesis
Two pathways down streams from the growth factor receptors
1) RAS/BRAF/MAP kinase pathway
2) PI-3K/AKT pathway
Produces gain-of-function mutations in either or both of these pathways
What is the most common genetic feature of papillary carcinomas
MAP kinase mutations Which do one of two things:
1) rearrangements in genes that encode the receptor tyrosine kinases RET/NTRK1
2) Activating point mutations in BRAF
What is the most common genetic feature of follicular thyroid carcinomas
Both of the following:
1) Gain of function mutation in PI3K
2) Loss of function mutation in PTEN
What is a very unique genetic abnormality seen only in follicular thyroid carcinomas
33-50% of follicular carcinomas possess a unique t(2;3) translocation that disrupts PAX8
- PAX8 is a homebox gene that is important for TH development in thyroid gland follicles
Also shows Peroxisome Proliferator Activated Receptor Gene (PPARG) gene mutations
- is a nuclear hormone receptor that is required for terminal differentiation of cells
Anaplastic carcinomas
Aggressive tumors that can arise de novo but more commonly develop from progression of papillary or follicular carcinomas
Have all the follicular and papillary gene mutations but also present with
- loss of function in TP53
Medullary thyroid carcinoma
Arises from parafollicular C-cells
- NOT follicular epithelium
Pathogenesis is from associated germ-line RET proto-oncogene mutations
- *very common in Multiple Endocrine Neoplasia type-2 (MEN-2)
- also can be sporadic
What is the major risk factor to predisposing thyroid cancer
Exposure to ionizing radiation
(Especially in the first two decades)
Most common cancer caused by this is papillary carcinoma
What cancers is deficiency of dietary iodine associated with?
Higher frequency of Follicular carcinomas
What is the most common form of thyroid cancer
Papillary carcinoma
- can occur at any age and account for vast majority of thyroid carcinomas associated with previous ionizing radiation
- are NON-FUNCTIONAL tumors and are always painless
- if they metastasis = cervical lymph nodes always. Sometimes is also seen in lungs
Common microscopic findings
- “psammoma bodies”
- “ Orphan-Anne-eye” nuclei
- “Pseudo-inclusions”
- bringing papillae
- *There are dozens of different variants but the most common is encapsulated follicular variant
- as long as there is no evidence of inital invasion, these tumors have no potential for malignant behavior**
With radioiodine scans = cold nodules
Are indolent lesions with ten-year survival rates of >95%
What are the main factors associated with prognosis of papillary carcinoma of the thyroid?
Age: >40 yrs = bad
Extra thyroid also extension found = bad
Presence of DISTANT metastasis
- cervical lymph node metastasis doesnt increase mortality
Follicular carcinomas
Accounts for 5-15% of primary thyroid cancers
More common in women (3:1) and manifest with older age than papillary (40-60yrs usually)
Very heavily tied with dietary iodine deficiency
Histologically shows very small follicles and looks kinda like normal thyroid tissues
- can be widely invasive or minimally invasive (minimal = sharply demarcated lesions that look kinda similar to follicular adenomas)
Most often are solitary “cold thyroid nodules”
- rarely can be hyper functional or hot
High rates of metastasis and are more likely than papillary carcinomas to be hematogenous
- can be found in lungs/bones and liver and rarely found in cervical lymph nodes
Prognosis and treatment of follicular carcinoma
Minimally invasive = 10% 10 yr
Widely invasive = 50% to yr
All are treated with surgical resection
Anaplastic carcinoma
Are undifferentiated tumors of thyroid follicular epithelium and accounts for less than 5% of thyroid tumors
Only older people get this >65
25% of patients have a history of well-differentiated thyroid carcinomas and another 25% show concurrent well-differentiated tumors that are respected earlier in life
Are very bulky and rapid growing masses that grow beyond the thyroid capsule into adjacent neck structures (causes mass effect symptoms)
- histologically = highly anaplastic and looks very messy
Are very aggressive and near 100% mortality**
- even with treatment still grows
- metastasis often occurs before symptoms even arise
Medullary carcinomas of the thyroid
Neuroendocrine tumors derived from parafollicular cells/ C cells of the thyroid
These tumors are functional and secrete calcitonin which needs to be monitor for diagnosis and follow-up during and after treatment
- can also secrete somatostatin, serotonin and VIP as well
70% produce sporadically
- 30% produce from familial causes such as Multiple Endocrine Neoplasia type 2A-2B (MEN) or familial medullary thyroid carcinoma without MEN
In sporadic and familial cases without MEN = occurs in 50-60s
In MEN = occurs in 20s or younger
Very commonly, sporadic cases shows mass effect symptoms such as dysphagia and hoarseness
- also shows symptoms related to excess VIP and somatostatin (diarrhea, low GH, etc.)
Medullary carcinoma pathogenesis and morphology
Both familial and sporadic forms are associated with gain of function driver mutations in the RET receptor tyrosine kinase
Morphology:
- gross = solitary nodule that manifests as multiple lesions throughout thyroid lobes with time. Larger nodules show hematologic
- microscopic = composed of polygonal and spindle-shaped cells. Often looks like nests or follicles and can present with calcitonin “amyloid deposits” in stroma
