Case and Research Letters
Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoma With Expression of Follicular T-Helper Cell Markers and Spontaneous Remission
Linfoma cutáneo primario de células T pleomórficas de pequeño y mediano tamaño CD4+ con expresión de marcadores de linfocito T helper folicular y resolución espontánea
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B) El infiltrado está constituido principalmente por linfocitos pleomórficos de pequeño y mediano tamaño (hematoxilina-eosina ×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Ayala, M.D. Ramón, M. Cabezas, E. Jordá" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Ayala" ] 1 => array:2 [ "nombre" => "M.D." "apellidos" => "Ramón" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Cabezas" ] 3 => array:2 [ "nombre" => "E." 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C and D, Healing of the calciphylaxis-induced ulcers after treatment with intralesional sodium thiosulfate.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Ossorio-García, D. Jiménez-Gallo, C. Arjona-Aguilera, M. Linares-Barrios" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Ossorio-García" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Jiménez-Gallo" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Arjona-Aguilera" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Linares-Barrios" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S000173101500513X" "doi" => "10.1016/j.ad.2015.10.013" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S000173101500513X?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016000706?idApp=UINPBA000044" "url" => "/15782190/0000010700000004/v1_201604280043/S1578219016000706/v1_201604280043/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219016000688" "issn" => "15782190" "doi" => "10.1016/j.adengl.2016.02.012" "estado" => "S300" "fechaPublicacion" => "2016-05-01" "aid" => "1310" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2016;107:354-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 680 "formatos" => array:3 [ "EPUB" => 38 "HTML" => 514 "PDF" => 128 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Acquired Symmetric Facial Hyperpigmentation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "354" "paginaFinal" => "356" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hiperpigmentación facial simétrica adquirida" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 686 "Ancho" => 1800 "Tamanyo" => 241140 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A and B, Multiple, confluent macules measuring a few millimeters in diameter, forming a poorly-defined, bluish-gray macule of mottled appearance on the forehead and extending into both parietal regions.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. 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"apellidos" => "Echeverría" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731015005116" "doi" => "10.1016/j.ad.2015.10.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731015005116?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016000688?idApp=UINPBA000044" "url" => "/15782190/0000010700000004/v1_201604280043/S1578219016000688/v1_201604280043/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoma With Expression of Follicular T-Helper Cell Markers and Spontaneous Remission" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor:</span>" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "357" "paginaFinal" => "359" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D. Ayala, M.D. Ramón, M. Cabezas, E. Jordá" "autores" => array:4 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Ayala" "email" => array:1 [ 0 => "dayalca83@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.D." "apellidos" => "Ramón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Cabezas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Jordá" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Clínico Universitario de Valencia, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Clínico Universitario de Valencia, Valencia, 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 de células T pleomórficas de pequeño y mediano tamaño CD4+ con expresión de marcadores de linfocito T <span class="elsevierStyleItalic">helper</span> folicular y resolución espontánea" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 718 "Ancho" => 1601 "Tamanyo" => 171500 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Well-defined erythematous nodular lesion on the right cheek, with an erosion affecting part of the surface. B, Complete resolution of the lesion after 4 weeks, with a scar corresponding to the site of biopsy.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The CD4<span class="elsevierStyleSup">+</span> small/medium-sized pleomorphic T-cell lymphoma (SMPTCL) is a type of primary cutaneous lymphoma included as a provisional entity in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> This lymphoma is characterized by a predominance of CD4<span class="elsevierStyleSup">+</span> small/medium-sized pleomorphic T cells and presents a favorable clinical course.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 62-year-old man with no past medical history of interest presented an asymptomatic tumor that had appeared on his right cheek a month earlier and had shown rapid growth. Physical examination revealed a well-defined erythematous nodule measuring 2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1.5<span class="elsevierStyleHsp" style=""></span>cm. The nodule had a rubbery consistency and presented a central erosion (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The lesion was biopsied. On histology, a diffuse, dense infiltrate was seen to occupy the full thickness of the dermis, with extension into the subcutaneous cellular tissue; there was no evidence of epidermotropism (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). This was a polymorphous infiltrate formed mainly of lymphocytes, histiocytes, and plasma cells. The predominant cells in the neoplastic infiltrate were small- and medium-sized lymphocytes with marked pleomorphism. Immunohistochemistry (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) was intensely positive for CD3, CD4, and CD5, and was negative for CD8 and CD30. Poorly defined infiltrates rich in CD20<span class="elsevierStyleSup">+</span> cells without light chain restriction were also evident. The sample was also positive for PD1 and Bcl-6. Molecular biology study revealed a monoclonal rearrangement of the T-cell receptor (TCR) beta gene. The Ki67 cell proliferation index was below 20%. Epstein-Barr virus expression was negative. Further tests included an analysis of lymphocyte populations and immunoglobulin levels, computed tomography of the neck, chest, abdomen, and pelvis, and a bone-marrow biopsy. All the results were normal or negative.