International Journal of Pediatric Otorhinolaryngology Extra
Volume 4, Issue 1 , Pages 36-41, January 2009

Lingual cyst with gastric epithelium: A clinicopathological and immunohistochemical analysis

  • Román Carlos-Bregni

      Affiliations

    • Centro Clínico de Cabeza y Cuello, 6 ave. 7-39 zona 10, ed. Las Brisas of. 501, Ciudad de Guatemala, Guatemala 01010
    • Corresponding Author InformationCorresponding author. Tel.: +502 2363 0769/70; fax: +502 2337 0705.
    • ,
  • Elisa C. Vidaurre

      Affiliations

    • Centro Clínico de Cabeza y Cuello, 6 ave. 7-39 zona 10, ed. Las Brisas of. 501, Ciudad de Guatemala, Guatemala 01010
    • ,
  • Pablo A. Vargas

      Affiliations

    • Department of Oral Pathology, Dental School, University of Campinas, Piracicaba-UNICAMP, Avenue Limeira 901, Caixa Postal 52, CEP 13414-903, Piracicaba, SP, Brazil
    • ,
  • Márcio A. Lopes

      Affiliations

    • Department of Oral Pathology, Dental School, University of Campinas, Piracicaba-UNICAMP, Avenue Limeira 901, Caixa Postal 52, CEP 13414-903, Piracicaba, SP, Brazil
    • ,
  • Jorge E. León

      Affiliations

    • Department of Oral Pathology, Dental School, University of Campinas, Piracicaba-UNICAMP, Avenue Limeira 901, Caixa Postal 52, CEP 13414-903, Piracicaba, SP, Brazil
    • ,
  • Oslei P. Almeida

      Affiliations

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

Received 29 March 2008; accepted 19 May 2008. published online 08 July 2008.

Article Outline

Summary 

Most cystic lesions of the oral cavity are intraosseous and lined by squamous epithelium. Although rare, various developmental cysts occur preferentially in the tongue, lined by dermal, thyroglossal, gastrointestinal or respiratory epithelium. Surgical excision is the treatment of choice for these cysts. We report the clinical, histological and immunohistochemical aspects of one lingual cyst lined by gastric epithelium affecting a 1-year-old boy. Immunohistochemical analysis showed similar profile of normal gastric epithelium, except by negativity for CK20, suggesting well-differentiation states. The pathogenesis lingual cyst lined by gastric epithelium remains uncertain, but it is considered they are derived from entrapment of embryonic epithelial rests.

Keywords: Tongue, Oral development cyst, Lingual cyst, Gastrointestinal epithelium, Immunohistochemistry

 

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1. Introduction 

Several types of developmental cysts, such as the dermoid cyst, lymphoepithelial cyst, cystic hygroma, thyroglossal duct cyst, and cystic teratoma have been described in the tongue [1], [2], [3], [4]. Besides these cysts, there is a controversial group lined by gastric, intestinal, respiratory and/or squamous epithelium, that occur mainly in the tongue and floor of the mouth, but also elsewhere in the mouth [5], [6], [7], [8]. These cysts have been termed cysts of foregut origin, whereas others with similar histology have been classified in the group of alimentary tract cysts. Nevertheless there is a tendency to call these cysts by the descriptive term, according to the lining epithelium. Moreover, few studies have evaluated the immunohistochemical (IHC) profile of development lingual cyst [9], [10].

The purpose of this work is to describe the clinicopathological and IHC features of one case of lingual cyst lined by gastric epithelium, and to discuss the differential diagnosis, emphasizing the terminology used for its classification.

