Primary Cutaneous Acral CD8+ T-cell Lymphoma Induced by Persistent Delayed Hypersensitivity to Gold Earrings

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B, Complete reepithelialization was achieved after partial skin grafts were placed." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Marín-Piñero, M. Iglesias-Sancho, J. Company-Quiroga, C. Martínez-Moran, P. Perez-Feal, I. Vazquez-Osorio, P. Rodriguez-Jiménez, J. Sánchez-Estella, A. Suárez-Valle, L. Buzón-Martín, E. Martín-Saez, S. García-Rodiño, A. Sáez-Vicente, D.M. Arranz-Sánchez, I. Cervigón-González, E. del Rio" "autores" => array:16 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Marín-Piñero" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Iglesias-Sancho" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Company-Quiroga" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Martínez-Moran" ] 4 => array:2 [ "nombre" => "P." "apellidos" => "Perez-Feal" ] 5 => array:2 [ "nombre" => "I." "apellidos" => "Vazquez-Osorio" ] 6 => array:2 [ "nombre" => "P." "apellidos" => "Rodriguez-Jiménez" ] 7 => array:2 [ "nombre" => "J." 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"apellidos" => "del Rio" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219021001591?idApp=UINPBA000044" "url" => "/15782190/0000011200000007/v1_202107020822/S1578219021001591/v1_202107020822/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S1578219021001554" "issn" => "15782190" "doi" => "10.1016/j.adengl.2021.04.001" "estado" => "S300" "fechaPublicacion" => "2021-07-01" "aid" => "2545" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2021;112:647-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "Practical Dermoscopy" "titulo" => "Violaceous Papule on the Trunk" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "647" "paginaFinal" => "648" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pápula violácea en tronco" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 455 "Ancho" => 805 "Tamanyo" => 56941 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Dermoscopic image of the lesion (DermLite 4). The reddish-violaceous homogeneous lesion is surrounded by a biphasic halo. The first halo has a yellowish-orange tinge (*) and the second halo on the periphery is reddish. The hair follicles remain intact." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F.J. Navarro-Triviño" "autores" => array:1 [ 0 => array:2 [ "nombre" => "F.J." 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Molinero Caturla, J. Sánchez Sánchez, J. Marcoval Caus, C. Muniesa Montserrat, J. Climent Esteller, O. Servitje Bedate" "autores" => array:6 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Molinero Caturla" "email" => array:1 [ 0 => "gsusmoli@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Sánchez Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Marcoval Caus" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Muniesa Montserrat" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Climent Esteller" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "O." "apellidos" => "Servitje Bedate" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Linfoma cutáneo primario T CD8+ tipo acral inducido por hipersensibilidad retardada persistente a pendientes de oro" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 947 "Ancho" => 3159 "Tamanyo" => 191992 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of the gene rearrangement study of the TCR beta receptor gene in the initial lesions (A) and those induced by the use test (B). Note the identical monoclonal peak in both tubes B and C in the different samples." ] ] ] "textoCompleto" => "IntroductionGold is a very stable metal in the epidermis and rarely causes allergic contact eczemas. However, when present in the dermis, it can form ions and remain for long durations and so has been associated with pseudolymphomatous allergic contact dermatitis caused by gold earrings. Persistent antigenic stimulus by gold is the cause we propose in the case we describe below, with the particular and exceptional circumstance that this is a true primary cutaneous lymphoma and not a pseudolymphomatous lymphomatoid contact dermatitis. This is the first report in the literature of indolent primary cutaneous acral CD8+ T-cell lymphoma induced by gold earrings.Case HistoryA 30-year-old woman, with no clinical history of interest except intolerance of jewelry, attended the clinic because of persistent papular lesions in both ear lobes. The lesions had appeared 1 year earlier. Growth had been slow and the lesions were located on the internal face of both lobes (the left-sided lesion had spread to the external face) at the site of the earring hole. These lesions were reddish and indurated to touch, measuring 8 and 10 mm in diameter (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and B). The patient reported using only 2 pairs of gold earrings in