Letter - Dermatopathology
The texture of collagen and immunoexpression of PRAME in dysplastic nevus syndrome lesions: relationship with melanoma
Paula Regina Martins Costaa, Gislaine Vieira-Damianib, Rafael Fantelli Stelinia, Leonardo Ávila Ferreirac, Maria Letícia Cintraa,
, Fernanda Teixeiraa
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a Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil
b Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, Capivari, SP, Brazil
c Department of Dermatology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil
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(A) Nevo displásico clássico (NDC): hiperplasia epidérmica regular, pequenos aglomerados de melanócitos na junção dermoepidérmica (setas amarelas) e fibroplasia da derme papilar (seta azul). (B, C) ND com atipia histológica de alto grau (NDAG): hiperplasia epidérmica irregular, agregados de melanócitos de volumes variados, em distribuição variada e com atipia citológica multifocal moderada a acentuada (setas amarelas) e fibroplasia da derme papilar (seta azul). (D) ND com atipia histológica de alto grau (NDAG): imunoexpressão nuclear do antígeno PRAME nos melanócitos presentes na junção dermoepidérmica. (A‐C) Hematoxilina & eosina; (D) imuno‐histoquímica; Aumento original 100<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>(A, B) e 400<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>(C, D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paula Regina Martins Costa, Gislaine Vieira‐Damiani, Rafael Fantelli Stelini, Leonardo Ávila Ferreira, Maria Letícia Cintra, Fernanda Teixeira" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Paula Regina Martins" "apellidos" => "Costa" ] 1 => array:2 [ "nombre" => "Gislaine" "apellidos" => "Vieira‐Damiani" ] 2 => array:2 [ "nombre" => "Rafael Fantelli" "apellidos" => "Stelini" ] 3 => array:2 [ "nombre" => "Leonardo Ávila" "apellidos" => "Ferreira" ] 4 => array:2 [ "nombre" => "Maria Letícia" "apellidos" => "Cintra" ] 5 => array:2 [ "nombre" => "Fernanda" "apellidos" => "Teixeira" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0365059622002392" "doi" => "10.1016/j.abd.2022.02.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002392?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2666275222002533?idApp=UINPBA00008Z" "url" => "/26662752/0000009800000001/v1_202301090939/S2666275222002533/v1_202301090939/pt/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S0365059622002501" "issn" => "03650596" "doi" => "10.1016/j.abd.2022.10.002" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "662" "copyright" => "Sociedade Brasileira de Dermatologia" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter - Tropical/Infectious and parasitic dermatology</span>" "titulo" => "Dermoscopic findings in human monkeypox infection" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "131" "paginaFinal" => "133" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1341 "Ancho" => 2500 "Tamanyo" => 252975 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Typical MPX vesiculopustular lesions with central ulceration at face (A) and penis (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Leandro Ourives Neves, Amanda Domingos Cordeiro, Bruna Dell’Acqua Cassão Rezende" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Leandro Ourives" "apellidos" => "Neves" ] 1 => array:2 [ "nombre" => "Amanda Domingos" "apellidos" => "Cordeiro" ] 2 => array:2 [ "nombre" => "Bruna Dell’Acqua Cassão" "apellidos" => "Rezende" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S266627522200282X" "doi" => "10.1016/j.abdp.2022.11.027" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266627522200282X?idApp=UINPBA00008Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365059622002501?idApp=UINPBA00008Z" "url" => "/03650596/0000009800000001/v2_202304080751/S0365059622002501/v2_202304080751/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0365059622002446" "issn" => "03650596" "doi" => "10.1016/j.abd.2021.02.014" "estado" => "S300" "fechaPublicacion" => "2023-01-01" "aid" => "656" "copyright" => "Sociedade Brasileira de Dermatologia" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter - Clinical</span>" "titulo" => "Vitiligo and atopic dermatitis in young girls: may Koebner phenomenon play a role?" 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Dermatopathology</span>" "titulo" => "The texture of collagen and immunoexpression of PRAME in dysplastic nevus syndrome lesions: relationship with melanoma" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "128" "paginaFinal" => "130" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Paula Regina Martins Costa, Gislaine Vieira-Damiani, Rafael Fantelli Stelini, Leonardo Ávila Ferreira, Maria Letícia Cintra, Fernanda Teixeira" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Paula Regina Martins" "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Gislaine" "apellidos" => "Vieira-Damiani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Rafael Fantelli" "apellidos" => "Stelini" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Leonardo Ávila" "apellidos" => "Ferreira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:4 [ "nombre" => "Maria Letícia" "apellidos" => "Cintra" "email" => array:1 [ 0 => "marialet@fcm.unicamp.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 5 => array:3 [ "nombre" => "Fernanda" "apellidos" => "Teixeira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Federal de Educação, Ciência e Tecnologia de São Paulo, Capivari, SP, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Dermatology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1361 "Ancho" => 2925 "Tamanyo" => 756736 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Dysplastic nevus syndrome: classical dysplastic nevus- on the left, the epidermis (E) shows melanocyte aggregates at the dermoepidermal junction (yellow arrows) and, on the right, the papillary dermis under the nevus is indicated by blue arrows ×400. Picrosirius red, without polarization (A) and under polarization (B).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Although Dysplastic Nevi (DN) present a degree of cytoarchitectural disorder, it is generally not difficult to distinguish them from cutaneous melanoma (CM). However, in some, this distinction can be difficult.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Patients with numerous DN<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and those with DN with high-grade atypia (DNHG)<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> are more likely to develop CM. These patients need close follow-up and any changing lesion must be excised to rule out malignancy, previously misdiagnosed as a dysplastic nevus. One of the remarkable microscopic findings of DN is fibroplasia of the papillary dermis.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> PRAME (PReferentially expressed Antigen in MElanoma) is an antigen associated with the majority of primary and metastatic cutaneous and uveal melanomas, with the exception of desmoplastic melanomas.