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Background
Perineural spread (PNS) is a unique phenomenon of nonneoplastic and neoplastic pathologies. PNS can be clinically asymptomatic and therefore can be overlooked during radiological evaluation. Furthermore, due to their elusive nature and reliance on radiological imaging for detection, instances of PNS are often undetected and mislabeled as idiopathic cranial neuropathies. Tumors with PNS spread have three times greater prevalence of regional recurrence, a 30 - 40% decrease in 5-year survival rate, and a 40% increase in distant metastasis, thus detection can greatly alter disease management and help improve guidance on patient outcomes.

Educational Goals / Teaching Points
The purpose of this exhibit is to recognize often overlooked head and neck neoplastic perineural spread on radiological imaging. Review and discussion of the pathophysiology and clinical presentation of PNS-staged malignancies will help to establish awareness of PNS and emphasize the importance of detection in a radiologist’s search methodology.

Key Anatomic/Physiologic Issues and Imaging Findings/Techniques
The exact etiology of neoplastic perineural spread remains unclear. However, the most widely recognized theory proposes a neurotropic interplay between nerve and tumor cells with various neural and stromal proteins, including matrix metalloproteinases, neural membrane proteins, and nerve transcription factors, to provide a biochemical highway for contiguous nerve-tumor adhesion, proliferation, and migration. The pterygopalatine fossa (PPF) is a cone-shaped depression deep to the infratemporal fossa and posterior to the maxilla on both sides of the skull. This space communicates with both the nasal and oral cavities, infratemporal fossa, orbit, pharynx, and middle cranial fossa through eight foramina. While not serving any specific function, this space allows for transit of several important structures through the different foramina consequently yielding a convenient pathway for tumor spread. The maxillary nerve (CN V2), mandibular nerve (CN V3), facial nerve (CN VII), and their divisions are the most commonly afflicted peripheral nerves. The most common tumors that demonstrate perineural spread include squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, and adenoid cystic carcinoma, but are often clinically silent. However symptomatic presentations of cranial nerve-specific deficits including facial neuralgia, numbness, paresthesia, and facial muscle weakness may be detected in some patients.

Conclusion
Due to its impact and prognosis-altering course, neoplastic PNS is a significant parameter of tumor diagnosis and staging that must be considered in malignant head and neck pathologies. Awareness, training, and improved search patterns are our best approaches to detect perineural spread of tumors.