the previous 6 years. Within a few hours, these caused pruritus, erythema, and scaling which resolved after removing them. Nevertheless, she continued to use them until the bilateral papular lesions in the earlobes appeared. Given the clinical suspicion of cutaneous pseudolymphoma or lymphomatoid contact dermatitis due to persistent antigenic stimulus by gold, we performed an excision biopsy of both earlobe lesions, as well as patch tests. The histopathological findings for both lesions were the same. A dense and diffuse lymphoid infiltrate was observed occupying the entire dermis but sparing the epidermis and skin appendages. This infiltrate was formed of atypical small and medium-sized CD8+ T lymphocytes with no necrosis or angiodestructive changes and with limited epidermotropism (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C and D). There was no evidence of lymphoid follicles with reactive germinal centers. Immunohistochemical study identified T lymphocytes positive for CD2, CD3, CD5, and CD7, with a clear predominance for CD8. TIA 1 and ß-F1 markers were positive whereas CD4, CD20, CD30, CD56, granzyme B, and EBERS were negative and Ki-67 positivity was weak (<5%). Study of T-cell receptor beta gene rearrangement showed monoclonal expansion in both lesions with the same clone (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), and primary cutaneous acral CD8+ T-cell lymphoma of both ear lobes was diagnosed. Study of extension, including positron-electron tomography/computed tomography, ruled out systemic extracutaneous spread. We also performed patch testing with the standard Spanish GEIDAC patch test series, applying the T.R.U.E Test® panel and supplementary allergens. The readout showed intense eczematous-vesicular positivity to gold sodium thiosulfate 1% and weaker positivity to nickel and cobalt (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). The dimethylglyoxime test on both gold earrings was negative, ruling out the presence of nickel. Skin biopsy of the patch positive to gold sodium thiosulfate showed a dense reactive lymphohistiocytic infiltrate in the upper half of the dermis. The positive reactions to nickel and cobalt were considered of past relevance, whereas the reactions to gold represented current relevance as the inducer of the aforementioned cutaneous lymphoma through intermittent antigenic stimulus over the course of 6 years. To confirm this possible association, 6 months later, and without any evidence of recurrence of the lesions, we decided to perform a test of continuous use of the gold earrings to observe whether new papular lesions similar to those biopsied might appear. This was indeed the case. Five weeks after daily use, papular-erythematous lesions very similar to the previous ones reappeared in both earlobes at the earring hole (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>A and B). An excision biopsy was performed once more with the same findings as the previous one both in histopathological and immunohistochemical terms (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>C and D). TCR-beta molecular analysis also showed monoclonality, with the same clone as the initial lesions (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). The use test and its result confirmed that gold had been able to cause the primary cutaneous acral CD8+ T-cell lymphoma in both earlobes. In the 6 months after the use test, no relapses were observed as the patient stopped using the gold earrings.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionPrimary cutaneous acral CD8+ T-cell lymphoma has been included as a provisional entity in the new revised classification of lymphoid neoplasms published by the World Health Organization in 2016,<a class="elsevierStyleCrossRef" href="#bib0005">1</a> along with indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Both entities are clonal disorders composed of cytotoxic CD8+ T lymphocytes and an indolent clinical course.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The cutaneous entity was originally described by Petrella et al.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> in 2007 under the denomination indolent CD8+ lymphoid proliferation of the ear, given its course and favorable prognosis. Subsequent publications extended the clinical, histopathological, and immunohistochemical description of this neoplasm and reported features differentiating it from other primary cutaneous cytotoxic T-cell lymphomas.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> Cutaneous lesions in form of erythematous papules and nodules have not just been described on the ear but also the face<a class="elsevierStyleCrossRefs" href="#bib0015">3,5</a> (nose, lower eyelid) and feet and hands,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> and so the term acral was added as a generic description of the site.