PIK3R1, HRAS and AR Gene Alterations Associated with Sclerosing Polycystic Adenoma of the Parotid Gland

Abstract

Sclerosing polycystic adenoma (SPA) is a rare neoplasm occurring in the salivary glands, mainly the parotid gland. Although it was originally thought to represent a non-neoplastic process, recent genetic data have proven its monoclonality, supporting its neoplastic origin. We report a case of a 73-year-old woman who presented with left neck swelling and pain. A 3 cm hypoechoic, heterogeneous, solid mass was identified on neck ultrasonography within the left parotid gland. Fine needle aspiration revealed benign acinar cells and lymphocytes. Left partial superficial parotidectomy was performed and a diagnosis of SPA was made. Targeted next-generation sequencing (NGS) revealed three clinically significant alterations in the PIK3R1, HRAS, and AR genes. Alterations in the PIK3R1 gene have been previously reported in cases of SPA; however, this study is the first to report two novel clinically significant genomic alterations in the HRAS and AR genes. AR protein expression by immunohistochemistry was strongly and diffusely positive in the neoplastic epithelial cells compared to the adjacent normal salivary gland tissue, which was dead negative for AR. This molecular profile will enhance our understanding of the molecular pathways underlying the development of this tumor. Although this entity was initially thought to be a reactive process, evidence from our case and similar cases strongly support the notion that it is neoplastic due to the presence of specific genetic alterations linked to it.

Keywords: AR; HRAS; PIK3R1; next generation sequencing; parotid gland; sclerosing polycystic adenoma.

Figure 1

Gross image of the left partial superficial parotidectomy specimen. A 2.8 cm circumscribed and lobulated mass was seen occupying the anterior portion of the parotid gland, with tan, white, focally yellow cut surface and cystic areas on cut section.

Figure 2

Microscopic images showing proliferation of acini, ducts, and cysts, with intraductal epithelial proliferation. Cysts are lined by cells with granular cytoplasm and apocrine features. Areas of fibrosis and chronic and xanthogranulomatous inflammation are also present. The tumor lacks anaplasia; however, a microscopic focus of perineural entrapment is seen. Images were taken at 50× and 400× magnification.

Figure 3

Microscopic images showing positive immunohistochemical protein expression of AR in the neoplastic epithelial cells (diffuse and strong nuclear staining) in (A) compared to the adjacent normal salivary gland tissue that was dead negative for AR in (B). Images were taken at 100× magnification. Abbreviations: H&E: hematoxylin and eosin; AR: androgen receptor.