388 Azañero et al.

Case Report
Clinical Pathology

Lingual cyst with respiratory W. D. Azañero1, R. Mazzonetto2,

J. E. León3, P. A. Vargas3,
M. A. Lopes3, O. P. de Almeida3

epithelium: a histopathological
1
Department of Oral Medicine, Oral Surgery
and Oral Pathology, Faculty of Stomatology,
University Cayetano Heredia, 430, Lima,
Perú; 2Department of Maxillofacial Surgery,

and immunohistochemical University of Campinas, Piracicaba-

UNICAMP, Av. Limeira 901, Caixa Postal 52,
CEP: 13414-903, Piracicaba-SP, Brazil;
3

analysis of two cases

Department of Oral Pathology, Dental
School, University of Campinas, Piracicaba-
UNICAMP, Av. Limeira 901, Caixa Postal 52,
CEP: 13414-903, Piracicaba-SP, Brazil

W. D. Azañero, R. Mazzonetto, J. E. León, P. A. Vargas, M. A. Lopes, O. P. de

Almeida: Lingual cyst with respiratory epithelium: a histopathological and
immunohistochemical analysis of two cases. Int. J. Oral Maxillofac. Surg. 2009; 38:
388–392. # 2009 International Association of Oral and Maxillofacial Surgeons.
Published by Elsevier Ltd. All rights reserved.

Abstract. Cysts of the tongue are rare, usually derived from epithelia of the embryonic
gastrointestinal and respiratory tracts, and classified according to the predominant
epithelium lining. These cysts are usually discovered during infancy, more
frequently in males, but they may not appear until well into adulthood. The authors
report two lingual cysts lined mainly with respiratory, and focally by squamous,
epithelium. Periodic acid-Schiff and mucicarmine staining revealed focal positivity
in intracystic mucoid material and goblet cells. Immunohistochemical analysis with
vimentin, cytokeratins (AE1/AE3, 34bE12, CK1, CK5, CK6, CK7, CK8, CK10,
CK13, CK14, CK16, CK18, and CK19), E-cadherin, b-catenin, and epithelial
Keywords: oral development cyst; lingual cyst;
membrane antigen showed a similar profile of normal respiratory epithelium, respiratory epithelium; immunohistochemistry.
suggesting well-differentiated states. Owing to their controversial origin, these cysts
should be named descriptively, as suggested by Manor et al., as lingual cysts with Accepted for publication 19 January 2009
respiratory epithelium. Available online 13 February 2009

Cysts of the tongue are rare, with variable
histology and usually of uncertain origin.
Various developmental cysts, such as epi-
dermoid, dermoid, lymphoepithelial, and
thyroglossal duct, have been described in
the tongue. The most common, although
only 89 cases have been described in the
English language literature, are lined pre-
dominantly with gastrointestinal, respira-
tory, squamous or cuboidal
epithelium2,11,12,16,20,21. These cysts may
be derived from epithelia of the upper
gastrorespiratory tract. The nomenclature
is confused and debatable, but according
to MANOR et al.12 they should be named
descriptively, as lingual cysts lined by
gastrointestinal and/or respiratory epithe-
lium. Few studies have evaluated the
immunohistochemical (IHC) profile of
developmental lingual cysts, which can
be useful to understand their origin and
to develop a more objective classifica-
tion4,22. The purpose of this article is to
describe the clinicopathological and IHC
features of two cases of lingual cysts lined
by respiratory epithelium.
Case reports
Case 1
A 4-year-old Caucasian boy was referred
because of a blue swelling on the tongue
that had been present since his birth.
According to his mother, the lesion had
gradually increased in size, and had made
breast-feeding difficult. The child did not
have other anomalies on physical exam-
ination, and his medical history was non-
contributory. Intraoral examination
showed a mobile, well-delimited, painless,
submucous soft nodular lesion measuring
1.5  1.5 cm, located in the right ventral
surface of the tongue, covered by normal
mucosa (Fig. 1a). The clinical diagnosis
included congenital mucous retention
cyst, lymphatic/blood vessels malforma-
tion, and developmental cyst. Material
obtained from a fine needle aspiration
(FNA), consisted of a viscous, transparent
and yellowish liquid. The cytological eva-
luation after periodic acid-Schiff (PAS)
and Diff-quick staining, demonstrated a
hemorrhagic, mucous background, few