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> According to Li et al.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> the acral predilection of the lesions (although they predominate on the ear and face<a class="elsevierStyleCrossRef" href="#bib0020">4</a>) may suggest an as yet to be determined specific immune stimulus, which in none of the 29 cases published to date<a class="elsevierStyleCrossRefs" href="#bib0020">4,6,7</a> has been associated with phenomena of type IV delayed hypersensitivity. Most cases show very characteristic histopathological, immunohistochemical, and molecular characteristics. An atypical dense and diffuse monomorphic lymphocyte infiltrate is usually observed, occupying the dermis with limited epidermotropism and no reactive lymphoid follicles. In no case has any necrosis or destruction of appendages and vessels been observed. The proliferative index is usually low, except in the 3 cases described by Greenblatt et al.,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> although the clinical course was also indolent. Systemic extracutaneous involvement has not been reported except in a single case.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Recurrences have not been reported in almost all patients after excission or local radiotherapy, except in 5 who did not return after a second treatment.<a class="elsevierStyleCrossRefs" href="#bib0020">4,6</a> The median duration of follow-up was 2 years.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Immunohistochemistry revealed positivity and predominance of CD8+ lymphocytes and a cytotoxic α/ß (ß-F1+) T-cell phenotype, and negativity for CD56, CD30, and granzyme B. Gene rearrangement study of the TCR gene showed monoclonality in 20 cases and negativity in 4, while no result was available in 5.<a class="elsevierStyleCrossRefs" href="#bib0020">4,6,7</a>In the literature, there are little more than 10 cases of rare pseudolymphomatoid allergic contact dermatitis caused by gold earrings,<a class="elsevierStyleCrossRefs" href="#bib0045">9–18</a> but in all cases, histopathology points to cutaneous pseudolymphoma and not true lymphoma. The main difference lies in the mixed character of the dermal cellular infiltrates and the presence of reactive lymphoid follicles.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13,18</a> In almost all cases, the characteristic CD8+ phenotype and clonality studies are lacking. Recently, Kiyohara et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> have reported a case of papular pseudolymphoma induced by a gold patch test and Rodríguez-Villa Lario et al.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> reported a case of pseudolymphoma B of the upper eyelid associated with a gold weight implant.Its etiopathogenesis appears to involve persistent antigenic exposure to gold located in the dermis, as the metal has a greater tendency to ionize in this location than in the epidermis,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> where it is usually much more stable. For the gold to be antigenic and induce a delayed type IV hypersensitivity reaction, it had to be converted to a small soluble form through the effect of amino acids from sweat and be absorbed. Once in the dermis, this soluble form can remain for a long time in the extracellular fluid or matrix and thus represent a sustained immune stimulus<a class="elsevierStyleCrossRef" href="#bib0105">21</a> able to induce pseudolymphomatous lymphomatoid allergic contact dermatitis<a class="elsevierStyleCrossRefs" href="#bib0045">9–13,17,18</a> or indeed lymphoma, as in our case. Given that the CD8+ lymphocytes are involved in triggering the innate immune response to haptens, one hypotheses that connects both entities is that a continual and lasting allergenic stimulus could induce clonal lymphoproliferative disease in a susceptible host instead of a reactive lymphocyte reaction. This capacity to remain in soluble form in the dermis could thus explain the frequently observed and well-known persistent positive results to gold sodium thiosulfate.This is the first report in the literature of indolent primary cutaneous acral CD8+ T-cell lymphoma induced by gold earrings. The causative agent was confirmed by the use test that once again reproduced the lesions with the same histological, immunohistochemical, and molecular findings as in the initial lesions. The presence of the same clone in 2 different lesions (the initial ones) and at different time points (those induced by the use test) is very suggestive of lymphoma.In none of the 29 reported cases of this lymphoma has onset been attributed to any contact allergen or to gold earrings, even though the most frequent site is the ear (17 out of 29 cases, 59%), with the helix being more often involved then the earlobe. Likewise, we have not found any cases published in the literature of true primary cutaneous lymphomas or systemic