Hypertrophic lichenoid dermatitis immune-related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma

J Cutan Pathol. 2020 Oct;47(10):954-959. doi: 10.1111/cup.13739. Epub 2020 Jun 10.

Abstract

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.

Keywords: XPO1 inhibitor; anti-PD-1/PD-L1 therapy; hypertrophic lichenoid dermatitis; immune-related adverse event; squamous cell carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Acitretin / administration & dosage
  • Acitretin / therapeutic use
  • Aged
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Squamous Cell
  • Dermatitis / immunology
  • Dermatitis / pathology
  • Drug Eruptions / pathology
  • Drug Therapy, Combination
  • Exportin 1 Protein
  • Female
  • Fluocinonide / administration & dosage
  • Fluocinonide / therapeutic use
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Hypertrophy / pathology
  • Immune Checkpoint Inhibitors / adverse effects*
  • Karyopherins / adverse effects
  • Karyopherins / antagonists & inhibitors*
  • Karyopherins / therapeutic use
  • Keratolytic Agents / administration & dosage
  • Keratolytic Agents / therapeutic use
  • Lichenoid Eruptions / chemically induced
  • Lichenoid Eruptions / immunology
  • Lichenoid Eruptions / pathology*
  • Melanoma / drug therapy
  • Melanoma / secondary*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors*
  • Treatment Outcome
  • Triamcinolone / administration & dosage
  • Triamcinolone / therapeutic use

Substances

  • Antibodies, Monoclonal, Humanized
  • Glucocorticoids
  • Immune Checkpoint Inhibitors
  • Karyopherins
  • Keratolytic Agents
  • Programmed Cell Death 1 Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Triamcinolone
  • Fluocinonide
  • pembrolizumab
  • Acitretin