Unusual presentation of granular cell tumour of buccal mucosa
- 1 Oral Maxillofacial Surgery, Auckland District Health Board, Auckland, New Zealand
- 2 Oral Maxillofacial Registrar, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
- 3 Oral Medicine, The University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Nedlands, Western Australia, Australia
- 4 Oral and Maxillofacial Surgery, Royal Perth Hospital, Perth, Western Australia, Australia
- Correspondence to Dr Zhi Yon Charles Toh; go4lightly@gmail.com
Abstract
Granular cell tumour (GCT) is a rare soft tissue lesion which many consider to have malignant potential of yet unknown aetiopathogenesis. Oral GCT lesions may occur in an area of leucoplakia and are predominantly present on the tongue. This case study highlights an uncommon presentation of this condition located on the buccal mucosa and illustrates the need for meticulous evaluation of suspicious lesions. Due to the malignant risk associated with GCT lesions, it is important to make the correct diagnosis and ensure complete surgical excision for these cases. Ongoing long-term follow-up is also indicated to monitor for recurrence or malignancy.
Background
In 2005, granular cell tumour (GCT) was first introduced in the WHO’s classification of tumours. Immunohistochemical analysis has demonstrated it to be a connective tissue neoplastic lesion arising from Schwann cells with strong and consistent expression of highly specific S-100 protein.1 It is considered by many researchers to be a true neoplasm based on its’ induction mechanism however, the aetiopathogenesis of this oral neoplasm remains uncertain.2 Clinicopathological data suggest the possibility of a local metabolic or reactive process.3 GCT can affect a wide age range but is more common between the fourth and sixth decades of life with a higher prevalence in females with dark skin tones.4 Gender predilection may be multifactorial. One of the factors could include female hormones aiding the differentiation of stem cells to form Schwann cells.5 GCT can be present in various anatomical sites with half of the cases in the head and neck region.6
Intraorally GCT presents in areas such as the lip, tongue, palate, gingiva and buccal mucosa. The tongue is the most common site of presentation, accounting for more than 70% of oral GCTs, while 5% of lesions have been reported to be located in buccal areas.7 8 Lesions that are superficial are often found in the overlying mucosa, while deeper lesions may be palpable as a firm mass. These tumours usually manifest as a solitary lesion, although multifocal lesions may be present in up to 10% of cases.9 A portion of the multifocal extraoral cases commonly found in children and young adults have been associated with systemic conditions such as neurofibromatosis and Noonan syndrome.10
Clinically GCT presents as a well circumscribed, asymptomatic, sessile nodule located in the submucosa. Typically, they are slow growing lesions no larger than 3 cm in diameter. These solitary nodules can present with a smooth, rough, pseudo-ulcerated or verrucous appearance.11 Histopathological findings show a non-encapsulated submucosal lesion with the presence of pseudo-epitheliomatous hyperplasia (PEH), pyknotic and eccentrically located nuclei. Other histological findings on H&E staining include a proliferation of oval and polygonal cells with eosinophilic granular cytoplasm infiltrating into the adjacent dermis. Granular cells may display a wide variation in cytological features ranging from a small vesicular nucleus to large polygonal or bipolar patterns with lysosomes accumulation being responsible for the granularity. Mature lesions tend to have a reduced cluster of desmoplastic cells in a densely fibrous tissue.12 13 Immunoreactivity of GCT shows positive staining for p75, S-100 myelin protein, vimentin, neuron-specific enolase (NSE) (NKI)/C3, PGP9.5 and inhibin α. All of these features are expressed in different tissues and are not unique to a particular cell type. Specifically, S-100, a protein of the E-F hand family, is used as a diagnostic indicator in immunostaining of GCTs. It is commonly found in granule cells, Schwann cells and non-neural lineages such as skeletal muscle cells and rhabdomyoma.14 Currently, diagnosis is based on histological findings with immunohistochemical positivity for S-100, NSE and SRY-related HMG-box 10 (SOX-10) being diagnostic.15
The authors present a rare case report and review of the literature for GCT of the buccal mucosa.
