Extramammary Paget Disease: A Report of 10 Cases

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Caso 1: placa eritematoexudativa de 10×12cm, moderadamente infiltrada y con bordes netos en la región inguinal derecha, que corresponde a una enfermedad de Paget extramamaria invasiva. B. Caso 3: placa eritematosa con exudado blanquecino de 6×4cm, moderadamente infiltrada y con bordes netos en el pliegue interglúteo, que corresponde a una enfermedad de Paget extramamaria in situ." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Blasco-Morente, A. Martín-Castro, C. Garrido-Colmenero, J. Tercedor-Sánchez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Blasco-Morente" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Martín-Castro" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Garrido-Colmenero" ] 3 => array:2 [ "nombre" => "J." 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Blasco-Morente, A. Martín-Castro, C. Garrido-Colmenero, J. Tercedor-Sánchez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "G." "apellidos" => "Blasco-Morente" "email" => array:1 [ 0 => "gonzaloblascomorente@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Martín-Castro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Garrido-Colmenero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Tercedor-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Gestión Clínica, Dermatología Médico Quirúrgica y Venereología, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Anatomía Patológica, Hospital Universitario Virgen de las Nieves, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de Paget extramamaria: 10 casos" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 846 "Ancho" => 1200 "Tamanyo" => 192773 ] ] "descripcion" => array:1 [ "en" => "A, Case 1: Erythematous, exudative plaque measuring 10×12cm, with moderate infiltration and well-defined borders on the right groin corresponding to invasive extramammary Paget disease. B, Case 3: Erythematous plaque with a whitish exudate measuring 6×4cm, moderate infiltration, and well-defined borders in the gluteal cleft corresponding to extramammary Paget disease in situ." ] ] ] "textoCompleto" => "IntroductionExtramammary Paget disease (EMPD) was first described by Crocker in 1889 as a localized carcinoma affecting the penis and scrotum in a 60-year-old goldsmith. The symptoms and histopathological characteristics were similar to those of mammary Paget disease, first described by James Paget in 1874.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> The disease is an extremely rare form of intraepithelial adenocarcinoma that may be accompanied by other malignant neoplasms.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> We report all cases of EMPD diagnosed during a 5-year period at a tertiary referral hospital.Case DescriptionsThe clinical and histologic characteristics of patients with EMPD are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. We recorded 10 cases (4 on the vulva, 3 in the perianal region, 2 on the right groin [<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A], and 1 on the gluteal cleft [<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B]) in 4 men and 6 women aged between 50 and 79 years. In all cases there was a diagnostic delay of between 1 and 5 years, and the patients received treatment that was ineffective for fungal infections in 5 cases (50%), chronic inflammatory disease (eczema and lichen simplex) in 5 cases (50%), Bowen disease in 1 case (10%), lichen sclerosus et atrophicus in 1 case (10%), and leukoplakia in 1 case (10%). The diagnosis of EMPD was confirmed in all cases by histopathologic study of the skin biopsy, and treatment was by radical removal of the lesion with wide margins. EMPD was in situ in 6 patients (60%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), and dermal invasion was detected in 4 patients (40%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). The disease persisted after surgery in 4 patients (66.7%) with EMPD in situ and in 3 patients (75%) with invasive disease. In addition, recurrence was detected in 1 case of EMPD in situ (16.7%) and in 1 case of invasive EMPD (25%); further surgery was necessary in both cases. A second neoplasm was detected in 4 patients: 2 (33.3%) with EMPD in situ had melanoma in situ (1 patient) and porocarcinoma and basal cell carcinoma (1 patient); 1 patient (25%) with invasive disease had chronic B-cell lymphoproliferative disorder; and 1 patient (25%) had low-grade papillary urothelial carcinoma. Two patients (20%), both with the invasive form, died from metastasized disease, one at 10 months and the other at 2 years. In the remaining 8 patients (80%), no recurrence was observed during a follow-up period ranging from 9 months to 4.5 years.