The classification of PNI in different group.

Ne0–no perineural invasion; Ne1–neurium invasion; Ne2–perineural space invasion; Ne3–nerve bundle invasion. The nerve structures (A, B) and representative stages of the invaded neural structure for classification (C–H). (A) A nerve bundle surrounded by the continuous layered epithelioid sheets of the perineurium (arrowhead). (B) The perineural space, an internal space between the nerve bundle and perineurium (arrowhead). (C) Neurium invasion of cancer cells in the outer perineural space and attached to the perineurium (arrowhead). (D) Perineurial cells of perineurium between the nerve bundle and cancer cells (arrowhead). (E) Perineural space invasion of cancer cells in the perineural space (arrowhead). (F) Cancer cells invading the perineural space and compressing the nerve bundle smoothly. The border between cancer cells and nerve bundles do not contain perineurial cells or perineurium (arrowhead). (G) Nerve bundle invasion by cancer cells. Cancer cells irregularly compress the nerve bundle, clearly invading between nerve fibers (arrowhead). (H) Invasive cancer cells clearly seen between nerve fibers (arrowhead). A, C, E, G show an original magnification of 100×, and B, D, F, H an original magnification of 400×. Figure arrowheads indicate the nerves.