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Endo-Repro Exam 2 > Lecture 4: Thyroid Pathology > Flashcards

Lecture 4: Thyroid Pathology Flashcards

1
Q

How do patients with thyroid storm typically present; if left untreated what is a common cause of death?

A
  • Febrile and present w/ tachycardia out of proportion to the fever
  • Death due to cardiac arrhythmias
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2
Q

What is the MOA of the antithyroid agent, propylthiouracil?

A
  • Inhibits the oxidation of iodide and thus blocks production of thyroid hormone
  • Also inhibits the peripheral deiodination of circulating T4 into T3
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3
Q

How does large doses of iodide given to an individual act as a goitrogen?

A

Blocks release of thyroid hormones by inhibiting the proteolysis of thyroglobulin

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4
Q

Inborn errors of thyroid metabolism causing congenital hypothyroidism is known as what?

A

Dyshormonogenetic goiter

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5
Q

What is the most common cause of hypothyroidism in iodine-sufficient areas of the world?

A

Autoimmune hypothyroidism i.e., Hashimoto thyroiditis

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6
Q

Which circulating autoantibodies are seen in association with Hashimoto Thyroiditis?

A
  • anti-thyroid peroxidase (TPO)
  • anti-thyroglobulin
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7
Q

What are the clinical features of Cretinism?

A
  • Mental retardation
  • Short stature
  • Coarse facial features
  • Protruding tongue
  • Umbilical hernia
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8
Q

What are 2 possible causes of Cretinism?

A
  • Areas w/o iodine supplementation
  • Result of genetic alterations in normal thyroid metabolic pathways i.e., dyshormonogenetic goiter
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9
Q

The term Myxedema is applied to what situation?

A

Hypothyroidism developing in older children or adults

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10
Q

Histologically there is an accumulation of what in Myxedema; leads to what clinical findings?

A
  • Matrix substances, such as glycosaminoglycans and hyaluronic acid in skin, subcutaneous tissue, and some visceral sites
  • Leads to nonpitting edema, a broadening and coarsening of facial features, enlarged tongue, and deepening of the voice
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11
Q

Measurement of what in the serum is the best screeing test for both hyper- and hypothyroidism?

A

Serum TSH

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12
Q

What will levels of TSH be like in pt with primary hypothyroidism and primary hyperthyroidism?

A
  • Primary hypothyroidism = ↑↑↑ TSH
  • Primary hyperthyroidism = ↓↓↓ TSH
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13
Q

What is a major cause of nonendemic goiter in the pediatric population?

A

Hashimoto Thyroiditis

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14
Q

Polymorphisms in which immune-regulation associated genes are implicated in Hashimoto Thyroiditis?

A

CTLA4 and PTPN22

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15
Q

In Hashimoto Thyroiditis there is diffuse enlargement of the thyroid which is (painful or painless)?

A

Painless

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16
Q

In Hashimoto Thyroiditis there is extensive infiltration of the parenchyma by what cells and also the development of well-developed what?

A
  • Mononuclear inflammatory infiltrate
  • Well-developed germinal centers
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17
Q

What characteristic cell type is seen as part of the metaplastic response to injury in Hashimoto Thyroiditis?

A

Hurthle cells = atrophic follicle cells w/ eosinophilic change + granular cytoplasm

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18
Q

The presence of what in fine-needle aspiration biopsy samples is characteristic of Hashimoto Thyroiditis?

A

Hurthle cells + heterogenous population of lymphocytes

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19
Q

How does the fibrosis seen in Hashimoto’s differ from Reidel Thyroiditis?

A

In Hashimoto’s the fibrosis does NOT extend beyond the capsule of the gland

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20
Q

In the case of Hashitoxicosis what is seen with levels of free T3 and T4, TSH, and radioactive iodine uptake?

A
  • T3 and T4 levels are elevated
  • TSH is diminshed
  • Radioactive iodine uptake is decreased
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21
Q

Patients with Hashimoto Thyroiditis are at an increased risk of developing what malignancy within the thyroid gland?

