Abstract
Background and Objective
PD-1 inhibitors have revolutionized cancer therapies and are being used to treat an expanding array of cancers. To best serve patients, clinicians should be familiar with the spectrum of skin manifestations associated with PD-1 inhibitor therapy. Here, we report a unique case of hypertrophic lichen planus (HLP) in a 64-year-old man treated with pembrolizumab; the presentation initially suggested a squamous cell carcinoma (SCC) morphology, then evolved into a morphology more typical of hypertrophic lichen planus. This case underscores the need for caution in diagnosing eruptive SCCs associated with PD-1 inhibitor therapy. In such instances, maintaining a high suspicion for lichenoid reactions as sequelae of PD-1 inhibitor treatment and starting an empiric trial of therapy for lichenoid dermatitis may be warranted to ensure timely management of lesions.
Methods
We describe a case of hypertrophic lichen planus mimicking squamous cell carcinoma in the setting of PD-1 inhibitory therapy with pembrolizumab. A PubMed literature review was conducted to identify other cases and determine the incidence of lichenoid reactions imitating squamous cell carcinoma in the setting of PD-1 inhibitor use.
Results
Our case is one of the few available pieces of literature describing eruptive hypertrophic lichen planus imitating SCC in the setting of PD-1 inhibitor use. Initial skin nodule biopsy appeared histologically compatible with squamous cell carcinoma. Repeat biopsy of the skin lesions revealed histological features consistent with hypertrophic lichen planus. Over time, lower extremity lesions evolved into a more typical appearance of hypertrophic lichen planus. Treatment with topical 0.05% clobetasol ointment and oral acitretin 25 mg led to complete resolution of lesions within 2–3 months.
Conclusions
This case underscores the significance of maintaining vigilance for lichenoid reactions as potential sequelae of PD-1 inhibitor therapy. It highlights the variability in initial presentation and the potential for lesions to transform over time. Timely recognition and appropriate management, including high-potency topical corticosteroids and oral acitretin, are crucial for achieving favorable outcomes in patients experiencing such reactions. More studies are necessary to fully analyze the rate of HLP occurrence as a consequence of PD-1 inhibitor use.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Clinicians should maintain a high suspicion for lichenoid reactions as sequelae of PD-1 inhibitor treatment. |
Severe cases of hypertrophic lichen planus may mimic well-differentiated squamous cell carcinoma. |
Timely recognition and appropriate management of skin reactions induced by PD-1 inhibitors are crucial for patient care. |
1 Introduction
Hypertrophic lichen planus (HLP) is an uncommon, chronic variant of lichen planus. HLP lesions are typically symmetric in distribution, and most commonly affect the dorsal surfaces of the hands and the shins [1].
This report is aimed at commenting on the prevalence of PD-1-inhibitor-induced lichenoid reactions, as well as how they may mimic squamous cell carcinoma (SCC) in hypertrophic cases. We report a case of PD-1-inhibitor-associated lichenoid reactions in which lesions with a keratoacanthoma (KA) morphology evolved into a more classic case of HLP. Lichenoid reactions have been reported to occur in as many as 25% of patients treated with pembrolizumab; therefore, clinicians must maintain a high degree of suspicion for hypertrophic HLP variants, given their clinical and histopathological similarities to SCC [2, 3]. This case adds to the body of evidence indicating that these reactions can mimic SCC and additionally highlights how the histological appearance of these reactions can change over time. Given the widespread use of PD-1 inhibitors, clinicians’ familiarity with the spectrum of presentation is important to ensure timely and appropriate management.
2 Case Report
A 64-year-old man with bilateral renal clear cell carcinoma and a medical history of right radical nephrectomy and left kidney cryoablations presented in December 2021 with worsening soreness and ulcerations of the mouth since October 2021. The patient was prescribed clotrimazole 10-mg troches to use four times daily and magic mouthwash to use as needed for pain. However, mucositis symptoms continued despite proper treatment. After several months, he began developing nodular verrucous growths on the dorsal hands and bilateral lower extremities, for which he was referred to dermatology (Fig. 1).
Biopsy of a right anterior shin lesion was performed, and the histopathology of the lesion was consistent with SCC extending to the deep margin, with notable surrounding lymphocytic inflammation (Fig. 2). Eruptive KAs in the setting of pembrolizumab treatment have been reported [4]. Interestingly, a patchy lichenoid lymphocytic infiltrate was present and might have provided an early clue as to an evolving hypertrophic lichenoid dermatitis.
The patient was referred for Mohs surgery for treatment of the SCC-like plaques on his dorsal hands. Follow-up after surgery indicated new nodularity within the suture lines, graft, and native skin. A repeated biopsy of the left dorsal hand lesions was performed to rule out recurrence. Histopathologic examination of the specimen revealed marked irregular epidermal hyperplasia with hypergranulosis, basal layer vacuolization, junctional necrotic keratinocytes, and accentuated lichenoid lymphocytic infiltrate at the bases of acanthotic rete ridges (Fig. 3). Additionally, by that time, the SCC-like lesions on his shins had evolved to ulcerated plaques with verrucous and violaceous borders (Fig. 4). A repeat biopsy of the right shin was performed, and histopathology also demonstrated hypertrophic lichenoid dermatitis.
