DOG1, p63, and S100 protein: a novel immunohistochemical panel in the differential diagnosis of oncocytic salivary gland neoplasms in fine-needle aspiration cell blocks

Abstract

DOG1 is a calcium-activated chloride channel protein that may have a potential role in secretory cells of salivary glands and tumors derived from them. Its role in cytologic specimens is not well documented. This study was performed to evaluate its utility in separating acinic cell carcinoma (AciCC) from other closely related differential diagnoses on cytologic samples. In addition, an immunohistochemical panel consisting of DOG1, p63, and S100 protein to assist in the subclassification of these salivary gland neoplasms with oncocytic differentiation was also investigated. Thirty-one fine-needle aspiration cell blocks (CBs) of oncocytic salivary gland neoplasms (16 Warthin tumors [WTs], 10 AciCCs, 3 mucoepidermoid carcinomas [MECs], and 2 oncocytomas [ONCs]), and 75 salivary gland resections (7 WTs, 27 AciCCs, 36 MECs, 2 high-grade adenocarcinomas, 2 ONCs, 1 papillary cystadenoma) were immunostained for DOG1, p63, and S100. DOG1 and p63 were very useful in distinguishing AciCC from WT on CB, because 100% of WTs were DOG1-negative and 87.5% were p63-positive, whereas 70% of AciCCs were DOG1-positive and 100% were p63-negative. The resection results correlated with those on CBs: 100% of WTs were DOG1-negative and 86% were p63-positive, whereas 93% of AciCCs were DOG1-positive and 89% were p63-negative. S100 and DOG1 were negative in both WTs and ONCs, with <10% S100 positivity in AciCCs. DOG1 was very helpful in separating AciCC from WT, MEC, and ONC. In summary, an immunohistochemical panel including DOG1, p63, and S100 can significantly improve the accuracy of diagnosing oncocytic salivary gland neoplasms on CBs.