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CHILDHOOD THYROID CARCINOMA
THEODOREINSHIP, M.D., AND RANDI . ROSVOLL, hI.D.
N A SERIES of publications during the pastI ecade, we have recorded our efforts to cd -
lect and evaluate data on all known cases of
thyroid carcinoma occurring in patients less
than 15 years of age.51-54 Our last publica-
tion52 listed 167 additional reported cases, bu t
we later found some that had been over-
looked. During the past 5 years, 148 new cases
have been repor ted. Many of these were single
case reports, an d others were listed together
with case reports for adults in large series. A
few may have been overlooked, but, so far
as we have been able to determine, there have
been 315 cases of childhood thyroid carci-
noma published in the world literature. Table
1 lists the cases reported since our last review
of the literature. We have made a sustained
effort during the past 12 years to discover as
many unpublished cases as possible. Question-
naires were sent to all children's hospitals and
all the larger hospitals in the United States
and Canada. Personal surveys have been car-
ried out by the authors throughout parts of
the United States, Canada, Western Europe,the Middle East, and Central America. Sur-
veys of the Philippine Islands, Japan, and
Formosa were recently conducted for us. We
realize that many other cases have occurred,
but, to date, we have located 247 unpublished
cases. Together with the 315 published cases,
the total of known cases of childhood thyroid
carcinoma is 562. Not all of the reported and
submitted cases could be accepted as being of
thyroid cancer. In several instances, there were
From the Department of Pathology, WashingtonHospital Center, Washington, D.C.
Presented at the Fourth International Goiter Con-
gress, London, England, July 7, 1960.This study was supported in part by a research grant
(CS 9263) from the National Cancer Institute, of theNational Institutes of Health, Public Health Service,
and the District of Columbia Division, American Can-
cer Society, Inc.We wish to express our gratitude to the many phy-
sicians and tumor clinic secretaries who contributedinformation about their patients.
We are also grateful to Dr. R. G. Arellani, Manila,Philippine Islands, for her survey and to Dr. A . Raad,
Sunnyside, Washington, for canvassing the medicalschools and hospitals of Japan and Formosa.* Present address: New England Deaconess Hospital,
Boston, Mass.
Received for publication Aug. 22, 1960.
insufficient data to determine whether thepatient had carcinoma or a benign lesion.
Other cases were not accepted because, in our
opinion, the tissue submitted represented an
unusual condition that we refer to as nontoxic
hyperplasia of childhood. T h e patient de-
scribed by Tsukanova46 may have had carci-
noma, but proof was lacking; in addition, a
number of the cases cited by Essigkel4 were
excluded for lack of convincing evidence.
T h e patients came from 37 states and 27
foreign countries. Most of those outside of
the United States were from Canada, England,
or France. Numerous investigators have com-
mented upon the high occurrence rate of thy-
roid carcinoma in the United States, and our
series illustrates this very clearly. Approxi-
mately 80% of the patients in this series lived
in the United States. One can only speculate
as to the cause of this disparity in geographical
distribution. Numerous factors may be in-
volved; one of importance is the more dili-
gent search for cases we have made in this
country than elsewhere. Th e sites of residenceof the patients are widely scattered, and there
is no apparent relationship to known goiter-
ous areas. It would appear from this study
that the thyroid carcinoma incidence in chil-
dren is unrelated to any specific geographical
region but rather is more frequently recorded
in areas in which interest in the disease is
high.
Several investigators have remarked on the
apparent increasing frequency of thyroid can-
cer. In Fig. 1 , the year of diagnosis is listedin each case. This illustrates the increase in
childhood thyroid carcinoma throughout the
past 6 decades. T h e first authentic case we
were able to find was treated in 1899 and re-
ported in 1902,13 and only 8 cases were pub-
lished in the next 25 years.51 Thereafter, the
numbers increased irregularly until a peak
was reached in 1953. It is difficult to explain
the peak a nd the subsequent decline, but i t is
probable that when more cases are reported
it will become less prominent.
