BACKGROUND: Oral hedgehog inhibitors (HHIs) have shown significant efficacy in 
the treatment of basal cell carcinoma (BCC). The evaluation of tumor regression 
has been performed using clinical photography and radiographic scans. 
Noninvasive imaging techniques, such as reflectance confocal microscopy (RCM) 
and high-definition optical coherence tomography (HD-OCT), have been shown to be 
valuable in detecting BCC in the skin.
OBJECTIVE: We monitored HHI-treated BCC using RCM and HD-OCT in vivo and 
correlated morphologic changes seen on imaging to changes in traditional 
histopathology.
METHODS: Six BCCs in 5 patients receiving HHIs (vismodegib or sonidegib) were 
examined by RCM and HD-OCT before and during treatment. Characteristic features 
were compared to histopathologic findings, including immunohistochemical 
analysis.
RESULTS: Characteristic features of BCC in RCM and HD-OCT decreased or 
disappeared completely during HHI treatment. Half of the clinically complete 
responding tumors still featured tumor residue. Pseudocystic structures ("empty" 
tumor nests in imaging) and widespread fibrosis (coarse bright fibers) were new 
findings and could be confirmed by histopathology.
LIMITATIONS: Our study was limited by the number of tumor samples and imaging 
timepoints.
CONCLUSION: Using RCM and HD-OCT, HHI-induced regression of BCC can be 
visualized noninvasively in the skin. The formation of pseudocysts and fibrosis 
were characteristic signs of BCC response to HHIs.