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2. Case 

A 1-year-old boy was referred to the Centro Clínico de Cabeza y Cuello, Ciudad de Guatemala, Guatemala, for evaluation of a congenital tumor on the tongue. According to the mother it was interfering with breast feeding. On physical examination there were no other alterations, and medical history was non-contributory. Intraoral examination showed a submucous firm nodular lesion, measuring 1.5cm in diameter, located in the tongue. There was a small ulcerated area, painful on palpation. The clinical diagnosis was of a cystic lesion or a benign mesenchymal tumor. Due the patient's age and clinical aspects, the lesion was removed by surgery under general anaesthesia. The histopathological analysis showed a cystic lesion lined by gastric epithelium resembling the fundus/body portion of the stomach (Fig. 1A). Ample ulcerated areas covered by fibrinopurulent exudates and granulation tissues were observed (Fig. 1B). The cystic wall showed prominent amount of smooth muscle. PAS (periodic acid-Schiff) and Mucicarmine staining revealed positivity in the surface mucous cells, while deep mucous cells of the fundic/body-type glands were positive only for PAS. These histopathologic features were consistent with lingual cyst with gastric epithelium. Giemsa stain was performed and curved or “S” shaped rod bacilli, suggestive of Helicobacter pylori (H. pylori), on the surface of cystic epithelium and intraluminal mucous material was found (Fig. 1C).

  • View full-size image.
  • Fig. 1. 

    (A) The cystic lesion of the tongue is lined by gastric epithelium resembling the fundus/body portion of the stomach (H&E, OM 20×). (B) Ulcerated areas covered by fibrinopurulent exudates and granulation tissues (H&E, OM 10×). (C) Note rod bacilli suggestive of Helicobacter pylori next to the surface of cystic lesion (Giemsa stain, OM 100×).

The infant is without symptoms or recurrence after 2 years follow-up.

A large panel of antibodies was used for IHC evaluation (Table 1). Cytokeratin (CK) AE1/AE3, epithelial membrane antigen (EMA) and β-catenin demonstrated uniform positivity in all cystic epithelium (Fig. 2A and B). The lining (surface) epithelium was positive for CK7, CK8, CK18, CK19, and 34βE12, this latter marking basal cells preferentially; while CK4 and E-cadherin was only focally positive. Deep mucous cells expressed CK8, CK18, and CK19; while the parietal cells expressed only CK8 and CK18 (Figs. 2C and D). Surprisingly the cystic epithelium was completely negative for CK20 (Table 2).

Table 1. Antibodies used for immunohistochemical evaluation of lingual cyst with gastric epithelium
AntibodySource/cloneDilution
CK-cocktailDako®a, AE1/AE31:500
CK-high molecular weightDako®a, 34βE121:200
CK1Novocastra®b, 34βB41:200
CK5Novocastra®b, XM261:400
CK6Novocastra®b, LHK6B1:200
CK7Dako®a, OV-TL12/301:400
CK8Dako®a, 35βH111:200
CK10Dako®a, DE-K-101:200
CK13Novocastra®b, KS-1A31:400
CK14Novocastra®b, NCL-L-LL0021:200
CK16Novocastra®b, LL0251:200
CK18Dako®a, DC101:400
CK19Dako®a, RCK 1081:200
CK20Dako®a, Ks20,81:500
EMADako®a, E291:400
β-CateninNovocastra®b, 17C21:100
E-cadherinDako®a, NCH-3841:200
VimentinDako®a, Vim 3B41:400

CK, cytokeratin; EMA, epithelial membrane antigen.

aDako A/S, Glostrup, Denmark.

bNovocastra Laboratories Ltda, Newcastle, England.

  • View full-size image.
  • Fig. 2. 

    Immunohistochemical findings of lingual cyst lined with gastric epithelium. (A) Strong immunoreactivity in all cystic epithelium for AE1/AE3 (IHC, OM 20×). (B) Uniform membranous immunoreactivity for β-catenin (IHC, OM 40×). (C) Uniform immunoreactivity for CK8 (IHC, OM 40×). (D) CK19 marked the lining epithelium and deep mucous cells. Note that the parietal cells are negative (IHC, OM 40×).

Table 2. Immunohistochemical findings of lingual cyst with gastric epithelium
AE1/334βE12CK4CK5/14CK7CK19CK8/18E-cadβ-catEMAOthersa
Epithelium
Lining/surface++b+c+b,c++++c++−
Fundic/body gland+−−−−+d+d,e−++−

E-cad: E-cadherin; β-cat: β-catenin; EMA: epithelial membrane antigen.

aVimentin, CK1, CK6, CK10, CK13, CK16, and CK20.

bOnly basal layer.

cFocal.

dDeep mucous cells.

eParietal cells.