PREVIOUSRRADIATION
I n tabulating the cases, i t became obvious
734
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No. 4 CHILDHOODHYROIDARCIN
TABLE
4 0
35
30ul
c4
.
g 2 5
c
OMA * Winship & Rosvoll 735
concerning childhood thyroid cancer have ap-
peared since that time. Most investigators
since 1950 have made some attempt to obtain
a history of irradiation. Such a history is not
always easily elicited, but in 1955 Clark7 re-
ported that all of the children he had treated
for thyroid cancer had had previous irradia-tion. Since then several investigators have
duplicated his record, and a number of other
investigators have reported such a history in
75 to SO of their patients. Simpson and co-
workers43 approached the question of irradi-
ation effect by obtaining follow-up data on
1,052 patients who had received X-ray treat-
ments during infancy. Their results showed
a significant increase in the number of thyroid
cancers over the expected normal.
Thirty-eight per cent of all the children withthyroid carcinoma are known to have received
therapeutic amounts of irradiation in in-
fancy or early childhood. If accurate his-
tories could have been obtained in all cases,
we believe that this percentage would have
been considerably higher. T h e nature of our
study precluded personal interviews, and, in
many instances, it was not possible to interro-
gate the parents or to examine hospital records
for a history of X-ray therapy. It can be as-
CASES PUBLISHED SINCE OUR LASTREVIE\&’ OF THE LITERATURES2
No.Year Author Location study cases
~
1953 Egmark et aI.l2 Stockholm, Sweden 1
1955 Logaldd? San I,uis, Argentina 11955 Buckwalter4 Iowa City, Iowa 81956 Fetterman16 Pittsburgh, Pa. 9
Kniseley &
Majarakis et ai.26 Chicago, Il l .lJhlmann47 Chicago, 111.Welti48 Paris, FranceM ~ C o r k l e ~ ~ San Francisco, Calif.Cohen & Hvmang Baltimore, Md.
Andre\ Oak Ridge, Tenn. 29956
19561956195719571957
3311
Theonies 8;Miiller45 Dresden, East
Germany
Tokyo, Japan
Pavia. Italv
1957
1957
1957
195719571958
1958
1958195819581958
Yanari 8:Moroto@
Malandra &
Dova2’Roberts38 Birmingham.irmingham,
EnglandLos Angeles, Calif.New York, N.Y.
Englanud ’
Los Angeles, Calif.New York, N.Y.
132
Ross40Rall e t a l 3 7
Becker dt
Baron2
Meissner & Legg=Farber 8c CraiglSPetit et a1.34Rabinoaiitz &
Katz3”
Mahoi:ner3 New Orleans, La.San Francisco,Calif.Boston, Mass.Boston, Mass.Los Angeles, Calif.
Johannesburg,Union of SouthAfrica
Bombay, IndiaVienna, AustriaDunedin, NewZealandSheffield, EnglandOslo, Norway
Atlanta, Ga.
Vancouver, B. C.,CanadaBoston, Mass.Montevideo,
135
218
1958
19581958
Shroff &Paymaster41
Stur & S ~ o b o d a ~ ~Adams 3r Purvesl
Wilson et a l .50
L@ken24Rooney &
Powe113~Moore lr
M ~ K e n z i e ~ ~
Castleman6Grosso et a1.20
195819581959
1959
19591959
19591959195919601960
19601960
Carro ei: al.5Crile’oMcGirr et aL30
Wilson t S r Asper49McNeill, &
UruguayMadrid, SpainCleveland, Ohio
1171
13Glasgow, ScotlandBaltimore, Md.
Dallas, TexasRochester, Minn.Houston, Texas
2591
Hayles e t a1.21Glass et aI.19
that interest in this disease increased sharply
after 1950. Tlhe accelerated interest was due in
part to a report that 10 of 28 children treated
for thyroid carcinoma at Memorial Sloan-
Kettering Cancer Center, New York, N.Y.,
had been irradiated during infancy for an
“enlarged” thymus gland.11 T h e following
year, we reported a collected series of 192
cases.51 Two-thirds of all the publications
41910T’
1920 1930 1940 1950 1960
FIG. 1 Years of diagnosis in 546 patients with thy-roid carcinoma. Date of diagnosis was unknown in 16cases.
