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CLINICAL STUDY
Thyroid cancer: is the incidence rise abating?
Genevie
`ve Sassolas
1,
*, Zakia Hafdi-Nejjari
1,
*, Laurent Remontet
2
, Nadine Bossard
2
, Aure
´lien Belot
2,4
,
Nicole Berger-Dutrieux
3
, Myriam Decaussin-Petrucci
3
, Claire Bournaud
1,5
, Jean Louis Peix
3
, Jacques Orgiazzi
3,5
,
Franc¸oise Borson-Chazot
1,5
and the Group of Pathologists of the Rho
ˆne Alpes Region
1
Hospices Civils de Lyon, Registre Rho
ˆne Alpin des Cancers Thyroı¨diens, Fe
´de
´ration d’Endocrinologie et Centre de Me
´decine Nucle
´aire Groupement
Hospitalier Est, 59 Boulevard Pinel, 69677 Bron Cedex, France,
2
Hospices Civils de Lyon, Service de Biostatistique, Laboratoire Biostatistique Sante
´,
Universite
´Lyon I, 69495 Pierre Be
´nite, France,
3
Hospices Civils de Lyon, Laboratoire d’Anatomie Pathologique, Service d’Endocrinologie et Service de
Chirurgie Endocrinienne, Centre Hospitalier Lyon Sud,69424 Lyon, France,
4
De
´partement des Maladies Chroniques et des Traumatismes,Institut de Veille
Sanitaire, 94 415 Saint-Maurice, France and
5
Universite
´de Lyon, Universite
´Lyon 1, Inserm U664, F-69008 Lyon, France
(Correspondence should be addressed to F Borson-Chazot; Email: francoise.borson-chazot@chu-lyon.fr)
*(G Sassolas and Z Hafdi-Nejjari contributed equally to this work)
Abstract
Objective: The aim of the present study was to determine recent trends in thyroid cancer incidence rates
and to analyze histopathological characteristics and geographical distribution.
Methods: Histologically proven 5367 cases were collected over the period 1998–2006 in France from
the Rho
ˆne-Alpes thyroid cancer registry. Geographical variations of incidence were analyzed using a
mixed Poisson model.
Results: The average incidence rates, age standardized to the world population, were 3.9/100 000 in
men and 12.3/100 000 in women, higher than those previously reported in France. After an initial
increase during the first 3 years, a steady level of incidence was observed for the period 2001–2006.
The annual incidence rate of microcarcinomas was correlated with that of all cancers in men and
women (rZ0.78 and 0.89; P!0.01) respectively. Papillary microcarcinomas represented 38% of
tumors and two-thirds of them measured less than 5 mm in diameter. They were fortuitously
discovered after thyroidectomy for benign diseases in 64% of cases. Histological marks of
aggressiveness differed according to the size of the tumor. Despite recent advances in diagnosis,
13% of tumors were diagnosed at advanced stage especially in men. Geographical distribution of
incidence based on subregional administrative entities showed lower incidence rates in rural than in
urban zones in men (relative rate: 0.72; 95% CI: 0.62–0.84) and women (relative rate: 0.85; 95% CI:
0.73–0.93).
Conclusion: The present study suggests that the rise in thyroid cancer incidence is now abating. It could
reflect standardization in diagnostic procedures. Further studies, performed on a more prolonged
period, are necessary to confirm these data.
European Journal of Endocrinology 160 71–79
Introduction
Although thyroid cancer is relatively rare, accounting
for around 1.5% of all cancers, its incidence has sharply
increased over the past 30 years and to date it is the third
cancer among the French women. This rise in incidence
has been extensively reported, in the USA (1), Ontario
(2), as well as European countries (3–5).Itwas
associated with a change in the distribution of
histological type, namely an increase in papillary
cancers, accounting for more than 80% of all thyroid
cancer in recent series (1, 4). A recent analysis
conducted from six French cancer registries representing
13% of the French population showed an annual percent
increase in the incidence of papillary cancers of 8.1% in
men and 9.0% in women for the period 1983–2000 (6).
