Case and Research Letter
Immunophenotypic Shift Associated With Angiocentricity and Cytoxic Characteristics in a Case of Mycosis Fungoides
Cambio de inmunofenotipo asociado a angiocentricidad y características citotóxicas en un caso de micosis fungoide
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"apellidos" => "Magliano" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S000173101630062X" "doi" => "10.1016/j.ad.2016.04.007" "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/S000173101630062X?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219016301639?idApp=UINPBA000044" "url" => "/15782190/0000010700000008/v2_201704100057/S1578219016301639/v2_201704100057/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219016301615" "issn" => "15782190" "doi" => "10.1016/j.adengl.2016.04.002" "estado" => "S300" "fechaPublicacion" => "2016-10-01" "aid" => "1402" "copyright" => "Elsevier España, S.L.U. and AEDV" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2016;107:695-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1253 "formatos" => array:3 [ "EPUB" => 61 "HTML" => 909 "PDF" => 283 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Multimodal Treatment of Calciphylaxis With Sodium Thiosulfate, Alprostadil, and Hyperbaric Oxygen Therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "695" "paginaFinal" => "697" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento multimodal de la calcifilaxis con tiosulfato sódico, alprostadil y oxigenoterapia hiperbárica" ] ] "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" => 965 "Ancho" => 1500 "Tamanyo" => 299350 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Calciphylaxis-related skin ulcers on the anterior aspect of the thighs. 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Vargas Nevado, N. López Navarro, E. Gallego Domínguez, E. Herrera Ceballos" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Á." "apellidos" => "Vargas Nevado" "email" => array:1 [ 0 => "avargasn88@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" => "N." "apellidos" => "López Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Gallego Domínguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Herrera Ceballos" "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 Universitario Virgen de la Victoria, Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario Virgen de la Victoria, Málaga, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cambio de inmunofenotipo asociado a angiocentricidad y características citotóxicas en un caso de micosis fungoide" ] ] "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" => 1125 "Ancho" => 1500 "Tamanyo" => 659020 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Large ulcerating necrotic plaque on the medial surface of the lower leg. B, Angiotropic infiltrate of atypical lymphocytes. Hematoxylin and eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×100.<span class="elsevierStyleHsp" style=""></span>C, Loss of CD4 expression. D, Loss of CD30 expression.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Immunophenotypic shift during the progression of mycosis fungoides (MF) is a rare event, and its prognostic significance is unknown.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a man aged 84 years who presented a 2-year history of generalized pruritus. Over the previous 5 months he had developed erythematous plaques of different sizes mainly on the trunk; the plaques had an annular or arcuate morphology and some showed desquamation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Biopsy of a plaque on the abdomen revealed a dermal infiltrate of atypical and pleomorphic (small, medium-sized and large) lymphocytes with hyperchromatic cerebriform nuclei, showing a tendency to epidermotropism, forming large intraepidermal aggregates (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Large lymphocytes accounted for less than 25% of the cells of the infiltrate. Immunohistochemistry was positive for CD2, CD3, CD4, CD5, CD6, and CD7. The CD8 antigen was focally positive in the dermis, the CD4:CD8 ratio was 4:1, and CD30 was intensely expressed in the intraepidermal lymphocytes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, C and D). Polymerase chain reaction analysis detected T-cell receptor (<span class="elsevierStyleItalic">TCR</span>) γ-chain gene clonal rearrangement. No expression of CD56, TIA-1, or granzyme B was detected. There were no significant changes on other additional laboratory tests. Based on these findings, we made a diagnosis of MF-type primary cutaneous T-cell lymphoma, stage<span class="elsevierStyleHsp" style=""></span>IB. Treatment was initiated with topical corticosteroids and psoralen–UV-A, with partial improvement of the skin lesions.