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3</a>&#41;&#46; The foamy cells were positive for Periodic Acid Schiff and CD68 antigen &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">What is your diagnosis&#63;</span><p id="par0010" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Viral wart&#59;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0020" class="elsevierStylePara elsevierViewall">Condyloma acuminatum&#59;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Verruciform xanthoma&#59;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0030" class="elsevierStylePara elsevierViewall">Adult xanthogranuloma&#46;</p></li></ul></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">From the histopathological findings&#44; the nodules were diagnosed as Verruciform Xanthoma &#40;VX&#41;&#46; Xanthogranuloma was excluded because Touton-type giant cells were not observed&#46; Both of the nodules were surgically removed&#44; and they showed the same histopathological features&#46; No recurrence had been observed during 1-year follow-up&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">VX occurs mostly in the oral cavity<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>&#59; however&#44; the genital area has also been involved &#40;verruciform genital-associated xanthoma&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Clinically&#44; VXs have a similar appearance to condyloma acuminatum or verruca vulgaris&#46; The histopathological examination demonstrated verrucous hyperplasia of the epidermis and a variable number of foamy cells within the dermal papillae&#46; As far as we reviewed&#44; only 6 cases of multiple VXs on the genital area have been reported including the present case &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;7</span></a> Those 6 cases consisted of 4 males and 2 females&#44; and the mean age was 53 years old &#40;range 29&#8210;83 years&#41;&#46; The size of the lesions ranged from 3 to 25&#8239;mm&#46; The number of nodule was 2 in our case&#44; whereas numerous nodules were observed in 1 case&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Pruritus was observed in 2 cases&#44; whereas others were asymptomatic&#46; In 1 case&#44; VX occurred at the site of the skin graft due to necrotizing fasciitis&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Although the cause of VX is unknown&#44; Zegarelli et al&#46; suggested that VX results from degenerative changes in the epidermis with a subsequent nonspecific histiocytic response&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The damage to the epithelium could trigger the following cascade&#58; 1&#41; Entrapment of epithelial cells in the papillary dermis&#44; 2&#41; Subsequent degeneration of these cells and lipid formation&#44; 3&#41; Engulfment of released lipids by macrophages&#44; and 4&#41; Accumulation of foam cells between the rete ridges&#46; On the other hand&#44; it was speculated that the Human Papillomavirus &#40;HPV&#41; was involved in the pathogenesis of VX&#46; Khaskhely et al&#46; reported VX in which HPV type 6a DNA was detected in the lesional tissues by Polymerase Chain Reaction &#40;PCR&#41; and sequence analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> By contrast&#44; another study examined HPV types 6&#44; 11&#44; 16&#44; 18&#44; 31&#44; 33&#44; and 35 by PCR&#44; which were all negative&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In the present case&#44; PCR amplification of HPV including serotypes 6&#44; 11&#44; 16&#44; 18&#44; 31&#44; 33&#44; 35&#44; 52b&#44; and 58 was performed&#44; with all negative results&#46; Therefore&#44; further studies of the etiology of VX are necessary&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors&#39; contributions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Natsuko Matsumura&#58; Collection&#44; analysis&#44; and interpretation of data&#59; drafting and editing of the manuscript&#59; critical review of the literature&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Toshiyuki Yamamoto&#58; Design and planning of the study&#59; editing and final approvement of the manuscript&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Figure "
            "rol" => "short"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histopathological findings showed upwardly protruding tumors with acanthosis and papillomatosis</p>"
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      ]
      2 => array:8 [
        "identificador" => "fig0015"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1275
            "Ancho" => 1675
            "Tamanyo" => 234240
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Figure "
            "rol" => "short"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Detail of histopathology&#58; The dermal papillae are covered by numerous foamy histiocytes with increased number of capillaries</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "fig0020"
        "etiqueta" => "Figure 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
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            "Ancho" => 1675
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          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Figure "
            "rol" => "short"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foamy macrophages in the papillary dermis showing CD68 positivity</p>"
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      ]
      4 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          0 => array:3 [
            "identificador" => "at0025"
            "detalle" => "Table "
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ND&#44; Not Described&#46;</p>"
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            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"><th 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" scope="col" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Age&#47;Gen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Duration of illness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Clinical hypothesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Size &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Location&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Symptoms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Progress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Trigger&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">HPV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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">1<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</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">29F&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">17-yr&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">Condyloma&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">ND&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">Vulva&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">None&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">Not change&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">ND&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">ND&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">2<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</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">42F&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-yr&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">ND&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 to 25&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">Vulva&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">ND&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">Increasing&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">ND&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">Negative&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">3<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</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">38M&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">2&#46;5-mo&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">Necrotizing fasciitis&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">8&#8239;&#215;&#8239;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">Penis and perineum&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">None&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">Enlarging&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">Skin grafting&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">ND&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">4<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</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">63M&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-yr&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">Condyloma&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 to 15&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">Scrotum&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">Pruritic&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">Increasing&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">ND&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">ND&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">5<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</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">67M&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-yr&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">ND&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">25&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">Scrotum&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">ND&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">Increasing&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">ND&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">HPV 6a&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">Our case&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">83M&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-yr&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">Condyloma&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 to 25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">Scrotum&nbsp;\t\t\t\t\t\t\n
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Vol. 98. Núm. 6.
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Vol. 98. Núm. 6.
Páginas 845-847 (1 novembro 2023)
Letter - Clinical
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Case for diagnosis. Multiple nodules on the scrotum: verruciform xanthomas
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Natsuko Matsumura
Autor para correspondência
natsukom@fmu.ac.jp

