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International Journal of Surgery xxx (2015) 1e6

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International Journal of Surgery


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Original research

Prevalence, diagnosis and management of ectopic thyroid glands


Giuseppe Santangelo a, b, *, Gianluca Pellino b, Nadia De Falco a, b, Giuseppe Colella c,
Salvatore D'Amato c, M. Grazia Maglione c, Roberto De Luca c, Silvestro Canonico b,
Massimo De Falco a, b
a

Fifth Division of General Surgery and Special Surgical Techniques, Second University of Naples, Naples, Italy
Division of General and Geriatric Surgery, Second University of Naples, Italy
c
Department of the Head and Neck Surgery, Second University of Naples, Naples, Italy
b

a r t i c l e i n f o

a b s t r a c t

Article history:
Received 6 April 2015
Received in revised form
25 April 2015
Accepted 10 May 2015
Available online xxx

Ectopic thyroid tissue (ETT) is an uncommon entity that may be found anywhere along the line of the
obliterated thyroglossal duct, usually from the tongue to the diaphragm.
We performed a retrospective analysis of patients undergoing surgical treatment for thyroid disease
between January 2000 and December 2013, seeking for ETT All patients with prior neck surgery or
trauma were excluded. The clinic-pathologic features, prevalence and diagnosis of the lesions were
collected and analyzed.
Out of 3092 included patients, 28 ETT were identied (0.9%). The anatomical site of ETT was as follows:
lateral cervical in 6 (21.4%), along the thyroglossal duct in 6 (21.4%), mediastinal in 5 (17.9%), lingual in 5
(17.9%), sublingual in 3 (10.7%), and submandibular in 3 (10.7%). Histopathology revealed 27 benign lesions and 1 (3.6%) papillary carcinoma.
ETT is found in less than 1% of patients receiving thyroid surgery. Diagnosis of ETT requires clinical
imaging. Surgery is a prudent choice due to the potential of malignant evolution of ETT.
2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Keywords:
Ectopic thyroid tissue
Thyroid
Surgery

1. Introduction
Ectopic thyroid tissue (ETT) may be found anywhere along the
line of the obliterated thyroglossal duct, usually from the base of
the tongue to the mediastinum [1]. It is the most frequent form of
thyroid dysgenesis (48e61% of the cases) with prevalence of 1 per
100,000e300,000 persons (75%e80% of cases occur in females) [1].
The mechanisms underlying thyroid morphogenesis have not been
clearly elucidated. Transcription factors seem to play a key role in
thyroid organogenesis, e.g. TITF1/NKX2-1, which is responsible for
the thyroid-specic expression of thyroglobulin (Tg) and thyroperoxidase, and the PAX8, HHEX, and FOXE1. These factors are not
only expressed in functioning thyroid cells but also in their

* Corresponding author. Division of General and Geriatric Surgery, Second University of Naples, Second University of Naples, Piazza Miraglia, 80100 Naples, Italy.
E-mail addresses: giuseppesantangelo@email.it (G. Santangelo), gipe1984@
gmail.com (G. Pellino), nadietta90@hotmail.it (N. De Falco), giuseppe.colella@
unina2.it (G. Colella), salvatore.damato@unina2.it (S. D'Amato), m.grazia.
maglione@gmail.com (M.G. Maglione), robertodeluca89@yahoo.it (R. De Luca),
silvestro.canonico@unina2.it (S. Canonico), massimo.defalco@unina2.it (M. De
Falco).

precursors, and are probably essential for the early stages of thyroid
morphogenesis [2,3].
ETT can co-exist with an eutopic thyroid, even if for the majority
of cases it occurs without. However, in all of cases of thyroid ectopia
there are no anatomical or vascular connections whith the orthotopic thyroid.
ETT is more frequently located in all the anatomical regions
along which embryonic thyroid germ migrates, or in the organs
with which it contracts relationships during embryogenesis, but it
can also arise between the foramen cecum to the mediastinum.
Lingual thyroid is the most common type of ETT [4], accounting
for 90% of cases, while sublingual types are less frequently
encountered; other locations involved in the head and neck regions
include trachea [5], submandibular gland [6], lateral cervical regions [7], maxilla [8], palatine tonsils [9], carotid bifurcation [10],
iris of the eye [11], and pituitary gland [12]. Besides, ETT has also
been found in cardiac tissue [13], ascending aorta [14], thymus [15],
esophagus [16], duodenum [17], gallbladder [18], stomach bed [19],
pancreas [20], mesentery of the small intestine [21], Porta Hepatis
[22], adrenal gland [23], ovary [24], fallopian tube [25], uterus [26]
and vagina [27]. ETT in the ovaries is known as Struma ovarii and

http://dx.doi.org/10.1016/j.ijsu.2015.12.043
1743-9191/ 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: G. Santangelo, et al., Prevalence, diagnosis and management of ectopic thyroid glands, International Journal of
Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.12.043

G. Santangelo et al. / International Journal of Surgery xxx (2015) 1e6

is considered a thyroid tissue teratoma [24].


