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ENRP Exam II > Thyroid Pathology (Martin) > Flashcards

Thyroid Pathology (Martin) Flashcards

1
Q

Embryology of thyroid

A

foramen cecum; 1st and 2nd pharyngeal pouches near base of the tongue, then descends downward

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2
Q

Follicular cells

A

AKA principal cells; produces T3 & T4; usually cuboidal but when under TSH stimulation - columnar

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3
Q

Colloid

A

contained within follicles; contains thyroglobulin - iodinated glycoprotein = inactive form of thyroid hormone

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4
Q

Goitrogrens

A

things we eat that suppress T3&T4 synthesis; increases TSH release; can cause formation of a goiter

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5
Q

Propylthiouracil

A

anti-thyroid agent that inhibits oxidation of iodide and peripheral deiodination

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6
Q

High dose of iodine

A

inhibit proteolysis of thyroglobulin; therefore cannot be converted into active thyroid hormone

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7
Q

Parafollicular cells

A

C cells; pale staining cells that secrete calcitonin; lowers calcium levels by promoting calcium deposition in bone and suppressing osteoclast activity

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8
Q

Thyrotoxicosis

A

HYPERthyroidism; hyper metabolic state with increased free T3&T4

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9
Q

True Thyroid Ophthalmopathy

A

proptosis (protuberance of the eyeball); only with Graves disease

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10
Q

Hyperthyroidism diagnosis

A

low TSH with increased free T4; if TSH is normal/elevated think secondary causes; radioactive test:
Graves = increased
Toxic adenoma = increased
Thyroiditis (inflammation) = decreased

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11
Q

Apathetic hyperthyroidism

A

older adults with masked symptomatology; unexplained weight loss and increased risk for cardiovascular disease (a-fib)

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12
Q

Thyroid storm

A

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

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13
Q

Hypothyroidism is more common in which sex?

A

10X more in females

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14
Q

Primary hypothyroidism

A

abnormal thyroid itself; congenital (PAX8 mut), acquired (iodine deficiency) or immune (Hashimoto’s thyroiditis); can see goiter

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15
Q

Secondary hypothyroidism

A

result of pituitary or hypothalamic (rare) failure

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16
Q

Myxedema

A

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

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17
Q

Most common cause of hypothyroidism wordwide

A

iodine deficiency

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18
Q

dyshormonogenetic goiter

A

congenital cause of hypothyroidism due to inborn errors of thyroid metabolism; most common are TPO mutation and SLC26A4 mutation seen in Pendred syndrome

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19
Q

Pendred syndrome

A

congenital cause of hypothyroidism + sensorineural deafness; mutation in SLC26A4

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20
Q

Most common cause of hypothyroidism in iodine-sufficient areas of the world

A

Hashimoto’s thyroiditis; antibodies to:
1. anti-microsomal
2. anti-thyroid peroxidase (TPO)
3. anti-thyroglobulin

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21
Q

What are the 3 common antibodies present in Hashimoto’s thyroiditis?

A
  1. anti-microsomal (least common)
  2. anti-thyroid peroxidase (TPO)
  3. anti-thyroglobulin
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22
Q

Thyroid hormone resistance syndrome

A

AD; Thyroid hormone receptor mutation (THRB); receptor cannot bind hormone; primary hypothyroidism

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23
Q

Cretinism

A

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

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24
Q

What are the three common subtypes of thyroiditis

A

inflammation due to:
1. Hashimoto’s thyroiditis
2. Granulomatous (de Quervain) thyroiditis
3. Subacute lymphocytic thyroiditis

25
Q

What are the 3 negative regulators of T-cell responses in Hashimoto’s thyroiditis

A
  1. CTLA4 = cytotoxic T-lymphocyte associated antigen 4
  2. PTPN22 = protein tyrosine phosphatase 22
  3. IL2RA = IL-2 receptor alpha chain
26
Q

What is the histological hallmark feature in Hashimoto’s thyroiditis?

