This case is similar to the previous, as nasopharyngeal carcinoma (NPC) can also be a non-keratinizing squamous cell carcinoma, but has a different etiology. This tumour is rare in North America, but is more common in China and South East Asia. Unlike non-keratinizing tumours elsewhere in the oropharynx, these tumours are not HPV related, hence the negative staining for p16. Tumours that are non-keratinizing or undifferentiated are associated with Ebstein-Barr Virus (EBV), with positive staining for EBV by immunohistochemistry or in situ hybridization. The keratinizing variant of NPC may be associated with HPV infection.
These tumours tend to metastasize early to the cervical lymph nodes and usually present as unilateral neck masses. A non-keratinizing tumour metastatic to the neck that is negative for p16 should prompt suspicion for this lesion and immunohistochemistry for EBV or hybridization for EBER should be considered.
Within the nasopharynx itself, undifferentiated NPC may have two interesting patterns:
Regaud pattern: A syncytial arrangement of cohesive cells with indistinct cell margins.
Schminke pattern: A diffuse cellular infiltrate of non-cohesive cells which may resemble a non-Hodgkin lymphoma.
Based upon these patterns, this tumour may also be known as a lymphoepithelioma, though the tumour consists only of epithelial elements, and the inflammatory cells are purely reactive.