Analysis of the Clinical Relevance of Histological Classification of Benign Epithelial Salivary Gland Tumours

Abstract

Introduction: A vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the case in benign epithelial salivary gland tumours. We have performed a literature review to investigate whether an accurate histological diagnosis of the 11 different types of benign epithelial salivary gland tumours is correlated to any differences in their clinical behaviour.

Methods: A search was performed for histological classifications, recurrence rates and risks for malignant transformation, treatment modalities, and prognosis of these tumours. The search was performed primarily through PubMed, Google Scholar, and all versions of WHO classifications since 1972, as well as numerous textbooks on salivary gland tumours/head and neck/pathology/oncology. A large number of archival salivary tumours were also reviewed histologically.

Results: Pleomorphic adenomas carry a considerable risk (5-15%) for malignant transformation but, albeit to a much lesser degree, so do basal cell adenomas and Warthin tumours, while the other eight types virtually never develop into malignancy. Pleomorphic adenoma has a rather high risk for recurrence while recurrence occurs only occasionally in sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and the membranous type of basal cell adenoma. Papillomas, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (solid, trabecular and tubular subtypes) very rarely, if ever, recur.

Conclusions: A correct histopathological diagnosis of these tumours is necessary due to (1) preventing confusion with malignant salivary gland tumours; (2) only one (pleomorphic adenoma) has a considerable risk for malignant transformation, but all four histological types of basal cell adenoma can occasionally develop into malignancy, as does Warthin tumour; (3) sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and Warthin tumour only occasionally recur; while (4) intraductal and inverted papilloma, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (apart from the membranous type) virtually never recur. No biomarker was found to be relevant for predicting recurrence or potential malignant development. Guidelines for appropriate treatment strategies are given.

Keywords: Benign salivary gland tumours; Biomarkers; Malignant transformation; PubMed; Recurrence; Salivary gland neoplasms; Treatment modalities.

Fig. 1

a Lymphadenoma, non-sebaceous type. In a few of the epithelial cell nests, a central ductal structure is present. b Sebaceous adenoma with solid nests of sebaceous cells (a, b adapted from Hellquist and Skalova [25]). c Well-encapsulated (arrow) oncocytoma consisting of rather large oncocytes. d Parotid nodular oncocytosis. Note the absence of capsules. e Cystadenoma where the cysts are separated by thin fibrous septa. There are smaller papillary intraluminal projections and the cysts are often filled with eosinophilic “proteinaceous debris”. f Palatal sialadenoma papilliferum with an exophytic mildly papillary surface epithelium and underlying cystic proliferation of salivary ducts. g Higher magnification of the ductal proliferation; note more columnar and taller cells and also thicker fibrous septa than in cystadenoma (e). h CK7 stain highlights the salivary ductal cells with some ducts opening up in the exophytic CK7 negative surface epithelium

Fig. 2

a An encapsulated intraductal papilloma in a minor salivary gland. b Higher magnification illustrating the delicate papillary network of cell-lined vascular fronds with the occasional goblet cell; atypia and mitoses are absent (a, b by courtesy of Dr Guy Betts, Manchester University NHS Foundation Trust, UK). c Non-encapsulated inverted papilloma with an endophytic growth pattern. The cells have an epidermoid and basal cell appearance and the tumour frequently contain smaller cysts. Inset Another example of inverted papilloma. d Canalicular adenoma of the upper lip with strands of single layered cells of one cell type and with the hallmark of a very paucicellular and vascular stroma; morules, i.e., squamous balls, may be present, either free in the lumen or attached (arrow). Inset Positive S100 staining, an enigmatic characteristic of canalicular adenoma. e Basal cell adenoma, primarily trabecular type, with anastomosing strands and cords of ductal and basaloid cells. Palisading of nuclei in the outer cells of the cords. f CK7 stain highlights the two cellular components of BCA (in contrast to only one in canalicular adenoma) with positive inner ductal cells and outer CK7 negative myoepithelial/basal cells