world cancer report - iarc

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