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Vol. 66, No. 2 2015
Northeast Florida Medicine
Pediatric Oncology
consideration for lobectomy in the young child at increased
risk.
11
All other FNA findings mentioned warrant surgery. A
complete laboratory evaluation including TFTs (TSH, T3,
T4), thyroid associated autoantibodies and calcitonin should
be obtained, but the role of RAI scanning to assess the nodule
is of unclear value in children.
Staging and Risk Stratification
A critical balance exists between trying to aggressively treat
the malignancy to achieve cure, while avoiding over-treating
with attendant increased morbidity of the treatment itself
when no additional benefit is realized by the patient. This is
particularly true with pediatric thyroid cancer where surgery
and radiation therapy have significant short and long-term
associated morbidities but the cancer rarely causes mortality.
Thus stratifying patients based on risk for disease recurrence
or progression is essential. The TNM (tumor size, node dis-
ease, distant metastases) system, the DeGroot classification
(Class 1 – tumor confined intra-thyroid, Class 2 – cervical
lymph node metastases, Class 3 – extra-thyroid extension of
the primary, Class 4 – distant metastases) and the MACIS
system (distant metastases, patient age, completeness of re-
section, local invasion and tumor size) are all predictors for
risk of recurrent disease. Kuo reported a series of 77 pediatric
patients and found the DeGroot classification superior to the
TNMsystem in predicting outcome.
14
In particular, the study
found five cases of recurrent disease staged as low risk by the
TNM system versus no patients with DeGroot 1 or 2 classi-
fications. The presence of gross invasion, DeGroot 3 disease,
was a significant predictor of local recurrence in a group of
105 patients reported by Robie and colleagues (p<.0001).
15
Wada and associates found that the presence of nodal metas-
tases detected clinically or by US/CT was predictive of local
or distant recurrence (p<.001).
16
The MACIS scoring system
was originally designed to predict survival risk in adults with
PTC with a score above 8 predictive of mortality at 20 years
of 27 percent.
4
Powers used the MACIS system in a group
of 48 children stratified between those with aggressive PTC
(11) and indolent PTC (37) and found a cutoff score of 4
useful in predicting recurrent or persistent disease.
17
From the basis of these reports one can conclude that
tumor characteristics on a macro level exist that can aid in
stratifying children with DTC into low and high risk catego-
ries for disease recurrence. As previously mentioned, young
patient age (<10 years) and aggressive histology should affect
risk assignment, as both are associated with more aggressive
disease. In addition, radiation-induced tumors have higher
risk of recurrent disease. Spinelli and colleagues found that
among a group of 56 childrenwithDTC, recurrence was 33.5
percent in the 22 patients from Belarus, exposed to radiation
from the Chernobyl nuclear disaster, versus 3 percent in 37
patients without radiation exposure (p<.0001).
18
Demidchik
increasing risk with doses up to 20-29 Gy. Interestingly,
they found no association between chemotherapy expo-
sure and thyroid cancer. Thyroid cancer is also associated
with diffuse lymphocystic thyroiditis, goiter, Gardner’s
syndrome, Cowden disease, Werner’s syndrome and
Carney’s complex.
5,6,9
Molecular Genetics
A comprehensive review of this topic is provided by
Yamashita and Saenko.
5
The genetic basis for DTC in
childhood thyroid cancer is now well established. Gene
rearrangements predominate with the RET proto-oncogene
in juxtaposition to various partner genes such as RET/PTC1
or 3. The tyrosine kinase activity of the proteins coded for
by this gene rearrangement transduce signals that lead to
stimulation of thyroid follicular cell proliferation, survival
and inhibited differentiation.
5
Of particular note is the
association of RET/PTC3 with the solid variant of PTC,
a short latency period, increased aggressiveness, increased
frequency in younger children and radiation-induction of the
tumor. In contrast to adult thyroid cancers, point mutations
(RAS, BRAF, GNAS genes) are rare (<20 percent of cases
with TP53 mutation predominant) and are found mostly
in FTC.
10
The rarity of point mutations in children versus
adults is explained in part by the longer latency period of
mutation associated thyroid cancer and the developmental
state of the thyroid in the child, in comparison to the mature
gland of the adult.
5
Presentation and Diagnosis
The most common presentation is an isolated thyroid
nodule.The potential that the nodule harbors a malignancy is
roughly 20 percent, which is significantly less than the historic
30-50percent rate found in studies fromthe radiationera.
11
US
and fine needle aspiration (FNA) have become the mainstays
in evaluating thyroid nodules in children.
1
US characteristics
suggestive of malignancy include indistinct margins, internal
calcifications andvariable echo-texture.
12
Inaddition, the value
of US in detecting occult nodal metastases in the neck was
clearly shown by Stulak, and directly led to more extensive
nodal dissection in40.5percent and42.9percent of initial and
reoperative patients.
13
FNA, oftenUS guided, is dependent on
a skilled technician and experienced pathologist to optimize
accuracy. Findings onFNAaremost oftencategorized as one of
the following; benign, indeterminate (includes inadequate and
nondiagnostic), suspicious, malignant, follicular or Hurthle
cell. Though controversy does exist, the best approach for
indeterminate findings, especially in a child < 10 years of age,
is lobectomy with completion thyroidectomy based on final
pathology.
4,11
Benign findings on FNA should be approached
with caution and require close follow-up of the nodule, with