Dual ectopia is very rare. Huang et al. [28] described a case of
dual ectopia with a normally located pretracheal thyroid gland.
Two cases of triple ectopia have been reported, of which one presented with three separate ectopic thyroid masses in the lateral
neck region with a co-existing eutopic goiter [29].
Any disease affecting the thyroid gland may also involve the ETT,
including malignancy.
ETTT may be associated with clinically evident thyroid
dysfunction or may become goiters. Hormonal changes can cause
enlargement in size or deciency or excess in circulating hormone
levels, resulting in evident clinical signs and symptoms. Hypothyroidism occurs in about 33% of patients with thyroid ectopia [30].
Malignant transformation is relatively uncommon(<1%) and can
appear with different histotypes: papillary, follicular, mixed follicular and papillary, Hurthle cell and medullary.
ETT is commonly asymptomatic. Symptoms are usually related
to size and location or to endocrine dysfunctions [31]. In this study
we performed a retrospective analysis of patients who underwent
surgical treatment for thyroid disease, analyzing clinical and
pathologic features of ETT, and addressing prevalence, anatomical
distribution, diagnosis and treatment.
2. Material and methods
Patients were identied through a database search of surgical
cases treated between January 2000 and December 2013 for
thyroid disease at three Units of Surgery of Second University of
Naples: the Fifth Division of General Surgery and Special Surgical
Techniques, The Division of General and Geriatric Surgery, and the
Department of Head and Neck Surgery.
Only patients undergoing neck surgery for the rst time were
included. Patients with prior neck surgical procedures or suffering
from head and neck region trauma were excluded.
Clinical and instrumental evaluation consisted of:
- Endocrinological assessment (serology)
- Ultrasonography
- Computer tomography (CT) or Magnetic resonance imaging
(MRI)
- Scintigraphy
- Fine needle aspiration cytology (FNAC)
- Fine needle aspiration biopsy (FNAB)
- Chest X-rays

Table 1 Features of patients.


N. patients included in our study

3092

N ectopic thiroids (%)


Gender n
Female (%)
Male (%)
Ectopic sites (%)
Sublingual
Lingual
Mediastinal
Lateral cervical
Along thyroglossal duct
Clinical presentation
Palpable mass
Asymptomatic
Dyspnea
Mediastinal syndrome
Thyroid hormone production (%)
Hypothyroidism
Euthyroidism
Hypertiroidism
Eutopic Thyroid in situ
Yes
No
Hystopatological aspect
Multinodular goiter
Follicular adenoma
Papillary carcinoma

28

0.9%

19
9

on 28
28

68%
32%

3
5
5
6
6

11%
18%
18%
21%
21%

19
6
1
2

68%
21%
4%
7%

4
17
7

14%
61%
25%

24
4

86%
14%

26
1
1

92%
3.50%
3.50%

thyoid in two cases, while in the remaining three cases the main
gland was not found; all patients were already receiving thyroid
hormone (l Tiroxina) for congenital hypothiroidism.
Common symptoms included progressive dysphagia to solid
food; on physical examination a rm, painless, midline mass was
noticed at the base of the tongue. The color ranged from light pink
to bright red, while the surface was smooth or irregular.
Thyroid function tests (including serum levels of T3, T4, TSH and
Tg) were carried out, demonstrating hypothyroidism in four cases
and hyperthyroidism in one.
Radionuclide thyroid imaging using Iodine123 was useful to
evaluate anatomical location and to conrm the thyroid nature of
ectopic tissue in these ve cases.
All patients performed a mass resection. Histopathological examination conrmed the nature of the ectopic lesions and also the
presence of a multinodular goiter in all cases.
3.2. Sublingual ectopic tissue

3. Results
We identied 3361 thyroidectomies performed in the sudy
time-frame. We exclulded 269 patients (262 already exposed to
neck surgical procedures and 7 for previous trauma in this region),
and hence we included 3092 patients in the study. (Table 1).
We observed 28 ETT with different locations: lateral cervical in 6
(21.4%), along the thyroglossal duct in 6 (21.4%), mediastinal in 5
(17.9%), lingual in 5 (17.9%), sublingualin 3 (10.7%), and submandibular in 3 (10.7%). We found ETT in the 0.9% of overall surgical
population.
Only 4 ETT showed normal thyroid tissue, whereas in the
remaining 24 (85.7%) thyroid tissue was affected by nodular
disease.