Case presentation
A 57-year-old female patient presented with right buccal mucosa leucoplakia. It was an incidental finding by her dentist. Her medical history was unremarkable. She was an active smoker with a smoking history of 40 pack years. On extraoral examination, the patient had no facial asymmetry, cranial nerve abnormality or cervical lymphadenopathy. Intraoral examination revealed a non-homogenous white plaque on the right buccal mucosa, involving 50% of the posterior right buccal region extending from molar to the premolar region (figure 1). The lesion was firm on bimanual palpation with no altered sensation to the buccal mucosal region.
Right buccal mucosal clinical view.
Investigations
Clinical photography was taken followed by a 5×5×3 mm incisional mucosal/submucosal biopsy. This was taken at the posterior margin of the lesion due to its increased firmness. Following H&E, S100 and SOX10 staining, the presence of a GCT was suspected.
Treatment
Following the incisional biopsy, excision was completed under local anaesthetic with a surgical blade. Macroscopically, the specimen from the right buccal mucosa was of irregular shape, tan in colour and measured 20×11×3 mm. A 3.0 Vicryl Rapid suture was used for wound closure and the excisional specimen was sent for histopathological analysis. Microscopically, the sections revealed squamous epithelium and underlying fibrous and fatty stroma, with a tumour occupying the stroma. Mucosal and stromal inflammation and fibrosis were compatible with the history of surgery at this site. The tumour was composed of polygonal cells with abundant eosinophilic cytoplasm and rounded, cytologically bland nuclei. No mitotic figures were seen. The cells were positive for S100 and SOX10. The overlying epithelium showed mild thickening with orthokeratosis and parakeratosis. No epithelial dysplasia or malignancy was identified (figure 2). Based on these findings, a diagnosis of GCT was made.
H&E stained sections revealing tumour occupying the stroma, composed of polygonal cells with abundant eosinophilic cytoplasm and rounded, cytological bland nuclei. No mitotic figures seen. The cells are positive for S100 and SOX10. The overlying epithelium shows mild thickening with orthokeratosis and parakeratosis.
Outcome and follow-up
The patient has subsequently been reviewed 6 months postsurgery without concerns. The wounds have healed uneventfully and no signs of local recurrence have been seen. The patient is planned for ongoing six monthly clinical and photographic reviews.
Discussion
GCT is an uncommon soft tissue neoplasm, which frequently involves the tongue within the oral cavity. Typical clinical presentation is that of relatively small (<3 cm) asymptomatic sessile nodular lesion overlying an intact epithelium. The lack of identifiable clinical features presents a significant challenge to diagnose GCT without a tissue biopsy. Differential diagnoses may include other peripheral nerve tumours (neurofibroma, schwannoma), soft tissue lesions (fibromas, lipomas, dermoid cyst) or salivary pleomorphic adenoma. Other benign granular cell lesions of the mouth include congenital granular cell epulis.9 16 Clinical appearance of ulceration and ill-defined borders can often mimic malignant pathology and may be misdiagnosed as squamous cell carcinoma.
GCT of the buccal mucosa is a rare entity with 30 reported cases in the literature. A literature review using web of science, SCOPUS and PubMed databases identified 17 studies which described a total of 30 cases with GCT of the buccal mucosa. Gender and age were reported in 16 and 15 cases, respectively. There is a gender distribution of 62% women and 38% men with an age range between 7 and 74 (mean age of 38.1). Most were described as firm painless nodular lesion. The evolution of lesion ranges from several weeks to 120 months with size of the lesion from 0.5 cm to 1.6 cm. From the six cases reported tumours with PEH occurred in three cases (table 1). Both GCT of the tongue and buccal mucosal have similar epidemiology.
