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INSIDE
Epidemiology
Aetiology
Pathology
Investigation and
diagnosis
Management of
differentiated
thyroid cancer
Rare thyroid
cancers
Background
THYROID nodules are common.
Most micronodular changes that
occur in the thyroid should almost
be regarded as within the range
of normality. Solitary thyroid
macronodules occur in about 5%
of the population.1 Of those people
with solitary nodules, fewer than
1 in 20 will be malignant.2,3 So
although thyroid nodules are very
common, clinical thyroid carcinoma
is rare, representing less than 1% of
all malignancies.
The incidence of thyroid cancer is
fewer than 10 per 100,000 within
the population annually. Ninety-five
per cent of these malignancies will
be differentiated carcinomas (80%
papillary, 15% follicular), 4% medullary and 1% anaplastic or undifferentiated. Differentiated tumours
overall have an extremely good
prognosis and fortunately represent
the bulk of thyroid malignancies. At
the other end of the spectrum are
the undifferentiated anaplastic carcinomas, which are among the most
malignant carcinomas.
However, subclinical malignancy
is probably far more common than
identified thyroid cancers — some
studies have demonstrated micropapillary carcinoma in up to 30%
of cadaveric thyroids in people who
have died of other causes.
cont’d next page
the author
Thyroid
cancer
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Associate Professor
Owen Ung
director, Centre for Breast Health,
and head, breast and endocrine
surgery, Royal Brisbane and
Women’s Hospital, Brisbane; and
visiting specialist, Wesley Hospital,
Brisbane and St Andrew’s War
Memorial Hospital Brisbane,
Queensland.
Copyright © 2014
Australian Doctor
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14 March 2014 | Australian Doctor |
23
How To Treat – Thyroid cancer
Epidemiology
25
4.5
Males
Males
4
Females
20
Females
3.5
Deaths per 100,000
New cases per 100,000
15
10
3
2.5
2
1.5
1
5
Figure 1: Age-specific thyroid cancer incidence rates, NSW, 2001-05.
Figure 2: Age-specific thyroid cancer mortality rates, NSW, 2001-05.
Source: Cancer Institute NSW1
Source: Cancer Institute NSW1
cent of thyroid cancers were detected
by the patient noting a lump in the
neck or another symptom, 16%
were diagnosed by the patient’s doctor noticing a lump in the neck, 11%
were found incidentally on imaging
for another health problem and
26% were incidentally discovered
85+ yrs
80-84 yrs
75-79 yrs
70-44 yrs
65-69 yrs
60-64 yrs
55-59 yrs
50-54 yrs
45-49 yrs
40-44 yrs
35-39 yrs
30-34 yrs
25-29 yrs
20-24 yrs
15-19 yrs
10-14 yrs
5-9 yrs
0-4 yrs
0
85+ yrs
80-84 yrs
75-79 yrs
70-44 yrs
65-69 yrs
60-64 yrs
55-59 yrs
50-54 yrs
45-49 yrs
40-44 yrs
35-39 yrs
30-34 yrs
25-29 yrs
20-24 yrs
15-19 yrs
5-9 yrs
0
10-14 yrs
0.5
0-4 yrs
THE thyroid cancer incidence, mortality and survival rates from the
NSW population are shown in figures 1 and 2.1 Figure 1 shows that
thyroid cancer is more common in
females than males and the incidence increases with age, particularly after 35 years. However it does
still occur in young adults.
Figure 2 shows that mortality
from thyroid cancer is very low, particularly in the younger age groups.
Across all age groups and both genders, long-term survival following
a diagnosis of thyroid cancer is the
norm.
Papillary carcinoma represents
the largest group of thyroid malignancies and is associated with the
best prognosis. The incidence of
papillary carcinoma appears to be
on the rise. Recent epidemiological
studies indicate that while part of
this increase is due to better detection, there does appear to be a real
increase in incidence. The causes are
unclear. Increased exposure to ionising radiation is one postulated contributing factor.
Much of the disease in our population is asymptomatic and detected
incidentally. A recent study examined the NSW Cancer Registry and
pathways to diagnosis.4 Forty per
during treatment for another benign
thyroid condition such as removal of
a multinodular goitre.
Thyroid cancer is more common
in women than men. The estimated
age-standardised incidence rates of
3.83 per 100,000 men and 10.65
per 100,000 women were well
below the observed 4.65 in men and
15.3 in women per 100,000 in the
NSW Cancer Registry study. The
conclusions were that the reported
incidence of thyroid cancer was
likely to be influenced by diagnostic
technology and medical surveillance
practices.
