Diagnostic Utility of PLAG1 Immunohistochemical Determination in Salivary Gland Tumors

Abstract

PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and the specificity of PLAG1 as a marker in the differential diagnosis of salivary gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8 myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma, and 4 epithelial-myoepithelial carcinoma among malignant tumors. PLAG1 was diffusely positive in 94.4% of PAs and in all myoepitheliomas, although with a lower staining intensity. Among malignant tumors, 2 (25%) polymorphous low-grade adenocarcinomas and 1 salivary duct carcinoma ex-PA were positive. In conclusion, PLAG1 is a marker with good specificity for PA and could be a useful diagnostic adjunct in the diagnosis of salivary gland tumors. In particular, this marker is negative in the most common salivary carcinomas, including adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma. However, some mimickers of PA, like polymorphous low-grade adenocarcinoma, may show occasional positivity for PLAG1, thus limiting its diagnostic use. In addition, carcinoma ex-PA shows consistent positivity, and therefore should be considered as a diagnostic possibility in case of a malignant tumor with PLAG1 expression.

PLAG1: An Immunohistochemical Marker with Limited Utility in Separating Pleomorphic Adenoma from Other Basaloid Salivary Gland Tumors

“…In their study of 101 cases of salivary gland lesions including 36 PAs, Rotellini et al [6] observed diffuse PLAG1 positivity in 94.4% of the PAs, which is comparable to the results in our cases of PA SE specimens. None of the BCAs in their cases were positive for PLAG1.…”

“…The transcriptional upregulation of PLAG1 leads to a high level of protein expression in PAs with PLAG1 rearrangements [4,5]. A few studies have analyzed the utility of PLAG1 in salivary gland neoplasms [6,7,8], but these have mostly been on surgical excision (SE) specimens. FNA materials present a diagnostically unique challenge because of the limited material on which the diagnosis is made.…”

Myoepithelial Neoplasms of Soft Tissue: An Updated Review of the Clinicopathologic, Immunophenotypic, and Genetic Features

“…2b), but is negative in myoepitheliomas lacking ductal differentiation [16]. Similarly, the majority of salivary pleomorphic adenomas are positive for PLAG1 [17,18] and frequent positivity is observed in 77 % of carcinomas ex pleomorphic adenoma in salivary gland, including those classified as the myoepithelial carcinoma subtype [19].…”

Canalicular Adenoma: A Clinicopathologic and Immunohistochemical Analysis of 67 Cases with a Review of the Literature

“…Periodic acid Schiff (PAS) with and without diastase, A review of publications in English (MEDLINE 1966-2014) was performed, with all cases reported with clinical, histologic, immunophenotypic and/or follow-up information on CanAd evaluated and included in the review, but excluding ''Quiz'' or ''Case of the Month'' type reports. Several studies were excluded if no specific or separable information was given about CanAd or if the illustrations were not characteristic [23,51,55,[59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Several of the cases seemed to have been included multiple times in different series reports [9,10,40,[79][80][81][82][83].…”