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After 4 weeks of follow-up, the tumor lesion underwent spontaneous regression until its complete disappearance, leaving only a scar at the site of biopsy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). No changes were observed in pigmentation, and the area was not infiltrated or indurated to palpation. After a year of follow-up, the patient remained asymptomatic, with no evidence of tumor recurrence.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Since the description of SMPTCL as a provisional entity in 2005, the disease has been reported in adults and children,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> but it accounts for only 2% of all primary cutaneous lymphomas.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Clinical presentation is usually as a solitary, fast-growing plaque or tumor, typically on the face, neck, or upper part of the trunk.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Histologically there is a dense, nodular, or diffuse dermal infiltrate that extends into the subcutaneous cellular tissue. There is a predominance of small/medium-sized pleomorphic CD4<span class="elsevierStyleSup">+</span> T cells, although up to 30% of the population can be large pleomorphic cells.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> A mixed inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, and histiocytes can be observed in some cases.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5,6</span></a> By definition, these lymphomas have a CD3<span class="elsevierStyleSup">+</span>, CD4<span class="elsevierStyleSup">+</span>, CD8<span class="elsevierStyleSup">−</span>, CD30<span class="elsevierStyleSup">−</span> immunophenotype, sometimes with a loss of T-cell markers. A monoclonal rearrangement of the TCR gene is detected in the majority of cases.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Various studies have evaluated the expression of follicular helper T cells (T<span class="elsevierStyleInf">FH</span>) markers in this type of primary cutaneous lymphoma.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">4,5</span></a> The T<span class="elsevierStyleInf">FH</span> cell is a specific subtype of CD4<span class="elsevierStyleSup">+</span> T<span class="elsevierStyleInf">H</span> cell, usually found in the germinal center of lymphoid follicles.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The function of these particular lymphocytes is to regulate the immune response of B cells, favoring their differentiation into immunoglobulin-secreting plasma cells or memory B cells. A number of criteria exist to differentiate T<span class="elsevierStyleInf">FH</span> lymphocytes from other T<span class="elsevierStyleInf">H</span> cell subtypes, including the expression of a series of markers such as CXCL13, CD10, Bcl-6, ICOS, and PD1. None of these markers is wholly specific to T<span class="elsevierStyleInf">FH</span> cells, as some of them have occasionally been detected in cases of mycosis fungoides and Sezary syndrome, as well as in adult T-cell lymphomas and leukemias.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> However, the combined expression of various of these markers in a lymphoproliferative disease is highly specific to an origin in neoplastic T<span class="elsevierStyleInf">FH</span> lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In our case, the cells were positive for the markers Bcl-6 and PD-1. This expression of T<span class="elsevierStyleInf">FH</span>-cell markers in the neoplastic lymphocytes may explain the foci of CD20<span class="elsevierStyleSup">+</span> B-cell infiltrates typically found in SMPTCL,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,5</span></a> as occurred in our case.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The prognosis of these lymphomas is excellent, particularly in cases with isolated lesions.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,6</span></a> In localized lesions, surgical excision or local radiotherapy are the preferred alternatives.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Only 2 cases of spontaneous regression of untreated SMPTCL have been reported.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> The heterogeneous nature of this entity has led some authors to propose the term <span class="elsevierStyleItalic">cutaneous proliferation of pleomorphic T lymphocytes of undetermined significance</span> to refer to cases in which it is impossible determine the benign or malignant nature of the disease, and thus avoid forcing a diagnosis to be made.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Although it is sometimes difficult to distinguish this type of cutaneous T-cell lymphoma from reactive lymphoproliferative disorders, SMPTCL is a recognizable disease with characteristic expression of T<span class="elsevierStyleInf">FH</span>-cell markers. In conclusion, we have presented an atypical case of SMPTCL with rapid, spontaneous resolution, and with expression of the markers Bcl-6 and PD1, which suggests a T<span class="elsevierStyleInf">FH</span> cell origin of the neoplastic disease.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ayala D, Ramón MD, Cabezas M, Jordá E. Linfoma cutáneo primario de células T pleomórficas de pequeño y mediano tamaño CD4+ con expresión de marcadores de linfocito T <span class="elsevierStyleItalic">helper</span> folicular y resolución espontánea. Actas Dermosifiliogr. 2016;107:358–360.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 718 "Ancho" => 1601 "Tamanyo" => 171500 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Well-defined erythematous nodular lesion on the right cheek, with an erosion affecting part of the surface. B, Complete resolution of the lesion after 4 weeks, with a scar corresponding to the site of biopsy.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 837 "Ancho" => 1700 "Tamanyo" => 561394 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, The low-power image shows a dense dermal infiltrate that extends into the subcutaneous cellular tissue but shows no epidermotropism. Hematoxylin and eosin, original magnification ×4. B, The infiltrate is formed mainly of small- and medium-sized pleomorphic lymphocytes. Hematoxylin and eosin, original magnification ×40.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1247 "Ancho" => 2000 "Tamanyo" => 767666 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A and B, Immunohistochemistry stains show the cells to be strongly positive for CD4 and very weakly positive for CD8. CD4 and CD8 stains, original magnification ×4.<span class="elsevierStyleHsp" style=""></span>C, Poorly defined infiltrates rich in CD20<span class="elsevierStyleSup">+</span> cells. CD20 stain, original magnification ×4. D and E, Cell expression of Bcl-6 and PD1. 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| año/Mes | Html | Total | |
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