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histopatol&#243;gicos e imuno&#8208;histoqu&#237;micos&#44; bem como a investiga&#231;&#227;o do rearranjo g&#234;nico dos receptores de c&#233;lulas&#8208;T clonais &#40;TCR&#41;&#46; A aplica&#231;&#227;o do algoritmo foi endossada pela Sociedade Internacional de Linfoma Cut&#226;neo &#40;SILC&#41; e foi considerada em artigos de revis&#227;o recentemente publicados&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Com o objetivo de estudar os aspectos histopatol&#243;gicos dos est&#225;gios iniciais da MF e confirmar a aplicabilidade do algoritmo proposto por Pimpinelli et al&#46;&#44; revisamos os primeiros exames histopatol&#243;gicos feitos em pacientes com MF que haviam sido acompanhados e tratados no ambulat&#243;rio de Fotodermatologia do Hospital Universit&#225;rio da Universidade Federal do Rio de Janeiro&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="par0015" class="elsevierStylePara elsevierViewall">Estudo observacional transversal&#44; com base na revis&#227;o dos primeiros exames histopatol&#243;gicos feitos em pacientes adultos &#40;18&#160;anos ou mais&#41; com MF&#44; diagnosticados&#44; tratados e acompanhados &#40;m&#237;nimo de 5&#160;anos&#41; no ambulat&#243;rio de Fotodermatologia do Hospital Universitario de janeiro de 2000 a dezembro de 2015&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Todos os pacientes inclu&#237;dos no estudo tiveram diagn&#243;stico final de MF&#44; foi estabelecido durante o per&#237;odo de acompanhamento pelos seguintes crit&#233;rios&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Evolu&#231;&#227;o cl&#237;nica t&#237;pica &#40;progress&#227;o de les&#245;es maculares as placas e da&#237; a tumores&#44; em alguns casos&#41;&#44; de acordo com a chamada forma cl&#225;ssica de Alibert&#8208;Bazin&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">5&#44;7</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Achados t&#237;picos em exames histopatol&#243;gicos subsequentes &#40;epidermotropismo de linf&#243;citos at&#237;picos e microabscessos de Pautrier&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a></p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">Os pacientes foram classificados como em est&#225;gio inicial de acordo com as proposi&#231;&#245;es da SILC e da Organiza&#231;&#227;o Europeia de Pesquisa e Tratamento de C&#226;ncer &#40;OEPTC&#47;EORTC&#41;&#46; Apresentavam doen&#231;a no est&#225;gio IA &#40;T1N0M0&#41;&#44; IB &#40;T2N0M0&#41; ou IIA &#40;T1 ou 2N1 ou 2M0&#41; de acordo com TNMB&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos apenas os casos com blocos de parafina dispon&#237;veis para an&#225;lise imuno&#8208;histoqu&#237;mica&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Dois dermatopatologistas experientes&#44; sem conhecimento do relato original&#44; revisaram ao mesmo tempo o exame histopatol&#243;gico inicial de cada paciente e concordaram na an&#225;lise dos par&#226;metros histol&#243;gicos espec&#237;ficos estabelecidos&#46; Todas as amostras correspondiam a bi&#243;psias por punch de&#160;4&#8208;5&#160;mm&#46; Os pacientes com mais de uma amostra foram avaliados considerando&#8208;se a an&#225;lise global conjunta das amostras para concluir no sentido de um diagn&#243;stico de compatibilidade para MF ou n&#227;o&#46; Foram avaliados apenas os cortes corados pela hematoxilina &#38; eosina e blocos de parafina foram selecionados para subsequente estudo imuno&#8208;histoqu&#237;mico&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Dados cl&#237;nicos foram coletados com o objetivo de caracterizar a popula&#231;&#227;o estudada e explorar os crit&#233;rios cl&#237;nicos propostos por Pimpinelli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> O estadiamento foi analisado em modo ordinal qualitativo&#44; de acordo com o protocolo TNMB vigente&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A t&#233;cnica de imuno&#8208;histoqu&#237;mica &#40;Servi&#231;o de Patologia&#44; Instituto Nacional de Infectologia Evandro Chagas&#47;Fiocruz&#41; foi aplicada quando crit&#233;rios cl&#237;nicos e histopatol&#243;gicos n&#227;o alcan&#231;aram os&#160;4&#160;pontos necess&#225;rios para o diagn&#243;stico&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> Cortes histol&#243;gicos reagiram com CD3 &#40;polyclonal de coelho&#44; 1&#47;100&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41;&#44; CD2 &#40;MRQ&#8208;11&#44; monoclonal de camundongo&#44; 1&#47;50&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41;&#44; CD5 &#40;SP19&#44; monoclonal do coelho&#44; 1&#47;100&#44; marca<span class="elsevierStyleSup">TM</span>da pilha&#41; e CD7 &#40;EP132&#44; monoclonal de camundongo&#44; 1&#47;100&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41; como anticorpos prim&#225;rios&#46; Para caracterizar a discord&#226;ncia dermoepid&#233;rmica&#44; foram consideradas somente as amostras com linf&#243;citos CD3<span class="elsevierStyleSup">&#43;</span> na epiderme&#44; a fim assegurar a presen&#231;a das c&#233;lulas nessa localiza&#231;&#227;o&#46; A investiga&#231;&#227;o do rearranjo de g&#234;nico de Receptores de C&#233;lulas&#8208;T clonais &#40;TCR&#41; n&#227;o est&#225; dispon&#237;vel em nosso laborat&#243;rio no momento&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As vari&#225;veis histopatol&#243;gicas&#44; cl&#237;nicas e imuno&#8208;histoqu&#237;micas estudadas s&#227;o apresentadas na forma de tabela&#44; como conte&#250;do suplementar online&#46; Os dados foram tabulados em planilhas do Excel 2011 &#40;Microsoft&#174; Excel&#174; for Mac 2011&#47;Version&#58; 14&#46;2&#46;0&#41; e analisados de forma descritiva&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">O estudo obedece a Resolu&#231;&#227;o&#160;466&#47;12 do Conselho Nacional de Sa&#250;de&#44; foi registrado na plataforma Brasil e foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa do HUCFF&#47;UFRJ &#40;CAAE&#160;59235916&#46;9&#46;0000&#46;5257&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0070" class="elsevierStylePara elsevierViewall">De&#160;102&#160;pacientes com MF inicial primeiramente selecionados&#44; 67&#160;tinham exames histopatol&#243;gicos com blocos de parafinas dispon&#237;veis para estudo imuno&#8208;histoqu&#237;mico&#46; Todos esses 67&#160;foram inclu&#237;dos&#44; uma vez que o seguimento confirmou diagn&#243;stico de MF segundo crit&#233;rios de inclus&#227;o do estudo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Homens e mulheres foram quase igualmente afetados&#46; A idade m&#233;dia encontrada de 53&#44;27&#160;anos&#46; A