Clinical and descriptive data of 30 buccal mucosal GCT
| Articles | No. of cases | Gender | Clinical lesion | Age (years) | Evolution | Size (mm) | PEH |
| A desmoplastic granular cell tumor of the oral cavity: report of a case19 | 1 | Male | Nodular | 7 | Several weeks | 10×6×6 | – |
| Firm, raised mass of the buccal mucosa20 | 1 | Male | Rough, irregular, non-ulcerated surface | 59 | 12 months | – | Present |
| Follow up study of 14 oral granular cell tumors21 | 1 | Female | White-yellow lesion | 23 | 24 months | – | Negative |
| Granular cell tumor: report of case in the buccal mucosa22 | 1 | Female | Yellowish, binodular lesion | 60 | 3 months | 5 | – |
| A granular cell tumor of the buccal mucosa—a case report23 | 1 | Female | Nodular, hard solid mass | 74 | 120 months | 14×16×10 | – |
| Granular cell tumor: report of 8 intraoral cases24 | 1 | Female | Nodular, rosy colour with clear delimitation | 40 | 5 months | – | – |
| Granular cell tumor of buccal mucosa—a case report25 | 1 | Male | Firm in consistency, non-tender, well defined proliferative growth | 45 | 3 months | 10×10 | – |
| Histogenesis of Abrikossoff tumor of the oral cavity26 | 1 | Male | – | – | – | – | Present |
| Oral granular cell myoblastoma: an immunohistochemical study27 | 1 | Female | – | 37 | – | – | Present |
| Oral granular cell tumors: report of twenty five cases with electron microscopy28 | 2 | Male Female |
– | 45 27 |
– – |
– | – |
| Granular cell lesions in head and neck: a clinicopathological study29 | 2 | Male Female |
– – |
28 31 |
– – |
10 8 |
Negative Negative |
| Oral granular cell tumors: an analysis of 10 new pediatric and adolescent cases and a review of the literature30 | 1 | Female | – | 17 | – | – | – |
| Case series: two cases of an atypical presentation of oral granular cell tumour31 | 1 | Female | Raised white patch | 45 | – | – | – |
| Granular cell tumor of the oral cavity, a case series including a case of metachronous occurrence in the tongue and the lung32 | 1 | Female | – | 34 | – | – | – |
| Granular cell tumor: a clinicopathologic study of 110 patients33 | 7 | – | – | – | – | – | – |
| Oral granular cell tumors: a clinicopathologic and immunocytochemical study5 | 6 | – | – | – | – | – | – |
| Oral granular cell tumors: a histological and immunocytochemical study34 | 1 | – | – | – | – | – | – |
Histology features of granular cells can vary widely with various cell and nucleus morphology. Immunochemistry staining for S-100 antibody is critical in making a definitive diagnosis. The first line treatment option for GCTs involves surgical resections and its low recurrence rate, low malignant transformation potential and slow growth rate for oral cases contribute to favourable prognoses. A broad surgical margin with the removal of a portion of adjacent soft tissue may be necessary to avoid recurrence as the tumour may lack a capsule or present with an ill-defined border.17 A study broadly categorised margins into wide, marginal and intralesional with recurrent risk of 30%, 40% and 100%, respectively.18 Ongoing clinical monitoring and follow-up to evaluate for malignant changes are therefore important.
Learning points
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This case demonstrates the need for thorough histological examination of the entire specimen. Without this, it is possible to miss important diagnoses.
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In this case, granular cell tumour (GCT) was clinically innocuous, residing within tissue presumed to be likely dysplastic epithelium.
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GCT can be malignant, adding weight to the importance of its detection.
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The authors believe GCT should be considered on the list of differential diagnoses for leukoplakic lesions of the buccal mucosa due to this.
Ethics statements
Patient consent for publication
Acknowledgments
I would like to express my gratitude to the other authors of this report: FS-CC, MJ and TC. Giving me the opportunity to write up on this interesting case presentation. In addition assisting in concept, contents and manuscript editing for which I am really thankful to them.
Footnotes
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Contributors FS-CC was responsible for concept, design, contents, manuscript editing. MJ was responsible for concept, design, histopathological analysis, manuscript editing. TC was responsible for concept, design data compilation, manuscript editing. ZYCT was responsible for literature search, data compilation and manuscript drafting. All the authors had approved the final draft of the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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