Thyroid Pathology (Martin) Flashcards
Embryology of thyroid
foramen cecum; 1st and 2nd pharyngeal pouches near base of the tongue, then descends downward
Follicular cells
AKA principal cells; produces T3 & T4; usually cuboidal but when under TSH stimulation - columnar
Colloid
contained within follicles; contains thyroglobulin - iodinated glycoprotein = inactive form of thyroid hormone
Goitrogrens
things we eat that suppress T3&T4 synthesis; increases TSH release; can cause formation of a goiter
Propylthiouracil
anti-thyroid agent that inhibits oxidation of iodide and peripheral deiodination
High dose of iodine
inhibit proteolysis of thyroglobulin; therefore cannot be converted into active thyroid hormone
Parafollicular cells
C cells; pale staining cells that secrete calcitonin; lowers calcium levels by promoting calcium deposition in bone and suppressing osteoclast activity
Thyrotoxicosis
HYPERthyroidism; hyper metabolic state with increased free T3&T4
True Thyroid Ophthalmopathy
proptosis (protuberance of the eyeball); only with Graves disease
Hyperthyroidism diagnosis
low TSH with increased free T4; if TSH is normal/elevated think secondary causes; radioactive test:
Graves = increased
Toxic adenoma = increased
Thyroiditis (inflammation) = decreased
Apathetic hyperthyroidism
older adults with masked symptomatology; unexplained weight loss and increased risk for cardiovascular disease (a-fib)
Thyroid storm
feared complication of hyperthyroidism; extreme and abrupt episode of potentially life threatening thyrotoxicosis due to some sort of stress; audible bruit; wide, staring gaze & lid lag; exophthalmos that can lead to corneal injury; medical emergency
Hypothyroidism is more common in which sex?
10X more in females
Primary hypothyroidism
abnormal thyroid itself; congenital (PAX8 mut), acquired (iodine deficiency) or immune (Hashimoto’s thyroiditis); can see goiter
Secondary hypothyroidism
result of pituitary or hypothalamic (rare) failure
Myxedema
hypothyroidism in adult; promotes atherogenic profile (increased cholesterol = hypercholesterolemia) and LDL = CVD mortality); non-pitting edema (accumulation of glycosaminoglycans); mimics depression; cold intolerant; overweight; increased TSH with low free T4
Most common cause of hypothyroidism wordwide
iodine deficiency
dyshormonogenetic goiter
congenital cause of hypothyroidism due to inborn errors of thyroid metabolism; most common are TPO mutation and SLC26A4 mutation seen in Pendred syndrome
Pendred syndrome
congenital cause of hypothyroidism + sensorineural deafness; mutation in SLC26A4
Most common cause of hypothyroidism in iodine-sufficient areas of the world
Hashimoto’s thyroiditis; antibodies to:
1. anti-microsomal
2. anti-thyroid peroxidase (TPO)
3. anti-thyroglobulin
What are the 3 common antibodies present in Hashimoto’s thyroiditis?
- anti-microsomal (least common)
- anti-thyroid peroxidase (TPO)
- anti-thyroglobulin
Thyroid hormone resistance syndrome
AD; Thyroid hormone receptor mutation (THRB); receptor cannot bind hormone; primary hypothyroidism
Cretinism
hypothyroidism in infancy or early childhood; commonly due to maternal iodine deficiency; deficiency before fetal thyroid is severe impact = severe intellectual disability, short stature, coarse facial features and protruding tongue
What are the three common subtypes of thyroiditis
inflammation due to:
1. Hashimoto’s thyroiditis
2. Granulomatous (de Quervain) thyroiditis
3. Subacute lymphocytic thyroiditis
What are the 3 negative regulators of T-cell responses in Hashimoto’s thyroiditis
- CTLA4 = cytotoxic T-lymphocyte associated antigen 4
- PTPN22 = protein tyrosine phosphatase 22
- IL2RA = IL-2 receptor alpha chain
What is the histological hallmark feature in Hashimoto’s thyroiditis?
