PTCH1 Mutation in a Patient With Metastatic Undifferentiated Carcinoma With Clear Cell Change

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Abstract

Clear cell basal cell carcinoma (BCC) is an unusual variant of BCC. Its pathogenesis, prognosis, and optimal management remain poorly described due to its rarity. This report presents a 51-year-old man with a history of excised BCC and cutaneous squamous cell carcinomas of the face, with multiple recurrent poorly differentiated carcinomas with clear cell changes of the shoulder for which further classification using conventional histologic means was not possible. His tumor tissue was sent to Foundation Medicine for testing, which revealed a high number of pathogenic genomic alterations, including a mutation in PTCH1. He was diagnosed with dedifferentiated BCC and started on vismodegib. He developed lung metastases while receiving vismodegib, and his disease continued to progress while he was undergoing treatment in a phase I clinical trial. Given the high number of pathogenic alterations suggestive of high tumor mutational burden, immunotherapy was considered and off-label authorization was obtained for treatment with a PD-1 antibody (pembrolizumab). He had a dramatic disease response after 4 infusions of pembrolizumab. Molecular testing was instrumental in determining the correct diagnosis and formulating appropriate treatment options for this patient. Molecular profiling of metastatic BCCs and its subtypes is essential to the development of effective targeted therapies and combination approaches.

Submitted June 15, 2018; accepted for publication April 19, 2019.Disclosures: Dr. Tsai has disclosed that she receives grant/research support from OncoSec Medical, Merck, and Bristol Myers-Squibb. Dr. Bastian has disclosed that he is a consultant for Lily Inc. The remaining authors have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.View associated contentCorrespondence: Katy K. Tsai, MD, Melanoma and Skin Cancer Program, UCSF Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, Box 1770, San Francisco, CA 94115. Email: katy.tsai@ucsf.edu
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