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736 CANCERuly-August 1961 Vol. 14
2 1
1925 1930 I935 I940 1945 1959 I955 I960
FIG . Years of diagnosis (striped blocks) and yearsof irradiation (hollow blocks) in 193 patients with thy-roid carcinoma.
sumed that such a history was not sought in
the cases reported prior to 1950. Furthermore,
many of the cases in this series were submitted
by pathologists who had no specific knowledgeof the patient’s history. We know that attempts
were made to obtain a history of previous ir-
radiation in only 277 patients. Of this group,
which represents less than half of the entire
series, a history of irradiation was obtained in
221 patients or approximately 80%. In the
greatest number of cases, X-ray therapy dur-
ing infancy was directed to the upper medi-
astinum for a so-called enlarged thymus
gland. T he next largest group consisted of
those treated during childhood for hyper-
trophied tonsils and adenoids. Others weretreated for hemangiomas, nevi, acne, eczema,
“cervical adenitis,” and numerous other be-
nign lesions. One patient had numerous ex-
posures to X rays because of a cardiac anom-
aly. One patient each had roentgen therapy
for a brain tumor, a retinoblastoma, and a
lymphoma. It was interesting to learn that
in Europe, i t has seldom been thought neces-
sary to irradiate the thymus gland except for
malignant lesions. Only 13 of the patients
with a history of irradiation were found tobe from Europe, and they had been treated
for angiomas, nevi, and similar lesions. The
dosage of X ray was only estimated in many
cases, but i t is probable that the thyroid gland
received an amount of irradiation within the
range of 500 to 800 r. The dosage administered
varied from 180 to 6,000 r, with an average of
600 r. The interval between the irradiation
and the diagnosis of thyroid cancer averaged
8.7 years with extremes of 3.6 to 14. years.
In contrast, the interval for adults in the few
reported cases was 15. to 40. years.35
Uhlmann47 indicated that thymic irradia-
tion was most popular and most widely used
between 1920 and 1925. Clark7 estimated the
period of greatest popularity of this form of
treatment to be 1928 to 1940, and radiologists
in Washington, D.C., have agreed.55 Simp-
explained than an exact period could
not be determined. She pointed out that thy-
mus glands were being irradiated long before
it became a popular treatment for tonsillitis.She also stated that the peak of popularity
for this form of therapy varied in different
localities. Figure 2 shows the year that 193
patients in this series received irradiation and
the year of diagnosis in each case. According
to these data, the period of greatest popu-
larity for this method of therapy was between
1940 and 1950. Obviously, factors other than
irradiation influence the production of thy-
roid carcinoma, and the data presented here
do not prove that X rays during infancy causethyroid cancer, but an undeniable relation-
ship must be admitted.
CLINICALATA
All of the desired clinical information was
not available in every case, so the data pre-
sented here were not always based on the total
number of cases in the series. The ethnic back-
ground of the patients was not determined
in every instance, but numerous groups were
represented. Thyroid carcinoma occurred inNegroes, Chinese, Japanese, Mexicans, Indi-
ans, and Persians, but Jewish and Italian pa-
tients were more numerous than were any
other groups.
In contrast to groups of adults with thyroid
carcinoma, in which female patients may out-
number male patients 3 to 1, the proportion
in this series was approximately 2 to I (62of the children were female). Uhlmann47
suggested that since both sexes have been ex-
posed to irradiation in almost equal numbers,one might expect a change in the sex ratio of
thyroid carcinoma in children if there were
any correlation between irradiation and cancer
development. In our series, the sex ratio was
approximately the same for the 2 groups.
Sixty-two per cent of the non-irradiated chil-
dren were female as compared to 60% of the
irradiated patients.
The age limit of 15 years was arbitrarily
chosen in 1948, when this study was begun.
The ages of the patients at the time a histo-
logical diagnosis was established varied from
4. months to 14.6 years, the average being
9.6 years. Twelve of the children were said
to have had congenital thyroid tumors that
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No. 4 CHILDHOODHYROIDARCINOMA Winship Q Rosuol l 737
later proved to be carcinomas. Thyroid cancer
occurred in members of the same family in 2instances-twin sisters in one family an d a
brother and a sister in another. T e n patients
had coincidental disease, 2 were mentally re-
tarded, and 1 each had a harelip, a congenital
heart defect, poliomyelitis, asthma, a braintumor, a lymphoma, and a retinoblastoma.
Five patients were treated for thyrotoxicosis,
although in only 3 cases was the diagnosis con-
firmed by laboratory tests.
Adequate details regarding the presenting
signs and symptoms were available for only
451 children. I n the majority, the first sign of
disease was a ntdu le in ei ther the region of the
thyroid gland or the lateral cervical chain of
lymph nodes. Slowly growing painless nodules
in the neck apparently created little suspicionof thyroid cancer when encountered in chil-
dren. This is reflected in the elapsed time
between the discovery of the neck nodule and
the institution of therapy. T h e shortest inter-
val recorded was 2 weeks and the longest 13
years, with an average of slightly more than
2 years. Nodules in the lateral area of the neck
were often regarded as chronic adenitis, lym-
phoma, tuberculosis, or branchial cleft cyst.