maioria dos pacientes apresentava m&#250;ltiplas les&#245;es de tamanhos vari&#225;veis &#40;98&#44;5&#37;&#41;&#44; afetavam &#225;reas foto&#8208;rotegidas &#40;98&#44;5&#37;&#41;&#44; com evolu&#231;&#227;o cr&#244;nica e progressiva &#40;o tempo m&#233;dio entre o in&#237;cio dos sintomas e o diagn&#243;stico final foi de&#160;51&#44;31&#160;meses&#44; variou de&#160;2&#160;a&#160;360&#160;meses&#41;&#46; A maioria dos pacientes apresentava les&#245;es em placas &#40;64&#44;2&#37;&#41;&#46; Poiquilodermia foi encontrada apenas em&#160;14&#44;8&#37; dos casos&#46; A fase IB representou&#160;52&#44;2&#37; da amostra&#46; O tempo m&#233;dio de seguimento foi de&#160;8&#44;25&#160;anos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia das vari&#225;veis histopatol&#243;gicas analisadas para a avalia&#231;&#227;o de bi&#243;psias com suspeita de MF &#233; apresentada na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Infiltrado linfoide perivascular superficial&#44; epidermotropismo sem microabscessos de Pautrier&#44; atipia linfocit&#225;ria&#44; especialmente representada pelo aumento do tamanho nuclear de linf&#243;citos localizados na epiderme&#44; hiperceratose e acantose foram os achados histopatol&#243;gicos predominantes &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Os resultados do estudo imuno&#8208;histoqu&#237;mico feito em&#160;23&#160;das&#160;24&#160;amostras eleg&#237;veis s&#227;o mostrados nas tabelas sob a forma de conte&#250;do suplementar online&#46; Um dos blocos de parafina selecionados n&#227;o forneceu tecido suficiente para completar as rea&#231;&#245;es&#46; Diminui&#231;&#227;o na express&#227;o de marcadores de c&#233;lulas&#8208;T e discord&#226;ncia dermoepid&#233;rmica &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">figs&#46; 3 e 4</a>&#41; foram observados na maioria dos casos&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">A impress&#227;o diagn&#243;stica com base na revis&#227;o dos achados histopatol&#243;gicos em conjunto com os dados referentes &#224; aplica&#231;&#227;o do algoritmo modificado de Pimpinelli et al&#46; &#233; mostrada na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0095" class="elsevierStylePara elsevierViewall">Fez&#8208;se um estudo observacional de delineamento transversal&#44; baseado na revis&#227;o de exames histopatol&#243;gicos de pacientes com suspeita diagn&#243;stica de MF&#44; que durante o per&#237;odo de seguimento tiveram o diagn&#243;stico de MF confirmado&#46; Os exames histopatol&#243;gicos foram complementados com o perfil imuno&#8208;histoqu&#237;mico com o objetivo de aplicar o algoritmo diagn&#243;stico proposto por Pimpinelli et al&#46; endossado por artigos recentes de revis&#227;o&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> sem a pesquisa de clonalidade dos receptores de c&#233;lulas&#8208;T&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Do ponto de vista cl&#237;nico&#44; a apresenta&#231;&#227;o de MF seguiu o que &#233; descrito na literatura&#44; mais comumente com m&#250;ltiplas m&#225;culas e&#47;ou placas de tamanhos variados&#44; afetavam &#225;reas fotoprotegidas&#44; com evolu&#231;&#227;o cr&#244;nica e progressiva &#40;per&#237;odo m&#233;dio de evolu&#231;&#227;o&#58; 51&#44;31&#160;meses&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">1&#44;5&#8211;7&#44;10</span></a> Esse perfil est&#225; de acordo com o que &#233; proposto por Pimpinelli et al&#46; em seu algoritmo de identifica&#231;&#227;o para MF em est&#225;gio inicial&#59; de modo que apenas um paciente &#40;1&#44;5&#37;&#41; marcou 1&#160;ponto&#44; enquanto o restante cumpriu o m&#225;ximo de&#160;2&#160;pontos&#46; Isso demonstra a boa correla&#231;&#227;o entre o que identificamos clinicamente com o que &#233; proposto pelo algoritmo&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">A revis&#227;o histopatol&#243;gica identificou altera&#231;&#245;es da camada c&#243;rnea&#44; com hiperceratose e paraceratose&#44; que s&#227;o altera&#231;&#245;es comuns nos est&#225;gios iniciais de MF&#44; especialmente quando se considera a queixa de prurido e a presen&#231;a de descama&#231;&#227;o em les&#245;es tipo placa&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;7&#44;8</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">O padr&#227;o de rea&#231;&#227;o tecidual predominante foram o infiltrado linfoide perivascular superficial com incontin&#234;ncia pigmentar e a fibroplasia da derme papilar&#44; enquanto padr&#227;o liquenoide perivascular superficial e profundo e o padr&#227;o difuso e confluente foram infrequentes&#46; Maiores percentagens de infiltrado em distribui&#231;&#227;o liquenoide foram descritas nos estudos de Nagaraghi et al&#46; e Massone et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;12</span></a> Entretanto&#44; nossos resultados sustentam que somente pacientes com est&#225;gios iniciais de MF&#44; com baixa carga tumoral&#44; foram inclu&#237;dos&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Epidermotropismo estava presente em&#160;68&#44;7&#37; dos pacientes analisados&#44; indicado pelo alinhamento de linf&#243;citos com halo ao logo da jun&#231;&#227;o dermoepid&#233;rmica ou situados em posi&#231;&#227;o suprabasal&#44; desacompanhados de espongiose&#46; O alinhamento dos linf&#243;citos ao longo dos queratin&#243;citos basais &#233; achado na avalia&#231;&#227;o histopatol&#243;gica dos exames de MF em est&#225;gios precoces<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> e foi descrito por Sanchez &#38; Ackermann&#44; em&#160;1979&#44; como crit&#233;rio para o seu diagn&#243;stico&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;15</span></a> Ao contr&#225;rio&#44; foliculotropismo e microabscessos de Pautrier foram raros&#44; como proposto na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13&#44;14</span></a> No entanto&#44; um grande estudo conduzido por Massone et al&#46;&#44; com avalia&#231;&#227;o de&#160;427&#160;pacientes com MF em fase inicial&#44; demonstrou maiores percentagens de microabscessos de Pautrier &#40;19&#37;&#41;&#44; semelhantes aos achados de Nagaraghi et al&#46; &#40;presentes em at&#233; 66&#37; dos pacientes com placa como les&#227;o cl&#237;nica elementar&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">A atipia de linf&#243;citos&#44; baseada no aumento de tamanho e&#47;ou contorno cerebriforme dos n&#250;cleos&#44; foi identificada em 63&#44;8&#37; dos pacientes&#46; A valoriza&#231;&#227;o de crit&#233;rios citol&#243;gicos&#44; tais como a hiperconvolu&#231;&#227;o ou aumento do tamanho nuclear&#44; para c&#233;lulas