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Brief communication
Clinicopathological and Immunohistochemical Study of Oral Amalgam Pigmentation
Estudio clínicopatológico e inmunohistoquímico de la pigmentación oral por amalgama
Beatriz Vera-Sireraa,
Corresponding author
vera_fra@gva.es

Corresponding author.
, Presentación Risueño-Matab, José M. Ricart-Vayác, Carmen Baquero Ruíz de la Hermosab, Francisco Vera-Sempered
a Departamento de Estomatología, Universidad de Valencia, Valencia, Spain
b Servicio de Cirugía Maxilofacial, Hospital Universitario La Fe, Valencia, Spain
c Servicio de Dermatología, Hospital Universitario La Fe, Valencia, Spain
d Servicio de Anatomía Patológica, Departamento de Patología, Hospital Universitario La Fe, Universidad de Valencia, Valencia, Spain
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estimates that over 50&#46;1&#37;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> of dental restorations taking place in the USA in 2009 employed silver amalgam&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Amalgam may produce local adverse effects&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;7</span></a> including mucosal pigmentation due to its metal components &#40;silver&#44; mercury&#44; and tin&#41;&#46; This is the most prevalent exogenous oral pigmentation<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> and can be confused with melanin pigmentation&#44; in which case biopsy studies are indicated&#46; In this sense&#44; we studied the clinical&#44; pathological&#44; and immunohistochemical characteristics of a series of cases of oral pigmentation due to amalgam&#44; all of which had undergone biopsy&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">We analysed all oral biopsies performed at Hospital Universitario La Fe&#44; in Valencia&#44; Spain&#44; during the period 2000&#8211;2010&#44; through the software application PAT-Win<span class="elsevierStyleSup">&#174;</span> v&#46;3&#46;4&#46;1&#46; We selected those which reported the existence of pigmentation due to amalgam&#44; excluding those from periapical lesions&#46; We obtained the clinical data of these biopsy cases through the MIZAR 2&#46;0 application&#44; noting age&#44; gender&#44; location&#44; duration&#44; reason for biopsy&#44; and service which conducted it&#46; In addition&#44; we also obtained the imaging studies prior to biopsy&#44; visualised with the IMPAX 6&#46;4&#46;0 platform&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">For each biopsy we carried out an observation with conventional and polarised light microscopy&#44; as well as staining for iron pigment &#40;Perls staining&#41; and melanin &#40;Masson-Fontana staining&#41;&#46; In addition&#44; we observed a histological section without any staining and subsequently conducted immunohistochemistry techniques for CD68&#44; CD117&#44; HLA-DR-&#945;-chain&#44; and metallothionein&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the characteristics of the antibodies employed&#46; All techniques were performed using the Dako<span class="elsevierStyleSup">&#174;</span> Envision-Plus&#8482; system&#44; and we conducted thermal antigen retrieval with EnVision Flex Target Retrieval solution &#40;Dako<span class="elsevierStyleSup">&#174;</span>&#41;&#46; We introduced positive and negative controls for evaluation in all the techniques&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">We collected 6 observations &#40;5 females and 1 male&#44; with a mean age of 56&#46;5 years&#41; of oral pigmentation due to amalgam&#46; Their clinical and anamnestic data are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; All presented blackish blue oral regions&#44; with a history of dental treatment&#46; None of the imaging studies prior to biopsy showed radiopacity in the pigmented areas&#46; In 4 patients&#44; the biopsy was conducted in order to rule out melanin lesion&#59; in 1 case the study was conducted due to marked cancerophobia and only in 1 case the resection was carried out for aesthetic reasons&#46; Pigmentation areas were measured between 0&#46;3 and 1<span class="elsevierStyleHsp" style=""></span>cm &#40;with a mean diameter of 0&#46;45<span class="elsevierStyleHsp" style=""></span>cm&#41;&#44; and were present for a period between 2 months and 5 years&#44; although 5 patients reported an enlargement in the 2&#8211;3 months prior to biopsy&#46; The most common location was the gingival mucosa &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; followed by the jugal and palatal&#46; All biopsies were obtained by oral surgeons&#44; except for 1 case which was conducted by a dermatologist&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">In all biopsies &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41; some unstained sections contained the black colour of the pigment&#44; with negative Perls and Masson-Fontana stains&#44; thus excluding iron and melanin pigmentation&#46; This pigmentation was observed as large deposits or in a fine granular form &#40;0&#46;1&#8211;0&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;m&#41; at the stromal&#44; vascular&#44; perineural&#44; and muscular levels or in the submucosal salivary glands&#46; The black&#44; granular deposits located on elastic or collagen fibres were present in all observations&#44; forming granular chains or in a disorderly manner&#46; In 3 observations we also noted large and coarse deposits in the submucosal or muscular corium&#46; Only the large deposits were surrounded by a fibrous capsule&#44; usually free of inflammatory reaction&#46; In order of frequency&#44; fine stromal deposits were followed by adventitial vascular pigmentation &#40;5 of 6 observations&#41; and in 3 cases there was muscle fibre pigmentation in the perimysium and endomysium&#44; often distant from other deposits&#44; suggesting that this had contributed to increased pigmentation&#44; as reported by 3 patients&#46; Only in 1 case&#44; with presence of large deposits&#44; was there a foreign-body type granulomatous reaction&#44; with giant cells which phagocytosed pigment&#46; Polarised