The changes shown in Fig. 3 suggested HLP, although, given the patient’s clinical history, a lichenoid reaction triggered by PD-1 inhibitor therapy was suspected. The lesions were treated with topical 0.05% clobetasol ointment twice daily and oral acitretin 25 mg daily, and dramatic amelioration of the lesions was observed after only 2 weeks. One month later, topical clobetasol was stopped and acitretin was continued. At 1-month follow-up, only post-inflammatory pigmentation remained, so acitretin was discontinued. Subsequent follow-up appointments 1 and 2 months later showed no signs of recurrence of the disease, and only red-brown patches indicative of post-inflammatory pigmentation remains (Fig. 5). The patient provided verbal consent to the writing of this case report at the time of follow-up.
3 Discussion
Immune checkpoint inhibitors such as pembrolizumab have been shown to significantly suppress tumor burden and metastasis; however, they also frequently cause cutaneous eruptions. LP-like eruptions have been reported to occur in as many as 25% of patients receiving PD-1 inhibitor therapy [2, 3] and have also been reported to induce KA [4]. Herein, we describe the first reported case of a SCC-like eruption that was secondary to PD-1 therapy and evolved into a HLP-like rash.
HLP classically presents as hyperkeratotic papules and plaques on the pretibial areas of the lower extremities [5]. Histologically, HLP presents as pronounced epidermal hyperplasia, hypergranulosis, and basal cell vacuolar degeneration [6]. Severe cases of hypertrophic LP in which features of pseudoepitheliomatous hyperplasia are evident may mimic well-differentiated SCC [7].
This case underscores the need for caution in diagnosing eruptive KAs associated with PD-1 inhibitor therapy. In such instances, an empiric trial of therapy for lichenoid dermatitis may be warranted before surgery is performed, particularly in cases with subtle lichenoid inflammation, as observed in the initial biopsy from our patient’s shin. This study is clinically valuable because of the rarity of reported cases of PD-1-inhibitor-induced HLP; however, it is limited by the small patient sample size in which HLP was observed. More studies are necessary to fully analyze the rate of HLP occurrence as a consequence of PD-1 inhibitor use.
References
Weston G, Payette M. Update on Lichen Planus and its clinical variants. Int J Women’s Dermatol. 2015;1(3):140–9. https://doi.org/10.1016/j.ijwd.2015.04.001.
Coleman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS. Inflammatory eruptions associated with immune checkpoint inhibitor therapy: a single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. J Am Acad Dermatol. 2019;80(4):990–7. https://doi.org/10.1016/j.jaad.2018.10.062.
Shi VJ, Rodic N, Gettinger S, et al. Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol. 2016;152(10):1128–36. https://doi.org/10.1001/jamadermatol.2016.2226.
Freites-Martinez A, Kwong BY, Rieger KE, Coit DG, Colevas AD, Lacouture ME. Eruptive keratoacanthomas associated with pembrolizumab therapy. JAMA Dermatol. 2017;153(7):694–7. https://doi.org/10.1001/jamadermatol.2017.0989.
Qian H, Jiao L, Fan Z, Wang L, Liu B, Miao G. Analysis of immunologic function changes in lichen planus after clinical treatment. Med Sci Monit. 2018;24:8716–21. https://doi.org/10.12659/MSM.910931.
Riahi RR, Cohen PR. Hypertrophic lichen planus mimicking verrucous lupus erythematosus. Cureus. 2018. https://doi.org/10.7759/cureus.3555.
Levandoski KA, Nazarian RM, Asgari MM. Hypertrophic lichen planus mimicking squamous cell carcinoma: the importance of clinicopathologic correlation. JAAD Case Reports. 2017;3(2):151–4. https://doi.org/10.1016/j.jdcr.2017.01.020.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Funding
Not applicable.
Conflict of Interest
Not applicable.
Ethics Approval
The patient provided consent for their photographs and medical information to be published in print and online, with the understanding that the information might be made publicly available.
Availability of Data and Material
Not applicable.
Code Availability
No custom code was used to generate or process the data described in the manuscript.
Consent to participate
Provided.
Consent for publication
Written informed consent for publication of their details was obtained from the patient/study participant/parent/guardian/next of kin.
Authors’ Contributions
The authors confirm contribution to the paper as follows: study conception and design: Lim, O, Maher, E; data collection: Lim, O, Maher, E, Miller, D; analysis and interpretation of results: Lim, O, Maher, E, Miller, D; draft manuscript preparation: Lim, O. All authors reviewed the results and approved of the final version of the manuscript. The patient provided consent for their photographs and medical information to be published in print and online, with the understanding that the information might be made publicly available.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
About this article
Cite this article
Lim, O., Maher, E. & Miller, D.D. PD-1 Inhibitor Induced Hypertrophic Lichen Planus: A Case Report. Drugs R D 24, 353–357 (2024). https://doi.org/10.1007/s40268-024-00461-x
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40268-024-00461-x