title: Noninvasive monitoring of basal cell carcinomas treated with systemic hedgehog inhibitors: pseudocysts as a sign of tumor regression.
abstract: 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.
  
  
  CONCLUSIONS
  Our study was limited by the number of tumor samples and imaging timepoints.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany. Electronic address: Tanja.Maier@med.uni-muenchen.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Maier
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kulichova
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.affiliation: Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000813:Anilides / Q000008:administration & dosage*; D001706:Biopsy; D001707:Biopsy, Needle; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D002280:Basal Cell Carcinoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D003560:Cysts / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage*; D012074:Remission Induction / Q000379:methods; D012494:Sampling Studies; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000813:Anilides; D001713:Biphenyl Compounds; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines; C561435:sonidegib
keywords: basal cell carcinoma; hedgehog inhibitor; high-definition optical coherence tomography; noninvasive diagnosis; reflectance confocal microscopy