vision showed whitish or reddish&#44; dual colouring refraction patterns&#46; Large deposits showed no refractive character&#59; this was only observable in the fine granular deposits&#44; which were more evident with polarisation&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Immunohistochemically &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; we found CD68&#43; macrophage involvement in the case suffering a granulomatous&#44; foreign-body type reaction&#46; In the remaining cases&#44; the presence of macrophages was low&#46; However&#44; the presence of CD117&#43; cells&#44; identifiable as mast cells&#44; was marked&#46; Mast cells appeared at the subepithelial level and in the submucosa suffering pigmentation&#44; as well as alongside large&#44; coarse deposits&#46; The expression of metallothionein was found in the mucosa&#44; at the basal and suprabasal levels&#44; coinciding with the presence of pigment in the corium&#46; A weaker expression of metallothionein was observed perivascularly and in stromal elements&#46; Moreover&#44; an increase in the number of HLA-DR&#43; cells&#44; often with dendritic morphology&#44; was observed in the mucosal epithelium and in stromal elements of the corium&#44; coinciding with areas of pigment deposit&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Oral pigmentation caused by amalgam is an adverse local effect<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;7</span></a> reported in patients undergoing dental treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> It is caused by different mechanisms&#44; including mechanical penetration into soft tissues&#44; corrosion phenomena&#44; and release of metallic components&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Pigmentation itself is harmless<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and relatively frequent&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> mainly affecting the mandibular gingival mucosa&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> followed by the buccal mucosa&#44; floor of mouth&#44; tongue&#44; retromolar mandibular area&#44; lips&#44; and palate&#46; It can also be observed in the maxilla and edentulous areas&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;12</span></a> It may be a cause for biopsy when mistaken with melanosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;13</span></a> especially when there is no radiopacity&#46; Metallic particles are radiopaque&#44; thus facilitating the recognition of pigmentation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> However&#44; less than 25&#37; of amalgam pigmentations are radiopaque<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;14</span></a> since their metallic particles are very small or are too dispersed to be visible in a radiographic study&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In biopsy series&#44; pigmentation is found in about 1&#46;5&#37; of all oral biopsies&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> thus giving an idea of the small number of cases in which they are biopsied&#46; In population groups without biopsy studies&#44; its presence is noted in 8&#46;22&#37; of the subjects&#44; reaching 11&#46;2&#37; among women&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> As in our cases&#44; this increased female incidence<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;15&#44;16</span></a> is attributed to the fact that the female population has a greater tendency to seek dental care and&#44; therefore&#44; a greater likelihood of exposure to dental restorative materials&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Amalgam consists of 3 phases<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#58; phase &#947; &#40;SnAg<span class="elsevierStyleInf">3</span>&#41;&#44; phase &#947;1 &#40;Hg<span class="elsevierStyleInf">3</span>Ag<span class="elsevierStyleInf">2</span>&#41;&#44; and phase &#947;2 &#40;Sn<span class="elsevierStyleInf">8</span>Hg&#41;&#44; with phase &#947;2 being the most corrodible&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> These phases have different degradation patterns&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> so they do not contribute equally to pigmentation&#46; Phase &#947;2 is degraded rapidly and does not participate in pigmentation&#46; Phase &#947;1 degrades slowly&#44; with loss of Hg&#46; Finally&#44; phase &#947; degrades slowest and is responsible for the pigmentation&#44; persisting as Ag and sulphur particles&#44; associated with basal membranes or conjunctive tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> There is no Hg in the pigment and Sn is lost by corrosion&#46; Therefore&#44; only Ag&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a> in granular form&#44; remains in the tissues and is responsible for pigmentation&#44; as observed in our cases&#46; As a cation&#44; Ag becomes fixed to basal membranes&#44; in collagen and elastic fibres and the perineuria&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> or may be phagocytosed by macrophages&#44; being the only remaining component&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#44;18</span></a> Although all 3 phases are radiopaque&#44; in the case of phase &#947; this radiopacity may disappear by fragmentation and dispersion after 1 year evolution&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> This explains the lack of radiopacity in many pigmentations<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;13&#44;14</span></a> and their possible confusion with melanosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11&#8211;13</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In our cases&#44; the fine granular deposits were the most frequent&#44; as has also been reported by other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Foreign-body type granulomas were observed in 1 case&#44; with a similar incidence to that reported in the largest published series&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> specifically 13&#46;4&#37; granulomas&#46; The presence of multinucleated