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Flashcards in Pathology Highlights Deck (117)
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1

What are 3 other causes of Hyperthyroidism besides Grave's?

1. Multinodular Goiter
2. Adenoma
3. Iodine Induced Hypothryoidism

2

What HLA type is associated with Grave's?

HLA-DR3

3

What is Plummer Syndrome?
• 2 causes?

Multinodular Goiter that is Toxic

Causes:
• Focal Patches
• Jod-Basedow Phenomenon (from iodine deficiency - opposite of Wolff-Chiakoff)

4

Who is most likely to get toxic mulinodular goiter?

Women with long standing sporadic endemic goiter

5

What histological feature differentiates toxic multinodular goiter from a follicular neoplasm?

TMG has a thin capsule while follicular neoplasms have a thick capsule

6

What is most commonly the cause of death in thyroid storm?

Tachyarrhythmia

7

T or F: carpal tunnel syndrome and delayed tendon relaxation are features of Grave's disease?

False, this are features of hypothyroidism

8

Who is most commonly affected by Hashimoto's Thyroiditis?

Women 45-65

9

What cells are responsible for mediating the autoimmune attack in Hashimoto's?
• what are some key markers to look for in the serum?

T cells (CD4+) mediate Hashimoto's

Key Markers:
• Anti-thyroglobulin Antibodies
• Anti-thyroid peroxidase Antibodies

10

What HLA type(s) is/are associated with Hashimoto's?

HLA-DR5****, and HLA-DR3

11

What is a feared complication of Hashimoto's Thyroiditis?

• Large Diffuse B-cell Lymphoma

12

What histological changes would you see in Hashimoto's?

Germinal Centers + Hurthle Cell Changes

13

What are the chances of subacute lymphocytic thyroiditis progressing to Hashimoto's?

1/3 progress to Hashimoto's

14

What would you expect to see in Histologically in Reidel's Thyroiditis that is associated with IgG4 autoimmune disease?

Fibrosis and Lymphocytes

***Note: this is typically a woman in her 40s***

15

Who most commonly presents with Granulomatosis Thyroiditis? (De Quervain's)

40-60 year old woman with hx of Flu-like symptoms and a painful thyroid (often present in the summer due to association with summertime viruses like coxsackie and adenovirus)

16

What do you expect to see histologically in someone who has Granulomatosis Thyroiditis?

Giant Cells and Granulomas

17

T or F: most neoplasms of the thyroid are benign

True

18

What features make a thyroid nodule more likely to be neoplastic?

• Solitary
• Young Person
• Male
• Hx of radiation to the head

19

Are hot or cold nodules more likely to be associated with mutations in the the TSH receptor and GNAS1?

Hot (BENIGN) nodules are most commonly associated with these mutations

20

What mutations are most commonly seen in cold nodules?
• where else are these mutations seen?

RAS and PIK3A mutations are most commonly seen in COLD nodules and in FOLLICULAR carcinomas of the thyroid

21

What are the key histological features of a thyroid Adenoma?

• Hurthle Cells (not that these are parafollicular C cells)
• ENCAPSULATION is the most important feature to look for
• this tissue will be impinging on NL thyroid tissue

22

What is the typical age of presentation of papillary thyroid CA?

20-50
**Remember mets have little prognostic significance**

23

What mutations are associated with Papillary thyroid CA?

RET and BRAF (worse px)

**Remember tall cell variants are also associated with a bad PX**

24

What mutations are associated with Follicular thyroid CA?

RAS and PI3K, PTEN is also associated with this

25

T or F: Like papillary CA, the px Follicular CA does not change much even with the presence of mets?

FALSE, extensive METs puts people with follicular CA at a much greater risk of dying
**Remember most mets from follicular are hematogenous**

26

What age groups commonly get medullary thyroid CA?

Young - MEN2 pts.

40's and 50's - sporadic and FMTC

27

What cell type is medullary thyroid CA composed of?

C-cells - these deposit CALCITONIN AMYLOID as they proliferate

•Spindle cell changes may also be seen on histo

28

What mutation is associated with Medullary thyroid CA?

RET => remember the association with MEN2

29

T or F: Medullary CA of the thyroid is a neuroendocrine tumor.

True

30

Who most commonly presents with anaplastic thyroid carcinoma?
• what do you expect to see histologically?

65 or older with a history of well differentiated thyroid cancer

Histo:
• Multinucleated Osteoclast-like cells and spindle shaped cells

31

What do you need to do for a women on thyroid hormone therapy that gets pregnant?

GIVE MORE T3 and T4 because she will have more TGB

32

T or F: hot nodules decrease activity elsewhere in the thyroid

True

33

What is derived from the 3rd branchial pouch?

