FormalPara Key Points

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).

Fig. 1
figure 1

Nodular growths on the hands and legs

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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.

Fig. 2
figure 2

Biopsy of a right anterior shin nodule showing islands of atypical keratinocytes with pink glassy cytoplasm invading into the dermis and extending to the deep margin (black arrow). Surrounding lymphocytic inflammation is noted (black circle)

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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.

Fig. 3
figure 3

Histology slide of the left dorsal hand, showing marked irregular epidermal hyperplasia (black arrow) with hypergranulosis (yellow arrows), basal layer vacuolization, junctional necrotic keratinocytes, and a lichenoid lymphocytic infiltrate (red arrows)

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Fig. 4
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Large, hyperkeratotic, and ulcerated plaques with violaceous borders on the anterior shin

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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.

Fig. 5
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The patient remains free from lesions, and the post-inflammatory pigmentation continues to fade

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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.