Carcinoma was localized in the thyroid
gland in only 23% of the children at the time
of initial examination. T h e others, except 7with pulmonary metastasis as the first sign of
disease, had cervical lymph node involvement
when first examined, and, in almost one-third
of these, metas1 atic disease was bilateral. Other
investigators have found an equally high pro-
portion of cervical node metastases in children
with thyroid cancer. Eighty per cent of the
patients reported by Hayles et a1.21 had me-
tastatic carcinoma in cervical nodes, and
CrilelO found involved lymph nodes in 77 .
Thirteen per cent of the patients had pul-monary metastases at the time of their first
examination, and this was the first sign of dis-
ease in 7. Five of these patients were mis-
takenly treated for tuberculosis for as long as
2 years before the diagnosis of thyroid cancer
TABLE
I N I T I A L P H Y SI CA L F I N D I N G SF O R 451 P A T I E N T S
Site involv. No. pt. Pt.
Nodules i n neck 34 1 76Nodules in thyroid only 103 23
1
TOTAL 451 100
ulm. metast. only 7
TABLE
S U M M A R Y O F I N I T I A L T H E R A P YF OR 45 P A T I E N T S
Type therapy No. pt. Pt.
Surgery only 156 34Surgery & X ra y 250 56
Biopsy & X ray 45 10
TOTAL 451 100__
was established. One patient presented a pain-
ful lesion in the skull as the first sign of dis-
ease. This subsequently proved to be meta-
static carcinoma from a small primary lesion
in the thyroid gland. Distant metastases (to
lung, mediastinum, bone, and axilla) were
found on initial examination in 75 pa-
tients. Some of the children had far advancedcancer when first seen, 2 were described as
moribund, and in 17 cases the surgeon used
the phrase inoperable or nonresectable to
describe the stage of disease.
THERAPY
Methods of therapy varied considerably, as
might be expected. So many technical varia-
tions were described that they could not be
listed individually, but general methods are
tabulated in Table 3. Total thyroidectomies
and neck dissections were performed in 147
patients, and the neck dissection was bilateral
in 19. In some of the procedures stated to be
total thyroidectomies, a small amount of thy-
roid tissue was deliberately left; in other cases,
it was specifically stated that all the thyroid
tissue had been removed, yet only 14 cases
of permanent hypoparathyroidism were re-
ported to us. All of the cases of operations in-
volving the resection of multiple cervical
lymph nodes were placed in the category of“neck dissection.” The terms most often used
for this procedure were “node dissection,”
“modified neck dissection,” “block dissection,”
and “radical neck dissection.” Only about one-
quarter of the neck dissections were performed
in the manner described by Martin,28 whereas
others consisted of a dissection designed to
remove all the node-bearing tissue from one
side of the neck, preserving the sternomastoid
muscle and the jugular vein. In some in-
stances, only groups of palpable lymph nodeswere removed. In 1 patient, a total thyroidec-
tomy was performed in conjunction with aradical neck dissection and a trans-sternal
anterior mediastinal node dissection. Thirty-
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738 CANCERuly-August 1961 Vol. 14
seven patients were treated by a lobectomy
and a neck dissection on the homolateral side.
A total thyroidectomy was the method of
initial therapy for 51 patients, and what was
usually described as a subtotal thyroidectomy
was carried out in 107 instances. A lobectomy
only was performed in 64 patients.In certain institutions, particularly in Eu-
rope, patients with thyroid cancer routinely
received irradiation in some form after sur-
gery. I n this series, 250 patients were treated
in this manner. Twelve were treated by the
use of teleradium and local radium (such as a
radium collar or interstitial therapy) and 5
by telecobalt. Th e others received roentgen
therapy. At times external irradiation was used
prophylactically, and in 15 patients i t was
offered as a form of palliation. Irradiation wasthe only method of therapy i n 45 patients.