cells was related to particle size&#44; so only particles measuring 2&#46;5&#8211;35<span class="elsevierStyleHsp" style=""></span>&#956;m were phagocytosed by giant cells&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> This demonstrates<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;12&#44;17&#44;20</span></a> a relationship between tissue response and particle size&#46; We only observed a fibrous capsule in large deposits and this was established at 4 weeks of metal implantation&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;17</span></a> in relation to corrosion of phase &#947;2&#46; It is interesting to note that&#44; in patients with increased pigmentation diameter&#44; we observed an aspect reported by other authors&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> consisting in perimysium pigmentation distant from other deposits&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Immunohistochemically&#44; we verified an elevated number of CD117&#43; mast cells&#46; Only 1 previous study<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> noted this fact&#44; indicating that this was independent of the size of pigment deposits&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> This finding is relevant&#44; as certain heavy metals &#40;Ag&#44; Hg&#44; Au&#41; can influence the function and survival of mast cells&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and can cause autoimmune reactions in predisposed individuals&#44; which would explain the appearance of lichenoid reactions&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Other data included the overexpression of metallothionein and HLA-DR&#46; Metallothionein is a ubiquitous protein involved in the detoxification of metals and free radicals&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Our study&#44; as well as others&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> found overexpression at the mucosal level&#44; above the pigment deposits&#44; and at the perivascular and stromal levels&#46; However&#44; we differ from those which only found immunoreactivity in macrophages near the deposits&#44;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> correlating overexpression with residual Hg deposits&#46; HLA-DR was overexpressed in intraepithelial dendritic cells&#44; as well as at the perivascular level and in stromal elements&#46; HLA-DR was expressed in antigen-presenting cells and its overexpression could be interpreted as a phenomenon induced by the metallic components in the context of pigment degradation processes&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interests</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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            0 => "Amalgama"
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        "titulo" => "Abstract"
        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Amalgam tattoo&#44; the most common exogenous oral pigmentation&#44; can sometimes be confused with melanotic lesions&#44; being then biopsied&#46; We present the clinicopathological characteristics of 6 biopsied cases &#40;5 females and 1 male&#41; of oral amalgam pigmentation&#46; The most common location was the gingival mucosa&#44; followed by the buccal and palatal mucosa&#46; Morphology and distribution &#40;stromal&#44; perivascular&#44; perineural&#44; and endomysial&#41; of pigmentation were variable&#59; there was only 1 case with fibrous capsular reaction and likewise only a single case of granulomatous foreign body reaction&#46; Morphological variability is conditioned by the timing and amount of the pigment deposit&#44; which is often associated with infiltration by mast cells &#40;CD117&#43;&#41;&#44; as well as overexpression of metallothionein and HLA-DR at different tissue levels&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El tatuaje por amalgama&#44; la pigmentaci&#243;n ex&#243;gena oral m&#225;s frecuente&#44; puede en ocasiones simular lesiones mel&#225;nicas y ser motivo de estudio bi&#243;psico&#46; Se presentan las caracter&#237;sticas clinicopatol&#243;gicas de 6 pacientes &#40;5 mujeres y un var&#243;n&#41; biopsiados por pigmentaci&#243;n oral por amalgama&#46; La localizaci&#243;n m&#225;s frecuente fue la mucosa gingival&#44; seguida de la yugal y palatina&#46; La morfolog&#237;a y distribuci&#243;n &#40;estromal&#44; perivascular&#44; perineural y endomisial&#41; de la pigmentaci&#243;n fue variable&#44; apreciando solo en un caso reacci&#243;n capsular fibrosa e igualmente&#44; solo en un caso&#44; reacci&#243;n granulomatosa tipo cuerpo extra&#241;o&#46; Esta variabilidad morfol&#243;gica esta condicionada por la cuant&#237;a y cronolog&#237;a del dep&#243;sito pigmentario&#44; que a menudo esta asociado a una infiltraci&#243;n por mastocitos &#40;CD117&#43;&#41;&#44; as&#237; como a una sobreexpresi&#243;n de metalotionina y HLA-DR a diferentes niveles tisulares&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Vera-Sirera B&#44; et al&#46; Estudio cl&#237;nicopatol&#243;gico e inmunohistoqu&#237;mico de la pigmentaci&#243;n oral por amalgama&#46; Acta Otorrinolaringol Esp&#46; 2012&#59;63&#58;376&#8211;81&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Image of pigmentation in the gingival mucosa &#40;lower left canine&#41;&#44; of 2 months evolution&#46; &#40;B&#41; Pigmentation in edentulous gum&#44; of 5 months of evolution&#44; near to 2 molars with amalgam restoration&#46;</p>"