</p><p id="par0020" class="elsevierStylePara elsevierViewall">At 6 months the patient developed a large ulcerating necrotic tumor plaque with erythematous-violaceous borders on the medial surface of the left lower leg (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Further biopsies were taken and a monomorphic infiltrate of large atypical lymphocytes was seen to affect the full thickness of the dermis with extension into the subcutaneous adipose tissue. There was a notable angiocentricity, with blood vessel necrosis and invasion of vessel walls by the atypical lymphocytes (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B). Our differential diagnosis based on these data included progression of MF or the onset and a new lymphoproliferative process (extranodal NK/T-cell lymphoma, nasal type; γ/δ T-cell lymphoma, angioinvasive (type E) lymphomatoid papulosis,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> or B-cell lymphoma rich in angioinvasive T cells<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a>). The new immunohistochemistry analysis was positive for CD3, CD5, CD7, and βF1, and showed expression of granzyme B and TIA-1. CD2, CD4, CD8, and CD30 expression was negative, as was CD56, CD20, EBER, and TCR-γ expression (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>, C and D). Clonality of the <span class="elsevierStyleItalic">TCR-γ</span> gene was once again demonstrated on PCR, with a clonal peak of identical size to that of the earlier lesions. The other additional tests, including computed tomography and bone-marrow biopsy were normal. Two months later the patient died as a result of rapidly progressive septicemia.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In the majority of cases of MF, immunophenotypic expression is CD3<span class="elsevierStyleSup">+</span>, CD4<span class="elsevierStyleSup">+</span> and CD8<span class="elsevierStyleSup">−</span>.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">3,4</span></a> Some cases show a cytotoxic/suppressor profile (CD3<span class="elsevierStyleSup">+</span>, CD4<span class="elsevierStyleSup">−</span>, CD8<span class="elsevierStyleSup">+</span>)<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">5,6</span></a> or other aberrant phenotypes. Immunophenotypic shift during disease progression is rare, with only 2 cases reported in the literature. In the first of those cases, 5 years after a diagnosis of CD4<span class="elsevierStyleSup">+</span>/CD8<span class="elsevierStyleSup">−</span> MF with lesions on the trunk, the patient presented cutaneous tumors associated with a loss of vision in the left eye. Histopathology of the globe showed infiltration of the vitreous by atypical CD8<span class="elsevierStyleSup">+</span> lymphocytes, with a CD4:CD8 ratio of 1:4. Although clonal rearrangement of the <span class="elsevierStyleItalic">TCR</span> gene was not mentioned, lesion progression to a tumor phase with concomitant involvement of the vitreous would suggest that the same lymphoproliferative process was the origin.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">7</span></a> In the second case, the diagnosis was also CD4<span class="elsevierStyleSup">+</span>/CD8<span class="elsevierStyleSup">−</span> MF. After a number of recurrences, the patient developed ulcerated lesions on the lower limbs; the immunohistochemical changes also consisted of a loss of CD4 expression and an increase in the number of CD8<span class="elsevierStyleSup">+</span> atypical lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">8</span></a> Clonal rearrangement of the <span class="elsevierStyleItalic">TCR</span> gene was detected, and comparison of the initial CD4<span class="elsevierStyleSup">+</span> lesions with the later CD8<span class="elsevierStyleSup">+</span> lesions showed the clonal peaks to be of identical size.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In our patient, neither CD4 nor CD8 expression was detected in the immunophenotypic study of the ulcerated tumor plaque, but the clonal peaks were of an identical size to those in the initial lesions; this therefore indicated that the lesions with distinct clinical and immunophenotypic characteristics were clonally related. To date, there are no reports of cases with loss of CD4 expression. The mechanism that produces the changes in immunophenotype is unknown. This phenomenon is considered common in the case of some childhood B- and T-cell leukemias; however, reports of such changes in the case of B-cell or T-cell lymphoma are rare in the literature.