Endocr Pathol
DOI 10.1007/s12022-015-9354-y
Pathology of Thyroglossal Duct: an Institutional Experience
Shuanzeng Wei & Virginia A. LiVolsi & Zubair W. Baloch
# Springer Science+Business Media New York 2015
Abstract Thyroglossal duct (TGD) is a developmental anom-
aly in which a remnant of the thyroid anlage is left in the neck
during its descent from the foramen cecum of tongue to final
pretracheal position. A persistent duct can lead to thyroglossal
duct cyst (TGDC). Histologically, TGDC contains an epithe-
lial lining of squamous or pseudostratified ciliated columnar
epithelium and ectopic thyroid gland tissue in the duct wall.
TGD-associated malignancy is rare, and the majority is papil-
lary thyroid carcinoma (PTC). A total of 242 patients with a
diagnosis of TGD-associated lesions were identified in our
institute. Two hundred and seventeen cases were diagnosed
as TGDC. Sixty-eight of 217 (31.3 %) cases of TGDC had
ectopic thyroid tissue in the cystic wall. Thirty-nine cases had
preoperative fine needle aspiration (FNA). Of these cases, 37
of 39 (94.9 %) demonstrated macrophages and 19 (48.7 %)
also showed cells of squamous and/or columnar epithelial
lining. Only two cases showed rare thyroid follicular cells.
Thyroid carcinoma was identified in 18 of 242 (7.4 %) cases.
All cases were diagnosed as PTC including 12 cases of classic
PTC (66.7 %), 3 cases of follicular variant (16.7 %), 2 cases of
tall cell variant (11.1 %), and 1 case of classic PTC with focal
tall cell features (5.6 %). Nine cases had TGD component
(either epithelial lining cysts or ectopic thyroid tissue). Ten
patients also underwent total thyroidectomy (67 %). Of these
patients, four had no tumor and one had an incidental medul-
lary carcinoma. Five of 10 (50 %) cases had incidental PTC
S. Wei (*) : V. A. LiVolsi : Z. W. Baloch
Department of Pathology and Laboratory Medicine, Hospital of the
University of Pennsylvania, 3400 Spruce Street,
Philadelphia, PA 19104, USA
e-mail: weishuanzeng@hotmail.com
V. A. LiVolsi
e-mail: linus@mail.med.upenn.edu
Z. W. Baloch
e-mail: baloch@mail.med.upenn.edu
with a size range of 0.10.3 cm. Five patients had follow-up
by imaging studies; no suspicious or nodular lesions were
found in the thyroid. In conclusion, we report an institutional
case cohort of 242 patients with TGD-associated lesions, in-
cluding 217 TGDC and 18 cases of PTC. Only seven cases
fulfilled the diagnostic criteria of TGD-associated PTC, i.e.,
the presence of components of TGD and a normal thyroid. In
the remaining 11 cases, we could not differentiate with cer-
tainty between pyramidal primary thyroid PTC/Delphian node
metastasis or TGD-associated PTC.
Keywords Thyroglossal duct . Thyroglossal duct cyst .
Papillary thyroid carcinoma
Introduction
Thyroglossal duct (TGD) is a developmental anomaly in
which a remnant of the thyroid anlage is left in the neck during
its descent from the foramen cecum of tongue to final
pretracheal position [13]. A failure of thyroglossal duct in-
volution is estimated to occur in 7 % of the adult population
[3]. A persistent duct can lead to a cervical cyst, i.e.,
thyroglossal duct cyst (TGDC), the most common congenital
abnormality in the neck [3, 4]. The TGDC commonly presents
as painless lesions located in the midline of the neck. Indica-
tions for excision include cosmetic reason, recurrent infec-
tions, sinus or fistula formation, and malignancy [3]. The sur-
gical management is carried out by performing the Sistrunk
procedure; this includes excision of the duct to the base
of the tongue and removal of the medial portion of the
hyoid bone [4].
Histologically, thyroglossal duct cysts contain an epithelial
lining of squamous or pseudostratified ciliated columnar epi-
thelium and ectopic thyroid gland tissue; the latter is usually
found in the duct wall [3]. Malignant changes in a TGD are

rare. To date, approximately 260 cases of TGD-associated
carcinoma have been published in the literature; either as
single-case reports or small case series [5, 6]. Papillary thyroid
carcinoma (PTC) is the most common malignancy arising in
TGD followed by squamous cell carcinoma [57].
Two anatomic caveats need to be considered before
rendering a diagnosis of TGD-associated PTC: (1) Ap-
proximately half of thyroid glands exhibit a pyramidal
lobe [810], which is the remnant of the inferior portion
of the TGD. The pyramidal lobe extends superiorly from
the isthmus and may be attached to the hyoid bone by
fibrous tissue [8]. (2) Delphian node is a midline
prelaryngeal lymph node located anterior to the
cricothyroid membrane and superior to the isthmus, which
is the most common sites of lymph node metastasis in
PTC [11]. Since metastatic thyroid papillary carcinoma
can often present as a cystic lesion [12], a carcinomatous
cyst located at the midline of neck is not always a TGD-
associated PTC. Both pyramidal lobe PTC and Delphian
node metastasis indicate thyroid carcinoma arising in the
thyroid gland, which is treated differently compared to
TGD-associated PTC.
In this study, we report the clinicopathological characteris-
tic of TGD lesions treated at our institution.
Materials and Methods
A total of 242 patients with a history of TGD lesions were
identified retrospectively in the electronic pathology database
of the University of Pennsylvania Health System (1989 to
2014). A retrospective medical record review was performed
to collect clinical information. This study was approved by the
University of Pennsylvania Institutional Review Board. Eight
patients were referred to the Hospital of the University of
Pennsylvania after the diagnoses were made at the outside
institution, and the outside surgical pathology slides were
reviewed.
PTC with a size less or equal to 10 mm was classified as a
papillary thyroid microcarcinoma (PTMC). Tall cell variant of
PTC was diagnosed when the tumor was composed of more
than or equal to 50 % tall cells [13].
Statistic software SPSS (SPSS, Inc., Chicago, IL) was used
for statistical analysis. MannWhitney U test was performed
for analysis of patients age. A p value of <0.05 was consid-
ered to be statistically significant.
Results
The case cohort included 242 patients with a diagnosis of
TGD-associated lesions. Two hundred and seventeen
cases were diagnosed as TGDC when patients presented
Endocr Pathol
with midline cervical cysts with histologically confirmed
squamous or columnar epithelial lining (Fig. 1a, b). Inci-
dental TGD remnant was found in seven patients who had
neck surgery for disease other than TGD-associated le-
sions. Of 224 patients, 116 (51.8 %) were female and
108 (48.2 %) were male. The mean age at diagnosis for
all patients was 44.2 15.5 years (range = 1579 years),
among which female was 43.1 15.2 years (range = 19
78 years) compared to 45.415.8 years of male (range=
1579 years). There was no statistical significance (p=
0.2499). Sixty-eight of 217 (31.3 %) cases of TGDC
had ectopic thyroid tissue in the cystic wall. Grossly, the
cysts measured from 0.2 to 7.0 cm (median = 2.0 cm).
Thirty-nine cases had preoperative fine needle aspiration
(FNA). Of these cases, 37 of 39 (94.9 %) demonstrated
macrophages and 19 (48.7 %) also showed cells of squa-
mous and/or columnar epithelial lining. Only two cases
showed rare thyroid follicular cells.
Thyroid carcinoma was identified in 18 cases of 242
(7.4 %). Of 18 patients, 13 (72.2 %) were female and 5
(27.8 %) were male, with a female/male ratio of 2.6:1. An
ultrasound-guided FNA was performed in four patients.
Three of them showed PTC, and one was consistent with
TGDC. All cases were diagnosed as PTC including 12
cases of classic PTC (66.7 %), 3 cases of follicular variant
(16.7 %), 2 cases of tall cell variant (11.1 %), and 1 case
of classic PTC with focal tall cell features (5.6 %)
(Table 1). Tumor size ranged from 0.3 to 3.5 cm, includ-
ing nine cases of PTMC. Lymph node metastases were
found in four (22.2 %) cases.
The criteria for TGD-associated PTC include evidence
of thyroglossal duct components and a normal thyroid
gland [7, 14]. In the current series, nine cases had either
epithelial lining cysts or ectopic thyroid tissue. Ten pa-
tients also underwent total thyroidectomy (67 %). Of
these patients, four had no tumor and one patient had
an incidental medullary carcinoma measuring 0.3 cm.
Five of 10 (50 %) patients had incidental PTMC with a
size range of 0.10.3 cm. Five patients had follow-up by
imaging studies; no suspicious or nodular lesions were
found in the thyroid.
Two patients had a history of irradiation therapy. One
of them received head and neck irradiation therapy for
acne more than 50 years ago, and another one received
radioactive iodine (RAI) for PTC arising in the thyroid
gland 26 years ago.
Postoperatively, three patients received RAI ablation
and four underwent T4 suppression therapy. One patient
received combined RAI and T4 suppression therapy.
Thirteen patients had follow-up with a mean period of
72 months (range from 2 to 216 months); only one PTC
recurred as lymph node metastasis 14 years after the
thyroidectomy.
Endocr Pathol

Fig. 1 a Thyroglossal duct cyst is

lined with squamous and
pseudostratified ciliated columnar
epithelium, and the thyroid tissue
is noted in the cystic wall. b High
power of a showing
pseudostratified ciliated columnar
epithelium, lymphocytic
infiltration, and inactive thyroid
tissue. c Classic PTC with
edematous papillary stroma in a
cyst. d PTC (left lower) and
adjacent ectopic thyroid tissue
(upper) embedded in fibrotic
cystic wall

Discussion cuboidal epithelium [15]. The literature indicates that between

5 and 62 % TGD lesions contain ectopic thyroid tissue, and
The thyroglossal duct is lined by stratified squamous epithe- the percentage varies depending on how thoroughly the issue
lium, pseudostratified ciliated epithelium, or stratified surrounding the lesion is examined [7]. In this study, 31 % of

Table 1 Patient clinicopathological characteristics

Case number Sex Age/years Diagnosis Size (cm) LN met TGD Thyroid FNA Treatment

1 F 11 PTC n/a No No n/a No No

2 F 21 PTC 1 No Yes N/thy No LT4
3 F 22 PTC T 1 No No 0.1 cm PTC F No RAI
4 F 25 PTC F n/a Yes Yes N/thy No RAI
5 F 25 PTC F 1.4 No Yes N/thy No No
6 F 27 PTC 1 No Yes N/image No LT4
7 F 27 PTC 0.7 No Yes N/image No No
8 F 29 PTC 0.9 No Yes N/image TGDC LT4
9 F 39 PTC 0.8 No No N/image No LT4
10 F 43 PTC 0.7 No No 0.3 cm PTC F PTC No
11 F 51 PTC 0.7 No No PTC 26 yearsb PTC No
12 F 55 PTCa 3.5 Yes No 0.3 cmc PTC RAI
13 F 74 PTC F 1.6 No No 0.1 cm PTC No No
14 M 21 PTC 0.3 No Yes n/a No No
15 M 21 PTC n/a No Yes n/a No No
16 M 29 PTC n/a Yes Yes N/thy No No
17 M 43 PTC 3.1 Yes No 0.3 cm PTC No No
18 M 52 PTC T n/a No No N/image No RAI/LT4

LN met lymph node metastasis, TGD components of TGD, PTC T tall cell variant PTC, PTC F follicular variant PTC, N/image no tumor by imaging
studies, N/thy negative by thyroidectomy, LT4 levothyroxine, RAI radioactive iodine, n/a not available
a
PTC with tall cell features
b
PTC-thyroidectomy 26 years ago
c
Medullary carcinoma

