To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma

Mackenzie Poole, Robert A. Schwartz, W. Clark Lambert, Albert Alhatem

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.

Original languageEnglish
Pages (from-to)903-915
Number of pages13
JournalArchives of Dermatological Research
Issue number4
StatePublished - May 2023
Externally publishedYes


  • Keratoacanthoma
  • Nivolumab
  • Programmed death-1 inhibitors
  • Squamous cell carcinoma


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