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Background . Perineural invasion (PNI) is an adverse prognostic histologic finding and increases the risk of local recurrence and metastasis.  Objective . We aimed to determine if dual immunohistochemical (IHC) staining with S-100 and AE1/3 would increase the detection of PNI on nonmelanoma skin cancers (NMSCs).  Methods . We collected 45 specimens of NMSCs in which there was clinical suspicion for PNI. Two dermatopathologists independently reviewed the tumors for the unequivocal presence of PNI.  Results . Unequivocal PNI was present on 10 of the 45 tumors by H&E staining and on 15 of the 45 tumors by IHC staining. Large nerves (>0.1 mm) were involved in 3 of 10 H&E-stained cases and 3 of 15 IHC-stained cases, with 2 of the 4 cases demonstrating large nerve involvement with both staining methods. Of the 8 cases of PNI detected only on IHC, 7 were small nerves (≤0.1 mm).  Limitations . All cases were selected because they were clinically suspicious for PNI, and this may be considered selection bias.  Conclusions . PNI detection may be increased using dual S-100 and AE1/3 staining, but the majority of additional cases detected were small nerves. The clinical significance, given the small size of the involved nerves, is unclear.

Dual S-100-AE1/3 Immunohistochemistry to Detect Perineural Invasion in Nonmelanoma Skin Cancers