A

Extranodal marginal zone B-cell lymphoma

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22
Q

Although similar in presentation to Hashimoto’s what morphological features are not as prominent in Subacute Lymphocytic Thyroiditis?

A

Fibrosis and Hurthle cell metaplasia are NOT prominent

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23
Q

Granulomatous Thyroiditis (De Quervain) is thought to be triggered by what?

A

Viral infection (i.e., hx of URI just before onset of sx’s)

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24
Q

What histological findings are associated with Subacute thyroiditis (de Quervain)?

A
  • Granulomatous inflammation w/ multinucleate giant cells
  • Initially has more neutrophilic infiltrate w/ microabscess formation; then replaced by a more generalized inflammatory infiltrate with macrophages and multinucleated giant cells
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25
Q

Granulomatous thyroiditis (De Quervain) will present with what sized thyroid and other distinguishing feature?

A

Variably enlarged thyroid that is PAINFUL!

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26
Q

What is the typical course of Granulomatous Thyroiditis (De Quervain)?

A
  • Transient inflammation of thyroid, usually diminishing within 2-6 weeks = Self-limited!
  • After recovery, normal thyroid function restored within 6-8 weeks
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27
Q

Riedel thyroiditis is characterized by replacement of thyroid tissue with what and has what type of infiltrate?

A

Extensive fibrosis of the thyroid and neck structures w/ tissue infiltration by lymphocytes and plasma cells

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28
Q

Riedel thyroiditis is considered a manifestation of _______ related systemic disease, which includes autoimmune pancreatitis, retroperitoneal fibrosis, and noninfectious aortitis

A

IgG4-related disease

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29
Q

Riedel thyroiditis presents as a ________ (consistency) and _________ (painful/painless) goiter

A

Riedel thyroiditis presents as hard as wood/cement and painless goiter

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30
Q

Subacute lymphocytic thyroiditis often occurs in association with what?

A

After a pregnancy (postpartum thyroiditis)

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31
Q

Although not always present, what is the classic triad of Graves disease?

A
  • Hyperthyroidism w/ gland enlargement = Diffuse hyperplasia
  • Infiltrative ophthalmopathy –> exophthalmos
  • Pretibial myxedema
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32
Q

Peak incidence of Graves disease is btw what ages; which sex is 10x more affected?

A

20-40 y/o and 10x more common in women

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33
Q

What is the most common antibody subtype seen in Graves disease?

A

Thyroid stimulating immunoglobulin (TSI)

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34
Q

What HLA subtypes are associated with Graves disease?

A

HLA-DR3 and B8

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35
Q

What are the levels of TSH like in Graves Disease?

A

LOW

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36
Q

The exopthalmos associated with Graves Disease is caused by what underlying process?

A
  • Infiltration of retroorbital space by T cells
  • Fibroblasts have TSH receptor and proliferate
  • EOM swelling from edema + inflammation
  • Accumulation of EC matrix components i.e., GAG and chondroitin sulfate
  • ↑ number and expansion of adipocytes
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37
Q

The exopthalmos associated w/ Graves disease appears to stem from activation of which cells in the orbit and via which receptor?

A

Orbital preadipocyte fibroblasts expressing TSH receptors

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38
Q

Diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells is characteristic of what?

A

Graves Disease

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39
Q

What is a histological characteristic of the follicular epithelial cells in untreated Graves Disease?

A

Taller and more crowded –> formation of small papillae which project into the follicular lumen and encroach on the colloid

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40
Q

How do the papillae seen in graves disease differ histologically from those of papillary carcinoma?

A

Lack fibrovascular cores

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41
Q

What feature of the colloid is a characteristic histological finding in Graves disease?

A

Scalloped margins of colloid

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42
Q

How does pre-operative therapy with iodine vs. propylthiouracil alter the morphology of the thyroid in Graves Disease?

A
  • Iodine causes involution of the epithelium and accumulation of colloid
  • Propylthiouracil exaggerates the epithelial hypertrophy and hyperplasia
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43
Q

Radioiodine scans of pt with Graves Disease will show what?

