Oncocytic mucoepidermoid carcinoma of a submandibular gland: a case report and review of the literature

Oncocytic mucoepidermoid carcinoma of a submandibular gland: a case report and review of the literature

Int. J. Oral Maxillofac. Surg. 2007; 36: 560–563 doi:10.1016/j.ijom.2006.12.017, available online at http://www.sciencedirect.com Case Report Head an...

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Int. J. Oral Maxillofac. Surg. 2007; 36: 560–563 doi:10.1016/j.ijom.2006.12.017, available online at http://www.sciencedirect.com

Case Report Head and Neck Oncology

Oncocytic mucoepidermoid carcinoma of a submandibular gland: a case report and review of the literature

L. Corcione1, G. Giordano1, L. Gnetti1, A. Multinu2, S. Ferrari2 1 Department of Pathology and Laboratory of Medicine, Section of Pathology, Parma University, Italy; 2Department of Otorhinolaryngology, Dentistry, Ophthalmology and Cervico-Facial Sciences, Section of Surgery, Parma University, Italy

L. Corcione, G. Giordano, L. Gnetti, A. Multinu, S. Ferrari: Oncocytic mucoepidermoid carcinoma of a submandibular gland: a case report and review of the literature. Int. J. Oral Maxillofac. Surg. 2007; 36: 560–563. # 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. This report describes the first recognized case of oncocytic mucoepidermoid carcinoma of a submandibular gland, and emphasizes the role of immunohistochemical study in the correct diagnosis of this tumour. This is only the second case in which this tumour has appeared as a completely cystic lesion. A review of the literature was carried out to clarify the clinical and pathological features of this rare malignancy.

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Salivary gland tumours are rare, comprising less than 3% of all neoplasms of the head and neck region19. In the study by SPIRO14, the majority of salivary tumours were located in the parotid gland (70%) followed by the minor salivary glands (22%) and submandibular gland (8%). In the series by ITO et al.5, neoplasms of the salivary gland affected more commonly adult patients with peak incidence between 40 and 50 years of age and a slight predominance in females. Pleomorphic adenoma was the most frequent tumour representing 54.2% of all cases, followed by mucoepidermoid carcinoma (13.5%), Warthin’s tumour (8.5%) and adenoid cystic carcinoma (7.9%). According to EVESON & CAWSON4 malignant tumours of salivary glands were more

and was slowly growing. On physical examination, the nodule was mobile and rubbery. A computed tomography (CT) scan showed a cystic lesion in the submandibular gland (Fig. 1) without any lymphadenopathy in the neck or tissue surrounding the gland. On surgical examination, it was found that the tumour was not fixed to adjacent structures and was contained within the submandibular salivary gland capsule. The patient underwent excisional biopsy. On macroscopic examination, the lesion was entirely cystic and measured 3.5 cm in diameter, its wall being 0.4 cm thick and its internal surface smooth. Histopathological examination of a resected specimen revealed that the lesion

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common in the submandibular and minor glands than in the parotid. Here is reported a case of a very rare subtype of submandibular malignant tumour, called oncocytic mucoepidermoid carcinoma. A review of the literature was performed in order to clarify the clinical and pathological features of this rare malignancy, and the differential diagnosis of cystic and non-cystic lesions in the submandibular region is discussed. Case report

A 74-year-old man, with a previous history of cardiac infarction and ischemic encephalopathia, presented with painless swelling in the submandibular region. This lesion had appeared 2 years before

Accepted for publication 17 December 2006 Available online 28 February 2007

# 2007 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Salivary oncocytic mucoepidermoid carcinoma

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Immunohistochemically, both the epithelium lining the cyst (Fig. 3c) and the small nodules of oncocytic cells (present within the fibrous tissue of the cystic wall) showed strong reactivity for mithochondrial antigen (Fig. 3d), keratin and alpha-1-antichymotrypsin. Immunohistochemical reactivity for keratin 14 demonstrated the squamous differentiation of cells present in the epithelium of the cyst (Fig. 3e) and also in small nodules present within the fibrous tissue of the cystic wall (Fig. 3f). Smooth muscle actin, vimentin and S-100 protein (S-100) were negative. The final pathological diagnosis was oncocytic mucoepidermoid carcinoma of a submandibular gland. One month after excisional biopsy, a CT scan did not reveal any enlargement of the lymph nodes in the submandibular and neck region.

Fig. 1. Axial CT scan with intravenous contrast showing well-defined, hypodense cystic mass within left submandibular gland (arrows: lesion).

Fig. 2. Histopathological examination of specimen, at low magnification, shows that the lesion was entirely cystic with fibrous wall (haematoxylin and eosin).

was a cyst with a fibrous wall (Fig. 2). The internal surface was lined with elements characterized by abundant, granular, eosinophilic cytoplasm, round nuclei with small prominent central nucleoli and occasional mucinous goblet cells (Fig. 3a). Small nodules of mucoepidermoid carcinoma, small nests of elements with abundant granular, eosinophilic cytoplasm, and round nuclei with small prominent central

nucleoli were observed within the fibrous tissue of the cystic wall (Fig. 3b). The panel of immunostains, including antibodies against mitochondrial antigen, keratin (Citok AE1, Citok AE3), vimentin, alpha-1-antichymotrypsin, smooth muscle actin, keratin 14 and S-100, was applied to representative sections of the tumour using the avidin–biotin complex (ABC) technique (Table 1).