Fig. 1. Clinical and microscopic aspects of the lingual cyst with respiratory epithelium in a 4-year-old boy. (a) Clinical appearance of the nodular
lesion affecting the ventral surface of the tongue. (b) Gross examination of the specimen. The cyst was enucleated in one piece. (c) Ciliated
pseudostratified respiratory epithelium delimiting the lumen cyst (H&E, OM X40).
lymphocytes and macrophages associated
with scarce anucleated and nucleated
epithelial cells. According to the clinical
picture and FNA findings, a suggestive
diagnosis of mucocele or retention
mucous cyst was considered. Considering
the patient’s age and possible diagnosis, a
marsupialization was performed. The
lesion persisted and a definitive surgical
removal was performed under general
anesthesia. Gross examination of the spe-
cimen showed a monolocular cystic cav-
ity, measuring 2.5  1.5  1.0 cm
(Fig. 1b). Microscopically, the capsule
was formed by a thick, uniform, edema-
tous connective tissue stroma, which dis-
played mild mononuclear inflammatory
infiltrates. The lining was predominantly
formed by ciliated pseudostratified colum-
nar respiratory epithelium, with scarce
goblet cells and foci of squamous epithe-
lium (Fig. 1c). PAS and mucicarmine
staining revealed focal positivity in both
intracystic mucoid material and goblet
cells. The final diagnosis was a lingual
cyst lined by respiratory and squamous
epithelium. After 3 years of follow-up
the tongue is normal, with no signs of
recurrence.
Case 2
A 21-year-old Peruvian man was referred
displaying an asymptomatic nodule on the
dorsum of the tongue. The patient had had
Thanks very much for the positive words
the lesion for about 10 years and it had
gradually increased in size. He was having
difficulty eating and talking. Otherwise, he
was well and his medical history was
noncontributory. Intraoral examination
showed a mobile, painless, submucous
nodular lesion of cystic consistency, mea-
suring 4.0 cm in diameter. It was located
in the anterior middle third of the dorsum
of the tongue, covered by normal mucosa
(Fig. 2a). An FNA was performed and
8 ml of brown, viscous fluid was obtained.
The cytological evaluation with Papani-
colau and PAS stain demonstrated a
mucous background, with scarce lympho-
cytes and nucleated epithelial cells. The
clinical picture and the cytological find-
ings suggested a cystic lesion. Under gen-
eral anesthesia the well-encapsulated cyst
was removed, preserving the adjacent
muscle tissue. The surgical specimen con-
tained a viscous, brown liquid; the wall
was smooth and measured 3.0 cm in dia-
meter (Fig. 2b). Histopathological exam-
ination showed a cyst lined by ciliated
pseudostratified columnar respiratory
epithelium, with numerous goblet cells
and focal areas of squamous epithelium.
The cyst wall was composed of fibrous
connective tissue. In the lumen of the cyst,
mucoid material and cellular debris were
identified (Fig. 2c). There were two small
areas of ulceration, which displayed adja-
cent granulation tissue. PAS and mucicar-
mine staining revealed positivity in the
389
goblet cells, but the intracystic mucoid
material was positive only for PAS. The
final diagnosis was of a lingual cyst lined
by respiratory and squamous epithelium.
The postoperative course was uneventful,
and after 2 years of follow-up the tongue is
normal in appearance and function.
A large panel of antibodies was used
for IHC evaluation (Table 1). Pan-cyto-
keratin (CK) AE1/AE3, CK19, E-cad-
herin, and b-catenin demonstrated
uniform positivity in all cystic epithe-
lium (Fig. 3a and b). CK7, CK8, and
CK18 marked the suprabasal layers,
while CK5, CK14 and 34bE12 marked
the basal layer of the ciliated pseudos-
tratified epithelium (Fig. 3c and d). CK7
and CK13 marked the suprabasal layers
and CK5, CK14 and 34bE12 marked all
layers of the squamous epithelium.
Epithelial membrane antigen (EMA)
marked all suprabasal layers of both
epithelium types (Table 2).
Discussion
The origin of oral development cysts con-
taining respiratory and/or gastrointestinal
epithelium is not known. They may arise
from islands of endoderm that originate
from the lining of the primitive stomo-
deum, and become entrapped in the mouth
during the fourth to fifth week of embryo-
nic development, a time at which the
390 Azañero et al.

Fig. 2. Clinical and microscopic aspects of the lingual cyst with respiratory epithelium in a 21-year-old man. (a) Clinical appearance of the
nodular lesion affecting the dorsal surface of the tongue. (b) The removed lingual cyst had smooth borders and contained a viscous, brown liquid.
(c) Cystic lesion showing ciliated pseudostratified respiratory epithelium. Note the proximity of the epithelial surface of the tongue (H&E, OM
X10).

