Emergence of Squamous Cell Carcinoma during Treatment of Basal Cell Carcinoma with Vismodegib

Basal cell carcinoma (BCC) accounts for 80% of all non-melanoma skin cancer [1]. Advanced disease is infrequently seen, but when present can be a surgical challenge or even life threatening. Recent studies show that mutations in the hedgehog (HH) signaling pathway are associated with the majority of BCC. Hedgehog protein binds to patched homologue 1 (PTCH1) transmembrane receptor, which prevents inhibition of PTCH-1 signaling by smoothened homologue (SMO). These mutations cause inactivation of PTCH1or activate SMO, which lead to uncontrolled proliferation of basal cell of skin, then development of basal cell carcinomas (BCC). Vismodegib is the first hedgehog signaling pathway inhibitor (SMO inhibitor), which has shown 21% complete response rate and significantly improved outcome in both locally advanced and metastatic BCC (43% and 30% response rates, respectively). Median survival was 7.6 months in both cohorts [2]. There are, however, reports of cutaneous squamous cell carcinomas (SCC) developing while on active treatment with vismodegib. Herein, we present a case of transition to squamous cell carcinoma after vismodegib treatment in a patient with a 10-year history of basal cell carcinoma.