These findings require further
investigation, as 5-10% of these
follicular neoplasms will prove to
be malignant. A definitive diagnosis cannot be made with fine-needle aspiration alone. The criteria
for establishing a diagnosis of
malignancy is capsular or vascular invasion, which requires complete histological examination by
performing at least a hemithyroidectomy.
Patients should be assured that
90% of atypical nodules will ultimately prove to be follicular adenomas or benign colloid nodules.
Hurthle cell variants are sometimes described. These have also
been called ‘oncocytic tumours’
and are of follicular cell origin.
Despite these distinctions such
variants are a subset of follicular lesions. These lesions may be
benign or malignant and the same
criteria for malignancy apply.
Follicular carcinomas have a
preferential propensity for haematogenous spread to bone, lungs,
brain and liver. The more poorly
differentiated or widely invasive
subtypes have a poorer prognosis
and may invade locally as well as
metastasise. Prognosis for these
patients, particularly if they are
older, is poorer, as up to 50% may
die of their disease.
There is also a subset with
RETPTC rearrangements that
may behave like papillary carcinomas. However, true embolic
lymph node metastases are
uncommon.
Aetiology
IT is estimated that one in 280 males and one
in 92 females will develop thyroid cancer by
75 years of age. The aetiology for thyroid carcinomas is multifactorial and generally not
predictable.1
The incidence of subclinical malignancy
in multinodular goitres does not seem to be
much higher than in the normal population.3
This means that multinodular goitres do not
require cancer screening just because they are
larger but should be monitored for compressive symptoms. Thyroid nodules in multinodular goitres should be investigated in their own
right, with the largest nodule investigated as
one would investigate a single dominant nodule.
Radiation
Radiation exposure is a known risk factor for
thyroid cancer. The incidence of thyroid malignancy is increased in populations exposed to
radiation contamination in Nagasaki, Hiroshima and Chernobyl.
Similarly, patients treated for childhood leukaemia with ‘mantle’ irradiation (ie, head and
neck region) have up to 20-50% increased risk
of thyroid malignancy, with a latent period of
between six and 35 years.
If nodules begin forming in patients previously treated with ‘mantle’ irradiation, total
thyroidectomy is recommended.
Genetic predisposition
Some individuals may have an inherited predisposition. Twenty per cent of patients with
medullary carcinoma have a multiple endocrine neoplasia (MEN type 2a or 2b) disorder.
As such, other family members with the same
mutation may be at high risk of medullary cancer and other related tumours or hyperparathyroidism. Patients with familial adenomatous
polyposis, Cowden’s disease, Peutz–Jeghers
syndrome or ataxia-telangiectasia are also at
high risk of thyroid malignancy. A RET protooncogene has been identified in some patients
with papillary carcinoma.
Pathology of differentiated thyroid cancer
PATHOLOGICAL
descriptions
are typically of well-developed
combinations of follicles for differentiated thyroid carcinoma.
Papillary carcinomas in particular may be associated with ‘Orphan
Annie eyes’ nuclei (nuclear grooving) and psammoma bodies. There
may be follicular variants of papillary carcinoma and as such, there
is some crossover between the
papillary and follicular carcinomas. The so-called ‘tall cell’ follicular variant papillary carcinoma
has a somewhat poorer prognosis.
Papillary microcarcinoma
Papillary microcarcinomas are
recognised as thyroid carcinomas
smaller than 1cm in diameter
and typically do not have clinical
24
| Australian Doctor | 14 March 2014
The overall survival
for patients with
treated papillary
microcarcinoma
approaches that
of the normal
population.
symptoms or signs.
Often they are ultrasounddetected or an incidental finding on thyroid pathology. The
overall survival for patients with
treated papillary microcarcinoma
approaches that of the normal
population and even though
regional nodes may be involved in
5% of cases, in a recent large population study, the 20- and 40-year
recurrence rates were only 6% and
9%, with no distant recurrences
seen at 20 years.5
Follicular neoplasm
Follicular neoplasms are typically solitary well-circumscribed
lesions. A fine-needle aspirate
may show an ‘atypical’ pattern
or a microfollicular appearance.
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Investigation and diagnosis
ALL patients presenting with
thyroid disease require baseline
thyroid function tests. A baseline
thyroglobulin is also helpful, particularly in the case of potential
thyroid malignancy — thyroglobulin should be very low post thyroidectomy, and immeasurable
post thyroidectomy with I-131.
Serial measurements are therefore
a useful marker of disease recurrence.
Ultrasound is also very useful
to evaluate the size and morphology of the gland and nodules, and
to direct a fine-needle aspiration
biopsy. Much is made of radioisotope scanning and the so-called
‘cold nodule’. It should be remembered that while ultrasound and
nuclear medicines scanning are
often done for thyroid nodules,
neither of these are specific for the
diagnosis of thyroid malignancy.