Inferior Thyroids and the Thymus

34

What is derived from the 4th branchial pouch?

Superior Parathyroid Glands

35

What is the most common cause of primary hyperparathyroidism?
• who typically present with it?
• how?

Pituitary Adenomas are the Most Common Cause
• Patient typically in 50s with Stones, Moans, and Bones

***Note: this is the most common cause of asymptomatic hypercalcemia***

36

What mutations are often associated with Primary Hyperparathyroidism?
• what do you expect to see histologically?

Cyclin D1 and MEN1

HISTO:
• Rim or normal parathyroid surrounds tissue that almost look like NL parathyroid but it LACKS FAT

37

What is the most common cause of hypoparathyroidism?
• hallmark symptoms?

Surgical Removal is the most common cause (followed by autoimmune disease and diGeorge Syndrome)

TETANY is the hallmark symptom (Chvostek, Trousseau)

38

What is the most common pathologic lesion of the pituitary?
• what should you look for histologically?

NON-FUNCTIONAL adenomas are the most common lesion of the pituitary

HISTO:
• Monomorphism and a Reticulin Network

39

What is a common gene mutated in FUNCTIONAL pituitary adenomas?

GNAS1 (most common mutation in GH adenomas and some ACTH adenomas)

40

If a family has a strong history of pituitary adenomas what genes might you expect are mutated?

MEN1 (Menin gene) could be mutated

41

If someone had an atypical, aggressive, and recurrent pituitary adenoma, what gene might be mutated?

P53

42

What other hormone is often secreted concurrently with GH in somatotroph adenomas?

Prolactin

43

What pituitary adenoma is PAS positive?

Corticotroph adenomas because glycosylated ACTH accumulates

44

What is NELSON SYNDROME?

Microadenoma that starts hypersecreting ACTH after adrenals are inappropriately removed because of Cushing syndrome

45

Someone has a recurring pituitary tumor that has been determined to be carcinoma because of chronic recurrence. Is it most likely functional or non-functional?

FUNCTIONAL

46

What are 3 causes of HypOpituitism?

1. Non-funcitoning Adenoma
2. Sheehan Syndrome
3. Empty Sella Syndrome

47

Why is the anterior pituitary more likely to infarct in Sheehan Syndrome?
• what is a key sign that a woman has Sheehan?

Anterior pituitary is supplied by a portal system, so it only has venous supply

Sheehan => POST PARDUM INABILITY TO LACTATE

48

Who do we most often see PRIMARY empty sella syndrome in?
• Secondary?

Primary:
• Obese person with multiple pregnancies

Secondary:
• Surgery on pituitary

49

What is the most common cause of hypothalamic suprasellar tumors?

Craniopharyngiomas

50

What is the age distribution of craniopharyngiomas?
• what are they derived from?
• What signaling pathway is often messed up?

• Bimodal
• Derived from Rathke's Pouch
• WNT/ß-catenin is often thrown off

51

Craniopharyngiomas histo?

• Wet Keratin
• Basaloid Cells
• Cholesterol Clefts

***Note: surgeons will comment on motor-oil like substance coming from the tumor***

52

What are the major factors contributing to the pathogenesis of T2DM?

• Circulating FAs (inflammasome activation => IL-1ß)
• Adipokines
• Inflammatory Mediators

53

What is the root cause of most of the chronic complications seen in DM?

Persistent Hyperglycemia

54

What manifestations of Diabetes are due to small vessel disease?

• HTN
• Hyaline Arteriolosclerosis
• Retinopathy
• Nodular Glomerular Sclerosis

55

What manifestations of Diabetes are due to osmotic damage?

• Neuropathy
• Cataracts

56

What is the leading cause of death in patients with DM?

Myocardial Infarction due to Large Vessel Disease and Athlerosclerosis

**Note: large vessel disease is also responsible for limb loss too***

57

What complication of Diabetes is associated with activation of PKC?

Retinopathy - PKC causes activation of VEGF that leads to neovascularization

58

What tissues are most affected by disturbances in the polyol pathway?

• Cornea
• Schwann Cells

***This is a problem in insulin independent tissues like Brain, RBCs, Intestine, Cornea, Kidney, Liver (BRICK L)***

59

Differentiate the vascular disease caused by DM in large vessels and small vessels.

Small - Hyaline Arteriolosclerosis

Large - Athlerosclerosis

60

What is the major cause of vision loss in DM?
• what happens in this type of eye disease?

• Retinopathy => PROLIFERATIVE

Pathogenesis:
• Neovascularization (PKC/VEGF mediated)
• Vitreous Hemorrhage
• Retinal Detachment

61

What do you do if you see evidence of retinopathy in a diabetic patient?