A

Diffusely ↑↑↑ uptake of iodine

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44
Q

Diffuse nontoxic (simple) goiter causes enlargement of the entire gland without producing what?

A

Nodularity

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45
Q

Toxic multinodular goiter is most often due to _________ mutations

A

Toxic multinodular goiter is most often due to TSH receptor mutations

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46
Q

What are some of the goitrogens that when ingested in large quantities may lead to the endemic form of diffuse nontoxic goiter?

A
  • Cassava root (thiocyanate)
  • Brassicaceae (i.e., cabbage, cauliflower, brussel sprouts, turnips..)
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47
Q

What are the 2 phases identified in the evolution of diffuse nontoxic goiter?

A
  • Hyperplastic phase
  • Phase of colloid involution
48
Q

The clinical manifestations of diffuse nontoxic (simple) goiters are most often due to what?

A

Mass effect as most pt’s are clinically euthyroid (normal T3 and T4)

49
Q

Virtually all long-standing simple goiters convert into what?

A

Multinodular goiters

50
Q

Which type of goiter produces the most extreme enlargements and are more frequently mistaken for neoplasms than any other thyroid disease?

A

Multinodular goiters

51
Q

What morphological feature is missing from multinodular goiters which is distinct from follicular neoplasms?

A

A prominent capsule is NOT present

52
Q

Older lesions of multinodular goiter show what histological change?

A

Areas of hemorrhage, fibrosis, calcification, and cystic change

53
Q

What are some of the signs/sx’s which can be produced by mass effect of both simple and multinodular goiters?

A
  • Dysphagia
  • Hoarsness
  • Stridor
  • SVC syndrome
54
Q

When an autonomous nodule develops within a long-standing multinodular goiter and produced hyperthyroidism this is known as what?

A

Toxic multinodular goiter (aka Plummer syndrome)

55
Q

How is a toxic multinodular goiter (plummer syndrome) distinct from Graves?

A

Does not produce infiltrative opthalmopathy and dermopathy

56
Q

What are the levels of T3 and T4 + TSH like in older pt (>55 y/o) with multinodular goiter?

A
  • ↑ T3 and T4
  • ↓ TSH
57
Q

Which type of nodule is more likely to be neoplastic (cold or hot)?

A

Cold nodules

58
Q

Thyroid nodules in which age group and sex are more likely to be neoplastic?

A

Younger pt’s and males

59
Q

What morphological features are the hallmark of all follicular adenomas and are important for making the distinction from multinodular goiters?

A

Solitary, spherical, encapsulated lesion demarcated from surrounding thyroid parenchyma by well-defined, intact capsule

60
Q

Careful evaluation of what morphological feature of follicular adenomas is important for making the distinction from follicular carcinomas?

A

Integrity of the capsule; should be intact (not invaded)

61
Q

Definitive diagnosis of thyroid adenomas can be made only after what?

A

Careful histologic examination of the resected specimen

62
Q

Thyroid papillary carcinomas are associated with gain-of-function mutations in which genes?

A
  • RET or NTRK1RTK’s
  • serine/threonine kinase BRAF
63
Q

What are the 2 most common fusion partners of RET observed in sporadic papillary cancers?

A

PTC1 and PTC2

64
Q

Presence of which mutation in papillary carcinomas correlates with adverse prognostic factors like metastatic disease and extrathyroidal extension?

A

BRAF

65
Q

Follicular thyroid carcinomas are associated with gain-of-function mutations in which genes or loss-of-function in?

A
  • G.O.F = RAS or PIK3CA
  • L.O.F = PTEN
66
Q

Which unique fusion gene product is seen in a minority of follicular carcinomas?

A

PAX8-PPARG

67
Q

Both familial and sporadic medullary thyroid carcinomas are associated with germline mutations in what gene; what chromosome?

A

RET on chromosme 10

68
Q

What is the major enviornmental risk factor predisposing to thyroid cancer?

