Case and research letter
Squamous cell carcinoma in an immunosuppressed patient on voriconazole
Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol
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B, Biopsy showed an epidermal folliculotropic infiltrate (hematoxylin eosin, original magnification ×4) and lymphocytes permeating the follicle (inset: hematoxylin eosin, original magnification ×40). C and D, Immunohistochemical staining showed abundant B cells (CD20<span class="elsevierStyleSup">+</span> and CD79<span class="elsevierStyleSup">+</span>; original magnification ×4). E and F, The lymphocytic infiltrate was composed almost entirely of CD4<span class="elsevierStyleSup">+</span> lymphocytes that surrounded the hair follicles.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.M. Otero Rivas, P. Sánchez Sambucety, L.M. Valladares Narganes, M.Á. Rodríguez Prieto" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.M." "apellidos" => "Otero Rivas" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Sánchez Sambucety" ] 2 => array:2 [ "nombre" => "L.M." "apellidos" => "Valladares Narganes" ] 3 => array:2 [ "nombre" => "M.Á." 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Carrascosa, G.E. Solano-López, E. Vargas, J. Fraga" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Carrascosa" "email" => array:1 [ 0 => "rachel170786@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" => "G.E." "apellidos" => "Solano-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "E." "apellidos" => "Vargas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Fraga" "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 La Princesa, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario La Princesa, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 809 "Ancho" => 1000 "Tamanyo" => 162789 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recurrence of squamous cell carcinoma in the area close to the graft.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Voriconazole is a second-generation triazole antifungal agent that inhibits the enzyme cytochrome P450, which is required for the synthesis of ergosterol, a sterol that maintains the integrity of the fungal cell wall.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> In 2002 voriconazole was approved by the US Food and Drug Administration for the treatment of serious fungal infections including those caused by <span class="elsevierStyleItalic">Fusarium</span> and <span class="elsevierStyleItalic">Aspergillus s</span>pecies.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The main adverse effects of voriconazole are visual disturbances, elevated transaminase levels, gastrointestinal upset, and skin rashes, including photosensitivity, cheilitis, and xerosis.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Prolonged use has been associated with the development of liver spots, actinic keratoses, squamous cell carcinoma (SCC), and even cutaneous melanoma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Most of the patients who develop SCC are immunocompromised (bone marrow, stem cell, or lung transplant recipients).<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We describe the case of a 30-year-old man with Fitzpatrick skin phototype II and low sun exposure who had been diagnosed with cystic fibrosis. In 1998, at the age of 17, he underwent a double lung transplant. He was prescribed immunosuppressive therapy with tacrolimus, prednisone, and mycophenolate mofetil. In 2007, the patient underwent a right lower lobectomy for tuberculosis and pulmonary aspergillosis and began antifungal treatment with voriconazole. In 2011, after 3 years of treatment with voriconazole, he developed a fast-growing nodule in the left parietal region and multiple actinic keratoses on the rest of the scalp (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The tumor was excised by Mohs micrographic surgery and closed using a full-thickness skin graft. Histology revealed a moderately differentiated SCC (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) with tumor-free margins. Voriconazole treatment was discontinued once the diagnosis was confirmed. Three months later, the patient developed a recurrence in the left parietal