Only a fine-needle aspirate can
provide a definitive diagnosis. The
specificity of fine-needle aspiration cytology for malignancy is
72% and the sensitivity is 87%.
The majority of cold nodules
are benign; for example, a large
thyroid cyst will be ‘cold’. Conversely, the ‘hot’ nodule is very
rarely malignant and therefore,
in this scenario the patient can
be reassured by such result. A
solitary hot nodule however, if of
significant size, does not obviate
the need for fine-needle aspiration
cytology, which is necessary for a
Table 1: Accuracy of fine-needle aspiration for predicting
malignancy6
Proposed categories
Risk of malignancy
Benign
<1%
Follicular lesion of undetermined
significance
5-10%
Neoplasm
Follicular neoplasm
Hurthle neoplasm
20-30%
Suspicious for malignancy
50-75%
Malignant
100%
Non-diagnostic
NA
will determine whether the gland
has diffuse toxicity or isolated
toxic nodules or nodule. This
information may guide treatment
for a patient with abnormal thyroid function but is non-contributory in the workup for thyroid
malignancy.
Fluorodeoxyglucose PET (FDGPET)/CT has 60% sensitivity for
malignancy and a negative predictive value of more than 80%. This
is not an indicator for routine use of
this test, as ultrasound-guided fineneedle aspiration is still the gold
standard. That said, if a PET scan
highlights a nodule in the thyroid,
then regardless of other investigations, this should be considered an
indication for surgery. I have already
mentioned limitations of this for
follicular neoplasms. The use of
malignant markers such as RET/
PTC, BRAF and RAS are promising
and may be helpful in a small subset of patients. Table 1 shows the
accuracy of fine-needle aspiration
cytology for predicting malignancy
in various sub-categories.
Predicting thyroid malignancy
definitive diagnosis. Even so, there
is a caution here: hot nodules may
sometimes yield an atypical fineneedle result.
Toxicity is the only indication
for nuclear scanning in thyroid
disorders; nuclear scanning should
not be ordered to investigate a thyroid nodule or to exclude thyroid
cancer unless toxicity is present. It
To some extent, thyroid nodule
size predicts malignancy. Solitary
nodules larger than 3.5-4cm in all
ages have a higher risk of malignancy and should be considered
for thyroidectomy even in the
presence of a benign fine-needle
aspirate.
Enlarging new solitary macronod-
ules should be subject to fine-needle
aspiration and managed accordingly.
There may be a place for conservatism in some cases. There are
certainly some patients with longstanding multinodular goitres and
longstanding large nodules that, if
unchanged over a long period of
time, may be considered benign
and observed.
Nevertheless, size of thyroid
nodules is in some cases an indicator of the need for surgery. A nodule size approaching 4cm requires
a discussion with a patient of the
possible need for surgery. At this
size, in any case, often patients
are beginning to become symptomatic. Fine-needle aspirate sampling of these large nodules may be
benign but the large nodule size in
itself contributes to false-negative
cytology.
Typically thyroid nodules have
mixed solid cystic components.
False-negative fine-needle aspiration rates for totally solid nodules
larger than 3cm may be as high as
17% and up to 30% for mixed
solid cystic nodules. Fine-needle
aspiration should therefore be performed using ultrasound guidance,
even if the nodule is palpable, as
it is the solid component that
requires biopsy. If the fine-needle
aspirate comes back indeterminate
for large nodules, then a thyroidectomy should be considered, particularly for Hurthle cell lesions.
Management of differentiated thyroid cancer
THE treatment of thyroid cancer
very much needs to be tailored to
the individual’s cancer type, stage
and location. Most patients will do
very well after treatment for their
thyroid cancer unless they have
one of the rare aggressive types (see
‘Rare thyroid cancers’, following
this Management section).
By and large there is a very effective operation for thyroid malignancy. Unlike other cancer types,
there is a very specific adjuvant
therapy in radioactive iodine.
Radioactive iodine is truly a targeted therapy, a ‘silver bullet’ that
targets thyroid cells and differentiated thyroid carcinoma, causing no
collateral damage to other tissues.
As such, metastatic nodal disease
and even distant metastases out of
surgical reach can still be effectively
treated for thyroid cancers that
take up iodine.
Radioactive iodine
Radioactive iodine (RAI or I-131)
is used following total thyroidectomy for a differentiated thyroid
cancer. No surgeon can guarantee
that every thyroid cell is removed,
particularly where the thyroid bed
is shaved off the trachea. Radioiodine therapy is very effective
in ablating minimal thyroid remnants.
