Table I:

Summary of neural phenotypes that could be of relevance to clinical outcome.

Phenotype	Definition	Criteria or Comments	Methods	References
Perineural invasion	Nerve invaded by or has at least 33% of its perimeter surrounded by tumor cells.	Detection enhanced by IHC.	H&E IHC: Pan-cytokeratin for epithelium, S100 or TUJ1 for nerve.	(59) (61–63)
Nerve-tumor distance	Shortest distance between any nerve and nearest tumor island.	PNI negative according to current criteria but nerve-tumor distance less than 27 μm*; could increase up to ~100 μm.	H&E IHC: Pan-cytokeratin for epithelium, S100 or TUJ1 for nerve. Software to measure distance.	(61, 62)
Nerve diameter	Smallest axis of cross-section of nerve.	Greater than 32 μm*; could increase up to ~50 μm. Nerves >2 mm from tumor bulk excluded.	H&E Software to measure distance.	(62)
Nerve density	Area or number of nerves divided by the area analyzed in a tissue section.	Requires further standardization	H&E IHC: Pan-cytokeratin for epithelium, S100 or TUJ1 for nerve.	(49, 79)

H&E: hematoxylin and eosin

IHC: immunohistochemistry