Week 7: Thyroid Cancer Flashcards
What is a thyroid nodule?
starts with the growth of a thyroid epithelial cell that escapes normal cell division regulation and leads to continuous growth and eventually leads to a clinically evident tumor mass
What causes thyroid nodules?
Mutations in both oncogenes and/or tumor suppressor genes
Types of thyroid nodules
- Solitary nodules (monoclonal)
- Multinodular goiters (polyclonal)
Prevalence of thyroid nodules and how thyroid nodules are found
Majority of nodules that are benign
Histological features of benign thyroid nodules
- follicular cells
- absence of capsular and vascular invasion
benign thyroid nodules AKA
Benign follicular adenomas
Workup of a thyroid nodule
Functional assessment
- check TSH (hypo or hyperthyroidism)
Anatomical assessment
- imaging
If TSH is low with thyroid nodule
Obtain radioactive iodine scan
To determine if the nodule is a “hot” nodule
What is a “hot” nodule?
Rarely malignant
if they take up a lot of radioactive iodine
What is a “cold” nodule
doesn’t uptake radioactive iodine
most are benign but some are malignant
What is the preferred imaging study for the thyroid and thyroid nodules
Ultrasound
Features of interest of thyroid nodules by ultrasound
What is Echogenicity and what does it indicate?
How dark or light appearing on ultrasound
Often less echogenic nodules are malignant (darker = malignant) AKA Hypoechoic
Ultrasound features of malignant thyroid nodules
Hypoechoic
microcalcifications
irregular margins
taller than wide
Size of nodules to be biopsied
1 cm or larger
Low suspicion thyroid nodules on ultrasound
Moderate suspicion thyroid nodules on ultrasound
Very low suspicion thyroid nodules on ultrasound
spongiform
partially cystic
lacking suspicious features such as having irregular margins
Thyroid cysts chance of malignancy
Very low
TI-RAD system
system used to report on thyroid nodule imaging
Features of highly suspicious thyroid nodules
Features of low suspicious thyroid nodules
Classifications of thyroid cancers
4 listed
- Well-differentiated thyroid carcinomas
- undifferentiated thyroid carcinomas
- medullary thyroid carcinoma
- thyroid lymphomas
Most common thyroid cancer
Papillary thyroid carcinoma
Papillary thyroid carcinoma derived from
Thyroid follicular cells
Histological features of Papillary thyroid carcinoma
- Orphan Annie Nuclei (clearing out of chromatin/white appearance to nuclei)
- Sonoma bodies (necrosis)
- can be calcifications
- nuclear grooves
Prevalence/ epidemiology of papillary thyroid carcinoma
most common thyroid cancer (70-90% of cases)
Female predominate
2.5:1
Aged 40-50
Risk for Papillary thyroid carcinoma
- Hx of radiation in childhood
- FHx of thyroid cancer
- female Aged 40-50
the trend of papillary thyroid carcinoma
Pathogenesis of papillary thyroid carcinoma
Activating point mutations in tyrosine kinase MAPK pathway in RAS or BRAF constitutively activating it
Also associated with RET gene
Physical features of papillary thyroid carcinoma
Can be multifocal and invades locally
Indolent
Prognosis of papillary thyroid carcinoma
25-year mortality in patients younger than 40-> 2%
small % of patients have increased mortality
- older patients
- large tumor size
- soft tissue invasion
- Distant metastases 2-10%
Follicular thyroid carcinoma prevalence
10% of all thyroid cancers
Follicular thyroid carcinoma epidemiology
10% of all thyroid cancers
aged 40-60
Female 3:1
Follicular thyroid carcinoma derived from?