lymphomas related to sustained contact allergenic induction.Conflicts of InterestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1542275" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1395160" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1542276" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1395161" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case History" ] 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" => "2019-11-05" "fechaAceptado" => "2020-08-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1395160" "palabras" => array:3 [ 0 => "Primary cutaneous acral CD8+ T-cell lymphoma" 1 => "Gold sodium thiosulfate" 2 => "Lymphomatoid contact allergic dermatitis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1395161" "palabras" => array:3 [ 0 => "Linfoma cutáneo primario T CD8+ tipo acral" 1 => "Tiosulfato sódico de oro" 2 => "Dermatitis alérgica de contacto linfomatoide" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Primary cutaneous CD8+ T-cell lymphoma has been included as a provisional entity within the new revised classification of lymphoid neoplasms of the World Health Organization in 20161. It was initially described as indolent CD8+ lymphoid proliferation of the ear2 and a total of 29 cases of such neoplasm have been published in the literature so far. None of them have been linked to delayed contact hypersensitivity reactions. We present a case of acral type primary cutaneous lymphoma T CD8+ involving both earlobes clearly related with the prolonged use of gold earrings, confirmed with epicutaneous tests, histopathology, immunohistochemical and molecular studies. Auricular skin lesions were induced again with a provocation test with identical histopathologycal and the same clonality, confirming both the diagnosis of lymphoma and its induction by the antigenic stimulus of gold." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El linfoma cutáneo primario T CD8+ tipo acral ha sido incluido como entidad provisional dentro de la nueva clasificación revisada de las neoplasias linfoides de la Organización Mundial de la Salud en 20161. Inicialmente fue descrito como proliferación linfoide CD8+ indolente de la oreja2, y se han publicado en la literatura un total de 29 casos de dicha neoplasia. Ninguno de ellos se ha relacionado con reacciones de hipersensibilidad retardada de contacto. Presentamos un caso de linfoma cutáneo primario T CD8+ tipo acral auricular bilobular en clara relación etiológica con el uso prolongado de unos pendientes de oro confirmada con pruebas epicutáneas, estudio histológico, inmunohistoquímico y molecular. Las lesiones cutáneas bilobulares fueron inducidas de nuevo con un test de uso e idénticos resultados a los iniciales y misma clonalidad, lo cual terminó de confirmar tanto el diagnóstico del linfoma como su inducción por el estímulo antigénico del oro." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Molinero Caturla J, Sánchez Sánchez J, Marcoval Caus J, Muniesa Montserrat C, Climent Esteller J, Servitje Bedate O. Linfoma cutáneo primario T CD8+ tipo acral inducido por hipersensibilidad retardada persistente a pendientes de oro. Actas Dermosifiliogr. 2021;112:649–653." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1620 "Ancho" => 2508 "Tamanyo" => 928102 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A and B, Reddish papules on both earlobes located at the earring holes. C, Staining with hematoxylin and eosin ×100; dense dermal lymphocytic infiltrate with very limited epidermotropism. D, Immunohistochemical staining for CD8 ×10; the neoplastic lymphocytes were mainly CD8+." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 947 "Ancho" => 3159 "Tamanyo" => 191992 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Images of the gene rearrangement study of the TCR beta receptor gene in the initial lesions (A) and those induced by the use test (B). Note the identical monoclonal peak in both tubes B and C in the different samples." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1189 "Ancho" => 1583 "Tamanyo" => 299719 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Patch tests showing intense positivity for gold sodium thiosulfate (infiltrated plaque with blistering)." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1676 "Ancho" => 2508 "Tamanyo" => 1064206 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A and B, Papular lesions at the same site 5 weeks after rechallenge with the gold earrings (use test). 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Brief Comunication

Primary Cutaneous Acral CD8+ T-cell Lymphoma Induced by Persistent Delayed Hypersensitivity to Gold Earrings

Linfoma cutáneo primario T CD8+ tipo acral inducido por hipersensibilidad retardada persistente a pendientes de oro

J. Molinero Caturlaa,

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gsusmoli@hotmail.com

Corresponding author.