Hurthle cells = abundant eosinophilic granular cytoplasm
Hashimoto’s thyroiditis morphology
yellow-tan firm nodule; mononuclear inflammatory infiltrate (lymphocytes) and Hurthle cells
Hashitoxicosis
transient thyrotoxicosis during Hashimoto’s thyroiditis due to disruption of follicles; increased T3&T4 with decreased TSH and decreased iodine uptake
Patients with Hashimoto’s are at increased risk for which lymphoma
marginal bone B-cell lymphoma
Subacute lymphocytic thyroiditis
painLESS thyroiditis; anti-thyroid peroxidase antibodies (TPO); unlike Hashimoto’s fibrosis and Hurthle cells are NOT present
Granulomatous (de Quervain) thyroiditis
triggered by viral infection to URI; NO antibodies; thyroid PAIN; inflammation and HYPERthyroidism for 2-6 weeks; increased T4&T3 with decreased TSH and iodine uptake (unlike Graves); will see multinucleated giant cells
Riedel thyroiditis
extensive fibrosis involving thyroid and neck structures; lots of lymphocytes and plasma cells; hard and fixed thyroid mass (cement or wood); anti-thyroid antibody suggest IgG4 related disease
The clinical triad seen in Graves disease
- hyperthyroidism
- ophthalmopathy (exophthalmos)
- pre-tibial myxedema (glycosaminoglycans)
Graves disease morphology
soft meaty surface; diffuse hypertrophy & hyperplasia of follicular cells; papillae lacking fibrovascular core; colloid with scalloped margins
What is the histological hallmark feature in Graves disease?
colloid with scalloped margins
What are the two types of goiters
- diffuse nontoxic (simple)
- multinodular
The two morphological phases of a diffuse nontoxic goiter
- hyperplastic = diffuse enlargement
- colloid involution = follicular cells involute and leave behind enlarged colloid-rich gland with a glassy cut surface
Multinodular goiter
recurrent episodes of hyperplasia and involution; irregular enlargement; can be >2000g (extreme enlargement); mass effects = airway obstruction, dysphagia and SVC syndrome
Plummer syndrome
toxic multi nodular goiter that produces hyperthyroidism; thyroid hormone release independent of TSH
Intrathoracic or Plunging goiter
when goiter grows behind the sternum and clavicles; can mimic a solitary tumor
Follicular adenoma
solitary mass; nonfuctional; NOT a pre-lesion to carcinoma; difficult to distinguish from follicular carcinoma; RAS or PPATy mut
Toxic adenomas
somatic TSH receptor gain of function mutation (TSHR or GNAS); hormone production independent of TSH stimulation; HOT thyroid nodule
What feature is indicative of carcinoma when distinguishing follicular adenoma from carcinoma?
capsular and/or vascular invasion; would need a surgical resection (FNA will not be sufficient)
What are the 4 thyroid carcinomas?
- Papillary (most common 80%)
- Follicular
- Anaplastic
- Medullary
Papillary carcinoma
most common; RET or NTRK and BRAF mut; associated with ionizing radiation; cervical node mass 1st sign; Psammoma bodies, Orphan Annie eye nuclei, intranuclear grooves, and branching papillae w/ fibrovascular core; excellent prognosis (depends on age >40 not good); extra-thyroidal extension
Follicular carcinoma
gain of function but in RAS and PAX8-PPARG fusion gene; capsular and/or vascular invasion; would need a surgical resection (FNA will not be sufficient)
Anaplastic carcinoma
TP53 mut; giant and spindle cells; cells are so undifferentiated that they will be negative for thyroid markers; they will be positive for epithelial markers: cytokeratin +
Medullary carcinoma
RET mut in sporadic cases (70%) and MEN 2A or 2B mut in familial cases; neuroendocrine neoplasm; parafollicular C cells that secrete calcitonin; hypocalemia is NOT prominent feature; paraneoplasm syndrome - secretes serotonin, ACTH and VIP
What is a major risk factor to thyroid carcinoma
exposure to ionizing radiation in childhood (typically used for acne tx)
What is the first clinical sign typically seen in papillary carcinoma?
cervical node mass 1st sign
Papillary carcinoma morphology
lymphatic invasion to cervical lymph node; branching papillae with fibrovascular core; psammoma bodies and ground glass or Orphan Annie eye nuclei and intranuclear grooves “pseudo-inclusions”
Orphan Annie eye nuclei
one of the hallmarks seen Papillary carcinoma morphology
What are the 4 common histological variants of papillary carcinoma
- Follicular
- Tall-cell
- Diffuse sclerosing (kids)
- Papillary micro carcinoma
Though medullary carcinoma is a neuroendocrine neoplasm derived of parafollicular C cells, what is NOT a prominent feature?
hypocalcemia
Medullary carcinoma is associated with a paraneoplastic syndrome that secretes which hormones?
serotonin, ACTH and VIP (vasoactive intestinal peptide)
Hashimoto’s thyroiditis
germinal centers (on the L) and Hurthle’s cells (on the R) and infiltrate of lymphocytes