The major part of the increase in papillary thyroid cancer
incidence has been related to small tumors, less than
2 cm in diameter (1), and in recent series micropapillary
cancers represent 40% of cases (1, 6). The current
hypothesis is that the increase in thyroid cancer
incidence is mainly due to the use of more efficient
diagnostic tools (7), particularly that of ultrasonography
(US) and fine needle aspiration biopsy (FNAB), leading to
an increased detection of small subclinical tumors. Wide
variations in thyroid cancer incidence exist between
countries and in the same country (8). The national
estimation of incidence rates in France for the period
1998–2000 ranged from 5 to 20 per 100 000 according
to administrative areas (9). These differences may reflect
differential exposure to thyroid cancer environmental
risk factors or differences in diagnostic practices.
Population-based cancer registries are major tools
for studying incidence. They give a synthetic view of a
European Journal of Endocrinology (2009) 160 71–79 ISSN 0804-4643
q2009 European Society of Endocrinology DOI: 10.1530/EJE-08-0624
Online version via www.eje-online.org
given pathology at a given time. The Rho
ˆne-Alpes (RA)
region thyroid cancer registry (TCR) has registered
5367 histopathologically confirmed cases from 1998 to
2006, in a region accounting for 10% of the French
population (six million inhabitants).
The aim of the present study was to determine recent
trends in incidence rates and to analyze histopatholo-
gical characteristics and geographical distribution.
Materials and methods
The TCR of the RA (TCR-RA) region is a population-
based collection initiated in 1998 and is constituted of
histologically proven incident cases, operated in a
region that includes approximately six million inhabi-
tants living in 8 de
´partements and 311 cantons. The
constitution of the registry was approved by the
Commission Nationale de l’Informatique et des Liberte
´s.
It was performed with the help of the histopathologists,
the surgeons, and the regional health agency. Patients
were informed by surgeons of their inclusion in the
registry according to French legislation and they were
aware of the possibility to refuse. Cases were transmitted
from various sources assuring satisfactory complete-
ness: pathology reports provided by the 30 histopathol-
ogy laboratories of the RA region, card index of 103
surgical wards, and hospital claims databases (10).
The following data were recorded: demographic
information, surgical procedure, major diameter of the
tumor (or the largest if multiple), histological criteria used
for tumor node metastasis (TNM) classification including
extrathyroidal development (ET) beyond the thyroid
capsule, focality, and lymph node metastases (LNM).
Histological subtypes were classified according to the
World Heath Organization (WHO) classifications (2004)
(11) in the following categories: papillary, follicular,
oxyphilic (variant of papillary and follicular), poorly
differentiated (insular), anaplastic, and medullary thyroid
carcinomas. There was no direct reevaluation of the
pathology. However, in order to have a homogeneous
diagnosis, a cautious reading of all pathological records
was performed by a pathologist member of the national
committee on thyroid cancer (NB-D). For staging by
pTNM, the fifth edition was applied to the whole series and
the sixth edition to the cases recorded from 2003 to 2006.
There was no reclassification. The study of papillary
variants according to the WHO 2004 classification was
applied to954 consecutive tumors, corresponding to 87%
of papillary thyroid cancers removed in 2005 and 2006.
The series was considered as representative since there
was no choice a priori and since the cases were highly
comparable with the whole series in terms of age, sex ratio,
proportion of microcarcinomas (36 vs 38%), and pTNM
staging (data not shown).
A total of 5367 incident cases of thyroid cancer were
registered in the TCR-RA during the 9-year period (1998–
2006). Ofthese, 1256 (23.4%) werediagnosed in men and
4111 (76.6%) in women. The mean age at diagnosis was
49G15 years for men and 50G15 years for women.
Surgical procedures consisted of total (or near total)
thyroidectomy in 79% of patients (mean age 49G17
years). Cervical lymph node dissection was not system-
atically performed in cases of limited disease without
evidence of lymph node involvement at clinical exami-
nation, pre and/or perioperative US and direct observation
at surgery. It was performed in 24% of cases, correspond-
ing to 1285 patients and consisted of central neck
dissection in 30%, central and lateral neck dissection in
60%, and more extensive dissection in the remaining 10%.
Statistical analyses
Incidence rates were calculated for the period 1998–2006
and expressed as incidence rates per 100 000 person-
years, age standardized both to the European and World
populations, to ensure comparison with published data.
The geographical variations of incidence (1998–2004)
were analyzed on a French ‘canton’ basis (i.e. a French
administrative entity) using a mixed Poisson model (12),
and separate analysis for males and females were
conducted. In the Rho
ˆne-Alpes Region, there are 311
cantons of which 56 (18%) are considered urban (INSEE
classification) and 255 (82%) rural and semirural. The
covariates introduced in the model with fixed effects were:
age, year of diagnosis, physician density (i.e. the number
of general practitioners per 1000 inhabitants), and the
urban/rural characteristic of the canton. Canton was
introducedin the model assuming a random effect and, for
each canton, its relative rates were estimated using a
shrinkage estimator (12) and mapped with software
Arcview 3.1.
Results
Overall age-adjusted incidence rates
A total of 5367 incident cases of thyroid cancer were
registered in the TCR-RA during the 9-year period (1998–
2006). The overall incidence rates, age standardized to
the European and world populations, were 4.82 and 3.9
per 100 000 men and 14.91 and 12.3 per 100 000
women respectively. Incidence rates increased during the
first 3 years of the study and were, thereafter, stable over
time for the period 2001–2006 (Table 1). Incidence rates
by age groups at diagnosis are shown in Fig. 1 in men and
women. Low rates were observed in children with a rapid
increase at puberty for girls. A maximal incidence of
35/100 000 was obtained in women of 55–59 years.
The world-standardized incidence rates of microcancers
(%1 cm) were 1.21/100 000 in men and 4.76/100 000
in women. There was a significant correlation between
the annual incidence rate of microcancers and that of all
cancers in men and women (rZ0.78 and 0.89; P!0.01)
respectively.
72 G Sassolas, Z Hafdi-Nejjari and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
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Histopathological subtypes
The distribution of histopathological types is given in
Table 2. Papillary thyroid carcinomas(PTC) accounted for
86.5% of all cancers. The distribution of PTC variants was
analyzed from a subset of 954 tumors. Among them, 36%
were microcarcinomas. When analyzing tumors more
than 1 cm in diameter, the proportion of classical
papillary variant was 44% and that of the follicular
variant was 46%, constituted in equal proportion of
invasive and encapsulated tumors. In invasive forms,
plurifocality was found in 30%, extrathyroid growth (ET)
in 16%, and LNM in 17% whereas in the encapsulated
follicular variant, plurifocality was found in only 10% and
neither ET nor LNM was found. The diffuse sclerosing
variant was found in 2% of cases and represented 5.8% of
the 0–30 years age group. It was associated with LNM in
75% of cases. LNM were also found in 60–75% of patients
with the tall cell or solid variant.
Follicular thyroid cancers represented 5.9% of cases
(Table 2); they were encapsulated in 60%, and widely
invasive in 40%. Twenty-eight percent of follicular
thyroid cancer belonged to the oncocytic variant. Poorly
differentiated (insular) carcinomas represented 1%,
whether pure or associated with differentiated papillary
or follicular component in 13% of them. Anaplastic and
medullary thyroid cancer represented 1.06 and 2.8%
respectively.
Stage at diagnosis
The respective distribution of pTNM scores according to
the fifth and sixth editions is shown in Table 3.As
expected, the proportions of pT1 and pT3 were higher
while those of pT2 and pT4 were lower in the sixth
compared with the fifth edition. The distribution of the
pTNM scores (fifth and sixth editions) by age groups is
shown in Fig. 2 (A and B). The main findings were a
progressive increase in pT1 with age, in both classi-
fications, a progressive decrease with age in LNM from
40% in children to 10% in older subjects (Fig. 2B). The
use of the sixth edition, resulted, in children and
adolescents, in a striking decrease in pT4 counter-
balanced by an increase in the proportion of pT3
tumors. Thus, extensive tumors classified as pT4 were
almost exclusively observed in older subjects and mainly
in men (Fig. 2B). As a whole, aggressive tumors
classified as pT3 or pT4 represented 13% of thyroid
cancer. The proportions of cancer types were different
from those of the whole series with 59% of papillary
cancers, 17% of follicular, 7% of oncocytic, 5.4% of
insular, 4% of medullary, and 6.6% of anaplastic.
Distant metastases led to the diagnosis of thyroid cancer
in 1% of patients.
Microcarcinomas represented 38.2% of all tumors
(2154 cases), 96.5% of them being papillary. A large
proportion of these tumors (64%) had a diameter of
%0.5 cm and 30% had a diameter of %0.2 cm. The
proportions of microcancers were significantly different
between men and women (33 vs 42% respectively;
P!0.005) and between age groups (P!0.004) with
the highest value of 49% in the 50–60 years group. The
effect of age was similar in men and women. Seventy
percent of microcancers were removed from patients
older than 45 years. In the whole group of microcancers
plurifocality was found in 27%, ET in 5.5%, and LNM in
5.2%. The relationship between tumor size, LNM, and
ET are shown in Fig. 3. The proportion of ET and LNM
Table 1 Incidence rates per 100 000 person-years of thyroid
cancers in the Rho
ˆne-Alpes region, by sex and year.
Men Women
Year
Standard
Europe
Standard
world
Standard
Europe
Standard
world
1998 3.37 2.47 10.27 8.35
1999 4.12 3.32 11.65 9.53
2000 4.27 3.43 13.78 11.28
2001 5.16 4.19 18.82 15.25
2002 5.78 4.77 17.14 13.83
2003 5.21 4.24 15.79 12.99
2004 5.70 4.49 16.55 13.41
2005 5.32 4.19 17.09 14.53
2006 5.02 3.95 15.67 12.70
Data have been age standardized both to the European and the world
population in order to allow for comparisons.
Figure 1 Incidence rates per 100 000
person-years of thyroid cancers by age
groups in men and women.
Epidemiology of thyroid cancer 73EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
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increased as a function of tumor size. It was lower than
5% in tumors less than 5 mm in diameter. The
microcancers were classified as ‘clinical’, expected
after US or FNAB or observed by the surgeon (36%),
or fortuitously discovered (64%). The mean size of
‘clinical’ microcancers was higher than that of
fortuitous cancers: 0.64G0.26 cm vs 0.35G0.22 cm;
P!0.01. In ‘clinical’ microcarcinomas, ET and LNM
were seen in 12% and multifocality in 35%, whereas in
fortuitous cancers the ET and LNM were noted in 1%
and multifocality in 19%. Globally, fortuitous cancers,
93% of them being microcarcinomas were found
in thyroids removed for benign disease: hyperthyroidism
in 11%, in the vicinity of adenomas in 32%, and in
multinodular goiters in 57%. The contribution of
fortuitously discovered microcancers dramatically
decreased with age (Fig. 2A). The proportions of cancers
discovered in goiters varied with age from 7% in patients
younger than 25 years, to 22% in patients 25–50 years,
to 31% in patients 50–60 years, and to 34% in patients
older than 60 years.
Time trend in the distribution of thyroid
cancer
As shown in Fig. 4, there was a strong parallelism
between the number of thyroid cancer over the study
period and the number of papillary tumors with a rapid
increase between 1998 and 2001 and further stabil-
ization. A similar pattern was observed for small
tumors, especially less than 1 cm in diameter. As
shown in Fig. 5, this increase with time was mainly
related to an increase in the number of microcancers
fortuitously discovered, and mainly concerned the
group of the smallest (!0.5 cm) in which fortuitous
cancers represented 72% in 2002 (vs 35% for the 0.5–
1 cm for the same period). By contrast, there was no
change over time in the number of non-papillary
tumors nor in the number of large tumors more than
4 cm in diameter (T3 or T4) observed in 9.8% of
patients (nZ506; Fig. 4).