Thyroid cells absorb just about
all the iodine in the body. Iodine
will be taken up by normal thyroid
cells and differentiated thyroid
cancer cells that take up iodine. In
order to stimulate iodine uptake,
high levels of thyroid-stimulating
Figure 3: Total
thyroidectomy
specimen with
a 1cm nodule/
carcinoma in the
mid/lower pole
of the left lobe
(right side of
image).
Radioactive iodine is
a ‘silver bullet’ that
targets thyroid cells
and differentiated
thyroid carcinoma,
causing no collateral
damage to other
tissues.
hormone (TSH) are required. This
is achieved prior to administration
by withholding thyroxine replacement and allowing the patient
to become hypothyroid. Alternatively, injectable thyrotropin
can be administered. The I-131 is
taken orally in liquid or capsule
form with minimal immediate side
effects. Although the patient may
be physically quite well, because
of the small amount of radioactivity they are required to remain in
a lead-lined isolation room for a
few days.
Following total thyroid ablation by surgery and RAI, lower
dose I-131 scanning can further
be used to monitor for recurrwww.australiandoctor.com.au
ence. Much higher doses are used
for treatment. The other benefit
of complete thyroid ablation is
to facilitate surveillance by measuring thyroglobulin. Following
thyroid ablation, thyroglobulin
should be absent and rising levels
would indicate recurrence.
Papillary carcinoma
Total thyroidectomy is the surgical treatment of choice for a
known papillary carcinoma diagnosed preoperatively and greater
than 1cm in diameter (see figure
3). Larger tumours have a slightly
less favourable risk profile. They
have a greater chance of lymph
node metastases as well as being
associated with such features as
multicentricity and extracapsular
invasion. Total thyroidectomy is
therefore recommended and for
larger tumours is often combined
with an ipsilateral central neck
node dissection. This can be readily done at the time of surgery
with minimal morbidity. Around
40-65% of such patients will be
node positive at presentation. If
more extensive nodal involvement
is determined preoperatively, then
a larger functional neck dissection
is sometimes required.
Perhaps the more important
reason, however, for performing a
total thyroidectomy is to facilitate
cont’d next page
14 March 2014 | Australian Doctor |
25
How To Treat – Thyroid cancer
from previous page
the administration of I-131. This
is because any residual functioning thyroid would compete with
metastatic deposits for the curative I-131. Total removal also
facilitates the use of follow-up
nuclear medicine scans to monitor
for recurrence.
Thyroidectomy is not without
some risks and these need to be
explained to the patient. For all
operations there is a 1 or 2% risk
of bleeding or infection. Given the
proximity of the thyroid to such
vital structures as the major airway,
carotid vessels and oesophagus,
postoperative complications take on
a greater urgency and patients need
to be closely monitored postoperatively for any airway compromise.
The recurrent laryngeal nerve
might be considered as one of the
most important nerves in the human
body as it supplies the vocal cord
and is important for speech, cough,
protection of the airway during
swallowing and indeed breathing if
both nerves are affected. The risk of
permanent damage to the recurrent
laryngeal nerve following thyroid
surgery should be less than 1% in
experienced hands. The other structures at risk with thyroid surgery
are the parathyroid glands. Figure
4 shows a thyroid dissection with
views of these aforementioned at
risk structures.
Follow-up
inferior
parathyroid
gland
superior
parathyroid
gland
tubercle of
Zuckerkandl
inferior
thyroid artery
recurrent laryngeal nerve
Figure 4: The trachea is seen in the centre of the picture. The left lobe of the thyroid contains within it a small thyroid
carcinoma and has been dissected free then retracted out of the neck to the patient’s right (left in picture). The recurrent
laryngeal nerve is seen adjacent to the trachea and the central neck lymph nodes contained within a fascia (held by
forceps) are being separated from the nerve and trachea.
Parathyroids and calcium
Papillary microcarcinoma
26
| Australian Doctor | 14 March 2014
The risk of
permanent damage
to the recurrent
laryngeal nerve
following thyroid
surgery should be
less than 1% in
experienced hands.
100%
Relative survival
For papillary microcarcinoma
or differentiated carcinomas less
than 1cm in diameter, hemithyroidectomy is sufficient treatment
without the addition of I-131.
These tumours might have been
discovered incidentally following a hemithyroidectomy or total
thyroidectomy for other benign
causes. For patients who have not
undergone a total thyroidectomy,
I-131 has negligible therapeutic
value if given for treatment or
diagnostic value for follow-up. In
such patients, administered radioiodine would mostly be taken up
by normal residual thyroid rather
than target differentiated tumour
cells. Likewise thyroglobulin is
not a useful tumour marker for
follow-up, due to its physiological
production by normal thyroid.