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionHospital Universitario Virgen de las Nieves, Granada, Spain is a tertiary referral hospital serving a population of 439 035 people, among whom 10 patients were diagnosed with EMPD from 2009 to 2013. EMPD is a very infrequent neoplasm whose exact incidence is unknown, although it accounts for no more than 6.5% of all Paget diseases and only a few hundred cases have been published in the literature.<a class="elsevierStyleCrossRefs" href="#bib0010">2–4</a> EMPD generally affects whites aged between 50 and 80 years, mainly women at a ratio of 2.4:1, as in our series, although in Asians it usually affects men.<a class="elsevierStyleCrossRefs" href="#bib0025">5–7</a> There are 2 theories on the origin of EMPD. According to the first, EMPD is considered an abnormal differentiation of the epidermal cells of the basal layer (primary EMPD); therefore, Paget disease would be considered an adenocarcinoma that is independent of a second neoplasm. According to the second theory, EMPD is an epidermal metastasis of an underlying carcinoma (secondary EMPD), although solitary lesions would remain unexplained.<a class="elsevierStyleCrossRefs" href="#bib0030">6,8</a> At least 6 cases of familial EMPD have been identified.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The clinical symptoms are insidious and often minor in the initial stages, with the result that patients do not request medical care until several years have passed, thus delaying diagnosis and treatment for a mean period of 2 years.<a class="elsevierStyleCrossRefs" href="#bib0010">2,9</a> The lesions consist of infiltrated brownish or erythematous plaques that are generally solitary with well-defined borders. They are occasionally edematous and exudative and can cause pruritus, pain, and a burning sensation. They may also be asymptomatic (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRef" href="#bib0020">4</a> The surface is sometimes rough, and there may be erosions, crusts, or lichenification.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The lesions rarely present as infiltrated nodules, vegetating lesions, or locoregional lymphadenopathies.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Unlike mammary Paget disease, EMPD is associated with underlying adnexal carcinoma in 24%-33% of cases and visceral cancer in 12%-15% of cases, including tumors of the gastrointestinal tract and urinary tract, mainly in organs with a contiguous lining and more commonly in the perianal region.<a class="elsevierStyleCrossRefs" href="#bib0030">6,10</a> Associated tumors generally include those affecting the breast, bladder, and cervix, although they can also affect the rectum, colon, prostate, ovaries, urethra, vagina, endometrium, and kidneys.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> We observed an association with skin cancer in 2 cases, one with urothelial involvement and the other with hematologic involvement. The neoplasm is found mainly at sites rich in apocrine glands, such as the external genitalia, the perianal region, the groin, and the axillas,<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> although it can also be found anywhere on the skin or mucosae.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> The most common site is the vulva (65%), as in the cases we report, although this figure only represents 2% of all primary vulvar tumors.<a class="elsevierStyleCrossRefs" href="#bib0020">4,9</a> The second most common site is the perianal region (20%), and the third is the male genitalia (14%).<a class="elsevierStyleCrossRefs" href="#bib0020">4,9</a> Exceptionally, the tumor is found in the axillas or groin, as in 2 of the cases reported here, in which the disease was invasive, probably because the atypical location of the lesion meant that diagnosis was delayed.<a class="elsevierStyleCrossRefs" href="#bib0020">4,9</a> Since this neoplasm is rare, there is no established protocol for its diagnosis, treatment, and follow-up, thus making it a challenge in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Diagnosis is based on symptoms and histopathology. Skin biopsy reveals cells with an abundant, pale cytoplasm, large pleomorphic nuclei, and, occasionally prominent nucleoli; the nuclei are sometimes eccentric and resemble signet rings (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRef" href="#bib0030">6</a> The differential diagnosis should include more common diseases such as eczematous lesions, lichen simplex chronicus, lichen sclerosus et atrophicus, lichen planus, inverse psoriasis, candidal intertrigo, erythroplasia of Queyrat, Bowen disease, superficial spreading amelanotic melanoma, and familial benign pemphigus.<a class="elsevierStyleCrossRefs" href="#bib0020">4,6</a> The treatment of choice is extensive surgical removal, although the disseminated nature and poorly defined margins of this tumor lead to recurrence in 16%-44% of cases<a class="elsevierStyleCrossRef" href="#bib0055">11</a>; therefore, Mohs micrographic surgery is increasingly used and can reduce the recurrence rate to 8%-28%.