Papillary thyroid carcinoma

Author: Prof Martin Jean Schlumberger

Creation date: March 2004
Scientific editor: Prof Sebastiano Filetti
1

Service de mdecine nuclaire. Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94805 Villejuif.
France. [email protected]

Abstract
Keywords
Definition
Etiology
Clinical description and diagnosis
Pathology
Prognostic factors
Epidemiology
Initial treatment
Follow up
Distant metastases
Complications of treatment with
Conclusion
References

131

Abstract
Papillary thyroid carcinoma (PTC) belongs to well-differentiated thyroid cancers. It is the most common of all
thyroid cancers and is among the most curable cancers. The annual incidence rate of PTC in different parts
of the world varies from 0.5-10 per 100.000 populations. Clinically, PTC presents as asymptomatic thyroid
nodules, it is usually single, firm, freely moveable during swallowing, and it is not distinguishable from a
benign nodule. A thyroid nodule should be suspected of being a carcinoma when it is found in children or
adolescents or in patients above 60 years, and when there is a history of progressive increase in size.
Hoarseness, dysphagia, cough and dyspnea are suggestive of advanced stages of the disease.
Histologically, PTC is an unencapsulated tumor with papillary and follicular structures. It is characterized by
changes in cell nuclei: nuclear overlapping, large sized nuclei, a ground glass appearance, longitudinal
nuclear grooves, and invaginations of cytoplasm into the nuclei. The tumor spreads through the lymphatic
vessels within the thyroid, to the regional lymph nodes, and less frequently to the lungs. Some oncogenes
are clearly involved in either patients with no history of radiation and thus irradiated (Chernobyl accident or
external irradiation). The most common rearrangements concern RET gene, RAS mutations and B-RAF
131

mutation. Treatment includes surgery,

therapy is required.
Keywords
Thyroid cancers,

I therapy, radiotherapy and thyroxin intake. Follow up after initial

131

I therapy, radiotherapy, thyroxin, pTNM staging system

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

Definition
Papillary thyroid carcinoma (PTC) belongs to welldifferentiated thyroid cancers, which include also
follicular and Hurthle cell carcinoma. These sorts of
tumors are the most common of all thyroid cancers
(>70%) and are among the most curable cancers.
However, some patients are at high risk of
recurrence or even death. These patients can be
identified at the time of diagnosis using wellestablished prognostic indicators. The extent of
initial treatment and follow-up should therefore be
individualized.
Etiology
Oncogenes
Recent advances in molecular biology have
improved the understanding of the pathogenesis of
thyroid carcinomas.
In papillary carcinomas occurring in patients with no
history of radiation, rearrangements of the tyrosine
kinase domains of the RET gene with the aminoterminal sequence of an unrelated gene are found in
2.5 to 33%, RAS mutations in 10%, and B-RAF
mutation in 40-60% of cases. Thus, abnormalities in
the RET/ RAS/ B-RAF/MAP kinase pathway are
found in 80% of cases with no important overlap. In
papillary carcinomas occurring after irradiation in
children, either in Belarus after the Chernobyl
accident or after external radiation, RET
rearrangements are found in 60 to 85% of cases
and B-RAF mutations are less frequent.
Thyroid irradiation
External irradiation to the neck during childhood
increases the risk of papillary carcinoma. The
latency period between exposure and diagnosis
of thyroid carcinoma is at least 5 years. The risk
is maximal at about 20 years, remains high for
about 20 years and then decreases gradually.
The risk is increased after a mean dose to the
thyroid as low as 10 cGy. Above this dose there
is a linear relationship between the dose (up to
1500 cGy) and the risk of carcinoma. Beyond this
point, the risk per Gray decreases, probably due
to cell killing. A major risk factor is a young age at
irradiation; above age 15 or 20 years the risk is
not increased. In children exposed to 1 Gy to the
thyroid, the excess risk of thyroid carcinoma
concerns 7.7% of the children. The risk of thyroid
carcinoma is not increased in adult patients given

