Which tumors demonstrate perineural invasion?

Tumors That Demonstrate Perineural Invasion

Multiple tumor types demonstrate perineural invasion, with squamous cell carcinoma (both cutaneous and mucosal), adenoid cystic carcinoma, and melanoma being the most common in the head and neck region, followed by lymphoma, basal cell carcinoma, and mucoepidermoid carcinoma. 1

Most Common Tumors with Perineural Invasion

Head and Neck Malignancies (Most Frequent)

• Squamous cell carcinoma (cutaneous and mucosal) is the most frequently encountered tumor with perineural spread in the head and neck, occurring in approximately 40% of head and neck squamous cell carcinomas 1, 2
• Adenoid cystic carcinoma is the second most common tumor demonstrating perineural invasion, particularly in salivary gland malignancies, and has a strong propensity for perineural spread that may preclude complete radical resection 1, 3
• Melanoma ranks third among tumors with perineural invasion in the head and neck region 1

Other Malignancies with Perineural Invasion

• Lymphoma (specifically non-Hodgkin lymphoma) demonstrates perineural tumor infiltration 1, 3
• Basal cell carcinoma shows perineural invasion, which is associated with the most aggressive tumor behavior and represents a high-risk feature requiring more aggressive management 1, 4
• Mucoepidermoid carcinoma exhibits perineural spread patterns 1
• Minor salivary gland malignancies demonstrate perineural tumor infiltration 3
• Basosquamous carcinoma has higher metastatic potential than typical basal cell carcinoma and must be managed as squamous cell carcinoma 4, 5

Additional Tumor Types

• Pancreatic cancer demonstrates perineural invasion with glutamate/NMDA receptor signaling as a tumor-specific driver 6
• Prostate cancer shows perineural invasion as a pathological hallmark 6
• Colorectal cancer exhibits perineural invasion patterns 6
• Breast cancer demonstrates perineural invasion with neural progenitor cell involvement as a specific driver 6
• Gastric cancer shows perineural invasion with epigenetic regulators as tumor-specific drivers 6
• Malignant schwannoma can demonstrate perineural tumor infiltration 3
• Other sarcomas may exhibit perineural spread 3

Critical Clinical Distinctions

Perineural invasion must be distinguished from perineural tumor spread: perineural invasion is local invasion detected on histopathologic diagnosis at the primary tumor site, while perineural tumor spread is macroscopic spread of tumor along the course of a nerve distant from the primary tumor site as detected on imaging 1

Prognostic Implications

• Perineural invasion is associated with worse prognosis across multiple tumor types, including increased risk of recurrence and decreased overall survival 1, 7
• In squamous cell carcinoma, perineural invasion significantly increases risk of recurrence and metastasis, particularly when nerves ≥0.1 mm diameter are involved 1, 8
• Perineural invasion in basal cell carcinoma poses greatly increased risk of recurrence, whether the tumor is basal or squamous cell cancer 1
• In head and neck cutaneous squamous cell carcinoma, perineural invasion decreases 5-year disease-free survival to 57.9%, with worse outcomes when >5 nerves are involved 7
• Extratumoral perineural invasion demonstrates worse disease-free survival compared to intratumoral or peripheral perineural invasion 9

Nerves Most Commonly Affected

• Trigeminal nerve (CN V) is most commonly affected by perineural tumor spread, particularly the second and third divisions 1, 3
• Facial nerve (CN VII) is the second most commonly affected nerve 1, 3
• Any nerve traveling in the vicinity of a malignancy may become involved 1