region, near the skin graft (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). As tumor adhesion to the cortex was observed during resection of the lesion, the periosteum was excised and an osteotomy of the outer table performed. Weeks later, the patient developed left and right cervical lymph node metastases, for which he underwent bilateral lymph node dissection (4/29 positive nodes on the right side and 1/32 on the left) and subsequently received adjuvant radiotherapy at a dose of 50<span class="elsevierStyleHsp" style=""></span>Gy (60<span class="elsevierStyleHsp" style=""></span>Gy for level-II lymph node metastases). After 6 months free of disease, the patient developed a right cervical node recurrence with microscopic spread to surrounding soft tissues. The lesion was completely removed and the patient is currently awaiting adjuvant treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Skin tumors in patients with chronic immunosuppression are more common and usually more aggressive than in the general immunocompetent population. Furthermore, despite the small number of cases described in the literature, there is increasing evidence linking prolonged voriconazole treatment in immunocompromised patients with the development of multiple cutaneous SCCs that are more aggressive and more likely to recur locally than those observed in the general population.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> While the prolonged immunosuppression of the patient in the present case was likely an important factor influencing both the development and the aggressive course of the SCC, it is likely that prolonged treatment with voriconazole was the determining factor. To date, at least 18 cases of voriconazole-associated SCC have been described (2 children and 16 adults),<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> all involving tumors in sun-exposed areas such as the face, neck, and dorsum of the hands. The scalp was affected in only in 6 these cases.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The mechanism that underlies the development of these tumors is unclear. A repeated, extensive, and intense phototoxic stimulus affecting sun-exposed areas may explain the appearance of preneoplastic lesions such as actinic keratoses, which subsequently progress to SCCs. Photocarcinogenesis is usually caused by cellular DNA damage, which in the present case was likely mediated by voriconazole and/or its metabolites, either directly or by oxidative stress.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Particular care should be taken when prescribing voriconazole to immunosuppressed patients, especially if it is anticipated that the treatment will be long term or if the patient has a low phototype (I-II).<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,8</span></a> It is recommended that these patents are closely monitored and take sun protection measures, which include avoiding sun exposure, wearing appropriate clothing, and using suncream.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4</span></a> In some cases it may be necessary to discontinue voriconazole treatment. The possibility of substituting voriconazole with another antifungal agent with a suitable spectrum (especially posaconazole or itraconazole) should also be considered.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></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: Carrascosa R, Solano-López GE, Vargas E, Fraga J. Carcinoma espinocelular en un paciente inmunosuprimido en tratamiento con voriconazol. Actas Dermosifiliogr. 2014;105:424–426.</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" => 862 "Ancho" => 1001 "Tamanyo" => 247184 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fast-growing tuberous lesion in the left parietal region.</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" => 613 "Ancho" => 1001 "Tamanyo" => 291519 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Moderately differentiated squamous cell carcinoma (hematoxylin eosin, original magnification ×10). The composition of the tumor, which consists of nests and strings of epithelial cells with extensive foci of keratotic differentiation, is shown in greater detail in the inset (hematoxylin eosin, original magnification ×400).</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" => 809 "Ancho" => 1000 "Tamanyo" => 162789 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recurrence of squamous cell carcinoma in the area close to the graft.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanoma associated with long-term voriconazole therapy: A new manifestation of chronic photosensitivity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.D. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 12 | 20 |