131

I for diagnosis or therapy. Conversely, a direct

tumorigenic effect on the thyroid of radioactive
131

I and short-lived
isotopes of iodine, both
isotopes, has been strongly suggested by the

increased incidence of papillary carcinomas in

children in the Marshall Islands after atomic
bomb testing, and more recently in Belarus and
Ukraine after the Chernobyl accident. In Belarus
and Ukraine, to date, about 1500 cases have
been reported in subjects who were younger than
10 at the time of the accident.
Other Factors
In countries where iodine intake is adequate,
papillary cancers represent more than 80% of all
thyroid carcinomas. There is no increase in
incidence of thyroid carcinomas in countries where
iodine intake is low, but there is a relative increase
in follicular and anaplastic carcinomas
A high incidence of papillary carcinomas has been
reported in patients with adenomatous polyposis
and Cowden's disease (multiple hamartoma
syndrome). About 5% of cases of papillary
carcinoma are familial, and several loci for
predisposing genes have been identified.
Clinical description and diagnosis
Most differentiated thyroid carcinomas present as
asymptomatic thyroid nodules, but occasionally the
first signs of the disease are lymph node
metastases
and
rarely
lung
metastases.
Hoarseness, dysphagia, cough and dyspnea are
suggestive of advanced stages of the disease.
At physical examination, the carcinoma, usually
single, is firm, freely moveable during swallowing,
and not distinguishable from a benign nodule. A
thyroid nodule should be suspected of being a
carcinoma when it is found in children or
adolescents or in patients above 60 years, in man,
when it is hard and irregular, when ipsilateral lymph
nodes are enlarged or compressive symptoms are
present, and when there is a history of progressive
increase in size. Virtually all patients are clinically
euthyroid and have normal serum thyrotropin
concentrations.
Whatever the presentation, fine needle aspiration
cytology is the best test for the diagnosis of papillary
thyroid carcinoma, provided that an adequate
specimen is obtained.
Thyroid ultrasonography is useful for assessing the
size of the nodule and detecting other nodules, and
to guide the fine needle biopsy of small or poorly
palpable nodules.
Pathology
Papillary carcinoma is an unencapsulated tumor
with papillary and follicular structures that is
characterized by changes in cell nuclei: nuclear
overlapping, large sized nuclei, a ground glass
appearance, longitudinal nuclear grooves, and

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

invaginations of cytoplasm into the nuclei.

Recognized histological variants are the
encapsulated, the follicular, the tall cell, the
columnar cell, the clear cell and the diffuse
sclerosing variants. Their typical nuclear features
characterize Papillary carcinomas. The tumor is
multicentric in 20 to 80% of cases; it is bilateral in
about one third of cases. It spreads through the
lymphatic vessels within the thyroid, to the
regional lymph nodes, and less frequently to the
lungs.
Prognostic factors
The overall 10-year survival rates for middleaged adults with thyroid carcinomas are about
80 to 95%. Five to 15% of patients have local or
regional recurrences and 5 to 10% have distant
metastases. Prognostic indicators of recurrence
and of death are age at diagnosis, histologic
type, and extent of the tumor.
There are many scoring systems for thyroid
carcinoma, among which the Pathological tumornode-metastasis (pTNM) staging system is the
most widely accepted (Table 1). Based on this
system, 80 to 85 % of patients are classified as
being at low risk of cancer-specific mortality
(stages I and II). Some patients have a higher
risk of recurrences, even if their risk of cancerspecific mortality is low. They include young (<
16 years) and older (> 45 years) patients, those
with certain histological subtypes (the tall-cell,
the
columnar-cell
and
diffuse-sclerosing
variants), and those with large tumors, extension
of the tumor beyond the thyroid capsule, or large
and/or multiple lymph node metastases.
Therefore, the extent of initial treatment and
follow-up should be adapted according to these
prognostic indicators.
Epidemiology
Although thyroid nodules are extremely
common, differentiated thyroid carcinomas are
relatively rare. Clinically detectable thyroid
carcinomas constitute less than 1% of all human
malignant tumors, and the annual incidence rate
in different parts of the world varies from 0.5-10
per 100.000 populations. These carcinomas are
rare in children and adolescents, and their
incidence increases in adults with age, the
median age at diagnosis being 45 to 50 years.
Thyroid carcinomas are 2 to 4 times more
frequent in women than in men.
Thyroid microcarcinomas, with a diameter < 1
cm, are found in 5-36% of adults in autopsy
studies, but are rare in children.
In recent years, an apparent increase has been