situadas na epiderme ou na derme &#233; disputada na literatura e parece ser considerada em publica&#231;&#245;es mais recentes&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16&#8211;18</span></a> Nossos resultados mostraram que atipia linfocit&#225;ria foi quase t&#227;o frequente quanto epidermotropismo&#44; estava de acordo com a an&#225;lise de autores anteriormente mencionados&#46; Por outro lado&#44; Massone et al&#46; identificaram linf&#243;citos at&#237;picos em apenas&#160;9&#37; dos pacientes e propuseram que crit&#233;rios arquiteturais&#44; que envolvam o padr&#227;o de distribui&#231;&#227;o do infiltrado associado ao achado de epidermotropismo&#44; seriam ser mais relevantes na fase inicial de MF&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A revis&#227;o histopatol&#243;gica considerou os achados compat&#237;veis com o diagn&#243;stico de MF em 64&#44;2&#37; dos casos&#46; Portanto&#44; em 35&#44;8&#37;&#160;&#40;24&#160;de&#160;67&#41; dos casos&#44; o exame histopatol&#243;gico por si s&#243; n&#227;o permitiu diagnosticar MF&#46; De fato&#44; as taxas de falsos negativos em um primeiro exame atingem 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> Entretanto&#44; ao lado de um quadro histopatol&#243;gico inespec&#237;fico&#44; deve&#8208;se enfatizar o valor da aus&#234;ncia de crit&#233;rios para se estabelecer outro diagn&#243;stico espec&#237;fico&#44; como eczemas ou psor&#237;ase&#46; Assim&#44; em&#160;24&#160;pacientes em que o diagn&#243;stico de MF n&#227;o pode ser feito&#44; esse tamb&#233;m n&#227;o poderia ser exclu&#237;do&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Ainda em rela&#231;&#227;o a esses&#160;24&#160;casos&#44; o principal aspecto desafiador para o diagn&#243;stico de MF foi a escassez de infiltrado&#44; compat&#237;vel com est&#225;gios iniciais da doen&#231;a&#44; e em correla&#231;&#227;o com les&#245;es clinicamente n&#227;o infiltradas&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13&#44;16</span></a> Al&#233;m disso&#44; os achados histopatol&#243;gicos podem ser mascarados pelo uso de medicamentos&#44; tais como corticosteroides t&#243;picos&#44; que minimizam o infiltrado linfocit&#225;rio e atenuam a presen&#231;a dessas c&#233;lulas na jun&#231;&#227;o dermoepid&#233;rmica&#46; Considerando que esses medicamentos s&#227;o de f&#225;cil acesso&#44; adquiridos sem prescri&#231;&#227;o&#44; observamos frequentemente em nossa pr&#225;tica cl&#237;nica que os pacientes fazem uso inadvertido desse grupo de subst&#226;ncias&#46; Pacientes com suspeita cl&#237;nica de MF devem idealmente interromper a aplica&#231;&#227;o de esteroides t&#243;picos&#44; bem como o uso de imunossupressores sist&#234;micos &#40;se for o caso&#41;&#44; de&#160;2&#160;a&#160;4&#160;semanas antes de fazer bi&#243;psia&#44; com o objetivo de n&#227;o prejudicar a an&#225;lise histopatol&#243;gica&#44; pode&#8208;se manter o uso de emolientes&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> O delineamento retrospectivo do estudo dificulta a determina&#231;&#227;o do uso de medicamentos no momento da primeira bi&#243;psia&#44; representa&#44; portanto&#44; uma limita&#231;&#227;o a ser considerada&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">A diminui&#231;&#227;o da express&#227;o de marcadores de c&#233;lulas T&#44; tais como CD2&#44; CD3&#44; CD5 e CD7&#44; em pacientes com MF tem por base a ideia de que&#44; &#224; medida que a doen&#231;a progride&#44; &#233; identificado um fen&#243;tipo anormal predominante&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;13</span></a> Redu&#231;&#227;o de CD2&#44; CD3 e&#47;ou CD5 em pelo menos 50&#37; das c&#233;lulas linfoides &#233; um crit&#233;rio importante para a identifica&#231;&#227;o de linfomas de c&#233;lulas&#8208;T&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> A perda de positividade parece ocorrer inicialmente nos linf&#243;citos que permeiam a epiderme e mais tarde naqueles presentes na derme&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;20</span></a> Entre CD2&#44; CD3&#44; CD5 e CD7&#44; aparentemente o crit&#233;rio mais espec&#237;fico seria a redu&#231;&#227;o da express&#227;o de CD7 para menos de&#160;10&#37; das c&#233;lulas linfoides&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Aplicando a an&#225;lise imunofenot&#237;pica em&#160;23&#160;casos que n&#227;o atenderam aos crit&#233;rios de diagn&#243;stico&#44; 22&#160;pontuaram no algoritmo&#46; O crit&#233;rio mais prevalente foi a redu&#231;&#227;o da positividade para menos de 50&#37; do infiltrado para CD2 e&#47;ou CD5&#44; &#233;&#44; portanto&#44; nesta an&#225;lise&#44; o crit&#233;rio mais sens&#237;vel&#44; semelhante ao proposto na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;20</span></a> Finalmente&#44; 13&#160;casos apresentaram o crit&#233;rio supostamente mais espec&#237;fico&#44; com redu&#231;&#227;o de CD7 para menos de 10&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;21</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Em&#160;2015&#44; Vandergriff et al&#46; publicaram um estudo para validar o algoritmo de Pimpinelli et al&#46; Os autores encontraram 87&#44;5&#37; de sensibilidade e 60&#37; de especificidade para o diagn&#243;stico e conclu&#237;ram que o algoritmo &#233; um m&#233;todo estatisticamente v&#225;lido&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Ainda que com reconhecida melhoria no diagn&#243;stico de MF inicial&#44; a pesquisa de rearranjo gen&#233;tico de TCR &#233; complexa&#44; n&#227;o est&#225; amplamente dispon&#237;vel e apresenta diferen&#231;as entre taxas de detec&#231;&#227;o segundo as t&#233;cnicas empregadas&#44; n&#250;mero de amostras e a fase de MF &#40;placa ou tumor&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">23&#8211;25</span></a> Mesmo sem incluir esse teste diagn&#243;stico complementar&#44; encontramos um aumento no percentual de diagn&#243;stico de MF&#44; de&#160;64&#44;2&#37;&#44; quando avaliada histopatologia de maneira isolada&#44; para 91&#37; quando aplicados os crit&#233;rios diagn&#243;sticos dispon&#237;veis do algoritmo&#46; Destacamos ainda que o desempenho do algoritmo poderia ter sido ainda melhor&#44; uma vez que os&#160;6&#47;67&#160;pacientes que n&#227;o obtiveram pontua&#231;&#227;o suficiente poderiam t&#234;&#8208;la atingido caso fosse pesquisado rearranjo de TCR e&#44; logicamente&#44; esse tivesse sido positivo&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0155" class="elsevierStylePara elsevierViewall">Embora a correla&#231;&#227;o cl&#237;nico&#8208;patol&#243;gica permane&#231;a como padr&#227;o&#8208;ouro&#44; a