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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#40;A and B&#41; Overview of oral biopsies showing pigment deposits in the corium &#40;HE&#44; 15&#215;&#41;&#46; &#40;C&#41; Fine granular deposits arranged in rows on the mucosal corium &#40;HE&#44; 400&#215;&#41;&#46; &#40;D&#41; Large&#44; deep submucosal pigment deposit&#44; surrounded by a dense fibrous capsule&#44; also pigmented &#40;HE&#44; 200&#215;&#41;&#46; &#40;E&#41; Two granulomas with multinucleated giant cells in proximity to a muscular plane&#44; with presence of large&#44; black deposits &#40;HE&#44; 200&#215;&#41;&#46; &#40;F&#41; Striated muscle fibres with pigmented contours of fibrous sheaths &#40;HE&#44; 200&#215;&#41;&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Discontinuous expression of metallothionein at the level of the basal layers of the mucosal epithelium&#44; coinciding with granular deposits and in small&#44; dense lumps of pigment material &#40;metallothionein&#44; 100&#215;&#41;&#46; &#40;B&#41; Expression of metallothionein at the level of the adventitial layer of small vessels &#40;metallothionein&#44; 400&#215;&#41;&#46; &#40;C&#41; Expression of HLA-DR marking intraepithelial dendritic cells&#44; as well as subepithelial stromal elements and at the perivascular level &#40;HLA-DR&#44; 250&#215;&#41;&#46; &#40;D&#41; Immunoreactive stromal elements against CD117&#44; identified as mast cells&#44; at the level of the mucosal corium &#40;CD117&#44; 150&#215;&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Ab&#44; antibody&#59; Poly&#44; polyclonal&#59; RtU&#44; ready to use&#46;</p>"
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                  \t\t\t\t">CD-68&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">Mouse monoclonal Ab&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">KP1&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">Dakoppats<span class="elsevierStyleSup">&#174;</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">RtU&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CD-117 &#40;c-kit&#41;&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">Rabbit polyclonal Ab&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">Ab Poly&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">Dakoppats<span class="elsevierStyleSup">&#174;</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">1&#47;400&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HLA-DR &#945;-chain&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">Mouse monoclonal Ab&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">TAL&#46;1B5&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">Dakoppats<span class="elsevierStyleSup">&#174;</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">1&#47;30&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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Metallothionein&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">Mouse monoclonal Ab&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">E-9&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">Dakoppats<span class="elsevierStyleSup">&#174;</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">1&#47;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab179919.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Antibodies Employed in the Study&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Observation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Size&#44; cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">History&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Biopsy&#47;exeresis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Rx opacity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&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">Female&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">36&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">Alveolar mucosa&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&#46;30&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">Root canal 44&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">Aesthetic reasons&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">&#8211;&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&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">Male&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">62&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">Palatine mucosa &#40;1&#47;3 post&#41;&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&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">Root canal 26&#43;restoration&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">Suspicion of melanoma&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">&#8211;&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&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">Female&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&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">Jugal mucosa&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&#46;80&#215;0&#46;40&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">Restoration 28&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">Suspicion of melanoma&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">&#8211;&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&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">Female&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&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">Jugal mucosa&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&#46;40&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">Apical surgery&#43;exodontia 33&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">Cancerophobia&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">&#8211;&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&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">Female&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&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">Gum mucosa&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&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">Restoration and root canal 23&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">Suspicion of melanoma&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">&#8211;&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  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&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">Female&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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">67&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
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ISSN: 21735735
Original language: English
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