Follicular cells
Follicular thyroid carcinoma Dx
is difficult to Dx by FNA (biopsy)
Risk factors of Follicular thyroid carcinoma
- Associated with childhood radiation
- FHx thyroid cancer
- Iodine deficiency
Follicular thyroid carcinoma Pathogenesis
point mutations in RAS oncogene
- 40%
Gene rearrangement
PAX8-PPARγ translocation
Follicular thyroid carcinoma genetics
RAS
or
PAX8 (chromosome 2) -PPARγ (Chromosome 3) translocation
Follicular thyroid carcinoma gross histology
uninodular
Lymph node is not usually involved
Distant metastases (usually in the lung and bone)
Prognosis of Follicular thyroid carcinoma
Hurthle cell carcinoma epidemiology
3-10% of differentiated thyroid cancers
Hurthle cell carcinoma features
tends to be more aggressive
lymph nod involvement is common
Highest incidence of metastases
Hurthle cell carcinoma prognosis
10 year disease-free survival is 41%
Well-differentiated thyroid carcinoma clinical presentation
Well-differentiated thyroid carcinoma Dx
thyroid ultrasound
Fine needle aspiration of nodules
Surgical Treatment of Well-differentiated thyroid carcinoma
Complications of total thyroidectomy
Damage to recurrent laryngeal and superior laryngeal artery (can cause tracheostomy placed)
Hoarseness
vocal paralysis
Hypocalcemia due to parathyroid gland function
Rx Treatment of Well-differentiated thyroid carcinoma
I-131 treatment
the radioactive form of iodine that destroys any form of the cancer present
How does I-131 treatment work for thyroid cancer
pretreatment of TSH or thyroid hormone withdrawal to maximize radioactive iodine uptake
low iodine diet
cause thyroid cell death by β-particle emission
Monitoring of well-differentiated thyroid carcinoma
Medullary thyroid carcinoma derived from
Parafollicular cells
Medullary thyroid carcinoma histological features
Medullary thyroid carcinoma epidemiology
4% of thyroid carcinomas
Medullary thyroid carcinoma associations
Most are sporadic but…
Familial neoplastic syndromes (25% of cases)
- Men 2A and @b, familial medullary thyroid carcinoma
Medullary thyroid carcinoma pathogenesis
RET somatic or germline mutations
HRAS and/or KRAS mutations
Medullary thyroid carcinoma charateristics
secretes:
calcitonin
sometimes secretes CEA
Medullary thyroid carcinoma clinical presentation
solitary nodule
predominatly located in the upper portion of each thyroid lobe
70% lymph node involvement
symptoms of compression
5-10% dital metasteses (Liver, Lungs, Bones)
Medullary thyroid carcinoma prognosis
Medullary thyroid carcinoma Treatment
types of Undifferentiated thyroid carcinoma
Anaplastic thyroid carcinoma
and
Anaplastic thyroid carcinoma epidemiology
0.9-9.8% of thyroid cancers
65 years old
female predominance 60-70% of cases
Anaplastic thyroid carcinoma derived from
Follicular cells
Anaplastic thyroid carcinoma associations
20% of patients have a Hx of undifferentiated thyroid cancer
20-30% have coexisting differentiated cancer
Mean age at Dx is 65
Anaplastic thyroid carcinoma clinical presentation
Anaplastic thyroid carcinoma evaluation
Anaplastic thyroid carcinoma prognosis
moratility approaches 100%
6 months without metastases
Treatment of Anaplastic thyroid carcinoma
- Surgery
- Radiotherapy
- Chemotherapy
Thyroid follicular cells proliferative pathways
Thyroid lymphoma epidemiology
2% of thyroid cancers
Thyroid lymphoma associations
Hashimoto’s Thyroiditis
Thyroid lymphoma types
60-80% are large B-cell lymphomas
30% are extranodal marginal zone lymphomas
Thyroid lymphoma histological features
Thyroid Lymphoma Clinical presentation
Thyroid lymphoma evaluation
Thyroid lymphoma treatment
Prognosis of Thyroid lymphoma
MEN1 AKA
Multiple Endocrine Neoplasia Type 1
MEN1 pathogenesis
Autosomal dominant inheritance of MEN1 gene
Produces Menin
tumor suppressor on chromosome 11
MEN1 tumors
Pituitary tumors
Parathyroid tumors
Pancreatic tumors
Dx of MEN1
Signs and symptoms of Parathyroid tumors
Signs and symptoms of Pituitary tumors
Signs and symptoms of Pancreatic tumors
MEN1 Treatment
MEN2A AKA
Multiple Endocrine Neoplasia Type 2A
MEN2A pathogenesis
Autosomal dominant inheritance
Germiline mutation in RET protooncogene
Tyrosine kinase receptor in cells of neural crest origin
MEN2A clinical presentation
Parathyroid hyperplasia
MEN2A structures involved
MEN1 structures involved
Treatment of MEN2A
MEN2B pathogenesis
autosomal dominant inheritance
Mutation in RET proto-oncogene
MEN2B components
MEN2B clinical presentations and structures invovled
What are mucosal neuromas? And what condition are they found in?
MEN2B
MEN2B hallmark
Marfinoid habitus
Genetic testing in MEN2