| 2024 October | 66 | 59 | 125 |
| 2024 September | 68 | 32 | 100 |
| 2024 August | 106 | 73 | 179 |
| 2024 July | 75 | 52 | 127 |
| 2024 June | 89 | 46 | 135 |
| 2024 May | 63 | 43 | 106 |
| 2024 April | 62 | 18 | 80 |
| 2024 March | 65 | 30 | 95 |
| 2024 February | 45 | 33 | 78 |
| 2024 January | 36 | 29 | 65 |
| 2023 December | 50 | 24 | 74 |
| 2023 November | 50 | 24 | 74 |
| 2023 October | 50 | 20 | 70 |
| 2023 September | 61 | 29 | 90 |
| 2023 August | 53 | 20 | 73 |
| 2023 July | 40 | 30 | 70 |
| 2023 June | 54 | 17 | 71 |
| 2023 May | 53 | 22 | 75 |
| 2023 April | 57 | 24 | 81 |
| 2023 March | 53 | 31 | 84 |
| 2023 February | 46 | 23 | 69 |
| 2023 January | 37 | 30 | 67 |
| 2022 December | 54 | 39 | 93 |
| 2022 November | 32 | 25 | 57 |
| 2022 October | 23 | 19 | 42 |
| 2022 September | 34 | 48 | 82 |
| 2022 August | 24 | 33 | 57 |
| 2022 July | 37 | 37 | 74 |
| 2022 June | 38 | 23 | 61 |
| 2022 May | 49 | 41 | 90 |
| 2022 April | 45 | 33 | 78 |
| 2022 March | 49 | 55 | 104 |
| 2022 February | 38 | 26 | 64 |
| 2022 January | 29 | 34 | 63 |
| 2021 December | 28 | 41 | 69 |
| 2021 November | 48 | 49 | 97 |
| 2021 October | 43 | 52 | 95 |
| 2021 September | 32 | 23 | 55 |
| 2021 August | 26 | 38 | 64 |
| 2021 July | 24 | 30 | 54 |
| 2021 June | 26 | 32 | 58 |
| 2021 May | 29 | 24 | 53 |
| 2021 April | 51 | 47 | 98 |
| 2021 March | 75 | 16 | 91 |
| 2021 February | 45 | 25 | 70 |
| 2021 January | 23 | 16 | 39 |
| 2020 December | 29 | 10 | 39 |
| 2020 November | 18 | 10 | 28 |
| 2020 October | 14 | 7 | 21 |
| 2020 September | 24 | 11 | 35 |
| 2020 August | 20 | 20 | 40 |
| 2020 July | 22 | 10 | 32 |
| 2020 June | 25 | 19 | 44 |
| 2020 May | 18 | 15 | 33 |
| 2020 April | 22 | 12 | 34 |
| 2020 March | 27 | 19 | 46 |
| 2020 February | 1 | 5 | 6 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 4 | 2 | 6 |
| 2019 November | 4 | 0 | 4 |
| 2019 October | 0 | 2 | 2 |
| 2019 September | 4 | 2 | 6 |
| 2019 August | 4 | 6 | 10 |
| 2019 July | 2 | 2 | 4 |
| 2019 June | 4 | 16 | 20 |
| 2019 May | 1 | 30 | 31 |
| 2019 April | 0 | 5 | 5 |
| 2019 March | 0 | 8 | 8 |
| 2019 February | 0 | 1 | 1 |
| 2018 December | 3 | 4 | 7 |
| 2018 November | 1 | 0 | 1 |
| 2018 September | 6 | 0 | 6 |
| 2018 June | 1 | 1 | 2 |
| 2018 May | 0 | 1 | 1 |
| 2018 March | 1 | 2 | 3 |
| 2018 February | 36 | 3 | 39 |
| 2018 January | 39 | 6 | 45 |
| 2017 December | 33 | 4 | 37 |
| 2017 November | 28 | 4 | 32 |
| 2017 October | 23 | 4 | 27 |
| 2017 September | 40 | 8 | 48 |
| 2017 August | 54 | 4 | 58 |
| 2017 July | 50 | 8 | 58 |
| 2017 June | 68 | 22 | 90 |
| 2017 May | 62 | 7 | 69 |
| 2017 April | 49 | 7 | 56 |
| 2017 March | 38 | 33 | 71 |
| 2017 February | 40 | 7 | 47 |
| 2017 January | 13 | 5 | 18 |
| 2016 December | 26 | 8 | 34 |
| 2016 November | 49 | 4 | 53 |
| 2016 October | 37 | 5 | 42 |
| 2016 September | 31 | 9 | 40 |
| 2016 August | 42 | 8 | 50 |
| 2016 July | 16 | 8 | 24 |
| 2016 June | 13 | 0 | 13 |
| 2016 May | 8 | 3 | 11 |
| 2016 April | 2 | 8 | 10 |
| 2016 March | 3 | 2 | 5 |
| 2016 February | 9 | 2 | 11 |
| 2016 January | 11 | 1 | 12 |
| 2015 December | 8 | 0 | 8 |
| 2015 November | 6 | 4 | 10 |
| 2015 October | 16 | 0 | 16 |
| 2015 September | 11 | 1 | 12 |
| 2015 August | 10 | 6 | 16 |
| 2015 July | 37 | 7 | 44 |
| 2015 June | 33 | 1 | 34 |
| 2015 May | 45 | 4 | 49 |
| 2015 April | 32 | 1 | 33 |
| 2015 March | 21 | 3 | 24 |
| 2015 February | 21 | 1 | 22 |
| 2015 January | 22 | 2 | 24 |
| 2014 December | 18 | 4 | 22 |
| 2014 November | 19 | 7 | 26 |
| 2014 October | 21 | 8 | 29 |
| 2014 September | 9 | 7 | 16 |
| 2014 August | 13 | 2 | 15 |
| 2014 July | 32 | 3 | 35 |
| 2014 June | 40 | 7 | 47 |
| 2014 May | 24 | 7 | 31 |
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