Vismodegib is useful to treat locally advanced or metastatic basal cell carcinomas (BCCs),1 but to our knowledge, its use as a neoadjuvant to shrink BCCs before surgery has not been reported. This case illustrates the role of vismodegib as a neoadjuvant agent. In addition, this case highlights the fact that a patient with Gorlin syndrome can develop resistant BCCs while taking vismodegib, a phenomenon not widely recognized although recently reported.2
Figure 1. Clinical and computed tomographic (CT) images of a 55-year old man with Gorlin syndrome. The patient's locally advanced basal cell carcinoma (BCC) regressed under treatment with neoadjuvant vismodegib but demonstrated areas of drug resistance. Residual BCC and resistant areas were excised. A, Locally advanced BCC on the right scalp prior to treatment. B, Tumor shrinkage after 51 weeks of vismodegib therapy showing development of 2 areas of resistant BCC (arrowheads). C, After surgical excision, the patient received full-thickness skin grafts to cover the right scalp and the right tragus/external auditory canal, shown here at 2 months after surgery. D, Pretreatment axial CT image shows bony defects of the calvarium under the BCC. E, Posttreatment CT scan shows shrinkage of the calvarial defect after vismodegib therapy.
Figure 2. Vismodegib-resistant basal cell carcinoma (BCC) tumors (hBCCSmos) show increased levels of Gli transcription factors and pik3c (phosphatidylinositol 3-kinase catalytic) enzymes. Tumor hBCCSmoR1 was on the tragus and hBCCSmoR2 was on the posterior scalp. A, Compared with normal skin from the same patient, both resistant tumors showed elevation of pik3c (isoform 2a) level. Tumor hBCCSmoR2 showed elevations of Gli1, ptch1 protein, and all isoforms of pik3c levels. Analysis was undertaken by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) performed in triplicate (RNeasy Mini Kit; Qiagen). Transcripts were quantified in triplicate using Brilliant II SYBR Green qRT-PCR Master Mix Kit (Agilent Technologies) with primers to human GLI1,4PTCH1,4 and PIK3C isoforms.5 B, Immunofluorescence analysis performed on formalin-fixed, paraffin-embedded tissue shows that Gli1 protein levels are elevated in tumor hBCCSmoR2 but not in hBCCSmoR1 compared with normal skin from the same patient. The top row of images depicts tissues viewed without fluorescence; the bottom row of images depicts tissues viewed with fluorescence. Immunofluorescence studies were performed with anti-Gli1 (1:500; Cell Signaling) and Hoechst 33342 (1:10 000; Invitrogen). Confocal images were acquired on a Leica SP2 AOBS Laser Scanning Microscope with an HCX PL APO 63X oil-immersion objective.
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