Immunohistochemical analysis of lichenoid reactions in patients treated with anti-PD-L1 and anti-PD-1 therapy

J Cutan Pathol. 2016 Apr;43(4):339-46. doi: 10.1111/cup.12666. Epub 2016 Feb 10.

Abstract

Background: Recent advances in the immunotherapeutic treatment of cancer have led to the development of multiple new directed therapies including monoclonal antibodies that block the immune checkpoint T-cell receptor programmed death 1 (PD-1) and the PD-1 ligand, programmed death ligand 1 (PD-L1). Various immune-related toxicities have been associated with these drugs including, most commonly, skin rashes.

Methods: Five cases of lichenoid dermatitis, including one case of lichenoid mucositis and one case of lichen sclerosus, associated with anti-PD-L1 and anti-PD1 therapy were compared with three biopsies of non-drug-related lichen planus (LP) and three lichen planus-like keratoses (LPLK) used as controls.

Results: Histopathologic and immunophenotypic analysis of these lichenoid lesions demonstrated significantly greater histiocytic infiltrates than observed in control lichenoid reactions (p = 0.0134). We also observed increased spongiosis and epidermal necrosis. No significant differences were seen in expression of CD3, CD4:CD8, CD20, PD-1, CD25, Foxp3, CXCL13 and PD-L1 expression.

Conclusions: These findings expand the literature of immune-related toxicities of PD-L1 and PD-1 blockade to include lichenoid dermatitis and lichenoid mucositis. Of note, these cutaneous side effects were amenable to topical treatment, without the need for medication dose reduction or discontinuation.

Keywords: drug reaction; immunotherapy; lichenoid reaction; programmed death 1; programmed death ligand 1.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors*
  • Female
  • Humans
  • Lichenoid Eruptions* / chemically induced
  • Lichenoid Eruptions* / pathology
  • Male
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor