Serum triiodothyronine Thyroxin and TSH in Endemic Coiter : a
comparison of Goitrous and non goitrous subjects in New Guinea.
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ETOFF S, DEWIND LT, DEGROOT LJ : Familial Syndrome
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Kuala
lumpur, 1974.
INTRODUCTION
When one thinks of cancer, one thinks of a highly malig-
nant tumor, that ordinarily kills the patient within a few years.
However, cancer of the thyroid gland generally does not con
firm to the pattem of carcinoma elsewhere and may run an ex
traordinarily course over a period of 20 or 30 years, without
causing serious symptoms.
Moreover the close relationship of benign tumors, grossly
and histologically, to low grade malignant tumors and tho dif-
ficulty experienced by clinicians and pathologists alike in dis
tinguishing adenoma from a carcinoma, has resulted in con-
fusion as to what constitute a cancer of the thyroid.
The litterature has mentioned such terms as lateral aberrant
thyroid and benign metastasizing goiter, to describe the low
grade carcinomas, which are so small or so benign in appearan-
ce that the primary tumor is not recognized. Nevertheless,
those tumors are metastasizing carcinoms and because they
may cause death, if not properly treated, they should deserve
serious consideration (Soetomo Tjokronegoro, 1934).
There are also thyroid tumors described as a typicaladeno-
rna or hyperplastic adenomas, wlth out showing any tendency to
invade bloodvessel or the surrounding tissue. These tumors
may recur locally if not completely removed and ultimately li-
ke other benign tumors possibly may become rnalignant. In
this study, those tumors are not included as malignant tumors
Only tumors showing invasion of bloodvessel or the usual ma-
nifestationa of malignancy are conaidared to be cancer (Warren
Meissner, 1953).
MATERIALS AND METHODS
Data are obtained by retrospective study of all thyroid di
seases, recoived by the Dept of Pathology, during a five year
period. All are re-exmined
and
reclassified
histologically,
according the International
Histological Classification of
Thyroid Tumors (Hedinger Sobin; WHO -1974 ).
The yoars 1972 - 1976 (inclusive) have been forselected
for this study, because after July 1977 a decentralisation of
the pathology servlces occur, due to the fact that several
hos-
pitals in the city of Semarang have their own pathology ser-
vices.
The thyroid speciments came from several parts of the pro-
vince of Central Java,especially from the Northern coastal area
and also frofi the Central part of Central Java. A small part,
Dibawakan pada Seminar Nasional 1 Gondok dan Kretin Endemik.
Semarang, 18 20 Desember 1978.
CANCER
OF
THE THYROID
dr Tirtosugondo and dr
Indrawijaya
Departmen of Pathological Anatomy
Diponegoro University Medical Faculty/
Kariadi Teaching Hospita
l
Semarang
Cermin Dunia
Kedokteran No. 14, 1879 l1
particularly the Southern area of Central Java, mostly sent
their material fo the nearby located pathological laboratory
in the city of Yogyakarta. Autopsy figures have not been in-
cluded in this study,as apart from coroner s cases, very few
autopsies are done.
We have also to keep in mind, that the material studied
are highly selective. The patients have been screened, firstly
by the patient himself, who does not often consult a doctor,
unless the nodule is giving evidence of growth or functional
activity; secondly by the internists or family-doctor and lastly
by the surgeon. Therefore, the figures presented certainly do
not give the true incidence of thyroid cancer, but only the re-
lative frequency as seen in the Dept of Pathology of a teach
ing hospital. Nevertheless, it may provide us with some useful
data.
The tissue sections were stained with the routine H E
staining method; special cases were also stained with the Van
Gieson, Reticulin and PAS staining method.
RESULTS
Out of a total of 39.216 surgical specimens, received du-
ring the five year period, 4405 were diagnosed as malignant
tumors. Totally there were 790 thyroid cases, consisting of
119 malignant subacute, 157 benign tumors, 437 nontoxic
goiters, 23 Grave s diseases, 45 thyroglossal ducts, 5 subacute
thyroiditis cases, 1 case of Riedel s thyroiditis, 2 Hashimoto s
diseases and 1 case of Cretinism. The relative frequency in
relation to other malignant tumors during that period was
estimated as 2,7%.
The histological classification is shown in Table-II and all
thyroid carcinomas are classified into four major groups.
TABLE I
Several types of Thyroid diseases, in relation to sex distribution
Type of disease
Male
Female
Total
Percentage
Carcinoma
23
96
119
15,1 %
Adenoma
21
136
157
19,9
Nontoxic goiter (nodu-
56
381
437
55,4
lar/diffuse)
Grave s disease
3
20
23
2,9
Thyroglossal duct
24
21
45
5,6
Subacute thyroiditis
1
4
5
0.6
Riedel s thyroiditis
1
--
--
0,1
Hashimoto s disease
--
2
2
0,3
Cretinism
--
1
1
0,1
T o t a l
129
661
790
100,0
The four majors types of carcinoma of the thyroid are :
1. Papillary carcinoma. All tumors with neoplastic papillae,
regardless of the presence of follicular or solid areas, are classi-
fied as papillary carcinomas. Tumors, without papillae are
also regarded as papillary carcinomas, if the nucleus is large,
pale, hypochromatic with invisible nucleolus(so called ground
glass type) and the mode of growth is infiltrating into the
surrounding tissue. All papillary tumors are regarded as ma-
lignant.
2. Follicular carcinoma. Tumors without neoplastic pa-
pillae, but display follicular or trabecular structures, are
classified in this group. Only follicular tumors, which show
vascular invasion or true capsular infiltration are considered
malignant.
3. Medullary carcinoma. This type contains amyloid in
the stroma.
4. Anaplastic carcinoma. This group includes undifferen-
tiated carcinoma, as well as spindle cell carcinoma, round cell
carcinoma, giant cell carcinoma and other rare types.
The predominant type in our material is the papillary car-
cinoma, in both sexes and in all the age groups, representing
68,9%
of all thyroid carcinomas. No medullary carcinoma
has been found in our five year record.
TABLE II
HISTOLOGICAL CLASSIFICATION
Percentage
No.
of cases
Type
1. Papillary carcinoma
82
68,9%
2. Follicular carcinoma
35
29,4
3. Anaplastic carcinoma
2
1,7
4. Medullary carcinoma
--
--
Total
119
100,0%
TABLE III
SEX DISTRIBUTION of patients with THYROID CA.
Sex
Papil-
lary Ca.
Folli-
Anaplas-
Medulla-
cular Ca. tic Ca.
ry Ca.
Total
Total
Female
69
23
2
94
Male
13
12
25
Total
82
35
2
119
TABLE IV
AGE DISTRIBUTION of patients with THYROID CA.
Years
Papilla-
ry Ca.
Follicu-
lar Ca.
Anaplas-
Medulla-
tic Ca.
ry Ca.
Total
10-19
6
-
6
20 - 29
11
3
14
30 - 39
18
3
21
40 - 49
17
11
2
30
50-59
13
12
25
60-69
13
5
18
70 - 79
4
1
5
Total
82
35
2
119
The sex distribution (Table-III) shows an excess in the
female patients with a female/male ratio approximately
3,8 : 1 for all histological fypes.
12
Cermin Dunia Kedokteran No. 14, 1979
Papillary carcinomas are found in all age groups, while
follicular carcinomas principally occur in the older age groups.
DISCUSSION
Carcinoma of the thyroid gland is not common. In this
study, the relative frequency of thyroid carcinoma is 2,7%
of all malignant tumors, between 1972 and 1976 inclusive.
Data from other Departments of Pathology connected with
teaching hospitals in several places in Indonesia, show the
following relative frequencies : Jakarta 1,9% (Kusumawidja-
ja, 1971), Bandung 1,55%
(TOPO
HARSONO, 1973), Suraba-
ya 2,6% LUSIDA
et al., 1977), Medan 1,35% (RIDJAB
et al., 1977). Ujung Pandang 2,4% (SYARIFUDIN et al.,
1977), Yogyakarta 1,5% (SOERIPTO et al., 1977). Therefore,
the relative frequencies of thyroid carcinoma as observed
in several pathology laboratories do not differ too much.
Population based cancer registration is not yet established
in Indonesia, and the true incidence rate of thyroid cancer
is still uncertain. However, we had calculated the age-standar-
dized minimum incidence rate of cancer in the population
of the city Semarang, between 1970 - 1974 inclusive, based
on microscopically diagnosed cancer. During that period, the
age-standardized minimum incidence rate for thyroid cancer
was as follows : males 0,90; females 2,12 and for both sexes
1,54 per 100.000 per year. (TIRTOSUGONDO et al., 1976).
The city Semarang is located in a non-goitrous area.
Western countries with comprehensive population based
cancer registries, show an incidence around 1% of all cancer
types.
On the other hand, age-standardized incidence rates re-
ported from Hawaii, Cali (Colombia) and Israel are high,
while Iceland, Mozambique and Yugoslavia have moderate
rates and most other countries show low rates (DOLL et.
al., 1966).
Etiological factors in carcinoma of the thyroid are obscure
and very controversial, particularly the association between
non-toxic goiter and carcinoma. In the past, an association
between endemic goiter and thyroid carcinoma was considered
important. Wegelin (1928) observed, that thyroid cancer was
tentimes more common at autopsy in Bern, Switzerland,
an endemic goiter area, than in Vienna and Prague, areas of
modest endemicity, where the incidence of thyroid cancer
was intermediate.
Recently the widely held believe that nodular non-toxic
goiter predisposes to the development of thyroid carcinoma
has been modified. PENDERGRAST et al. (1961) have shown
that the marked fall in the incidence of goiter in the U.S.A.
since the First World War, after the introduction of iodised
salt, has not been accompanied by a decrease in the mortality
or morbidity from thyroid cancer.
Previously, SAXEN and SAXEN (1954) reported that
thyroid cancer in Finland is equally prevalent in areas with
and without endemic goiter. Following the introduction of
iodised salt in Bern (Switzerland), thyroid cancer has not
decreased in incidence, although the pattern has changed;
a decrease in the incidence of follicular carcinoma was accom-
panied by a rise in the incidence of papillary carcinoma,
resulting in an unchanged overall incidence (WALTHARD,
1961). WAHNER et al. (1966) have produced evidence of an
association between follicular carcinoma and nodular endemic
goiter in Cali, Colombia and also a clear lack of correlation
between papillary carcinoma and endemic goiter. Riccabona
(1973) in his survey in Tyrol, Autria, which is an endemic
goiter area, also concluded that the incidence of thyroid can-
cer was no greater than that reported in goiter free areas.
De Smet (1960) working in the Congo, Africa, also stated that
he had not observed the evolution of endemic goiter into carci-
noma.
As mentioned above, our material mostly came from pa-
tients who live in the northern part of Central Java province,
a non-endemic goiter area. Only 113 specimens came from
areas (14,3% out of the total of 790 thyroid specimens),
where endemic goiter is known or presumed to exist (Bo-
yolali, Salatiga, Wonosobo, Banjarnegara and Wonogiri).
TABLE
V
Thyroid specimens from endemic goiter areas, received between
1972-1976,
inclusive
Carcinoma
Adenoma
Nodular/diffuse Cretin Thyroglos- Total
non-toxic goiter
sal duct
No. of
14
19
17
1
2
113
Cases
We have not been able to find any malignant transfor-
mations or changes in the nodular goiters until so far. Certain-
ly, our material is not large enough to draw any positive con-
clusion. More data, especially from endemic goiter areas in
Central Java should be compiled. Of course, it is still possible
that many nodules, particularly the solitary ones, are poten-
tially cancerous from the onset.
But, it is interesting to note, that the predominant type
of thyroid carcinoma from the endemic goiter areas of the
follicular type. (Table-VI).
TABLE
VI
Distribution of thyroid cancer types in non-endemic goiter and endemic
goiter areas, from material received
by
the Dept
of
Pathology,
1972-
1976.
Cancer type
Endemic
Non-endemic
goiter area
goiter area
Both.
Papillary
2 (14,3%)
80 (76,2%)
82
Follicular
12 (85,7%)
23
(21,9%)
35
Anaplastic
2 (
1,9%)
2
T
o
t a
1
14 (100,0%)
105
(100,0%)
119
Taking into consideration, the observation and conclusion
of Wahner et al. (1966) and also more recently the observa-
tion of Mc Gill (1978) in Kenya, Africa, and lastly our own
figures regarding that carcinoma of the thyroid gland from
patients who live in endemic-goiter areas are predominantly
of the follicular type, we may suggest a possible positive
correlation between follicular carcinoma and endemic goiter.
Cermin Dunia Kedokteran
No.
14, 1979
15
Again, more adequate data should be collected from re-
gions knows as endemic goiter areas in the province of Central
Java, especially in connection with the cancer problem.
Therefore, we would like to suggest the introduction of fme
needle aspiration biopsy
for cytologic examination as a
method to improve our knowledge in the real incidence and
cancer risk factors in endemic goiter areas. In contrast to
the large needle biopsy, which most surgeons believe should
be done in the hospital, the fine needle aspiration biopsy
is a simple office procedure and certainly more applicable
to meet our purpose. (Crile et al., 1973; Wang et al., 1976
Gerahengorn et al.,1977).
SUMMARY
1. Thyroid carcinoma accounts only 2,7% of all malignant
tumors, diagnosed at the Dept of Pathology Kariadi Hospital/
Diponegoro University-Medical Faculty, during the years
1972 - 1976 inclusive. The female/male ratio is approximately
3,8 : 1.
2. Papillary carcinoma is the major type (68,9%) of all
thyroid cancers (119 cases) and occurs in all age groups.
On the other hand, follicular carcinoma (29,4%) is principally
found in the older age groups.
3. Specimens of thyroid cancer from patients living in
endemic goiter areas show a preponderance of the follicular
type. A possible correlation between
follicular carcinoma
and endemic goiter has been suggested.
4, More adequate data should be collected from endemic
goiter areas in Cent;al Java and fine needle aspiration biopsy
for cytologic examination has been proposed as a method to
improve our knowledge concerning the cancer problem in
goitrous areas.
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1 6
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