Three cases, two female and one male, were found (age range
31e48 years). They came to our observation with an history of a
painless midline neck swelling increased slightly in size. On clinical
examination the patients showed a mobile, well circumscribed
mass, palpable in the midline of the neck just over the hyoid bone.
We performed ultrasound scanning for all these patients; it
showed an hypoechoic mass with a peri-vascular lesion.
Endocrinological tests demonstrated euthyroidism in two cases,
while hyperthyroidism in only one case. Scintigraphy conrmed an
ectopic thyroid tissue uptake. In all cases, FNAC showed no malignant cells.
All patients underwent surgical excision of ETT with total
thyroidectomy.
Histopathological examination showed multinodular goiter
both for ectopic tissue and ectopic gland.

3.1. Lingual ectopic tissue


3.3. Submandibular ectopic tissue
We found ve cases of lingual ectopic tissue: four females and
one male, aged between 6 and 45 years. We observed eutopic

In this location three cases were found; one mass located in the

Please cite this article in press as: G. Santangelo, et al., Prevalence, diagnosis and management of ectopic thyroid glands, International Journal of
Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.12.043

G. Santangelo et al. / International Journal of Surgery xxx (2015) 1e6

right submandibular region and two in the left.


Two female with a recent onset of a painless mass in the left side
presented difculty at swallowing; the swelling developed in the
previous eleven and seven mounths. In one of these cases the patient had asymptomatic swelling in the right submandibular region
about eighteen months prior to visit.
Thyroid functional tests were normal in all but one patient, who
had hypertiroidism in the previous month.
Scintigraphy showed thyroid tissue uptake.
FNAC was negative for malignant thyroid cells in two cases,
showing characteristics of follicular lesion in the third.
Surgical excision of the ETT was performed in all these cases,
associated with total thyroidectomy.
Histopathological examination showed ectopic goiter in the rst
two cases, while the third showed a follicular adenoma.
In all three cases, the ETT was affected by multinodular goiter.
3.4. Lateral cervical ectopic tissue
We found six cases (four females and two males, range
39e53years).
Two patients, 45 and 49 years-old female, showed painless mass
on the left of the lateral cervical region, developed two and four
months before respectively.
Four cases (two females and two males) were diagnosed during
an ultrasound pre-operative scanning.
Thyroid functional tests showed hypertiroidism in two cases
and eutiroidism in the other cases.
Scintigraphy showed in all six cases uptake by ectopic tissue.
FNAC of ectopic nodules in 5 cases showed benign characters,
while in one case showed an indeterminate aspect.
Patients underwent ectopic tissue excision, associated with total
thyroidectomy.
The histopathological ndings showed benign features with a
nodular goiter aspect; in fact all six patients presented multinodular goiter.
3.5. Along the tract of the thyroglossal duct
Six cases (three female and three male, range 48e75 years) in
this location were observed.
All patients reported swelling along the tract of the thyroglossal
duct; physical examination revealed a painless, non-tender mass.
Ultrasound revealed multinodular goiter in all cases, showing a
mass not connected to the thyroid gland, with a solid (three cases),
cystic (three cases) or mixed (two cases) echoic patter.
TSH, FT3 and FT4 were normal.
Scintigraphy showed normal uptake for solid and mixed pattern,
while it showed only slight peripheral uptake for the cystic
structure.
FNAC, carried out in cases of cystic nodule, showed benign
features in ve cases (Thy 2 e Bethesda System) and also
compatible aspects with follicular lesion in one mixed nodule (Thy
4 e Bethesda System).
Patients underwent surgical excision of ETT, associated with
total thyroidectomy.
Histopathological examination showed colloidal e cystic goiter
in three cases, and multinodular goiter in the other three cases.
Instead, thyroids histopathology showed micro-multinodular
goiter in all six cases.
3.6. Mediastinal ectopic tissue
We found ve cases in this location (three female and two male,
range 36e51 years).