A

Exposure to ionizing radiation, especially during the first 2 decades of life

69
Q

Deficiency of dietary iodine is linked with higher frequencies of what type of thyroid cancer?

A

Follicular carcinomas

70
Q

Between what ages is the highest prevalence of papillary thyroid carcinoma?

A

25-50 y/o

71
Q

Which malignancy of the thyroid accounts for the majority of thyroid carcinomas associated with ionizing radiation?

A

Papillary carcinoma

72
Q

When present, how do the papillae of papillary carcinoma differ from those seen in areas of hyperplasia?

A

Are more complex and have dense fibrovascular cores

73
Q

What are the hallmark morphological features of the nuclei of thyroid papillary carcinomas?

A
  • Optically clear or empty appearance
  • Ground-glass or Orphan Annie eye nuclei
74
Q

The diagnosis of thyroid papillary carcinomas can be made based on what morphological features?

A

NUCLEAR features, even in absence of papillary architecture

75
Q

Which morphological feature seen on FNA is unique to thyroid papillary carcinoma and is almost never seen in follicular and medullary carcinomas?

A

Concentrically calcified structures, Psammoma bodies

76
Q

Metastasis of thyroid papillary carcinoma to which LN’s is seen in up to 50% of cases?

A

Cervical LN’s

77
Q

Which variant of papillary carcinoma has nuclear features of papillary carcinoma and an almost totally follicular architecture?

A

Follicular variant

78
Q

The follicular variant of papillary carcinoma has a higher frequency of mutations in which gene?

A

RAS

79
Q

Follicular variant papillary carcinomas can be either encapsulated or poorly circumscribed; which has a better prognosis?

A

Encapsulated

80
Q

The follicular variant of papillary carcinoma has a higher propensity for spread how?

A

Angioinvasion

81
Q

Which thyroid papillary carcinoma variant is more commonly seen in older patients and tends to follow a more aggressive course?

A

Tall-cell variant

82
Q

Tall-cell variant of papillary carcinomas most often harbor which mutations?

A
  • BRAF
  • RET/PTC translocations
83
Q

Which thyroid papillary carcinoma variant occurs in younger pt’s, including children?

A

Diffuse sclerosing variant

84
Q

The diffuse slcerosing variant of papillary carcinoma is often associated with a prominent lymphocytic infiltrate, simulating what other disease of the thyroid?

A

Hashimoto thyroiditis

85
Q

Metastases to where are seen in almost all cases of the diffuse sclerosing variant of papillary carcinoma?

A

Lymph node metatases

86
Q

What is often the first manifestation calling attention to a thyroid papillary carcinoma?

A

Mass in cervical LN

87
Q

Which sx’s associated with thyroid papillary carcinoma suggest more advanced disease?

A

Hoarsness, dysphagia, cough, or dyspnea

88
Q

Some patients with thyroid papillary carcinoma will have hematogenous spread; which organ is most commonly affected?

A

Lung

89
Q

What is the prognosis (10-year survival) of papillary thyroid carcinomas?

A

Excellent; 10-year survival >95%

90
Q

What factors is the prognosis of papillary thyroid cancers dependent on?

A
  • Age (less favorable in those >40 y/o)
  • Presence of extrathyroidal extension
  • Presence of distal metastases (stage)
91
Q

What are 2 therapeutic options for papillary thyroid carcinoma?

A
  • Surgery
  • Radioactive iodine (I131)
92
Q

Peak incidence of follicular thyroid carcinomas is btw what ages?

A

40-60 y/o

93
Q

How is the distinction between follicular adenomas and minimally invasive follicular carcinomas made?

A

Extensive histo sampling of tumor-capsule thyroid interace to exclude capsular and/or vascular invasion

94
Q

Metastasis from follicular carcinoma is most often via which route and to which sites?

A
  • Hematogenous –> angioinvasion
  • Bone, lung, and liver = common
95
Q

Most follicular carcinomas are treated how?

