Case and Research Letters
Cerebral Involvement as the First Extracutaneous Manifestation of Mycosis Fungoides
Micosis fungoide con afectación cerebral como primera manifestación extracutánea
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B: Biopsia de tejido cerebral que muestra un infiltrado linfoide de predominio perivascular (HE, ×200). C: Tinción inmunohistoquímica que pone de manifiesto el infiltrado linfocitario CD4+ en tejido cerebral (CD4, ×100). D: Expresión del antígeno CD30 en escasas células linfoides del tejido cerebral (CD30, ×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. de Quintana-Sancho, E. Acebo-Mariñas, J. Gardeazabal-García, A. Aperribay-Esparza" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "de Quintana-Sancho" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Acebo-Mariñas" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Gardeazabal-García" ] 3 => array:2 [ "nombre" => "A." 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"apellidos" => "Sánchez-Caminero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731015002136" "doi" => "10.1016/j.ad.2015.03.010" "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/S0001731015002136?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015002140?idApp=UINPBA000044" "url" => "/15782190/0000010600000008/v1_201510011018/S1578219015002140/v1_201510011018/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Cerebral Involvement as the First Extracutaneous Manifestation of Mycosis Fungoides" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "693" "paginaFinal" => "695" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. de Quintana-Sancho, E. Acebo-Mariñas, J. Gardeazabal-García, A. Aperribay-Esparza" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "de Quintana-Sancho" "email" => array:1 [ 0 => "adriandeq@gmail.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" => "E." "apellidos" => "Acebo-Mariñas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Gardeazabal-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "A." "apellidos" => "Aperribay-Esparza" "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 Universitario Cruces, Barakaldo, Vizcaya, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Cruces, Barakaldo, Vizcaya, 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 con afectación cerebral como primera manifestación extracutánea" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1833 "Ancho" => 2519 "Tamanyo" => 1292637 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Diffuse white matter signal abnormality, especially in the frontal and periventricular regions (arrows). B, Brain tissue biopsy showing a predominantly perivascular lymphoid infiltrate (hematoxylin-eosin, ×200). C, Immunohistochemical staining showing the CD4<span class="elsevierStyleSup">+</span> lymphocytic infiltrate in brain tissue (CD4, ×100). D, Expression of CD30 antigen in sparse lymphoid cells of brain tissue (CD30, ×40).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Mycosis fungoides is the most common cutaneous lymphoma. The probability of systemic involvement depends on disease extension and is very low during the early stages, when the clinical course is usually indolent. However, the risk of extracutaneous disease 20 years after diagnosis is 10% in patients with generalized plaques and 35.5% in patients with tumorous lesions.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The most common finding is enlarged regional lymph nodes, although any organ can be affected, especially the lungs, spleen, liver, and gastrointestinal tract.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Central nervous system (CNS) involvement is very uncommon, even more so in the absence of extracutaneous disease.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 47-year-old woman with erythematous-desquamative lesions that first appeared 6 years previously and were diagnosed as stage 1b mycosis fungoides after 4 inconclusive biopsies. During a 4-year follow-up period she received treatment with potent topical corticosteroids, psoralen-UV-A, interferon, and oral bexarotene. During the last year, the patient developed tumorous lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A), with 14% Sézary cells (<<span class="elsevierStyleHsp" style=""></span>1000/μL) in peripheral blood and unremarkable findings on a computed tomography (CT) scan of the chest, abdomen, and pelvis (stage IIb). The dose of oral bexarotene was increased and local radiation therapy started, and a partial response was observed. Skin biopsy of a rapidly growing tumorous lesion revealed large cell transformation with marked positivity for CD30 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B-D) that had not been present in the previous biopsies. A few