A

Hurthle cells = abundant eosinophilic granular cytoplasm

27
Q

Hashimoto’s thyroiditis morphology

A

yellow-tan firm nodule; mononuclear inflammatory infiltrate (lymphocytes) and Hurthle cells

28
Q

Hashitoxicosis

A

transient thyrotoxicosis during Hashimoto’s thyroiditis due to disruption of follicles; increased T3&T4 with decreased TSH and decreased iodine uptake

29
Q

Patients with Hashimoto’s are at increased risk for which lymphoma

A

marginal bone B-cell lymphoma

30
Q

Subacute lymphocytic thyroiditis

A

painLESS thyroiditis; anti-thyroid peroxidase antibodies (TPO); unlike Hashimoto’s fibrosis and Hurthle cells are NOT present

31
Q

Granulomatous (de Quervain) thyroiditis

A

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

32
Q

Riedel thyroiditis

A

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

33
Q

The clinical triad seen in Graves disease

A
  1. hyperthyroidism
  2. ophthalmopathy (exophthalmos)
  3. pre-tibial myxedema (glycosaminoglycans)
34
Q

Graves disease morphology

A

soft meaty surface; diffuse hypertrophy & hyperplasia of follicular cells; papillae lacking fibrovascular core; colloid with scalloped margins

35
Q

What is the histological hallmark feature in Graves disease?

A

colloid with scalloped margins

36
Q

What are the two types of goiters

A
  1. diffuse nontoxic (simple)
  2. multinodular
37
Q

The two morphological phases of a diffuse nontoxic goiter

A
  1. hyperplastic = diffuse enlargement
  2. colloid involution = follicular cells involute and leave behind enlarged colloid-rich gland with a glassy cut surface
38
Q

Multinodular goiter

A

recurrent episodes of hyperplasia and involution; irregular enlargement; can be >2000g (extreme enlargement); mass effects = airway obstruction, dysphagia and SVC syndrome

39
Q

Plummer syndrome

A

toxic multi nodular goiter that produces hyperthyroidism; thyroid hormone release independent of TSH

40
Q

Intrathoracic or Plunging goiter

A

when goiter grows behind the sternum and clavicles; can mimic a solitary tumor

41
Q

Follicular adenoma

A

solitary mass; nonfuctional; NOT a pre-lesion to carcinoma; difficult to distinguish from follicular carcinoma; RAS or PPATy mut

42
Q

Toxic adenomas

A

somatic TSH receptor gain of function mutation (TSHR or GNAS); hormone production independent of TSH stimulation; HOT thyroid nodule

43
Q

What feature is indicative of carcinoma when distinguishing follicular adenoma from carcinoma?

A

capsular and/or vascular invasion; would need a surgical resection (FNA will not be sufficient)

44
Q

What are the 4 thyroid carcinomas?

A
  1. Papillary (most common 80%)
  2. Follicular
  3. Anaplastic
  4. Medullary
45
Q

Papillary carcinoma

A

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

46
Q

Follicular carcinoma

A

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)

47
Q

Anaplastic carcinoma

A

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 +

48
Q

Medullary carcinoma

A

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

49
Q

What is a major risk factor to thyroid carcinoma

A

exposure to ionizing radiation in childhood (typically used for acne tx)

50
Q

What is the first clinical sign typically seen in papillary carcinoma?

A

cervical node mass 1st sign

51
Q

Papillary carcinoma morphology

A

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”

52
Q

Orphan Annie eye nuclei

A

one of the hallmarks seen Papillary carcinoma morphology

53
Q

What are the 4 common histological variants of papillary carcinoma

A
  1. Follicular
  2. Tall-cell
  3. Diffuse sclerosing (kids)
  4. Papillary micro carcinoma
54
Q

Though medullary carcinoma is a neuroendocrine neoplasm derived of parafollicular C cells, what is NOT a prominent feature?

A

hypocalcemia

55
Q

Medullary carcinoma is associated with a paraneoplastic syndrome that secretes which hormones?

A

serotonin, ACTH and VIP (vasoactive intestinal peptide)

56
Q
A

Hashimoto’s thyroiditis
germinal centers (on the L) and Hurthle’s cells (on the R) and infiltrate of lymphocytes

57
Q
A
58
Q
A

ENRP Exam II (10 decks)

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