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Herein, we describe two cases of treatment-naïve, medium-to-large-sized KS nodules with complex architectural and vascular features, assessed by means of dermoscopy, and the US. We speculate that non-invasive recognition of complex KS lesional structure may aid in the adequate management of intralesional chemotherapy.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Patient 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">An eighty-two-year-old male with biopsy-proven, long-standing, classic KS and an otherwise unremarkable medical history complained of a newly formed lesion on the left heel, clinically appearing as a violaceous 9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>mm nodule, with a peripheral scaly collarette. Dermoscopy showed two violaceus, large vascular areas separated by a white grayish structureless area (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a‒b). At the B-mode examination, the lesion presented an oval hypoechoic structure with well-demarcated edges and with an inner median normoechoic septum delimitating two separate subunits. Color Doppler examination revealed that the subunits were supplied by two different blood vessels. Moreover, their blood flow did not communicate to a significant degree (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c/Video 1 – supplementary material).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Patient 2</span><p id="par0020" class="elsevierStylePara elsevierViewall">A sixty-three-year-old male with biopsy-proven, long-standing, classic KS and an unremarkable history came in for consultation due to the appearance of an angiomatous 7<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>mm nodule on his right arm, presenting with a smooth surface and a faded border. Dermoscopy highlighted two violaceous structureless areas on a pinkish-brownish background, divided by a somewhat paler area laying in-between; moreover, no vascular structures could be appreciated (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>d‒e). On B-mode ultrasonography, the nodule presented two contiguous subunits and a septum-like structure could be noted in the center of the lesion. eFlow mode images confirmed the presence of distinct vascular peduncles supplying each subunit (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>f).</p><p id="par0025" class="elsevierStylePara elsevierViewall">Adequate for size intralesional treatment with vincristine was offered in both cases, meaning the quantity of vincristine infiltrated was proportional to the largest diameter of the nodule, as measured clinically and dermoscopically.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> More specifically, 0.09<span class="elsevierStyleHsp" style=""></span>mL and 0.07<span class="elsevierStyleHsp" style=""></span>mL of vincristine sulfate (Vincristina Teva, Teva Italia Srl®, Assago, Italy) at a concentration of 1<span class="elsevierStyleHsp" style=""></span>mg/mL were administered in Patients 1 and 2, respectively.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Complete response was achieved in both cases, with no clinical evidence of recurrence in 12 months of follow-up.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Intralesional drug administration is particularly advantageous in nodular KS lesions, leveraging the presence of a pseudo-capsule for drug containment and concentration. Therapeutic failures and even paradoxical worsening in the days following the injection are rare but have been described. Known predisposing factors include large (7‒8<span class="elsevierStyleHsp" style=""></span>mm) lesional size and plantar and lateral plantar localization of the nodule.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Septations delimiting autonomous vascular spaces within nodular KS lesions may theoretically lead to drug entrapment, relative over-filling, and subsequent inflammatory activation in surrounding tissues upon treatment. We presented two KS cases in which dermoscopy revealed whitish grayish structureless areas corresponding to septa upon ultrasonography. Further research is required to demonstrate a causal relationship between structural complexity and a proportion of the therapeutic failures observed with intralesional chemotherapy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although no definite recommendations can be given at this time, we argue that it would be cautious to screen nodular KS lesions for dermoscopic features suggestive of septations prior to intralesional treatment. Should any be noticed, a sonographic study as well as US-guided vincristine administration could be offered.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Financial support</span><p id="par0045" class="elsevierStylePara elsevierViewall">None declared.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Authors' contributions</span><p id="par0055" class="elsevierStylePara elsevierViewall">Gianluca Nazzaro: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Athanasia Tourlaki: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Carlo Alberto Maronese: Approval of the final version of the manuscript; elaboration and writing of the manuscript; obtaining, analyzing, and interpreting the data; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the literature; critical review of the manuscript.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Enrico Zelin: Approval of the final version of the manuscript; critical review of the manuscript.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Emanuela Passoni: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the manuscript.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Lucia Brambilla: Approval of the final version of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of studied cases; critical review of the manuscript.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Patient 2" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Financial support" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Authors' contributions" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-02-08" "fechaAceptado" => "2021-03-09" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Study conducted at the Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0095" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary material" "identificador" => "sec0035" ] ] ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1691 "Ancho" => 3341 "Tamanyo" => 576312 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0065" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical, dermoscopic (Dermlite DL200 Hybrid handheld device, 3<span class="elsevierStyleHsp" style=""></span>Gen, San Juan Capistrano, CA) and sonographic (ARIETTA 850 multifrequency 15.0‒18.0<span class="elsevierStyleHsp" style=""></span>MHz linear array transducer, Hitachi Medical Systems®, Zug, Switzerland) appearance of studied lesions from patients 1 (A‒C) and 2 (D‒F).</p>" ] ] 1 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc1.mp4" "ficheroTamanyo" => 19200292 "Video" => array:2 [ "flv" => array:5 [ "fichero" => "mmc1.flv" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "mp4" => array:5 [ "fichero" => "mmc1.m4v" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kaposi sarcoma: a continuing conundrum" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.A. 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