world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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Papillary<br />
carcinoma<br />
RET/PTC<br />
TRK<br />
BRAF<br />
RAS<br />
MET<br />
RAS<br />
β-catenin<br />
p53<br />
THYROID<br />
EPITHELIAL<br />
CELL<br />
PTEN<br />
Fig. 5.140 Proposed genetic model of thyroid tumour formation. Genes in bold type have a well-established<br />
role.<br />
an intermediate degree of clinical malignancy.<br />
Insular carcinoma invades both<br />
lymphatics and veins, and nodal and distant<br />
metastases are common.<br />
Approximately 33% of tumours displaying<br />
oncocytic (Hürthle cell) features show histological<br />
evidence of malignancy (e.g.<br />
nuclear features typical of papillary carcinoma)<br />
or invasive growth. The remainder<br />
behave as adenomas and may be treated<br />
conservatively.<br />
There is evidence of familial risk in a small<br />
percentage of papillary and follicular thyroid<br />
carcinomas. The associations of<br />
Gardner syndrome (familial adenomatous<br />
polyposis) and Cowden disease (familial<br />
goitre and skin hamartomas) with differentiated<br />
thyroid carcinoma provide welldefined<br />
examples. About 25 to 35% of all<br />
medullary thyroid carcinomas are identified<br />
as a component of one of the clinical<br />
syndromes. These syndromes include:<br />
multiple endocrine neoplasia type 2A<br />
(MEN2A) which is associated with<br />
medullary thyroid carcinoma, pheochro-<br />
LOH 3q,18q<br />
RAS<br />
p53<br />
Gsp<br />
PAX8-PPARγ<br />
POORLY DIFFERENTIATED<br />
AND UNDIFFERENTIATED<br />
CARCINOMA<br />
Follicular<br />
carcinoma<br />
Follicular<br />
adenoma<br />
LOH3p<br />
Toxic<br />
adenoma<br />
Growth factors which may contribute to<br />
tumour development at multiple sites<br />
include:<br />
Thyroid stimulating hormone (TSH)<br />
Insulin-like growth factor 1(IGF-1)<br />
Transforming growth factor β (TGF-β)<br />
mocytoma and hyperparathyroidism;<br />
multiple endocrine neoplasia type 2B<br />
(MEN2B) which is associated with medul -<br />
lary thyroid carcinoma, pheochromocytoma,<br />
mucosal neuromas, and marfanoidlike<br />
features; and familial medullary thyroid<br />
carcinoma.<br />
The genes implicated in the pathogenesis<br />
of thyroid carcinoma generally form a<br />
subset of important cell growth and differentiation<br />
regulatory factors that can<br />
be separated into membrane and nuclear<br />
factors. Two different mechanisms are<br />
involved in the genesis of papillary thyroid<br />
and medullary thyroid carcinomas.<br />
As a result of intrachromosomal<br />
rearrangements, the RET proto-oncogene<br />
becomes attached to the promoter of<br />
one of three genes expressed constitutively<br />
in the follicular cell, which results<br />
in the so-called “papillary thyroid carcinoma<br />
oncogene” (RET/PTC1, 2, and 3).<br />
Germline point mutations of the RET<br />
proto-oncogene, which is normally<br />
expressed in the thyroid parafollicular<br />
cell, are found in more than 95% of individuals<br />
with hereditary medullary thyroid<br />
carcinoma (codons 609, 611, 618, 620, or<br />
634). Mutation of codon 634 is the most<br />
commonly observed and is found in<br />
about 80% of all patients with hereditary<br />
medullary thyroid carcinoma. A germline<br />
point mutation in the tyrosine kinase portion<br />
of the RET receptor (codon 918) has<br />
been identified in 95% of individuals with<br />
MEN2B [10].<br />
Management<br />
Patients with malignant lesions diagnosed<br />
on the basis of fine needle aspiration, as<br />
well as patients with a suspicious aspiration,<br />
combined with other risk factors<br />
(such as prior radiation exposure or local<br />
symptoms) should have surgical resection.<br />
It has been recommended that total<br />
thyroidectomy should be performed at<br />
around the age of six years in children who<br />
are MEN2A gene carriers and shortly after<br />
birth in children with the MEN2B mutation<br />
[11]. Benign nodules can be monitored by<br />
ultrasound examination. Acceptable surgical<br />
procedures include lobectomy, subtotal<br />
thyroidectomy, near-total thyroidectomy<br />
and total thyroidectomy. Modified radical<br />
neck dissection is indicated in case of<br />
lymph node metastases. All patients who<br />
have undergone a total or near-total thyroidectomy<br />
for a papillary or follicular car-<br />
Fig. 5.141 Five-year relative survival after diagnosis<br />
of thyroid <strong>cancer</strong>.<br />
Thyroid <strong>cancer</strong><br />
259