TGDC patients had normal-looking thyroid tissue in the fi-
brous wall of the cyst.
The FNA specimen of TGDC typically consists of cystic
fluid containing macrophages, neutrophils, and scant epitheli-
al cells in a mucoid or proteinaceous background. Squamous
cells are the most frequent epithelial cells seen, and ciliated
columnar cells are occasionally found [16]. In this study, most
cases (94.9 %) which underwent preoperative FNA showed
macrophages and 19 (48.7 %) showed cells of epithelial lin-
ing. Only two cases showed rare thyroid follicular cells; this is
not surprising, as the scattered ectopic thyroid tissue is located
in the fibrotic cystic wall and hence not easily accessed by the
needle.
Papillary thyroid carcinoma can arise from the ectopic thy-
roid tissue and comprises the majority of TGD-associated car-
cinomas. Squamous cell carcinoma constitutes approximately
5 % of TGDC carcinomas; these apparently are derived from
the actual cyst lining. Patients with TGDC-associated squa-
mous cell carcinoma tend to have worst prognosis [17].
Not all cervical midline PTCs are TGD-associated PTC.
Distinguishing TGD-associated PTC from either primary py-
ramidal thyroid lobe PTC or Delphian node metastasis is im-
portant for staging and treatment. Approximately half of thy-
roid glands exhibit a pyramidal lobe [810]; this extends su-
periorly from the isthmus and can be attached to the hyoid
bone by fibrous tissue [8]. The mean length of the pyramidal
lobe was reported to be 24.1 mm with 51.6 % of the lobes
exceeding 20 mm [10]. Additionally, thyroid follicle cells in
the pyramidal lobe are usually not active, leading to unreliable
identification of this accessory structure by scintigraphic im-
aging [10]. Thus, PTC arising in a pyramidal lobe could be
misinterpreted as TGD-associated carcinoma.
Within the thyroid gland, there is an intricate lymphatic
network which permeates the gland, encircles the follicles,
and connects the two lateral lobes through the isthmus [18].
Thus, primary thyroid carcinoma has the potential to metasta-
size through the intrathyroidal lymphatics within the thyroid
rather than into ectopic thyroid tissue. Frequently, metastatic
PTC in lymph node is cystic [12]. Therefore, a TGDC-
associated PTC should be carefully examined to exclude Del-
phian node metastasis.
It is recommended that only the cases with evidence of a
thyroglossal duct remnant and a normal thyroid gland should
be diagnosed as TGD-associated carcinoma [7, 14]. In this
study, nine cases had squamous/columnar epithelium lining
cysts and/or ectopic thyroid tissue in the cystic wall. Ten pa-
tients received total thyroidectomy, of which five showed in-
cidental PTMC with a size from 0.1 to 0.3 cm; three of these
PTMC were morphologically different from the TGD-
associated PTC.
Although the originally proposed therapeutic criteria re-
quired a thyroidectomy, high sensitive imaging techniques
present a good alternative to evaluate the thyroid and thus
Endocr Pathol
avoid unnecessary thyroid surgery. In our series, five patients
had follow-up imaging for 617 years (mean=10 years) and
no suspicious nodular lesions were identified in the thyroid.
The TGD-associated PTC, in the presence of a clinically
and radiologically normal thyroid gland, can be managed ad-
equately by performing the Sistrunk procedure. However, pa-
tients with advanced disease may require aggressive manage-
ment in addition to the Sistrunk procedure, including a total
thyroidectomy with or without neck dissection, followed by
radioactive iodine therapy and thyroid-stimulating hormone
suppression [19, 20].
Choi et al. [5] analyzed 163 cases of TGDC carcinoma
reported from 1990 to 2012. They found that 36 % had con-
comitant PTC in the thyroid. Among the 52 patients who
received neck dissection, 69 % had cervical nodal involve-
ment and 16 (10 %) had recurrence. In this series, four patients
developed lung metastasis and two died of the disease [5]. In
the current study, five patients (50 %) showed incidental
PTMC measuring 0.10.3 cm within the thyroid gland and
four (22.2 %) showed lymph node metastasis. Tumor recur-
rence was noted in lymph node in only one patient 14 years
after the thyroidectomy.
Conclusions
We report an institutional case cohort of 242 patients with
TGD-associated lesions, including 217 TGDC and 18 cases
of PTC. Only seven cases fulfilled the diagnostic criteria of
TGD-associated PTC. In the remaining 11 cases, we could not
differentiate with certainty between pyramidal primary thy-
roid PTC/Delphian node metastasis or TGD-associated PTC.
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