Pathology Highlights Flashcards
1
Q
What are 3 other causes of Hyperthyroidism besides Grave’s?
A
- Multinodular Goiter
- Adenoma
- Iodine Induced Hypothryoidism
2
Q
What HLA type is associated with Grave’s?
A
HLA-DR3
3
Q
What is Plummer Syndrome?
• 2 causes?
A
Multinodular Goiter that is Toxic
Causes:
• Focal Patches
• Jod-Basedow Phenomenon (from iodine deficiency - opposite of Wolff-Chiakoff)
4
Q
Who is most likely to get toxic mulinodular goiter?
A
Women with long standing sporadic endemic goiter
5
Q
What histological feature differentiates toxic multinodular goiter from a follicular neoplasm?
A
TMG has a thin capsule while follicular neoplasms have a thick capsule
6
Q
What is most commonly the cause of death in thyroid storm?
A
Tachyarrhythmia
7
Q
T or F: carpal tunnel syndrome and delayed tendon relaxation are features of Grave’s disease?
A
False, this are features of hypothyroidism
8
Q
Who is most commonly affected by Hashimoto’s Thyroiditis?
A
Women 45-65
9
Q
What cells are responsible for mediating the autoimmune attack in Hashimoto’s?
• what are some key markers to look for in the serum?
A
T cells (CD4+) mediate Hashimoto’s
Key Markers:
• Anti-thyroglobulin Antibodies
• Anti-thyroid peroxidase Antibodies
10
Q
What HLA type(s) is/are associated with Hashimoto’s?
A
HLA-DR5**, and HLA-DR3
11
Q
What is a feared complication of Hashimoto’s Thyroiditis?
A
• Large Diffuse B-cell Lymphoma
12
Q
What histological changes would you see in Hashimoto’s?
A
Germinal Centers + Hurthle Cell Changes
13
Q
What are the chances of subacute lymphocytic thyroiditis progressing to Hashimoto’s?
A
1/3 progress to Hashimoto’s
14
Q
What would you expect to see in Histologically in Reidel’s Thyroiditis that is associated with IgG4 autoimmune disease?
A
Fibrosis and Lymphocytes
Note: this is typically a woman in her 40s
15
Q
Who most commonly presents with Granulomatosis Thyroiditis? (De Quervain’s)
A
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
Q
What do you expect to see histologically in someone who has Granulomatosis Thyroiditis?
A
Giant Cells and Granulomas
17
Q
T or F: most neoplasms of the thyroid are benign
A
True
18
Q
What features make a thyroid nodule more likely to be neoplastic?
A
- Solitary
- Young Person
- Male
- Hx of radiation to the head
19
Q
Are hot or cold nodules more likely to be associated with mutations in the the TSH receptor and GNAS1?
A
Hot (BENIGN) nodules are most commonly associated with these mutations
20
Q
What mutations are most commonly seen in cold nodules?
• where else are these mutations seen?
A
RAS and PIK3A mutations are most commonly seen in COLD nodules and in FOLLICULAR carcinomas of the thyroid
21
Q
What are the key histological features of a thyroid Adenoma?
A
- 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
Q
What is the typical age of presentation of papillary thyroid CA?
A
20-50
Remember mets have little prognostic significance
23
Q
What mutations are associated with Papillary thyroid CA?
A
RET and BRAF (worse px)
Remember tall cell variants are also associated with a bad PX
24
Q
What mutations are associated with Follicular thyroid CA?
A
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
