1. Update on Thyroid Cancer
KY Chapter ACS Meeting
September 8, 2017
Cortney Y. Lee, MD, FACS
Associate Professor of Surgery
Section of Endocrine Surgery

2. Objectives Review the evaluation and management of thyroid nodules.
Discuss FNA diagnosis including Bethesda Criteria.
Summarize types of thyroid cancer including differences in treatment.
Explain the new diagnosis of NIFTP and how it affects treatment/management.
Describe the surgical management of thyroid cancer.
Compare the shift in use of radioactive iodine in lieu of recent ATA guidelines.

3. “Can the thyroid in the state of enlargement be removed
“Can the thyroid in the state of enlargement be removed? Emphatically experience answers no…every stroke of the knife will be followed by a torrent of blood and lucky will it be for him if his victim lives long enough for him to finish his horrid butchery. No honest and sensible surgeon would ever engage in it.” - Samuel Gross 1848

4. Father of Thyroid Surgery
Emil Theodor Kocher
( )
Nobel Prize 1909
Study of the thyroid

5. Another nodule?!!!
Thyroid nodules

6. Thyroid disease 30 million Americans with thyroid problems
15 million Synthroid scripts written annually
1 of 10 women has a thyroid nodule
60% women have a nodule by 60 yo
Abnormalities found on exam or incidentally on imaging
ATA guidelines on thyroid nodules and differentiated thyroid cancer
Search “ATA guidelines” 2

7. What if I find a nodule? TSH ULTRASOUND is best imaging test
If normal/high, proceed with US/FNA
If low, nuclear uptake scan (only indication)
ULTRASOUND is best imaging test
FNA if indicated
ATA 2015 guidelines

8. 1 cm
1.5 cm
2 cm
No FNA
2015 ATA Thyroid Nodule/DTC Guidelines

9. 2009 ATA Guidelines for Nodules

10. 2015 ATA Guidelines for Nodules

11. US
Size
FNA
2015 ATA Thyroid Nodule/DTC Guidelines

12. Thyroid Nodule Cliff Notes
Workup: TSH, US, FNA
Uptake scan is ONLY for hyperthyroidism
FNA criteria for nodules
Solid ~1.0 to1.5 cm
Complex/Spongiform ~ 2 cm
Simple cysts – no FNA

13. What is “Bethesda”?
Thyroid FNA

14. Fine Needle Aspiration)
Office procedure with ultrasound guidance
Must get an adequate sample
6 groups of at least 10 cells each
2 passes minimum
Immediate cytopathology helps adequacy
Once adequate, three possible answers:
Benign (Bethesda II)
Malignant (Bethesda VI)
Indeterminant (Bethesda III, IV, V)

15. Repeat FNA (+/- genetic classifier) OR surgery
Benign
Indeterminant
Malignant
Chance of cancer
≤3%
Chance of cancer
5-75%
Chance of cancer ≥97%
Repeat US
Surgery
Repeat FNA (+/- genetic classifier) OR surgery
Total
(vs. lobe)
+/- lymph nodes
Stable
Growth
If surgery, lobe.
If benign, follow.
No f/u
Repeat FNA

16. Key words in FNA reports
Adequate
“No malignancy”
Drying artifact
Obscured by blood
Paucicellular
Follicular cells
Hurthle cells
Lymphocytes
Macrofollicles
Macrophages
Thin colloid
Cellular
Cytologic atypia
Microfollicles
Nuclear grooves
Intranuclear inclusions
Thick colloid
Unfortunately, not all pathologists use the Bethesda categories, which can make interpretation difficult.

17. Common descriptions
Benign – bland follicular cells, abundant colloid, macrophages, Hurthle cell change
Hashimoto’s – lymphocytes, Hurthle cells
Follicular/Hurthle cell nodules – cellular with predominantly follicular or Hurthle cells, microfollicles, little to no colloid
Papillary – Nuclear grooves, intranuclear inclusions, powdery chromatin

18. Algorithm for FNA result
6 Bethesda Categories
2015 ATA Thyroid Nodule/DTC Guidelines

19. Bethesda Categories 2015 ATA Thyroid Nodule/DTC Guidelines
The Bethesda System for Reporting Thyroid Cytopathology.
ES Cibas, SZ Ali. Thyroid. Nov 2009, 19(11):
2015 ATA Thyroid Nodule/DTC Guidelines

