Thyroid Nodules--Clinical/Pathologic/Pathophys Correlates Flashcards
how common are thyroid nodules
30-60%;
- 25 year old - 10%
- 70 year old 55%
risk of cancer in thyroid nodule
small (10-15%) but not insignificant
how are most thyroid nodules detected
noted by pt, noted by third party, detected by other tests,
- 1/3 via testing: US > CT > PET
normal thyroid structure
- butterfly shaped organ in neck; L and R lobes
- follicular cells with parafollicular/C cells
- follicles round, dark, uniform, and filled with colloid
what does a nodule look like
well circumscribed, different color from surroundign thyroid
types of thyroid neoplasms
- benign - adenoma (most common)
- malignant- papillary, carcinoma, follicular/Hurthle, anaplastic, medullary
- lymphoma, sarcoma
- metastatic
rank the malignant thyroid tumors from most to least common
papillary (85-90%)
Follicular/Hurthle (5%)
Medullary (5%)
Anaplastic (
Thyroid adenoma
benign neoplasm, solitary nodule
- composed of follicular cells/Hurthle cell
- smaller follicles
how do you distinguish between adenoma and carcinoma
have to look at specimen
Follicular/Hurthle cell Carcinoma
- 2 types (minimally invasive - vascular or capsular invasion, widely invasive - more extensive invasion)
Papillary carcinoma
- most common malignant
- well differentiated
- multifocal– often will take out whole gland since often multifocal
- lymphatic spread
- excellent prognosis
features of papillary carcinoma
- 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
Anaplastic carcinoma
- 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
Medullary Carcinoma
- 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
Lymphomas
- 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
Metastatic cancers to thyroid
melanoma, lung, head and neck, renal, breast, colon
Things to look for in hx
growth, pain, cough/voice change, irradiation, family hx (about 10% familial)
what to look for on physical exam
size, consistency (rock hard more concerning), fixation (nl thyroid should move with swallowing), lymphadenopathy
3 key tests for thyroid
TSH, US, fine needle aspiration biopsy (if meets criteria)
if FNAB suspicious/indeterminate
will only do scan if low TSH
Dip quick stain
Dip fine needle aspiration int his too see if good biopsy
Hurthle cells
- have more pink, grainy cytoplasm
- follicular cells with different microscopic appearance
papillary carcinoma of thyroid cytologic features
- highly cellular, \+/- colloid - nuclear enlargement, elongation - nuclear grooves, pseudoinclusions - multiple small to large nucleoli - Psammoma bodies (rarely seen) - papillary cellular aggregate
anaplastic cancer cytology
large, wacky cells, huge nucleoli, multinucleated
lympnoma cytology
very uniform, really no cytoplasm
Bethesda diagnostic categories for thyroid nodules
non-diagnostic, benign, ACUS(indeterminate), suspicious for follicular neoplasm, suspicious for malignancy, malignant
management for malignant nodules
remove thyroid, +/- LN depending on US
management for nodule suspicious for malignancy
thyroidectomy +/- LN depending on US
management for nodule suspicious for follicular neoplasm
lobectomy–look at capsule to determine if foll. carcinoma or just adenoma
proto-oncogene
normal gene which codes for a protein that promotes normal cell division
oncogene
mutated gene which codes for a protein that causes unregulated cell division
tumor suppressor gene
normal gene which codes for a protein that restrains cell division or that promotes cell differentiation, DNA repair or apoptosis
(example: p53)
most common genetic pathway messed up in thyroid cancer
- MAP kinase
- usually signals through Ras to BRAF and to MEK-ERK system– stimulates cell growth and division
tumors result from
oncogene activation or tumor suppressor gene loss
- cancers result from multiple sequential genetic mutations
- cells transformed by genetic mutations likely to develop more mutations
Most common mutations in Papillary Ca
- proto-oncogene RET/PTC (20%)– rearrangement–now becomes expressed
- pt mutation in Ras (20%)
- BRAF point mutation (40%)
- can have p53 inactivating point mutation
most common mutation in thyroid cancer
BRAF point mutation
do thyroid tumors have multiple mutations
usually just one but can have more
Follicular Carcinoma mutations
- pt mutation in RAS
- PI3 kinase pathway or Map kinase
- Pax8-PPARgamma rearrangement (20-40%)– get fusion protein
what has to happen to get anaplastic carcinoma
need to have activating mutation and also inactivating of tumor suppressor (p53 or beta catenin)
which cancer has highest 2- year outcome
papillary thyroid carcinoma