, J. Sánchez Sáncheza, J. Marcoval Causa, C. Muniesa Montserrata, J. Climent Estellerb, O. Servitje Bedatea

a Servicio de Dermatología, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain

b Servicio de Anatomía Patológica, Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Gold is a very stable metal in the epidermis and rarely causes allergic contact eczemas&#46; However&#44; when present in the dermis&#44; it can form ions and remain for long durations and so has been associated with pseudolymphomatous allergic contact dermatitis caused by gold earrings&#46; Persistent antigenic stimulus by gold is the cause we propose in the case we describe below&#44; with the particular and exceptional circumstance that this is a true primary cutaneous lymphoma and not a pseudolymphomatous lymphomatoid contact dermatitis&#46; This is the first report in the literature of indolent primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma induced by gold earrings&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case History</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 30-year-old woman&#44; with no clinical history of interest except intolerance of jewelry&#44; attended the clinic because of persistent papular lesions in both ear lobes&#46; The lesions had appeared 1&#160;year earlier&#46; Growth had been slow and the lesions were located on the internal face of both lobes &#40;the left-sided lesion had spread to the external face&#41; at the site of the earring hole&#46; These lesions were reddish and indurated to touch&#44; measuring 8 and 10&#160;mm in diameter &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A and B&#41;&#46; The patient reported using only 2 pairs of gold earrings in the previous 6 years&#46; Within a few hours&#44; these caused pruritus&#44; erythema&#44; and scaling which resolved after removing them&#46; Nevertheless&#44; she continued to use them until the bilateral papular lesions in the earlobes appeared&#46; Given the clinical suspicion of cutaneous pseudolymphoma or lymphomatoid contact dermatitis due to persistent antigenic stimulus by gold&#44; we performed an excision biopsy of both earlobe lesions&#44; as well as patch tests&#46; The histopathological findings for both lesions were the same&#46; A dense and diffuse lymphoid infiltrate was observed occupying the entire dermis but sparing the epidermis and skin appendages&#46; This infiltrate was formed of atypical small and medium-sized CD8<span class="elsevierStyleSup">&#43;</span> T lymphocytes with no necrosis or angiodestructive changes and with limited epidermotropism &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and D&#41;&#46; There was no evidence of lymphoid follicles with reactive germinal centers&#46; Immunohistochemical study identified T lymphocytes positive for CD2&#44; CD3&#44; CD5&#44; and CD7&#44; with a clear predominance for CD8&#46; TIA 1 and &#223;-F1 markers were positive whereas CD4&#44; CD20&#44; CD30&#44; CD56&#44; granzyme B&#44; and EBERS were negative and Ki-67 positivity was weak &#40;&#60;5&#37;&#41;&#46; Study of T-cell receptor beta gene rearrangement showed monoclonal expansion in both lesions with the same clone &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#44; and primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma of both ear lobes was diagnosed&#46; Study of extension&#44; including positron-electron tomography&#47;computed tomography&#44; ruled out systemic extracutaneous spread&#46; We also performed patch testing with the standard Spanish GEIDAC patch test series&#44; applying the T&#46;R&#46;U&#46;E Test&#174; panel and supplementary allergens&#46; The readout showed intense eczematous-vesicular positivity to gold sodium thiosulfate 1&#37; and weaker positivity to nickel and cobalt &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; The dimethylglyoxime test on both gold earrings was negative&#44; ruling out the presence of nickel&#46; Skin biopsy of the patch positive to gold sodium thiosulfate showed a dense reactive lymphohistiocytic infiltrate in the upper half of the dermis&#46; The positive reactions to nickel and cobalt were considered of past relevance&#44; whereas the reactions to gold represented current relevance as the inducer of the aforementioned cutaneous lymphoma through intermittent antigenic stimulus over the course of 6 years&#46; To confirm this possible association&#44; 6 months later&#44; and without any evidence of recurrence of the lesions&#44; we decided to perform a test of continuous use of the gold earrings to observe whether new papular lesions similar to those biopsied might appear&#46; This was indeed the case&#46; Five weeks after daily use&#44; papular-erythematous lesions very similar