20. Bethesda Categories Molecular/Genetic Testing Category % cancer
Recommendation I
Nondiagnostic
1-4%
Repeat FNA II
Benign
0-3%
US follow up
III
AUS/FLUS
5-15% IV
Follicular neoplasm/Suspicious for follicular neoplasm
15-30%
Surgery (lobe) V
Suspicious for malignancy
60-75%
Surgery (lobe vs. total) VI
Malignant
97-99%
Surgery (likely total)
Molecular/Genetic
Testing
Discuss follicular and hurthle cell cancer– about diagnosis (invasion, etc)
The Bethesda System for Reporting Thyroid Cytopathology.
ES Cibas, SZ Ali. Thyroid. Nov 2009, 19(11):

21. Gene Expression (i.e. Afirma)
Designed to assist in the indeterminate categories (mainly Bethesda III and IV)
Classifies indeterminate as:
Benign = <6% risk of malignancy
Suspicious = ~40% risk of malignancy
Use to avoid unnecessary surgery
Afirma suspicious ≠ cancer

23. FNA Cliff Notes Assure adequacy
Request Bethesda classification by your pathologists
Follicular neoplasm ≠ cancer
Genetic/molecular tests can help

24. “If you had to pick a cancer…”
Thyroid cancer

25. Rising incidence of thyroid cancer
Increased incidental findings (imaging)
Significant cancers are also increasing
Mortality is stable

26. Thyroid Cancer
Papillary, Follicular, Hurthle cell, Medullary, Anaplastic
Surgery ideal for all
RAI used postoperatively in some
Pregnancy– surgery can usually be delayed until after delivery
Can observe very small cancers in poor surgical candidates
Mention that Hurthle cell = oncocytic and that Hurthle is a variant of follicular

27. Types of thyroid cancer
Diagnosis on FNA?
RAI avid?
Prognosis
10yr / 20 yr survival (%)*
Papillary
Yes
Best
95.5 / 94.7
Follicular No
Most (2/3)
80.5 / 71.1
Hurthle
Some (1/3)
84.4 / 78.7
Medullary
Yes (occ.)
None
82.9 / 79.7
Anaplastic
Usually not needed
Worst
Fatal
For benign FNAs– if susp US features, repeat US/FNA in 1 year. If low/intermediate– repeat US in 1-2 years. If very low risk, maybe never but if so >2 years.
When repeating FNAs, some say wait 3 months, but it’s not been shown that waiting that long is necessary to get a better answer.
*Survival data from Mayo Clinic

28. TNM for Thyroid Cancer T Categories N Categories Tx Not assessed
T0 No evidence of 1°
T1a ≤ 1 cm
T1b cm
T cm
T3 >4 or minimal ETE
T4a gross ETE
T4b invading spine or major vessels (arteries)
All anaplastic T4a or T4b
Nx Nodes not assessed
N0 Nodes negative
N1a Central nodes (VI)
N1b Lateral nodes (II-V, VII)
M Categories
Mx Not assessed
M0 No distant mets
M1 Distant mets
2015 ATA Thyroid Nodule/DTC Guidelines

29. Staging for PTC & FTC < 45 yo ≥ 45 yo Stage I Any T, any N, M0
T1 (<2 cm), N0, M0
Stage II
Any T, any N, M1
T2 (2-4 cm), N0, M0
Stage III
T3, N0, M0 or T1-3, N1a, M0
Stage IVA
T4a or any T, N1b, M0
Stage IVB
T4b (any N, M0)
Stage IVC
* The staging system will change in January 2018 (one change is age to 55)
2015 ATA Thyroid Nodule/DTC Guidelines

30. Factors that influence prognosis
Age (40yo for men, 50yo for women)
Size of primary
Extrathyroidal invasion
Aggressive variants (tall cell, columnar)
Extent of nodal metastases
Distant mets
Sex (questionably worse for men)

31. New Diagnosis: NIFTP
International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
NIFTP= Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
Previously classified as FVPTC

32. “Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma”. YE Nikiforov, et al. JAMA Oncol Aug 1; 2(8):

33. “Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma”. YE Nikiforov, et al. JAMA Oncol Aug 1; 2(8):

34. How does NIFTP change things?
Changes surgical management
No need for completion or RAI
Patient DOES need follow up (like a cancer)
Risk % of malignancy in Bethesda will change
Affects utility of molecular/genetic tests