reported in the incidence of thyroid carcinomas

that is mainly related to an increased incidence of
small carcinomas in adults, and this increase was
attributed to an improvement in diagnostic
techniques.
Initial treatment
Surgery
The goal of surgery is to remove all neoplastic
tissue in the neck. Therefore, the thyroid gland and
affected cervical lymph nodes should be resected.
Although some controversies still exist regarding the
extent of thyroid surgery, there are strong
arguments in favor of a total thyroidectomy for all
patients.
Total
thyroidectomy
reduces
the
recurrence rate as compared with more limited
surgery because many papillary carcinomas are
multifocal and bilateral. Removal of most if not all of
131

the thyroid gland facilitates total ablation with

I.
The argument against total thyroidectomy is that it
increases the risk of surgical complications such as
recurrent
laryngeal
nerve
injuries
and
hypoparathyroidism, and yet often some thyroid
tissue remains, as detected by post-operative
131

I. This is the reason why only

scanning with
skilled surgeons should operate papillary thyroid
carcinomas.
In low-risk patients (those with papillary carcinomas
less than 1 cm in diameter, if unifocal and
intralobar), a lobectomy may be appropriate.
Surgery of lymph nodes is routinely performed. It
includes dissection of the central compartment
(paratracheal and tracheoesophageal areas, level
VI) and may also include dissection of the
supraclavicular area and the lower third of the
jugulocarotid chain. A modified neck dissection is
performed if there are palpable lymph node
metastases in the jugulo-carotid chain. Dissection is
preferable to lymph node picking. This type of lymph
node dissection was proven to improve the
recurrence and survival rates in several series, and
several arguments support its routine use: about
two thirds have lymph node metastases, more than
80% of whom have involvement of the central
compartment; metastases are difficult to detect in
lymph nodes located behind the vessels or in the
paratracheal groove.
131

I therapy

131

I therapy is given post-operatively for three

reasons: it destroys normal thyroid remnants,
thereby increasing the sensitivity of subsequent

131

I -total body scan and the specificity of

measurements of serum thyroglobulin for the

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

detection of persistent or recurrent disease; it

may destroy occult microscopic carcinoma,
thereby decreasing the long-term recurrence
131

rate, and it permits a post-ablative I -total body

scan, a sensitive tool for persistent carcinoma.
131

Table 2:.Indications for I Ablative Treatment

in Patients with Thyroid Carcinoma
After Initial Surgery
No indication
low risk of cancer-specific mortality and lowrelapse
pTNM stage I
Indication :
Definite
- distant metastases
- incomplete tumor resection
- complete tumor resection but high
- risk for mortality/recurrence:
- pTNM stages II-III.
Probable:
- age : < 16 years
- histologic subtype : papillary tall-cell,
columnar-cell, diffuse sclerosing;
- elevated serum Tg concentrations >
3 months after surgery on L-T4.

131

Postoperative
I therapy should be used
selectively (Table 2). In low-risk patients, the
long-term prognosis after surgery alone is so
131

favorable that
I ablation is not usually
recommended. However, patients who are at
high risk of recurrence are routinely treated with
131

I, because it decreases both recurrence and

death rates.
131

Postoperatively, I therapy is administered 4 to

6 weeks after surgery, during which no thyroid
hormone treatment is given. A diagnostic total
131

body scan with 2 mCi (74 MBq) I is performed

only when thyroidectomy has been partial.
Another total body scan is done 4 to 7 days later,
and thyroxin therapy is initiated.
131

Total ablation (no visible uptake on a

I total
body scan performed 6 to 12 months later with 2
mCi (74 MBq) is achieved after administration of
both 100 mCi (3700 MBq) and 30 mCi (1000
MBq) in almost all patients who had a total
thyroidectomy. After less extensive surgery,
ablation is achieved in only two-thirds of patients
with 30 mCi (1000 MBq). Therefore, total
thyroidectomy should be performed in all patients
who have to be treated with

131

I. Total ablation

requires a dose of at least 300 Gy is delivered to

thyroid remnants, and a dosimetric study allows
estimating more precisely the dose of
should be administrated.