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3. Discussion 

Oral development cyst with gastrointestinal epithelium was first described by Toyama in 1927 [11]. Gorlin and Jirasek published the first review of gastric heterotopias of the head and neck in 1970 [12]. This cyst presents many terminologies such as cyst with heterotopic gastrointestinal mucosa, gastrointestinal duplication cyst, choristomatic gastrointestinal cyst and gastric mucosal choristoma, the latter with cystic and solid subtypes. This cyst has been more commonly described in the duodenum, gallbladder, common bile duct, jejunum, Meckel's diverticulum, ileum, appendix, colon and rectum, forming spherical, tubular, or diverticular lesions that mimic the structure of the normal gastrointestinal tract [1], [13]. These features qualifies the term duplication cyst by the fact that it may have a coat of smooth muscle, it is attached to a portion of the alimentary system, and possesses a mucosal lining similar to some portion of the alimentary tract [14]. Indeed, this cyst may also be considered as choristoma because it is a tumor-like mass of normal cells with an organized architecture in an abnormal location, and not necessarily have a muscular coat [15]. The presence of parietal, chief, and mucous cells, as well as closely associated smooth muscle fibers, indicates a high degree of differentiation [16].

The origin of oral development cyst containing gastrointestinal epithelium is not known. One of the most recent concepts suggests that they arise from islands of endoderm that originate from the lining of the primitive stomodeum and become entrapped in the mouth during the fourth to fifth week of embryonic development, a time at which the entire gastrointestinal endoderm is undifferentiated [17]. The foregut contains components of the endoderm and mesoderm that lead to the development of the trachea, bronchi, esophagus, liver, stomach, and intestine. Abnormal budding off of the embryonic tracheoesophageal septum can lead to the formation of a cyst in relation to the tracheobronchial tree, mediastinum, liver, pancreas, tongue, and upper digestive tract [18]. Thus, since both epithelia (respiratory and gastrointestinal) are of endodermal origin it is conceivable that primitive uncommitted endoderm could differentiate in a multi-directional manner [5], [6].

The nomenclature of lingual cysts lined by gastrointestinal and/or respiratory epithelium is confusing. As cited by Shear and Speight in their fourth edition of Cysts of the Oral and Maxillofacial Regions [19], at the moment it is better to nominate these cysts as suggested by Manor et al. [7] and Shear [6], considering the main type of epithelial lining. This is more objective, and it can help to group together case reports and small series of the same cysts, but classified using different terms. Following this line, the present cyst was classified as lingual cyst lined by gastric epithelium.

Lingual cysts with gastrointestinal or respiratory epithelium are rare benign lesions, involving predominantly the anterior two-thirds of the tongue and floor of the mouth. Most affected patients are children, with a slight preference for males. As it is usually a relatively large mass, when affecting a newborn, difficulties in breast feeding, swallowing and breathing are the most common symptoms. The patient here reported was a baby and besides breast-feeding difficulties, presented pain related to areas of ulceration. The epithelial lining of the cyst is mainly gastric. Discontinuous or focal areas of smooth muscle may be seen in the cyst wall, supporting the belief that this entity should be categorized as an enteric duplication cyst [1], [5], [7], [20].

The main differential diagnosis of lingual cyst in an infant include ranula, lymphoepithelial cyst, lingual thyroid, thyroglossal duct cyst, dermoid cyst, mucoid retention cyst, cystic hygroma, haemangioma, and neurofibroma [1], [2], [3]. The congenital ranula, a retention cyst due to congenital atresia of the ducts of the submandibular or sublingual salivary glands, is a lesion on the floor of the mouth that can appear to involve the ventral surface of the tongue [21]. The lymphoepithelial cysts are lined by epithelium, which becomes entrapped by lymphoid tissue. Lingual thyroids and intralingual thyroglossal duct cysts usually involves the posterior third of the tongue; this latter is lined by respiratory epithelium and usually ectopic thyroid tissue is present in the cyst wall [22], [23]. Histologically, dermoid cysts of the floor of the mouth are classified according to Meyer's classification into three histologic varieties: dermoid, epidermoid, and teratoid. Dermoid and epidermoid cysts have morphology similar to their counterparts on the skin, whereas teratoid cyst is more controversial, but should present ciliated respiratory epithelium, and derivatives of ectoderm, mesoderm, and/or endoderm [24]. Recently, Shen et al. [10] reported 31 cases of oral teratoid cyst, 24 of them congenital.

