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

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-yearold woman with metastatic melanoma who began treatment with an ICIpembrolizumab-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.

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.…”

“…This occurred in 23 lichenoid cirAEs (18.6%). Other effective treatments used in conjunction with topical and systemic medications included narrowband UV-B phototherapy and oral acitretin . Specifically, when patients developed palmoplantar lesions, they saw improvement when treated with phototherapy .…”

Hypertrophic lichenoid dermatitis during pembrolizumab treatment

“…1 Lichenoid dermatitis and its hypertrophic variant are also reported as cutaneous irAEs. [2][3][4] Hypertrophic lichenoid dermatitis should be distinguished from well-differentiated squamous cell carcinoma (SCC) because of their clinical and histological similarities. 2,3 In the present case, a differential diagnosis from SCC was needed because the architecture of the acanthosis resembled downward growth of SCC.…”

“…[2][3][4] Hypertrophic lichenoid dermatitis should be distinguished from well-differentiated squamous cell carcinoma (SCC) because of their clinical and histological similarities. 2,3 In the present case, a differential diagnosis from SCC was needed because the architecture of the acanthosis resembled downward growth of SCC. However, a diagnosis of SCC could be excluded because the cellular atypia of keratinocytes was not obvious and his skin lesions improved with topical corticosteroids.…”

Pembrolizumab-Induced Hypertrophic Lichenoid Dermatitis and Bullous Pemphigoid in One Patient

“…HLD is rarely reported as a side effect of Pembrolizumab and its exact pathogenesis remains unknown. [ 13 14 15 ] Honda et al , (2021) reported CD8+ T cell infiltration in the upper dermis with the expression of PD-L1 on the epidermal keratinocytes. [ 14 ] Those findings suggest that inhibiting the interaction between PD-L1 on keratinocytes and PD-1 on dermal T cells may cause epidermal hypertrophy.…”