Thyroid CA

Question 1

Thyroid nodules

Answer 1

• Frequency is 5x higher in females
• Only 5% are malignant, 95% benign
• It is important to make the distinction if the lesion is diffuse enlargement (goiter) or focal enlargement (neoplasia)

Question 2

Worrisome findings on evaluation of thyroid nodule

Answer 2

• Extremes of age
• Male sex (higher % of malignant lesions in males)
• Subacute presentation
• Increasing size/fast growth rate
• Painlessness
• Family Hx
• Xray exposure
• Change in voice (hoarseness)
• Size of nodule >2.5cm
• Hard and/or fixed lesion
• Lack of other glandular pathology
• Adenopathy
• Normal TSH and negative antiTPO titers suggest CA

Question 3

Using ultrasound to Dx thyroid nodules

Answer 3

• Complex cysts look like simple cysts but can harbor papillary CA
• Differs in that there is an area of hyperechoicness in complex, but none in simple (all hypoechoic)
• Hyperechoic is most consistent w/ benign lesion
• Hypoechoic nodule is more consistent w/ malignancy, as is increased vascularity
• Calcifications: starry-night look (specks of hyperechoicness) consistent w/ malignancy
• Shaggy borders indicates infiltration of surrounding tissue and malignancy
• But overall ultrasound is not very good at Dxing thyroid CA, want to do FNA
• Used to determine size of nodule

Question 4

Thyroid nodule FNA

Answer 4

• Cytology classification (min 60 cells): non diagnostic, benign, undetermined, follicular neoplasm, suspicious for malignancy, malignant
• Can Dx from FNA: MNG, chronic thyroiditis, cysts, papillary CA, papillary-follicular CA
• Cannot Dx follicular CA from adenoma via FNA

Question 5

Thyroid scan

Answer 5

• Give low dose I123 and see if the nodule is hot (takes up iodine) or cold (doesn’t take up iodine)
• Cold nodules are consistent w/ but not diagnostic of CA
• Hot nodules are benign

Question 6

Pathogenesis of differentiated thyroid CA (DTC)

Answer 6

• 80% are papillary, 15% follicular, 5% anaplastic (medullary thyroid CA is a C cell CA)
• Biggest risk factor: Xray exposure
• Papillary thyroid CA: papillary pillars (fingers), on high mag there are cells w/ orphan annie (punched out) nuclei and coffee been grooves
• Papillary thyroid CA spreads primarily via lymph, whereas follicular CA spreads primarily via blood
• Thus papillary has better prognosis
• Anaplastic has worst prognosis (100% mortality)

Question 7

Tumorigenesis

Answer 7

• Most come from inactivation of tumor suppressor genes
• One of the most implicated is mutations in the RAS oncogene that leads to increased DNA susceptibility to other mutations (initiating event-> more mutations-> CA)
• Disease-specific mutations: PTC/ret gene mutations implicated in papillary CA (PTC/ret fusion leads to increased MAP kinase and thus cell division)
• BRAF mutations and papillary CA
• PPARg-PAX8 fusion and follicular CA
• P53 mutations and anaplastic CA

Question 8

Rx of thyroid CA

Answer 8

• Total thyroidectomy is ideal Rx and for staging the tumor
• Then prep for post-op 131I Rx (if mets) and follow-up Tg levels
• Give LT4 after I131 if done (want TSH to be high for I131 so it is taken up by CA cells) to suppress TSH
• While on the LT4 suppression (TSH low) remeasure Tg levels and compare to baseline (preop)
• Tg will be the marker to track recurrence of disease, since nearly all thyroid CA secrete Tg
• Rising Tg value in face of suppressed serum TSH means recurrence of CA (brain>bone>lung>local)
• Can do I131 whole body scan, but its expensive and not great
• Follow the pt w/ Tg/TSH every 6 mo for first 5 yrs, then every yr after 5 yrs of CA free

Question 9

Prognostic parameters

Answer 9

• No mets
• <2cm in size
• Females do better than males

Question 10

Indications for I131 Rx in PTC

Answer 10

• Metastatic disease (absolute)
• The rest are relative indications
• Tumore size >2.5cm
• Age >45
• Detectable post-op Tg level
• Male gender
• I131 only reduced mortality in stage 3 disease

Question 11

Side effects of I131

Answer 11

• Hypothyroidism, hospitalization
• Decreased sperm counts, rise in LH/FSH and transient amenorrhea, premature meanopause
• May increase breast CA risk
• Salivary gland dysfxn
• Bone marrow suppression
• Pulmonary fibrosis
• At high doses possibly bladder and gastric CA