Influence of p16 Protein Immunostaining on Histopathological Features of Pleomorphic Adenoma and Carcinoma ex- Pleomorphic Adenoma

Abstract

The objective of this study was to evaluate the role of p16 in histologic characteristics and transition of Pleomorphic Adenoma (PA) to Carcinoma ex-PA (CxPA). So, 60 PA and 4 CxPA were histologic reviewed based on microscopic characteristics proposed by Hellquist, Triantafyllou and Dulguerov (PA) and Morais, Antony and Toluie (CxPA). Immunostaining for p16 was associated in different parenchyma and stroma of both tumors and Fisher's/chi-square tests and Mann-Whitney test were performed (SPSS v20.0, p<0.05). In PA the periductal cells were predominantly p16- and that ductal and myoepithelial cells showed a significant increase in p16+ cells (p<0.001). In CxPA, none of the cases showed p16+ in periductal cells, most parotid cases showed p16+ in ductal cells, and one case of parotid and the submandibular case showed mild immunostaining for myoepithelial cells. There was a small reduction in p16+ in CxPA compared to PA (p=0.537), but in both tumors there was less p16+ cells in solid stroma than other (p<0.001). The p16+ cases of PA had a higher capsular thickness (p=0.047). So, the loss of p16 immunostaining does not seem to be associated with the transition from PA to CxPA, but in both tumors the loss of p16+ cells are related to microscopic aggressiveness.

Keywords: Adenoma, Pleomorphic; Genes, p16; Salivary gland neoplasms.

Figure 1

Histological Features and Immunostaining for p16 in PA. A: classic pattern pleomorphic adenoma showing myxoid (a), hyaline (b) and solid (c) stroma; B: classic pattern pleomorphic adenoma showing chondroid (a) and solid (b) stroma; C: hypocellular pattern pleomorphic adenoma showing predominantly myxoid stroma (a); D: hypercellular pattern pleomorphic adenoma showing predominantly solid stoma (a); E: Hypocellular pattern pleomorphic adenoma showing multinodular distribution (a); F: hypocellular pattern pleomorphic adenoma showing partial capsule rupture (a); G: keratin pearl-shaped squamous metaplasia (a); H: crystalloids (a); I: oncocytic metaplasia; J: pigmentations (a); K: positive immunostaining for p16 in luminal ductal cells, and negative in non-luminal ductal cells; L: positive immunostaining for p16 in chondroid stroma; M: positive immunostaining for p16 in myxoid stroma (myoepithelial cells); N: negative immunostaining for p16 in solid stroma

Figure 2

Histological Features and Immunostaining for p16 in CxPA. A: carcinoma ex pleomorphic adenoma hypercellular pattern showing solid stroma (a); B: carcinoma ex pleomorphic adenoma hypercellular pattern showing hyaline (a) and myxoid (b) stroma; C: classical pattern pleomorphic carcinoma ex-adenoma showing large amounts of ductal cells (a); D: carcinoma ex-pleomorphic adenoma showing extensive cellular and nuclear pleomorphism; E: carcinoma ex-pleomorphic adenoma showing keratin pearl (a); F: carcinoma ex-pleomorphic adenoma showing large areas of intratumoral hemorrhage (a); G: positive immunostaining for p16 in luminal ductal cells, and negative in non-luminal ductal cells; H: positive immunostaining for p16 in myxoid stroma (myoepithelial cells); I: negative immunostaining for p16 in solid stroma