Geographical variations of incidence rates
Table 4 shows the number of cases and the incidence
rates per 100 000 person-years according to the
urban/rural characteristic of the cantons. The incidence
in rural cantons was 28% lower than in urban cantons
in men (relative rate 4.3/6Z0.72) and 15% in women
(relative rate 14.4/17Z0.85). The Poisson mixed model
with adjustment on all covariates confirmed these
results. Indeed, the rural/urban characteristic was
found statistically significant: the ratio was estimated
at 0.72 (95% CI: 0.62–0.84) in men and 0.82 (95% CI:
Table 3 Distribution of pTNM staging according to the fifth and sixth
editions.
Fifth edition Sixth edition
Men (%) Women (%) Men (%) Women (%)
pT1 31.7 40.5 45.9 61.7
pT2 38.2 40.2 26.2 20
pT3 12.1 4.5 22.4 14.6
pT4 16.8 14.6 4.8 2.9
Table 2 Histopathological characteristics of the 5367 incident cases of thyroid cancer diagnosed between 1998 and 2006 in the French
Rho
ˆne-Alpes region.
Number and proportion Mean age at diagnosis (year)GS.D. LNM ET
Total 5367
Men 1256 (23.4%) 49G15
Women 4111 (76.6%) 50G15
Papillary 4642 (86.5%)
Men 1012 (80.5%) 48G15 176 (17%) 162 (16%)
Women 3630 (88.2%) 49G15 434 (12%) 494 (13%)
Follicular 321 (5.9%)
Men 106 (8.4%) 52G16 6 (5.6%) 16 (15.6%)
Women 215 (5.2%) 51G19 13 (6%) 32 (15%)
Oncocytic 104 (1.9%) 60G15 4 (0.3%) 32 (30%)
Poorly differentiated 52 (1%) 62G16 10 (20%) 23 (44%)
Medullary 154 (2.8%) 51G18 53 (34%) 22 (14.2%)
Anaplastic 57 (1.06%) 72G13 26 (46%) 53 (95%)
Papillary variants 954
Variant %1 cm 342 (36%) 5.2% 5.5%
Variant O1 cm 612 (64%)
Classical 266 (28%) 40% 30%
Follicular 286 (30%) 8% 8%
Tall cell 4 (0.4%) 75% 75%
Diffuse sclerosing 20 (2.1%) 75% 30%
Solid 10 (1%) 60% 70%
Focal insular 7 (0.7%) 0% 45%
Oncocytic 16 (1.67%) 0% 6.25%
74 G Sassolas, Z Hafdi-Nejjari and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
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0.73–0.93) in women. General practitioner density did
not appear to have a significant effect on incidence
whether in men or in women. Figure 6 shows canton
variability of the incidence in women after adjustment
in women’s age and in the rural/urban characteristic of
the canton.
Discussion
The RA-TCR provides an overview of the presentation of
thyroid cancer as it was diagnosed during the past
decade from a six million French population. After an
initial rise, observed for the first 3 years, steady
incidence rates were observed, both in men and
women for the following 6 years. During the first 3
years, there was mainly an increase in small papillary
tumors less than 1 cm in diameter whereas large
tumors more than 4 cm in diameter were stable. The
difference between 1998 and 2001 was constituted for
53% of tumors fortuitously discovered. Changes with
time in the practice of pathologists with more careful
examination of whole surgical specimens and changes
with time in the consideration of in situ tumors
as declarable cancers were probably the main
determinants of the increase. Satisfactory completeness
was reached after 2000 as shown by the comparison
with hospital discharge databases (10). The incidence
rates of the last 6 years are elevated, slightly higher
than those reported for the more recent years, whether
observed (4, 13–15) or estimated from French cancer
registries covering 13% of the national population (9,
16). The fact that the changes in papillary tumors and
small-size tumors less than 1 cm in diameter parallel
those of the general incidence suggest the major
influence of small papillary cancers on incidence rates
(1, 6, 13, 15). The present study shows a near
Figure 2 Distribution of pTNM stages (fifth and sixth edition) by age.