aplica&#231;&#227;o dos crit&#233;rios cl&#237;nicos&#44; histopatol&#243;gicos e imuno&#8208;histoqu&#237;micos do algoritmo de Pimpinelli et al&#46; foi &#250;til no diagn&#243;stico de MF precoce e pode contribuir para uma melhoria de resultados para o paciente&#44; propiciar tratamento espec&#237;fico mais precoce&#46; Nossos resultados motivaram a ado&#231;&#227;o dos crit&#233;rios do algoritmo na rotina pr&#225;tica em nosso departamento&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Como limita&#231;&#245;es do presente estudo destacamos seu car&#225;ter retrospectivo&#44; o tamanho reduzido da amostra e a falta da pesquisa de clonalidade do rearranjo do TCR&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0165" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0170" class="elsevierStylePara elsevierViewall">Gustavo Moreira Amorim&#58; An&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Daniele Carvalho Quintella&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Jo&#227;o Paulo Niemeyer&#8208;Corbellini&#58; Concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Luiz Claudio Ferreira&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Marcia Ramos e Silva&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Tullia Cuzzi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflitos de interesse</span><p id="par0200" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">O diagn&#243;stico de micose fungoide &#233; desafiador pela inespecificidade dos achados cl&#237;nicos e histopatol&#243;gicos&#46; A literatura indica um atraso m&#233;dio de 4 a 6 anos para um diagn&#243;stico conclusivo&#46; O refinamento dos crit&#233;rios histopatol&#243;gicos para o diagn&#243;stico de pacientes em est&#225;gios iniciais da doen&#231;a &#233; considerado de interesse&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudar os aspectos histopatol&#243;gicos da micose fungoide precoce e a aplicabilidade&#44; em forma retrospectiva&#44; do algoritmo diagn&#243;stico proposto por Pimpinelli et al&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional&#44; retrospectivo&#44; transversal&#44; baseado na revis&#227;o de exames histopatol&#243;gicos de pacientes com suspeita de micose fungoide&#46; Os prontu&#225;rios m&#233;dicos foram revisados e an&#225;lise imuno&#8208;histoqu&#237;mica complementar foi feita&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 67 pacientes&#46; As caracter&#237;sticas histopatol&#243;gicas mais frequentes foram infiltrado linfoide perivascular superficial &#40;71&#44;6&#37;&#41;&#44; epidermotropismo &#40;68&#44;7&#37;&#41;&#44; atipia linfocit&#225;ria &#40;63&#44;8&#37;&#41;&#44; hiperceratose &#40;62&#44;7&#37;&#41; e acantose &#40;62&#44;7&#37;&#41;&#46; Quarenta e tr&#234;s pacientes alcan&#231;aram 4 pontos no algoritmo por avalia&#231;&#227;o cl&#237;nica e histol&#243;gica&#46; A imuno&#8208;histoqu&#237;mica foi feita em&#160;23&#160;dos&#160;24&#160;pacientes com menos de 4 pontos&#46; Desses&#160;23&#44; 22&#160;pontuaram 1 ponto&#44; permitindo um total de 61 pacientes&#160;&#40;91&#37;&#41; com o diagn&#243;stico de micose fungoide precoce&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Seu car&#225;ter retrospectivo&#44; tamanho reduzido da amostra e aplica&#231;&#227;o incompleta do algoritmo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A aplica&#231;&#227;o do algoritmo Pimpinelli et al&#46;&#44; mesmo que de forma incompleta&#44; aumentou o percentual de casos diagnosticados como micose fungoide&#46; A aplica&#231;&#227;o rotineira do algoritmo pode contribuir para o manejo precoce espec&#237;fico e&#44; consequentemente&#44; melhores resultados evolutivos nesse grupo de pacientes&#46;</p></span>"
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                  \t\t\t\t">17&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adelga&#231;ada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">02&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acantose irregular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acantose psoriasiforme&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">06&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Degenera&#231;&#227;o vacuolar da camada basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">06&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Infiltrado linfoide</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perivascular superficial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perivascular superficial e profundo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">09&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Liquen&#243;ide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Difuso e confluente<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Comprometendo a hipoderme<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">01&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Epidermotropismo sem microabscesso de Pautrier</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Epidermotropismo com mcroabscessos de Pautrier</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">08&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Foliculotropismo com mucinose folicular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Foliculotropismo sem mucinose</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">02&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Incontin&#234;ncia pigmentar</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Atipia linfocit&#225;ria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Convolu&#231;&#227;o de n&#250;cleos na epiderme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Convolu&#231;&#227;o de n&#250;cleos na derme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Aumento do tamanho nuclear na epiderme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Aumento do tamanho nuclear na derme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C&#233;lulas gigantes multinucleadas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">02&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Eosin&#243;filos</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">05&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fibroplasia da derme papilar</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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Investigação
Validação de algoritmo baseado em dados clínicos, histopatológicos e imuno‐histoquímicos para diagnóstico de micose fungoide em estágio inicial
Gustavo Moreira Amorima,
Autor para correspondência
gustavomoreiraamorim@hotmail.com

Autor para correspondência.
