Hypertrophic Lichen Planus with Histological Features of Squamous Cell Carcinoma Associated with Immune Checkpoint Blockade Therapy

Abstract

Immune checkpoint blockade (ICB) is highly effective for the treatment of metastatic cancers, but its side effects are incompletely understood. The objective of this article is to highlight hypertrophic lichen planus (HLP) with histological features diagnosed as squamous cell carcinoma (SCC), which is a potential cutaneous reaction to ICB. Two patients (75 and 69 years) presented with lesions diagnosed as SCC on biopsy, which developed after 3-9 months on ICB therapy. Biopsies demonstrated endophytic, atypical, or cystic squamous proliferations consistent with cutaneous SCC. However, the clinical presentation including monomorphic nature of the lesions and lichenoid inflammation in the background were consistent with HLP. Patients initially received topical 5-fluorouracil (5-FU) to reduce the hyperkeratotic lesions followed by topical steroids. The eruptions readily responded to this treatment regimen. Dermatologic immune-related adverse events (irAEs) are the most common irAEs associated with ICB therapy. Our findings indicate that HLP resembling SCC on biopsy is a potential side effect of ICB that can be correctly diagnosed on careful clinical exam and is responsive to ICB cessation and topical steroid with or without 5-FU treatment. The Oncologist 2020;25:366-368 KEY POINTS • Immune checkpoint blockade is associated with cutaneous immune-related adverse events including lichen planus. • Hypertrophic lichen planus can appear as squamous cell carcinoma histologically and clinical context is key for the proper diagnosis. • Hypertrophic lichen planus can be safely treated with topical steroids with or without topical 5-fluorouracil in cases with severe hyperkeratotic lesions. • Immune checkpoint blockade may be safely continued if clinical presentation is consistent with hypertrophic lichen planus.

Immune-Checkpoint Induced Skin Toxicity Masked as Squamous Cell Carcinoma: Case Report on Mimickers of Dermatological Toxicity with PD-1 Inhibition

“…There are case reports in the literature describing similar scenarios of lichen planus misdiagnosed as squamous cell carcinoma after skin biopsy as there are overlapping clinical, and histopathological features between the two entities [12][13][14][15]. Similar to other case reports, lesions appeared after several months of PD-1/PD-L1 blockade for our patients [14,35,36].…”

“…Skin irAEs remain poorly characterized and the spectrum of reactions remains to be fully elucidated. There are several case reports in the literature describing patients on ICIs who were initially diagnosed with squamous cell carcinomas, but further review revealed it was a lichenoid reaction due to PD-L1/PD-1 checkpoint inhibition [12][13][14][15]. Here, we report on two cases of ICI-induced dermatitis eruptions which were initially diagnosed with squamous cell carcinoma, but the clinical course and further pathological clarification were more consistent with a skin irAE.…”

Management of Cutaneous Immune-Related Adverse Events in Patients With Cancer Treated With Immune Checkpoint Inhibitors

“…Twenty-five articles that discussed 123 lichenoid cirAEs were identified following treatment with immunotherapy . One hundred six lichenoid eruptions (86.2%) developed following PD-1/PD-L1 inhibitor monotherapy.…”

Cutaneous Adverse Reactions of Immunotherapy in Patients with Advanced Melanoma

“…Nail involvement with dystrophy, ridging, and hyperkeratosis have also been reported. Several other clinical types of lichen planus have been described in case reports and case series, including erosive and hypertrophic variants, bullous lichen planus pemphigoids, and inverse lichen planus [ 51 ].…”

“…Unlike typical lichen planus, apoptotic keratinocytes—associated with variable parakeratosis, necrosis, epidermal spongiosis, and eosinophils—may be seen. Recent reports also describe a clinical type of hypertrophic lichen planus with squamous cell carcinoma-like histology [ 51 ].…”