Pedi Thyroid carcinomas

Question 1

What percentage of pediatric thyroid nodules are

malignant?

Answer 1

About 26% (ranges have been published from < 1%, citing a
referral bias in children with risk factors for thyroid cancer,
to as high as 36%; most of the literature suggests an
increased risk of thyroid carcinomas in pediatric thyroid
nodules compared with adults)
Regardless of the exact percentage, the 2009 revised
American Thyroid Association (ATA) recommends the same
diagnostic and therapeutic approach for children as for

adults (clinical evaluation, serum thyroid-stimulating hor-
mone [TSH], ultrasonography, FNA).

Question 2

What are the most common benign thyroid

nodules?

Answer 2

Multinodular goiter (sporadic)
Hashimoto thyroiditis
Hemorrhagic, colloid, and simple cysts
Follicular adenomas
Hürthle cell adenomas

Question 3

What is the most important environmental risk
factor for the development of pediatric thyroid
carcinoma?

Answer 3

Radiation exposure

Question 4

What genetic syndromes are associated with an

increased risk of medullary thyroid cancer?

Answer 4

MEN 2A
MEN 2B
Familial medullary thyroid carcinoma

Question 5

Name the syndrome associated with the following
constellation of syndromes:
● Familial adenomatous polyps, papillary thyroid
carcinoma, autosomal dominant (adenomatous
polyposis coli [APC]) gene
● Primary pigmented nodular adrenocortical disease

(primary adrenal hypercorticism); lentigines, ephe-
lides, and blue nevi of the skin and mucosa;

nonendocrine and endocrine tumors including
papillary and follicular thyroid carcinoma
● Premature aging (progeria), osteosarcoma, soft
tissue sarcoma, and follicular or papillary thyroid
carcinoma
● Macrocephaly, autism or developmental delay,
penile freckling or other benign skin lesions,
vascular anomalies such as arteriovenous (AV)
malformations or hemangiomas, and GI polyps

Answer 5

● Gardner syndrome
● Carney complex type 1
● Werner syndrome
● PTEN hamartoma syndrome (Cowden syndrome,
Bannayan-Riley-Ruvalcaba syndrome)

Question 6

What is the most common pediatric thyroid

tumor (malignant or benign)?

Answer 6

Follicular adenoma (benign)

Question 7

What is the most common malignant thyroid

tumor in children?

Answer 7

Papillary thyroid carcinoma (83%): 60% papillary, 23%
follicular variant papillary. Less commonly, follicular thyroid
carcinoma (10%), medullary thyroid carcinoma (5%), and
other rarer cancers may arise.

Question 8

What factors increase the risk that a thyroid

nodule is in fact thyroid carcinoma?

Answer 8

● Male
● History of thyroid cancer in one or more first-degree
relatives
● History of previous hemithyroidectomy for thyroid cancer
History of radiation exposure (external beam, ionizing
radiation, etc.)
● Associated genetic syndrome increasing the risk for
thyroid cancer (e.g., MEN 2A, MEN 2B, Familial Medullary
Thyroid Carcinoma [FMTC], Cowden, Carney, Werner,
PTEN hamartoma syndrome, etc.)
● Firm, fixed, rapidly growing nodule
● New-onset hoarseness or vocal cord paralysis
● Dysphagia
● Odynophagia
● Lymphadenopathy (up to three-fourths of patients)
● FDG avidity on PET scanning

Question 9

Does a 5-year-old diagnosed with thyroid
carcinoma have a higher risk of advanced disease
than an 18-year-old with the same tumor?

Answer 9

Yes. Prepubertal children are more likely to have advanced
disease (regional metastasis, extracapsular extension, and
invasion into surrounding tissue). Overall prognosis is still
excellent.

Question 10

Children diagnosed with medullary thyroid
carcinoma generally have a solitary thyroid nodule
or are diagnosed during workup for which three
associated syndromes?

Answer 10

● MEN 2A (or Sipple syndrome): RET (rearranged during

transfection) proto-oncogene mutation; parathyroid hyper-
plasia, pheochromocytoma, medullary thyroid carcinoma

● MEN 2B: RET proto-oncogene; mucosal neuromas,
marfanoid habitus, thickened corneal nerves, medullary
thyroid carcinoma, rare parathyroid hyperplasia
● Familial medullary thyroid carcinoma

Question 11

What laboratory workup should be performed

for a child in whom thyroid cancer is suspected?