<a class="elsevierStyleCrossRefs" href="#bib0010">2,6</a> At our center, local persistence after surgery was recorded in 7 cases (70%) and recurrence in 2 (20%). Alternative approaches include carbon dioxide laser treatment, topical imiquimod, cryotherapy, radiotherapy, and photodynamic therapy, although the recurrence rate is very high (50%-60%).<a class="elsevierStyleCrossRefs" href="#bib0010">2,4,12,13</a> Systemic chemotherapy with 5-fluorouracil, mitomycin C, docetaxel, and etoposide is used in inoperable cases, although few complete responses have been achieved.<a class="elsevierStyleCrossRefs" href="#bib0020">4,5,9</a> During the EMPD workup, every attempt should be made to rule out associated neoplasms and identify signs of recurrence, which affects up to 35% of patients with EMPD in situ and 67% of invasive cases.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Screening for associated neoplasms should include gynecologic and abdominal ultrasound, colonoscopy, and mammography. EMPD remains in situ in more than 65% of cases, as with the patients in the present study, in whom the survival rate was greater than 90% at 5 years and spontaneous regression was occasionally observed after partial surgical removal.<a class="elsevierStyleCrossRefs" href="#bib0020">4,6</a> Survival decreases dramatically in invasive disease or in the presence of associated tumors, as in the 2 patients who died in the present series. The low incidence of this disease and its nonspecific clinical picture should alert us to the need for high clinical suspicion in order to avoid delays in diagnosis and therapy, which can worsen the prognosis in these patients.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres418521" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec401980" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres418520" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec401979" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflicts of Interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-01-21" "fechaAceptado" => "2014-05-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec401980" "palabras" => array:3 [ 0 => "Extramammary Paget disease" 1 => "Adenocarcinoma" 2 => "Rare tumor" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec401979" "palabras" => array:3 [ 0 => "Enfermedad de Paget extramamaria" 1 => "Adenocarcinoma" 2 => "Tumor raro" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Extramammary Paget disease (EMPD) is a very rare form of intraepithelial adenocarcinoma. We report the cases of EMPD diagnosed in a referral hospital over a 5-year period from 2009 to 2013. Ten cases of EMPD were diagnosed in 4 men and 6 women aged between 50 and 79 years. Erroneous clinical diagnoses led to diagnostic delays of 1 to 5 years in all cases. Six patients had in situ lesions and dermal invasion was observed in the other 4 cases. Four patients had a second neoplasm and 2 of the patients with invasive EMPD died. Because EMPD is rare and its clinical presentation is nonspecific, a high degree of clinical suspicion is required to avoid delays in diagnosis and treatment." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La enfermedad de Paget extramamaria (EPEM) es una forma extremadamente rara de adenocarcinoma intraepitelial. Presentamos los casos de EPEM diagnosticados en los últimos 5 años en un hospital de referencia (2009-2013). Se trata de 10 casos, 4 varones y 6 mujeres, con edades comprendidas entre los 50-79 años. Todos ellos sufrieron un retraso diagnóstico de uno a 5 años debido a sospechas diagnósticas erróneas. Seis casos correspondieron a EPEM in situ y en 4 existía invasión dérmica. Existió una segunda neoplasia en 4 pacientes y 2 con EPEM invasiva fallecieron. La baja incidencia de esta enfermedad y su clínica inespecífica nos debe alertar sobre la necesidad de establecer una alta sospecha clínica para evitar retrasos diagnósticos y terapéuticos." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Blasco-Morente G, Martín-Castro A, Garrido-Colmenero C, Tercedor-Sánchez J. Enfermedad de Paget extramamaria: 10 casos. Actas Dermosifiliogr. 2015;106:61–65." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 846 "Ancho" => 1200 "Tamanyo" => 192773 ] ] "descripcion" => array:1 [ "en" => "A, Case 1: Erythematous, exudative plaque measuring 10×12cm, with moderate infiltration and well-defined borders on the right groin corresponding to invasive extramammary Paget disease. B, Case 3: Erythematous plaque with a whitish exudate measuring 6×4cm, moderate infiltration, and well-defined borders in the gluteal cleft corresponding to extramammary Paget disease in situ." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 625 "Ancho" => 1703 "Tamanyo" => 308251 ] ] "descripcion" => array:1 [ "en" => "A, Case 9: infiltration of the epidermis with no involvement of the dermis by cells with abundant, eosinophilic cytoplasm and evident nucleoli (Paget cells) grouped in nests (hematoxylin-eosin, original magnification ×4). *Occasional formation of small glands (×20). B, Case 2: presence of Paget cells in the epidermis and dermis (hematoxylin-eosin, original magnification ×4). CK immunostaining with low- and high-molecular-weight keratins (AE1 and AE3) showing positivity in the epidermis, follicular epithelium, and (more intense) in Paget cells, with invasion of the reticular dermis by individual cells and small groups of cells (×4). CK indicates cytokeratin." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: CE, chronic eczema; CI, candidal intertrigo." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">8 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">9 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">10 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Location \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right groin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right groin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gluteal cleft \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Perianal region and lymphadenopathy in right groin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Perianal region \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Perianal region \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulva \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulva \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Physical examination \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="10" align="center" valign="top">Moderately infiltrated erythematous plaque with well-defined borders</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exudative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exudative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hyperkeratotic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eroded \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desquamative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Exudative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eroded \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eroded \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desquamative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Course, y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Previous diagnoses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI, CE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CE, Bowen disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lichen sclerosus et atrophicus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Leukoplakia, lichen simplex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CE \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Previous treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical corticosteroids, antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Emollient cream \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical antifungals \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical corticosteroids and emollient cream \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Dermal invasion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Definitive treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="6" align="center" valign="top">Radical surgical removal with a 3-cm margin</td><td class="td" title="table-entry " align="left" valign="top">Radical vulvectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Right hemivulvectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Radical vulvectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Vulvar tumor removal \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Persistence/recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0/0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Associated neoplasm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low-grade urothelial papillary carcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chronic B-cell lymphoproliferative disorder \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Porocarcinoma, basal cell carcinoma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Melanoma in situ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">Follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death within 2 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 mo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Death within 10 mo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.5 y \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 y \t\t\t\t\t\t\n 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E-Case Report

Extramammary Paget Disease: A Report of 10 Cases

Enfermedad de Paget extramamaria: 10 casos

G. Blasco-Morentea,

Corresponding author

gonzaloblascomorente@gmail.com

Corresponding author.