to the previous ones reappeared in both earlobes at the earring hole &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A and B&#41;&#46; An excision biopsy was performed once more with the same findings as the previous one both in histopathological and immunohistochemical terms &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>C and D&#41;&#46; TCR-beta molecular analysis also showed monoclonality&#44; with the same clone as the initial lesions &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; The use test and its result confirmed that gold had been able to cause the primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma in both earlobes&#46; In the 6 months after the use test&#44; no relapses were observed as the patient stopped using the gold earrings&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma has been included as a provisional entity in the new revised classification of lymphoid neoplasms published by the World Health Organization in 2016&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> along with indolent T-cell lymphoproliferative disease of the gastrointestinal tract&#46; Both entities are clonal disorders composed of cytotoxic CD8<span class="elsevierStyleSup">&#43;</span> T lymphocytes and an indolent clinical course&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The cutaneous entity was originally described by Petrella et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> in 2007 under the denomination indolent CD8<span class="elsevierStyleSup">&#43;</span> lymphoid proliferation of the ear&#44; given its course and favorable prognosis&#46; Subsequent publications extended the clinical&#44; histopathological&#44; and immunohistochemical description of this neoplasm and reported features differentiating it from other primary cutaneous cytotoxic T-cell lymphomas&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Cutaneous lesions in form of erythematous papules and nodules have not just been described on the ear but also the face<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;5</span></a> &#40;nose&#44; lower eyelid&#41; and feet and hands&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and so the term acral was added as a generic description of the site&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> According to Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> the acral predilection of the lesions &#40;although they predominate on the ear and face<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#41; may suggest an as yet to be determined specific immune stimulus&#44; which in none of the 29 cases published to date<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a> has been associated with phenomena of type IV delayed hypersensitivity&#46; Most cases show very characteristic histopathological&#44; immunohistochemical&#44; and molecular characteristics&#46; An atypical dense and diffuse monomorphic lymphocyte infiltrate is usually observed&#44; occupying the dermis with limited epidermotropism and no reactive lymphoid follicles&#46; In no case has any necrosis or destruction of appendages and vessels been observed&#46; The proliferative index is usually low&#44; except in the 3 cases described by Greenblatt et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> although the clinical course was also indolent&#46; Systemic extracutaneous involvement has not been reported except in a single case&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Recurrences have not been reported in almost all patients after excission or local radiotherapy&#44; except in 5 who did not return after a second treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6</span></a> The median duration of follow-up was 2 years&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Immunohistochemistry revealed positivity and predominance of CD8<span class="elsevierStyleSup">&#43;</span> lymphocytes and a cytotoxic &#945;&#47;&#223; &#40;&#223;-F1<span class="elsevierStyleSup">&#43;</span>&#41; T-cell phenotype&#44; and negativity for CD56&#44; CD30&#44; and granzyme B&#46; Gene rearrangement study of the TCR gene showed monoclonality in 20 cases and negativity in 4&#44; while no result was available in 5&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6&#44;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In the literature&#44; there are little more than 10 cases of rare pseudolymphomatoid allergic contact dermatitis caused by gold earrings&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;18</span></a> but in all cases&#44; histopathology points to cutaneous pseudolymphoma and not true lymphoma&#46; The main difference lies in the mixed character of the dermal cellular infiltrates and the presence of reactive