entire gastrointestinal endoderm is undif- embryonic tracheoesophageal septum trointestinal) are of endodermal origin, it
ferentiated. The foregut contains compo- can lead to the formation of a ciliated cyst is conceivable that primitive uncommitted
nents of the endoderm and mesoderm that of foregut origin in relation to the tracheo- endoderm could differentiate in a multi-
lead to the development of the trachea, bronchial tree, mediastinum, liver, pan- directional manner5,16,21.
bronchi, esophagus, liver, stomach and creas, tongue, and upper digestive tract7. MANOR et al.12 reviewed 53 lingual cysts
intestine. Abnormal budding off of the Since both epithelia (respiratory and gas- reported in the English language literature
between 1942 and 1997 and added a single
Table 1. Antibodies used for immunohistochemical evaluation of lingual cyst with respiratory case of their own. Searching up to March
epithelium. 2008, the authors found 35 additional
Antibody Source/Clone Dilution cases. The terminology used in the litera-
* ture for cysts of the tongue is confusing,
CK-cocktail Dako1 , AE1/AE3 1:500
CK-high molecular weight Dako1*, 34bE12 1:200 because usually the possible origin is con-
CK1 Novocastra1#, 34bB4 1:200 sidered. MANOR et al.12 suggested descrip-
CK5 Novocastra1#, XM26 1:400 tive terms, including the type of
CK6 Novocastra1#, LHK6B 1:200 epithelium lining. Until further informa-
CK7 Dako1*, OV-TL12/30 1:400 tion is accumulated, these descriptive
CK8 Dako1*, 35bH11 1:200 terms seem to be practical and accordingly
CK10 Dako1*, DE-K-10 1:200 the present cases were diagnosed as lin-
CK13 Novocastra1#, KS-1A3 1:400 gual cysts lined by respiratory epithelium.
CK14 Novocastra1#, NCL-L-LL002 1:200 These cysts are rare, and less frequent
CK16 Novocastra1#, LL025 1:200
CK18 Dako1*, DC10 1:400
than those with gastrointestinal character-
CK19 Dako1*, RCK 108 1:200 istics. According to MANOR et al.,12 of 52
EMA Dako1*, E29 1:400 reported cases, 12 were lined mainly by
b-catenin Novocastra1#, 17C2 1:100 respiratory epithelium, 25 by gastrointest-
E-cadherin Dako1*, NCH-38 4 1:200 inal epithelium and 15 were mixed. Apart
Vimentin Dako1*, Vim 3B4 1:400 from the cystic lining, other characteristics
CK, cytokeratin; EMA, epithelial membrane antigen. were similar. Most of the patients are
* children, with the age ranging from new-
Dako A/S, Glostrup, Denmark.
#
Novocastra Laboratories Ltda, Newcastle, England. born to 42 years (mean age 5.5 years).
 Thanks very much for the positive words 391

Fig. 3. Immunohistochemical findings from the lingual cyst with respiratory epithelium. (a) CK19 expression in the cystic epithelium. Note that
the luminal cells were strongly marked (IHC, OM X20). (b) Uniform positivity in all cystic epithelium for b-catenin (IHC, OM X40). (c) CK5
marked the basal layer of the ciliated pseudostratified epithelium (IHC, OM X40). (d) The luminal cells expressed CK7, while the basal cells were
negative (IHC, OM X40).

There is a slight predilection for males
(1.6:1), affecting predominantly the ante-
rior two-thirds of the tongue. Most cases
are asymptomatic, but depending on size,
the patient can have feeding/swallowing
and respiratory difficulties. The authors’
first patient was 4 and the second 21 years
old. Both cases affected the anterior region
of the tongue, one was 1.5 cm (case 1) and
the other 4.0 cm (case 2) in diameter. The
first patient was a 4-year-old child, and his
mother reported he had eating difficulty.
The second cyst was larger, but the patient
was a young adult, and he reported only
slight discomfort. Cystic lesions are
known to grow with time.
The differential diagnosis of cystic lesion
in the tongue include lymphoepithelial
cyst, lingual thyroid, thyroglossal duct cyst,
epidermoid cyst, dermoid cyst, mucocele,
mucous retention cyst, cystic hygroma and
hemangioma8,10,13,15,18. Lymphoepithelial
cysts are lined by surface or salivary gland
epithelium, showing characteristic lym-
phoid aggregates. Lingual thyroids and
intralingual thyroglossal duct cysts involve
the posterior third of the tongue and they
can occlude the oropharyngeal airway in
neonates. The latter is lined by respiratory
epithelium and usually ectopic thyroid tis-
sue is present in the cyst wall6,9. Histolo-
gically, dermoid cysts of the floor of the
mouth are classified according to Meyer’s
classification into 3 histologic varieties:
dermoid, epidermoid, and teratoid. The
dermoid cyst is an epithelial-lined cavity
that shows skin appendages in the wall of
the cyst. The epidermoid cyst has no skin
appendages, whereas the lining of the ter-
atoid cyst ranges from simple squamous to
ciliated respiratory epithelium and contains
derivatives of ectoderm, mesoderm, and/or
endoderm14. Dermoid cysts appear mainly
in those 15–35 years of age1. SHEN et al.22
reported 31 cases of oral teratoid cysts; 24
of which were congenital. The affected
sites were the floor of the mouth (22 cases)
and tongue (8 cases).
FNA is a safe method for detecting
cystic, non-cystic or vascular lesions,
and it is important to help to establish
the correct diagnosis. In both cases
described here, it was possible to deter-
mine that the lesions were cystic by FNA,
but it was not possible to determine if they
were mucoceles, mucous retention cysts
or developmental cysts, which was con-
firmed histologically. Although image
evaluation, particularly magnetic reso-
nance imaging (MRI), is useful for assess-
ment, it was not performed in these cases.
VOLCHOK et al.23 reported the case of a
61-year-old man who presented with a

