Case and Research Letter
Cytotoxic CD4/CD8 Double-Negative Mycosis Fungoides
Micosis fungoide doble CD4-CD8 negativo de fenotipo citotóxico
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A. MF transformada con placas y tumores, algunos erosionados. B. MF eritrodérmica con parches eritematosos descamativos que afectaban más del 80% de la superficie corporal. C. MF como morfea con placas esclerosas hiperpigmentadas en tórax. D. MF ictiosiforme con placas con escamas secas de tamaño moderado ictiosiformes localizadas en la región lumbar. E. MF granulomatosa con placas y tumores, algunos redondos lisos y otros ulcerados F. MF hipopigmentada y colagenomas eruptivos.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "O.J. Valencia-Ocampo, L.A. Correa, J.C. Wolff-Idárraga, M.M. Velásquez-Lopera" "autores" => array:4 [ 0 => array:2 [ "nombre" => "O.J." "apellidos" => "Valencia-Ocampo" ] 1 => array:2 [ "nombre" => "L.A." "apellidos" => "Correa" ] 2 => array:2 [ "nombre" => "J.C." "apellidos" => "Wolff-Idárraga" ] 3 => array:2 [ "nombre" => "M.M." 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"apellidos" => "Ballano Ruiz" "email" => array:1 [ 0 => "adrian.baru@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S." "apellidos" => "Bakali Badesa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M.C." "apellidos" => "Gómez Mateo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M.C." "apellidos" => "Yus Gotor" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Obispo Polanco, Teruel, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Miguel Servet, Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Micosis fungoide doble CD4-CD8 negativo de fenotipo citotóxico" ] ] "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" => 1443 "Ancho" => 948 "Tamanyo" => 606668 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histological image showing lymphocytic infiltrate throughout the thickness of the epithelium, with a parabasal distribution, marked epidermotropism, and the presence of Pautrier microabscesses. These lymphocytes are also observed in the superficial dermis. The lymphocytes are atypical, with angular, cerebriform, cleft nuclei.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Mycosis fungoides (MF) is usually characterized by infiltrate containing T α/β helper memory cells with a classic immunophenotype (βF1<span class="elsevierStyleSup">+</span>, CD3<span class="elsevierStyleSup">+</span>, CD4<span class="elsevierStyleSup">+</span>, CD5<span class="elsevierStyleSup">+</span>, CD8<span class="elsevierStyleSup">−</span>, CD45RO<span class="elsevierStyleSup">+</span>). However, the broad clinical and histological spectrum and unusual phenotypic variants associated with MF make diagnosis difficult.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 42-year-old man with no past history of interest was seen for asymptomatic lesions that had appeared 2 years earlier. These polymorphic and evanescent lesions consisted of psoriasiform and circular eczematous elements, some with circinate morphology (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and had been treated with multiple topical and oral treatments for the clinical diagnosis of dermatomycosis, eczema, and psoriasis. Fever, weight loss, profuse sweating, and other systemic clinical signs were absent. An initial biopsy revealed superficial lymphohistiocytic dermatitis with a psoriasiform pattern. A second biopsy showed atypical lymphocytic infiltrate (with angular, cerebriform, cleft nuclei) throughout the thickness of the epithelium, with a parabasal distribution, marked epidermotropism, and the presence of Pautrier microabscesses. These lymphocytes were also evident in the superficial dermis. The immunophenotype was positive for T-cell markers (cytoplasmic CD3 and CD2), with partial loss of CD5, and negative for CD4, CD8, CD7, and CD45RO. Analyses revealed negative T cell receptor (TCR) α and TCRβ gene rearrangement, and negative staining for CD30, PD1, and CD56. Cytotoxic markers (granzyme B, perforin, and TIA1) were detected (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>), and in situ hybridization for Epstein-Barr virus early transcripts (EBERs) was negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Based on the finding of a cutaneous epidermotropic T cell lymphoma with a cytotoxic phenotype, the differential diagnosis included other cytotoxic lymphomas such as gamma/delta lymphoma, CD8<span class="elsevierStyleSup">+</span> lymphomatoid papulosis, and CD8<span class="elsevierStyleSup">+</span> epidermotropic cytotoxic T-cell lymphoma. The clinical–pathological correlation was essential to establish diagnosis of CD4<span class="elsevierStyleSup">-</span>/CD8<span class="elsevierStyleSup">-</span> cytotoxic MF. The results of a tumor extension analysis performed with positron emission tomography-computed tomography (PET-CT) were normal. Levels of lactate dehydrogenase and β2-microglobulin were normal, and peripheral blood flow cytometry revealed no findings of interest. The patient was treated with an ascending dose of methotrexate (up to 20 mg/wk), to which he showed a partial clinical response 12 weeks later. This was combined with narrowband ultraviolet B phototherapy 3 times per week, a regimen that the patient has continued.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Partial loss of T lymphocyte markers and positive cytotoxic markers have been described in cases of MF, although more frequently in late disease stages.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Cases of CD4<span class="elsevierStyleSup">-</span>/CD8<span class="elsevierStyleSup">-</span> double-negative MF are rare. They are more common in early disease stages than in advanced forms,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> and tend to involve unusual clinical pictures (e.g. circinate or other polymorphic lesions) in addition to the classic lesions.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> However, the prognosis of this disease does not seem to be determined by the cellular phenotype.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> It is important to look out for these immunohistochemical variants of MF, and to bear in mind that a clinical–pathological correlation is essential to establish a correct diagnosis.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0025" 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: Ballano Ruiz A, Bakali Badesa S, Gómez Mateo MC, Yus Gotor MC. Micosis fungoide doble CD4-CD8 negativo de fenotipo citotóxico. Actas Dermosifiliogr. 2022;113:199–201.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1648 "Ancho" => 905 "Tamanyo" => 219995 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diffuse, ring-shaped, polymorphic, erythematous–desquamative lesions.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1443 "Ancho" => 948 "Tamanyo" => 606668 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histological image showing lymphocytic infiltrate throughout the thickness of the epithelium, with a parabasal distribution, marked epidermotropism, and the presence of Pautrier microabscesses. These lymphocytes are also observed in the superficial dermis. The lymphocytes are atypical, with angular, cerebriform, cleft nuclei.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1092 "Ancho" => 1368 "Tamanyo" => 454560 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Histological images showing (A) CD4<span class="elsevierStyleSup">-</span>, (B) CD8<span class="elsevierStyleSup">-</span>, (C) cytoplasmic CD3<span class="elsevierStyleSup">+</span>, and (D) granzyme-B<span class="elsevierStyleSup">+</span> staining.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.H. 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| año/Mes | Html | Total | |
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