09 01 05 Entgr Management Of Well Differentiated Thyroid Cancer

1. Management of Well Differentiated
Thyroid Cancer
Vivek Ramarathnam, M.D.
SIU- Otolaryngology
Grand Rounds
9/1/2005

2. Thyroid Nodules
Between 4-7% of individuals in US have
palpable thyroid nodules
More common in women
Increase in frequency with age
Fewer than 10% of solitary nodules are
malignant
- Papillary (75%)
- Follicular (15%)

3. Thyroid Carcinoma
1.5% of all newly diagnosed cancers
Number increasing over last 25 years;
4.8 to 8.0 cases per 100,000
Female predominance (11.7 female to 4.2
male cases/100,000
Death rate 0.5 cases per 100,000

4. Nodules and Carcinoma Rates
Rates of carcinoma in a single nodule:
5-17%
Rates of carcinoma in multinodular patients:
5-13%

5. Risk Factors for Malignancy
Prior irradiation
Family history
Male sex
Nodules in individuals <15, >45
Symptoms of invasiveness: development of
hoarseness, progressive dyshagia, or
dyspnea

6. Physical Examination
Pulse rate, Blood Pressure
Neck Lymphadenopathy
Deviation of Trachea
Palpation of Thyroid gland
(Size, consistency, mobility, presence or
absence of tenderness, multinodularity)
Attention of thyroid mass to surrounding
anatomy

7. Preoperative Evaluation
Individuals with symptoms potentially of invasive
carcinoma- dysphonia, dysphagia, or stridor
Flexible laryngoscopy
MRI allows soft tissue evaluation (cervical
esophageal invasion)
CT, readily available, iodinated contrast used can
delay the use of RAI postoperatively 4-6 weeks
Selected patients, panendoscopy

8. Thyroid Picture

9. Thyroid Anatomy
Arteries- Paired arteries, superior, inferior
arteries
Venous drainage- parallels arterial drainage,
superior thyroid veins drain into internal
jugular vein, inferior thyroid veins to
brachiocephalics
Lymphatics- intraglandular lymphatic
network, paratracheal, upper, mid, and lower
jugular nodes

10. Thyroid Hormone Physiology
Growth- hormones work in bone formation
CNS- brain maturation
Basal metabolic rate
Cardiovascular and respiratory systems
Metabolic effects

11. Thyroid Histology

12. Thyroid Hormone Regulation
TSH stimulates both
iodine uptake and its
organification

13. Management steps with a Thyroid
Nodule
1.TSH level
- 95% of all nodules are hypofunctional
(cold)
3.If TSH normal, obtain a ultrasound and
perform FNA
- if firm and palpable FNA can be performed
without image guidance

14. Ultrasound Imaging and Nodules
US reports thyroid size and appearance, 3D
description of specific nodules, presence of
paratracheal nodes, and evidence of invasive
qualities.
Useful in individuals undergoing FNA and
have difficult lesions to palpate.
 Also beneficial in complex cysts, and
nodules with questionable multinodularity

15. Management steps with a Thyroid
Nodule
If TSH high, treat with thyroid hormone
replacement and FNA when patient is
euthyroid
TSH level low; may have hyperfunctioning
nodule and should be evaluated with thyroid
scan. Low likelihood of malignancy

16. Evaluation of solitary nodule
FNA (fine needle aspiration)
4 types of interpretations:
1) Benign
2) Malignant
3) Suspicious for follicular or Hurthle cell
tumor
4) Insufficient for diagnosis

17. Overview of Nodule workup

18. Case Presentation
22 female referred for enlarging thyroid mass
Right lobe of thyroid. Last year 2.8 cm and
now 3.4 cm in greatest diameter. Complex
mass described per US report. Otherwise
asymptomatic. Mother- hyperthyroid.
Medications: Effexor XR, Ortho patch
FNA- Cellular follicular lesion

19. Papillary Carcinoma

20. Follicular Carcinoma

21. Fine needle aspiration
Procedure requires skill by operator, as well
as by cytopathologist
Even in skilled hands, approximately 10% of
biopsy findings nondiagnostic
Sensitivity 92%, Specificity- 91-97.5%

22. Findings on FNA
Benign finding- Followed serially by US
If nodule has increased in size ~15%, repeat
FNA should be performed
Follicular neoplasm- 80% of these nodules
are benign, 20% represent thyroid carcinoma
Papillary carcinoma- accuracy of FNA
approaches 100%

23. Fine needle aspiration
Suspicious for follicular or Hurthle cell tumor
Diagnosis of follicular of Hurthle cell tumor
from follicular carcinoma or Hurthle cell
carcinoma requires presence or absence of
capsular or vascular invasion seen on
histologic examination of surgical specimens
Follicular and Hurthle cell tumors diagnosed
by FNA have malignancy rate of 10-20%

24. Case Presentation
Pt underwent Right lobectomy with
isthmusectomy
Frozen section- Follicular neoplasm
Final pathology- Follicular adenoma

25. Management of FNA results
Follicular neoplasm
-Thyroid lobectomy, allow histiopathologic
diagnosis to dictate need for total
-Serial US, TSH suppression, repeat FNA
- Plan for lobectomy with frozen section, if
reveals follicular variant of papillary,
perform total
- Perform total thyroidectomy

26. Staging

27. Staging

28. 5 year survival rates
47.1%45.3%Stage 4
79.4%95.8%Stage 3
100%100%Stage 2
100%100%Stage 1
Follicular CancerPapillary Cancer

29. Risk Analysis
AGES (age, grade, extent, size)
AMES (age, metastases (distant), extent,
size)
MACIS (metastasis, patient age,
completeness of resection, local invasion,
and tumor size)

30. AGES
Hay ID, et al. 61
st
American Thyroid Association Annual Meeting 1986
Papillary CA
N= 860
Age= 0.5 x age
Grade2 = 1
Grade3-4 =3
Extrathyroidal=1
E(distant)= 3
Size= 0.2 x cm

31. Hay ID, et al.

32. Surgical Management
Wein, RO, Weber RS, Contemporary Management of Differentiated
Thyroid Carcinoma. Otolaryngol Clin N Am 2005
“ Surgery therapy for the majority of well-
differentiated thyroid carcinomas should be
tailored to the eradication of macroscopic
disease while preserving the patient’s
capacity for functional speech and
swallowing and parathyroid preservation.”

