1. Thyroid Malignancies In Children
Bhaskar N. Rao, M.D.
St. Jude Children’s Research Hospital
10/03

2. THYROID CANCER Staging
T0 No evidence of tumor
T1 tumor <1 cm
T2 tumor 1-4 cm
T3 tumor >4 cm
T4 tumor any size beyond capsule
N0 No nodal mets
N1 regional nodes
N1a ipsilateral cervical nodes
N1b bilateral or mediastinal
M0 N0 distant mets M1 distant mets

3. THYROID CANCER Staging (Pap/follicular)
Age <45 Stage 1 Any T Any N M0
Age >45 Stage 1 T1 N0 M0
Stage 2 T2/T3 N0 M0
Stage 3 T4 or N0 M0
T1-4 N1 M0
Stage 4 T1-4 Any N M1
Anaplastic All cases are stage IV
Staging (Medullary)
Stage 1 T1 N0 M0
2 T2-4 N0 M0
3 Any T N1 M0
4 Any T Any N M1

4. Thyroid Cancer Epidemiology
20,000 new cases/year in the US
more often in women and whites
Peak incidence: 40 (women), 60 (men)
Lifetime risk: 1%
Histology: Papillary - 80% Follicular - 11% Hurthle cell - 3% Medullary - 4% Anaplastic - 2%

5. Thyroid Cancer Epidemiology - Children
Low incidence in childhood
1.5% of all tumors < 15 years
peak 7-12 years
10% of all head and neck cancer
10% are diagnosed in childhood
2/3 in girls
Indolent course, even with metastases
Survival > 90%
Up to 8% of secondary pediatric cancers

6. Thyroid Cancer Epidemiology - Children
Low dose RT used for Thymus, Hemang, Acne
Average dose 600cgy. One million people at risk
One fourth will develop nodules
Most (75%) Benign Hyperplasia, Adenoma, Fibrosis
Treatment Lobectomy – Post-op Hormones

7. Thyroid Cancer Epidemiology - Children
Increased risk of Carcinoma
Most are Papillary Carcinomas (20-50%)
Latency median 20 years
Most are multicentric, with lymph nodes
Other tumors – Salivary Gland, Parathyroid, Bone, Soft tissue Sarcomas, Thyroid lymphomas

8. Thyroid Cancer Histology
Papillary
80% incidence increases with younger age
High incidence of bilaterality, regional nodes
Follicular
Rare in children
Distinguished from adenoma by vascular or capsular invasion
Medullary
arise from calcitonin-secreting c-cells
Anaplastic
Extremely aggressive, high mortality
Tumor Variable Affecting Prognosis
Histology
Size
Local invasion
Lymph node
Distant metastases

9. Thyroid Cancer Epidemiology - Children
Thyroid cancer has proven to be a common SNM
Between 1980 & centers in Europe reported 239 SMN’s
18 of 239 (7.5%) were thyroid cancers
6 / 18 primary was Hodgkins all received chemo + RT (25-42gy)
7 / 18 primary was ALL all had CS RT (18-24gy)
2 Ewings, 1 Wilms, 1 NB and 1 NPC

10. Thyroid Cancer Pediatric vs. Adult
Thyroid nodules
By far most thyroid nodules are benign and are either colloid nodules, adenomas or manifestations of thyroiditis
They may be cystic or solid
Most cystic are generally benign (degenerated colloid)
They may be toxic or non toxic
Thyroid Cancer Pediatric vs. Adult
Thyroid masses more likely to be cancer
50% of solitary nodules are malignant
More often larger, multicentric
Higher rate of metastasis at diagnosis
regional lymph nodes: 65% (35% adult [papillary])
distant: 20% (10% adult [follicular])
Higher rate of recurrence
40% <20y (also >60y); 20% adults
80% locoregional, 20% distant (similar)

11. Thyroid Cancer Diagnostic Imaging
Traditionally I131 Now I123 or Technitium scans
Nodules hyperfunctional (hot) with increased avidity
Functional cold same as rest of gland
Minimum 1 cm diameter for cold nodules
Hot functional nodules practically benign
Cold – incidence of malignancy higher

12. Thyroid Cancer Diagnostic Imaging
USG – differentiate multinodular vs solitary
CT or MRI – invasive lesion or sub-sternal location
Specific / sensitive is F.N.A.
Malignant, suspicious, benign or inadequate
If it is suspicious I123 , hot, rarely malignant
cold 20% or higher

