Review articleCombined isolated trigeminal and facial neuropathies from perineural invasion by squamous cell carcinoma: A case series and review of the literature

•Perineural invasion is a specific form of metastatic spread guided by neurotrophic factors.•The trigeminal and facial nerves are the cranial nerves most frequently affected, alone or in combination.•The pterygopalatine and auriculotemporal branches are the most relevant trigeminal-facial anastomoses.•Neuroimaging of perineural invasion requires attention to specific anatomic locations of interest at the base of the skull.

Perineural invasion is a targeted cellular proliferation guided by neurotrophins, rather than a simple diffusion of tumor in a path of least resistance. Invasion of cranial nerves by squamous cell carcinoma can represent an important diagnostic dilemma. It commonly presents as a distinct clinical neurological syndrome of combined isolated trigeminal and facial neuropathies. The focal cancer source may have been overlooked or remain occult. This case series illustrates diverse clinical presentations and neuroimaging challenges in four patients with squamous cell carcinoma of the cranial nerves. Anatomical pathways linking the trigeminal and facial nerves are reviewed, with emphasis on the auriculotemporal and pterygopalatine nerves. A successful neuroimaging strategy requires a targeted multimodality analysis of specific anatomical loci at the base of the skull. Attention must be directed to subtle radiological findings, such as obliteration of fat planes and linear enhancement along nerve branches, rather than bulky tumor tissue or bony invasion. Despite advances in microsurgical dissection and targeted radiotherapy, recovery of established neuropathic deficits is not expected. The prognosis remains poor in cases of advanced disease, emphasizing the importance early diagnosis by clinical acumen and focused neuroimaging.