Table 2. Immunohistochemical findings of lingual cyst with respiratory epithelium.

AE1/3 34bE12 CK13 CK5/14 CK7 CK19 CK8/18 E-cad b-cat EMA Others*
Epithelium
Respiratory + +a +a +b + +b + + +b
Squamous + + +b + +b + + + +b
a
Only basal layer.
b
Only suprabasal layers.
*
vimentin, CK1, CK4, CK6, CK10, and CK16; E-cad: E-cadherin; b-cat: b-catenin; EMA: epithelial membrane antigen.
392 Azañero et al.
cystic lingual mass that microscopically
was lined by ciliated respiratory epithe-
lium with invasive, moderately differen-
tiated adenocarcinoma involving the cyst
wall. Malignancy arising in cysts with
respiratory and/or gastrointestinal epithe-
lium in other areas of the body has been
reported; however, this seems to be the
first report of adenocarcinoma arising in a
lingual cyst with respiratory epithelium.
The possibility of malignancy within these
cysts, especially in adult patients, should
be considered.
Surgical excision is the treatment of
choice for these lesions. The approach
to resection is based on accessibility to
the mass, size, and concern for postopera-
tive airway obstruction secondary to lin-
gual swelling19. Both the authors’ patients
received general anesthesia and there were
no post-surgical disturbances or recur-
rences.
In normal pseudostratified respiratory
epithelium, CK5 and CK14 are found in
the basal cells; CK7, CK8, CK18 are
localized primarily in cells at the luminal
surface, while CK19 is expressed in both
basal and suprabasal cells. b-catenin, E-
cadherin, and EMA are homogeneously
expressed. In non-keratinizing stratified
squamous epithelia, normally CK4,
CK13, and CK14 are expressed. CK20
is practically absent in these epithelium
types3,17. There is little information about
the immunoprofile of lingual cysts lined
with respiratory and/or gastrointestinal
epithelium. CORIC et al.4 described the
IHC features in a case of congenital oral
cyst, which presented squamous, intest-
inal, and respiratory epithelia. The squa-
mous epithelium was positive for AE1/
AE3, CK7 and CK19. The intestinal and
ciliated epithelia expressed AE1/AE3,
CK7, CK8 and CK19. CK20, carcinoem-
bryonic antigen (CEA) and chromogranin
were negative. SHEN et al.22 studying 31
cases of oral teratoid cyst showed that the
expression of AE1, CK7, CK8/18, and
CK19 varied in superficial, suprabasal
and basal cells of squamous epithelium
but was strong in respiratory, gastrointest-
inal and simple columnar epithelium; only
gastrointestinal epithelium expressed
CK20 heterogeneously. They concluded
that these various types of epithelia
showed the same CK expression seen in
their normal counterpart, similar to the
present findings (Table 2).
In conclusion, the authors presented two
new cases of lingual cyst with respiratory
epithelium, and reinforced the idea that a
descriptive term for cysts is preferable, as
suggested by MANOR et al.12 The IHC pro-
file corresponds to similar normal respira-
tory and squamous epithelium. Surgery is
the best treatment, and usually there are no
recurrences or tongue dysfunction. The
pathogenesis of these cysts is uncertain,
but entrapment of epithelia from the foregut
is the main hypothesis considered.
Acknowledgements. The authors thank Ana
Cristina do Amaral Godoy for immuno-
histochemistry assistance.
Supported by: The State of São Paulo
Research Foundation (FAPESP).
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Corresponding author
Address:
Wilson Delgado Azañero
Department of Oral Medicine
Oral Surgery and Oral Pathology
Faculty of Stomatology
University Cayetano Heredia
Av. Honorio Delgado
430. Lima
Perú
Tel.: +51 1 381 1940
fax: +51 1 381 1940
E-mail: jorgeesquiche@yahoo.com.br
doi:10.1016/j.ijom.2009.01.003