Answer 11

● Thyroid function testing: tri-iodothyronine (T3), thyroxine
(T4), TSH; generally normal in malignancy
● Calcitonin: Elevated in medullary thyroid carcinoma
● Thyroglobulin: If elevated, can be used for postoperative
surveillance; routine preoperative measurement is not
recommended by the ATA
● Carcinoembryonic antigen: Elevated in medullary thyroid
cancer (except in advanced disease)

● 24-hour urine metanephrines: Functional pheochromo-
cytomas or paragangliomas may result in hypertensive

crises if untreated.
● Genetic screening: If patient is at high risk for hereditary
disorders

Question 12

What is the first step in the imaging workup for

pediatric thyroid cancer?

Answer 12

Ultrasonography: location, number of nodules, size, micro-
calcifications, infiltrative margins, hypervascularity, extrac-
apsular spread, regional metastases, height relative to width

on transverse view; can also be used to guide FNA biopsy

Question 13

True or False. FNA biopsy is less accurate for
diagnosing thyroid malignancy in pediatric
patients than in the adult population.

Answer 13

False. There is no difference in diagnostic accuracy. FNA is

first-line test for tissue diagnosis and management plan-
ning. Patient compliance may require FNA with sedation.

Question 14

True or False. Scintigraphy does not often help to

distinguish malignant from benign thyroid disease.

Answer 14

True. Scintigraphy is useful for identifying ectopic thyroid

tissue (ectopic lingual thyroid). Hot nodules can be malignant.

Question 15

When should a CT scan be considered in the

workup of pediatric thyroid cancer?

Answer 15

CT of the neck and chest should be considered with

extensive disease, extracapsular spread, mediastinal in-
volvement, or regional lymphadenopathy. The risk of

pulmonary metastases is as high as 20% in some series and
increases with regional metastases. Pulmonary metastases
can also be detected using radioactive iodine scanning.

Question 16

How are thyroid cancers in children staged?

Answer 16

TNM staging
T-stage
● T1: < 2 cm
● T2: 2 to 4 cm
● T3: > 4 cm limited to the thyroid gland or with minimal
extrathyroidal extension
● T4a: Any size; extrathyroidal extension to involve adjacent
soft tissues, larynx, trachea, esophagus, or recurrent
laryngeal nerve
● T4b: Any size, extrathyroidal extension to involve the
prevertebral fascia or encase the carotid artery or
mediastinal great vessels
N-stage
● N1a: Metastases to level VI
● N1b: Metastases to any cervical or mediastinal lymph
node(s)
M-stage
● M1: Distant metastases
Well-Differentiated:
● Stage I: Any T, any N, M0
● Stage II: Any T, any N, M1
Note: Medullary thyroid carcinoma has the same TNM
system, but stages I, II, III, IVA, IVB, and IVC are delineated.

Question 17

The American Joint Committee on Cancer (TNM)
system was developed to determine the risk of
death, but it does not describe the risk of
recurrence. How do the 2009 ATA guidelines
describe this risk?

Answer 17

Low-risk
● No local or distant metastases
● All macroscopic tumor has been resected.
● No tumor invasion of locoregional tissues or structures
Tumor does not have aggressive histology or vascular
invasion.
● If 131I is given, there is no uptake outside the thyroid bed
on the first post-treatment whole-body scan.
Intermediate-risk
● Microscopic invasion of tumor into the perithyroidal soft
tissues at initial surgery
● Cervical lymph node metastasis or 131I uptake outside the
thyroid bed done after thyroid remnant ablation
● Tumor with aggressive histology or vascular invasion
High-risk
● Macroscopic tumor invasion
● Incomplete tumor resection
● Distant metastases
● Possibly thyroglobulinemia disproportionate to what is
seen on the post-treatment scan

Question 18

In general, what is the extent of resection recommended for a solitary thyroid lesion in a child?

Answer 18

Hemithyroidectomy. Subtotal or completion thyroidectomy
should be performed if frozen or permanent pathology
confirms thyroid cancer.

Question 19

When might thyroid lobectomy alone be sufficient

as surgical therapy in the pediatric population?

