Thyroid Pathology Flashcards
Essential action of the thyroid
Increase BMR
How is T3 and T4 released?
Thyroglobulin (Tg) is synthesized and stored in colloid.
Iodide is transported into the cell and incorporated into Tg to form iodinated tyrosines.
Tg is endocytosed and cleaved to release free T3 and T4.
What are 3 subtypes of Primary Hyperthyroidism?
Diffuse hyperplasia (Graves disease) Hyperfunctioning multinodular goiter Hyperfunctioning thyroid adenoma
Which kind of hyperthyroidism is most common?
Primary hyperthyroidism
What is the 1 secondary hyperthyroidism?
Pituitary adenoma
Describe the 3 variants of hyperthyroidism:
Apathetic hyperthyroidism
Regular hyperthyroidism
Thyroid storm
Apathetic hyperthyroidism - older adults w/ masked symptomatology; unexplained weight loss; CVD
Regular hyperthyroidism - sweating, flushing, psychiatric changes, palpitations/tachycardia, exophthalmos, jitters
Thyroid storm - extreme and abrupt episode of potentially life-threatening thyrotoxicosis
Which drug can precipitate thyroid storm?
Amiodarone
What are the the levels of TH and TSH in primary and secondary hyperthyroidism?
Primary: elevated TH, low TSH
Secondary: elevated TH, high TSH
Treating the manifestations of hyperthyroidism:
Treating the underlying disease of hyperthyroidism:
Manifestation: beta-blockers, NSAIDs
Underlying Dz: high-doses of iodide (Wolff-Chaikoff effect), Thionamide, Radioiodine ablation, surgery
Graves disease is the most common…
What 3 things is it characterized by?
Etiology of hyperthyroidism.
- Hyperthyroidism w/ gland enlargement
- Infiltrative ophthalmopathy
- Pretibial myxedema - infiltrative dermopathy and scaly, indurated skin
Graves disease-associated orbitopathy/ophthalmopathy is characterized by… (2)
Thickened EOM + Retraction of eyelids w/ associated proptosis
5 steps of pathogenesis of Graves disease affecting the orbit
- Lymphocytes invade pre-orbital space
- Fibroblasts have TSH receptor
- EOM swelling
- Matrix accumulates
- Adipocytes expand
Levels of the following in Graves disease:
T3/4
TSH
TSI (thyroid-stimulating Ig)
T3/4 - high
TSH - low
TSI (thyroid-stimulating Ig) - high
Features of Congenital Hypothyroidism (Cretinism) (4)
Where is it endemic?
It can be a result of…
MR, GR, coarse facial features, umbilical hernias.
Areas without iodine supplementation (depends on time of onset in the mother).
Genetic alterations in normal thyroid metabolic pathways.
Myxedema occurs in which ages?
What are symptoms? (4)
Adults and older children
Mental and physical sluggishness
Weight gain
Cold intolerance
Cardiac effect - lower CO, hypercholesterolemia
Hashimoto thyroiditis =
It is the most common cause of…
How does the thyroid gland appear?
What is the level of thyroid function? Any exceptions?
What’s the progression?
Auto-Abs against thyroglobulin (Tg) and thyroid peroxidase (TPO).
Most common cause of hypothyroidism in iodide-sufficient areas.
Thyroid is diffuse, painless and enlarged.
Hypothyroid (usually), but can be hyperthyroid if Hashitoxicosis.
Progression:
- Immune-mediated insult
- Hyperactivity and enlargement
- Follicular cell exhaustion
How does Hashimoto’s thyroiditis appear on histology? (2)
Lymphocytic infiltrate w/ germinal centers.
Atrophic cells with eosinophilic change (Hurthle cell metaplasia).
What auto-antibodies are there in Hashimoto’s vs. Graves?
Hashimoto’s:
- TSHR-Ab (TSI) - 10-20%
- hTg-Ab - 80-90%***
- hTPO-Ab - 90-100%***
Graves:
- TSHR-Ab (TSI) - 80-95%***
- hTg-Ab - 50-70%
- hTPO-Ab - 50-80%
Subacute lymphocytic thyroiditis presents how?
Example:
What may it progress to?
A transient period of thyroid hormone irregularities.
- hyperthyroidism (occasionally hypothyroidism)
- goiter
Postpartum thyroiditis.
May progress to permanent hypothyroidism.
Granulomatous (de Quervain’s) thyroiditis presents how?
What is its origin?
What does it usually get lumped in with?
Painful granulomata.
Possibly viral (i.e. mumps).
Subacute thyroiditis.
Associated disease with HLA-B35 =
Granulomatous (de Quervain’s) thyroiditis
What occurs to the thyroid tissue in Riedel thyroiditis?
What cells are in high concentration?
Which group of disease is it in? What are the hallmarks?
It is a fibrosing process that extends into the adjacent tissue. “Feels like cement”.
Plasma cells and lymphocytes (in addition to fibrosis).
IgG4-related disease - fibrosis and IgG4+ plasma cells are hallmarks of these diseases.
Hashmoto’s in review
Cause
Histology
Thyroid state
Level of TPO Ab’s
Cause: autoimmune
Histology: lymphocytes
Thyroid state: hypothyroid
Level of TPO Ab’s: high titer
Subacute lymphocytic thyroiditis in review
Cause
Histology
Thyroid state
Level of TPO Ab’s
Cause: autoimmune
Histology: lymphocytes
Thyroid state: hypo- or hyperthyroidism
Level of TPO Ab’s: high titer
Granulomatous (de Quervain’s) thyroiditis
Cause
Histology
Thyroid state
Level of TPO Ab’s
Cause: unknown (viral?)
