Epidermal cyst formation and hyperkeratosis in a patient treated with vismodegib for locally advanced Basal cell carcinoma.

SHORT COMMUNICATION Vismodegib, a Hedgehog (Hh) pathway inhibitor, was approved by the US Food and Drug Administration (FDA) in 2012 for the treatment of locally advanced (la) and metastatic (m) basal cell carcinoma (BCC). Interim results of the largest clinical study of vismodegib have shown complete (17.5%) or partial (39.8%) response, and stable (39.0%) or progressive (2.8%) disease in 251 cases of laBCC and mBCC (1). Formation of squamous cell carcinoma (SCC) within the tumour area, as well as occurrence of SCC at other body sites, has been reported in patients treated with vismodegib (2–6). To our knowledge this is the first report of formation of epidermal cysts and hyperkeratosis within the tumour area during treatment with vismodegib. A 52-year-old man was referred to our hospital with a recurrent BCC that was treated with cryotherapy 15 years previously, followed by multiple incomplete excisions. An area of scar tissue and minimal hyper-keratosis was visible on the nose, extending to his right cheek and upper lip (Fig. 1A). Several biopsies were taken, and showed infiltrative BCC invading the deep dermis; there was subtle hyperkeratosis, but no evidence of SCC or BCC with squamous differentiation (Fig. 2A). To avoid mutilating surgery, the patient was enrolled in a clinical trial with oral vismodegib 150 mg daily (7). This trial was approved by the ethics and scientific committee of the Maastricht University Medical Centre. After 7 weeks of treatment, hyperke-ratosis increased and comedo-like lesions developed on the nose (Fig. 1B). Sequential skin biopsies showed epidermal cysts, but no residual BCC was found. Because of the impressive hyperkeratosis, we feared for progression into SCC despite the absence of malig-nancy in repeated biopsies, taking the possibility of a sampling error into account. Therefore, we performed Mohs' micrographic surgery 5 months after initiation of vismodegib therapy, which was continued until the day before surgery. Five stages of Mohs' surgery with 19 frozen sections, including nose amputation, were necessary to achieve clear margins. Histological examination showed residual infiltrative BCC, accompanied by epidermal cyst formation and some hyperkeratosis, but no evidence of SCC (Fig. 2B). Immunohistochemi-cal analysis confirmed residual BCC cells by positive staining for Ber-Ep4, whereas epidermal cysts stained negative. DISCUSSION Pseudocyst-like structures as a result of tumour regression during the use of vismodegib have been reported previously; however, they were characterized by a different histology with so-called pseudocystic areas consisting of extensive fibrosis and some residual BCC cells …