131

I that

External Radiotherapy
External radiotherapy to the neck and mediastinum
is indicated only in patients older than 45 years in
whom surgical excision is incomplete or impossible,
and in whom the tumor tissue does not take up

131

I.

Follow up
The goals of follow-up after initial therapy are to
maintain adequate thyroxin therapy and to detect
persistent or recurrent thyroid carcinoma. Most
recurrences occur during the first years of follow-up,
but some occur later. Therefore, follow-up is
necessary throughout the patient's life.
Thyroxin treatment
The growth of thyroid tumor cells is controlled by
thyrotropin (TSH), and inhibition of thyrotropin
secretion with thyroxin improves the recurrence and
survival rates. Therefore, thyroxin is given to all
patients with thyroid carcinoma, whatever the extent
of thyroid surgery and other treatment. The initial
dose is about 2.0 g/kg body weight in adults;
children require higher dose. The adequacy of
therapy is monitored by measuring serum TSH
three months after the treatment is begun, the initial
goal being a serum TSH concentration of 0.1
U/ml and a serum free triiodothyronine
concentration within the normal range to avoid
overdosing.
Early Detection of Recurrent Disease
Clinical and Ultrasonographic Examinations.
Palpation of the thyroid bed and lymph node areas
should be routinely performed but is poorly
sensitive. Ultrasonography is performed in all
patients. Lymph nodes that are small, thin or oval, in
the posterior neck chains, and when they decrease
in size after an interval of three months are
considered benign. Serum thyroglobulin is
undetectable in 20% of patients receiving thyroxin
treatment who have isolated lymph node
metastases. These false negative can be found with
neck ultrasonography, with an ultrasound-guided
node biopsy performed in suspicious cases for
cytology and thyroglobulin measurement in the fluid
aspirate.
X-Rays. Chest X-rays are no longer routinely
performed in patients with undetectable serum
thyroglobulin concentration. The reason is that
virtually all patients with abnormal X-rays have
detectable serum thyroglobulin concentrations.

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

Serum
Thyroglobulin
(Tg)
Determinations.
Thyroglobulin is a glycoprotein that is produced only
by normal or neoplastic thyroid follicular cells. It
should not be detectable in patients who have had
total thyroid ablation, and its detection in them
means the presence of persistent or recurrent
disease.
The sensitivity of good Tg assays is 1 ng/ml or even
less. The results can be artefactiously altered by
serum anti-Tg antibodies, which are found in about
15% of patients with thyroid carcinoma, and these
antibodies should always be sought by a
radioimmunoassay or by a recovery test. In IRMA
methods, interferences induce falsely reduced or
falsely negative serum Tg measurements.
The production of Tg by both normal and neoplastic
thyroid tissue is in part TSH-dependent. Thus, when
interpreting the serum Tg value, the serum TSH
value should be taken into account, as well as the
presence or absence of thyroid remnants. When
serum Tg is detectable during thyroxin treatment, it
will increase after the treatment is discontinued.
131

131

I -Total Body Scan. The results of I total body

scan depend on the ability of neoplastic thyroid
131

tissue to take up I in the presence of high serum

TSH concentrations, which are achieved by
withdrawing thyroxin for 4 weeks. However, some
patients poorly tolerate the resulting hypothyroidism.
This can be attenuated by substituting the more
rapidly metabolized triiodothyronine for thyroxin for
three weeks and withdrawing it for two weeks. The
serum TSH concentration should be above some
arbitrary value (30 U/ml) in patients managed in
131

