30 ACTA MEDICA MARTINIANA 2014 14/3 DOI: 10.1515/acm-2015-0004

BASAL CELL ADENOMA OF THE UPPER

Uhliarova B1, Hanulova K1, Fruhwaldova S1,2, Konarcik J3, Smitka M3, Svec M1

Department of Otorhinolaryngology, 1F.D. Roosevelt Faculty Hospital and 2Children Faculty Hospital, Banska Bystrica, Slovakia, 3Martin Biopsy Center Ltd., Banska Bystrica, Slovakia

A b s t r a c t

Basal cell adenoma is an uncommon type of monomorphous adenoma of the salivary gland. Its most frequent location is the . Its recurrence rate and conversion to basal cell after inadequate sur- gical excision is high. We present a 68-year-old female patient with a basal cell adenoma of the upper lip arising from minor salivary gland.

Key words: basal cell adenoma, minor salivary gland tumors, upper lip.

INTRODUCTION

Salivary gland neoplasms represent less than 1% of all tumors, and 3-5% of all head and neck neoplasms. Minor salivary gland tumors are infrequent, accounting for 10-15% of all salivary neoplasms, with very high (50%) proportion of malignant tumors (1, 2). Basal cell adenoma of the salivary glands is a rare tumour, recognised as an independent entity in the Second Edition of the Salivary Gland Tumours Classification of the World Health Organization (3). Basal cell adenoma is a benign epithelial neoplasm with a uniform histologic appearance dominated by basaloid cells. Histologically, 4 characteristic patterns have been described: solid, trabecular, tubular and membranous (4). It is characteristic by the presence of a basaloid cellular layer with a stockade pattern and rounded by hyaline substance (5). The absence of myoepithelial cells, present in benign mixed tumors and other salivary gland neoplasms, has been referred as characteristic of this tumour (6). However, other authors suggest the concurrence of myoepithelial cells, based in the presence of S-100 stromal fusiform cells (7).

CASE REPORT

A 68-year-old female was admitted to our ENT department because of a painless submu- cosal nodule in the right upper lip. She had first noted the lesion about a year ago, after which it had gradually increased in size. On examination the nodule was circumscribed, mobile and rubbery in consistency and 2 to 2.5 cm in diameter. The overlying mucosa was smooth with a pinkish color showing evidence of superficial vascularity. Medical history was unremarkable, and no other abnormalities were found on clinical examination. With the suspected diagnosis of minor salivary gland tumor, a contrasted cervicofacial computerized tomography (CT) was performed. A 2 cm well-defined hyper-take nodule in the maxillary right labial mucosa was present (Figure 1, 2). Radiologically negative lymphatic nodes were observed in the parotid gland, submandibular and jugulodigastric region. Due to its radiological features and slow progression, it was interpreted as a benign lesion, such as fibroma or minor salivary gland tumor such as .

Corresponding author: Barbora Uhliarova, MD, PhD. ENT Department, F.D. Roosevelt Faculty Hospital, Nam. L. Svobodu 1, 975 01 Banska Bystrica, Slovakia; Phone: +421484412945; e-mail: [email protected] ACTA MEDICA MARTINIANA 2014 14/3 31

Fig. 1. Basal cell adenoma of the upper lip – contrast CT image in coronal plane

Fig. 2. Basal cell adenoma of the upper lip – contrast CT in axial plane.

The tumor was completely removed under general anesthesia (Figure 3). As the specimen was completely encapsulated, the lesion 1.8 x 2 cm in size was excised without any diffi- culty with clinically normal margins. The sectional surface of the lesion was solid and gray- white in color. The specimen underwent histotechnical procedures and was stained with hematoxylin and eosin. In the microscopic study, an encapsulated lesion was observed. It was composed of isomorphic basaloid cells formed in trabecules (Figure 4). In order to confirm the diagnosis on hematoxylin-eosin slides, immunohistochemistry was performed. 32 ACTA MEDICA MARTINIANA 2014 14/3

The immunohistochemical findings showed expresivity to cytokeratin (CK) A1/A3 (epithelial marker used for differential diagnosis between myoepithelioma/myoepithelial carcinoma or “undifferentiated carcinoma” and non-epithelial tumors), CK 34 (myoepithelial marker, also positive for basal and squamous epithelial cells), epithelial membrane antigen (ductal - luminal cell marker; apical staining pattern; bubbly positive in sebaceous cells), focal positivity to S-100 (myoepitelial marker) and low positivity for glial fibrillary acidic protein (myoepithelial marker; highly positive in pleomorphic adenoma and myoepithelioma). Ki-67 (cell proliferation marker; differential diagnosis between benign and malignant tumors; prognostic factor) was < 5%. Taken as a whole, these findings supported the final diagnosis of basal cell adenoma in the upper lip. No complications in the postsurgical period were observed. Subsequent follow-up after 2 years showed no sign of recurrence (Figure 5).