, Daniele Carvalho Quintellab, João Paulo Niemeyer‐Corbellinic, Luiz Claudio Ferreirad, Marcia Ramos‐e‐Silvae, Tullia Cuzzia,b,d
a Programa de Pós‐Graduação em Anatomia Patológica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
b Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
c Serviço de Dermatologia, Hospital Universitário, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
d Instituto Nacional de Infectologia, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brasil
e Disciplina de Dermatologia, Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
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com base na revis&#227;o dos primeiros exames histopatol&#243;gicos feitos em pacientes adultos &#40;18&#160;anos ou mais&#41; com MF&#44; diagnosticados&#44; tratados e acompanhados &#40;m&#237;nimo de 5&#160;anos&#41; no ambulat&#243;rio de Fotodermatologia do Hospital Universitario de janeiro de 2000 a dezembro de 2015&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Todos os pacientes inclu&#237;dos no estudo tiveram diagn&#243;stico final de MF&#44; foi estabelecido durante o per&#237;odo de acompanhamento pelos seguintes crit&#233;rios&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Evolu&#231;&#227;o cl&#237;nica t&#237;pica &#40;progress&#227;o de les&#245;es maculares as placas e da&#237; a tumores&#44; em alguns casos&#41;&#44; de acordo com a chamada forma cl&#225;ssica de Alibert&#8208;Bazin&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">5&#44;7</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Achados t&#237;picos em exames histopatol&#243;gicos subsequentes &#40;epidermotropismo de linf&#243;citos at&#237;picos e microabscessos de Pautrier&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a></p></li></ul></p><p id="par0035" class="elsevierStylePara elsevierViewall">Os pacientes foram classificados como em est&#225;gio inicial de acordo com as proposi&#231;&#245;es da SILC e da Organiza&#231;&#227;o Europeia de Pesquisa e Tratamento de C&#226;ncer &#40;OEPTC&#47;EORTC&#41;&#46; Apresentavam doen&#231;a no est&#225;gio IA &#40;T1N0M0&#41;&#44; IB &#40;T2N0M0&#41; ou IIA &#40;T1 ou 2N1 ou 2M0&#41; de acordo com TNMB&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos apenas os casos com blocos de parafina dispon&#237;veis para an&#225;lise imuno&#8208;histoqu&#237;mica&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Dois dermatopatologistas experientes&#44; sem conhecimento do relato original&#44; revisaram ao mesmo tempo o exame histopatol&#243;gico inicial de cada paciente e concordaram na an&#225;lise dos par&#226;metros histol&#243;gicos espec&#237;ficos estabelecidos&#46; Todas as amostras correspondiam a bi&#243;psias por punch de&#160;4&#8208;5&#160;mm&#46; Os pacientes com mais de uma amostra foram avaliados considerando&#8208;se a an&#225;lise global conjunta das amostras para concluir no sentido de um diagn&#243;stico de compatibilidade para MF ou n&#227;o&#46; Foram avaliados apenas os cortes corados pela hematoxilina &#38; eosina e blocos de parafina foram selecionados para subsequente estudo imuno&#8208;histoqu&#237;mico&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Dados cl&#237;nicos foram coletados com o objetivo de caracterizar a popula&#231;&#227;o estudada e explorar os crit&#233;rios cl&#237;nicos propostos por Pimpinelli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> O estadiamento foi analisado em modo ordinal qualitativo&#44; de acordo com o protocolo TNMB vigente&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A t&#233;cnica de imuno&#8208;histoqu&#237;mica &#40;Servi&#231;o de Patologia&#44; Instituto Nacional de Infectologia Evandro Chagas&#47;Fiocruz&#41; foi aplicada quando crit&#233;rios cl&#237;nicos e histopatol&#243;gicos n&#227;o alcan&#231;aram os&#160;4&#160;pontos necess&#225;rios para o diagn&#243;stico&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> Cortes histol&#243;gicos reagiram com CD3 &#40;polyclonal de coelho&#44; 1&#47;100&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41;&#44; CD2 &#40;MRQ&#8208;11&#44; monoclonal de camundongo&#44; 1&#47;50&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41;&#44; CD5 &#40;SP19&#44; monoclonal do coelho&#44; 1&#47;100&#44; marca<span class="elsevierStyleSup">TM</span>da pilha&#41; e CD7 &#40;EP132&#44; monoclonal de camundongo&#44; 1&#47;100&#44; Cell Marque<span class="elsevierStyleSup">TM</span>&#41; como anticorpos prim&#225;rios&#46; Para caracterizar a discord&#226;ncia dermoepid&#233;rmica&#44; foram consideradas somente as amostras com linf&#243;citos CD3<span class="elsevierStyleSup">&#43;</span> na epiderme&#44; a fim assegurar a presen&#231;a das c&#233;lulas nessa localiza&#231;&#227;o&#46; A investiga&#231;&#227;o do rearranjo de g&#234;nico de Receptores de C&#233;lulas&#8208;T clonais &#40;TCR&#41; n&#227;o est&#225; dispon&#237;vel em nosso laborat&#243;rio no momento&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">As vari&#225;veis histopatol&#243;gicas&#44; cl&#237;nicas e imuno&#8208;histoqu&#237;micas estudadas s&#227;o apresentadas na forma de tabela&#44; como conte&#250;do suplementar online&#46; Os dados foram tabulados em planilhas do Excel 2011 &#40;Microsoft&#174; Excel&#174; for Mac 2011&#47;Version&#58; 14&#46;2&#46;0&#41; e analisados de forma descritiva&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">O estudo obedece a Resolu&#231;&#227;o&#160;466&#47;12 do Conselho Nacional de Sa&#250;de&#44; foi registrado na plataforma Brasil e foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa do HUCFF&#47;UFRJ &#40;CAAE&#160;59235916&#46;9&#46;0000&#46;5257&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="par0070" class="elsevierStylePara elsevierViewall">De&#160;102&#160;pacientes com MF inicial primeiramente selecionados&#44; 67&#160;tinham exames histopatol&#243;gicos com blocos de parafinas dispon&#237;veis para estudo imuno&#8208;histoqu&#237;mico&#46; Todos esses 67&#160;foram inclu&#237;dos&#44; uma vez que o seguimento confirmou diagn&#243;stico de MF segundo crit&#233;rios de inclus&#227;o do estudo&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Homens e mulheres foram quase igualmente afetados&#46; A idade m&#233;dia encontrada de 53&#44;27&#160;anos&#46; A maioria dos pacientes apresentava m&#250;ltiplas les&#245;es de tamanhos vari&#225;veis &#40;98&#44;5&#37;&#41;&#44; afetavam &#225;reas foto&#8208;rotegidas &#40;98&#44;5&#37;&#41;&#44; com evolu&#231;&#227;o cr&#244;nica e progressiva &#40;o tempo m&#233;dio entre o in&#237;cio dos sintomas e o diagn&#243;stico final foi de&#160;51&#44;31&#160;meses&#44; variou de&#160;2&#160;a&#160;360&#160;meses&#41;&#46; A maioria dos pacientes apresentava les&#245;es em placas &#40;64&#44;2&#37;&#41;&#46; Poiquilodermia foi encontrada apenas em&#160;14&#44;8&#37; dos casos&#46; A fase IB representou&#160;52&#44;2&#37; da amostra&#46; O tempo m&#233;dio de seguimento foi de&#160;8&#44;25&#160;anos&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A frequ&#234;ncia das