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The authors studied the density and texture of the collagen underlying DN, excised from 15 patients with dysplastic nevus syndrome (DNS), in the 1994‒2019 period, and the expression of PRAME in their cells.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">Institutional Review Board approval (no. 3,548,935) was obtained. The patients were regularly monitored at the Dermatology Outpatient Clinic. From the nevi that were excised from these patients during this period, 56 were diagnosed histologically as junctional DN, and had enough remaining embedded tissue for additional sections. Nevi were diagnosed with low/moderate (n = 32, DNLG) or moderate/severe (n = 24, DNHG) grade/cytoarchitectural disorder (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A‒D). Each specimen was studied in two ways: 1) By staining with picrosirius red and observation under polarized light on digitized images (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), to assess collagen density and texture under the nevus, using ImageJ software (<a href="http://rsb.info.nih.gov/ij">http://rsb.info.nih.gov/ij</a>) to measure the contrast of the grey level co-occurrence matrix, second angular momentum, entropy and anisotropy, and 2) By conventional immunohistochemical methods, for its PRAME (Mab EPR20330; Abcam, #219650) expression, according to the method by Googe et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> For statistical analysis, the software used was the SAS System for Windows.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Results</span><p id="par0015" class="elsevierStylePara elsevierViewall">Nine of the fifteen patients were female, eight had a previous history of CM at some point in their life, 51/56 DN were diagnosed up to 40 years of age, and no lesion recurred after excision. Collagen under the DN of patients with a personal history of CM had significantly higher optical density values (p = 0.0259) compared to those without this precedent, denoting a more compact texture. DNHG (n = 24/56) had significantly lower contrast (p = 0.0140) and entropy (p = 0.0353) values compared to DNLG, reflecting greater collagen organization. These results confirm the greater predisposition of these DNS patients to CM. As Babacan et al. found by histochemical methods,<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> it seems that the modulation of the extracellular matrix evolves in parallel with the cytoarchitectural disorder. PRAME was not overexpressed in DN from patients with DNS. The nuclear PRAME staining of DN melanocytes was categorized as absent in 51 DN and focally present<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> in 5 DNHG lesions (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Googe et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> found only focal immunoreactivity for PRAME in just over 10% of nevi, including dysplastic ones.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conclusion</span><p id="par0020" class="elsevierStylePara elsevierViewall">DNHG and DN with underlying compact texture appear to be markers of patients at increased risk of developing melanoma.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Acknowledgements/ Funding sources</span><p id="par0025" class="elsevierStylePara elsevierViewall">The antibody and further items used for the development of this work was purchased with the help of FAEPEX-Uncamp (Fund to support teaching, research and extension), Grant #2015/20. Paula R. M. Costa received a scholarship from CNPq/ Pibic (the National Council for Scientific and Technological Development). We reviewed the content of the manuscript, followed by Ms Diane Ellis, B.A. in education. Biostatistician Cleide Aparecida Moreira Silva, Research Committee, Biostatistics Division, Medical Sciences School, Unicamp, provided statistical consultation.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Author’s contribution</span><p id="par0030" class="elsevierStylePara elsevierViewall">Paula Regina Martins Costa: Study concept; data collection; writing of the manuscript.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Gislaine Vieira-Damiani: Analysis and interpretation, critical review.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Rafael Fantelli Stelini: Data collection; research guidance.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Leonardo Ávila Ferreira: Data collection; research guidance.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Maria Letícia Cintra: Data collection; writing of the manuscript; effective participation in the research guidance.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Fernanda Teixeira: Data collection; manuscript critical review; writing of the manuscript.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1630584" "titulo" => "Abbreviations" ] 1 => array:2 [ "identificador" => "sec0005" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "sec0010" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "sec0015" "titulo" => "Conclusion" ] 4 => array:2 [ "identificador" => "sec0020" "titulo" => "Acknowledgements/ Funding sources" ] 5 => array:2 [ "identificador" => "sec0025" "titulo" => "Author’s contribution" ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-12-26" "fechaAceptado" => "2022-02-16" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec1630584" "palabras" => array:5 [ 0 => "DN" 1 => "DNHG" 2 => "CM" 3 => "DNLG" 4 => "DNS" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "⋆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, 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" => 2143 "Ancho" => 2925 "Tamanyo" => 1173478 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Dysplastic nevus syndrome:</span> (A) Classical Dysplastic Nevus (CDN): regular epidermal hyperplasia, small clusters of melanocytes at the dermoepidermal junction (yellow arrows) and papillary dermis fibroplasia (blue arrow); (B, C) DN with High-Grade histological atypia (DNHG): irregular epidermal hyperplasia, melanocyte aggregates of varying volumes, in varied distribution and with moderate to marked multifocal cytological atypia (yellow arrows) and papillary dermis fibroplasia (blue arrow); (D) DN with High-Grade histological atypia (DNHG): nuclear immunoexpression of the PRAME antigen in the melanocytes present at the dermoepidermal junction. (A‒C) Hematoxylin & eosin; (D) immunohistochemistry; ×100 (A, B) and ×400 (C, D).</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" => 1361 "Ancho" => 2925 "Tamanyo" => 756736 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Dysplastic nevus syndrome: classical dysplastic nevus- on the left, the epidermis (E) shows melanocyte aggregates at the dermoepidermal junction (yellow arrows) and, on the right, the papillary dermis under the nevus is indicated by blue arrows ×400. Picrosirius red, without polarization (A) and under polarization (B).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The limited specificity of histological examination in the diagnosis of dysplastic nevi" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. 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