Table 1. Primary antibodies used for immunophenotyping Antibody

Manufacturer

Dilution

Method

Mitochondrial antigen Citok AE1/AE3 Citok 14 Vimentin Alpha-1-antichymotrypsin Smooth muscle actin S-100 protein

BioGenex Dako Neomarkers Neomarkers Dako Neomarkers BioGenex

1:500 1:100 1:100 1:500 1:800 1:500 1:500

ABC ABC ABC ABC ABC ABC ABC

Discussion

In 1897, Schaffer described the presence of swollen eosinophilic granular cells in the human salivary gland, pharynx, trachea and oesophagus, and in 1931, a German pathologist, Hamperl, used the term oncocyte, taken from the Greek word, ‘onkousthai’ (i.e. swollen), for this peculiar cell type1. Later, other authors demonstrated by ultrastructural investigation17 and immunohistochemical stains13 that these elements are epithelial cells, and that their cytoplasm is abundantly eosinophilic and granular because of the presence of numerous mitochondria. The tumours composed entirely of oncocytic cells can be observed in many organs such as kidney9 thyroid6 and stomach16. Neoplasms of the salivary glands characterized by oncocytic cells include Warthin’s tumour, oncocytoma and oncocytic carcinoma10. The oncocytic changes can be a prominent features of mixed tumours with a mucoepidermoid component. These mixed neoplasms, denominated oncocytic mucoepidermoid carcinomas, have been observed in many glandular tissues such as lacrimal gland7,11, bronchus15 trachea8 and thyroid18. The oncocytic differentiation can be demonstrated by using immunohistochemical stains that reveal positivity for antibodies against mitochondrial antigen, keratin (Citok AE1, Citok AE3) and alpha-1-antichymotrypsin. Salivary oncocytic mucoepidermoid carcinoma is a very rare subtype of malignant neoplasm, with only 12 previous cases reported in the English literature3. The age of these patients ranged from 20 to 78 years, with male predominance (9 males, 3 females)3. The prognosis of oncocytic mucoepidermoid carcinoma seems

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Corcione et al. escape diagnosis, and their incidence is truly higher. Acknowledgements. The Authors wish to thank Professor Alex Gillan for the revision of the English language and Mrs Gabriella Becchi for technical assistance. They are also grateful to Professor Juan Rosai for his expert opinion in this case. References

Fig. 3. The cyst is lined by epithelium composed of oncocytes and occasional mucous goblet cells (a, haematoxylin and eosin, 200; arrows: a goblet cell). Small nodules of oncocytic and epidermoid cells with mucous goblet cells are present within fibrous tissue of cystic wall (b, haematoxylin and eosin, 200; arrows: goblet cells). Immunohistochemically, both the epithelium lining the cyst (c, 200) and the small nodules of oncocytic and epidermoid cells present within the fibrous tissue of the cystic wall show strong reactivity for mitochondrial antigen (d, 100). Immunohistochemical reactivity for keratin 14 reveals presence of squamous component in epithelium of cyst (e, 200) and in the small nodules (f, 200).

to depend on clinical stage, tumour grade and adequate treatment3. In all cases previously reported, the neoplasm involves parotid gland and macroscopically can be partially cystic, multicystic with solid foci or completely solid3. Only one case has been described of a oncocytic mucoepidermoid as an entirely cystic lesion3. The present case of oncocytic mucoepidermoid carcinoma is thus the first involving submandibular gland and is only the second case reported to be entirely cystic. To make a correct diagnosis, it is important to evaluate microscopic as well as immunohistochemical features of this rare neoplasm. In fact, the oncocytic and squamous differentiation in the present case were demonstrated by immunoreactivity for antibodies against mitochondrial antigen and keratin 14.

Although, in a submandibular gland, this malignancy is exceptional, it should be considered when there is submandibular enlargement. Cystic oncocytic mucoepidermoid carcinoma must be differentiated from other non-neoplastic cystic swellings of the submandibular region, such as submandibular branchial cyst, dermoid/epidermoid cyst, mucocele, rare cases of hydatid cyst, cystic hygroma and salivary duct cyst2. It is equally important to differentiate oncocytic mucoepidermoid carcinoma from other salivary and non-salivary neoplasms that are responsible for submandibular enlargements12,20. Clinically, the majority of cystic swellings of the submandibular region are considered mucoceles, and they often are not submitted for histological examination. It is the authors’ view that cystic tumours of this region may

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Salivary oncocytic mucoepidermoid carcinoma 13. Shintaku M, Honda T. Identification of oncocytic lesions of salivary glands by anti-mitochondrial immunohistochemistry. Histopathology 1997: 31: 408–411. 14. Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2807 patients. Head Neck Surg 1986: 9: 27–31. 15. Stafford JR, Pollock WJ, Wenzel BC. Oncocytic mucoepidermoid tumor of the bronchus. Cancer 1984: 54: 94– 99. 16. Takubo K, Honma N, Sawabe M, Arai T, Izumiyama-Shimomura N, Kammori M, Sasajima K, Esaki Y. Oncocytic adenocarcinoma of the stomach. Am J Surg Pathol 2002: 26: 458–465.

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20. Wakoh M, Yonezu H, Otonari T, Sano T, Matsuzaka K, Inoue T, Wada N. Two cases of schwannoma with marked cystic changes. Dentomaxillofac Radiol 2005: 34: 44–50. Address: G. Giordano Dipartimento di Patologia e Medicina di Laboratorio Sezione di Anatomia Patologica Viale Gramsci 14 43100 Parma Italy Tel: +39 0521 290391 Fax: +39 0521 292710 E-mail: [email protected]