Case and Research Letters
Coincident Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoproliferative Disorder in Two Sisters
Trastorno linfoproliferativo primario de células T pleomórficas pequeñas/medianas CD4+ coincidente en dos hermanas
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Violaceous, infiltrated papules, some of which are excoriated and crusted, on the face (A) and distal area of the upper limbs (B-D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Granizo-Rubio, C. Caviedes-Vallejo, N. Chávez-Dávila, V. Pinos-León" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Granizo-Rubio" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Caviedes-Vallejo" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Chávez-Dávila" ] 3 => array:2 [ "nombre" => "V." 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Ponce, Y. Peñate, T. Montenegro" "autores" => array:3 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "Ponce" "email" => array:1 [ 0 => "sauloponce90@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">⿎</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Y." "apellidos" => "Peñate" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "T." "apellidos" => "Montenegro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Complejo Hospitalario Universitario Insular – Materno Infantil, Las Palmas de Gran Canaria, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Complejo Hospitalario Universitario Insular – Materno Infantil, Las Palmas de Gran Canaria, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⿎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trastorno linfoproliferativo primario de células T pleomórficas pequeñas/medianas CD4+ coincidente en dos hermanas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1508 "Ancho" => 1207 "Tamanyo" => 607841 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0145" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemistry showing positive staining for CD4 (original magnification ×2) in the lesions in the cervical region (A) and on the left cheek (B). Immunohistochemistry showing positive staining for PD-1 (original magnification ×2) in the lesions in the cervical region (C) and on the left cheek (D).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Primary cutaneous CD4<span class="elsevierStyleSup">+</span> small/medium-sized pleomorphic T-cell lymphoproliferative disorder (CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD) is an uncommon entity that was first included as an independent entity (named CD4<span class="elsevierStyleSup">+</span> primary cutaneous small/medium-sized pleomorphic T-cell lymphoma) in the 2005 classification of lymphoid neoplasms of the WHO-EORTC (World Health Organization–European Organization for Research and Treatment of Cancer). Given its apparent indolent character, the nomenclature was changed in 2016 to CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD, although this remained a provisional entity. We present the first case of simultaneous appearance of CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD in 2 sisters.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Two sisters, aged 54 and 58 years, were seen for similar lesions located on the left cheek and cervical area, respectively, that had appeared 2 and 3 years earlier, respectively. Neither of the sisters reported any potential triggers. The patients did not live together, but both lived in rural areas. The physical examination revealed firm, infiltrated, erythematous cupuliform papules with neat borders (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Histology showed a dense lymphohistiocytic infiltrate in the dermis and hypodermis with tropism for adnexal structures. Epidermotropism was absent. The infiltrate consisted of small-to-medium-sized pleomorphic lymphocytes, with mild-to-moderate atypia (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Immunohistochemistry was positive for CD3, CD4, and PD-1, and negative for CD10 and Bcl-6, and revealed large isolated CD30<span class="elsevierStyleSup">+</span> cells and preserved CD7/CD5/CD2 immunostaining (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Accompanying CD8<span class="elsevierStyleSup">+</span> and CD20<span class="elsevierStyleSup">+</span> cell populations were also observed. Monoclonal T-cell receptor (TCR)-beta rearrangement was observed for both samples, with no clonal overlap between samples. The results of the staging workup (cervical thoracic abdominal pelvic computed tomography scan and lactate dehydrogenase analysis) were negative. It was decided to adopt a wait-and-see approach, and spontaneous remission was observed after 6 months in both patients.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD is classified as a provisional entity within the category of cutaneous lymphomas, of which it accounts for approximately 2% of cases. Although it can occur at any age, it typically affects adults that have reached the fifth decade of life, and no clear sex predisposition is described.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–8</span></a> The pathogenesis of this entity is unknown and controversial; a recent series of 62 patients, of whom 11 underwent genomic analyses, reported no associated genomic alteration.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD typically presents as solitary lesions in the upper body (mainly the head or neck), usually in the form of asymptomatic nodules, plaques, or erythematous tumors.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Histology reveals infiltrate composed of small-to-medium-sized pleomorphic lymphocytes with mild-to-moderate cellular atypia, the absence of obvious epidermotropism, and, in some cases, tropism for adnexal structures.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The immunohistochemical profile of these cells is CD3<span class="elsevierStyleSup">+</span>, CD4<span class="elsevierStyleSup">+</span>, CD30<span class="elsevierStyleSup">-</span>, CD8<span class="elsevierStyleSup">-</span>, with variable loss of T-cell markers (CD7, CD5, and CD2) and variable positivity for follicular T-helper cell markers (PD-1, Bcl-6, and CXCL-13).