I administration should be
this way; if it is not,
delayed until it is. Intra-muscular injection of
recombinant human thyrotropin (rhTSH) is an
alternative (0.9mg intramuscular for 2 consecutive
131

days with I administration on the day following the

second injection and TBS and serum Tg
determination 2 days later), because thyroxin
treatment should be continued and side effects are
minimal. Its efficiency for the detection of persistent
and recurrent disease is comparable to that of
thyroxin withdrawal in most patients.
131

I scanning is planned, patients should be

When
instructed to avoid iodine-containing medications
and iodine-rich foods, and urinary iodine should be
measured in doubtful cases. Pregnancy must be
excluded in women of childbearing age. For routine
131

I is given;
diagnostic scans, 4mCi (148 MBq)
higher doses may reduce the uptake of a
131

I. The scan is
subsequent therapeutic dose of
done and uptake, if any, is measured 72 h after the
dose using a double-head gamma camera equipped

with high-energy collimators. False-positive results

are rare.
131

Post- I Therapy Total Body Scan. Assuming

equivalent fractional uptake after administration of a
131

diagnostic and a therapeutic dose of I, uptake too

low to be detected with 2 to 5 mCi (74-185 MBq)
may be detectable after the administration of 100
mCi (3700 MBq). Thus, a total body scan should be
routinely performed 3 to 5 days after a high dose.
Follow-up strategy
If the total body
131

scan

performed

after

the

administration of I to destroy the thyroid remnant,

no iodine uptake outside the thyroid bed is seen.
Physical examination is performed and serum TSH,
FT3 and Tg are measured during thyroxin treatment
three months later. At 6 to 12 months later, the
present protocol includes a determination of serum
Tg following rhTSH stimulation and a neck
ultrasonography
(Fig.
1).
Recent
reports
131

I -TBS does not provide any

demonstrated that
useful information in these patients. If serum
thyroglobulin
following
TSH
stimulation
is
undetectable and neck ultrasonography is normal,
the risk of recurrence is less than 0.5% at 10 years.
Low-risk patients are considered cured, and the
dose of thyroxin is decreased to maintain a low but
detectable serum TSH concentration (around 0.5
U/ml). In higher-risk patients, higher doses of
thyroxin are given, the goal being a serum TSH
0.1
U/ml.
Clinical,
concentration
of
<
ultrasonographic and biochemical evaluation is
performed annually; any other testing is
unnecessary as long as the patients serum Tg
concentration is undetectable.
If serum Tg is detectable following TSH stimulation,
the attitude depends on the level of Tg: in those
patients with a relatively low Tg level (<10ng/ml),
another determination is obtained following rTSH
stimulation 6 to 36 months later, because with
longer follow up serum Tg became undetectable in
2/3 of these patients. In those with high serum Tg
levels and in particular in those with increasing
serum Tg at consecutive determinations, 100 mCi
131

(3700 MBq) I is administered with a TBS 3-5 days

later. If no uptake is detected, a FDG PET scan may
be performed.
In patients receiving thyroxin in whom serum Tg
becomes detectable, serum Tg should be measured
after TSH stimulation. If the serum Tg concentration
131

I should be
increases above 10 ng/ml, 100 mCi
given.
In low-risk patients who have had a total
thyroidectomy but who were not given

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

131

I post-

operatively, the follow-up protocol is based on Tg

determinations and neck ultrasonography. In lowrisk patients who underwent a lobectomy, yearly
follow-up consists of a neck examination and of
serum Tg determination during thyroxin treatment.
Ultrasonography will show abnormalities in the
remaining lobe in most patients with detectable Tg
concentrations. If the size is small, fine needle
biopsy may be impossible, and surgery is frequently
the only option.
Local or regional recurrences
Local or regional recurrences occur in 5 to 15% of
patients with PTC. Some are related to incomplete
initial treatment (in a thyroid remnant or in lymph
nodes),
and
the
others
indicate
tumor
aggressiveness (in the thyroid bed after total
thyroidectomy or in soft tissues).
A local or regional recurrence that is palpable or
easily visualized with ultrasonography or CT scan
should be excised. Total excision may be facilitated
by total body scanning 4 days after administration of
131

100 mCi (3 700 MBq) I, because additional tissue

that should be excised may be identified. Surgery is
performed one day later, preferably using an intraoperative probe. The completeness of resection is
verified 1 to 2 days after surgery by another total
body scan.
External radiotherapy is indicated in patients with
soft tissue recurrences that cannot be completely
excised and that do not take up

131

I.