In four cases, patients showed multinodular aspect of thyroid


gland.
A 36-year-old male (without eutopic thyroid) already received
thyroid hormone (l Tiroxina) for congenital hypothyroidism. He
came to our attention for the onset of dyspnea one year before. A
chest X-ray demonstrated a mediastinal mass.
Thyroid tests were normal.
In this case, Chest CT was performed, showing a mediastinal
encapsulated mass separated from mediastinal viscera which displaced and compressed the trachea, reducing the caliber.
Scintigraphy showed a mass uptake, revealing thyroid origin.
In the remaining four cases, two of these came to our observation for an incidental nding on the chest X-rays (performed for
other reasons). They were asymptomatic.
Two patients showed a mediastinal compression syndrome.
Functional test showed normal levels in two asymptomatic
cases and hypertiroidism in two cases.
The chest CT showed mediastinal mass (an hypodense mediastinal mass in three cases without contrast enhancement, while in
the other cases, in the context of the mass, an area with nodular
contrast enhancement was described).
Scintigraphy showed uptake in all cases.
The patients were subjected to the mediastinal mass excision
through sternotomy, associated to total thyroidectomy (four cases).
Histopathological examination showed multinodular goiter in
four cases (including one case without eutopic gland).
In one case found with a nodue at CT scan histological ndings
reported a micro-macro nodular goiter with a lump of papillary
carcinoma of 1.9 cm.
In these cases a thoracic approach was advocated.
4. Discussion
ETT is a rare clinical entity dened as not located anterolaterally
to the second to fourth tracheal cartilages thyroid tissue [1].
ETT may be found anywhere along the line of the obliterated
thyroglossal duct, usually from the tongue to the diaphragm [2],
even if the midline region is the most common localization.
Ectopic thyroid is uncommon, with a prevalence approximately
of 1 per 100,000e300,000 persons [3]. The true prevalence is
probably underestimated, considering that its clinical prevalence(patients with tyroid disease) varies between 1:4000 and
1:10000.
Although the molecular mechanisms involved in thyroid
dysgenesis are not fully known, studies have shown that mutations
in regulatory genes expressed in the developing thyroid could be
responsible [2,3].
Lingual thyroid is the most frequent ectopic location; it accounts
for approximately 90% of ectopic thyroid cases [4].
In our series the prevalence is 0.9% (28 cases on 3092)
depending on the location: 5 lingual, 3 sublingual, 3 submandibular, 6 lateral cervical, 6 along the thyroglossal duct, 5 mediastinal
ectopies.(Table 2).
Compared with other reports in literature, our work shows a

Table 2 Ectopic thyroid tissue localization.


Localization
Lingual
Sublingual
Lateral cervical
Submandibular
Along thyroglossal duct
Mediastinal
Total

Female
5
3
6
3
6
5
28

4
2
4
3
3
3
19

Male

68%

1
1
2
0
3
2
9

Mean age
23
37
60
44
60
41

32%

Please cite this article in press as: G. Santangelo, et al., Prevalence, diagnosis and management of ectopic thyroid glands, International Journal of
Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.12.043

G. Santangelo et al. / International Journal of Surgery xxx (2015) 1e6

large series of ectopic thyroid tissues, underlying a low prevalence


for lingual location.
ETT can occur at any age [32]. At our Hospital, we have facilities
to operate on patients in the elderly as well as pediatric patients,
even with advanced procedures [33e47]. Concerning age, In our
series, the ageof ETT patients ranged between 6 and 74 years.
We found onset lower age for lingual location (mean age 6
years), while the highest mean age (74 years) was found for the
tract along the thyroglossal duct. (Table 2).
We noticed a predominance of female representation (68%), in
agreement with literature about ectopic thyroid (65e80%).
Malignant transformation is relatively uncommon: the probability of carcinoma arising in such tissue is less than 1%.
ETT may occur both with and without a normally located thyroid gland.
According to literature, only four cases without eutopic gland
were reported, while twenty-four cases of eutopic gland with
multinodular pathology were reported. In our series, only a case of
mediastinal location showed papillary carcinoma of ectopic tissue.
Hypothyroidism occurs in about 33% of patients with ETT [30].
Thyroid function tests assessing T3, T4, TSH and Tg serum levels
were carried out in all cases; they resulted useful in suggesting the
presence of ETT in 4 cases who had no eutopic thyroid.
Euthyroidism state was found in 17 patients (61%).
A plausible reason for the difference of the thyroid function
status, may be the heterogeneous age distribution: hypothyroidism
was in prevalence found in lingual localization (with the lower
mean age) and without an eutopic thyroid.
The majority of patients are generally asymptomatic while some
cases are detected accidentally. Symptoms are usually related to
size and location of the ectopic tissue as well as associated endocrine dysfunctions.
Our series showed common symptoms related to size and locations: in lingual, sublingual or lateral cervical location: swallowing difculty, dysphagia, and growth of a palpable mass in these
regions.
An ultrasound pre operative scanning showed four cases of
lateral cervical locations otherwise unrecognized; in these cases
there was a diagnostic dilemma between an ectopy and a possible
lymphatic metastasis [48], that was solved by FNAC.
Considering the complex anatomic structure of the neck, ETT
located at this site require; CT scans to obtain a detailed picture of

masses relation to the other structures of this region.