Many of the children had tracer studies with
radioactive iodine I131)after surgery, but only
64 were given therapeutic amounts. Gratify-
ing results were obtained in 20 patients whose
pulmonary metastases disappeared after the
use of 1131. It is of interest that the patho-
logical diagnosis in 18 of these cases was
papillary carcinoma, and in the other 2 it was
follicular carcinoma. In the case of Freed-
berg’s18 patient, the pulmonary lesions dis-
appeared after th e use of Il3I, and the lungshave remained clear for 10 years. The lungs
cleared in another patient, but metastases
appeared in 1 of the long bones 11 years after
the initial surgery.
Multiple operative procedures were neces-
sary to remove recurrent o r residual cancer in
2301, of the patients treated by Crile.10 Ap-
proximately the same percentage of patients in
our series required multiple operations after
the initial definitive surgery. This is surpris-
ing, considering that surgeons from all overthe world performed these operations. Forty-
five patients required an operation for re-
current tumor within 1 year. During the sec-
ond year, 25 patients had additional surgery,
and 10 patients had secondary procedures
during the third year. Thereafter, fewer op-
erations were necessary, but 4 patients re-
quired additional surgery more than 20 years
after the initial operation. In the majority of
instances, only 1 subsequent surgical proce-
du re was required, but a few patients had mul-
tiple operations, and l has had 7 operations
on the neck in 10 years. When irradiation was
the primary therapy, the patients were often
treated more than once, and, in some, sec-
TABLE
PATHOLOGICAL CLASSIFICATION OF364 CASES OF CANCER
Type ca.
PapillaryFollicular
No. pt. Pt.
261 7270 19
9
TOTAL 364 100
ndifferentiated 33
ondary skin changes were evident. Subsequent
to X-ray treatment for thyroid cancer, 1 pa-
tient each developed an astrocytoma, a neuro-
genic sarcoma of the spinal cord, an ependy-
moma, and a fibrosarcoma of the neck.
Nearly all of the surgically treated patients
received desiccated thyroid for varying periods
of time, yet many had progression of the dis-ease or developed metastases. I n the great ma-
jority of patients, no changes were observed,
an d regression of tumor was reported in only
8 instances.
PATHOLOGY
T h e primary tumors were not always fully
described, but for those accurately measured,
the average size was 3.2 cm. I n the large series
of cases in adults published by Frazell and
Foote,lT 15% of the primary tumors measured
less than 1. cm. and were classified as occult
carcinomas. In our series, only 9% qualified
as occult cancers. One lesion measured only
0.3 cm., and i n 1 specimen the primary tumor
was never found although the entire thyroid
gland was examined. I n 69 cases, the tumors
measured 2. cm r less, and the remainder
were larger. T h e follicular cancers were gen-
erally larger than the papillary, and almost
all of the undifferentiated tumors were bulky.
An occasional tumor was described as encap-sulated, and most of these were follicular. Only
6 of the cancers were described as being asso-
ciated with nodular goiters. Although no ac-
curate statistics are available to determine the
relationship between nodular goiter and car-
cinoma in children, it has been estimated that
from 20 to 52% of thyroid nodules prove to
be malignant.54
Slides from 364 patients were submitted to
us for examination. These ar e classified in
Tab le 4.
As in all large series of cases in this country,
papillary carcinomas predominated. All of the
tumors containing papillary formations were
placed in this category, although almost all of
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No. 4 CHILDHOODHYROIDARCINOMA Winship (17. Rosvol l 739
them contained a few scattered follicles in
either the primary or secondary carcinoma.
The tumors listed as follicular were those
made up of malignant follicles only. It has
been assumed that undifferentiated cancer of
the thyroid gland occurs only in elderly pa-
tients, but 33 children had lesions of thistype. T h e undifferentiated category was com-
posed of tumors that had nei ther follicles nor
papillary structures. Most of these tumors had
a uniform cell type and were solid, but others
showed areas of hemorrhage, necrosis, and de-
generation. T h e tumors classified as undiffer-
entiated were more heterogeneous than were
those in the other 2 categories an d migh t have
been divided into numerous subvarieties.
T o simplify the classification, we divided
the Undifferentiated tumors into 3 subgroups.The largest subgroup was that for the small
cell carcinomas composed of sheets of small
cells wi th large dark nuclei. Eighteen of the
tumors were placed in this category. T h e sec-
ond largest subgroup was that for spindle
an d giant cell carcinomas composed of vary-
ing proportions of spindle cells simulating
fibrosarcomas and usually with varying num-
bers of bizarre giant cells. There were only
spindle and giant cell tumors in our series.