Histology: granulomata
Thyroid state: hypo- or hyperthyroidism
Level of TPO Ab’s: low or absent titer
Riedel thyroiditis
Cause
Histology
Thyroid state
Level of TPO Ab’s
Cause: unknown (IgG4-related)
Histology: fibrosis
Thyroid state: euthyroid (normal function)
Level of TPO Ab’s: variable
Diffuse non-toxic goiter
What “types” of goiter can it be?
Endemic goiter - iodine deficiency
-Goitrogens: Cassava root (thiocyanate) and Brassicaceae (broccoli, cauliflower, cabbage and radishes)
Sporadic goiter: more common in females and unknown etiology.
What symptoms often come with diffuse goiters?
What is the thyroid function like?
Symptoms due to mass effect: dysphagia, hoarseness, stridor, SVC syndrome.
Usually euthyroid.
What are some features of a multinodular goiter? (3)
What symptoms?
What is unique about them?
Hyperplasia, regression (involution) cycle.
Varied response of nodules to stimuli.
Neoplastic nature of some nodules (adenomas).
Mass effect symptoms - same as diffuse goiters.
May become strikingly large!
What does Radioisotope scanning (thyroid scintigraphy) used for?
What “types” of nodules might it reveal? (2)
What should be done if you find one of these nodules?
Determining which nodule is responsible for hyperfunction (if so, it can be treated w/ excision or ablation).
Hot or cold nodules.
- hot nodules will be treated with iodine or surgery.
- cold nodules are more likely to be neoplastic and get a US and FNA.
Benign thyroid nodules (2)
Hyperplastic (adenomatoid) nodules + Follicular adenomas
Follicular adenomas =
They are benign, but what must you evaluate to be certain? (2)
Discrete clonal population of follicular cells w/ “thyroid autonomy”.
- Capsule intact - no growth pattern of follicular carcinoma.
- No nuclear features of papillary carcinoma.
What is the most common malignant tumor of the thyroid gland?
What age do they most often occur?
How do they present?
What imaging should be ordered?
Papillary thyroid carcinoma
25-50 y/o
Typically w/o symptoms as a palpable nodule.
Order a US.
What histologic finding is seen in Papillary thyroid carcinoma?
What are 2 mutations associated with it?
Psammoma bodies and papillary architecture.
RET-PTC mutations + BRAF mutations
What is the diagnostic feature allowing for a diagnosis of Papillary thyroid carcinoma?
Nuclear characteristics - enlarged nuclei w/ “clear” appearance.
“Orphan Annie Eye nuclei”
Follicular variant of Papillary thyroid carcinoma have which histological features?
What genetic changes are common?
Follicular architecture, but nuclear features of papillary carcinoma.
More cases w/ RAS mutations (similar to follicular carcinomas/adenomas) - less with RET-PTC and BRAF mutations
Tall cell variant of Papillary thyroid carcinoma has a predilection for which age group?
Older patients
Which thyroid carcinoma is considered highly aggressive?
Tall cell variant of papillary carcinoma
Diffuse sclerosing variant of Papillary carcinoma
What age groups?
Where are the metastases?
What is the disease survival rates at 10 years?
Kids and young adults.
Greater incidence of distant mets (10-15%) - lung, brain, bone and liver. Despite these mets, mortality rates are comparable to those of conventional PTCs.
93% survival rate at 10 years.
Follicular carcinomas are more common in which areas?
Which mutations are associated?
How common are they?
More common in areas w/ goiter from iodide deficiency.
PAX8/PPARG mutations.
Less common than PTC (5-15%).
What classic histological findings are found in Follicular carcinoma? (2)
It is still considered a…
Invasive properties: invasion of the capsule (mushroom) and angioinvasion.
Differentiated thyroid carcinoma.
What are therapeutic options for differentiated thyroid carcinoma? (2)
What if refractory? (2)
Surgery + radioactive iodine
Chemotherapy + tyrosine kinase inhibitors (in progress)
Anaplastic carcinoma tends to affect which age group?
How common?
What is the progression?
What mutations are common?
Elderly patients.
Uncommon - 5% of thyroid carcinoma.
Highly aggressive - present w/ mass effect and patients die within 1 year of local invasion.
TP53
Genetics/mutations and thyroid malignancies:
RET/PTC rearrangements + BRAF (MAP kinase signaling) =
PAX8-PPARG =
RAS + PTEN =
TP53 =
RET/PTC rearrangements + BRAF (MAP kinase signaling) = Papillary carcinoma
PAX8-PPARG = Follicular carcinoma
RAS + PTEN = non-specific follicular neoplasms
TP53 = Anaplastic carcinoma
What is the function of C cells?
Secretion of calcitonin
What kind of cancer is thyroid medullary carcinoma (MTC)?
What are 3 histological findings in thyroid medullary carcinoma?
NE carcinoma derived from C cells
Histology:
- blue cells w/ dispersed chromatin
- amyloid
- C-cell hyperplasia
Sporadic MTC makes up how many cases of MTC?
What “kind” of tumors there they?
Mean age:
Progression:
70-80% of MTC cases
Unifocal tumors
Mean age = 50 y/o
Aggressive - 50% rate of LN mets at time of diagnosis.
Familial MTC has the…
What “kind” of tumors are they?
Mean age:
Best prognosis of all forms (100% at 15 years)
Multifocal tumors
Mean age = 43 y/o
10-year survival rates of MTC when…
Confined to the thyroid
Spreads to cervical LNs
Mets at distant sites
Confined to the thyroid - 90%
Spreads to cervical LNs - 70%
Mets at distant sites - 20%
What mutation of which gene, on which chromosome, are found in familial MTC?
RET proto-oncogene on chr. 10