Answer 19

Small (< 1 cm), low-risk, unifocal, intrathyroidal papillary
carcinomas in the absence of prior head and neck
irradiation or radiologic or clinical cervical
lymphadenopathy

Question 20

When should total thyroidectomy be considered

in patients with indeterminant thyroid nodules?

Answer 20

Large tumors (> 4 cm), when marked atypia is seen on
biopsy, when the biopsy is read as “suspicious for papillary
carcinoma,” in patients with a family history of thyroid
carcinoma, and in patients with a history of radiation
exposure

Question 21

Discuss the pros and cons of subtotal or near-total

thyroidectomy.

Answer 21

Pros
● Potentially limit morbidity associated with recurrent
laryngeal nerve injury and parathyroid devascularization
● Unlikely to increase recurrence rates
● May be able to maintain a euthyroid state
Cons
● Can interfere with postoperative radioactive iodine
treatment for microscopic and distant disease
● May impact postoperative surveillance

Question 22

When should you consider elective neck dissection
in pediatric patients with well-differentiated thyroid
carcinoma?

Answer 22

Lateral neck dissection should be performed only for
clinically positive nodal disease. If such disease is present,
elective dissection of levels IIA, III, IV, and VB should be
performed. If there is disease in level IIA, some authorities
recommend dissection of level IIB. Levels I, IIB, and VA
should also be included if there is clinically evident disease.
Central neck dissection (level VI) should be performed
therapeutically for clinically involved central or lateral neck
nodes and electively (ipsilateral or bilateral) for patients
with advanced primary tumors (T3 or T4).

Question 23

When should radioactive iodine be considered in

the management of pediatric thyroid carcinoma?

Answer 23

Indicated:
● All patients with known distant metastases, gross
extrathyroidal extension, and primary tumor size > 4 cm
● Selected patients with 1- to 4-cm thyroid cancers
confined to the thyroid with documented lymph node metastases or other high-risk features when the combination of age, tumor size, lymph node status, and individual histology predicts an intermediate to high risk of recurrence or death from thyroid cancer.
Not indicated:
● Solitary tumor < 1 cm in diameter without high-risk
features
● Multifocal cancer if all tumors are < 1 cm and intra-
thyroidal without high-risk features

Question 24

What are the potential side effects of radioactive
iodine ablation for the management of pediatric
thyroid cancer?

Answer 24

Short-term effects: Nausea (immediate, temporary), xero-
stomia, altered taste, dental carries, cytopenias, menstrual

irregularities (temporary), decreased sperm counts (tem-
porary)

Long-term effects: Xerostomia, altered taste, cytopenias,
nasolacrimal duct obstruction, increased lifetime risk of
secondary malignancy (leukemias, salivary gland, urinary,
and GI)

Question 25

What is the extent of surgical intervention recommended for medullary thyroid carcinoma?

Answer 25

Total thyroidectomy (when there is high risk for multi-
centricity and recurrence) and elective bilateral central

compartment dissection
Lateral dissection is reserved for clinically evident disease or
lymph node metastases in the adjacent central neck
compartment. Elective lateral neck dissection should
include levels IIA, III, IV, and VB. The superior level VII nodes
should also be addressed in this situation.

Question 26

A 9-month-old female infant is brought to your
office for consideration of prophylactic
thyroidectomy to prevent the development of
thyroid carcinoma. Why might you consider this
operation?

Answer 26

RET gene mutation positivity
For MEN 2B (high-risk) mutations, resection may be
considered in the first year of life (includes central neck
dissection if patient is > 1 year).
In MEN 2A or familial medullary thyroid cancer syndromes
(lower risk), resection can be delayed until early childhood
(age of 3 to 6 years is suggested in the literature, but no
real consensus has been reached; timing of surgery
depends on other risk factors; in general < 8 to 10 years of
age) unless a high-risk mutation is identified.

Question 27

True or False. Because of their young age, risk for
recurrence, and aggressive disease at diagnosis,
pediatric patients diagnosed with thyroid
carcinoma uniformly do poorly compared with
their adult counterparts.

Answer 27

False. The survival rate for pediatric patients is better than
that for adults. Long-term survival for well-differentiated
thyroid carcinoma is > 90%. Medullary thyroid carcinoma
has relatively low 30-year survival rates, but the 5-year
survival rate is > 90%.