Distant metastases
Distant metastases, mostly in the lungs and bones,
occur in 5 to 10% of patients with PTC. Lung
metastases are more frequent, and are almost the
only site of distant spread in children. Bone
metastases are more common in older patients.
Other less common sites are the brain, liver and
skin.
Diagnosis
Clinical symptoms of lung involvement are
uncommon. The pattern of lung involvement may
vary from macronodular to diffuse infiltrates. The
latter, when not detected by chest X-ray, are usually
131

diagnosed with
I total body scan and may be
confirmed by CT ; enlarged mediastinal lymph
nodes are often present in children. Nearly all
patients with distant metastases have high serum
Tg concentration, unless the metastases are not
visible on X-rays, and two thirds of patients have
uptake in the metastases.
Treatment

131

131

Patients with metastases that take up I should be

treated with 100 to 150 mCi (3700 to 5550 MBq)
every 4 to 6 months. The effective radiation dose,
that depends on the ratio between total uptake and
the mass of thyroid tissue, is correlated to the
131

I therapy. Lower doses (1 mCi(37

outcome of
MBq)/kg body weight) are given to children. There is
131

I given to
no limit to the cumulative dose of
patients with distant metastases, although above a
cumulative dose of 500 mCi (18 500 MBq), further
131

I therapy has little benefit but significantly high

risk of leukemia. External radiotherapy is given to
bone metastases visible on X-rays. Chemotherapy
is poorly effective and should be reserved to
patients with progressive and non functioning
metastases ; new drugs directed against specific
targets are under study.
Treatment Results
Complete responses have been obtained in 45% of
131

patients with distant metastases with

I uptake.
Overall survival after the discovery of distant
metastases is about 40% at 10 years. Young
patients with well-differentiated tumors that take up
131

I and have metastases that are small when

discovered have a more favorable outcome.
131

Complications of treatment with

Acute Side Effects

Acute side effects (nausea, sialadenitis) after
131

treatment with I are common but usually mild and

resolve rapidly. Radiation thyroiditis is usually trivial,
but if the thyroid remnant is large, the patient may
have enough pain to warrant corticosteroid therapy
for a few days. Tumor in certain locations -brain,
spinal cord and paratracheal- may swell in response
131

to TSH stimulation or after

I therapy, causing
compressive symptoms that should be prevented by
corticosteroid administration. Radiation fibrosis may
develop in patients with diffuse lung metastases, if
high doses (> 150 mCi (5 550 MBq)) are
administered at short intervals (< 3 months).
131

I Genetic Defects and Infertility

Particular attention must be paid
administration of

to

131

avoid

I in pregnant women.

131

After
I treatment, spermatogenesis may be
transiently depressed, and women may have
transient ovarian failure. Genetic damage induced
131

I before conception has been a

by exposure to
major subject of concern. However, the only

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

anomaly reported to date is an increased frequency

131

of miscarriages in women treated with I during the

year preceding the conception. Therefore, it is
recommended that conception be postponed for one
131

year after treatment with I. There is no evidence

that pregnancy affects tumor growth in women
receiving adequate thyroxin therapy. Thyroxin
treatment should be monitored carefully (at least
every 2 months with TSH measurement) during
pregnancy.
Carcinogenesis and Leukemogenesis

131

Mild pancytopenia may occur after repeated

I
therapy, especially in patients with bone metastases
who are also treated with external radiotherapy. The
overall relative risk of secondary carcinoma and of
leukemia was found to be increased in patients
131

I (> 500
treated with a high cumulative dose of
mCi (18,500 MBq)) or in association with external
radiotherapy. Because, the dose-effect relationship
131

is linear, any therapeutic dose of I may increase

the risk of leukemia and of solid tumors.

