Multiple Keratoacanthoma-like Lesions in a Patient Treated with Pembrolizumab

Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center

“…Although it is not clear why these anticancer drugs cause secondary skin neoplasia, there is a hypothesis that they may induce paradoxical activation of the mitogen‐activated protein kinase pathway in keratinocytes, leading to keratoacanthoma or squamous cell carcinoma 24,25 . Actually, the occurrence of eruptive squamous cell carcinomas or keratoacanthomas associated with ICI is rare, but case reports have increased recently 26–30 . Some of the reported cases have a past history of molecular‐targeted agents or a combination immunotherapy with the Toll‐like receptor 9 agonist 26,27 and other cases have no past history of other chemotherapy 28–30 .…”

“…It has not been known exactly why secondary skin neoplasia occurs. However, based on the fact that it is characterized by epidermal dysplasia and hyperplasia on the UV‐exposed area in old age, and that some cases were improved with topical steroid therapy, the hypothesis that ICI raises an immunological reaction against subclinical UV‐induced epidermal dysplasia resulting in transient epithelial proliferation is suggested 28 . Because both molecular‐targeted agents and ICI‐induced secondary tumors have been reported, whether PD‐1/PD‐L1 inhibitors alone could cause keratoacanthoma merits further study.…”

“…[26][27][28][29][30] Some of the reported cases have a past history of molecular-targeted agents or a combination immunotherapy with the Toll-like receptor 9 agonist 26,27 and other cases have no past history of other chemotherapy. [28][29][30] In previously reported cases, eruptive keratoacanthoma-like lesions appeared on the ultraviolet (UV)-exposed areas in old age between 2 and 18 months after immunotherapy. 27,[29][30][31][32] It has not been known exactly why secondary skin neoplasia occurs.…”

Development of cutaneous squamous cell carcinoma during pembrolizumab therapy

“…Kento MIZUTANI, 1 Takehisa NAKANISHI, 1 Makoto IKEJIRI, 2 Hiroto YUASA, 3 Yoshiaki MATSUSHIMA, 1 Makoto KONDO, 1 Yasuo NAKAI, 1 Koji HABE, 1 Kaname NAKATANI, 2 Keiichi YAMANAKA 1…”

“…Development of keratoacanthoma or cSCC during pembrolizumab was reported. These lesions are limited to sun-exposed areas, 1,2 and ultraviolet (UV)-induced carcinogenesis is suspicious for cSCC development. In our case, the beneficial effect of pembrolizumab in the nodal metastatic urethral cancer suggests elicitation of inflammatory reaction to cSCC and related conditions, which may actualize occult multiple skin lesions with UVinduced mutated cells and HPV-involved keratinocytes.…”