vari&#225;veis histopatol&#243;gicas analisadas para a avalia&#231;&#227;o de bi&#243;psias com suspeita de MF &#233; apresentada na <a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#46; Infiltrado linfoide perivascular superficial&#44; epidermotropismo sem microabscessos de Pautrier&#44; atipia linfocit&#225;ria&#44; especialmente representada pelo aumento do tamanho nuclear de linf&#243;citos localizados na epiderme&#44; hiperceratose e acantose foram os achados histopatol&#243;gicos predominantes &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figs&#46; 1 e 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Os resultados do estudo imuno&#8208;histoqu&#237;mico feito em&#160;23&#160;das&#160;24&#160;amostras eleg&#237;veis s&#227;o mostrados nas tabelas sob a forma de conte&#250;do suplementar online&#46; Um dos blocos de parafina selecionados n&#227;o forneceu tecido suficiente para completar as rea&#231;&#245;es&#46; Diminui&#231;&#227;o na express&#227;o de marcadores de c&#233;lulas&#8208;T e discord&#226;ncia dermoepid&#233;rmica &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">figs&#46; 3 e 4</a>&#41; foram observados na maioria dos casos&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">A impress&#227;o diagn&#243;stica com base na revis&#227;o dos achados histopatol&#243;gicos em conjunto com os dados referentes &#224; aplica&#231;&#227;o do algoritmo modificado de Pimpinelli et al&#46; &#233; mostrada na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Discuss&#227;o</span><p id="par0095" class="elsevierStylePara elsevierViewall">Fez&#8208;se um estudo observacional de delineamento transversal&#44; baseado na revis&#227;o de exames histopatol&#243;gicos de pacientes com suspeita diagn&#243;stica de MF&#44; que durante o per&#237;odo de seguimento tiveram o diagn&#243;stico de MF confirmado&#46; Os exames histopatol&#243;gicos foram complementados com o perfil imuno&#8208;histoqu&#237;mico com o objetivo de aplicar o algoritmo diagn&#243;stico proposto por Pimpinelli et al&#46; endossado por artigos recentes de revis&#227;o&#44;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">1&#44;5&#44;6</span></a> sem a pesquisa de clonalidade dos receptores de c&#233;lulas&#8208;T&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Do ponto de vista cl&#237;nico&#44; a apresenta&#231;&#227;o de MF seguiu o que &#233; descrito na literatura&#44; mais comumente com m&#250;ltiplas m&#225;culas e&#47;ou placas de tamanhos variados&#44; afetavam &#225;reas fotoprotegidas&#44; com evolu&#231;&#227;o cr&#244;nica e progressiva &#40;per&#237;odo m&#233;dio de evolu&#231;&#227;o&#58; 51&#44;31&#160;meses&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">1&#44;5&#8211;7&#44;10</span></a> Esse perfil est&#225; de acordo com o que &#233; proposto por Pimpinelli et al&#46; em seu algoritmo de identifica&#231;&#227;o para MF em est&#225;gio inicial&#59; de modo que apenas um paciente &#40;1&#44;5&#37;&#41; marcou 1&#160;ponto&#44; enquanto o restante cumpriu o m&#225;ximo de&#160;2&#160;pontos&#46; Isso demonstra a boa correla&#231;&#227;o entre o que identificamos clinicamente com o que &#233; proposto pelo algoritmo&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">A revis&#227;o histopatol&#243;gica identificou altera&#231;&#245;es da camada c&#243;rnea&#44; com hiperceratose e paraceratose&#44; que s&#227;o altera&#231;&#245;es comuns nos est&#225;gios iniciais de MF&#44; especialmente quando se considera a queixa de prurido e a presen&#231;a de descama&#231;&#227;o em les&#245;es tipo placa&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;7&#44;8</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">O padr&#227;o de rea&#231;&#227;o tecidual predominante foram o infiltrado linfoide perivascular superficial com incontin&#234;ncia pigmentar e a fibroplasia da derme papilar&#44; enquanto padr&#227;o liquenoide perivascular superficial e profundo e o padr&#227;o difuso e confluente foram infrequentes&#46; Maiores percentagens de infiltrado em distribui&#231;&#227;o liquenoide foram descritas nos estudos de Nagaraghi et al&#46; e Massone et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;12</span></a> Entretanto&#44; nossos resultados sustentam que somente pacientes com est&#225;gios iniciais de MF&#44; com baixa carga tumoral&#44; foram inclu&#237;dos&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Epidermotropismo estava presente em&#160;68&#44;7&#37; dos pacientes analisados&#44; indicado pelo alinhamento de linf&#243;citos com halo ao logo da jun&#231;&#227;o dermoepid&#233;rmica ou situados em posi&#231;&#227;o suprabasal&#44; desacompanhados de espongiose&#46; O alinhamento dos linf&#243;citos ao longo dos queratin&#243;citos basais &#233; achado na avalia&#231;&#227;o histopatol&#243;gica dos exames de MF em est&#225;gios precoces<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a> e foi descrito por Sanchez &#38; Ackermann&#44; em&#160;1979&#44; como crit&#233;rio para o seu diagn&#243;stico&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;15</span></a> Ao contr&#225;rio&#44; foliculotropismo e microabscessos de Pautrier foram raros&#44; como proposto na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13&#44;14</span></a> No entanto&#44; um grande estudo conduzido por Massone et al&#46;&#44; com avalia&#231;&#227;o de&#160;427&#160;pacientes com MF em fase inicial&#44; demonstrou maiores percentagens de microabscessos de Pautrier &#40;19&#37;&#41;&#44; semelhantes aos achados de Nagaraghi et al&#46; &#40;presentes em at&#233; 66&#37; dos pacientes com placa como les&#227;o cl&#237;nica elementar&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">A atipia de linf&#243;citos&#44; baseada no aumento de tamanho e&#47;ou contorno cerebriforme dos n&#250;cleos&#44; foi identificada em 63&#44;8&#37; dos pacientes&#46; A valoriza&#231;&#227;o de crit&#233;rios citol&#243;gicos&#44; tais como a hiperconvolu&#231;&#227;o ou aumento do tamanho nuclear&#44; para c&#233;lulas situadas na epiderme ou na derme &#233; disputada na literatura e parece ser considerada em publica&#231;&#245;es mais recentes&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16&#8211;18</span></a> Nossos resultados mostraram que atipia linfocit&#225;ria foi quase t&#227;o frequente quanto epidermotropismo&#44; estava de acordo com a an&#225;lise de autores anteriormente mencionados&#46; Por outro lado&#44; Massone et al&#46; identificaram linf&#243;citos at&#237;picos em apenas&#160;9&#37; dos pacientes e propuseram que crit&#233;rios arquiteturais&#44; que envolvam o padr&#227;o de distribui&#231;&#227;o do infiltrado associado ao achado de epidermotropismo&#44; seriam ser mais relevantes na fase inicial de MF&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A revis&#227;o histopatol&#243;gica considerou os achados compat&#237;veis com o diagn&#243;stico de MF em 64&#44;2&#37; dos casos&#46; Portanto&#44; em 35&#44;8&#37;&#160;&#40;24&#160;de&#160;67&#41; dos casos&#44; o exame histopatol&#243;gico por