Perineural Spread of Squamous Cell Carcinoma to the Skull Base following Treatment of Oropharyngeal P16-Positive Squamous Cell Carcinoma: A Case Series

Background Oropharyngeal squamous cell carcinoma (OPSCC) secondary to human papilloma virus (HPV) is increasing in incidence and this subset generally has an improved prognosis compared with those with HPV-negative OPSCC. Metastasis for OPSCC most commonly occurs in the lung; however, there have been reports of unusual patterns of metastasis in p16-positive OPSCC, including the brain, kidney, skin, skeletal muscle, axillary, and intra-abdominal lymph nodes. Skull base metastasis is an even rarer entity, with only one case report in the literature. We present a case series of metastatic squamous cell carcinoma (SCC) to the ipsilateral Meckel’s cave and pterygopalatine fossa following definitive therapy of p16-positive OPSCC.

Methods A case series was conducted in 2016 at a tertiary care facility.

Results Three patients with a history of stage IV p16-positive OPSCC status-postmultimodality therapy presented with paresthesias in the maxillary (three of three) and mandibular (2 of three) distribution of the trigeminal nerve, masseteric weakness (one of three), facial pain (two of three), and headache (two of three). All three patients were male, with an average age of 54 years (range: 46–59 years). Two of the three patients were nonsmokers. A mass centered in the pterygopalatine fossa and Meckel’s cave was identified in all three patients on MRI, ipsilateral to the primary site of disease. An endoscopic endonasal transpterygoid approach was utilized to biopsy these lesions, confirming the diagnosis of SCC. One of the three specimens underwent p16 staining which was positive. The mean time to presentation following definitive treatment was 5.7 months (range: 3–8 years). Each patient received additional therapy, including cisplatin, 5-fluorouracil and cetuximab, intensity-modulated radiation therapy, and PD-1 and PDL-1 immunotherapy, with progression of disease in two patients and stable disease in one at 8 to 12 months of follow-up.

Conclusion New onset V2 or V3 numbness shortly after treatment of oropharyngeal HPV-positive SCC may represent an atypical metastatic spread to Meckel’s cave and the pterygopalatine fossa. The mechanism of spread is likely neurotropic along V3, causing metastases to the skull base.