, A. Martín-Castrob, C. Garrido-Colmeneroa, J. Tercedor-Sáncheza

a Unidad de Gestión Clínica, Dermatología Médico Quirúrgica y Venereología, Hospital Universitario Virgen de las Nieves, Granada, Spain

b Anatomía Patológica, Hospital Universitario Virgen de las Nieves, Granada, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0020" class="elsevierStylePara elsevierViewall">Extramammary Paget disease (EMPD) was first described by Crocker in 1889 as a localized carcinoma affecting the penis and scrotum in a 60-year-old goldsmith. The symptoms and histopathological characteristics were similar to those of mammary Paget disease, first described by James Paget in 1874.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The disease is an extremely rare form of intraepithelial adenocarcinoma that may be accompanied by other malignant neoplasms.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> We report all cases of EMPD diagnosed during a 5-year period at a tertiary referral hospital.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Descriptions</span><p id="par0010" class="elsevierStylePara elsevierViewall">The clinical and histologic characteristics of patients with EMPD are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. We recorded 10 cases (4 on the vulva, 3 in the perianal region, 2 on the right groin [<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A], and 1 on the gluteal cleft [<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B]) in 4 men and 6 women aged between 50 and 79 years. In all cases there was a diagnostic delay of between 1 and 5 years, and the patients received treatment that was ineffective for fungal infections in 5 cases (50%), chronic inflammatory disease (eczema and lichen simplex) in 5 cases (50%), Bowen disease in 1 case (10%), lichen sclerosus et atrophicus in 1 case (10%), and leukoplakia in 1 case (10%). The diagnosis of EMPD was confirmed in all cases by histopathologic study of the skin biopsy, and treatment was by radical removal of the lesion with wide margins. EMPD was in situ in 6 patients (60%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), and dermal invasion was detected in 4 patients (40%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). The disease persisted after surgery in 4 patients (66.7%) with EMPD in situ and in 3 patients (75%) with invasive disease. In addition, recurrence was detected in 1 case of EMPD in situ (16.7%) and in 1 case of invasive EMPD (25%); further surgery was necessary in both cases. A second neoplasm was detected in 4 patients: 2 (33.3%) with EMPD in situ had melanoma in situ (1 patient) and porocarcinoma and basal cell carcinoma (1 patient); 1 patient (25%) with invasive disease had chronic B-cell lymphoproliferative disorder; and 1 patient (25%) had low-grade papillary urothelial carcinoma. Two patients (20%), both with the invasive form, died from metastasized disease, one at 10 months and the other at 2 years. In the remaining 8 patients (80%), no recurrence was observed during a follow-up period ranging from 9 months to 4.5 years.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Hospital Universitario Virgen de las Nieves, Granada, Spain is a tertiary referral hospital serving a population of 439&nbsp;035 people, among whom 10 patients were diagnosed with EMPD from 2009 to 2013. EMPD is a very infrequent neoplasm whose exact incidence is unknown, although it accounts for no more than 6.5% of all Paget diseases and only a few hundred cases have been published in the literature.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> EMPD generally affects whites aged between 50 and 80 years, mainly women at a ratio of 2.4:1, as in our series, although in Asians it usually affects men.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a> There are 2 theories on the origin of EMPD. According to the first, EMPD is considered an abnormal differentiation of the epidermal cells of the basal layer (primary EMPD); therefore, Paget disease would be considered an adenocarcinoma that is independent of a second neoplasm. According to the second theory, EMPD is an epidermal metastasis of an underlying carcinoma (secondary EMPD), although solitary lesions would remain unexplained.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,8</span></a> At least 6 cases of familial EMPD have been identified.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The clinical symptoms are insidious and often minor in the initial stages, with the result that patients do not request medical care until several years have passed, thus delaying diagnosis and treatment for a mean period of 2 years.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,9</span></a> The lesions consist of infiltrated brownish or erythematous plaques that are generally solitary with well-defined borders. They are occasionally edematous and exudative and can cause pruritus, pain, and a burning sensation. They may also be asymptomatic (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The surface is sometimes rough, and there may be erosions, crusts, or lichenification.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The lesions rarely present as infiltrated nodules, vegetating lesions, or locoregional lymphadenopathies.