si s&#243; n&#227;o permitiu diagnosticar MF&#46; De fato&#44; as taxas de falsos negativos em um primeiro exame atingem 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> Entretanto&#44; ao lado de um quadro histopatol&#243;gico inespec&#237;fico&#44; deve&#8208;se enfatizar o valor da aus&#234;ncia de crit&#233;rios para se estabelecer outro diagn&#243;stico espec&#237;fico&#44; como eczemas ou psor&#237;ase&#46; Assim&#44; em&#160;24&#160;pacientes em que o diagn&#243;stico de MF n&#227;o pode ser feito&#44; esse tamb&#233;m n&#227;o poderia ser exclu&#237;do&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Ainda em rela&#231;&#227;o a esses&#160;24&#160;casos&#44; o principal aspecto desafiador para o diagn&#243;stico de MF foi a escassez de infiltrado&#44; compat&#237;vel com est&#225;gios iniciais da doen&#231;a&#44; e em correla&#231;&#227;o com les&#245;es clinicamente n&#227;o infiltradas&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;13&#44;16</span></a> Al&#233;m disso&#44; os achados histopatol&#243;gicos podem ser mascarados pelo uso de medicamentos&#44; tais como corticosteroides t&#243;picos&#44; que minimizam o infiltrado linfocit&#225;rio e atenuam a presen&#231;a dessas c&#233;lulas na jun&#231;&#227;o dermoepid&#233;rmica&#46; Considerando que esses medicamentos s&#227;o de f&#225;cil acesso&#44; adquiridos sem prescri&#231;&#227;o&#44; observamos frequentemente em nossa pr&#225;tica cl&#237;nica que os pacientes fazem uso inadvertido desse grupo de subst&#226;ncias&#46; Pacientes com suspeita cl&#237;nica de MF devem idealmente interromper a aplica&#231;&#227;o de esteroides t&#243;picos&#44; bem como o uso de imunossupressores sist&#234;micos &#40;se for o caso&#41;&#44; de&#160;2&#160;a&#160;4&#160;semanas antes de fazer bi&#243;psia&#44; com o objetivo de n&#227;o prejudicar a an&#225;lise histopatol&#243;gica&#44; pode&#8208;se manter o uso de emolientes&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> O delineamento retrospectivo do estudo dificulta a determina&#231;&#227;o do uso de medicamentos no momento da primeira bi&#243;psia&#44; representa&#44; portanto&#44; uma limita&#231;&#227;o a ser considerada&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">A diminui&#231;&#227;o da express&#227;o de marcadores de c&#233;lulas T&#44; tais como CD2&#44; CD3&#44; CD5 e CD7&#44; em pacientes com MF tem por base a ideia de que&#44; &#224; medida que a doen&#231;a progride&#44; &#233; identificado um fen&#243;tipo anormal predominante&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;13</span></a> Redu&#231;&#227;o de CD2&#44; CD3 e&#47;ou CD5 em pelo menos 50&#37; das c&#233;lulas linfoides &#233; um crit&#233;rio importante para a identifica&#231;&#227;o de linfomas de c&#233;lulas&#8208;T&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a> A perda de positividade parece ocorrer inicialmente nos linf&#243;citos que permeiam a epiderme e mais tarde naqueles presentes na derme&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;20</span></a> Entre CD2&#44; CD3&#44; CD5 e CD7&#44; aparentemente o crit&#233;rio mais espec&#237;fico seria a redu&#231;&#227;o da express&#227;o de CD7 para menos de&#160;10&#37; das c&#233;lulas linfoides&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Aplicando a an&#225;lise imunofenot&#237;pica em&#160;23&#160;casos que n&#227;o atenderam aos crit&#233;rios de diagn&#243;stico&#44; 22&#160;pontuaram no algoritmo&#46; O crit&#233;rio mais prevalente foi a redu&#231;&#227;o da positividade para menos de 50&#37; do infiltrado para CD2 e&#47;ou CD5&#44; &#233;&#44; portanto&#44; nesta an&#225;lise&#44; o crit&#233;rio mais sens&#237;vel&#44; semelhante ao proposto na literatura&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;20</span></a> Finalmente&#44; 13&#160;casos apresentaram o crit&#233;rio supostamente mais espec&#237;fico&#44; com redu&#231;&#227;o de CD7 para menos de 10&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;21</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Em&#160;2015&#44; Vandergriff et al&#46; publicaram um estudo para validar o algoritmo de Pimpinelli et al&#46; Os autores encontraram 87&#44;5&#37; de sensibilidade e 60&#37; de especificidade para o diagn&#243;stico e conclu&#237;ram que o algoritmo &#233; um m&#233;todo estatisticamente v&#225;lido&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Ainda que com reconhecida melhoria no diagn&#243;stico de MF inicial&#44; a pesquisa de rearranjo gen&#233;tico de TCR &#233; complexa&#44; n&#227;o est&#225; amplamente dispon&#237;vel e apresenta diferen&#231;as entre taxas de detec&#231;&#227;o segundo as t&#233;cnicas empregadas&#44; n&#250;mero de amostras e a fase de MF &#40;placa ou tumor&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">23&#8211;25</span></a> Mesmo sem incluir esse teste diagn&#243;stico complementar&#44; encontramos um aumento no percentual de diagn&#243;stico de MF&#44; de&#160;64&#44;2&#37;&#44; quando avaliada histopatologia de maneira isolada&#44; para 91&#37; quando aplicados os crit&#233;rios diagn&#243;sticos dispon&#237;veis do algoritmo&#46; Destacamos ainda que o desempenho do algoritmo poderia ter sido ainda melhor&#44; uma vez que os&#160;6&#47;67&#160;pacientes que n&#227;o obtiveram pontua&#231;&#227;o suficiente poderiam t&#234;&#8208;la atingido caso fosse pesquisado rearranjo de TCR e&#44; logicamente&#44; esse tivesse sido positivo&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclus&#227;o</span><p id="par0155" class="elsevierStylePara elsevierViewall">Embora a correla&#231;&#227;o cl&#237;nico&#8208;patol&#243;gica permane&#231;a como padr&#227;o&#8208;ouro&#44; a aplica&#231;&#227;o dos crit&#233;rios cl&#237;nicos&#44; histopatol&#243;gicos e imuno&#8208;histoqu&#237;micos do algoritmo de Pimpinelli et al&#46; foi &#250;til no diagn&#243;stico de MF precoce e pode contribuir para uma melhoria de resultados para o paciente&#44; propiciar tratamento espec&#237;fico mais precoce&#46; Nossos resultados motivaram a ado&#231;&#227;o dos crit&#233;rios do algoritmo na rotina pr&#225;tica em nosso departamento&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Como limita&#231;&#245;es do presente estudo destacamos seu car&#225;ter retrospectivo&#44; o tamanho reduzido da amostra e a falta da pesquisa de clonalidade do rearranjo do TCR&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Suporte financeiro</span><p id="par0165" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Contribui&#231;&#227;o dos autores</span><p id="par0170" class="elsevierStylePara elsevierViewall">Gustavo Moreira Amorim&#58; An&#225;lise estat&#237;stica&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Daniele Carvalho Quintella&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Jo&#227;o Paulo Niemeyer&#8208;Corbellini&#58; Concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#59; revis&#227;o cr&#237;tica da literatura&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Luiz Claudio Ferreira&#58; Elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o