13. Thyroid Cancer Pediatric vs. Adult
Better overall survival
>95% for children
75-90% for adults
Better survival with metastases
86% of children
32% of adults
Thyroid Cancer Pediatric vs. Adult
Thyroid malignancies in pediatric population – how is it different?
Papillary ca. constitutes 85-90% of all malignant lesions with medullary second, forming 5%
Unlike adults follicular not as common and when present it is usually in the adolescent population
Thyroid lymphomas and metastasis are hardly ever seen in pediatric population
In familial medullary ca. prophylactic thyroidectomy is done in kids before they attain age 5yr
PARADOX:
often presents with extensive disease and progression or recurrence in a significant number of patients
is rarely fatal
Suggests biologic rather than treatment factors have a greater effect on outcome

14. Approach to a malignant thyroid nodule Clinically suspicious nodule >1cm
Increased suspicion
Male
Nodule > 4cm
Age < 15 yr
H/O XRT exposure
H/O
Pheochromocytoma
Hyperparathyroidism
Gardner’s
FAP
Carney’s complex
Cowden’s syndrome
Highly suspicious
Rapid nodule growth
Fixation
Family history
V.C paralysis
Lymph nodes
Neck invasion
TSH
FNA of nodule/ lymph nodes
If insufficient FNA → repeat FNA (imparts 50% extra chance)
US solid or cystic and assist in FNA and determining the size of the nodule
Cystic nodules may be followed

15. Thyroid Carcinoma Fine needle aspiration important
Distinguishing benign/malignant follicular difficult
Thyroid nodules containing follicular cytopathologic features have 20-30% malignancy
Thyroid malignancy rate is 6.8% without atypia and % with atypia
Allows for conservative approach in selected patients

16. Thyroid Cancer Surgical Options
Total Thyroidectomy in patients with invasive or metastatic or bilateral or previous RT
For others – controversy varies with surgery and complication rates
Unilateral P.C. or F.C. < 1.5 cm lobectomy + isthmus
If > 1.5 cm opposite lobe 30-80% recurrence rate is 10%
Recurrence associated with 30% mortality with 50% desease found in central neck
Total Thyroidectomy recurrence less than 5%

17. sup. parathyroid
recurrent laryngeal n.

18. Thyroid Cancer Surgery Risk vs. Benefit
Total Thyroidectomy
High risk groups: radiation, MTC, Anaplastic
Simplifies use of radioiodine
Follow thyroglobulin levels
Increased risk without increased survival benefit
15% each-recurrent laryngeal nerve injury, hypoparathyroidism
30% higher than lobectomy

19. Thyroid Cancer in Childhood
sup. parathyroid
Challenges of Thyroid Cancer Management
recurrent laryngeal n.
No prospective randomized trials of treatment
The prognosis is generally excellent

20. Thyroid Carcinoma Minimally Invasive Surgery
Criteria by Niccoli et al. (Am J Surg, 2001)
Nodules less than 3.5 cm
Total thyroid volume less than 15ml
No previous neck surgery or irradiation
Absence of thyroiditis/invasion
Total 336 pts. One-third total thyroidectomy
Conversion 4.5%
Yamashita et al.
25-30 mm transverse upper lateral neck
Total 39 pts. Recurrent nerve injury one
Tumor size 1.9 – 5.5 cm
Surgery 56 mm (36-90 minutes)
Other approaches described Axillary Approach

21. Approach to a thyroid nodule (Papillary on FNA-high risk)
Papillary ca. (dx. By FNA) and high risk
Total thyroidectomy
If L.N positive
Central neck disec
Lateral neck disec.(level II-IV, sparing spinal accessory nerve, int. jugular, SCM)

22. Management post lobectomy for papillary (<1cm- low risk)
Their recurrence and cancer specific mortality rates are almost zero
Supress TSH with thyroxine
Tg and whole body I scan are insensitive
Physical exam with local neck US seem to be the best suggested follow up

23. Follow up papillary P/E q 3-6 mo for 2yrs with periodic US
6 & 12mo then annually
RI scans q 12mo
Periodic CXR/ CT chest
For locoregional recurrences → surgery followed by RI
Tg rise >10ng/ml → RI therapy with mCi

24. Thyroid Carcinoma Follicular lesion
Follicular carcinoma represent 10-20%
Prognostic factors include size, age, metastasis
Witte et al., report L.N., size, stage, mets, sex
Advised total thyroidectomy + L.N. dissection and
ipsilateral or bilateral L.N. dissection for T3, T4
Follicular lesion
TSH high → Thyroxine/Surg
Follicular TSH normal → Surgery
TSH low → Thyroid scan hot
cold

25. Approach to thyroid nodule (Follicular on lobectomy)
Invasive
Follicular carcinoma on lobectomy
Further local and metastatic work up
< 1cm → observe/ re-resect
> 1 cm → completion thyroidectomy followed by I 131

26. Approach to a thyroid nodule Medullary carcinoma
Medullary on FNA
Calcitonin levels
CEA
Pheo screening
Serum calcium
Screen for RET proto-oncogene
Neck US