World J. Surg.
23, 177–181, 1999
Clinically Significant, Isolated Metastatic Disease to the Thyroid Gland
Herbert Chen, M.D.,1 Theresa L. Nicol, M.D.,2 Robert Udelsman, M.D.1
1
Division of Endocrine and Oncologic Surgery, Department of Surgery, Blalock 688, The Johns Hopkins Hospital, 600 North Wolfe Street,
Baltimore, Maryland 21287, USA
2
Department of Pathology, The Johns Hopkins Medical Institutions and The Johns Hopkins Thyroid Tumor Center, 600 North Wolfe Street,
Baltimore, Maryland 21287, USA
Abstract. Despite being second only to the adrenal glands in terms of
relative vascular perfusion, the thyroid gland is a rare site of metastatic
disease; but when thyroid metastases occur, long-term survival has been
reported to be dismal. To determine the incidence and management of
isolated, metastatic disease to the thyroid, we reviewed our clinical
experience. Between June 1986 and August 1994 ten patients underwent
thyroidectomy for isolated, metastatic disease of nonthyroidal origin
(mean 6 SD age 58 6 6 years, 30% female). The primary tumors were
renal cell carcinomas (RCCs) (n 5 5), esophageal adenocarcinoma (n 5
1), pulmonary squamous cell carcinoma (n 5 1), gastric leiomyosarcoma
(n 5 1), lingual squamous cell carcinoma (n 5 1), and parotid gland
carcinoma (n 5 1). Three patients underwent preoperative fine-needle
aspiration (FNA), all of which were suggestive of metastatic disease. The
mean time from resection of the primary tumor to thyroid metastases was
3.5 6 6.0 years (range 0 –19.5 years). Total thyroidectomy (n 5 5) or
lobectomy (n 5 5) was performed without morbidity or mortality. After a
median follow-up of 5.2 years six patients are alive and two are free of
disease. Moreover, no patients have had recurrent disease in the neck.
Thus carcinomas metastatic to the thyroid represent a rare cause of
clinically significant thyroid disease, with RCCs comprising 50%. Most
thyroid metastases (80%) present within 3 years of primary tumor
resection, but with RCC they can occur as late as 19 years. The diagnosis
of metastatic disease should be suspected in patients with even a remote
history of cancer, especially RCC, and an FNA revealing clear cell or
spindle cell carcinoma. Contrary to previous reports, long-term survival
can be achieved after resection of the metastatic tumor. Furthermore,
thyroidectomy may also palliate/prevent the potential morbidity of tumor
recurrence in the neck.
Resection of metastatic disease has been shown to be beneficial
for a variety of tumors. Surgical resection of isolated metastases to
the liver prolongs survival in patients with colorectal cancer [1–3],
neuroendocrine tumors [4], and leiomyosarcoma [5]. Similarly,
resection of lung metastases from soft-tissue sarcoma is associated
with up to a 25% disease-free survival at 5 years [6]. The role of
surgical therapy for tumors metastatic to other solid organs has
not been as extensively studied.
Despite being second only to the adrenal glands in relative
vascular perfusion, the thyroid gland is a rare site of clinically
significant metastatic disease [7]. However, autopsy series dem-
onstrate a 1.9% to 24.2% incidence of metastatic disease to the
thyroid in patients who die as a result of primary or metastatic
Correspondence to: R. Udelsman, M.D.
WORLD
Journal of
SURGERY
© 1999 by the Société
Internationale de Chirurgie
tumors [8 –10]. When thyroid metastases are clinically recognized,
long-term survival has been reported to be dismal [11]. However,
one recent study reported a mean survival of 34 months with
thyroidectomy with or without adjuvant therapy, in contrast to 25
months for patients treated nonsurgically [12]. This group of
patients included those with metastatic disease outside the thyroid
gland. To determine the incidence and management of patients
with isolated metastatic disease to the thyroid gland, we reviewed
our clinical experience over an 8-year period.
