Case for Diagnosis
S100-protein–negative Mouth Lesion
Lesión de la mucosa oral negativa para la proteína S100
K. Saez de Gordoa
, L. Alos, R. Albero-González
Corresponding author
Servicio de Anatomía Patológica, CDB, Hospital Clínic, Barcelona, España
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"apellidos" => "Saez de Gordoa" "email" => array:1 [ 0 => "saezdegord@clinic.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Alos" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Albero-González" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Anatomía Patológica, CDB, Hospital Clínic, Barcelona, España" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lesión de la mucosa oral negativa para la proteína S100" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:6 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 602 "Ancho" => 802 "Tamanyo" => 159831 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Medical history</span><p id="par0005" class="elsevierStylePara elsevierViewall">An 83-year-old woman with a past medical history of atrial fibrillation and hypothyroidism presented with a 1-year history painful and bleeding lesion of the hard palate.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Physical examination</span><p id="par0010" class="elsevierStylePara elsevierViewall">A 5cm nodular reddish lesion was found on the hard palate, with some surrounding pigmentation (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). No locoregional lymphadenopathies were described.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Histopathology</span><p id="par0015" class="elsevierStylePara elsevierViewall">Histopathological examination revealed the presence of a non-pigmented, submucosal cellular proliferation of atypical characteristics consisting of large, discohesive, epithelioid and spindle cells, with pleomorphic nuclei, visible nucleoli, and multiple mitotic figures (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B-D). Due to the absence of a specific morphological pattern, a broad differential diagnosis was considered.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Other supplementary tests</span><p id="par0020" class="elsevierStylePara elsevierViewall">The initial immunohistochemical study performed included epithelial (broad-spectrum keratins: CK AE1/AE3), hematological (CD20 and CD68), muscular (α-actin), and melanocytic markers (S100 protein). All tested negative, with appropriate positive external and/or internal controls (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A and B). A second immunohistochemical panel conducted included EMA, p40, CK19, CD45, desmin, ERG, and SOX10. Tumor cells exhibited intense expression of SOX10 (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>C), which prompted further study, and eventually revealed the diffuse expression of PRAME and HMB45, and focal positivity for Melan-A (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>D-F).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">What is your diagnosis?</span></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Diagnosis</span><p id="par0030" class="elsevierStylePara elsevierViewall">The definitive histopathological diagnosis was invasive melanoma of the oral mucosa.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Course of the disease and treatment</span><p id="par0035" class="elsevierStylePara elsevierViewall">The molecular analysis performed using the NGS Oncomine<span class="elsevierStyleSup">TM</span> Focus panel (Thermo Fisher Scientific) detected gains in the KIT (4q12) and CDK4 (12q14.1) genes, without any mutations or fusions being reported in the studied DNA and RNA regions.</p><p id="par0040" class="elsevierStylePara elsevierViewall">A PET-CT scan performed during the staging process revealed the presence of bilateral lung nodules with metabolic activity. The patient did not start cancer treatment due to rapid disease progression and died 2 months after diagnosis.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">Oral mucosal melanoma (OMM) is a rare neoplasm, representing between 0.2% and 0.5% of all oral neoplasms and 1% of melanomas.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> The most commonly affected locations are the hard palate and the maxillary and mandibular gingiva.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2,3</span></a> Compared to its cutaneous counterpart, OMM occurs in older patients (around the 5<span class="elsevierStyleSup">th</span> decade of life), and is more common in white individuals than in darker skin types, although with a lower predisposition than cutaneous melanoma.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The most common clinical presentation is an asymptomatic flat or nodular lesion that may have satellite lesions too.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3</span></a> OMMs are often pigmented whether uniformly or heterogeneously. Nonetheless, they can also exhibit an amelanotic lesion in 10% to 30% of the patients. Ulceration and bleeding may occur, especially in later stages of the disease.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A recent literature search revealed 2 case series, which reported on 1 case of OMM with negative immunohistochemistry for the S100 protein in each of them.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">4,5</span></a> Prasad et al. reported 1 negative case of a series of 35 patients.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> The tumor tested positive for the remaining markers (T311, A103, HMB45, and D5), with sensitivity rates of 94%, 85%, 71%, and 74%, respectively. Yu et al. reported a series of 6 cases of OMM with a tumor that tested negative for the S100 protein and Melan-A, and positive for HMB4<span class="elsevierStyleSup">5</span>. In this study, the sensitivity rates of HMB45<span class="elsevierStyleSup">5</span> and Melan-A were 100% and 67%, respectively.</p><p id="par0060" class="elsevierStylePara elsevierViewall">For the molecular profile of OMM, changes in copy number and amplifications are a common finding, including amplifications of 4q12 (KIT) and 12q14 (CDK4) as seen in this case.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion, the expression of the S100 protein for the diagnosis of OMM shows high sensitivity though it can be negative in up to 3% of the cases. Therefore, in the initial study of an undifferentiated malignant tumor in this region, using multiple melanocytic markers is recommended to safely exclude the diagnosis of melanoma.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Medical history" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Physical examination" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Histopathology" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Other supplementary tests" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Diagnosis" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Course of the disease and treatment" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 8 => array:2 [ "identificador" => "xack748922" "titulo" => "Acknowledgements" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:2 [ 0 => array:6 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 602 "Ancho" => 802 "Tamanyo" => 159831 ] ] ] 1 => array:6 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 606 "Ancho" => 806 "Tamanyo" => 171991 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral malignant melanoma: a review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. 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"fecha" => "2005 Oct" "volumen" => "34" "paginaInicial" => "540" "paginaFinal" => "545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16138892" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0060" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distinct sets of genetic alterations in melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Curtin" 1 => "J. Fridlyand" 2 => "T. Kageshita" 3 => "H.N. Patel" 4 => "K.J. Busam" 5 => "H. Kutzner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa050092" "Revista" => array:7 [ "tituloSerie" => "N Engl J Med." "fecha" => "2005 Nov 17" "volumen" => "353" "paginaInicial" => "2135" "paginaFinal" => "2147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16291983" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1473309922008167" "estado" => "S300" "issn" => "14733099" ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack748922" "titulo" => "Acknowledgements" "texto" => "<p id="par0075" class="elsevierStylePara elsevierViewall">We wish to thank Dr. Pedro Jares for his collaboration in the molecular study of the case and Dr. Carles Martí for providing relevant clinical data.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00017310/0000011500000006/v1_202406021150/S0001731024003430/v1_202406021150/en/main.assets" "Apartado" => array:4 [ "identificador" => "6161" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Casos para el diagnóstico" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/00017310/0000011500000006/v1_202406021150/S0001731024003430/v1_202406021150/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731024003430?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 12 | 29 |
| 2024 October | 148 | 56 | 204 |
| 2024 September | 144 | 46 | 190 |
| 2024 August | 208 | 97 | 305 |
| 2024 July | 166 | 48 | 214 |
| 2024 June | 215 | 62 | 277 |
| 2024 May | 265 | 70 | 335 |
| 2024 April | 44 | 33 | 77 |
