Pathology and Genetics of Head and Neck Tumours

226 Tumours of the salivary glands  

 Definition

A malignant tumour composed of variable proportions of two cell types, which typically form duct-like structures. The biphasic morphology is represented by an inner layer of duct lining, epithelialtype cells and an outer layer of clear, myoepithelial-type cells.

Synonyms

 Adenomyoepithelioma {176}, clear cell adenoma {494,2228}, glycogen-rich adenoma {913}, glycogen-rich adenocarcinoma {1758}, clear cell carcinoma {407}.

Epidemiology

 Epithelial-myoepithelial carcinoma (EMC) represents around 1% of the salivary gland tumours. It is more prevalent in women (F: M=2:1). The patients range in age from 13 to 89 years, with the peak incidence in the 6th and 7th decades {436,493,614,784,1580}. Only two cases have been reported in the paediatric group {436,1775}.

Localization

EMC occurs mostly in major salivary glands, mainly in the parotid (60%), but also in the minor glands of oral mucosa and the upper {436,493,614,784,1580} and lower respiratory tract {610,1126, 1174,2002}.

Clinical features

 EMC forms a painless, slow-growing mass. Tumours arising in minor glands frequently present as ulcerated, submucosal nodules and have less well-defined margins. Rapid growth, facial nerve palsy and/or associated pain are suggestive of concomitant high-grade areas.

 Macroscopy

 EMC is characteristically a multinodular mass, with expansive borders and lacking a true capsule. Cystic spaces may be present. Tumours of the minor glands are poorly circumscribed. Histopathology

EMC has a lobulated growth pattern with a mixed tubular and solid architectural arrangement. Papillary and cystic areas can be identified in around 20% of the cases. Tumours from minor salivary and sero-mucinous glands show infiltration of surrounding tissues and there is ulceration of the overlying mucosa in about 40% of the cases. The hallmark of EMC histology is the presence of bi-layered duct-like structures: the inner layer is formed by a single row of cuboidal cells, with dense, finely granular cytoplasm and central or basal, round nucleus. The outer layer may show single or multiple layers of polygonal cells, with well-defined borders; the cytoplasm is characteristically clear and the nucleus is vesicular and slightly eccentric. The double-layered pattern is preserved in papillary-cystic areas but solid tumour areas may be exclusively formed by clear cells. PAS positive, hyaline, eosinophilic strands of basement membrane-like material surround the duct-like structures and, in solid areas, divide the clear cells into theques. Coagulative necrosis at the centre of tumour nodules is uncommon. In rare cases, squamous differentiation and spindle cells are observed as well as an oncocytic appearance in the inner cell layer of neoplastic ducts. Perineural and vascular invasion are frequent and bone invasion may occur. None to 1-2 mitoses per 10 HPF can be identified in the clear cell population of EMC. Rare cases of dedifferentiation have been reported {42,783}. Immunoprofile Myoepithelial markers (smooth muscle actin, HHF35, p63 and/or calponin) stain the clear cell compartment. The luminal cells stain with cytokeratins.

Differential diagnosis

The differential diagnosis of EMC includes all primary salivary gland tumours that are predominantly formed by clear cells: pleomorphic adenoma, myoepithelioma, oncocytoma and mucoepidermoid carcinoma. Differential diagnosis with clear cell carcinoma, NOS relies on the demonstration of the peculiar amyloid-like quality of the stroma and on the absence of myoepithelial markers. Metastatic kidney and thyroid carcinoma may be distinguished using immunohistochemistry; CD10 and high-molecular weight cytokeratin in the former and thyroglobulin in the latter. EMC foci can be encountered within carcinoma ex pleomorphic adenoma as part of the carcinomatous component.

Genetics

A limited number of cases (6) have been karyotyped {656,1650,1751}, half of them showing non-distinctive chromosomal alterations and the remaining normal karyotypes.

Prognosis and predictive factors

Recurrence occurs in around 40% of cases and metastasis in 14%. The most common metastatic sites are cervical lymph nodes, lung, liver and kidney. Death from disease complications occurs in less than 10% of the patients {436,493,614,784,1580}. Five- and 10 year overall survival rates are 80% and 72%, respectively {784}. Size and rapid tumour growth are associated with worse prognosis {42,783}. Margin status is a major pathological prognostic factor. Incomplete surgical excision is associated with recurrence and metastasis. The poorer prognosis associated with tumours located in minor salivary glands may be due to the higher frequency of recurrences due to incomplete surgery. Atypia is associated with unfavourable outcome {784} whenever present in more than 20% of tumour area. EMC is usually diploid {784,992}. Aneuploidy and high mitotic counts have been reported in cases with unfavourable prognosis {784}. Areas of dedifferentiation also predict poor outcome, with recurrence and metastasis in 70% of patients {42,783}.