intelectual em conduta proped&#234;utica e&#47;ou terap&#234;utica de casos estudados&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Marcia Ramos e Silva&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Tullia Cuzzi&#58; Aprova&#231;&#227;o da vers&#227;o final do manuscrito&#59; concep&#231;&#227;o e planejamento do estudo&#59; elabora&#231;&#227;o e reda&#231;&#227;o do manuscrito&#59; obten&#231;&#227;o&#44; an&#225;lise e interpreta&#231;&#227;o dos dados&#59; participa&#231;&#227;o efetiva na orienta&#231;&#227;o da pesquisa&#59; revis&#227;o cr&#237;tica do manuscrito&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflitos de interesse</span><p id="par0200" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Fundamentos</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">O diagn&#243;stico de micose fungoide &#233; desafiador pela inespecificidade dos achados cl&#237;nicos e histopatol&#243;gicos&#46; A literatura indica um atraso m&#233;dio de 4 a 6 anos para um diagn&#243;stico conclusivo&#46; O refinamento dos crit&#233;rios histopatol&#243;gicos para o diagn&#243;stico de pacientes em est&#225;gios iniciais da doen&#231;a &#233; considerado de interesse&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudar os aspectos histopatol&#243;gicos da micose fungoide precoce e a aplicabilidade&#44; em forma retrospectiva&#44; do algoritmo diagn&#243;stico proposto por Pimpinelli et al&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">M&#233;todos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Estudo observacional&#44; retrospectivo&#44; transversal&#44; baseado na revis&#227;o de exames histopatol&#243;gicos de pacientes com suspeita de micose fungoide&#46; Os prontu&#225;rios m&#233;dicos foram revisados e an&#225;lise imuno&#8208;histoqu&#237;mica complementar foi feita&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram inclu&#237;dos 67 pacientes&#46; As caracter&#237;sticas histopatol&#243;gicas mais frequentes foram infiltrado linfoide perivascular superficial &#40;71&#44;6&#37;&#41;&#44; epidermotropismo &#40;68&#44;7&#37;&#41;&#44; atipia linfocit&#225;ria &#40;63&#44;8&#37;&#41;&#44; hiperceratose &#40;62&#44;7&#37;&#41; e acantose &#40;62&#44;7&#37;&#41;&#46; Quarenta e tr&#234;s pacientes alcan&#231;aram 4 pontos no algoritmo por avalia&#231;&#227;o cl&#237;nica e histol&#243;gica&#46; A imuno&#8208;histoqu&#237;mica foi feita em&#160;23&#160;dos&#160;24&#160;pacientes com menos de 4 pontos&#46; Desses&#160;23&#44; 22&#160;pontuaram 1 ponto&#44; permitindo um total de 61 pacientes&#160;&#40;91&#37;&#41; com o diagn&#243;stico de micose fungoide precoce&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Limita&#231;&#245;es do estudo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Seu car&#225;ter retrospectivo&#44; tamanho reduzido da amostra e aplica&#231;&#227;o incompleta do algoritmo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conclus&#245;es</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A aplica&#231;&#227;o do algoritmo Pimpinelli et al&#46;&#44; mesmo que de forma incompleta&#44; aumentou o percentual de casos diagnosticados como micose fungoide&#46; A aplica&#231;&#227;o rotineira do algoritmo pode contribuir para o manejo precoce espec&#237;fico e&#44; consequentemente&#44; melhores resultados evolutivos nesse grupo de pacientes&#46;</p></span>"
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acantose irregular&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acantose psoriasiforme&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">06&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Degenera&#231;&#227;o vacuolar da camada basal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">06&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Infiltrado linfoide</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perivascular superficial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perivascular superficial e profundo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">09&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Liquen&#243;ide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Difuso e confluente<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Comprometendo a hipoderme<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">01&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Epidermotropismo sem microabscesso de Pautrier</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">68&#44;7&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Epidermotropismo com mcroabscessos de Pautrier</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#44;9&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">08&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Foliculotropismo com mucinose folicular</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">03&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Foliculotropismo sem mucinose</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">02&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Incontin&#234;ncia pigmentar</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#44;2&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">39&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Atipia linfocit&#225;ria</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Convolu&#231;&#227;o de n&#250;cleos na epiderme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20&#44;3&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Convolu&#231;&#227;o de n&#250;cleos na derme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Aumento do tamanho nuclear na epiderme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#44;1&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Aumento do tamanho nuclear na derme</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#44;8&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">C&#233;lulas gigantes multinucleadas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#44;0&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">02&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Eosin&#243;filos</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#44;5&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">05&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Fibroplasia da derme papilar</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74&#44;6&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">50&#47;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2326234.png"
              ]
            ]
          ]
          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Nos 3 casos&#44; o padr&#227;o difuso e confluente era focal&#44; de modo que predominava o padr&#227;o perivascular superficial e profundo&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">No &#250;nico caso em que o infiltrado se estendia focalmente &#224; hipoderme&#44; o padr&#227;o predominante era o perivascular superficial e profundo&#46;</p>"
            ]
          ]
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