Corresponding author.
, Toshiyuki Yamamoto
Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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Table 1. Reports focusing on verruciform xanthoma in multiple sites on the genital area
Texto Completo
Dear Editor,

An 83-year-old male visited us complaining of multiple nodules on the scrotum that first appeared 20 years previously. They had been increasing in size and recently started to bleed easily. Physical examination revealed 2 exophytic and pedunculated red nodules sized 25 × 25 mm and 13 × 13 mm, which protruded from both sides of the scrotum (Fig. 1). He has a history of prostate cancer, obstructive hypertrophic cardiomyopathy, aortic regurgitation, chronic atrial fibrillation, chronic renal failure, and submucosal tumors of the esophagus. A biopsy specimen showed upwardly protruding tumors with acanthosis and papillomatosis (Fig. 2). The dermal papillae were covered by numerous foamy histiocytes and hyperplasia of capillaries (Fig. 3). The foamy cells were positive for Periodic Acid Schiff and CD68 antigen (Fig. 4).

Figure 1.

Well-circumscribed, exophytic and pedunculated nodules on the scrotum

(0.15MB).
Figure 2.

Histopathological findings showed upwardly protruding tumors with acanthosis and papillomatosis

(0.19MB).
Figure 3.

Detail of histopathology: The dermal papillae are covered by numerous foamy histiocytes with increased number of capillaries

(0.22MB).
Figure 4.

Foamy macrophages in the papillary dermis showing CD68 positivity

(0.24MB).
What is your diagnosis?

  • a)

    Viral wart;

  • b)

    Condyloma acuminatum;

  • c)

    Verruciform xanthoma;

  • d)

    Adult xanthogranuloma.

Discussion

From the histopathological findings, the nodules were diagnosed as Verruciform Xanthoma (VX). Xanthogranuloma was excluded because Touton-type giant cells were not observed. Both of the nodules were surgically removed, and they showed the same histopathological features. No recurrence had been observed during 1-year follow-up.

VX occurs mostly in the oral cavity1; however, the genital area has also been involved (verruciform genital-associated xanthoma).2 Clinically, VXs have a similar appearance to condyloma acuminatum or verruca vulgaris. The histopathological examination demonstrated verrucous hyperplasia of the epidermis and a variable number of foamy cells within the dermal papillae. As far as we reviewed, only 6 cases of multiple VXs on the genital area have been reported including the present case (Table 1).3–7 Those 6 cases consisted of 4 males and 2 females, and the mean age was 53 years old (range 29‒83 years). The size of the lesions ranged from 3 to 25 mm. The number of nodule was 2 in our case, whereas numerous nodules were observed in 1 case.3 Pruritus was observed in 2 cases, whereas others were asymptomatic. In 1 case, VX occurred at the site of the skin graft due to necrotizing fasciitis.5

Table 1.

