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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many unpublished cases as possible.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but, to date, we have located 247 unpublished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



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.



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



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-




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



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




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



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




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.

REFERENCES

1. ADAMS, . D., and PURVES,. D.: Effective treat-ment of case of metastatic thyroid carcinoma by Pa

and desiccated thyroid. A u s t r a l a s i a n A n n . Med 7: 306-309, 1958.

2. BARON,. H.: Does irradiation of infants and chil-dren cause cancer of thyroid? Laryngoscope 68: 1267-1280, 1958.

3. BECKER . F., and MAHORNER,.: Carcinoma ofthyroid gland in children. In XVII” Congrks de laSocietC Internationale de Chirurgie, 1957; Prods Ver-baux. EXDO&et Discussions des Ouestions a 1’Ordre duJour.‘ Brissels, Belgium. Impr imGie Mkdicale et Scien-tifique. [1958]; pp. 873-880.

4. BUCKWALTER,. A.: Childhood thyroid carcinoma;pathologic considerations and their therapeutic impli-cations. J. CZin Endocrinol 15: 1437-1452, 1955.

5. CARRO,. P.; CUETO,. L. P., and VIVANCOS,. A.;Cancer de tiroides por radiacion en la infancia. Rar.din. espafi 75: 259-261, 1959.

6. CASTLEMAN,., Ed.: Case 45501, I n Case records

of t he Massachusetts General Hospital; weekly clini-copathological exercises. N e w England J Med 261:1239-1243, 1959.

7. CLARK, . E.: Association of irradiation with can-cer of thyroid in children and adolescents. J A. M A .159: 1007-1009, 1955.



No. 4 CHILDHOODHYROIDA R C I N OMA Winship Q Rosvoll 743

8. CLARK,R . L., JR.; WHITE, E. C., and RUSSELL,W. 0 :Total thyroidectomy for cancer of thyroid; sig-nificance of intraglandular dissemination. Ann. Szirg.

9. COHEN, . A and HYMAN,.: Carcinoma of thy-roid in children. A m. Surg. 23: 240-246, 1957.

10. CRILE,G., JR.: Carcinoma of thyroid in children.

Ann. Surg. 150: 959-964, 1959.

11. DUFFY,B . J., JR., and FITZGERALD,. J . : Thyroidcancer in childhood and adolescence; report on 28 cases.J. Clin. Endocrinol. 10: 1296-1308, 1950.

12. EGMARK,.; LARSSON,. G ; LILJESTRAND,., andRAGNHULT,.: Iodine-concentrating thyroid carcinomas;report of 3 cases. Ackz rudiol 39: 423-433, 1953.

13. EHRHARDT,0.:Zur Anatomie und Klinik derStruma maligna. Beitr klin. C h i r . 35: 343-464, 1902.

14. ESSIGKE,G.: Znm Vorkommen der bosartigenSchilddrusengeschwilste im Kindesalter.Miinchen. med .

Wchnschr. 97: 472-475, 1955.

15. FARBER,., Ed., and CRAIG, . M., Asst. Ed.: Clini-cal Pathological Conference; the Children's Center,Boston, Mass. J. Pea iut. 53: 494-502, 1958.

16. FmTERMAN, G H.: Carcinoma of thyroid in chil-dren ; report of 10 cases. A . M A . J Dis. Child 92: 581-587, 1956.

L, E. L ., and FOOTE,F. W., JR.: Papillarycancer of thyroid; review of 25 years of experience.

Cancer 11: 895-922, 1958.

18. FREEDIHZRC,. S.: Personal communication.

19. GLASS, . G.; WALDRON,. W.; ALLEN,H. C., JR.,and BROWN,W. G.: Rational approach to thyroid ma-lignancy problem. Am Surgeon 26: 81-86, 1960.

20. GROSSO, . F.; PASEYRO,., and MAGGIOLO,.:Contribucion a1 diagnostic0 del cancer del tiroides; aproposito d e 40 observaciones de carcinoma infiltrativo.Ann. 1;cic m e d Montevideo 44: 53-80, 1959.

21. HAYLFS,. B.; KENNEDY,. L. J.; BEAI-IRS,.H.,

and WOOLNER,. 15.: Management of child with thy-roidal carcinoma. ./. A . M . A . 173: 21-28, 1960.

22. KNISELEY, M., and ANDREW,G. A , : Transfor-mation of thyroidal carcinoma to clear-cell type. A m . J

Clin. Z ath. 26: 1427-1438, 1956.

23. LOGALDO,.: Carcinoma de la glindula tiroidesen una niila de diez anbs. Rev Asoc. me d. argent. 69:292-295, 1955.

24. L ~ K E N ,. C.: Thyreoideacancer hos 11 %rgam-me1 pike. [Abstr.] A'ord. med. 59: 198, 1958.

25. LYNN,H. B., and LINKER, . M.: Carcinoma ofthyroid in childhood. Zn Case discussions from the Uni-versity of Louisville Hospitals. J. Kentucky Sta te M . A .57: 447-451, 1959.

26. MAJARAKIS,. D.; SLAUGHTER,. P., and COLE,W. H.: Thyroid cancer in childhood and adolescence.

J Clin. Endocrinol. 16: 1487-1490, 1956.

