Letter - Clinical
Spontaneous regression of Merkel cell carcinoma with positive detection of Merkel cell polyomavirus by PCR and immunohistochemistry
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(A) Proliferation consisting of small basophilic cells, with large, ovoid, hyperchromatic nucleoli, and finely dispersed chromatin (Hematoxylin & eosin, ×400). (B) Immunohistochemical reactivity for CK20 in a perinuclear dot-like pattern, ×400. (C) Immunohistochemical reactivity for chromogranin A, ×400. (D) Immunohistochemical nuclear reactivity for MCPyV (CM2B monoclonal antibody), ×40.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Merkel cell carcinoma (MCC) is a rare cutaneous neoplasm, characterized by the proliferation of anaplastic cells, with an aggressive clinical course. It is more frequently diagnosed in caucasian males after the seventh decade of life and in immunosuppressed individuals.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2008, Feng et al. observed the DNA of a new polyomavirus in 8 of 10 MCCs, named Merkel cell polyomavirus (MCPyV). The viral DNA was integrated into the DNA of the tumor cells in a clonal pattern, suggesting that the viral infection preceded the clonal expansion of these cells.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A 76-year-old patient reported fast-growing nodules on the leg, with eight weeks of evolution. The physical examination showed a firm, erythematous, semispherical nodule measuring 4 cm on the left leg, surrounded by similar satellite lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). These findings regressed considerably three weeks after a shave biopsy of the main lesion was performed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Histopathological analysis showed a dermal tumor with extensive proliferation of small basophilic cells, with large, ovoid, hyperchromatic nucleoli and finely dispersed chromatin (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). Immunohistochemistry was positive for CK20, with a perinuclear, dot-like pattern, and chromogranin A (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B,C), and negative for TTF-1 and CK7, confirming the diagnosis of MCC. MCPyV DNA was detected by PCR and the major viral T-antigen was detected by nuclear positivity in immunohistochemistry using CM2B monoclonal antibody (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D). Despite the observed partial regression, surgical excision was performed with wide margins, and there was no recurrence of the condition after two years of follow-up. Histopathology of the surgical specimen revealed residual neoplasia circumscribed by connective tissue strands and dermal fibrosis.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Although there is no standard protocol, the treatment is based on the excision with wide margins for localized or locoregional disease, with adjuvant radiotherapy for large tumors. When there are distant metastases, radiotherapy and adjuvant chemotherapy are combined.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The pathogenesis of MCC is considered multifactorial. Studies have reported a P53 mutation and high levels of bcl2 proto-oncogene expression in tumor cells, supporting rapid tumor expansion and growth.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Spontaneous regression of MCC is rare and was described in 1986, with fewer than 40 similar cases being reported since then. Regressions after biopsy or incomplete excision have also been described and may be due to the activation of the T-cell-mediated immune response after surgical trauma, although the exact mechanisms remain unknown.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Unlike melanoma cases, the reported cases of MCC with spontaneous regression usually had a better prognosis and progressed to cure.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The presence of MCPyV in MCC is thought to stimulate the triggering of an immune response against viral antigens and tumor cells.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Considering the presence of MCPyV in the present report, it is postulated that viral antigen exposure after the biopsy may have triggered host immune activation and tumor regression.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, the present report aims to draw attention to the rare possibility of spontaneous regression of MCC and its association with MCPyV.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0055" class="elsevierStylePara elsevierViewall">FUNADERM (<span class="elsevierStyleItalic">Fundo de Apoio à Dermatologia</span>) in 2019.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors' contributions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Thiago Rubim Batista Bellott Nascimento: Design and planning of the study; drafting and editing of the manuscript; collection, analysis, and interpretation of data; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Flávio Barbosa Luz: Approval of the final version of the manuscript; effective participation in research orientation; critical review of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Rafael Brandão Varella: Approval of the final version of the manuscript; collection, analysis, and interpretation of data; critical review of the manuscript.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Mayra Carrijo Rochael: Approval of the final version of the manuscript; effective participation in research orientation; critical review of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0080" 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" => "2021-03-05" "fechaAceptado" => "2021-04-20" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Department of Pathology, Universidade Federal Fluminense, Rio de Janeiro, Brazil.</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" => 1529 "Ancho" => 2175 "Tamanyo" => 532201 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tumor lesion on the left leg, before and after the shave biopsy. (A) A red, firm, 4-cm nodule on the left leg, with adjacent similar papules, before the shave biopsy. (B) Clinical aspect of tumor regression three weeks after the shave biopsy.</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" => 2194 "Ancho" => 2925 "Tamanyo" => 1381553 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathological and immunohistochemical staining. (A) Proliferation consisting of small basophilic cells, with large, ovoid, hyperchromatic nucleoli, and finely dispersed chromatin (Hematoxylin & eosin, ×400). (B) Immunohistochemical reactivity for CK20 in a perinuclear dot-like pattern, ×400. (C) Immunohistochemical reactivity for chromogranin A, ×400. (D) Immunohistochemical nuclear reactivity for MCPyV (CM2B monoclonal antibody), ×40.</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" => "Merkel cell carcinoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.H. Wong" 1 => "J. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5858/2009-0165-RSR2.1" "Revista" => array:7 [ "tituloSerie" => "Arch Pathol Lab Med." 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| Ano/Mês | Html | Total | |
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| 2024 Novembro | 11 | 5 | 16 |
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| 2023 Novembro | 74 | 84 | 158 |
| 2023 Outubro | 67 | 91 | 158 |
| 2023 Setembro | 71 | 84 | 155 |
| 2023 Agosto | 56 | 30 | 86 |
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| 2023 Junho | 52 | 41 | 93 |
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