Materials and Methods
Patients who underwent thyroidectomy at the Johns Hopkins
Hospital between June 1986 and August 1994 for a metastatic
lesion from a nonthyroidal primary malignancy were identified
from the Johns Hopkins Hospital pathology database. To be
included in this study, patients had to have a clinically recognized,
isolated, metastatic, nonthyroidal lesion that either presented as a
thyroid nodule or caused clinically significant symptoms. Tumors
that directly invaded the thyroid gland from adjacent organs were
excluded. All lesions were confirmed to be of metastatic origin by
histologic comparison of the resected thyroid specimen with the
primary tumor.
On pathologic review, 10 consecutive patients met these criteria
during this interval, and their medical records were retrospectively
analyzed. All fine-needle aspirations (FNAs), frozen sections, and
permanent histology were re-reviewed by a single pathologist.
The extent of thyroidectomy in each patient was determined by
the surgeon. In general, our practice is to resect all gross disease
with negative margins. If the contralateral thyroid lobe is nodular,
we prefer to perform a bilateral procedure. Actuarial survival
times were calculated using Kaplan-Meier analysis.
Results
Patient Demographics
The median age of the 10 patients who underwent thyroidectomy
for metastatic disease to the thyroid gland was 53 years (range
48 –70 years). Seven patients were male and 3 were female. Three
178 World J. Surg. Vol. 23, No. 2, February 1999

Table 1. Pathology and surgery.

Primary tumor Metastatic tumor

Uni- or
Surgery Pathology Surgery bilateral
Bilateral nephrectomy Renal cell carcinoma Left lobectomy Unilateral
Right nephrectomy Renal cell carcinoma Total thyroidectomy Unilateral
Right nephrectomy Renal cell carcinoma Right lobectomy Unilateral
Left nephrectomy/partial right nephrectomy Renal cell carcinoma Total thyroidectomy Bilateral
Left nephrectomy Renal cell carcinoma Right lobectomy Unilateral
None Esophageal adenocarcinoma Total thyroidectomy Bilateral
Subtotal gastrectomy Gastric leiomyosarcoma Total thyroidectomy Unilateral
Left pneumonectomy Pulmonary squamous cell carcinoma Right lobectomy Unilateral
Base of tongue excision Lingual squamous cell carcinoma Total thyroidectomy Unilateral
Parotidectomy Parotid gland carcinoma Left lobectomy Unilateral

patients had a history of thyroid cancer or a synchronous thyroid
cancer at the time of exploration for the metastatic lesion. One
had a follicular variant of papillary thyroid cancer treated by
thyroid lobectomy 16 years previously, and two had concomitant
papillary thyroid cancer in the ipsilateral lobe of the thyroid with
the metastatic lesion, one of which was an occult lesion.
Symptoms or Signs of Metastatic Disease at Presentation
The median interval from the initial treatment of the primary
tumor to resection of the thyroid metastases was 2 years (range
0 –19.5 years). Of the 10 patients, 2 presented with thyroid nodules
on physical examination and 2 had nodules discovered during
imaging studies. An additional 2 patients had disease manifested
by symptoms of hoarseness and dyspnea, respectively. In four
patients thyroid nodules from metastatic disease were discovered
during other operations, including parotid resection for parotid
gland carcinoma (n 5 1), parathyroidectomy for primary hyper-
parathyroidism (n 5 1), and neck dissection for squamous cell
carcinoma of the tongue (n 5 1). The fourth patient had
metastatic papillary cancer found in a mediastinal lymph node
during diagnostic mediastinoscopy for squamous cell carcinoma of
the lung. During thyroidectomy for papillary thyroid cancer, a
metastatic nodule from the squamous cell carcinoma was found.
