The dermoid, epidermoid, and teratoid cysts are non-odontogenic lesions derived from the germinative epithelium (1). Dermoid cysts may be found in any part of the body, particularly in areas where embryonic elements are fused. The majority of cases have been reported in ovaries, testicles, hands, and feet (1-3). These lesions are lined with epidermis and contain skin appendages such as sebaceous glands, sudoriferous glands, and hair follicles. When there is an absence of these skin appendages, the cysts are classified as epidermoid or epidermal cysts. They are not related to the dermoid cysts of the gonads, which are denominated as teratomas (1-4).
Epidermoid cysts are benign subcutaneous lesions, comprising 85-90% of all excised cysts (5). Most epidermoid cysts develop in the midline or sublingual region of the mouth floor, the buccal mucosa is not a usual site of occurrence (6-11). To date, only five articles have been published with six cases of epidermoid cysts arising in the buccal mucosa region (1-3, 12, 13). Therefore, the aim of this study was to describe the clinical, histopathological, and immunohistochemical features of a case of epidermoid cyst located in the buccal mucosa. To the authors’ knowledge, this is the first report of an oral epidermoid cyst describing an intense foreign body gigantocellular inflammatory reaction against an epithelial keratin component. Although the usual diagnosis for epidermoid cysts is based on histopathological findings, this case report addresses new information regarding the immunohistochemical pattern that may be found in these lesions.
A 29-year-old man visited the Stomatology outpatient clinic of the Federal University of Ceará, Sobral Campus, Brazil, complaining of a painless intraoral swelling in the buccal mucosa (firstly noticed four years earlier). According to the patient, the lesion had been traumatized and caused mild dysphagia. During the extra-oral examination, facial asymmetry was observed in the right labial commissure. During the clinical examination, there was no presence of palpable lymph nodes in the head and neck region. Additionally, a 3.5 cm nodular, sessile, and ulcerated lesion of rubbery consistency was observed in the right buccal mucosa, (Figure 1, a-d).
Due to these clinical findings, the initial diagnosis was benign salivary gland lesions. More precisely, the pleomorphic adenoma was the main diagnostic hypothesis. Due to the possibility of the occurrence of low grade malignant lesions associated with a relatively long time of development, an incisional biopsy was performed under local anesthesia, (Figure 2, a-d).
Initially, anesthesia of the mental nerve and infiltrative terminal anesthesia in the proximities of the lesion were performed. The anesthesia was kept a safe distance from the lesion to prevent infusion of the anesthetic into the lesion and allow preservation of its reference margins. Following this procedure, aspiration puncture of the lesion was performed, and a yellow liquid similar to the mucin was obtained. The probable presence of mucin inside the lesion changed the diagnostic hypothesis to mucocele, and an excisional biopsy was performed, (Figure 2, a-d). The area of the incision was delimited with a scalpel blade so that separation of the tissues could be performed and, consequently, expose the lesion. It was shown to be translucent and yellowed, well delimited and not adhered to the tissues. During the tissue separation procedure, the slip of a surgical instrument accidentally caused a partial rupture of the lesion, revealing a yellow and viscous liquid similar to mucin. The surgical wound was closed using a 4.0 silk suture, and the specimen was stored in 10% formol for further anatomopathological study. The macroscopic aspect of the surgical specimen showed a well-delimited brownish nodule with a soft consistency and measuring 2 x 1.8 x 0.9 mm. A translucent material was observed after the transverse section of the surgical specimen.
A microscopic exam showed a cystic cavity partially lined with stratified pavimentous epithelium, (Figure 3), containing an intraluminal eosinophilic material compatible with degenerated keratin and hemorrhagic areas (Figure 4, a). In the cystic lumen, squamous cells, along with dispersed cells with morphology similar to that of keratinocytes, were observed in the midst of this degenrated keratin. Some squamous cells exhibited an eosinophilic cytoplasm containing keratohyalin granules (Figure 4, b). Additionally, rupture of the epithelial lining was observed, leaving the degenerated keratin in direct contact with the adjacent conjunctive tissue, which stimulated a giant-cell-type reaction. This finding was characterized by a massive presence of multinucleated giant cells and inflammatory cells reacting to the keratin (Figure 5, a, b). Thus, the final diagnosis was epidermoid cyst associated with an exuberant giant-cell-type inflammatory reaction.