A recent study of 900 patients
with papillary microcarcinoma
over a 60-year period with a
mean follow-up at 13.5 years
showed nodal metastases in 30%
of patients, extrathyroidal spread
in 2% and distant metastases in
0.3%. Eighty-five per cent (85%)
of these patients had had a total
or near-total thyroidectomy and
the overall survival of this group
of patients was close to that of
the normal population. There
appeared to be no increase in
recurrence rates for those undergoing a simple lobectomy. The
20- and 40-year recurrence rates
were 6% and 9% respectively
with no distant metastases at 20
years.
There are a number of guidelines
that have been produced to inform
management of this small low-risk
group of patients and there are
some variations in the recommendations. The bottom line is that,
in general, extensive therapy is
usually not required but treatment
should be individualised.
Following thyroid ablation, thyroglobulin is a useful marker for
disease recurrence. Some patients
develop thyroglobulin antibodies
—for them, a low thyroglobulin
may not be an accurate marker of
non-recurrence. Follow-up measures therefore include a combination of physical examination,
thyroglobulin measurement +/neck ultrasound scan and radionuclide imaging at intervals or as
indicated.
All patients will be on thyroid
replacement hormone with an
aim to keep the TSH suppressed.
Because of malignant transformation, cells sometimes lose the ability to take up iodine and, in these
cases, nuclear scanning may be
unreliable. The difficulty arises for
patients with a rising thyroglobulin and negative nuclear scan. In
these instances other modalities
including non-iodine isotopes may
be necessary. Ultrasound scan and
selective fine-needle aspiration can
also be helpful, as can anatomical imaging with CT or MRI. I
emphasise again that these difficult cases represent a minority of
those patients with differentiated
thyroid malignancy.
80%
60%
40%
20%
There are two parathyroid glands
on each side of the neck. The
position of the parathyroids is not
always constant owing to variation of embryological descent
from the pharyngeal pouches to
the final full term position in the
neck. For the most part however,
the parathyroids are adjacent to
the thyroid gland.
Both the inferior and superior parathyroid gland have a
common blood supply — the inferior thyroid artery. Damage to
them or their blood supply while
separating them from the thyroid
may lead to hypocalcaemia.
Careful capsular dissection
of the thyroid, dividing only the
small vessels rather than the inferior thyroid artery trunk and leaving the parathyroids intact with
blood supply is the best way of
preserving function.
Nevertheless, following total
thyroidectomy,
hypocalcaemia
due to hypoparathyroidism will
sometimes occur and require
supplementation with calcium
with or without calcitriol (vitamin
D). If needed, once supplementation has begun, the patient will
need to be slowly weaned off their
replacement calcium and vitamin
D as the parathyroids recover.
Permanent hypocalcaemia occurs
in fewer than 1% of cases.
Prognosis
0%
0 123 45
Years since diagnosis
Males
Females
Source: Cancer Institute of NSW – Thyroid Cancer Monograph 2008
Figure 5. Relative survival of thyroid cancer by gender, NSW, 1999-2003
Staging of differentiated
thyroid cancer
There are several thyroid cancer
staging systems that, for practical purposes, do not really help
to determine individual manage-
ment. These decisions are made
according to characteristics of
the tumour at presentation, such
as size, extrathyroidal spread,
local invasion and regional nodal
involvement. In all the staging syswww.australiandoctor.com.au
tems, differentiated thyroid carcinomas, particularly in patients
younger than 45 years of age, are
stage I regardless of tumour size or
cervical node involvement if there
is no disease further away.
Young patients with well-differentiated papillary carcinoma have
a prognosis approaching that of
the normal population. Follicular
carcinoma has a slightly poorer
prognosis — as do older patients
diagnosed with papillary or follicular carcinoma. Bear in mind that,
although elderly patients have a
poorer overall prognosis, they also
have other competing mortality
risks and are still less likely to die
of their thyroid cancer. Mortality
and survival rates from NSW are
shown in figures 2 and 5.
cont’d page 28
How To Treat – Thyroid cancer
Rare thyroid cancers
References
Medullary thyroid cancer
Anaplastic thyroid cancer
MEDULLARY
thyroid
cancer (MTC) is a neuroendocrine
tumour derived from the parafollicular C cells. C cell hyperplasia
is a precursor of MTC. MTC is
a tumour particularly associated
with MEN type 2a or 2b. Point
mutations of the RET proto-oncogene allow identification of gene
carriers in 95-100% of cases. As
these tumours are undifferentiated,
they are not susceptible to I-131
therapy and the only treatment
effectively available for the thyroid
and regional nodes is surgery.
Early diagnosis or prevention is
the key for high-risk families. The
smaller the presenting MTC, the
lower the risk of regional disease
or indeed distant metastases.