months later the patient complained of recent memory loss and depression. The physical examination revealed nystagmus and dysmetria. An emergency CT scan of the brain ruled out acute disease. Similarly, a subsequent CT scan of the chest, abdomen, and pelvis revealed no significant abnormalities; nevertheless, the patient was admitted to hospital. Magnetic resonance imaging of the brain revealed diffuse white matter signal abnormalities, especially in the frontal region (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), which was compatible with infectious encephalitis. Analysis of cerebrospinal fluid revealed pleocytosis dominated by T lymphocytes with no atypia. Culture was negative. Biopsy of brain tissue revealed infiltration by CD4<span class="elsevierStyleSup">+</span>CD8<span class="elsevierStyleSup">–</span> T-cell lymphoma (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B and C) with no large cell transformation and isolated CD30<span class="elsevierStyleSup">+</span> cells (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D). Chemotherapy was started according to the BAM protocol (carmustine, methotrexate, and cytarabine). However, the disease progressed, with biopsy-confirmed kidney metastases and multiple pulmonary nodules compatible with metastasis. Large cell transformation was not observed in brain tissue or kidney tissue; therefore, the case was considered to be a localized phenomenon affecting the skin. Unfortunately, the patient died from respiratory insufficiency 3 months after the onset of neurological symptoms.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">In contrast with other cutaneous lymphomas, such as aggressive epidermotropic CD8<span class="elsevierStyleSup">+</span> T-cell lymphoma, involvement of the CNS as a result of mycosis fungoides is exceptional, accounting for 1.6% of a series of 187 patients.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> However, CNS involvement was found in 11% to 14% of autopsies performed on patients who died of mycosis fungoides.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Some authors report meningeal involvement to be the most common finding,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> whereas others claim that intraparenchymal brain involvement is the most common, with both forms able to occur simultaneously.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The male-to-female ratio for this disease is 4:1, and in most cases, symptoms appear between 3 and 5 years after diagnosis of mycosis fungoides.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> The most frequent symptoms include confusion and depression, which are associated with lethargy and nausea. Optic and facial nerve involvement is common, as are gait disorders. The prognosis is poor, with a mean survival of 4.5 months after diagnosis.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">As for risk factors associated with CNS involvement, the series of Stein et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> showed that patients with at least 2 of 4 risk factors (T3-T4, N3, M1, and B1) had a 1 in 6 risk of CNS involvement at 10 years of follow-up compared with a 1 in a 100 risk in patients with 1 or none of the 4 risk factors.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The literature contains barely 10 cases of mycosis fungoides affecting the CNS associated with large cell transformation.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,7,8</span></a> Patients with mycosis fungoides and large cell transformation have a 5% probability of CNS involvement, compared with 1.6% of patients with no large cell transformation.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Furthermore, while patients with large cell transformation usually present extracutaneous symptoms before cerebral involvement (lymph nodes and viscera), some patients with large cell transformation develop cerebral metastasis without previously having developed extracutaneous symptoms, as in the case we present.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> These patients should have an annual cerebral CT scan.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> As for CD30 expression, some studies show a better prognosis in patients with large cell transformation and CD30<span class="elsevierStyleSup">+</span> cells.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Mycosis fungoides very rarely affects the CNS. Patients with large cell transformation are usually at increased risk, sometimes without previously having developed extracutaneous symptoms. Such patients should undergo radiological evaluation, and physicians should be on the alert for neurological symptoms.