Fig. 3. Blunt dissection of the encapsulated mass.

Fig. 4. Basal cell adenoma of the upper lip – histopathological image Encapsulated lesion (A), that is composed of isomorphic basaloid cells formed in trabecules (B), hema- toxylin-eosin, magnification x100 (A), x400 (B). ACTA MEDICA MARTINIANA 2014 14/3 33

Fig. 5. One year after surgery – no signs of recurrence.

DISCUSSION

Tumors originating in the minor salivary glands are infrequent, and represent less than 20% of all salivary neoplasms. Minor salivary gland tumors can be located anywhere in the upper aerodigestive tract, though the most frequently affected locations are: (50%), (15%), cheek mucosa (12%), tongue (5%) and floor of the mouth (5%) (8, 9). The proportion of malignant tumors of the minor salivary glands is very high (50%) – the preferential locations being the floor of the mouth (90%), the retromolar trigone (90%), the tongue (85%) and the lower lip (60%). In contrast, neoplasms of the upper lip are usually benign tumors (75%) (8, 10). Like in major salivary gland, pleomorphic adenoma is the most common benign histological type and adenocarcinoma and are the most common malignant tumors (11, 12). With respect to basal cell adenoma, it is an uncommon benign salivary gland neoplasm, that represents 1% of all salivary gland tumors. The most frequent location is the parotid gland (13). In this paper we reported a case of basal cell adenoma arising from the minor salivary gland of the upper lip.

Microscopically, minor salivary glands tumors constitute a heterogeneous group of neoplasms with great histomorphologic variation. Within the adenomas group, monomorphic tumours are very uncommon. They are defined as epithelial benign tumours of the salivary glands which are not pleomorphic adenomas. Within this group, basal cell adenoma must be signalled. This tumour is subdivided in solid, trabecular, tubular and membranous subtypes. Histologically, basal cell adenoma is characterized by the presence of uniform and regular basaloid cells. These cells have two differenced morphologies and are intermingled. One group consists in small cells with little cytoplasm and intensive basaloid rounded nuclei that are usually located in the periphery of the tumoral nests or islands. The other group is formed by large cells with abundant cytoplasm and pale nuclei that are located in the centre of the tumoral nests. A basal membrane-like structure rounds these tumoral nests, separating them from the surrounding connective tissue. Globally, as it has been referred in classic texts, the tumor adopts an ameloblastoma-like pattern (5, 14).

Epidemiologically, tumors of the minor salivary glands can appear at any age with the maximum incidence in the fourth decade of life for benign lesions and the peak incidence 34 ACTA MEDICA MARTINIANA 2014 14/3 for malignant tumors corresponds to the period between the fifth and seventh decades of life. In the opinion of most authors prevalence in favour of women exists, but other authors report a similar frequency for both genders (8, 9, 11).

Clinically, benign salivary gland neoplasms are usually painless, slow growing tumors, however, some cases exhibiting rapid growth have been reported, especially in the palate. Basal cell adenoma most often presents as a slow-growing encapsulated tumour that do not exceeds 3-cm of major diameter. It is a firm mobile painless mass and a brownish ap - pearance is usually observed (13, 14, 15). Differential diagnosis of intraoral solid, asymptomatic nodules include minor salivary gland tumours and benign and malignant mesenchymal lesions such as lipoma, neurofibroma and rhabdomyosarcoma. The encapsulation and mobility of the nodule are the signs of benignity, although a biopsy must always be performed (11, 12, 16).

