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1</a>B and C&#41;&#46; The tumor was removed&#44; and a partial skin graft was performed&#46; Histopathology revealed an infiltrating squamous and crateriform neoplasm with masses in the dermis composed of keratinocytes with a pale abundant cytoplasm and slight nuclear atypia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C and D&#41;&#44; thus enabling a diagnosis of keratoacanthoma&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">HLP is a T cell&#8211;mediated chronic idiopathic inflammatory skin disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> While the pathogenesis of the disease is not clearly defined&#44; eosinophils&#44; Koebner phenomenon&#44; and chronic venous insufficiency seem to play a key role&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> Oral and genital lichen planus and HLP can undergo malignant transformation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> The environmental risk factors for squamous cell carcinoma are chronic inflammation&#44; smoking&#44; human papillomavirus coinfection&#44; exposure to arsenic&#44; irradiation&#44; and immunosuppression&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Malignant transformation is uncommon<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and usually takes the form of well-differentiated cutaneous squamous cell carcinoma&#44; including keratoacanthoma and verrucous carcinoma&#44; although cases of metastatic cutaneous squamous cell carcinoma have been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The differential diagnosis includes pseudoepitheliomatous hyperplasia&#44; squamous cell carcinoma&#44; irritant seborrheic keratosis&#44; hypertrophic lupus erythematosus&#44; and pretibial epidermolysis bullosa&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Histopathology of HLP reveals orthokeratosis&#44; epidermal hyperplasia with acanthosis&#44; hypergranulosis&#44; vacuolar damage of the basement membrane&#44; and interface lichenoid infiltrate with eosinophils&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a> However&#44; hypergranulosis and damage to the basement membrane are variable and may also be observed in pseudoepitheliomatous hyperplasia&#44; which in turn may be difficult to differentiate from squamous cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Pseudoepitheliomatous hyperplasia is characterized by hyperplasia of the epidermis and adnexal epithelium&#44; as well as by irregular acanthosis&#46; Unlike cutaneous squamous cell carcinoma&#44; it does not invade the dermis&#44; does not infiltrate neurovascular structures&#44; and does not present cellular atypia&#46; Immunohistochemistry of squamous cell carcinoma reveals overexpression of p53 and perforating elastic fibers&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;8</span></a> Gene sequencing can contribute to the differential diagnosis&#44; since C15orf48 is overexpressed in squamous cell carcinoma&#44; whereas KRT9 is overexpressed in pseudoepitheliomatous hyperplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Similarly&#44; the clinical history and physical examination are essential&#46; HLP should be suspected when a patient presents with pretibial hypertrophic papules and plaques&#44; Wickham striae&#44; involvement of the oral and&#47;or genital mucosa&#44; and ungual abnormalities&#44; as well as absence of skin lesions associated with exposure to sunlight and risk factors for keratinocyte carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6</span></a> Lastly&#44; follow-up and biopsy make it possible to rule out malignant transformation if the lesions undergo rapid growth&#44; ulceration&#44; and bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment is based on topical&#44; 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Case and Research Letters
Hypertrophic Lichen Planus: Importance of Follow-Up and Clinicopathologic Correlation
Liquen plano hipertrófico: importancia del seguimiento y de la correlación clinicopatológica
S. Guillen-Climenta,
Corresponding author
santigc85@gmail.com

Corresponding author.