lymphoid follicles&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;18</span></a> In almost all cases&#44; the characteristic CD8<span class="elsevierStyleSup">&#43;</span> phenotype and clonality studies are lacking&#46; Recently&#44; Kiyohara et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> have reported a case of papular pseudolymphoma induced by a gold patch test and Rodr&#237;guez-Villa Lario et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> reported a case of pseudolymphoma B of the upper eyelid associated with a gold weight implant&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Its etiopathogenesis appears to involve persistent antigenic exposure to gold located in the dermis&#44; as the metal has a greater tendency to ionize in this location than in the epidermis&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> where it is usually much more stable&#46; For the gold to be antigenic and induce a delayed type IV hypersensitivity reaction&#44; it had to be converted to a small soluble form through the effect of amino acids from sweat and be absorbed&#46; Once in the dermis&#44; this soluble form can remain for a long time in the extracellular fluid or matrix and thus represent a sustained immune stimulus<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> able to induce pseudolymphomatous lymphomatoid allergic contact dermatitis<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;13&#44;17&#44;18</span></a> or indeed lymphoma&#44; as in our case&#46; Given that the CD8<span class="elsevierStyleSup">&#43;</span> lymphocytes are involved in triggering the innate immune response to haptens&#44; one hypotheses that connects both entities is that a continual and lasting allergenic stimulus could induce clonal lymphoproliferative disease in a susceptible host instead of a reactive lymphocyte reaction&#46; This capacity to remain in soluble form in the dermis could thus explain the frequently observed and well-known persistent positive results to gold sodium thiosulfate&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">This is the first report in the literature of indolent primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma induced by gold earrings&#46; The causative agent was confirmed by the use test that once again reproduced the lesions with the same histological&#44; immunohistochemical&#44; and molecular findings as in the initial lesions&#46; The presence of the same clone in 2 different lesions &#40;the initial ones&#41; and at different time points &#40;those induced by the use test&#41; is very suggestive of lymphoma&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In none of the 29 reported cases of this lymphoma has onset been attributed to any contact allergen or to gold earrings&#44; even though the most frequent site is the ear &#40;17 out of 29 cases&#44; 59&#37;&#41;&#44; with the helix being more often involved then the earlobe&#46; Likewise&#44; we have not found any cases published in the literature of true primary cutaneous lymphomas or systemic lymphomas related to sustained contact allergenic induction&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2019-11-05"
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            0 => "Primary cutaneous acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma"
            1 => "Gold sodium thiosulfate"
            2 => "Lymphomatoid contact allergic dermatitis"
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            0 => "Linfoma cut&#225;neo primario T CD8<span class="elsevierStyleSup">&#43;</span> tipo acral"
            1 => "Tiosulfato s&#243;dico de oro"
            2 => "Dermatitis al&#233;rgica de contacto linfomatoide"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Primary cutaneous CD8<span class="elsevierStyleSup">&#43;</span> T-cell lymphoma has been included as a provisional entity within the new revised classification of lymphoid neoplasms of the World Health Organization in 2016<span class="elsevierStyleSup">1</span>&#46; It was initially described as indolent CD8<span class="elsevierStyleSup">&#43;</span> lymphoid proliferation of the ear<span class="elsevierStyleSup">2</span> and a total of 29 cases of such neoplasm have been published in the literature so far&#46; None of them have been linked to delayed contact hypersensitivity reactions&#46; We present a case of acral type primary cutaneous lymphoma T CD8<span class="elsevierStyleSup">&#43;</span> involving both earlobes clearly related with the prolonged use of gold earrings&#44; confirmed with epicutaneous tests&#44; histopathology&#44; immunohistochemical and molecular studies&#46; Auricular skin lesions were induced again with a provocation test with identical histopathologycal