Although basal cell adenoma is a benign lesion, some authors consider this neoplasm as a low-grade malignant tumor, according to a high recurrence rate after inadequate excision and conversion to basal cell adenocarcinoma (14, 15). Generally, minor salivary glant tumors have a high recurrence rate (5-30%) when surgical removal is incomplete, and the possibility of malignant transformation must be taken into consideration. Six percent of all benign minor salivary gland tumors are considered to relapse, versus 65% of all malignant lesions. This capacity to relapse is related to the histopathological characteristics of the tumor, and particularly to the initial treatment provided. Any rupture of the capsule or incomplete excision will leave residual tumour cells behind, resulting in recurrence (10, 17). The present case did not show any local recurrence 24 months after surgery. However taking into consideration the characteristics of salivary gland neoplasms, which may recur after many years, patient will be followed up at least 5 years.

CONCLUSION

Basal cell adenoma is a rare benign salivary gland tumor with a high rate of recurrence and a potential malignant conversion to basal cell adenocarcinoma. Therefore, precise identification, adequate surgical excision and long-term followed up are required in the management of upper lip lesions.

REFERENCES

1. Speight PM, Barrett AW. Salivary gland tumours. Oral Dis 2002; 8: 229-240. 2. Yih WY, Kratochvil FJ, Stewart JC. Intraoral minor salivary gland neoplasms: review of 213 cases. J Oral Maxillofac Surg 2005; 63: 805-810. 3. Seifert G, Sobin LH. The World Health Organization s Histological Classification of Salivary Gland Tumors. Cancer 1992; 70: 379-385. 4. De Souza SC, Soares de Araújo N, Correa A. Immunohistochemical aspects of basal cells adenoma and canalicular adenoma of salivary glands. Oral Oncol 2001; 37: 365-368. 5. Nagao K, Matsuzaki O, Saiga H, Sugano I, Shigematsu H, Kaneko T, et al. Histopathologic studies of basal cell adenoma of the parotid gland. Cancer 1982; 50: 736-745. 6. Dardick I, Daley TD, Van Nostrand AWP. Basal cell adenoma with myoepithelial cell-derived stroma: a new major salivary gland tumor entity. Head Neck Surg 1986; 8: 256-267. 7. Batsakis JG, Brannon RB. Dermal analogue tumors of major salivary glands. J Laryngol Otol 1981; 95:155- 164. 8. Vincente OP, Marques NA, Aytes LB, Escoda CG. Minor salivary gland tumors: A clinicopathological study of 18 cases. Med Oral Patol Oral Cir Bucal 2008; 13: E582-588. 9. Jaber MA. Intraoral minor salivary gland tumors: a review of 75 cases in a Libyan population. Int J Oral Maxillofac Surg 2006; 35: 150-154. ACTA MEDICA MARTINIANA 2014 14/3 35

10. Ito FA, Ito K, Vargas PA, De Almeida OP, Lopes MA. Salivary gland tumors in a Brazilian population: a retrospective study of 496 cases. Int J Oral Maxillofac Surg 2005; 34: 533-536. 11. Toida M, Shimokawa K, Makita H, Kato K, Kobayashi A, Kusunoki Y, et al. Intraoral minor salivary gland tumors: a clinicopathological study of 82 cases. Int J Oral Maxillofac Surg 2005; 34: 528-532. 12. Jansisyanont P, Blanchaert RH Jr, Ord RA. Intraoral minor salivary gland neoplasm: a single institution experience of 80 cases. Int J Oral Maxillofac Surg 2002; 31: 257-261. 13. Minicucci EM, De Campos EBP, Weber SAT, Domingues MAC, Ribeiro DA. Basal cell adenoma of the upper lip from minor salivary gland origin. Eur J Dent 2008; 2: 213-216. 14. González-García R, Nam-Cha SH, Muñoz-Guerra MF, Gamallo-Amat C. Basal cell adenoma of the parotid gland. Case report and review of the literature. Med Oral Patol Oral Cir Bucal 2006; 11: E206-209. 15. Bernacki EG, Batsakis JG, Johns ME. Basal cell adenoma. Distinctive tumor of salivary glands. Arch Otolaryngol 1974; 99: 84-88. 16. Ono Y, Takahashi H, Inagi K, Nakayama M, Okamoto M. Clinical study of benign lesions in the oral cavity. Acta Otolaryngol 2002; Suppl 547: 79-84. 17. Daniels JS, Ali I, Al Bakri IM, Sumangala B. Pleomorphic adenoma of the palate in children and adolescents: a report of 2 cases and review of the literature. J Oral Maxillofac Surg 2007; 65: 541–549.

Received: June, 26, 2014 Accepted: October, 26, 2014