For patients with MTC confined
to the thyroid gland, the 10-year
survival rate should exceed 95%
but it drops to 75% if there is
regional nodal disease and 40%
if there are distant metastases at
presentation.
Calcitonin is a reliable marker
for tumour recurrence following
treatment. Preoperative baseline
measures are useful before surgery.
For families with MEN, genetic
screening is available to identify children at risk. For carriers,
prophylactic total thyroidectomy
is very effective in preventing the
development of medullary thyroid
cancer.
The workup for patients with
medullary carcinoma involves very
careful ultrasonographic examination of the thyroid and regional
nodes and fine-needle aspiration of
any areas of suspicion. If regional
nodal disease is suspected, then a
formal functional neck dissection
is required. Most patients presenting with invasive MTC will have
regional nodal involvement at the
time of diagnosis. Contralateral
cervical lymph node metastases
will occur in about one-third of
patients with measurable primary
tumours. If the surgery has been
successful in removing the disease,
the calcitonin level should drop to
immeasurable levels.
The risk factors for recurrence and decreased survival
are advanced age, extracapsular
tumour extension at presentation
and progression of cervical nodal
disease particularly beyond the
neck. Radioactive iodine ablation
is ineffective and the use of external beam radiation is controversial
and generally not considered helpful.
The disease can be indolent following treatment and 10-year survival rates of up to 85% have been
reported, although biochemical
cure rates (undetectable calcitonin)
rates are much lower. Management is determined by the ongoing
monitoring of calcitonin, with surgery reconsidered when necessary.
This
aggressively
malignant
tumour represents fewer than 1%
of clinically recognised thyroid
cancers. The annual adjusted age
incidence is about two per million
per year with a peak incidence in
the 6th-7th decade of life. Small
series report 55-77% of cases
occurring in females.
Anaplastic carcinoma may be
associated with previous or concurrent thyroid disorders and is
sometimes seen in patients who
have had a differentiated thyroid
carcinoma that has undergone further malignant transformation.
Typically, anaplastic carcinoma
presents with a rapidly enlarging
neck mass causing local compressive symptoms such as dysphagia,
dysphonia, stridor, dyspnoea and
neck pain or tenderness.
Cervical regional nodal involvement is found in more than 40%
of patients at presentation.
Patients may also present with
vocal cord paralysis due to nerve
infiltration.
Anaplastic carcinomas directly
invade aggressively into trachea,
oesophagus, vessels and muscle
and more than half of patients
will have distant metastases at
the time that they seek treatment.
The median survival is only 3-4
months and, unfortunately for
most patients, complete surgical
resection is rarely possible. Surgery therefore is used for local
control of symptoms.
External beam radiotherapy
may have a role for palliative local
control.
Chemotherapy has generally
been unsuccessful in altering the
outcome of this disease. There
have been some recent phase 2 trials with paclitaxel reporting up to
a 53% response rate.
invasive and attached to her anterior strap muscles. It was necessary
to remove some of the overlying
muscle during her thyroidectomy,
suggesting there would be some
extracapsular local spread. The
central paratracheal lymph nodes
did not look obviously abnormal
at surgery. Given the tumour characteristics however, a central neck
dissection was performed. All
seven lymph nodes were involved
with papillary carcinoma. Consistent with the operative findings,
the pathology confirmed extracapsular invasion with infiltration
into the muscle. It was no surprise
to find microscopic involvement
of margins, but the tumour was
deemed to have been removed
cleanly at the time of surgery.
Therese attended a multidisciplinary thyroid cancer clinic and a
course of adjuvant radioactive
iodine was recommended.
Postoperatively, Therese had
made a good recovery with no
hypocalcaemia and an as-expected
postoperative voice. One parathyroid gland was found within
the neck node specimen, a hazard
of more extensive surgery. There
were three remaining parathyroid
glands visualised at the time of her
surgery and she experienced no
hypocalcaemia. A week after her
surgery Therese felt her voice was
cont’d page 30
For patients with
MTC confined to the
thyroid gland, the
10-year survival rate
should exceed 95%
but it drops to 75%
if there is regional
nodal disease and
40% if there are
distant metastases.
Case study
THERESE is a 55-year-old woman
who presented with a lump in her
neck that she had noticed three
weeks earlier. She had been previously asymptomatic although
a little more physically aware of
her nodule since discovering it.
Her sister had had Hashimoto’s
thyroiditis but there was no family history of thyroid cancer. She
had no history of previous surgery
or irradiation exposure. She was
clinically euthyroid but had been
taking 50µg of thyroxine for some
time.