The third subgroup, that for medullary car-
cinomas, was a less uniform category, but
the tumors were usually composed of rela-
tively large cells divided into large masses
by distinct strands of fibrous tissue. Not all
of the medullary tumors were anaplastic.
Some of them appeared quit e indolent histo-
logically, and a few of the patients with these
tumors have lived for long periods-I for 23years.
A careful scarch for bilateral involvement
of the thyroid lobes was not always carried
out and was reported in only 17 cases (7 ).Th is is in contrast to the investigation of
Clark and coworkers8 who serially sectioned
whole thyroid glands and found bilateral in-
volvement in more than 80% of the cases. In
TABLE
M E T H O D S A N D R E S U L T S O F T R E A T M E N TI N 148 P A T I E N T S F O L L O W E D FOR
M O R E THAN 10 YEARS
T y p e No. pt. No. pt. pt.treatment treated died surv.
Surgery only 51 5 90.0Surgery & X ray 82 11 86 .4Biopsy & X ray 15 10 33.0
TOTAL 148 26 82 .3
a group of tumors in adults recently exam-
ined at the Washington Hospital Center,
multicentr ic foci of carcinoma were found in
both lobes in 16 of 18 cases.
I t has often been stated tha t papillary carci-
noma metastasizes first to the cervical lymph
nodes, while the first spread of follicular car-cinoma is via the blood stream. We did not
find this to be true. The first metastases from
both types of tumor generally appeared in the
cervical nodes, and blood-borne metastases oc-
curred with almost equal frequency. In this
series, 76 of the cervical lymph nodes that
were involved contained papillary, 14 follic-
ular, and 10% undifferentiated carcinoma.
These figures are very similar to those in
Table 4 for the primary tumors. Except for
a small increase in the number of undifferen-tiated tumors, no particular cell type was
found to predominate in the patients who
had been irradiated during childhood.
I n a small number of patients recently re-
por ted,l7 thyroid cancers became progressively
more malignant in appearance as time elapsed.
There are 3 such patients recorded in our
files, all of whom had been heavily treated
b y roentgen therapy and all of whom had
lived for more than 15 years. Originally, the
tumors were mixed papillary and follicular,
indistinguishable from any other slow-grow-
ing papillary cancer, but at autopsy they were
found to be undifferentiated and anaplastic
in appearance. This alteration is not fully
understood, but 2 possible explanations occur.
I n 1 case, the original papillary tumor con-
tained small foci of undifferentiated carci-
noma similar to the tumor found at autopsy.
I t is possible that this element began to grow
and gradually replaced the papillary element.
The other possibility is that metaplasia to a
more malignant type resulted from irradi-ation.
FOLLOW-UP
T h e 5-year period ordinarily accepted as the
primary goal for patients with cancer is of
relatively little value in the study of thyroid
cancer. Our study has shown that these pa-
tients a re not necessarily free of disease after
having been asymptomatic for long periods of
time. One-quarter of the patients who sur-
vived more than 5 years required further
treatment for recurrent cancer. One patient
was symptom free for 17 years when recur rent
tumor appeared in the neck. Another had a
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740 CANCERuly-August 1961 Vol. 14
lobectomy 25 years after the contralateral lobe
had been removed. The second cancer had
been present 19 years and was histologically
identical with the original lesion. It was im-
possible to determine whether this represented
a second primary or a growth of a metastatic
focus from the original tumor. Other patientsreturned for additional roentgen therapy, and
many received II3l after the 5-year period.
Approximately 40% of the deaths occurred
after the patients had lived 5 years.
Very few publications have tabulated pa-
tients followed for more than 10 years. The
only large series is that of Frazell and Footel?
who followed 209 patients for more than 10
years. Children are ideal subjects for a long
follow-up project; only 2 in this group died
of intercurrent disease. We are attempting tofollow the patients in this series for at least
20 years, but this will require the co-opera-
tion of a great number of physicians and
tumor clinic secretaries.