33. Lobectomy vs. Total Thyroidectomy
Shaha AR, Shah JP, Loree TR Ann Surg Oncol 1997
Low risk patients need selective treatment
Retrospective review of 1038 patients, 465
patients in low risk group, 403 patients
papillary and 62 patients follicular
Median follow-up 20 years. No statistical
difference in overall failure rate or local
recurrence rate between lobectomy vs. total
thyroidectomy

34. Reasons for Total Thyroidectomy
Hay ID et al. Surgery 1987
Removes not only the primary tumor but also
microscopic contralateral disease ~80%
Prevents local recurrence (5-24%) or anaplastic
(<1%) transformation in the contralateral lobe
Decreased need for 2
nd
operation with increased risk
Thyroglobulin surveillance for recurrence
 Radioactive iodine scanning/therapy

35. Complications of Total Thyroidectomy
Hypoparathyroidism ~ 10%
Recurrent laryngeal nerve paralysis ~1%

36. Sites of Invasive Spread
McCaffrey, TV et al. Mayo Clinic, 50-year experience. Head Neck 1994
30%Other structures
12%Larynx
53%Strap musculature
47%Recurrent laryngeal nerve
21%Esophagus
37%Trachea

37. Surgical Considerations
Tracheal involvement
- Window and sleeve resections
- Larger defects, sternocleidomastoid and
pectoralis major myoperiosteal flaps over T-
tubes
- Tracheal resection with re-anastomosis

38. Esophageal Invasion
Tends to invade only the outer muscular
layers
Limited resection without intraluminal entry is
posssible
When intraluminal invasion encountered,
primary closure vs. free tissue transfer for
larger resections

39. Recurrent laryngeal nerve
Falk SA, McCaffrey TV. Otolaryngol Head Neck Surg 1995
Retrospectively compared patients and noted
that complete resection of tumor and nerve
sacrifice offered no survival benefit over
potentially incomplete resection of tumor and
nerve preservation

40. Laryngeal Involvement
Vertical partial laryngectomy, unilateral
disease
Supracricoid partial laryngectomy, extensive
anterior invasion
Total laryngectomy, extensive laryngeal
spread

41. Regional metastasis
Intraglandular lymphatics
First nodal drainage paralaryngeal,
paratracheal, prelaryngeal nodes VI
Second level of drainage II, III, IV, V
Elective neck dissection in setting of papillary
CA will detect occult spread in 50% of
patients; reported no added benefit on
survival

42. Regional metastasis
Radiologic imaging for regional spread include US,
CT, and MRI
US- most accurate when combined with FNA, Serial
tests can evaluate changes in nodal size
Imaging criteria for CT/MRI: recurrent disease,
clinical lymph node metastases, vocal cord paralysis,
fixation of mass to adjacent structures, symptoms of
upper aerodigestive involvement
Type of neck dissection dictated by extent of disease

43. Neck dissection
Ferlito A., Pellitteri PK, Robbins KT et al. Review article. Acta Otolaryngol 2002
Selective dissection for extension of tumor noted,
direct involvement of non-lymphatic structures
In high risk patients (male >45, with large 4cm
cancer) recommend ipsilateral paratracheal node
dissection given highest risk of containing
metastases
Low risk, palpate region if no enlarged lymph nodes,
elective neck dissection not carried out

44. Postoperative treatment
Radioactive iodine ablation decreases the
local recurrence and mortality rates in
patients with stage 2 and stage 3 well-
differentiated thyroid carcinoma
Use of postoperative RAI and thyroid
hormone supression has been advocated for
patients with tumors > 1.5 cm

45. Long term potential complications of
Thyrotropin (TSH) Suppression
Increased bone loss, particularly in
postmenopausal women
Hyperthyroidism
Cardiac hypertrophy
Cardiac arrythmias

46. Radioactive Iodine Side Effects
Radiation thyroiditis (when large remnant
present), sialoadenitis, taste dysfunction,
nausea

47. Postoperative Treatments
Thyroglobulin levels in the absence of normal
thyroid tissue, is a sensitive and specific
marker for the presence of thyroid cancer
Ideally this assay should be performed when
the thyrotropin (TSH) level is elevated
Recombinant human TSH
Ongoing clinical surveillance

48. Postoperative followup
Woodrum DT, Gauger PG Journal of Surgical Oncology 2005

49. Other Therapies
Not first line therapy, external beam radiation
may have a role in treatment of non-RAI avid
tumors, gross residual tumor, or unresectable
disease
Also clinical trials involving gene therapy and
tumor redifferentiation research

50. Conclusions
Strategy for Thyroid Nodules
Understanding prognosis- low, intermediate,
high risk
Total Thyroidectomy and Radioiodine
Ablation for High Risk
In the future, have more effective screening
and therapies