A

Total thyroidectomy followed by radioactive iodine

96
Q

Serum levels of what are used for monitoring follicular carcinoma recurrence?

A

Serum thyroglobulin; as should be barely detectable

97
Q

Anaplastic (undifferentiated) thyroid carcinoma tend to occur most often in whom?

A

Elderly pt’s

98
Q

What is the prognosis of anaplastic (undifferentiated) thyroid carcinoma; most common cause of death?

A
  • Highly aggressive w/ almost 100% mortality within one year
  • Death from compromise of vital structures in the neck (mass effect)
99
Q

Microscopically anaplastic (undifferentiated) thyroid carcinomas can have what 3 variable types of morphology and cells?

A

1) Large, pleomorphic giant cells
2) Spindle cells w/ a sarcomatous appearance
3) Mixed spindle and giant cells

100
Q

The neoplastic cells of anaplastic (undifferentiated) thyroid carcinoma express which epithelial marker and are negative for which marker of thyroid differentiation?

A
  • (+) cytokeratin
  • (-) thyroglobulin
101
Q

How do anaplastic (undifferentiated) thyroid carcinomas most often present clinically; what signs/sx’s?

A
  • Rapidly enlarging bulky mass in neck
  • Sx’s such as: cough, dyspnea, hoarsness,anddysphagia
102
Q

Anaplastic (undifferentiated) thyroid carcinoma is associated with inactivating mutations of what?

A

TP53

103
Q

Which variant of follicular thyroid carcinoma is dominated by cells with abundant granular, eosinophilic cytoplasm?

A

Hurthle cell or oncocytic variant

104
Q

Since medullary thyroid carcinomas are neuroendocrine neoplasms, the tumor cells may elaborate what polypeptide hormones?

A
  • Calcitonin (always)
  • Serotonin
  • ACTH
  • VIP
105
Q

Medullary thyroid carcinomas may arise in what 3 ways?

A
  • Sporadic MTC
  • Familial (FMTC)
  • Associated with MEN types 2A and 2B
106
Q

When do medullary thyroid carcinomas associated with MEN 2A or 2B arise vs. those that are sporadic or familial?

A
  • MEN 2A/2B arise in younger pt’s; may be during first decade
  • Sporadic and familial arise in adulthood w/ peak incidence of 40-50 y/o
107
Q

Which type of medullary thyroid carcinoma presents as a unifocal solitary nodule?

A

Sporadic MTC

108
Q

Which medullary thyroid carcinoma presents with bilaterality and multicentricity?

A

Familial MTC

109
Q

Which morphological feature present in familial medullary thyroid cancers is believed to be a precursor lesion?

A

Multicentric C-cell hyperplasia

110
Q

Misfolded calcitonin polypeptides are often seen deposited in the stroma of medullary thyroid carcinomas as what; can be stained how?

A
  • Amyloid deposits (A Cal)
  • Congo Red Stain —> “Apple-green” birefringence
111
Q

Blue cells with dispersed chromatin admixed with deposits of amyloid is characteristic of what thyroid neoplasm?

A

Medullary thyroid carcinom

112
Q

The presence of multiple prominent clusters of C cells scattered thoughout the parenchyma of a medullary thyroid carcinoma should raise suspicion for what?

A

An inherited predisposition EVEN if a family hx is not present

113
Q

Is hypocalcemia a prominent feature of sporadic medullary thyroid carcinomas?

A

NO

114
Q

Which biomarker is useful in the presurgical assessment of tumor load and in calcitonin-negative medullary thyroid carcinomas?

A

Carcinoembryonic antigen

115
Q

Medullary carcinomas arising in which setting are generally more aggressive and metastasize more frequently?

A

MEN-2B

116
Q

Asymptomatic MEN-2 patients with germline RET mutations are offered what?

A

Prophylactic thyroidectomy as early as possible

117
Q

Medullary thyroid carcinomas arising in which setting have the best prognosis of all forms?

A

Familial MTC

Endo-Repro Exam 2 (11 decks)

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