Thyroid Nodules and Neoplasms

Question 1

6 Steps in Nodule Eval

Answer 1

1- Hx

• any symptoms of hyperthyroid? (hormonally active)
• any symptoms of pushing on neighboring structures?(pressure sensation, dysphagia, dysphonia, dyspnea)-family hx or risk factors (radiation)

2- PE - differentiate thyroid and non-thyroid; malignant may be more firm and fixed and more likely cervical node involvement BUT otherwise not helpful in determining benign or malignant

3- Labs - thyroid function

- TSH -
    - If low then think hyperthyroid and confirm w/ free T4
    - If high then treat their hypothyroidism first then re-evaluate (nodule may just be due to excess TSH stimulation)
    - If normal ... move on to US and fine needle biopsy

4 - RAI uptake and scan ONLY if pt has hyperthyroidism; tells etiology

5- US - study of choice

    - Meas nodules and find non-palpable nodules
    - ID characteristics of benign v. malignant

6 - Fine Needle Aspiration - easy and inexpensive
- High negative predictive value; 98% chance it is just benign

Question 2

Hot v Cold Nodules (+ how to treat ea)

Answer 2

• “Hot nodule” - autonomously functioning; rarely malignant; treat hyperthyroidism (no need for US)
• “Cold nodule” - hypo-functioning or non-functioning compared to rest of thyroid; 5-8% are malignant so do US

Question 3

Thyroid Neoplasia Classification

Answer 3

Follicular (95%)

• Folicular adenoma (benign)
• Follicular carcinoma
• Oncocytic carcinoma (same cell type but look diff)
• Papillary carcinoma
• Anaplastic carcinoma (poor prognosis)

Para-follicular (3%)
-Medullary thyroid carcinoma (C cells - calcitonin sec)

Other - lymphoma or mets (2%)

Question 4

Papillary Carcinoma

Answer 4

• Gross - large lesion w/ papillary surface
• Histo -
  
  • Papillary or follicular growth pattern
  • Nuclei - grooves, inclusions, elongation, clearing, overlapping
  • Psammoma body (onion - layers of calcification)
• Cyto - hypercellular papillae, same nuclear features as histo
• Classification
  
  • Microscopic (<1 cm) or clinically relevant (>1 cm)
  • Extracapsular or extrathyroidal extension
  • Mets - usually to cervical nodes but does not mean worse prognosis
• Genetics - BRAF point mutations, RET-PTC translocations, RAS point mutations

Question 5

Follicular Adenoma

Answer 5

• Gross- encapsulated mass lesion
• Histo -
  
  • Tons of follicles
  • Distinct capsule so no evidence of invasion
  • Normal nuclei
• Cyto - see many follicular cells in micronodules w/ less colloid
• Benign; do not metastasize; removed then no additional therapy needed

Question 6

Follicular Carcinoma

Answer 6

• Gross - usually encapsulated but can be more aggressive or multifocal
• Histo
  
  • Identical to adenoma but invade capsule or vessels
• Cyto - identical to adenoma (not sufficient to make diagnosis - must see architecture to decide if adenoma or carcinoma)
• Classification
  
  • Minimally invasive - thru tumor capsule
  • Angio-invasive - thru vessels
  • Widely invasive - throughout or outside of thyroid
• Mets - esp if widely invasive; usually go to bone or lung NOT nodes b/c hematogenous spread
• Genetics - RAS point mutations, PAX8-PPAR gamma translocation

Question 7

Oncocytic Carcinoma

Answer 7

• Gross - Brown/mahogany lesion; usually encapsulated unless aggressive
• Histo
  
  • Follicular or solid growth pattern
  • Eosinophilic cytoplasm, enlarged round nuclei and prominent nucleoli
    
    • Same cell line as follicular tumors but different appearance so named for it - oncocytic OR Hurthle cells (fried egg b/c nucleolus)
  • Invasion of capsule or vessels
• Cyto - Hurthle cells, hypercellular, less colloid, not sufficient to decide adenoma or carcinoma
• Classification
  
  • Minimally invasive - thru tumor capsule
  • Angio-invasive - thru vessels
  • Widely invasive - throughout or outside of thyroid
• Mets - most are low grade so do not metastasize; likely bone or lung but occasionally nodes

Question 8

Anaplastic Carcinoma

Answer 8

• Gross - rapidly growing and widely invasion
• Histo -
  
  • Anaplastic tumor cells (very un-differentiated); some giant cells
• Cyto - can see giant cells
• Invasion into larynx and esophagus
• Poor prognosis - usually not surgical and <6 mo life expectancy

Question 9

Medullary Carcinoma

Answer 9

• Gross - unilateral or bilateral mass lesions
• Histo
  
  • Variable growth pattern
  • Nuclear - salt and pepper chromatin; neuroendocrine like
  • C cell hyperplasia esp in hereditary forms
  • Amyloid in them
  • Pos for calcitonin and might be pos for CEA
• Genetics - RET point mutation
• Cyto - can see amyloid in specimen
• Classification
  
  • Hereditary (20% - more likley to have C cell hyperplasia and be bilateral)
    
    • MEN2a
    • MEN2b
    • Familial Medullary Carcinoma
  • Sporadic (80%)

Question 10

MEN2a v. MEN2b

Answer 10

• MEN2a -parathyroid, medullary carcinoma and pheo
• MEN2b -medullary carcinoma, pheo, GI and ocular ganglioneuromas (can be anywhere in GI tract including mouth), skeletal deformity

Question 11

General Thyroid Cancer Tx Approach

Answer 11

1 - surgery (thyroidectomy, maybe nodes)

2 - adjuvant RAI (need TSH stimulation by injecting TSH or by stopping TH replacement to inc RAI uptake)

*** RAI IDs additional mets, destroys mets and destroys any normal tissue left behind (makes later monitoring more clear)

3- TSH suppression so that it does not stimulate thyroid; dec risk of recurrence

4 - +/- chemo and radiation if remnants

5- MONITOR FOR LIFE

    - 20-30% have re-occurence (esp first 10 yrs)
    - Use TBG as tumor marker
    - US of thyroid and neck
    - Diagnostic whole body radioiodine scan in case of distant mets in high risk pts (must be stimulated again - give TSH or stop hormone therapy)