and the same clonality&#44; confirming both the diagnosis of lymphoma and its induction by the antigenic stimulus of gold&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El linfoma cut&#225;neo primario T CD8<span class="elsevierStyleSup">&#43;</span> tipo acral ha sido incluido como entidad provisional dentro de la nueva clasificaci&#243;n revisada de las neoplasias linfoides de la Organizaci&#243;n Mundial de la Salud en 2016<span class="elsevierStyleSup">1</span>&#46; Inicialmente fue descrito como proliferaci&#243;n linfoide CD8<span class="elsevierStyleSup">&#43;</span> indolente de la oreja<span class="elsevierStyleSup">2</span>&#44; y se han publicado en la literatura un total de 29 casos de dicha neoplasia&#46; Ninguno de ellos se ha relacionado con reacciones de hipersensibilidad retardada de contacto&#46; Presentamos un caso de linfoma cut&#225;neo primario T CD8<span class="elsevierStyleSup">&#43;</span> tipo acral auricular bilobular en clara relaci&#243;n etiol&#243;gica con el uso prolongado de unos pendientes de oro confirmada con pruebas epicut&#225;neas&#44; estudio histol&#243;gico&#44; inmunohistoqu&#237;mico y molecular&#46; Las lesiones cut&#225;neas bilobulares fueron inducidas de nuevo con un test de uso e id&#233;nticos resultados a los iniciales y misma clonalidad&#44; lo cual termin&#243; de confirmar tanto el diagn&#243;stico del linfoma como su inducci&#243;n por el est&#237;mulo antig&#233;nico del oro&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Molinero Caturla J&#44; S&#225;nchez S&#225;nchez J&#44; Marcoval Caus J&#44; Muniesa Montserrat C&#44; Climent Esteller J&#44; Servitje Bedate O&#46; Linfoma cut&#225;neo primario T CD8<span class="elsevierStyleSup">&#43;</span> tipo acral inducido por hipersensibilidad retardada persistente a pendientes de oro&#46; Actas Dermosifiliogr&#46; 2021&#59;112&#58;649&#8211;653&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A and B&#44; Reddish papules on both earlobes located at the earring holes&#46; C&#44; Staining with hematoxylin and eosin &#215;100&#59; dense dermal lymphocytic infiltrate with very limited epidermotropism&#46; D&#44; Immunohistochemical staining for CD8 &#215;10&#59; the neoplastic lymphocytes were mainly CD8<span class="elsevierStyleSup">&#43;</span>&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Images of the gene rearrangement study of the TCR beta receptor gene in the initial lesions &#40;A&#41; and those induced by the use test &#40;B&#41;&#46; Note the identical monoclonal peak in both tubes B and C in the different samples&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Patch tests showing intense positivity for gold sodium thiosulfate &#40;infiltrated plaque with blistering&#41;&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A and B&#44; Papular lesions at the same site 5 weeks after rechallenge with the gold earrings &#40;use test&#41;&#46; C and D&#44; Identical findings in the biopsy of these lesions with hematoxylin and eosin staining and immunohistochemical study &#215;100 as in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C and D &#40;initial lesions&#41;&#46;</p>"
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                          "etal" => false
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                            0 => "T&#46; Petrella"
                            1 => "E&#46; Maubec"
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                        "fecha" => "2014"
                        "volumen" => "36"
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Article information

ISSN: 15782190
Original language: English

DOI:10.1016/j.adengl.2021.05.006

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Year/Month	Html	Pdf	Total

2024 November	12	11	23
2024 October	66	32	98
2024 September	87	21	108
2024 August	107	63	170
2024 July	89	35	124
2024 June	73	35	108
2024 May	73	46	119
2024 April	99	43	142
2024 March	101	34	135
2024 February	87	39	126
2024 January	82	39	121
2023 December	70	18	88
2023 November	78	32	110
2023 October	60	31	91
2023 September	70	34	104
2023 August	40	17	57
2023 July	74	33	107
2023 June	60	26	86
2023 May	63	40	103
2023 April	48	30	78
2023 March	50	25	75
2023 February	40	28	68
2023 January	46	29	75
2022 December	52	44	96
2022 November	36	32	68
2022 October	32	21	53
2022 September	46	40	86
2022 August	30	35	65
2022 July	25	40	65
2022 June	27	38	65
2022 May	37	43	80
2022 April	59	41	100
2022 March	72	75	147
2022 February	58	41	99
2022 January	60	59	119
2021 December	50	41	91
2021 November	76	57	133
2021 October	82	78	160
2021 September	37	41	78
2021 August	47	34	81
2021 July	68	27	95
2021 June	27	23	50
2021 May	98	45	143

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