Most patients with papillary carcinomas can be

cured. However, both initial treatment and follow-up
should be individualized according to prognostic
indicators and thereafter to any evidence of disease
in order to improve their quality of life.
References
Mazzaferri EL, Kloos RT. Current approaches to
primary therapy for papillary and follicular thyroid
cancer. J Clin Endocrinol Metab 2001; 86:1447-63.
Schlumberger M. Papillary and follicular thyroid
carcinoma. N Engl J Med 1998; 338:297-306.
Schlumberger MJ, Filetti S, Hay ID. Nontoxic goiter
and thyroid neoplasia. In: Williams Textbook of
th

Endocrinology, 10 edition, Larsen RP, Kronenberg

HM, Melmed S, Polonsky KS, Eds. Saunders,
Philadelphia, 2002, pp 457-90.
Sherman SI. Thyroid carcinoma. Lancet 2003; 361:
501-11.
Thyroid Cancer Task Force. AACE/AAES
medical/surgical guidelines for clinical practice:
management of thyroid carcinoma. Endocrine
Practice 2001;7:203-220.

Conclusion

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

Table 1. TNM Staging System for Papillary and Follicular Carcinoma of the Thyroid
Development of the definition of TNM
1992

2002

Primary tumor (T)

T0: No evidence of primary tumor
T1: Tumor 1cm limited to the thyroid
T2: Tumor>1-4cm limited to the thyroid
T3: Tumor>4cm limited to the thyroid

No evidence of primary tumor

Tumor 2cm limited to the thyroid
Tumor>2-4cm limited to the thyroid
Tumor>4cm limited to the thyroid or any tumor with minimal
extrathyroid extension (e.g.; extension to stern thyroid
muscle or perithyroid soft tissues

T4: Any size extending beyond the thyroid

capsule
T4a

Tumor of any size with extension beyond the thyroid

capsule and invades any of the following: subcutaneous
soft tissues, larynx, trachea, oesophagus, recurrent
laryngeal nerve
Tumor invades prevertebral fascia, mediastinal vessels
encases carotid artery.

T4b
Regional Lymph Node (N):
(In the 2002 system, to be classified as N0 or
N1, at least 6 lymph nodes should be examined
at histology. Otherwise, the tumor is classified aNx).
N0: No regional lymph node metastasis
N1: Regional Lymph Node metastasis
N1a
N1b

Distant metastases (M)

M0: No distant metastasis
M1: Distant Metastasis

1992
Age <45
Stage I: Any T, any N, M0
Stage II: Any T, any N, M1
Stage III: none
Stage IV: none
Age45 years
Stage I: T1, N0, M0
Stage II: T2-T3, N0, M0
Stage III: T4,N0,M0 or any T,N1,M0
Stage IV: Any T, any N, M1
Stage IVA
Stage IVB
Stage IVC

No regional lymph node metastasis

Regional lymph node metastasis
Metastases in pretracheal and paratracheal,
including prelaryngeal and delphian lymph nodes
Metastases in other unilateral, bilateral or
contralateral cervical or upper mediastinal lymph nodes.
No distant metastasis
Distant Metastasis

TNM staging
2002
Any T, any N, M0
Any T, any N, M1
None
none

T2, N0, M0
T3, N0, M0 or any T1-3, N1a, M0
T1-3, N1b, M0 or T4a, Any N, M0
T4b, Any N, M0
Any T, Any N, M1

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf

Figure 1: Follow-up of Patients after Total Thyroid Ablation, Based on Serum Thyroglobulin
Determinations and neck ultrasonography. The decision level depends upon the assay used to measure
serum Tg.

TG: serum throglobulin; TSH: thyrotropin; rh TSH: recombinant human thyrotropin, US: ultrasonography, FT3 : Free
Triiodothyronine, TBS: total body scan, LTA: levothyroxine

Schlumberger MJ. Papillary thyroid carcinoma. Orphanet encyclopedia, March 2004

http://www.orpha.net/data/patho/GB/uk-PTC.pdf