27. MALANDRA,. , and DOVA, .: Sulle neoformazionicistopapilli fere della tiroide. Tumori 43: 417-429, 1957.

28. MARTIN,H.: Surgery of thyroid tumors. Cancer7: 1063-1099, 1954.

29. MCCORKLE, . J.: Surgical removal of metastaticmalignant disease of thyroid gland from anterior-superior mediastinum. Am. J Surg. 94: 217-222, 1957.

30. MCGIRR,E. M.; CLEMENT,W . E.; CURRIE,A. R.,and KENNEDY,. S : Impaired dehalogenase activity ascause of goitre with malignant changes. Scottish M J

4: 232-241, 1959.

31. MCNEILL, . P. , and GOODE, . V.: Surgical treat-

ment of carcinoma of thyroid. A m . Surgeon 26: 118-120,1960.

32. MEISSNER, . A., and LEGG,M. A.: Persistent thy-

149: 858-866, 1959.

roid carcinoma. ]. CEin. Endocrinol. 18: 91-98, 1958.

33. MOORE, . R., and MCKENZIE,A. D.: Thyroid

cancer in children. Canad. J Surg. 2: 175-179, 1959.

34. PETIT,D. W.; CATZ,B. , and STARR, .: Thyroidcancer i n youth. California Med. 89: 394-396, 1958.

35. QUIMBY, E. H., and WERNER,. C.: Lat e radiation

effects in roentgen therapy for hyperthyroidism; theirpossible bearing on use of radioactive iodine. J A . M . A .

140: 1046-1047, 1949.

36. RABINOWITZ,., and KATZ, .: Carcinoma of thy-roid following irradiation of neck. South African M . J32: 723-725, 1958.

37. RALL, J. E.; ALPERS, . B.; LEWALLEN, . G ;SONENBERG,.; BFRMAN, ., and RAWSON,. W.: Radi-

ation pneumonitis and fibrosis; complication of radio-iodine treatment of pulmonary metastases from cancerof thyroid. J Clzn Endocrinol. 17: 1263-1276, 1957.

38. ROBERTS,K . D.: Thyroid carcinoma in child-

hood in Great Britain. A r c h . Dis Childhood 32: 58-60,

1957.

39. ROO NLY , . R ., and POWELL,R. W.: Carcinomaof thyroid in children after x-ray therapy in early

childhood. J A . M . A . 169: 1-4, 1959.40. Ross, D. E.: Cancer of thyroid gland in children.

Surg Gynec. Obs t 104: 433-440, 1957.

41. SHROFF, . D., and PAYMASTER,. C.: Carcinomaof thyroid; (clinical study of 108 cases). Indian J Surg20: 346-353, 1958.

42. SIMPSON, . L.: Personal communica tion.

43. SIMPSON,. I>.; HEMPELMANN,. H., and FULLER,I>. M.: Neoplasia in children treated with x-rays in in-fancy for thymic enlargement. Radio logy 64: 840-845,1955.

44. STUR.0.. nd SWOBODA..: Zwei Falle ton Schild-driisenkarzinom im Kindesalter. Neue O s t e r r . ZtschrKinderh. 3: 73-78, 1958.

45. THEONIES, ., and MULLER,G.: Zur Struma ma-

ligna im Kindesalter. Arztl. Wchnschr. 12: 441-448,1957.

46. TSUKANOVA,. A , : [Adenoma of accessory thyroidgland lobe in 14-year-old boy.] Vestnik otorinolaring.

20: 116-117, 1958.

47. UHLMANN,. M.: Cancer of thyroid and irradia-

tion. J A . M . A . 161: 504-507, 1956.

48. WELTI,H.: Cancer de la thyroi'de chez l'enfant;a propos de quatre observations personnelles. Mkm.

Acad. chir . 82: 1002-1007, 1956.

49. WILSON,E. H., and ASPER,S. P., JR.: Role ofX-ray therapy to neck region in production of thyroidcancer in young people: report of 37 cases. A v c h . Int .

Med. 105: 244-251, 1960.

50. WILSON, . M.; KILPATRICK,.; ECKERT, .; CUR-R A N , R. C.; JEPSON,R. P.; BLOMFIELD,. W., and MIL-LER, H.: Thyroid neoplasms following irradiation. Br i t

51. WlNSHIP, T : Carcinoma of thyroid in children.

52. WINSI-IIP, .: Carcinoma of thyroid in childhood.

53. WINSHIP. .. and CHASE.W. W.: Childhood thv-

M . J. 2: 929-934, 1958.

Tr. Am . Goiter A [1951]: 364-389, 1951.

Pediatrics 18: 459-466, 1956.

roid carcinoma in Western Europe. Arch. chir. neeil.5: 253-261, 1953.

54. WINSHIP,T., and CHASE,W. W.: Thyroid carci-noma in children. Su r g Gynec. ch Obs t 101: 217-224,1955.

55. WINSHIP,T. and ROWOLL,R. V.: Unpublished

data.

56. YANARI, . and MOROTO, .: [Thyroid cancer inchildren.] Saishin Zguku 12: 33-38, 1957.

chilhodd tiroid

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