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–4</span></a> The true nature of these cells is not entirely clear. Accompanying the neoplastic T cells are populations of CD20<span class="elsevierStyleSup">+</span> B cells and CD8<span class="elsevierStyleSup">+</span> T cells, as well as some large, isolated, pleomorphic CD30<span class="elsevierStyleSup">+</span> cells (<30%). The proliferative (Ki-67) index is usually less than 50%.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A monoclonal TCR gene rearrangement has been described in more than 80% of cases in the majority of published series.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD has a very favorable prognosis, with a 5-year survival rate of 80–90%.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> In the most extensive (n = 136) case series published,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Beltraminelli and coworkers reported no extracutaneous involvement in 45 patients followed for a mean period of 64 months. Systemic involvement has only been described in a series of 24 patients published by García-Herrera et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The authors reported 5 cases of extracutaneous involvement and proposed that rapid growth, a high proliferative index, and scarce CD8<span class="elsevierStyleSup">+</span> infiltrate were poor prognostic factors, although the study population consisted of patients with very heterogeneous characteristics. We believe that based on their characteristics (large, fast-growing lesions with variable expression of CD4, loss of CD7, a high proliferative index, and extracutaneous involvement), these lesions would be better classified as primary cutaneous peripheral T-cell lymphoma not otherwise specified. No other cases of systemic involvement have been described in any of the other published series.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–8</span></a> Treatment options include surgery (first-line treatment in patients with solitary lesions), topical corticosteroids, and phototherapy. Only 3 cases of complete spontaneous remission are described in the literature.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,9,10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The differential diagnosis includes other cutaneous B-cell and T-cell lymphomas, as well as reactive lymphoproliferative processes and pseudolymphomas, the latter of which are difficult to differentiate.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The presence of pleomorphism and cellular atypia, the loss of T-cell markers, positivity for follicular T-helper cells, and monoclonal TCR rearrangement are findings that can help guide the diagnosis of CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD, although these findings may also be present to a lesser extent in reactive processes.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–5</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion, we present 2 new cases of CD4<span class="elsevierStyleSup">+</span> PCSM-TLPD and describe for the first time 2 simultaneous cases of this entity in sisters. Both patients achieved spontaneous remission, of which there are few reports in the current literature. The true nature of this entity and its differential diagnosis from reactive lymphoproliferative processes has been the subject of some controversy since its classification as a form of cutaneous lymphoma. The simultaneous appearance of this lesion in 2 sisters supports a reactive origin, given the possibility of exposure to similar environmental factors, as well as a possible influence of as-yet-unknown genetic factors.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ponce S, Peñate Y, Montenegro T. Trastorno linfoproliferativo primario de células T pleomórficas pequeñas/medianas CD4+ coincidente en dos hermanas. Actas Dermosifiliogr. 2020;111:271–273.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 832 "Ancho" => 1207 "Tamanyo" => 197512 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0135" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Firm, infiltrated, erythematous cupuliform papules in the posterior cervical region (A) and on the left cheek (B).</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1332 "Ancho" => 1207 "Tamanyo" => 629103 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0140" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histological images of the lesions in the cervical region (A) and on the left cheek (B) showing lymphohistiocytic infiltrate in the dermis and hypodermis with tropism for adnexal structures and the absence of epidermotropism (hematoxylin-eosin, original magnification ×2). Histological images of the lesions in the cervical region (C) and on the left cheek (D) showing infiltrate consisting of pleomorphic cells with mild-to-moderate atypia (hematoxylin-eosin, original magnification ×20).</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1508 "Ancho" => 1207 "Tamanyo" => 607841 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0145" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Immunohistochemistry showing positive staining for CD4 (original magnification ×2) in the lesions in the cervical region (A) and on the left cheek (B). Immunohistochemistry showing positive staining for PD-1 (original magnification ×2) in the lesions in the cervical region (C) and on the left cheek (D).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reappraisal of the provisional entity primary cutaneous CD4+ small/medium pleomorphic T-cell lymphoma: a series of 10 adult and pediatric patients and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.L. Baum" 1 => "B.K. Link" 2 => "V.T. Neppalli" 3 => "B.L. Swick" 4 => "V. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2010.07.028" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol." 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