In all cases of mediastinal masses, (CT) was performed.
Chest X rays, performed for other reasons, diagnosed two
mediastinal locations; they were asymptomatic.
Radionuclide thyroid imaging with I123 was crucial to conrm a
thyroid nature of these ectopic masses and their location. It showed
also absence or presence of thyroid in its normal location.
In our series we always performed this imaging technique
(specicity 100%).
FNAB is one of the most accurate diagnostic methods for
detection of neck solid masses and gives correct diagnosis in
95e97% of cases about thein nature [49].
In our series FNAC was performed in all cases of neck location,
resulting useful to make a preoperative diagnosis of ectopic thyroid
tissue.
A variety of management methods of the ectopic thyroid tissue
have been reported [49,50].
The appropriate management is necessary depending on several
factors, including size and location of the ectopic thyroid, then the
presence of local symptoms, the status of thyroid function(Charts 1
and 2), and histological ndings.
We emphasize about underestimated prevalence of thyroid
ectopia that is increasing considering clinically evident prevalence.
Our series shows a prevalence of 0.9%.
In our cases, surgical excision associated to total thyroidectomy,
in a state of thyroid in situ was the treatment chosen: thyroidectomy was justied by the frequent nodular diseases related to
ectopia.
In conclusion, ETT consist of a rare disease potentially undergoing the same pathological changes of an eutopic thyroid gland.
Patients with a cervical mass in the anterior midline should be
primarily subjected to history screening, physical examination and
thyroid function examinations.
A careful ultrasound evaluation of all neck regions performed
pre-operatively by surgeons was suggested to prevent
misdiagnosis.
Radionuclide thyroid imaging with I123 is crucial to conrm
thyroid nature of ectopic tissue and its location.
It can also document absence or presence of thyroid in its
normal location.
FNAC performed for submandibolar and neck locations is useful
to make a preoperative diagnosis of ETT.

Neck or other localizaons

Ultrasonography

I123 scingraphy

thyroid ssue
uptake

Thyroid origin

No thyroid ssue
uptake

Ectopic thyroid
ssue
Surgery
Metastasis

Fine need aspiraon biopsy (fnab)+


thyroglobuline dosage

Thyroid origin

Fig. 1. Ectopic Thyroid Tissue with eutopic thyroid in situ (nodular disease affected).

Please cite this article in press as: G. Santangelo, et al., Prevalence, diagnosis and management of ectopic thyroid glands, International Journal of
Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.12.043

G. Santangelo et al. / International Journal of Surgery xxx (2015) 1e6

Thyroglobuline dosage

Endocrinological
evaluaon

undetectable

Hypothyroidism

detectable

Hyper/eu
thyroidism

Ectopic thyroid
ssue

Thioid agenesis

I123
shingraphy
thyroid hormone
(l Tiroxina)

Ultrasonography
RMN

Surgery
Thyroid hormone suppressive therapy

Localizaon

Fig. 2. Absency of eutopic thyroid.

These are certainly the correct standards for a denitive diagnosis. Surgical excision of ectopic thyroid is recommended, along
with total thyroidectomy, if affected by nodular disease (Charts 1
and 2).
Ethical approval
Ethical approval was requested and obtained from the Second
University of Naples ethical committee.
Funding
All Authors have no source of funding.
Author contribution
Giuseppe Santangelo: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data; also partecipated substantially in the drafting and
editing of the manuscript.
Gianluca Pellino: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data; also partecipated substantially in the drafting and
editing of the manuscript.
Nadia De Falco: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data.
Giuseppe Colella: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data.
Salvatore D'Amato: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data.
M. Grazia Maglione: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data.
Roberto De Luca: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data.
Silvestro Canonico: Partecipated substantially in conception,

design, and execution of the study and in the analysis and interpretation of data; also partecipated substantially in the drafting and
editing of the manuscript.
Massimo De Falco: Partecipated substantially in conception,
design, and execution of the study and in the analysis and interpretation of data; also partecipated substantially in the drafting and
editing of the manuscript.
Conicts of interest
All Authors have no conict of interests.
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Please cite this article in press as: G. Santangelo, et al., Prevalence, diagnosis and management of ectopic thyroid glands, International Journal of
Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.12.043