On examination there was a firm,
hard, 3-4cm mass on the left side of
the neck. It moved with swallowing and was thus consistent with a
thyroid nodule. Ultrasound scan
confirmed a heterogeneous mass
occupying much of the left lobe. The
right lobe was relatively normal with
a couple of small 5mm and 9mm
micronodules.
A fine-needle aspirate was performed under ultrasound guidance and findings were consistent
with papillary carcinoma. There
were no palpable abnormal cervical lymph nodes and no abnormal
nodes were seen on a repeat ultrasound scan of the neck. It was rec-
28
| Australian Doctor | 14 March 2014
ommended that Therese undergo
a total thyroidectomy and left
central neck (level VI/VII) cervical
node dissection.
Therese’s tumour was locally
www.australiandoctor.com.au
1. S tavrou EP, et al. Thyroid Cancer
in NSW. Cancer Institute NSW,
Sydney, 2008.
2. W
ong C, et al. Thyroid nodules:
rational management. World Journal of Surgery 2000; 24:934-41.
3. B
rito JP, et al. Prevalence of thyroid
cancer in multinodular goitre versus
single nodule: a systematic review
and meta-analysis. Thyroid 2013;
23:449-55.
4. K
ahn C, et al. Pathways to the
diagnosis of thyroid cancer in New
South Wales: a population-based
cross-sectional study. Cancer
Causes and Control 2012; 23:3544.
5. S tang M, Carty S. Recent developments in predicting thyroid
malignancy. Current Opinion in
Oncology 2008; 21:11-17.
6. H
ay ID, et al. Papillary thyroid
microcarcinoma: a study of 900
cases observed in a 60-year period.
Surgery 2008; 144:980-87.
How To Treat – Thyroid cancer
from page 28
hoarse. At postoperative review, 1-2
weeks later it seemed to be improving. Her preoperative examination confirmed normal vocal cord
movement so at six weeks this was
repeated. She had normal laryngeal
function and her voice continued to
return to normal.
A couple of months after surgery Therese received her adjuvant
radioactive iodine. Pretreatment
blood tests showed a TSH in
excess of 100mU/L, which is quite
optimal for the administration of
radioactive iodine. Her thyroglobulin was undetectable and she had
negative thyroglobulin antibodies.
A postoperative thyroid nuclear
scan showed some minor uptake
in the left thyroid bed with no
evidence of nodal or distant functional metastatic disease.
Therese’s post-treatment blood
tests and therapeutic scan results
taken together indicate very low
or negligible residual disease following her surgery and RAI,
which suggests a good prognosis.
She was recommenced on thyroxine at 100 µg with the first posttreatment blood tests planned in
four months’ time.
Conclusion
DIFFERENTIATED thyroid cancer
can be readily treated with a very
good outcome. Although thyroidectomy is a highly technical procedure, the gland can be completely
removed with a high degree of
safety. The unique iodine metabolism that occurs within the thyroid facilitates the effective use of
radioactive isotopes for diagnosis,
treatment and surveillance. When a
patient presents with a differentiated
thyroid cancer there is every reason
for optimism and reassurance. It is
unfortunate however, that we still
have no good answers for anaplastic
carcinoma. Fortunately, it represents
a very small (less than 1%) proportion of thyroid malignancies.
Surgery is the mainstay of treatment for every category of thyroid malignancy and radioactive
iodine plays a very important role
for differentiated thyroid cancers.
For papillary microcarcinoma,
most patients will only require
a hemithyroidectomy, therefore
maintaining normal function without the need for thyroid hormone
replacement. Papillary microcarci-
Online resources
Australian and New Zealand
Endocrine Surgeons
www.endocrinesurgeons.org.au
American Association of
Endocrine Surgeons
www.endocrinesurgery.org
British Association of Endocrine
and Thyroid Surgeons
www.baets.org.uk
noma has an excellent prognosis
but the remaining thyroid remnant
should be monitored. Completion
thyroidectomy is always an option
in the future should concerns arise.
Monitoring for thyroid cancer is
straightforward and in general not
overly invasive.
Instructions
How to Treat Quiz
Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points.