• Treat it fast and aggressively

62

T or F: diabetic neuropathy is most often bilateral and symmetric.

TRUE - can cause GASTROPARESIS and BLADDER DYSFUNCTION

63

What are the 3 glomerular lesions seen in diabetic nephropathy?

1. Basement membrane thickening
2. Diffuse Mesangial Sclerosis
3. Nodular Glomerulosclerosis

64

Other than indicating kidney involvement of DM, what is the significance of microalbuminuria in patients with DM?

Increased risk of CV death

65

What is nephrosclerosis?

Nodular Gross appearance of kidney in long standing DM

66

What changes are seen in end-stage renal disease?

1. Arteriolosclerosis
2. Fibrotic Cortex
3. Sclerotic Glomeruli
4. Thickened Arteries
5. Thyroidization of Tubules

67

What histology would you expect to see in Necrotizing Papillitis?

Lack of Cellularity with Pink Cellular Exudates

68

What rash associated with diabets has RED/BROWN margins?

Necrobiosis Lipodica

69

What should you start looking for in a patient with Acanthosis Nigricans?

DM is common, but this is also associated with paraneoplastic syndromes

70

What is the earliest histopathologic change in neurons in DM?

Segemental Demyelination (less blue staining with luxol fast blue stain)

71

What causes decreased immune function in patients with DM?

Impaired Neutrophil Mobilization
• increased expression of CD11b on neutrophils and ICAM, VCAM, and E-selectin on endothelial cells

Impaired Oxidative Burst (aldose reducase steals all of the NADPH

72

What causes decreased immune function in patients with DM?

Impaired Neutrophil Mobilization
• increased expression of CD11b on neutrophils and ICAM, VCAM, and E-selectin on endothelial cells

Impaired Oxidative Burst (aldose reducase steals all of the NADPH

73

What is the most common cause of ACTH dependent Cushing's syndrome?

Cushing DISEASE
• ACTH secreting pituitary adenoma

74

Why do hypertrophic adrenals in Cushing's look so yellow?

Because there is a ton of lip in the ER

75

What are 3 important causes of endogenous ACTH independent Cushing's Sydrome?
• which is most common?

1. 10% are adenomas (MOST COMMON)
2. 5% adrenal Carcinomas
3. McCune Albright Syndrome

76

In what type of Cushing's would you expect to see contralateral adrenal atrophy?

Endogenous ACTH independent Cushing's syndrome caused by some type of CORTISOL secreting tumor

77

What causes Conn syndrome?
• who presents with it?

Conn Syndrome = Primary Hyperaldosteronism (low renin, high aldosterone HTN)

Typical presentation is a 30-40 year old women who is hypertensive and hypokalemic

78

IF Primary Hyperaldosteronism is caused by an adenoma, what side is that adenoma most likely to reside on?

Most Common on the LEFT side

79

What would you expect to see in the histology of someone who is being treated for Conn Syndrome?

Spironolactone Bodies

80

What are 3 general causes of Secondary Hyperaldosteronism?

1. Low Renal Perfusion - nephrosclerosis or renal artery stenosis

2. Arterial Hypovolemia and Edema - CHF, liver failure, liver cirrhosis, and nephrotic syndrome

3. Pregnancy - ESTROGEN INDUCED INCREASE IN RENIN ACTIVITY

81

What is the inheritance of 21ß-hydroxylase deficiency?
• what labs abnormal in these people?

Autosomal Recessive
• Elevated 17-hydroxyprogesterone

82

What labs will be abnormal in 11ß-hydroxylase Deficiency?

Elevated:
• DHEA, and Adrostrendione, DOC = causes of the HTN

Depressed:
• Renin

83

What labs will be abnormal in 17 alpha hydroxylase deficiency?

Elevated:
• DOC, FSH and LH

Depressed:
• DHEA, Estrogen, testosterone, Androstiendione

84

What labs will be abnormal in someone with a 3ß-hydroxysteriod dehydrogenase deficiency?
• how do males with this disease present?

Labs: increased (delta5 pregnenolone) / (progesterone) ratio

Males: may have pseudohermaphroditism

85

What is the triad of McCune Albright syndrome?
• mutation?

Cafe-au-lait
Fibrous Dysplasia
Autonomous Endocrine Hyperfunction

86

What are 3 causes of acute adrenal insufficiency?

1. Withdrawl of glucocorticoids
2. Stress to great for adrenals (consider ppl. with Addison's etc.)
3. Massive Hemorrhage (anticoagulation, traumatic delivery, Waterhouse FS)

87

What are 4 causes of secondary adrenal insufficiency?