Primary Tumor Characteristics
The primary tumors that were metastatic to the thyroid gland in
these 10 patients are listed in Table 1. Of the five renal cell
carcinomas, three were grade III tumors and two were grade II
using the practical microscopic grading system (I–IV) based on
nuclear morphology [13]. Three of the five tumors were unilateral,
and two were bilateral. The operations performed to resect the
five primary renal cell carcinomas included three unilateral ne-
phrectomies, one bilateral nephrectomy, and one right nephrec-
tomy with a partial left nephrectomy. Resection of the primary
tumors was performed for four of the five other primary tumors
and consisted of subtotal gastrectomy, left pneumonectomy, exci-
sion of the base of the tongue, and parotidectomy. The patient
with esophageal adenocarcinoma underwent primary radio/che-
motherapy.
Metastatic Tumor Characteristics
The characteristics of the metastatic tumors from these 10 pa-
tients are also listed in Table 1. Two of the ten patients had
metastatic disease involving both lobes of the thyroid, which had
originated from a primary renal cell carcinoma and an esophageal
adenocarcinoma, respectively. The other eight patients had uni-
lateral thyroid metastases. Five patients underwent total thyroid-
ectomy for resection of metastases, and five had thyroid lobecto-
mies/isthmusectomies.
Fine-Needle Aspiration Results
Three of the ten patients underwent preoperative FNA. All three
FNAs were consistent with metastatic disease. In one case FNA
revealed an anaplastic, malignant spindle cell tumor resembling
the resected gastric leiomyosarcoma. In the other two cases, the
FNAs were interpreted as a spindle cell tumor and a clear cell
carcinoma, respectively; and both were later found to be renal cell
carcinomas.
Patient Outcomes
There was no operative morbidity or mortality associated with
thyroidectomy. With a median follow-up of 5.2 years, median
survival has not been reached. Actuarial patient survival as
determined by Kaplan-Meier analysis is shown in Figure 1. Six
patients are currently alive, and two are free of disease with up to
10 years of follow-up. Moreover, none of the 10 patients has had
recurrent disease in the thyroid bed or contralateral lobe.
Discussion
The thyroid gland has a rich blood supply of approximately 560
ml/100 g tissue/min, which is reported to be second only to the
adrenal gland [7]. From autopsy studies, the incidence of meta-
static tumors to the thyroid ranges from 1.9% to 24.2% [8 –10]. In
these series the most common primary site was either breast or
lung [8 –10]. However, these cases included patients who had
disseminated or nonclinically significant thyroid metastases (or
both). A better estimate of the incidence of clinically significant
metastases to the thyroid comes from more recent clinical series
Chen et al.: Metastatic Disease to the Thyroid
Fig. 1. Actuarial patient survival after thyroidectomy for metastatic dis-
ease to the thyroid gland.
involving preoperative FNAs performed for thyroid masses, which
report incidences of 5.7% to 7.5% [14, 15].
In this report, we describe 10 patients with isolated metastases
to the thyroid gland during an 8-year period. Other investigators
have reported similar numbers of patients with metastases to the
thyroid gland over longer periods. McCabe et al. reported one of
the largest series of 17 patients over a 23-year period [11], but only
10 of 17 patients in their series underwent thyroidectomy for
curative resection [11]. Moreover, they found that metastases to
the thyroid was associated with a poor prognosis; the mean
survival was 12 months, and there were no long-term survivors
[11]. The most common primary tumor in their series was head
and neck squamous cell cancer. More recently, a study of 43
patients at the Mayo Clinic with metastatic disease to the thyroid
over a 10-year period was reported, with patients who had
prolonged disease-free intervals (10 –26 years); it suggested that in
a patient with a thyroid nodule and a history of cancer metastatic
disease should be considered until proved otherwise [12]. In their
report, most of the patients presented with, or had a history of,
metastases to organs other than the thyroid gland (i.e., not
isolated to the thyroid), and the mean survival was just under 3
years in those who underwent resection of thyroid metastases with
thyroidectomy [12]. Our series reflects a group of patients with
isolated thyroid metastases; and after a median follow-up of 5.2
years months, 60% of patients are alive and two are disease-free.
