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

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.