(A) pTNM fifth edition, 5310 cases (1998–2006): 0–14 years, 40
cases; 15–19 years, 80 cases; 20–29 years, 437 cases; 30–40
years, 979 cases; 41–50 years, 1188 cases; 51–60 years, 1329
cases; O60 years, 1257 cases. pT1 results are presented as all
cases, cases pT1 ‘clinical’, and cases pT1 ‘fortuitous’. (B) sixth
edition, 2548 cases (2003–2006): 0–14 years, 13 cases; 15–19
years, 35 cases; 20–29 years, 231 cases; 30–40 years, 456 cases;
41–50 years, 530 cases; 51–60 years, 650 cases; O60 years, 633
cases. NC(ZN1aCN1b).
Figure 3 Relationship between size of carcinomas, extrathyroidal
extension (ET), and lymph node metastases (LNM): %0.2 cm,
NZ658; O0.2– %0.3 cm, NZ276; O0.3– %0.4 cm, NZ195;
O0.4– %0.5 cm, NZ263; 0.5%1 cm, NZ762; O1– %2 cm,
NZ1320; O2– %4 cm, NZ1323; O4 cm, NZ506. Mean tumor
sizes were 2.4G2.0 cm in men and 1.7G1.0 cm in women.
Epidemiology of thyroid cancer 75EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
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stabilization in incidence rates, and in the proportions of
all groups of tumors classified by size and histopathol-
ogy. To our knowledge, such steadiness in thyroid
cancer incidence rates has not yet been reported. It
could be the reflection of the standardization in
diagnostic procedures in the region. However, the
study period is relatively short, and more prolonged
observations in our region and other areas are
mandatory to ascertain the existence of a plateau in
the incidence of thyroid cancer. It must be noticed that a
similar tendency toward stabilization in incidence was
recently reported for prostate cancer for the 1999–
2003 period, after an initial sharp increase during the
eighties and nineties (17).
As previously reported, the great majority of tumors
were papillary. The microscopic criteria for the diagnosis
of PTC have changed over the last four decades and
its morphologic spectrum has varied considerably.
Variants of PTC have been described in the last WHO
classification and differ in marks of aggressiveness, i.e.
extrathyroidal invasion and LNM. In the present study,
variants of papillary cancers were carefully examined
in a large number of papillary tumors, representative
of the whole series in terms of sex ratio, proportion of
microcarcinomas, and pTNM stages. Except for a higher
proportion of microcarcinomas, the distribution was
comparable with that reported in a retrospective study
including 652 tumors diagnosed over a 30-year
period (18). Conventional papillary carcinomas
accounted for 28% of PTC and for 44% of PTC more
than 1 cm in diameter, and were associated with LNM
in 40% of cases. This proportion may be, however,
underestimated since lymph node dissection was not
systematic in patients without suspicious lymph node at
preoperative clinical or US examination. As previously
reported, macroscopic LNM was nearly constant in the
diffuse sclerosing, tall cell, and solid variants, which are
considered as aggressive and prone to recurrences (19,
20). The more frequent variant was follicular, observed
in the present series in 46% of cases with an equal
distribution of invasive and encapsulated forms, who
differed markedly in terms of aggressiveness. If diagnosis
of invasive FVPTC is easy, that of the encapsulated form
is only defined by its nuclear features that can be subtle
and necessitates caution in its interpretation (21).
The diagnosis of these forms may overlap either with
adenoma or with minimally invasive follicular carci-
noma. Molecular biology of thyroid cancer is now
expanding and it is likely that it will help in the near
future for the distinction between cancer subtypes and
for the determination of prognosis (22).
Large tumors, more than 4 cm in diameter, rep-
resented 10% of the whole series without any change
with time over a 9-year period. As expected, men
presented more often than women with such large size
cancers and patients were older at diagnosis. The
proportion of the various histopathological types
differed from that of the whole series with a higher
proportion of follicular, poorly differentiated, and
undifferentiated cancers. Taken together, tumors with
limited (pT3) or extensive (pT4), extrathyroidal
Table 4 Number of cases and incidence rates per 100 000 person-
years according to the urban/rural characteristic of the cantons.
Urban canton
Rural or semi-rural
cantons
Number of
cases
Incidence
rate
Number of
cases
Incidence
rate
Men 473 6.0 493 4.3
Women 1472 17 1667 14.4
Total 1945 11.8 2160 9.4
Figure 5 Number of cases per year of micropapillary cancers
subclassified by size and by conditions of discovery.