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: de Quintana-Sancho A, Acebo-Mariñas E, Gardeazabal-García J, Aperribay-Esparza A. Micosis fungoide con afectación cerebral como primera manifestación extracutánea. Actas Dermosifiliogr. 2015;106:693–695.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1833 "Ancho" => 2519 "Tamanyo" => 1512614 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Mycosis fungoides in the tumor phase. B, Biopsy (detail) of a tumorous lesion. Note the diffuse large cell lymphoid infiltrate in the dermis (hematoxylin-eosin, original magnification, ×400). C, Immunohistochemical staining showing predominance of CD4<span class="elsevierStyleSup">+</span> T lymphocytes (CD4, ×400). D, Expression of CD30 antigen in cells of the lymphoid infiltrate (CD30, ×400).</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" => 1833 "Ancho" => 2519 "Tamanyo" => 1292637 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Diffuse white matter signal abnormality, especially in the frontal and periventricular regions (arrows). B, Brain tissue biopsy showing a predominantly perivascular lymphoid infiltrate (hematoxylin-eosin, ×200). C, Immunohistochemical staining showing the CD4<span class="elsevierStyleSup">+</span> lymphocytic infiltrate in brain tissue (CD4, ×100). D, Expression of CD30 antigen in sparse lymphoid cells of brain tissue (CD30, ×40).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics and outcome of patients with extracutaneous mycosis fungoides" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E.C. De Coninck" 1 => "Y.H. Kim" 2 => "A. Varghese" 3 => "R.T. Hoppe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.2001.19.3.779" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 5 | 19 |
| 2024 October | 109 | 46 | 155 |
| 2024 September | 120 | 38 | 158 |
| 2024 August | 147 | 63 | 210 |
| 2024 July | 109 | 45 | 154 |
| 2024 June | 116 | 38 | 154 |
| 2024 May | 101 | 37 | 138 |
| 2024 April | 102 | 30 | 132 |
| 2024 March | 101 | 46 | 147 |
| 2024 February | 69 | 39 | 108 |
| 2024 January | 75 | 29 | 104 |
| 2023 December | 75 | 28 | 103 |
| 2023 November | 75 | 31 | 106 |
| 2023 October | 72 | 26 | 98 |
| 2023 September | 90 | 30 | 120 |
| 2023 August | 66 | 21 | 87 |
| 2023 July | 87 | 32 | 119 |
| 2023 June | 68 | 31 | 99 |
| 2023 May | 95 | 31 | 126 |
| 2023 April | 57 | 22 | 79 |
| 2023 March | 63 | 17 | 80 |
| 2023 February | 73 | 25 | 98 |
| 2023 January | 52 | 35 | 87 |
| 2022 December | 101 | 55 | 156 |
| 2022 November | 50 | 40 | 90 |
| 2022 October | 56 | 34 | 90 |
| 2022 September | 38 | 41 | 79 |
| 2022 August | 39 | 45 | 84 |
| 2022 July | 38 | 37 | 75 |
| 2022 June | 46 | 31 | 77 |
| 2022 May | 54 | 37 | 91 |
| 2022 April | 104 | 61 | 165 |
| 2022 March | 119 | 61 | 180 |
| 2022 February | 90 | 41 | 131 |
| 2022 January | 75 | 43 | 118 |
| 2021 December | 52 | 61 | 113 |
| 2021 November | 72 | 61 | 133 |
| 2021 October | 130 | 58 | 188 |
| 2021 September | 58 | 41 | 99 |
| 2021 August | 75 | 44 | 119 |
| 2021 July | 43 | 36 | 79 |
| 2021 June | 36 | 49 | 85 |
| 2021 May | 59 | 38 | 97 |
| 2021 April | 103 | 63 | 166 |
| 2021 March | 83 | 34 | 117 |
| 2021 February | 60 | 35 | 95 |
| 2021 January | 49 | 26 | 75 |
| 2020 December | 45 | 25 | 70 |
| 2020 November | 43 | 31 | 74 |
| 2020 October | 20 | 20 | 40 |
| 2020 September | 55 | 24 | 79 |
| 2020 August | 37 | 26 | 63 |
| 2020 July | 41 | 12 | 53 |
| 2020 June | 43 | 45 | 88 |
| 2020 May | 32 | 28 | 60 |
| 2020 April | 36 | 22 | 58 |
| 2020 March | 37 | 18 | 55 |
| 2020 February | 1 | 8 | 9 |
| 2020 January | 6 | 15 | 21 |
| 2019 December | 8 | 4 | 12 |
| 2019 November | 4 | 1 | 5 |
| 2019 October | 0 | 5 | 5 |
| 2019 September | 4 | 1 | 5 |
| 2019 August | 4 | 3 | 7 |
| 2019 July | 4 | 3 | 7 |
| 2019 June | 4 | 29 | 33 |
| 2019 May | 7 | 34 | 41 |
| 2019 April | 4 | 14 | 18 |
| 2019 March | 4 | 5 | 9 |
| 2019 February | 0 | 3 | 3 |
| 2019 January | 4 | 3 | 7 |
| 2018 December | 4 | 0 | 4 |
| 2018 November | 2 | 0 | 2 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 9 | 0 | 9 |
| 2018 May | 0 | 1 | 1 |
| 2018 February | 24 | 3 | 27 |
| 2018 January | 26 | 7 | 33 |
| 2017 December | 32 | 8 | 40 |
| 2017 November | 18 | 2 | 20 |
| 2017 October | 27 | 5 | 32 |
| 2017 September | 18 | 11 | 29 |
| 2017 August | 24 | 3 | 27 |
| 2017 July | 19 | 8 | 27 |
| 2017 June | 24 | 9 | 33 |
| 2017 May | 29 | 15 | 44 |
| 2017 April | 15 | 5 | 20 |
| 2017 March | 11 | 73 | 84 |
| 2017 February | 19 | 11 | 30 |
| 2017 January | 10 | 11 | 21 |
| 2016 December | 19 | 13 | 32 |
| 2016 November | 25 | 18 | 43 |
| 2016 October | 21 | 19 | 40 |
| 2016 September | 0 | 1 | 1 |
| 2016 July | 1 | 1 | 2 |
| 2016 June | 5 | 2 | 7 |
| 2016 April | 4 | 0 | 4 |
| 2016 March | 1 | 0 | 1 |
| 2015 December | 0 | 2 | 2 |
| 2015 November | 0 | 1 | 1 |
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