Immunohistochemical analyses (Figures 6, a-d and Figure 7, a-d) were performed using the standard streptavidin-biotin-peroxidase method in 5 μm thick tissue sections that had been obtained from paraffin-embedded blocks and mounted on silanized microscopic slides. The steps from deparaffinization to the heat-induced epitope retrieval were performed with an EZ Prep solution (Ventana; Tucson, AZ, USA) for 30 minutes. The primary antibodies used in this study included Cytokeratin AE1/3, Cytokeratin 34βE12, Cytokeratin 5/6, CD138, and Bcl-2. The BenchMarkTM XT IHC/ISH (Ventana; Tucson, AZ, USA) automated slide stainer was used, and the indirect immunoperoxidase was detected by the XT Ultraview DAB v3 system (Ventana; Tucson, AZ, USA) followed by the use of diaminobenzidine (DAB). The sections were subsequently counterstained with Mayer hematoxylin. Positive extrinsic and intrinsic control samples were used in each assay. With regard to the epithelial component, a strong marking for all the cytokeratins used and CD138 was observed, but there was no marking observed for Bcl-2. With respect to the intraluminal cystic component, a strong marking was observed for the analyzed cytokeratins, a medium marking for CD138, and an absence of marking for Bcl-2. With regard to the inflammatory component, only the antibody Bcl-2 showed focal marking for inflammatory cells.
The patient was clinically followed for 12 months after surgery, and has shown no signs of recurrence of the lesion.
Swellings in the buccal mucosa may lead to a series of clinical diagnoses, since some conditions may present in a similar manner making the diagnostic process difficult. Among the oral alterations compatible with the clinical condition presented in the present study, the following may be mentioned: infectious processes of odontogenic origin affecting the facial spaces of the masseter and buccinator muscles (1), pleomorphic adenoma (14), lymphoepithelial cysts (15) dermoid cysts (1), mucocele (16), and foreign body granulomatous reactions to cosmetic fillers (17). With regard to the present case, after the aspiration puncture had been performed, the clinical hypothesis of mucocele was strongly supported, in spite of it being atypical in the buccal mucosa, particularly due to the transoperative features, although other diagnoses could also have been suggested.
Dermoid cysts have been classified into three categories: epidermoid cysts (the cystic cavity is lined with epithelium without skin appendages), dermoid cysts (the cystic cavity includes skin appendages such as hair, hair follicles, sebaceous, and sudoriferous glands), and teratoid cysts (in addition to the skin appendages in the cystic cavity one could observe elements of the mesoderm such as bone, muscle, gastrointestinal, and respiratory tissue), (1).
Epidemiologically, New and Erich (18) reviewed 1459 epidermoid cysts and found 7% of the cases related to the head and neck region and 1.6% involved the oral cavity. Taylor et al. (19) observed that 6.5% of 541 dermoid cysts of the head and neck region were located intraorally. Rare cases have been related in the tongue, lips, and in intraosseos sites in the mandible and maxilla (2). The large majority of these lesions affect the midline or sublingual region of the floor of the mouth, and may be topographically classified as sublingual or submental, taking into consideration their anatomic relationship with the mylohyoid muscle (1).
The etiology of these tumors is considered unknown. A suggested theory is that either the epithelium is sequestrated in lines of fusion during the embryonic process or the epithelial tissue is implanted in the tissues in a traumatic manner (1, 2, 20). However, the traditional view of the process of fusion of the epithelium has been contested because it does not explain the presence of skin appendages in dermoid cysts or the absence of dermoid cysts in known zones of fusion such as the palate. Ozan et al. (1) and Rajayogeswaran et al. (2) do not believe in these traditional explanations for the appearance of the lesion in the buccal mucosa.
There are two types of epidermoid cysts: the congenital and the acquired ones (3, 4, 20). The congenital type develops at any point of fusion in the development of the body where the ectodermal tissue becomes included in the line of fusion of the body during the embryonic process. The post-traumatic, acquired type, or implantation keratinizing epidermoid cyst, is characterized, by the majority of the authors, as the result of some previous trauma at the site. It is generally produced by a blunt instrument or object, which may have driven epithelial cells into the dermis. When healing occurs, the epithelial cells may behave as a cutaneous graft, multiplying and producing a central mass of keratin that continues to grow slowly by expansion. Post-traumatic cysts are found under the epithelium of the skin, immediately below the site of the scar. Clinically, its presence is characterized by a slow, painless growth, with firm and well circumscribed edema, which is palpable below the normal surface of epithelium (3, 20). In the clinical history of the present case, it is not known for sure if any trauma occurred before the appearance of the lesion.
According to this study (Table 1), only six cases of epidermoid cysts arising in the bucal mucosa have been described in the literature (1-3, 12, 13). In contrast with this study’s findings, a slight predilection for the female sex and for the left buccal mucosa has been observed at a ratio of 2:1, (1, 12, 13). Free mobility of the lesion in the tissues has been observed in the majority of cases (1-3). Moreover, the time of evolution ranged from 6 months to 3 years, and local trauma along with painful symptomatology appears to be the factor that draws the patient's attention to the presence of the lesion in the oral cavity (Table 1), (2, 13).