Figure 4 Number of cases per year, of papillary tumors, and of
tumors classified by size.
76 G Sassolas, Z Hafdi-Nejjari and others EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
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extension were still found in 13% of cases despite recent
advances in the early diagnosis. Since most invasive
tumors of young people quoted as pT4 in the fifth
edition pTNM classification were reclassified as pT3 in
the sixth edition; pT4 stages were only observed in older
subjects. This is in agreement with the poor prognosis of
extensive thyroid cancer in the elderly.
In the present study, there was a strong relationship
between the annual incidence of microcarcinomas and
that of thyroid cancer. Papillary microcancers rep-
resented 2540 cases, i.e. 38% of the series. This
proportion is of the same order of that reported in
French (6) and North American series (1). The
proportion of microcancers was higher in women, and
increased with age to attain 60% in the fifties. In the
present series, the overall proportion of aggressive
microcancers with ET growth or LNM was lower than
that reported in other studies (23, 24). Lymph node
dissection was systematically performed when poten-
tially metastatic lymph nodes were found before or
during surgery, but prophylactic dissection of the
central compartment was not the rule in the case of
small tumors without clinical or ultrasonographic
evidence of lymph node involvement (25). This attitude
probably leads to an underestimation of microscopic
LNM (26). However, considering the group of ‘clinical’
microcancers, the respective proportions of LNM and
multifocality are comparable with those recently
reported (27, 28). The lower proportion of aggressive
microcancers may be due to the high proportion of very
small cancers less than 0.5 cm in diameter. Most of
them have been fortuitously discovered, by extensive
pathological study, in multinodular goiters, submitted to
total thyroidectomy for non-cancer purposes. The high
proportion of incidental cancer, observed in the present
study, may be explained by the high prevalence of
goiters in the RA region. Thyroid surgery is frequently
indicated for large multinodular goiters and the
incidence of thyroid surgery in the RA region has
been estimated with 58/100 000 inhabitants in 2002
(data not shown). A previous report has suggested that
incidental discovery of microcarcinoma was a favorable
prognostic factor (29). Accordingly, fortuitously dis-
covered microcancers were of smaller size than clinical
forms with fewer stigmas of aggressiveness. Whatever
the circumstances of diagnosis, histological marks of
aggressiveness clearly differed according to the size of
the tumor. This was even more evidenced when both
criteria of aggressiveness were combined in the same
tumor. A threshold of 0.5 cm for developing ET growth
and LNM appears reasonable as previously suggested
(30). It must be noticed that, despite these clear
differences in tumor aggressiveness in relation to
tumor size, all tumors up to 2 cm in diameter without
ET are now equally considered as pT1 stage in the sixth
edition of the pTNM classification.
Variations in incidence rates were observed between
subregional administrative entities. Incidence rates
were higher in urban cantons than in rural zones.
There was no influence of the density of general
practitioners. One hypothesis to explain such a disparity
between urban and non-urban zones could imply
differences in care offered and accessibility to specialists
involved in thyroid cancer, namely endocrinologists and
surgeons who are more likely to have their practice in
urban zones. Other epidemiological studies are needed
to explore potential differential effects of risk factors on
incidence rates of thyroid cancers in the RA region.
In conclusion, stabilization in the incidence of thyroid
cancer, which may reflect standardization in diagnostic
Figure 6 Incidence rates in
women after adjustment on
women’s age and on the urban/-
rural characteristic of the canton.
Epidemiology of thyroid cancer 77EUROPEAN JOURNAL OF ENDOCRINOLOGY (2009) 160
www.eje-online.org
procedures, was observed during the study period.
Higher incidence rates were observed in urban zones
suggesting differences in care access. Further studies,
performed on a more prolonged period, are necessary to
confirm these data.
Declaration of interest
The authors declare that there is no conflict of interest that could be
perceived as prejudicing the impartiality of the research reported.