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Thyroid cancer — 14 March 2014
GO ONLINE TO COMPLETE THE QUIZ
www.australiandoctor.com.au/education/how-to-treat
1. Which TWO statements are correct
regarding epidemiology of thyroid
cancers?
a) Solitary thyroid macronodules occur in
about 5% of the population but fewer than
one in 20 will be malignant
b) The annual incidence of thyroid cancer is
fewer than 10 per 100,000
c) Ninety-five per cent of thyroid malignancies
are undifferentiated
d) It is estimated that one in 4000 women is
at risk of developing thyroid cancer
by age 75
2. Which THREE statements are correct
regarding the aetiology of thyroid
cancers?
a) Thyroid malignancy may not be more
common in patients with goitres
b) Exposure to external ionising radiation is a
recognised risk factor for developing thyroid
cancer
c) Children with leukaemia treated by ‘mantle’
irradiation have a 20-50% increased risk of
thyroid malignancy
d) There is no heritable risk of thyroid cancer
3. Which TWO statements are correct
regarding the pathology of thyroid
cancers?
a) Differentiated thyroid carcinoma has welldeveloped combinations of follicles
b) Hurthle cell variants are always caused by
malignant thyroid cancers
c) Papillary carcinomas are associated with
‘Orphan Annie eyes’ nuclei and psammoma
bodies
d) N
inety per cent of atypical nodules will
ultimately prove to be malignant
4. W
hich TWO statements are correct
regarding investigation and diagnosis of
thyroid cancers?
a) Baseline thyroid function tests including
thyroglobulin are recommended for
suspected thyroid cancer
b) F
luorodeoxyglucose (FDG)-PET/CT has 60%
sensitivity for malignancy
c) If thyroid function tests are normal, a nuclear
medicine scan should be requested for a
suspected thyroid cancers
d) T
he specificity of fine-needle aspiration
cytology for malignancy is 72% and
sensitivity 87%
5. W
hich TWO statements are correct
regarding the management of
differentiated thyroid cancers?
a) Radioactive iodine (RAI or I-131) is used
as an alternative curative option to total
thyroidectomy for a differentiated thyroid
cancer.
b) A
djunctive I-131 is potentiated by
withholding thyroxine replacement after total
thyroidectomy
c) There is no indication for monitoring
thyroglobulin following total thyroid ablation
d) L
ow doses of I-131 are used to monitor for
recurrences following curative treatment
6. Which TWO statements are correct
regarding the management of papillary
thyroid cancers?
a) L
arger papillary thyroid tumours have a
greater chance of lymph node metastases
b) Total thyroidectomy is second-line treatment
for papillary carcinoma greater than 1cm
c) T
he risk of permanent damage to the
recurrent laryngeal nerve following thyroid
surgery is more than 25%
d) The major airway, carotid vessels and
oesophagus should all be closely monitored
postoperatively
7. Which TWO statements are correct
regarding the management of medullary
thyroid cancers?
a) E
arly diagnosis or prevention is the key for
managing patients at high risk
b) Ultrasound is not useful in assessing
medullary thyroid cancers
c) I-131 is the best curative option for
medullary thyroid cancers
d) Calcitonin is a reliable marker for medullary
cancer recurrence following treatment
8. Which TWO statements are correct
regarding anaplastic thyroid cancers?
a) A
naplastic thyroid cancers may transform
from differentiated thyroid carcinoma
b) Anaplastic thyroid cancer typically presents
with symptoms associated with a rapidly
enlarging neck mass
c) S
urgery is curative for most anaplastic
thyroid cancers
d) Chemoradiotherapy is curative in late
metastatic presentations
9. Annelise is a 67-year-old woman who
presents with a lump on the left neck
that she has had for a year. Which
THREE statements are correct regarding
investigation and diagnosis of her
presentation?
a) FNA sampling of thyroid nodules over 4cm is
highly sensitive for thyroid cancer
b) Regardless of the fine-needle aspiration
result, a thyroid nodule over 3.5cm should
be considered for thyroidectomy
c) Neither ultrasound nor nuclear medicine
scans are specific for diagnosing thyroid
malignancy
d) 5-10% of fine-needle aspiration results
showing an ‘atypical’ pattern will prove to be
malignant
10. The FNA showed a well-differentiated
thyroid cancer. Which TWO statements
are correct regarding Annelise’s
management?
a) Thyroid cancer staging is a vital component
of her management
b) Annelise should be advised that
thyroidectomy has a 1-2% risk of bleeding
or infection
c) Annelise may have her I-131 given as an
outpatient if she is well with it
d) For Annelise, the goal of thyroid replacement
hormone after treatment is to keep her TSH
suppressed
CPD QUIZ UPDATE
The RACGP requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2014-16 triennium.
You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept
the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
how to treat Editor: Dr Steve Liang
Email: [email protected]
Next week Kidney stones are a common urological presentation, with incidence peaking between 30 and 60 years. The overall burden of kidney stone disease is high, and for that reason recurrence
prevention is an important goal for healthcare practitioners. The next How to Treat looks at the pathogenesis, diagnosis and management of this debilitating condition. The authors are Dr Michael Wines,
urologist, and Dr Helen Nicholson, advanced urology trainee, both of Sydney Adventist Hospital, Wahroonga, NSW
30
| Australian Doctor | 14 March 2014
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