F, female; M, male; NI, not informed.
The two first cases of epidermoid cyst in the buccal mucosa described in the literature, were published by Schneider, Mesa in 1978 (12), and involved women in the fourth decade of their lives. The authors believed that the cases were supported by the theory of implantation of the histogenesis of surface epithelium. Gutman et al. (13) related an atypical case of intradermal nevus which appeared to involve the wall of an epidermoid cyst. The lesion presented as a painful edema in the right buccal mucosa and was traumatized by biting it, which eventually drained material similar to puss on the surface of the mucosa. The authors believed that the cyst comprised the major portion of the lesion, and originated independently of the associated nevus (13). Rajayogeswaran et al.2 described the case of a 25-year-old patient who presented a visible edema in the left cheek, which was discovered accidentally after an occlusal trauma. This fact may be similar to the present case, since the patient only sought dental treatment after trauma in the region which produced painful symptomatology. Ozan et al. (1) published the case of a 38-year-old patient who presented a visible edema in the left cheek posterior to the commissure. The patient presented a swelling six months previously and had submitted to an unsuccessful antibiotic therapy. The patient denied any history of surgery and/or previous trauma in the region. However, the authors of this study believe that a non-noticeable trauma had occurred during masticatory activity and caused the ulceration of the covering mucosa.
The presence of a trauma may explain the presence of the foreign body gigantocellular inflammatory reaction associated with the present case and the partially lined cystic wall. After the trauma, the contact between the epithelial keratin and the conjunctive tissue may have accurred, stimulating an intense giant-cell type reaction followed by degeneration of the epithelial lining. To the authors’ knowledge, no cases of oral epidermoid cysts associated with intense foreign body gigantocellular inflammatory reaction have been published. Similarly to the current case, Orozco-Covarrubias et al. (21) reported a case series of 75 pediatric patients with extra-oral dermoid cysts. Of these cases, 17 lesions showed foreign body giant-cell reactions.
There is scarce information about the immunoprofile of oral epidermoid cysts. Nakamura (22) described the epidermoid cyst features in 10 cases of skin lesions. Negative immunoreactivity to apoptosis-related molecules (ssDNA, cleaved lamin A, gamma-H2AX, and cleaved caspase-3) was observed. CD138 was immunohistochemically expressed in the squamous epithelium (mainly in the basal and spinous layers) but not in the keratinizing components. These findings were observed in the current case, in which the used the apoptosis-signaling antibody (Bcl-2) used was also negative. This molecule is considered an oncogene that inhibits programmed cell death (22-24), and, similarly, CD138 immunoexpression was detected in the present case in the squamous epithelium layers, except in the upper part of the spinous layer. This antigen is a cell surface molecule usually expressed in basal and suprabasal layers, functioning as a mediator of cell adhesion (22, 25). In another study, Terada (26) observed positive marking for the cytokeratins CK5/6 and CK34BE14 in an epidermoid cyst of the skin associated with a squamous cell carcinoma. The same immunoprofile was shown in the present report, in which both squamous epithelium and dispersed keratin in the cystic lumen showed strong immunoreactivity. Cytokeratins correspond to a vast group of filamentous proteins related to at least 54 human functional genes that are expressed in all epithelial cells (27, 28). The epithelium of the oral mucosa present in the histological samples of the present case, which functioned as internal positive control, showed abundant and homogeneous immunomarking for both CK5/6 and CK34BE14.
International scientific literature is unanimous with regard to the treatment modality for epidermoid cysts, which consists of complete surgical removal of the lesion and afterwards sending the specimen for histopathological analysis (1-5, 13, 17). Dermoid and epidermoid cysts rarely undergo malignant transformation. According to Ozan et al. only isolated cases of malignancy or pre-malignancy have been associated with the lining of epidermoid cysts. Bhatt et al. described the case of a squamous cell carcinoma that appeared in the epithelium of an epidermoid cyst in the floor of the mouth, associated with the sublingual gland (1, 5). Devine, Jones (29), reported a case of carcinomatous transformation of a sublingual dermoid cyst. To sum up, the previous authors emphasized that although the malignant transformation of these lesions is rare, dentists must be more careful with every persistent sublingual edema and have a low threshold for the excision of specimens for histopathologic examination (5).
According to the clinical characteristics observed in the present case, although relatively uncommon in the buccal mucosa, the epidermoid cyst must be included in the differential diagnosis of swellings in this anatomic site. This lesion may be similar to various common oral pathological entities, such as the mucocele. In addition, further immunohistochemical studies should be conducted in order to gain better understanding of the biologic aspects relative to this lesion, especially the phenomena related to the process of cell death.