Funding
This research received funding from the Commission Epidemiologie du
Conseil de Radioprotection D’EDF (Electricite
´de France; 2001, 2002,
2004), Ligue National Contre le Cancer., Comite
´du Rho
ˆne (2003),
Canceropole Rho
ˆne-Alpes-Auvergne (CLARA 2003), and from Region
Rho
ˆne-Alpes (2006–2008).
Acknowledgements
We would like to thank Pr Jacques Este
`ve for his continuous inspiring
support, Registre du Cancer de l’Ise
`re (Dr Franc¸ ois Menegoz
(deceased), Dr Marc Colonna), Registre Rho
ˆne-Alpes des cancers de
l’enfant (Dr Claire Berger), Thyroid cancer group of Institut de Veille
Sanitaire (Dr Laurence Cherie-Challine, Pr Laurence Leenhardt), Dr
Anne-Marie Schott, Dr Elisabeth Adjaj, Dr Florent de Vathaire, Pr
Martin Schlumberger for their valuable advice and support, and the
pathologists, surgeons, and endocrinologists of the Rho
ˆne-Alpes
region for their collaboration. The following laboratories of
histopathology contributed to this work: Service d’anatomie patholo-
gique, Centre Hospitalier Lyon Sud, 69495 Pierre Be
´nite Cedex.
Laboratoire central d’anatomie et cytologie pathologiques, Ho
ˆpital
Edouard Herriot, 69437 Lyon Cedex 03. Service de pathologie du
nord, Groupe Hospitalier du Nord, Centre de biologie et pathologie,
69317 Lyon Cedex 04. Service d’anatomie et cytologie pathologiques,
Ho
ˆpital d’instruction des arme
´es Desgenettes, 69275 Lyon cedex 03.
De
´partement d’anatomie et cytologie pathologiques, Centre Le
´on
Be
´rard, 69373 Lyon Cedex 08. Cabinet d’anatomie et cytologie
pathologiques, 69760 Limonest. Centre d anatomie et de cytologie
pathologiques, 69658 Villefranche sur Saone Cedex. Cy-Path-cabinet
me
´dical de pathologie, 69007 Lyon. Centre de pathologie ACP, 69287
Lyon Cedex 02. De
´partementd’anatomieetcytologie,UFde
pathologie Gastro-enterologique, he
´patique et endocrinienne, CHU
de Grenoble, 38043 Grenoble Cedex 09. Cabinet de pathologie
me
´dicale, Anatomie et cytologie pathologiques, 38100 Grenoble.
Centre me
´dical d’anatomie et de cytologie pathologiques, 38200
Vienne. Centre d’anatomie et de cytologie pathologiques, 38302
Bourgoin Jallieu Cedex. Service d’anatomie et cytologie pathologiques,
Centre Hospitalier de Valence, 26953 Valence Cedex 09. Centre de
pathologie, 26201 Monte
´limar Cedex. Cabinet d’anatomie pathologi-
que et de cytologie, 26006 Valence Cedex. Service d’anatomie et
cytologie pathologique, CHU Saint-E
´tienne, Ho
ˆpital Nord, 42055
Saint Etienne Cedex 2. Anatomie et cytologie pathologiques, Centre
Hospitalier de Roanne, 42328 Roanne Cedex. De
´partement d’anato-
mie et de cytologie pathologiques, 42234 Roanne Cedex. Institut de
pathologie du Forez, 42001 Saint Etienne Cedex 1. Centre de
pathologie, 42270 Saint-Priest-en-Jarez. Groupe d’anatomie patholo-
gique et de cytologie, 42952 Saint Etienne Cedex 09. Laboratoire
d’anatomie et de cytologie pathologiques, Ho
ˆpital de Fleyriat, 01012
Bourg en Bresse Cedex. Cabinet d’anatomie pathologique et cytologie,
01000 Bourg en Bresse. Service d’anatomie et de cytologie
pathologiques, Centre Hospitalier Chambe
´ry. 73011 Chambe
´ry.
Cabinet de pathologie, 73003 Chambe
´ry Cedex. Cabinet d’anatomie
et de cytologie pathologiques, 74007 Annecy Cedex. Centre de
pathologie du Mont-Blanc, 74105 Annemasse Cedex.
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Received 12 October 2008
Accepted 22 October 2008
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