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Unlike mammary Paget disease, EMPD is associated with underlying adnexal carcinoma in 24%-33% of cases and visceral cancer in 12%-15% of cases, including tumors of the gastrointestinal tract and urinary tract, mainly in organs with a contiguous lining and more commonly in the perianal region.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,10</span></a> Associated tumors generally include those affecting the breast, bladder, and cervix, although they can also affect the rectum, colon, prostate, ovaries, urethra, vagina, endometrium, and kidneys.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> We observed an association with skin cancer in 2 cases, one with urothelial involvement and the other with hematologic involvement. The neoplasm is found mainly at sites rich in apocrine glands, such as the external genitalia, the perianal region, the groin, and the axillas,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> although it can also be found anywhere on the skin or mucosae.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The most common site is the vulva (65%), as in the cases we report, although this figure only represents 2% of all primary vulvar tumors.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,9</span></a> The second most common site is the perianal region (20%), and the third is the male genitalia (14%).<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,9</span></a> Exceptionally, the tumor is found in the axillas or groin, as in 2 of the cases reported here, in which the disease was invasive, probably because the atypical location of the lesion meant that diagnosis was delayed.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,9</span></a> Since this neoplasm is rare, there is no established protocol for its diagnosis, treatment, and follow-up, thus making it a challenge in clinical practice.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Diagnosis is based on symptoms and histopathology. Skin biopsy reveals cells with an abundant, pale cytoplasm, large pleomorphic nuclei, and, occasionally prominent nucleoli; the nuclei are sometimes eccentric and resemble signet rings (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The differential diagnosis should include more common diseases such as eczematous lesions, lichen simplex chronicus, lichen sclerosus et atrophicus, lichen planus, inverse psoriasis, candidal intertrigo, erythroplasia of Queyrat, Bowen disease, superficial spreading amelanotic melanoma, and familial benign pemphigus.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a> The treatment of choice is extensive surgical removal, although the disseminated nature and poorly defined margins of this tumor lead to recurrence in 16%-44% of cases<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a>; therefore, Mohs micrographic surgery is increasingly used and can reduce the recurrence rate to 8%-28%.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,6</span></a> At our center, local persistence after surgery was recorded in 7 cases (70%) and recurrence in 2 (20%). Alternative approaches include carbon dioxide laser treatment, topical imiquimod, cryotherapy, radiotherapy, and photodynamic therapy, although the recurrence rate is very high (50%-60%).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4,12,13</span></a> Systemic chemotherapy with 5-fluorouracil, mitomycin C, docetaxel, and etoposide is used in inoperable cases, although few complete responses have been achieved.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5,9</span></a> During the EMPD workup, every attempt should be made to rule out associated neoplasms and identify signs of recurrence, which affects up to 35% of patients with EMPD in situ and 67% of invasive cases.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Screening for associated neoplasms should include gynecologic and abdominal ultrasound, colonoscopy, and mammography. EMPD remains in situ in more than 65% of cases, as with the patients in the present study, in whom the survival rate was greater than 90% at 5 years and spontaneous regression was occasionally observed after partial surgical removal.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a> Survival decreases dramatically in invasive disease or in the presence of associated tumors, as in the 2 patients who died in the present series. The low incidence of this disease and its nonspecific clinical picture should alert us to the need for high clinical suspicion in order to avoid delays in diagnosis and therapy, which can worsen the prognosis in these patients.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of Interest</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>"
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          "identificador" => "xpalclavsec401979"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Case Descriptions"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Discussion"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Conflicts of Interest"
        ]
        8 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-01-21"
    "fechaAceptado" => "2014-05-22"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec401980"
          "palabras" => array:3 [
            0 => "Extramammary Paget disease"
