Endo-thryoid pathology Flashcards
features of anaplastic carcinoma of thyroid
- rare, undifferentiated malignant tumor of the thyroid
- population: elderly
- highly aggressive -poor prognosis (die within year of local invasion)
- local invasion presents with mass effect (dysphagia , SOB)
- gene mutation: TP53
- microscopy shows areas of papillary carcinoma with high -grade tumor (poor differentiation and necrosis)
which population is most likely to get the tall cell variant of PTC and how does it act?
older patients
aggressive
features of medullary thyroid carcinoma
- amyloid (calcitonin deposits within tumor as amyloid)
- high levels of calcitonin (hypocalcemia)
- c-cell hyperplasia (seen with immunostain)
- blue cells with dispersed chromatin
- +congo red stain and apply green biferengence
clinical features of hashimotos
- initial hyperthyroidism (hashitoxicosis)
- progression to hypothyroidism (low T4, high TSH)
- diffuse PAINLESS enlargement of gland (goiter)
histo of the thryroid
- pools of pink colloid
- follicular cells ( produce TH)
- parafollicular C-cells (produce calcitonin)
follicular variant of PTC
- follicular architecture , but have the Orphan annie eye nuclei
- fewer associations with RET-PTC and BRAF
- more associated with RAS and PTEN mutation (like follicular CA and adenoma)
most common malignant tumor of the thyroid gland?
papillary thyroid carcinoma
actions of TH on the body
- essential action: increase in (BMR) basal metabolic rate
- liver: increase gluconeogenesis/fat & cholesterol synthesis/bile acid conversion from cholesterol
- adipose: increase fatty acid mobilization
- heart: increase HR and hypertrophy
- pituatary: decrease TSH, increase GH
- muscle: increase protein breakdown/ fat oxidation/ glucose utilization
- bone: increase growth and resorption
define apathetic hyperthyroidism
older adults with masked symptomatology
- unexplained weight loss
- cardiovascular disease
define cretinism
hypothyroidism in neonates and infants (congenital) usually caused by iodide deficiency during gestation (or result of genetic alteration in normal thryoid metabolic pathway)
-sx: mental retardation, growth retardation, coarse facial features, enlarged tongue, umbilical hernia
is primary or secondary hyperthyroidism more common
primery thyrotoxicosis
example of secondary is pituitary adenoma
define myxedema
hypothyroidism in older children or adults
- clinical features based on decreased BMR and SNS activity
sx: - myxedema ( accumulation of glycosaminoglycans in the skin and soft tissue resulting in deepining of voice and enlarged tongue)
- weight gain
- slowing mental/physical activity (“sluggish)
- muscle weakness
- cold intolerance/decreased sweating
- bradycardia, low Cardiac output –> SOB, fatigue
- oligomenorrhea,
- hypercholesterolemia
- constipation
average age of papillary thyroid carcinoma dx? usual presentation? major risk factor? histo? gene mutation?
age: 25-50yo
- usually no sx (palpable nodule; get US)
- RF: exposure to ionizing radiation in childhood
histo: papillae lined by cells with clear “ORPHAN ANNIE EYE” nuclei and nuclear grooves, often associated with psmammoma bodies
- gene: RET-PTC mutation, BRAF gof mutation
* common to spread to cervical LN but prognosis is excellent
define riedel thyroiditis
chronic inflammation of the thyroid gland with extensive fibrosis of the gland (extends from thyroid into adjacent tissues)
- IgG4-related disease
- presents as hypothyroidism with “hard as wood” nontender thryoid gland , and euthyroid levels
- histo: fibrosis, lymphocytes, PLASMA CELLS
- *clinically mimics anaplastic carcinoma but patients are younger (40s) and malignant cells are absent
hallmark of IgG4 related diseases ? examples?
fibrosis
IgG4+ plasma cell infiltrate
(causes epithelial damage and organ damage)
examples: Riedels thyroiditis, autoimmune pancreatitis, sclerosing mediastinitis, idiopathic retroperitoneal fibrosis
what is hashimotos thyroiditis (most common cause of hypothyroidism in iodine adequate areas)
autoimmune destruction of thyroid gland–> hypothyroidism
- autoantibodies againt thyroglobulin and thyroid peroxidase (TPO)
- HLA-DR5 associated
sx of hyperthyroidism
perspiration facial flushing nervouness excitability restlessness emotional instability insomnia exophthalmos muscle wasting palpitations (heart racing) tachycardia goiter
What is Graves Disease? and the classic triad?
diffuse thyroid hyperplasia –> primary hyperthyroidism
- autoimmune disease (thyroid stimulating hormone receptor antibody- TSHR-Ab; thyroid stimulating IG -TSI)
- most common cause of hyperthyroidism
- characterized by:
1. hyperthyroidism with gland enlargement (goiter), 2.infiltrative ophthalmopathy (thickened EOM, retraction of eyelids, proptosis/popping, red stripe in horizontal line)
3. pretibial myxedema (common on shins, infiltrative dermopathy with scaly, tough, indurated skin)
how does graves thyroiditis appear on histo
- swollen enlarged gland with enlarged convoluted follicles and “bubbly” colloid.