1. Hypopituitism
2. Trauma
3. Removal of ACTH secretory tumors
4. Granulomatous Disease

88

What two stains can you use on adrenal medullary tumors?

Chromogranin
Synaptophysin

89

What Syndromes/mutations are often associated with Pheochromocytomas?

MEN2A/B => RET
Neurofibromatosis => NF1
VHL
Sturge Weber

90

What do you expect to see histologically in a pheochromocytoma?

• Basophilic Cytoplasm
• ZELLBALLEN (cells in clusters)

91

What are 4 possible triggers for pheochromocytoma?

1. Postural Changes
2. Emotional Stress
3. Excercise
4. Urination

92

What cells do neuroblastomas arise from?
• WHERE do they most commonly arise?

• Post Ganglionic Sympathetic Neurons
• Common in the Adrenal Medulla

93

What are some clinical indicators of Neuroblastoma?

1. Palpable Abdominal Mass
2. Diastolic HTN
3. VMA and HMA

94

Who do we most commonly see Adrenal Cortical Adenomas in?
• Histological Appearance?

Mostly in women 30-50 years old = THESE ARE TYPICALLY NON-FUNCTIONAL

Histo:
• Neoplastic Cells are Vacuolated from Intracytoplasmic Lipid

95

Where is adrenal cortical carcinoma most likely to metastasize to?

• Adrenal Vein
• Vena Cava
• Lymph

96

Are adrenal cortical carcinomas typically functional or non-functional?

• Typically these are functional

**Median survival is only 2 yrs

97

Who most commonly gets pancreatic neuroendocrine tumors (NETs)?
• are these typically functioning or non-functioning?

Middle aged people get these and most (75%) are NON-FUNCTIONING

98

What do you stain pancreatic NETs with?

Chromogranin A (carcinoid tumor stain) will stain these cells whether or not they are functional

99

What hereditary disorders are associated with Pancreatic NETs?

MEN1
VHL syndrome
Neurofibromatosis
Tubular Sclerosis

100

How are pancreatic NETs graded?

1. Ki-67 stain
2. Number of Mitosis

101

Glucagonoma
3 key findings

Anemia
Diabetes
Necrotic Migratory Erythema

102

Somatostatinoma
3 key findings

Achlorhydria
Diabetes
Steatorrhea

103

Cell type that gives rise to Gastrinomas?

G-cells (gastrin stimulates parietal cells)

104

What is the most common functional Pancreatic NET?

Insulinoma

105

What is the only pancreatic net that is NOT automatically considered malignant?

Insulinomas are the only ones considered not malignant

106

VIPoma
3 key findings

Diarrhea
Hypokalemia and Acidosis
Hypovolemia

107

How do people with Insulinomas often present?

EPISODIC sever hypoglycemia (often precipitated by Fasting or Excercise)

***Labs will show a high insulin to glucagon ratio***

108

What Histological features are seen in Insulinomas?

• Abundant Amyloid in the Islets with a cord/nest configuration that is often separated by other tissue with a capsule

109

Why might a child be born and immediately have a severe hypoglycemic episode?

Maternal Diabetes is often the cause because hyperglycemia in the mother leads to the need for the child to secrete more insulin

110

Who gets Hyperinsulinism besides children born of mothers who have maternal DM?

People with Beckwith Wiedelmann Syndrome
People with mutations in the Beta cell Potassium Channel

111

T or F: most people with Gastrinomas have Mets at the time of dx/

True

112

What is the association of Gastrinomas and MEN?

MEN 1 is associated with gastinomas in 25% of gastrinoma cases

**SO LOOK FOR CONCURRENT HYPERPARATHYROIDISM**

113

Who most often presents with a glucagonoma?

Peri/Post menopausal women with extremely high glucagon levels

114

Why would people with somatostatinomas tend to get Cholelithiasis?

Inhibition of CCK prevents gallbladder contraction

115

VIPomas are also known as WDHAs (watery diarrhea hypokalemia achlorhydria) syndrome is associated with what Neural Crest Tumors?

Neuroblastomas
Ganglioneuroblastomas
Ganglioneuromas
Pheochromocytomas

116

What is the most common manifestation of MEN1?
• what is the most common cause of death?

Hyperparathryoidism

Most common cause of death:
• Pancreatic Tumors (remember gastrinomas (ZOLLIGER ELLISON SYNDROME), insulinomas)

117

How do MEN2 A and B differ clinically?

MEN2A:
• Parathyroid Hyperplasia

MEN2B:
• Neuromas and ganglioneuromas
• Marfan's-like-appearance