            1 => "Adenocarcinoma"
            2 => "Rare tumor"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec401979"
          "palabras" => array:3 [
            0 => "Enfermedad de Paget extramamaria"
            1 => "Adenocarcinoma"
            2 => "Tumor raro"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Extramammary Paget disease (EMPD) is a very rare form of intraepithelial adenocarcinoma. We report the cases of EMPD diagnosed in a referral hospital over a 5-year period from 2009 to 2013. Ten cases of EMPD were diagnosed in 4 men and 6 women aged between 50 and 79 years. Erroneous clinical diagnoses led to diagnostic delays of 1 to 5 years in all cases. Six patients had in situ lesions and dermal invasion was observed in the other 4 cases. Four patients had a second neoplasm and 2 of the patients with invasive EMPD died. Because EMPD is rare and its clinical presentation is nonspecific, a high degree of clinical suspicion is required to avoid delays in diagnosis and treatment.</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Paget extramamaria (EPEM) es una forma extremadamente rara de adenocarcinoma intraepitelial. Presentamos los casos de EPEM diagnosticados en los &uacute;ltimos 5 a&ntilde;os en un hospital de referencia (2009-2013). Se trata de 10 casos, 4 varones y 6 mujeres, con edades comprendidas entre los 50-79 a&ntilde;os. Todos ellos sufrieron un retraso diagn&oacute;stico de uno a 5 a&ntilde;os debido a sospechas diagn&oacute;sticas err&oacute;neas. Seis casos correspondieron a EPEM <span class="elsevierStyleItalic">in situ</span> y en 4 exist&iacute;a invasi&oacute;n d&eacute;rmica. Existi&oacute; una segunda neoplasia en 4 pacientes y 2 con EPEM invasiva fallecieron. La baja incidencia de esta enfermedad y su cl&iacute;nica inespec&iacute;fica nos debe alertar sobre la necesidad de establecer una alta sospecha cl&iacute;nica para evitar retrasos diagn&oacute;sticos y terap&eacute;uticos.</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Blasco-Morente G, Mart&iacute;n-Castro A, Garrido-Colmenero C, Tercedor-S&aacute;nchez J. Enfermedad de Paget extramamaria: 10 casos. Actas Dermosifiliogr. 2015;106:61&#8211;65.</p>"
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 846
            "Ancho" => 1200
            "Tamanyo" => 192773
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Case 1: Erythematous, exudative plaque measuring 10<span class="elsevierStyleHsp" style=""></span>&times;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>cm, with moderate infiltration and well-defined borders on the right groin corresponding to invasive extramammary Paget disease. B, Case 3: Erythematous plaque with a whitish exudate measuring 6<span class="elsevierStyleHsp" style=""></span>&times;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm, moderate infiltration, and well-defined borders in the gluteal cleft corresponding to extramammary Paget disease in situ.</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 625
            "Ancho" => 1703
            "Tamanyo" => 308251
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A, Case 9: infiltration of the epidermis with no involvement of the dermis by cells with abundant, eosinophilic cytoplasm and evident nucleoli (Paget cells) grouped in nests (hematoxylin-eosin, original magnification &times;<span class="elsevierStyleHsp" style=""></span>4). *Occasional formation of small glands (&times;<span class="elsevierStyleHsp" style=""></span>20). B, Case 2: presence of Paget cells in the epidermis and dermis (hematoxylin-eosin, original magnification &times;<span class="elsevierStyleHsp" style=""></span>4). CK immunostaining with low- and high-molecular-weight keratins (AE1 and AE3) showing positivity in the epidermis, follicular epithelium, and (more intense) in Paget cells, with invasion of the reticular dermis by individual cells and small groups of cells (&times;<span class="elsevierStyleHsp" style=""></span>4). CK indicates cytokeratin.</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: CE, chronic eczema; CI, candidal intertrigo.</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="char" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Woman&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Right groin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Right groin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gluteal cleft&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Perianal region and lymphadenopathy in right groin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Perianal region&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Perianal region&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vulva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vulva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vulva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vulva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Physical examination&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="10" align="center" valign="top">Moderately infiltrated erythematous plaque with well-defined