Letter - Clinical
Is Merkel cell carcinoma associated with high and chronic arsenic dose exposure?
Irving Llibran Reyna-Rodríguez, Valeria F. Garza-Davila, Jorge Ocampo-Candiani, Sonia Chavez-Alvarez
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Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario “Dr. José E. Gonzalez”, Monterrey, Mexico
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"tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "292" "paginaFinal" => "294" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Irving Llibran Reyna-Rodríguez, Valeria F. Garza-Davila, Jorge Ocampo-Candiani, Sonia Chavez-Alvarez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Irving Llibran" "apellidos" => "Reyna-Rodríguez" ] 1 => array:2 [ "nombre" => "Valeria F." "apellidos" => "Garza-Davila" ] 2 => array:2 [ "nombre" => "Jorge" "apellidos" => "Ocampo-Candiani" ] 3 => array:4 [ "nombre" => "Sonia" "apellidos" => "Chavez-Alvarez" "email" => array:1 [ 0 => "dr.sonia.chavez@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario “Dr. José E. Gonzalez”, Monterrey, Mexico" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1127 "Ancho" => 3008 "Tamanyo" => 224000 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Clinical image showing multiple flesh-colored nodules in the right axillary region. (B) The lesion a couple of weeks after initial presentation. (C) Dermoscopy of the axillary nodules showing irregular vessels.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Merkel cell carcinoma (MCC) is a highly aggressive primary cutaneous tumor of neuroendocrine origin. It occurs predominantly in Caucasian male adults in photo-exposed areas. Despite being a rare tumor with an incidence of 0.1–1.6 cases per 100,000 habitants, diagnostic yield has increased these numbers.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> We present a Hispanic man in his 70 s from the Northern region of Mexico, known for high levels of arsenic in its water, presented at our clinic for evaluation of a localized dermatosis. He had a family history of maternal breast cancer and stomach cancer in his 2 sisters. Physical examination revealed multiple painless and rapidly growing flesh-colored and red-violaceous nodules on the right axillary region (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This began 2 months prior, accompanied by weight loss and fatigue. He had not sought medical attention before. Dermoscopic findings (polarized light) demonstrated milky pink and white structureless areas. An excisional skin biopsy was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Histopathology revealed a flattened epidermis due to a nodular infiltrate located in the papillary and reticular dermis. At a higher magnification, the cluster of cells appeared monotonous with an epithelioid/lymphomyeloid appearance with abundant mitosis. Most cells had a loss of the nucleus-to-cytoplasm ratio, but they still retained an abundant cytoplasm with a prominent nucleus. Immunohistochemistry stained positive for AE1/AE3, CK20 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and synaptophysin. Negative immunohistochemistry included CK7, SOX-10, S100, HMB45, CD45, TTF-1, vimentin. The clinical, pathological and immunohistochemical findings were consistent with Merkel cell carcinoma. Merkel cell carcinoma has been associated with exposure to ultraviolet radiation, immunosuppression, and polyomavirus infection.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Diagnosis is made with immunohistochemistry which also helps make a distinction from histologically similar tumors. Dermatopathology shows a nodular or diffuse infiltrate composed of small blue cells with hyperchromatic nuclei and scarce cytoplasm. Mitoses are frequently abundant, and apoptosis is often widespread. 2 AE1/AE3, CK20, synaptophysin chromogranin, neuron-specific enolase and neurofilament stains are positive; CK7, TTF1, CDX2, S100, CD45, and vimentin are negative.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The main differential diagnoses before immunohistochemistry include metastatic neuroendocrine carcinoma (TTF1+, CK7+, CK20−), small cell melanoma (S100+, Melan-A/MART1+, HMB45*, SOX10*, vimentin+, CK20−) and lymphoma (CD45+, CD43+, CD3+, CD20+, CK20−, chromogranin−, synaptophysin−).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Exposure to high rates of arsenic in the environment or from contaminated water has been associated with an increased incidence of malignancies. Very few MCC cases (a total of 14) have been associated with arsenic.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> The treatment of choice in the early stages is surgical excision accompanied by radiotherapy. In advanced stages, there is no established curative therapy, relying on palliative chemotherapy.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It has a low survival rate even when tumors are localized or treated with new therapies such as immunotherapy targeting Programmed cell Death-1 (PD-1) or its Ligand (PD-L1).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Our patient refused to receive any therapies. He developed cutaneous metastasis and involvement of internal organs in one month and died two months later. The patient’s family and personal history of malignancies made us rethink the relationship between the environment in his native region and the development of Merkel carcinoma. They were native to Torreon, Coahuila, Mexico, a geographic zone with high arsenic levels. More objective evidence is required regarding this possible association. We intend to awaken an interest on Merkel pathogenesis and environmental factors.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0010" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0015" class="elsevierStylePara elsevierViewall">Irving Llibran Reyna-Rodríguez: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; final approval of the final version of the manuscript.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Valeria F Garza-Davila: Data collection, or analysis and interpretation of data; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; final approval of the final version of the manuscript.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Jorge Ocampo-Candiani: Data collection, analysis and interpretation; effective participation in the research guidance; critical review of the literature; final approval of the final version of the manuscript.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Sonia Chavez-Alvarez: The study concept and design; data collection, or analysis and interpretation of data; writing of the manuscript or critical review of important intellectual content; data collection, analysis and interpretation; effective participation in the research guidance; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; final approval of the final version of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-10-12" "fechaAceptado" => "2022-06-17" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Dermatology Department, Universidad Autonoma de Nuevo Leon, Facultad de Medicina y Hospital Universitario “Dr. José E. Gonzalez”, Monterrey, Mexico.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1127 "Ancho" => 3008 "Tamanyo" => 224000 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Clinical image showing multiple flesh-colored nodules in the right axillary region. (B) The lesion a couple of weeks after initial presentation. (C) Dermoscopy of the axillary nodules showing irregular vessels.</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" => 853 "Ancho" => 3008 "Tamanyo" => 297961 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Specimen (10× magnification) with hematoxylin-eosin showing a well-defined non-encapsulated tumor in the dermis (Hematoxylin eosin). (B) A magnification (200×) with hematoxylin-eosin showing small to medium monotonous cells with an epithelioid/lymphomyeloid appearance and abundant mitosis. 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 12 | 8 | 20 |
| 2024 Outubro | 104 | 80 | 184 |
| 2024 Setembro | 149 | 90 | 239 |
| 2024 Agosto | 176 | 124 | 300 |
| 2024 Julho | 133 | 102 | 235 |
| 2024 Junho | 116 | 60 | 176 |
| 2024 Maio | 80 | 61 | 141 |
| 2024 Abril | 203 | 115 | 318 |
| 2024 Março | 286 | 90 | 376 |
| 2024 Fevereiro | 97 | 89 | 186 |
| 2024 Janeiro | 74 | 60 | 134 |
| 2023 Dezembro | 40 | 49 | 89 |