- Bubbly personality = overactive thyroid
malignant proliferation of follicles surrounded by a fibrous capsule with INVASION through the capsule. occurs more commonly in areas with goiter from iodide deficiency
follicular carcinoma
how to distinguish follicular carcinoma vs adenoma
- invasion through capsule/mushroom (carcinoma)
- angioinvasion/ hemotagenous spread (carcinoma)
-therefore entire capsule must be seen microscopically and FNA does examine capsule there is not able to make distinction
define subacute lymphocytic thyroiditis
*autoimmune pathogenesis (TPO Abs)
-usually a transient period of thyroid hormone irregularities (hyperthyroidism, goiter) but can progress to permanent hypothyroidism
-ex: postpartum thyroiditis
PAINLESS type
can hypo and hyper thyroidism manifest with goiters?
yes
what occurs when TSH binds to follicular cell receptor in the thyroid
- thyroglobulin (TG) is produced and stored in colloid
- iodide is transported into the cell from ECF and incorporated into TG to form iodinated tyrosine precursors
- TG in endocytosed and cleaved to release free T3 and T4
(stimulates all step AND HYPERPLASIA)
labs found in graves dz
High T3/T4
Low TSH
HIGH TSI (thyroid stimulating Igs)
which population is most likely to get the diffuse sclerosing variant of PTC and how does it act?
kids/young adults
- greater incidence of distant metastasis to brain, bone, liver, lung
- but responds very well to tx and has good prognosis
when are multi nodular goiters most likely to cause trachea compression and become toxic “raised T3/T4 levels with undetectable TSH “
> 55 yo
*these can become very large and have mass effect before becoming toxic
define subacute granulomatous thyroiditis (aka De Quervian’s thyroiditis)
- PAINFUL type
- transient thyroiditis that follows a viral infection (i.e. mumps)
- sx: tender thyroid with transient hyperthyroidism
- self-limited but very rarely process to hypothyroidism
- associated with HLA B35
gene mutations associated with follicular carcinoma
RAS and PTEN mutations (non specific - seen in follicular variant of PTC)
PAX8/PPARG mutation is more specific
dx feature of papillary thyroid carcinoma that allow for diagnosis
Orphan Annie Eye nuclei
define thyroid storm and the Burch Wartofsky Score
sudden and severe onset of thyrotoxic manifestations
(“hyperthyroid crisis”)
score: (appears like infection) fever/febrile cardiac sx (tachycardia, CHF) GI sx (diarrhea, jaundice) precipitating history (pregnancy/postpartum, hemithyroidectomy, amiodarone meds)
pathogenesis of Graves Dz affecting the orbit
- lymphocytes invade preorbital space (and secrete thyroid stimulating Abs)
- fibroblasts have TSH receptor (TSH receptor binds to thyroid stimulating Abs and initiates cascade)
- EOM swelling / myofibroblast thickening
- matrix accumulation
- adipocytes expansion
diffuse nontoxic goiter common causes? and sx?
- endemic –> iodine defiency
- goitrogens (cassave root, brassicacaeae)
- sporadic goiter (more common in women)
- sx: Usually Euthryoid; sx come from Mass effect
- dysphagia, hoarseness, stridor, SVC syndrome (flushed face)
___ goiter can grow into the mediastinum; but is generally benign
substernal goiters
histo features of hashimotos
- chronic inflammation with lymphocytic infiltrate within germinal centers and also Hurthle cell metaplasia (eosinophilic change of the cells that line the follicle due to follicle atrophy
- becomes lymph node like therefore increased risk of B cell lymphoma
tx of hyperthyroidism
tx sx: beta blockers, NSAIDs
tx underlying dz: high doses of iodide (wolff-chaikoff effect), thionamide, radio iodine ablation, surgery
neuroendocrine carcinoma derived from malignant proliferation of parafollicular C cells
medullary thyroid carcinoma
a benign neoplasm with proliferation of follicular cells (discrete clonal population of follicular cells) with “thyroid autonomy”; has intact capsule and no features of papillary carcinoma
follicular adenomas
genes associated with medullary thyroid carcinoma familial and sporadic form
familial cases: MEN 2a/2b associated with germline RET mutation
(BEST prognosis of all forms, multifocal)
sporadic MTC: somatic RET mutations
(more common, unifocal tumors, avg age =50 yo, very aggressive (50% LN mets at dx) )
tx options for differentiated thryoid carcinoma (including FTC and PTC)
- surgery
- radioactive iodine
* if refractory: chemo or tyrosine kinase inhibitors
what is the purpose of radioisotope scanning of thyroid nodules? what is a sign of neoplasia? what is a more useful work up?
- determines if a specific nodule is responsible for hyperfunction (i.e hot nodule) (if yes can be treated with excision or ablation) in the setting of thyroid nodule and low TSH
- cold nodules are more likely to be neoplastic (vs hot nodules) and should be worked up with US [however both are more likely to be benign by incidence]
- ultrasound FNA biopsy is more useful - can be used to determine cellular constituents of a nodule (cytology)