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We have presented the first case of MF with shift to a double-negative immunophenotype (CD4<span class="elsevierStyleSup">−</span>/CD8<span class="elsevierStyleSup">−</span>), associated with lymphocytes with a greater degree of atypia, pleomorphism, and larger size; these lymphocytes adopted an angiocentric distribution and acquired a cytotoxic profile with TIA-1 expression. Looking at the clinical course both of our case and of the previous cases, we can state that this phenomenon may be associated with disease progression, although more cases are required to be able to draw significant conclusions.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" 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: Vargas Nevado Á, López Navarro N, Gallego Domínguez E, Herrera Ceballos E. Cambio de inmunofenotipo asociado a angiocentricidad y características citotóxicas en un caso de micosis fungoide. Actas Dermosifiliogr. 2016;107:697–699.</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" => 1176 "Ancho" => 1400 "Tamanyo" => 601595 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Infiltrated, desquamating erythematous plaques with an arcuate morphology on the trunk. B, Dense infiltrate formed of atypical lymphocytes with epidermotropism. Hematoxylin and eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×20.<span class="elsevierStyleHsp" style=""></span>C, Positivity for CD4. D, Positivity for CD30 in the epidermotropic infiltrate.</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" => 1125 "Ancho" => 1500 "Tamanyo" => 659020 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Large ulcerating necrotic plaque on the medial surface of the lower leg. B, Angiotropic infiltrate of atypical lymphocytes. Hematoxylin and eosin, original magnification<span class="elsevierStyleHsp" style=""></span>×100.<span class="elsevierStyleHsp" style=""></span>C, Loss of CD4 expression. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 12 | 5 | 17 |
| 2024 October | 61 | 46 | 107 |
| 2024 September | 85 | 19 | 104 |
| 2024 August | 99 | 62 | 161 |
| 2024 July | 84 | 35 | 119 |
| 2024 June | 92 | 32 | 124 |
| 2024 May | 85 | 32 | 117 |
| 2024 April | 77 | 24 | 101 |
| 2024 March | 79 | 24 | 103 |
| 2024 February | 58 | 31 | 89 |
| 2024 January | 41 | 27 | 68 |
| 2023 December | 50 | 35 | 85 |
| 2023 November | 50 | 34 | 84 |
| 2023 October | 61 | 18 | 79 |
| 2023 September | 55 | 32 | 87 |
| 2023 August | 52 | 19 | 71 |
| 2023 July | 50 | 38 | 88 |
| 2023 June | 52 | 23 | 75 |
| 2023 May | 52 | 21 | 73 |
| 2023 April | 39 | 33 | 72 |
| 2023 March | 52 | 27 | 79 |
| 2023 February | 41 | 22 | 63 |
| 2023 January | 41 | 24 | 65 |
| 2022 December | 49 | 41 | 90 |
| 2022 November | 29 | 30 | 59 |
| 2022 October | 23 | 23 | 46 |
| 2022 September | 22 | 53 | 75 |
| 2022 August | 20 | 35 | 55 |
| 2022 July | 30 | 36 | 66 |
| 2022 June | 28 | 28 | 56 |
| 2022 May | 44 | 37 | 81 |
| 2022 April | 35 | 29 | 64 |
| 2022 March | 42 | 41 | 83 |
| 2022 February | 39 | 19 | 58 |
| 2022 January | 42 | 34 | 76 |
| 2021 December | 27 | 34 | 61 |
| 2021 November | 28 | 44 | 72 |
| 2021 October | 38 | 54 | 92 |
| 2021 September | 39 | 36 | 75 |
| 2021 August | 32 | 31 | 63 |
| 2021 July | 24 | 29 | 53 |
| 2021 June | 29 | 27 | 56 |
| 2021 May | 41 | 49 | 90 |
| 2021 April | 130 | 75 | 205 |
| 2021 March | 48 | 17 | 65 |
| 2021 February | 33 | 28 | 61 |
| 2021 January | 20 | 28 | 48 |
| 2020 December | 23 | 20 | 43 |
| 2020 November | 23 | 28 | 51 |
| 2020 October | 15 | 13 | 28 |
| 2020 September | 25 | 20 | 45 |
| 2020 August | 23 | 21 | 44 |
| 2020 July | 23 | 17 | 40 |
| 2020 June | 37 | 34 | 71 |
| 2020 May | 26 | 24 | 50 |
| 2020 April | 28 | 16 | 44 |
| 2020 March | 25 | 21 | 46 |
| 2020 February | 4 | 0 | 4 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 4 | 0 | 4 |
| 2019 November | 4 | 0 | 4 |
| 2019 August | 4 | 0 | 4 |
| 2019 July | 4 | 0 | 4 |
| 2019 June | 4 | 0 | 4 |
| 2019 May | 4 | 0 | 4 |
| 2019 April | 4 | 3 | 7 |
| 2019 March | 2 | 0 | 2 |
| 2019 January | 2 | 0 | 2 |
| 2018 December | 1 | 0 | 1 |
| 2018 November | 5 | 0 | 5 |
| 2018 October | 1 | 0 | 1 |
| 2018 September | 2 | 0 | 2 |
| 2018 February | 25 | 4 | 29 |
| 2018 January | 41 | 7 | 48 |
| 2017 December | 40 | 10 | 50 |
| 2017 November | 23 | 5 | 28 |
| 2017 October | 37 | 12 | 49 |
| 2017 September | 23 | 12 | 35 |
| 2017 August | 30 | 7 | 37 |
| 2017 July | 30 | 5 | 35 |
| 2017 June | 30 | 10 | 40 |
| 2017 May | 30 | 8 | 38 |
| 2017 April | 31 | 13 | 44 |
| 2017 March | 17 | 16 | 33 |
| 2017 February | 30 | 4 | 34 |
| 2017 January | 14 | 7 | 21 |
| 2016 December | 19 | 23 | 42 |
| 2016 November | 21 | 27 | 48 |
| 2016 October | 67 | 37 | 104 |
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