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

Introduction: Basal cell carcinoma accounts for 80% of all non-melanoma skin cancer. Vismodegib is the hedgehog signaling pathway inhibitor, which has shown improved outcome in both locally advanced and metastatic basal cell carcinoma. There are, however, reports of cutaneous squamous cell carcinomas developing while on active treatment with vismodegib. 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. Case presentation: 44-year-old Caucasian man with 10 year history of basal cell carcinoma on his left chest wall and left shoulder was treated with local resection and actively on vismodegib. He presented with enlarging and infected mass. He underwent left forequarter amputation of his left arm, shoulder and clavicle. Pathology reported basosquamous cell carcinoma with scapula invasion and axillary lymph node metastases. Staging was stage III T4N1M0. He continued on vismodegib post-operation. Three months after his amputation, the patient presented with a recurrent left shoulder mass with nonhealing surgical wound. Imaging revealed vascular invasion. Biopsy of the lesion was consistent with invasive squamous cell carcinoma with genomic profiling of PIK3R1, PTCH1 and STK11 gene mutations. At the patient’s request he was subsequently transferred to another facility for a second surgical opinion. Conclusion: Biopsy and genetic analyses of basal cell carcinoma lesions should be considered in every case that has treatment plan for hedgehog signaling pathway inhibitor to evaluate for potential secondary squamous cell carcinoma growth. Further study is needed to confirm the mechanism of basal cell resistance to anti-smoothened therapy and eventual squamous cell carcinoma growth.