, S. Porcar Sauraa, C. Monteagudob,c, M.D. Ramón Quilesa
a Servicio de Dermatología, Hospital Clínico Universitario, Valencia, Spain
b Servicio de Anatomía Patológica, Hospital Clínico Universitario, Valencia, Spain
c Departamento de Patología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hypertrophic lichen planus &#40;HLP&#41; can undergo malignant transformation&#44; leading to the development of squamous cell carcinoma&#44; although this is an uncommon complication&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> Furthermore&#44; the histopathology findings of HLP&#44; inflammatory reactive changes&#44; and squamous cell carcinoma are usually similar&#44; thus making diagnosis challenging&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">A 70-year-old man consulted for very pruritic hypertrophic&#44; erythematous-violaceous polygonal papules and plaques that had gradually appeared on both legs &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#46; The lesions were accompanied by xerosis and cutaneous signs of chronic venous insufficiency&#46; No lesions were observed at other sites&#46; Given the suspected diagnosis of HLP&#44; serology testing for hepatotropic virus was requested&#46; The results were negative&#44; and biopsy specimens were taken from 2 lesions&#46; The histopathology study revealed epidermal hyperplasia with acanthosis&#44; prominent papillomatosis&#44; and marked hyperkeratosis&#44; with focal loss of the stratum basale in the distal portion of the rete ridges and a discrete lymphocytic infiltrate&#44; as well as underlying stromal repair processes &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A and B&#41;&#46; The patient was prescribed emollients and mometasone furoate cream&#44; with partial improvement of both the symptoms and the lesions&#46; After 5<span class="elsevierStyleHsp" style=""></span>months of follow-up&#44; the patient presented with a tumor measuring 1&#46;4<span class="elsevierStyleHsp" style=""></span>cm in diameter on the right pretibial region&#46; The tumor was crateriform with a central hyperkeratotic area and a painful infiltrated base &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B and C&#41;&#46; The tumor was removed&#44; and a partial skin graft was performed&#46; Histopathology revealed an infiltrating squamous and crateriform neoplasm with masses in the dermis composed of keratinocytes with a pale abundant cytoplasm and slight nuclear atypia &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>C and D&#41;&#44; thus enabling a diagnosis of keratoacanthoma&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">HLP is a T cell&#8211;mediated chronic idiopathic inflammatory skin disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> While the pathogenesis of the disease is not clearly defined&#44; eosinophils&#44; Koebner phenomenon&#44; and chronic venous insufficiency seem to play a key role&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> Oral and genital lichen planus and HLP can undergo malignant transformation&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> The environmental risk factors for squamous cell carcinoma are chronic inflammation&#44; smoking&#44; human papillomavirus coinfection&#44; exposure to arsenic&#44; irradiation&#44; and immunosuppression&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Malignant transformation is uncommon<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and usually takes the form of well-differentiated cutaneous squamous cell carcinoma&#44; including keratoacanthoma and verrucous carcinoma&#44; although cases of metastatic cutaneous squamous cell carcinoma have been described&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The differential diagnosis includes pseudoepitheliomatous hyperplasia&#44; squamous cell carcinoma&#44; irritant seborrheic keratosis&#44; hypertrophic lupus erythematosus&#44; and pretibial epidermolysis bullosa&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Histopathology of HLP reveals orthokeratosis&#44; epidermal hyperplasia with acanthosis&#44; hypergranulosis&#44; vacuolar damage of the basement membrane&#44; and interface lichenoid infiltrate with eosinophils&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5&#44;6</span></a> However&#44; hypergranulosis and damage to the basement membrane are variable and may also be observed in pseudoepitheliomatous hyperplasia&#44; which in turn may be difficult to differentiate from squamous cell carcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Pseudoepitheliomatous hyperplasia is characterized by hyperplasia of the epidermis and adnexal epithelium&#44; as well as by irregular acanthosis&#46; Unlike cutaneous squamous cell carcinoma&#44; it does not invade the dermis&#44; does not infiltrate neurovascular structures&#44; and does not present cellular atypia&#46; Immunohistochemistry of squamous cell carcinoma reveals overexpression of p53 and perforating elastic fibers&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6&#44;8</span></a> Gene sequencing can contribute to the differential diagnosis&#44; since C15orf48 is overexpressed in squamous cell carcinoma&#44; whereas KRT9 is overexpressed in pseudoepitheliomatous hyperplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Similarly&#44; the clinical history and physical examination are essential&#46; HLP should be suspected when a patient presents with pretibial hypertrophic papules and plaques&#44; Wickham striae&#44; involvement of the oral and&#47;or genital mucosa&#44; and ungual abnormalities&#44; as well as absence of skin lesions associated with exposure to sunlight and risk factors for keratinocyte carcinoma&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;6</span></a> Lastly&#44; follow-up and biopsy make it possible to rule out malignant transformation if the lesions undergo rapid growth&#44; ulceration&#44; and bleeding&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment is based on topical&#44; systemic&#44; and intralesional corticosteroids&#44; as well as acitretin&#44; methotrexate&#44; mycophenolate mofetil&#44; ciclosporin&#44; and hydroxychloroquine&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3&#44;5</span></a> Treatment is with surgery if keratinocyte carcinoma appears during the course of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion&#44; we present the case of a patient with HLP in whom keratoacanthoma developed during follow-up&#46; This association is infrequent&#44; although it illustrates the importance of follow-up&#46; Correct diagnosis and treatment are based on the correlation between clinical and histopathological features&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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