Development of cutaneous squamous cell carcinoma during pembrolizumab therapy

Mizutani, Kazuki; Nakanishi, Takehisa; Itō, Makoto; Yuasa, Hiroto; Matsushima, Yoshiaki; Kondo, Makoto; Nakai, Yasuo; Habe, Koji; Nakatani, Kaname; Yamanaka, Keiichi

doi:10.1111/1346-8138.15614

Cited by 2 publications

(3 citation statements)

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“…Eruptions have been treated with topical 4,10 and intra‐lesional steroids, 7,10 topical imiquimod, 6 cryotherapy, 6,7 intralesional 5‐flourouracil, 12,13 electrocautery and curettage, 14 and surgical excision 13 . Two patients had spontaneous regression 5,11 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, RAS mutations have been shown to underlie the development of SCCs and other squamoproliferative lesions occurring in melanoma patients treated with BRAF inhibitor targeted monotherapies. 2,3 There are now 22 cases (including our own) reported of eruptive KAs occurring in patients treated with anti-PD1 immunotherapies in the context of treatment for metastatic SCC, [4][5][6][7] metastatic lung adenocarcinoma, 8 renal cell carcinoma, 9,10 pancreatic cancer, 6 apocrine carcinoma, 11 metastatic ureteral carcinoma, 12 melanoma, 7,8,[13][14][15] and mesothelioma. 8 These have arisen in the setting of other anti-PD1-associated skin eruptions, including lichenoid eruptions, 6,8,9,12 bullous pemphigoid-like eruptions 14 and a psoriasis flair.…”

Section: Introductionmentioning

confidence: 99%

“…2,3 There are now 22 cases (including our own) reported of eruptive KAs occurring in patients treated with anti-PD1 immunotherapies in the context of treatment for metastatic SCC, [4][5][6][7] metastatic lung adenocarcinoma, 8 renal cell carcinoma, 9,10 pancreatic cancer, 6 apocrine carcinoma, 11 metastatic ureteral carcinoma, 12 melanoma, 7,8,[13][14][15] and mesothelioma. 8 These have arisen in the setting of other anti-PD1-associated skin eruptions, including lichenoid eruptions, 6,8,9,12 bullous pemphigoid-like eruptions 14 and a psoriasis flair. 13 The pathogenic mechanism underlying the development of eruptive squamoproliferative lesions in the context of PD1 inhibitors is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Multiple eruptive squamoproliferative lesions during anti‐PD1 immunotherapy for metastatic melanoma: Pathogenesis, immunohistochemical analysis and treatment

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Jackett

Cheung

et al. 2022

Dermatologic Therapy

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Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4: CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

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