Reports focusing on verruciform xanthoma in multiple sites on the genital area

Patients  Age/Gen  Duration of illness  Clinical hypothesis  Size (mm)  Location  Symptoms  Progress  Trigger  HPV 
13  29F  17-yr  Condyloma  ND  Vulva  None  Not change  ND  ND 
24  42F  20-yr  ND  3 to 25  Vulva  ND  Increasing  ND  Negative 
35  38M  2.5-mo  Necrotizing fasciitis  8 × 5  Penis and perineum  None  Enlarging  Skin grafting  ND 
46  63M  4-yr  Condyloma  10 to 15  Scrotum  Pruritic  Increasing  ND  ND 
57  67M  4-yr  ND  25  Scrotum  ND  Increasing  ND  HPV 6a 
Our case  83M  20-yr  Condyloma  13 to 25  Scrotum  Pruritic  Increasing/bleeding  External factor  Negative 

ND, Not Described.

Although the cause of VX is unknown, Zegarelli et al. suggested that VX results from degenerative changes in the epidermis with a subsequent nonspecific histiocytic response.8 The damage to the epithelium could trigger the following cascade: 1) Entrapment of epithelial cells in the papillary dermis, 2) Subsequent degeneration of these cells and lipid formation, 3) Engulfment of released lipids by macrophages, and 4) Accumulation of foam cells between the rete ridges. On the other hand, it was speculated that the Human Papillomavirus (HPV) was involved in the pathogenesis of VX. Khaskhely et al. reported VX in which HPV type 6a DNA was detected in the lesional tissues by Polymerase Chain Reaction (PCR) and sequence analysis.7 By contrast, another study examined HPV types 6, 11, 16, 18, 31, 33, and 35 by PCR, which were all negative.9 In the present case, PCR amplification of HPV including serotypes 6, 11, 16, 18, 31, 33, 35, 52b, and 58 was performed, with all negative results. Therefore, further studies of the etiology of VX are necessary.

Financial support

None declared.

Authors' contributions

Natsuko Matsumura: Collection, analysis, and interpretation of data; drafting and editing of the manuscript; critical review of the literature.

Toshiyuki Yamamoto: Design and planning of the study; editing and final approvement of the manuscript.

Conflicts of interest

None declared.

References
[1]
W.G. Shafer.
Verruciform xanthoma.
Oral Surg Oral Med Oral Pathol, 31 (1971), pp. 784-789
[2]
K.M. Stiff, P.R. Cohen.
Vegas (Verruciform genital-associated) xanthoma: a comprehensive literature review.
Dermatol Ther, 7 (2017), pp. 65-79
[3]
D.J. Santa Cruz, S.A. Martin.
Verruciform xanthoma of the vulva.
Am J Clin Pathol, 71 (1979), pp. 224-228
[4]
J. Sopena, R. Gamo, L. Iglesias, J.L. Rodriguez-Peralto.
Disseminated verruciform xanthoma.
Br J Dermatol, 151 (2004), pp. 717-719
[5]
L. Cumberland, A. Dana, B. Resh, J. Fitzpatrick, G. Goldenberg.
Verruciform xanthoma in the setting of cutaneous trauma and chronic inflammation: report of a patient and a brief review of the literature.
J Cutan Pathol, 37 (2010), pp. 895-900
[6]
J. Joo, M.A. Fung, J. Jagdeo.
Successful treatment of scrotal verruciform xanthoma with shave debulking and fractionated carbon dioxide laser therapy.
Dermatol Surg, 40 (2014), pp. 214-217
[7]
N.M. Khaskhely, H. Uezato, T. Kamiyama, M. Maruno, K.I. Kariya, M. Oshiro, et al.
Association of human papillomavirus type 6 with a verruciform xanthoma.
Am J Dermatopathol, 22 (2000), pp. 447-452
[8]
D.J. Zegarelli, E.C. Aegarelli-Schmidt, E.V. Zegalli.
Verruciform xanthoma: a clinical, light microscopic, and electron microscopic study of two cases.
Oral Surg Oral Med Oral Pathol, 38 (1974), pp. 725-734
[9]
N. Agarwal-Antal, J. Zimmermann, T. Scholz, Noyes, S.A. Leachman.
A giant verruciform xanthoma.
J Cutan Pathol, 29 (2002), pp. 119-124

Study conducted at the Department of Dermatology, Fukushima Medical University, Fukushima, Japan.

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