35. Cancer Cliff Notes Papillary is most common and has best prognosis
Follicular and Hurthle cell cancers CANNOT be diagnosed on FNA– only on final pathology
New NIFTP is not cancer, but not benign
Medullary pts need genetic evaluation

36. What changes with cancer?
Surgery for cancer

37. Surgical Options Total (or near-total) thyroidectomy
No role for subtotal thyroidectomy
Small PTC/FTC can be treated with lobectomy
If known nodal involvement, entire compartment should be addressed
Central (VI) vs. Lateral (II-V)
Prophylactic central node dissection
Pro: staging, could change treatment; decrease need for future central neck surgery
Con: more risk to parathyroids, higher risk of temporary hypoparathyroidism, doesn’t change outcome

38. Nodal Basins
Imperative to perform detailed US of nodal basins (II-VI) preoperatively
Can change surgical decision making
Anatomic compartment dissections
Not “berry picking”

39. Postsurgical treatment & follow up
It’s out. Now what?
Postsurgical treatment & follow up

40. How do we follow thyroid cancer?
Thyroglobulin (Tg)
Made by normal thyroid and most thyroid cancers
Used as a tumor marker after resection of tumor
Not used to diagnosis cancer prior to surgery US
Nodes
Remaining thyroid (if applicable)

41. TSH Suppression Thyroid hormone suppresses cancer Goal TSH
Low risk, Tg <0.2 TSH
Low risk, Tg >0.2 TSH
Intermediate risk TSH
High risk TSH <0.1
If excellent response to therapy, TSH up to

42. Why give radioactive iodine?
Primary goal: ablation of thyroid remnant
Recommended ablative dose of mCi
Can also treat non-imagable micrometastases
Can be therapeutic
Need higher dose (100+ mCi)
Given 1-2 months after surgery
Low iodine diet for 2 weeks prior to treatment
Must elevate TSH prior to treatment

43. Two methods of TSH elevation
Hormone withdrawal
Patient stops short-acting thyroid hormone 2 weeks prior to treatment
Cheap, effective, miserable
Thyrogen (recombinant human TSH)
Shots for a few days prior to treatment
Expensive, but avoids swing in hormone levels (less life-altering)

44. Who needs RAI?
2015 ATA Thyroid Nodule/DTC Guidelines

46. (continued)

47. Who needs RAI?
Clearly indicated in large cancers (>4cm) and cancers with aggressive features, invasion or lateral nodal mets
Not indicated in cancers ≤ 1cm
Clear benefit not demonstrated in most cancers <4 cm without suspicious features or nodal involvement

48. Changes in recommendations
Indication for RAI is decreasing
Less need for RAI changes surgical planning
Lobectomy may be a viable option in low-risk cancers
Requires a change in our standard treatment and follow up of thyroid cancer
Ongoing evolution

49. Cut-throat surgeons…
Why surgery?!

50. Thyroid Surgery Outpatient surgery (or overnight)
Incisions much smaller than in past
Recovery
~1 week off work
No restrictions (except for driving for 4-5 days)
Low risk in experienced hands (temp, permanent)
Voice – injury to recurrent laryngeal nerve (<5%, <1%)
Hypocalcemia – injury to parathyroids (10-15%, 2-5%)
Post op hematoma (<1%)

51. “High-volume” Thyroid Surgeon
The more the surgeon does, the better the outcomes
Number/year ranges from 25 to 100

52. Tricks of the trade Nerve monitoring Latest technology
Special ET tube with wires
Can avoid dreaded bilateral injury by stopping if first side is injured

53. More Tricks of the Trade
Autotransplantation
Transplant normal parathyroids into the muscle
Will eventually make their own hormone
PTH monitoring in the OR
Monitor the levels of parathyroid hormone
Helps guide medication after surgery

54. Big and small
5 g g

55. Summary: 10 Years of Thyroid Cancer Progression
Bethesda classification of FNA
Genetic/molecular evaluation of indeterminate nodules
RAI use more limited resulting in changes in surgical treatment (lobes for low-risk cancer)
NIFTP– no longer cancer, but not benign–changing the way we evaluate nodules
Less complications with >25 cases/yr

56. Useful websites American Thyroid Association (ATA)
Search “ATA guidelines”
American Association of Endocrine Surgery (AAES)
EndocrineSurgery.org
EndocrineDiseases.org (patient education)

57. Questions? Cortney Y. Lee, MD, FACS Associate Professor of Surgery
Section of Endocrine surgery
Clinic: (859)