Morphologic diversity in human papillomavirus-related oropharyngeal squamous cell carcinoma: Catch Me If You Can!

As the human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma epidemic has developed in the past several decades, it has become clear that these tumors have a wide variety of morphologic tumor types and features. For the practicing pathologist, it is critical to have a working knowledge about these in order to make the correct diagnosis, not to confuse them with other lesions, and to counsel clinicians and patients on their significance (or lack of significance) for treatment and outcomes. In particular, there are a number of pitfalls and peculiarities regarding HPV-related tumors and their nodal metastases that can easily result in misclassification and confusion. This article will discuss the various morphologic types and features of HPV-related oropharyngeal carcinomas, specific differential diagnoses when challenging, and, if established, the clinical significance of each finding.