Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive: A Pitfall in the Interpretation of Oropharyngeal Biopsies

Clear cell carcinoma (CCC) is a low-grade malignancy that commonly arises in minor salivary glands of the oropharynx and other sites. EWSR1-ATF1 gene fusions seem to be specific for this salivary neoplasm. Testing for EWSR1-ATF1 has expanded the histologic spectrum of CCC. As one important example, many CCCs have a predominantly squamous phenotype with few clear cells, a finding that can cause confusion with squamous cell carcinoma (SqCC). P16 immunohistochemical staining to determine human papillomavirus (HPV) status has become standard practice for all oropharyngeal carcinomas showing squamous differentiation. The purpose of this study was to determine whether this practice could contribute to the difficulty in distinguishing CCC from p16-positive SqCC. The authors’ surgical pathology archives were searched for cases of CCC. All cases were evaluated with p16 immunohistochemistry, high-risk HPV RNA in situ hybridization (ISH), and EWSR1 gene break-apart fluorescence ISH. Sixteen CCCs were identified. All harbored an EWSR1 rearrangement. Eleven patients were women and 5 were men. They ranged in age from 30 to 85 years (mean, 58 y). The CCCs arose in the oropharynx (tongue base or tonsil) (n=8, 50%), oral cavity (n=4, 25%), and nasopharynx (n=4, 25%). Each case demonstrated clear cells, but the proportion was highly variable (10% to 90%, mean 48%), with 7 of 16 cases having
Source: The American Journal of Surgical Pathology - Category: Pathology Tags: Original Articles Source Type: research