In addition to the lesions previously mentioned, a mass in the tongue of a newborn or child, include many other entities, as bronchogenic cyst [25], pyogenic granuloma [26], congenital cystadenoma [27], lipoma [28], myofibroma [29], nerve sheath myxoma [30], fibromatosis [31], leiomyoma [32], glial choristoma [33], and congenital granular cell tumor [34]. Surgical excision is the treatment of choice for these lesions. Approach to resection is based on accessibility to the mass, size of the mass, and concern for postoperative airway obstruction secondary to lingual swelling [31]. The case here reported was treated surgically, under general anaesthesia, and similar to most cases previously reported, the patient was well after surgery, with no recurrence after 2 years of follow-up.

H. pylori is known to colonize heterotopic mucosa in various sites, including cases of Meckel diverticulum and heterotopic gastric mucosa in the rectum [35]. It is interesting to consider that in our case, Giemsa stain revealed curve and “S” shaped rod bacilli suggestive of H. pylori on both cell surfaces and extracellular mucoid material. Unhappily we were not able to perform immunoreactions to confirm if it was in fact H. pylori. It is known that H. pylori is most commonly seen in the gastric antrum followed by the duodenum and less frequently on the body and cardia of the stomach. The cyst wall lined by gastric epithelium in this case resembles the superficial epithelial cells typically lining the fundus/body portion of the stomach. It is well established that H. pylori is present in saliva of most individuals, so it is possible that the bacilli we found by the Giemsa stain is in fact H. Pylori.

The normal gastric mucosa is immunopositive for CK8, CK18, CK19, CK20, EMA, β-catenin, and E-cadherin, and inconstant for CK7. The mucus-secreting cells stain weaker for CK8, CK18, and CK19 than both chief and parietal cells, and basal cells are CK5 and CK14 positive, although the latter in the gastric mucosa is variable [36], [37]. There are only two IHC studies on lingual cysts. The first describes one case of congenital oral cyst, which presented squamous, intestinal, and respiratory epithelium. It was positive for AE1/AE3, CK7 and CK19 in the squamous epithelium, and for AE1/AE3, CK7, CK8 and CK19 in intestinal and ciliated epithelia. CK20, carcinoembryonic antigen (CEA) and chromogranin showed no reaction [9]. In other study evaluating 31 cases of oral teratoid cyst, the expression of AE1/AE3, CK7, CK8/18, and CK19 varied in superficial, suprabasal and basal cells of squamous epithelium, but expression was strong in respiratory, gastrointestinal and simple columnar epithelium. Only the gastrointestinal epithelium expressed CK20, but heterogeneously [10]. The IHC findings of this report showed similar results, except that it was negative for CK20 similar to the reported by Coric et al. [9]. This is unexpected because normal gastrointestinal epithelium is characteristically CK20 positive.

In summary, it is reported a case of lingual cyst lined with gastric epithelium, affecting a 1-year-old boy. Surgical excision is the treatment of choice for these lesions, usually with good results and no recurrences. The IHC profile of the gastric epithelium suggests well differentiated states of cell maturation, and it is similar to its normal counterpart, on this case the gastric fundus/body regions. It is worth to note that this case and also one previously reported [9] were unexpectedly CK20 negative.

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Acknowledgements 

The authors thank Ana Cristina do Amaral Godoy for the immunohistochemistry assistance. This work was supported by FAPESP, São Paulo, Brazil.

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PII: S1871-4048(08)00042-7

doi:10.1016/j.pedex.2008.05.005

International Journal of Pediatric Otorhinolaryngology Extra
Volume 4, Issue 1 , Pages 36-41, January 2009

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