Other published reports include another series from the Mayo
Clinic with 14 patients over a 55-year period [16] and other series
with similar numbers of patients [9, 16 –20]. The overall experi-
ence from these series of patients with metastases to the thyroid
is variable, but long-term survival after thyroidectomy is occasion-
ally reported [20].
Although some patients with metastatic disease to the thyroid
present with symptoms such as dysphagia, stridor, hoarseness, or
a palpable neck mass [9, 17–19], most of the patients in our series
and others [11, 12] were asymptomatic at presentation. Therefore
most of these patients have their thyroid metastases discovered by
routine follow-up physical examinations or imaging studies after
resection of the primary tumor. The initial diagnostic study of
choice in these patients is FNA, which is extremely accurate in
diagnosing metastatic lesions to the thyroid gland [12, 14, 15]. In
this series, all three preoperative FNAs suggested metastatic
disease rather than primary thyroid cancer. Historically, prior to
179
the development of FNA, open biopsy was required for diagnosis
[11].
Renal cell carcinoma (RCC) was the most common metastatic
tumor to the thyroid, accounting for 50% of the lesions. It is now
more commonly recognized as a clinically significant cause of
curable thyroid metastases, comprising the majority of metastatic
tumors to the thyroid in two other series [12, 19]. Moreover,
Congiu et al. have reported that the first sign of RCC in 25% of
patients is thyroid metastases [21]. In recent years, there have
been several case reports showing that long-term survival is
possible after thyroidectomy for metastases from RCC [20 –24]. In
this series four of five patients with RCC are alive after thyroid-
ectomy with a median follow-up of 5.2 years. Therefore in patients
with RCC routine screening for thyroid metastases may be a
desirable practice.
There is no clear consensus regarding the role of surgery in
metastatic disease to the thyroid [11]. Most authors recommend a
thyroid lobectomy/isthmusectomy in the absence of other meta-
static disease [9, 11, 17–19, 21] or for palliation of airway
obstruction [16]. However, due to the limited number of patients,
it is difficult to make definite recommendations. It seems clear
that resection of all thyroid metastases should be attempted with
at least a thyroid lobectomy. In the case of bilateral metastases or
for a large lesion, a total or near-total thyroidectomy may be
required. In the absence of a randomized, prospective trial
comparing surgical and nonsurgical therapies for treatment of
isolated metastases to the thyroid, the true benefit of thyroidec-
tomy is unclear. Prolonged survival in the absence of locally
recurrent disease suggests that resection may be beneficial.
Conclusions
Our study is limited by its retrospective nature and the small
number of patients. Nonetheless, it represents a single-institution
perspective and demonstrates the potential benefit of thyroidec-
tomy in this subset of patients. We have shown that clinically
significant metastases to the thyroid gland appear to be relatively
infrequent. Diagnosis requires a high level of suspicion in patients
with a history of cancer, especially RCC, and FNA is the
diagnostic procedure of choice. Contrary to other reports, long-
term survival can be achieved after resection of the metastatic
tumor with thyroidectomy.
