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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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      "seccion" => array:1 [
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Suchak"
                            1 => "S&#46; O&#8217;Connor"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "T&#46; Petrella"
                            1 => "E&#46; Maubec"
                            2 => "P&#46; Cornillet-Lefebvre"
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                            4 => "M&#46; Pluot"
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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,
Autor para correspondencia
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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    "titulo" => "Primary Cutaneous Acral CD8<span class="elsevierStyleSup">&#43;</span> T-cell Lymphoma Induced by Persistent Delayed Hypersensitivity to Gold Earrings"
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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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                      "titulo" => "Multicenter case series of indolent small&#47;medium-sized CD8<span class="elsevierStyleSup">&#43;</span> lymphoid proliferations with predilection for the ear and face"
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                      "titulo" => "Indolent CD8-positive lymphoid proliferation of the face&#46; A distinct primary cutaneous T-cell lymphoma&#63;"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "T&#46; Petrella"
                            1 => "E&#46; Maubec"
                            2 => "P&#46; Cornillet-Lefebvre"
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                          "etal" => false
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                            0 => "J&#46;W&#46; Hagen"
                            1 => "C&#46;M&#46; Magro"
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                  ]
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                      "doi" => "10.1097/DAD.0b013e318297f7fd"
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                      "titulo" => "Primary cutaneous acral CD8 positive T-cell lymphoma with extra-cutaneous involvement&#58; a long-standing case with an unexpected progression"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Alberti-Violetti"
                            1 => "D&#46; Fanoni"
                            2 => "M&#46; Provasi"
                            3 => "L&#46; Corti"
                            4 => "L&#46; Venegoni"
                            5 => "E&#46; Berti"
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                  ]
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                        0 => array:2 [
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                        ]
                      ]
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                  ]
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