borders</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Exudative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Exudative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hyperkeratotic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eroded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Desquamative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Exudative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eroded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eroded&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Desquamative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Course, y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Previous diagnoses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CI, CE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CE, Bowen disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lichen sclerosus et atrophicus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Leukoplakia, lichen simplex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Previous treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical corticosteroids, antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Emollient cream&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical corticosteroids and emollient cream&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Topical corticosteroids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Dermal invasion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Definitive treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="6" align="center" valign="top">Radical surgical removal with a 3-cm margin</td><td class="td" title="table-entry  " align="left" valign="top">Radical vulvectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Right hemivulvectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radical vulvectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Vulvar tumor removal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Persistence/recurrence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2/1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3/1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0/0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Associated neoplasm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Low-grade urothelial papillary carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Chronic B-cell lymphoproliferative disorder&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Porocarcinoma, basal cell carcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Melanoma in situ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">Follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Death within 2 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Death within 10 mo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4.5 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1.5 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4.5 y&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2014.11.009

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Year/Month	Html	Pdf	Total

2024 November	16	14	30
2024 October	124	43	167
2024 September	140	35	175
2024 August	179	60	239
2024 July	114	39	153
2024 June	134	34	168
2024 May	118	39	157
2024 April	114	25	139
2024 March	134	32	166
2024 February	151	28	179
2024 January	134	31	165
2023 December	212	26	238
2023 November	255	26	281
2023 October	234	27	261
2023 September	198	36	234
2023 August	93	18	111
2023 July	144	38	182
2023 June	147	23	170
2023 May	115	30	145
2023 April	97	20	117
2023 March	99	34	133
2023 February	81	24	105
2023 January	69	30	99
2022 December	68	39	107
2022 November	32	24	56
2022 October	26	27	53
2022 September	29	40	69
2022 August	25	47	72
2022 July	28	41	69
2022 June	30	31	61
2022 May	48	34	82
2022 April	97	38	135
2022 March	110	50	160
2022 February	112	28	140
2022 January	76	49	125
2021 December	52	49	101
2021 November	57	38	95
2021 October	58	47	105
2021 September	70	40	110
2021 August	65	29	94
2021 July	54	23	77
2021 June	61	31	92
2021 May	39	18	57
2021 April	59	59	118
2021 March	66	23	89
2021 February	67	21	88
2021 January	55	25	80
2020 December	43	16	59
2020 November	32	16	48
2020 October	21	18	39
2020 September	30	18	48
2020 August	17	29	46
2020 July	19	21	40
2020 June	27	28	55
2020 May	18	30	48
2020 April	25	35	60
2020 March	23	21	44
2020 February	5	10	15
2020 January	4	12	16
2019 December	6	6	12
2019 November	4	4	8
2019 October	0	2	2
2019 September	0	3	3
2019 August	6	5	11
2019 July	4	8	12
2019 June	8	2	10
2019 May	7	7	14
2019 April	4	11	15
2019 March	2	4	6
2019 February	2	22	24
2019 January	2	2	4
2018 December	2	5	7
2018 November	3	0	3
2018 October	10	0	10
2018 September	5	0	5
2018 May	0	1	1
2018 March	0	1	1
2018 February	18	1	19
2018 January	29	8	37
2017 December	32	10	42
2017 November	30	5	35
2017 October	28	9	37
2017 September	22	6	28
2017 August	19	7	26
2017 July	20	6	26
2017 June	35	11	46
2017 May	23	18	41
2017 April	35	8	43
2017 March	22	19	41
2017 February	15	7	22
2017 January	30	12	42
2016 December	24	17	41
2016 November	40	15	55
2016 October	24	12	36
2016 September	0	6	6
2016 August	0	1	1
2016 July	5	0	5
2016 June	17	1	18
2016 May	21	17	38
2016 April	22	5	27
2016 March	12	2	14
2016 February	9	5	14
2016 January	13	1	14
2015 December	15	1	16
2015 November	15	1	16
2015 October	11	1	12
2015 September	6	2	8
2015 August	6	3	9
2015 July	16	12	28
2015 June	8	6	14
2015 May	6	6	12
2015 April	7	6	13
2015 March	11	12	23
2015 February	13	3	16

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