Résumé
Secondaire seulement à la corticosurrénale en ce qui concerne la
perfusion vasculaire relative du corps humain, la thyroı̈de est, par
contre, rarement le site de métastase. Cependant, lorsqu’une
métastase de la thyroı̈de est constatée, la survie à long terme est
médiocre. Afin de déterminer l’incidence et le traitement des
métastases isolées de la thyroı̈de, nous avons revu notre expéri-
ence clinique. Entre juin 1986 et août 1994, 10 patients ont eu une
thyroı̈dectomie pour maladie métastatique de la glande dont
l’origine n’était pas la thyroı̈de (âge moyen 5 58 6 6, 30% de
femmes). La nature des tumeurs primitives était un adénocarci-
nome du rein (RCC) (n 5 5), un adénocarcinome de l’oesophage
(n 5 1), un cancer pulmonaire (épithélium malpighien; n 5 1), un
léiomyosarcome gastrique (n 5 1), un cancer épithélial de la
langue (n 5 1) et un cancer de la parotide (n 5 1). Trois patients
ont eu une biopsie par aspiration à l’aiguille préopératoire: les
180
résultats avaient suggéré dans tous les cas une maladie métasta-
tique. La durée moyenne entre la résection de la tumeur primitive
et la survenue de métastases au niveau de la thyroı̈de a été de
3.5 6 6.0 ans (extrêmes 0 –19.5 ans). On a réalisé soit une
thyroı̈dectomie totale (n 5 5) soit une lobectomie (n 5 5), sans
aucune mortalité ou morbidité. Après un suivi médian de 5.2 ans,
6 patients sont toujours en vie et deux, sans maladie. On n’a
constaté aucun cas de récidive au niveau du cou. Ainsi le cancer
responsable de métastases au niveau de la thyroı̈de représente
une cause rare de maladie cliniquement parlante, le cancer du
rein étant à l’origine dans 50% des cas. La plupart des métastases
de la thyroı̈de (80%) sont constatées en moins de 3 ans après la
résection primitive, mais, en cas de cancer du rein, elles peuvent
se voir jusqu’à 19 ans après. Le diagnostic de maladie métasta-
tique devrait être soupçonné chez tout patient ayant un antécéd-
ent de cancer aussi éloigné soit-il, surtout de cancer rénal, et
lorsque la cytologie montre un cancer à cellules claires ou
fusiformes. Au contraire de ce qui a été dit, on peut voir des
survies prolongées après résection de tumeur métastatique. Une
thyroı̈dectomie pourrait également être indiquée à titre palliatif
de façon a prévenir la morbidité associée à une récidive tumorale
au niveau du cou.
Resumen
A pesar de que apenas ocupa el segundo lugar, luego de las glándulas
suprarrenales, en cuanto a perfusión vascular relativa, la tiroides es
un sitio raro de enfermedad metastásica. Sin embargo, cuando se
presentan metástasis tiroideas, el pronóstico a largo plazo resulta
ominoso. Nos propusimos revisar nuestra experiencia clı́nica con el
objeto de determinar la incidencia y el manejo de la enfermedad
metastásica aislada de la glándula tiroides. En el periodo de junio de
1986 a junio de 1994, 10 pacientes fueron sometidos a tiroidectomı́a
por enfermedad metastásica de origen no tiroideo (edad promedio
58 6 6, 30% sexo femenino). Los tumores primarios fueron carci-
nomas de células renales (CCR) (5), adenocarcinoma del esófago (1)
y carcinoma de la glándula paratiroides (1). En tres pacientes se
practicó preoperatoriamente aspiración con aguja fina, y en todos
hubo sugerencia de enfermedad metastásica. El tiempo promedio
entre la resección del tumor primario y las metástasis tiroideas fue de
3.5 6 6.0 años (rango 0 –19.5). El tratamiento quirúrgico consistió en
tiroidectomı́a total (5) o lobectomı́a (5), sin morbilidad ni mortali-
dad. En un seguimiento promedio de 5.2 años, hay 6 pacientes vivos
y 2 se encuentran libres de enfermedad. Además, ninguno exhibe
enfermedad recurrente de localización cervical. Se deduce que los
carcinomas metastásicos de la tiroides constituyen una causa rara de
enfermedad tiroidea clı́nicamente significativa, con el CCR repre-
sentando el 50% de los casos. La mayorı́a de las metástasis tiroideas
(80%) se presentan dentro de los primeros 3 años siguientes a la
resección del tumor primario, pero en los CCR tal fenómeno puede
ocurrir hasta 19 años más tarde. Se debe sospechar la presencia de
enfermedad metastásica aun en pacientes con historia remota de
cáncer, especialmente si se trata de un CCR, y cuando la aspiración
con aguja fina revela un carcinoma de células claras o de células
fusiformes. En contra de lo que aparece en reportes previos, es
posible una supervivencia prolongada luego de la resección del
tumor metastásico. Además, la tiroidectomı́a también puede ser
paliativa o preventiva de la morbilidad potencial que significa una
recurrencia tumoral en la región cervical.
