Hypertrophic lichen planus (HLP) is a cutaneous subtype of the T-cell-mediated autoimmune disorder, lichen planus, a chronic inflammatory disease that can affect the skin, scalp, oral mucosa, esophagus, and anogenital area (1–3). HLP commonly presents on the lower extremities as pruritic papules and verrucous, polygonal plaques with white lines known as Wickham striae (4, 5). Histologically, HLP presents as hyperplasia limited to the epidermis, lymphocytic infiltration of the dermoepidermal junction, hypergranulosis, acanthosis, and hyperorthokeratosis (6). HLP is also characterized by features of pseudoepitheliomatous hyperplasia, making it difficult to distinguish from cutaneous squamous cell carcinoma (cSCC) (7). The similar clinical and histopathological characteristics between HLP and cSCC often create diagnostic challenges for dermatologic providers. Additionally, HLP can exhibit malignant transformation into cSCC (8–10). This uncertainty, along with the discomfort that is associated with HLP, may result in either aggressive or inadequate treatment strategies that can undermine the patient’s quality of life (5, 10).

Here, we report a case series of three female patients who were referred to a single tertiary center with a diagnosis of cSCC and were ultimately diagnosed with HLP after further review of biopsy results and their entire clinical picture. We suggest that the challenge of diagnosing HLP can be overcome with careful clinicopathological correlation. It is important for clinicians to understand the pathogenesis of HLP and have good clarity regarding diagnoses of “multifocal cSCC,” especially when patients are not responding to therapy. We also discuss treatment options for HLP, including oral retinoids in combination with high-potency topical steroids along with newer therapeutic options including JAK inhibitors (11). We hope to provide dermatologists, dermatologic surgeons, and dermatopathologists with the clinical and histopathologic characteristics of HLP and HLP-directed treatment strategies that are crucial to distinguishing HLP from cSCC to decrease patient morbidity from unnecessary interventions.

A PubMed search of articles indexed for MEDLINE and a Google Scholar search using the terms “hypertrophic lichen planus” and “squamous cell carcinoma” revealed fewer than 26 reported cases of HLP misdiagnosed as cSCC (Supplementary Table S1, which lists literature describing lichen planus misdiagnosed as squamous cell carcinoma). HLP and cSCC share clinical and histopathological features, which can lead to the misdiagnosis of HLP as cSCC (12–15). This diagnostic dilemma is further complicated by evidence that HLP can undergo malignant transformation and focally progress to cSCC (6, 8, 9). Our case series demonstrates the importance of assessing the overall clinical picture in the setting of presumed multifocal cSCC to avoid non-indicated procedures.

In our case series, initial misdiagnosis for each patient was likely due to a combination of clinical and histopathological similarities between HLP and cSCC, and a lack of clinicopathological correlation. The mean duration of time with an SCC diagnosis prior to an HLP diagnosis was 4 years (range 1–8 years). After correctly identifying HLP in our patients, therapy was initiated with oral or topical retinoids and high-potency topical steroids, with a mean improvement time of 6 weeks (Table 1).

Clinically, HLP plaques are frequently located on the distal lower extremities and are associated with follicular accentuation (4, 5). Additionally, patients may have no history of sun damage and no predisposing risk factors for cSCC (13). Histologically, HLP is notable for hyperorthokeratosis, wedge-shaped hypergranulosis, and irregular psoriasiform hyperplasia limited to the epidermis (Figure 3), while cSCC presents with cytologic atypia, extension beyond the superficial dermis, and other invasive characteristics (6, 13).

The pathogenesis of HLP is T-cell-mediated, involving the Janus kinase 2 (JAK2)/the signal transducer and activator of transcription 1 (STAT1) pathways. IFN-γ, IL-21, and pSTAT1 have been found in the dermal infiltrate of HLP lesions (16, 17). IFN-γ was shown to prime keratinocytes and increase keratinocyte susceptibility to CD8⁺ T-cell-mediated cytotoxicity through the induction of major histocompatibility complex expression. These cell-mediated cytotoxic responses are dependent on JAK2 and STAT1 signaling, as demonstrated by JAK2 and STAT1 knockouts, which protected IFN-γ-primed keratinocytes from cell-mediated cytotoxic responses (17). These recent developments have supported the use of topical and systemic JAK inhibitors in cutaneous inflammatory and immune-mediated processes (18). Furthermore, other recently published studies have identified SPRR1B, miRNA27b, and miRNA137 gene expressions and a − 308 G/A polymorphism in TNFα as potential biomarkers for oral lichen planus (19, 20). Additional future directions for HLP pathogenesis research include the identification of potential genetic biomarkers to further differentiate HLP from cSCC.

The current first-line therapy for HLP is topical corticosteroids; however, second-line non-steroidal treatments, such as acitretin, sulfasalazine, griseofulvin, topical calcineurin inhibitors, and narrow-band ultraviolet B radiation, are also associated with increased response rates (5, 21). With advancements in understanding HLP pathogenesis, JAK inhibitors, such as tofacitinib and baricitinib, have been successfully adopted into some lichen planus treatment plans and have served as effective therapeutic agents (17, 22, 23). Additionally, the IL-4Rα antagonist and biological immunomodulator dupilumab shows promise as an effective therapy for lichen planus (24–27). JAK inhibitors and dupilumab should be further evaluated in randomized-controlled trials for widespread use in the treatment of HLP. Treatments for cSCC differ from those of HLP and include, but are not limited to, cryotherapy, laser therapy, excision, and Mohs micrographic surgery, depending on the size, location, and aggressiveness of the lesion (23).

HLP is a chronic cutaneous subtype of lichen planus, a T-cell-mediated autoimmune disorder. Clinically, HLP presents as pruritic, hypertrophic papules and plaques on the lower limbs and can significantly impair patient quality of life. Patients with HLP share clinical and histopathological findings with cSCC, including pseudoepitheliomatous hyperplasia, often leading to misdiagnosis. Misdiagnosis can lead to inadequate treatment strategies and further affect patient wellbeing. The current effective first-line treatment for HLP is topical corticosteroids. Recent research into the pathogenesis of HLP implicates the JAK2/STAT1 pathway in increasing keratinocyte susceptibility to CD8⁺ T-cell-mediated cytotoxic responses. These advancements suggest JAK inhibitors may be effective in treating HLP, and in fact, there have been recent case reports of successful HLP treatment with JAK inhibitors. Additional future directions may include the identification of potential biomarkers of HLP, which may guide therapy. Finally, a comprehensive review of the patient’s presentation is vital to identifying features consistent with a diagnosis of HLP, as misdiagnosis as cSCC may result in unnecessary interventions that can increase patient morbidity and the use of medical resources.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author/s.

Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

NK: Writing – original draft, Writing – review & editing. LL: Supervision, Writing – original draft, Writing – review & editing. PS: Writing – original draft. JD: Conceptualization, Supervision, Writing – original draft, Writing – review & editing.