Although 152 patients have been followed
more than 5 years, only those followed for
more than 10 years have been included in the
present analysis. At this time, 117 have been
followed for more than 10 years, another 28
for more than 20 years, and 3 others for more
than 30 years (Fig. 3). In this group of 148
patients, the average age at the time of diag-
nosis was 10 years and 64 were of the
female sex. The average duration of symp
toms and the physical findings were also simi-
lar to those of the entire group. The patients
were treated as shown in Table 5.In the first category were included those
patients treated by total or subtotal thyroidec-
tomies with or without neck dissections and
those who had lobectomies with or without
neck dissections. Only 5 patients treated by
these methods died of the disease. The pa-tients in the second group were treated by
some of the methods enumerated, but the
surgery was usually less radical. In addition
to surgery, each patient had some form ofradiation therapy. Eleven of these patients
died after having lived for 10 years. Many of
the patients in the third category had ad-
vanced disease. No attempts were made sur-
gically to eradicate the accessible tumor, but
biopsy specimens were obtained for each pa-
tient prior to the institution of irradiation
therapy.
The tumors were staged according to the
extent of their growth at the time of the first
examination. Those restricted to 1 lobe were
251
10 15 20 25 30 35
years
FIG.3. Years of survival in 148 patients with thyroidcarcinoma.
classified as stage 1 lesions. If homolateral
cervical lymph nodes were involved, the case
was classed as stage 2. Tumors involving both
lobes of the thyroid gland or cervical nodes
on the contralateral side were classed as stage
3, and those with distant metastases were listed
as stage 4 Using these criteria, it was found
that the majority of patients who lived for
more than 10 years had stage 1 and 2 lesions.I t is of interest that 3 of the patients with
tumors originally described as inoperable lived
for more than 10 years, and 1 is still alive
after 20 years.
Seventy per cent of the patients had papil-
lary carcinoma, 22 had follicular carcinoma,
and 8 had undifferentiated carcinoma. This
is approximately the same proportion of types
as found in the entire series. The histological
appraisal of a thyroid tumor had limited
value in determining the prognosis in a givencase. Many patients with well differentiated
thyroid cancers had fulminating disease, while
some with undifferentiated tumors have lived
for many years despite inadequate therapy.
The exception was the spindle and giant cell
carcinoma that was rapidly fatal in both pa-
tients in this series.
In 30 patients, pulmonary metastases either
were present at the time of first examination
or appeared later. There was evidence of met-
astatic carcinoma in the lungs of 5 patients
when they were first examined, but the me-
tastasis in 1 patient appeared 23 years after
the first operation. One patient has had pul-
monary metastases for 22 years and another
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No. 4 CHILDHOODHYROIDA R C I N O MA Winship Q Rosuoll 741
for 17 years, while 7 have had pulmonary
lesions for more than 10 years. The lungs of
1 patient who had had pulmonary metastases
for 15 years cleared after the use of i I 3 l . T h e
lung lesions disappeared after I131 therapy in
9 patients.
Forty-six of the long term survivors hadmore than 1 operation to control disease.
Thirty-four were re-operated upon only once,
but the others had multiple procedures. One
patient had 6 operations and still has cancer.
Two others had metastatic carcinoma removed
from the brain, 1 approximately 1 year after
the thyroid operation and the other 12 years
after the operation. Both are living, 23 and 26
years respectively after the original surgery,
but 1 is known to have residual disease in the
lungs.Sixty-six per cent of the patients in this
group received some form of therapeutic ir-
radiation. i n most instances, it followed an
operative procedure, bu t in 15 cases it was the
only form of treatment. Roentgen therapy was
used for the majority of the patients, but 7
were treated by the use of radium and 1 each
by radioactive cobalt and phosphorus.
The presence of recurrent or residual thy-
roid cancer is ofLen impossible to detect in the
neck, mediastinum, and lungs. If it can beassumed that the patients whose lungs cleared
after the administration of 1131 are cured, then
only 18 (15%) of those who have lived for
more than 10 years have residual disease. One
patient, now 47 years old, has had thyroid
carcinoma for 34 years. i n 1952, the most re-
301
5 10 15 20 25 30
years
FIG.4. Years from diagnosis to death in 100 patientswith thyroid carcinoma.
cent effort to eradicate the disease in the neck
was abandoned as hopeless. Another patient
has had massive pulmonary metastases that
have been described by the radiologist as vir-
tually unchanged in 17 years. This patient
has had no therapy except that a biopsy
specimen of a lymph node in the neck wastaken and a small dose of irradiation was given
to this area.