World J. Surg. Vol. 23, No. 2, February 1999
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Chen et al.: Metastatic Disease to the Thyroid
Invited Commentary
Svante Jansson, M.D., Ph.D.
Department of Surgery, Sahlgrenska University Hospital, Göteborg,
Sweden
In the present paper Chen and coworkers report 10 consecutive
patients with isolated metastatic tumors to the thyroid gland
diagnosed during an 8-year period. Only patients who had under-
gone thyroid surgery were included. Three patients were diag-
nosed before surgery by fine-needle aspiration biopsy (FNA). The
patients were detected through clinical signs or symptoms (n 5 4)
or as “accidental” findings during imaging studies or surgery for
other disorders. Fifty percent of the primary tumors were renal
cell carcinoma (RCC); the others were various other tumors. The
patients were treated with total thyroidectomy (n 5 5) or lobec-
tomy (n 5 5). After a medium follow-up of 5 years, eight patients
were alive and two were in complete remission.
This is an interesting series in many ways, indicating that
especially with metastases from RCC long-term survival can be
achieved after resection of solitary thyroid metastases. The reason
metastases from certain tumors have a preference for certain sites
is interesting. For instance, why does breast cancer or prostatic
cancer frequently give rise to metastases in bone? Why do
adrenals and sometimes ovaries frequently harbor metastases?
The thyroid gland, on the other hand, is seldom a site for
metastatic tumors. It seems not to be a result of high vascularity.
Other unknown factors are probably more important for such
“tumor taxis.”
The present series is limited and probably selective. To get an
idea of the degree of selection it would have been of interest to
know how many patients diagnosed during the same period with
metastases to the thyroid gland never underwent surgery because
of disseminated tumor or for other reasons were not offered
surgery.
181
The finding that 50% of the patients had primary RCC also
indicates a selection bias, as no case of breast cancer and only one
patient with lung cancer were included. Breast and lung cancer
are the most common tumors giving rise to secondaries in the
thyroid.
In the present series two lesions were detected during imaging
studies without obvious clinical findings, thus being “thyroid
incidentalomas.” Four others were diagnosed as incidental find-
ings during surgical procedures for other diseases. Thus 6 of 10
patients could be regarded as being detected by chance only. This
also illustrates a higher degree of selection.
It is well known that solitary metastases of RCC respond well to
surgical excision irrespective of metastatic site. It is therefore no
reason to believe that a solitary RCC in the thyroid would be more
dangerous than, for instance, solitary lung metastases. Thus the
role of surgery must of course be related to the prognosis for the
primary tumor. It would also be of interest to know if the patients
in the present series had antitumor treatment in addition to
surgery in view of the seemingly good results.
The authors recommend FNA as the diagnostic procedure of
choice. In the present series, however, only three patients were in
fact investigated by FNA, which makes the authors’ experience
limited in this respect to allow such a conclusion. Surely, open
biopsy, as the authors point out, is seldom needed nowadays.
Although limited and selected, the present series is interesting
and carries an important message that some patients with limited
metastases confined to the thyroid gland might benefit from
surgical excision of the metastases. As recently reported by Lin
and co-workers [1], delay in diagnosis of thyroid metastases is a
reason for short survival.
Reference
1. Lin, J.D., Weng, H.F., Ho, Y.S.: Clinical and pathological characteris-
tics of secondary thyroid cancer. Thyroid 8:149, 1998