Thyroid Nodules--Clinical/Pathologic/Pathophys Correlates

Question 1

how common are thyroid nodules

Answer 1

30-60%;

• 25 year old - 10%
• 70 year old 55%

Question 2

risk of cancer in thyroid nodule

Answer 2

small (10-15%) but not insignificant

Question 3

how are most thyroid nodules detected

Answer 3

noted by pt, noted by third party, detected by other tests,

- 1/3 via testing: US > CT > PET

Question 4

normal thyroid structure

Answer 4

• butterfly shaped organ in neck; L and R lobes
• follicular cells with parafollicular/C cells
• follicles round, dark, uniform, and filled with colloid

Question 5

what does a nodule look like

Answer 5

well circumscribed, different color from surroundign thyroid

Question 6

types of thyroid neoplasms

Answer 6

• benign - adenoma (most common)
• malignant- papillary, carcinoma, follicular/Hurthle, anaplastic, medullary
• lymphoma, sarcoma
• metastatic

Question 7

rank the malignant thyroid tumors from most to least common

Answer 7

papillary (85-90%)
Follicular/Hurthle (5%)
Medullary (5%)
Anaplastic (

Question 8

Thyroid adenoma

Answer 8

benign neoplasm, solitary nodule

• composed of follicular cells/Hurthle cell
• smaller follicles

Question 9

how do you distinguish between adenoma and carcinoma

Answer 9

have to look at specimen

Question 10

Follicular/Hurthle cell Carcinoma

Answer 10

• 2 types (minimally invasive - vascular or capsular invasion, widely invasive - more extensive invasion)

Question 11

Papillary carcinoma

Answer 11

• most common malignant
• well differentiated
• multifocal– often will take out whole gland since often multifocal
• lymphatic spread
• excellent prognosis

Question 12

features of papillary carcinoma

Answer 12

• papillae with vascular core
• optically clear nuclei; “open eyed nuclei”– have dark nucleus pushed to outside
• nuclei tend to be large
• nuclear pseudoinclusions
• nuclear grooves, rare or absent mitoses
• Psammoma Bodies (calcification)
• Have follicular variant that aren’t forming papillary fronds by trying to form follicular structures– still have odd nuclear features

Question 13

Anaplastic carcinoma

Answer 13

• older age group (poor survival)
• rapidly growing– often will have lump for months to years without changes then suddenly starts growing rapidly
• 3 patterns (spindle cell, giant cells, squamoid cells
• necrosis and hemorrhage
• anaplastic– undifferentiated, ugly look – not looking like thyroid

Question 14

Medullary Carcinoma

Answer 14

• solid proliferation of cells with granular cytoplasm (C cells)
• highly vascular stroma
• hyalinized collagen and/or amyloid
• may have Psammoma bodies (calcification)
• Immunostains: Thyroglobulin -, Calcitonin +, Chromogranin +
• can’t tell difference with other thyroid tumors
• Note chromogranin from neuroendocrine

Question 15

Lymphomas

Answer 15

• can arise in thyroid
• background autoimmune thyroiditis can eventually lead to lymphoma with chronic inflammation
• large, fleshy masses
• DDx- anaplastic ca of thyroid
• positive LCA, usually B cell
• gene rearrangement

Question 16

Metastatic cancers to thyroid

Answer 16

melanoma, lung, head and neck, renal, breast, colon

Question 17

Things to look for in hx

Answer 17

growth, pain, cough/voice change, irradiation, family hx (about 10% familial)

Question 18

what to look for on physical exam

Answer 18

size, consistency (rock hard more concerning), fixation (nl thyroid should move with swallowing), lymphadenopathy

Question 19

3 key tests for thyroid

Answer 19

TSH, US, fine needle aspiration biopsy (if meets criteria)

Question 20

if FNAB suspicious/indeterminate

Answer 20

will only do scan if low TSH

Question 21

Dip quick stain

Answer 21

Dip fine needle aspiration int his too see if good biopsy

Question 22

Hurthle cells

Answer 22

• have more pink, grainy cytoplasm

- follicular cells with different microscopic appearance

Question 23

papillary carcinoma of thyroid cytologic features

Answer 23

- highly cellular, 
\+/- colloid
- nuclear enlargement, elongation
- nuclear grooves, pseudoinclusions
- multiple small  to large nucleoli
- Psammoma bodies (rarely seen)
- papillary cellular aggregate

Question 24

anaplastic cancer cytology

Answer 24

large, wacky cells, huge nucleoli, multinucleated

Question 25

lympnoma cytology

Answer 25

very uniform, really no cytoplasm

Question 26

Bethesda diagnostic categories for thyroid nodules

Answer 26

non-diagnostic, benign, ACUS(indeterminate), suspicious for follicular neoplasm, suspicious for malignancy, malignant

Question 27

management for malignant nodules

Answer 27

remove thyroid, +/- LN depending on US

Question 28

management for nodule suspicious for malignancy

Answer 28

thyroidectomy +/- LN depending on US

Question 29

management for nodule suspicious for follicular neoplasm

Answer 29

lobectomy--look at capsule to determine if foll. carcinoma or just adenoma

Question 30

proto-oncogene

Answer 30

normal gene which codes for a protein that promotes normal cell division

Question 31

oncogene

Answer 31

mutated gene which codes for a protein that causes unregulated cell division

Question 32

tumor suppressor gene

Answer 32

normal gene which codes for a protein that restrains cell division or that promotes cell differentiation, DNA repair or apoptosis (example: p53)

Question 33

most common genetic pathway messed up in thyroid cancer

Answer 33

- MAP kinase | - usually signals through Ras to BRAF and to MEK-ERK system-- stimulates cell growth and division

Question 34

tumors result from

Answer 34

oncogene activation or tumor suppressor gene loss - cancers result from multiple sequential genetic mutations - cells transformed by genetic mutations likely to develop more mutations

Question 35

Most common mutations in Papillary Ca

Answer 35

- proto-oncogene RET/PTC (20%)-- rearrangement--now becomes expressed - pt mutation in Ras (20%) - BRAF point mutation (40%) - can have p53 inactivating point mutation

Question 36

most common mutation in thyroid cancer

Answer 36

BRAF point mutation

Question 37

do thyroid tumors have multiple mutations

Answer 37

usually just one but can have more

Question 38

Follicular Carcinoma mutations

Answer 38

- pt mutation in RAS - PI3 kinase pathway or Map kinase - Pax8-PPARgamma rearrangement (20-40%)-- get fusion protein

Question 39

what has to happen to get anaplastic carcinoma

Answer 39

need to have activating mutation and also inactivating of tumor suppressor (p53 or beta catenin)

Question 40

which cancer has highest 2- year outcome

Answer 40

papillary thyroid carcinoma