Frazell and Footel7 stated that there was
no statistical data to substantiate the sus-
pected hazards of pregnancy on the course of
thyroid carcinoma. There were 11 women
in this group with residual tumor who have
borne from 1 to 5 normal children. One pa-
tient had toxemia of pregnancy; in another,
nephritis was a complication; bu t in n o in-
stance was activation of the thyroid cancerreported during the period of the pregnancy.
We have no evidence to suggest that I131 has
any deleterious effect on the ovaries of any
of the treated patients.
MORTALITY
One hundred and two patients died during
the follow-up period, but only 100 (17.7%
of the entire group) died of thyroid carcinoma.
One died of a neurogenic sarcoma in the
spinal cord, and another died of a brain
tumor. Autopsies failed to reveal residual thy-
roid carcinoma in either of these patients.
The average age of these patients at the
time of diagnosis was 9 years, and 57 of them
were female patients. inquiries concerning
irradiation during infancy were made for only
11 patients, and 4 had been treated for an
“enlarged thymus gland.” Although the dura-
tion of symptoms based on the memory of the
parents is not always reliable, the average
for this group was stated to be 18 months, ascompared to 25 months for the rest of the
series.Many of the patients who died had ad-
vanced disease when first examined. Using
the system of staging we applied to the long
term survivors, 53 were classified as stage 4
and only 6 as stage 1. Two patients died with-
out therapy of any kind, 25 had been treated
by surgery only, 26 by a combination of sur-
gery and X ray, and 47 by biopsy and X ray.
T h e 2 patients who received no therapy
were described as moribund. Eight deaths
were classified as postoperative, and 18 others
occurred during the first year. Fifty-nine pa-
tients died during the first 5 years, 17 in the
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742 CANCERuly-August 1961 Vol. 14
TABLE
C L IN IC A L S T A G E OF DISEASE I N 148 CASES
No. pt.:
Living Died aft.Stage >10 yr . 10 yr.
1234
TOTAL
45671 719
148
TABLE
S I T E S OF D IS E A S E IN 25 A U T O P S Y CASES
No. pt. with:
Locat. Total Pap. Follic. Undiff.dis. pt. carc. carc. carc.
3689
26
.
~~~
Neck only 7 3 2 2Neck & lungs 10 5 1 4Lungs only 3 2 1 . . .
1 1 3idespread 5
TOTAL 2 5 11 5 9
__
second 5-year period, and 24 died after having
had disease for 10 years or more (Fig. 4).
Study of the microscopic slides failed to
show any distinguishing features that could
be used as indicators of prognosis. T h e distri-
bution of types was similar to that for the en-
tire group except for a greater proportion of
undifferentiated tumors. Fifty-eight patients
died of papillary cancer, 16 of follicular, and
26 of undifferentiated. In the latter category,
there were 2 spindle and giant cell tumors,
11 small cell carcinomas, and 13 medullary
carcinomas.
Autopsies were performed on 25 of the pa-
tients. Table 7 shows the types of carcinoma
an d the sites of residual and metastatic disease
in this group of patients.
Widespread disease was found in only 5 pa-tients. Thi s number of cases is too small to be
of great significance, but the findings indi-
cate that the cause of death in the majority
of instances, regardless of type, is involvement
of the neck and thorax.
SUMMARY
A total of 562 cases of childhood thyroid
carcinoma has been collected from all parts
of the world.A definite increase in the incidence of this
disease is shown, being most marked between
the years 1945 an d 1957.
Almost 80% of the patients questioned were
found to have received irradiation during
infancy or childhood for an “enlarged thy-
mus,” hypertrophied tonsils and adenoids,
nevi, or angiomas.
O n initial physical examination, tumor was
localized to the thyroid gland in only 23%
of the patients. I n al l the others, metastases
had occurred.
Only 35% of the patients were treated by
surgery alone. All the others were treated by
either surgery and X ray or biopsy and X ray.
Twenty-three per cent required secondary
operations from a few months to 25 years after
the original surgery.
Slides from 364 patients were sent to us for
histological examination. Most of the tumors
were classified as papillary carcinomas but allknown types were represented.
At the present time, 148 patients have been
followed from 10 to 34 years. I t appears that
the type of tumor had relatively little rela-
tionship to longevity but that the extent of
disease was the most important single factor
in survival.
Almost 18% of the en tire group died of the
disease. Most of them died during the first
postoperative year, but 24 died after having
had disease for more than 10 years.Autopsies performed on 25 patients showed
the cause of death, in most instances, to be
carcinoma of the neck an d thorax.
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