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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Multiple morphological features are often used in the histopathological diagnosis of cutaneous melanoma&#46; These can be categorized into two major types such as architectural &#40;pagetoid infiltration and solar elastosis&#41; and cytological features &#40;melanocytic atypia and rate of mitoses&#44; among others&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Several features have prognostic implications&#44; the most important being the presence of ulceration and Breslow thickness&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Molecular biology is changing the way we see and classify melanocytic lesions&#44; and there have been interesting advances in this field over the past few years&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Moreover&#44; it is remarkable how heterogeneous melanoma can be in terms of its histopathological appearance&#46; Although this is probably due to multiple factors&#44; mutational status is gaining interest as it might determine some clinical and histopathological features such as the degree of pagetoid spread or the shape and size of melanoma cells&#46; In a previous study&#44; Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> defined some histopathological features associated with the presence of BRAF mutations&#46; BRAF mutated melanomas displayed an increased upward migration and nest formation of intraepidermal melanocytes&#44; a sharper demarcation towards the surrounding skin&#44; thickening of the involved epidermis&#44; rounder&#44; larger and more pigmented melanoma cells&#44; and thickening of the involved epidermis&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Histopathological reports of tumor characteristics are subject to interobserver variability&#44; so diagnosis and description of melanoma can often be problematic&#46; In melanocytic lesions&#44; several studies have reported a low level of agreement for some semi-quantitative features&#44; such as lymphocytic infiltration or regression&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">3&#8211;6</span></a> In addition&#44; the differential diagnosis between dysplastic nevi and early-stage invasive melanoma can sometimes be challenging too&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand&#44; some prognostic features generally have high interobserver reproducibility&#44; such as Breslow thickness and the presence of ulceration&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;6&#44;9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The main objective ot the study was to evaluate the concordance between the two groups for each pathologic feature assessed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Clinician panel and review procedure</span><p id="par0040" class="elsevierStylePara elsevierViewall">Our study was conducted by two groups of researchers&#44; the first one included two dermatopathologists from the same institution &#40;IVO&#41; and the second&#44; one pathologist &#40;HUDO&#41; and one dermatologist &#40;HM&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The dermatologist performed the histological assessment always under supervision and accompanied by the pathologist and had experience in dermatopathology &#40;held a 4-month internship in the dermatopathology unit at Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain and a 15-day short internship in Ackerman Academy&#44; New York City&#44; NY&#44; United States&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study was conducted in two stages&#46; Stage &#35;1 was the pre-selection of the histologic features to be studied&#44; as well as their definitions&#46; This was done considering previous literature&#44; specifically Viros et al&#46; research work&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and preliminary meetings of the research group in which a subset of 40 samples with different mutational status was examined&#46; We decided to include some extra features based on their prevalence&#46; This stage also included an assessment of the level of agreement in a training set of 10 samples to identify and resolve discrepancies in the assessment of the definitive variables&#46; This assessment was performed separately by each of the two groups&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Finally&#44; the last stage was performed the same way but with the final sample set on which the present study was conducted&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cases studied</span><p id="par0060" class="elsevierStylePara elsevierViewall">The histological sections were obtained consecutively from IVO pathology files from January 2004 through December 2004&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Demographic data including age&#44; sex&#44; location&#44; type of melanoma&#44; Breslow thickness and Clark level were retrieved from the IVO Melanoma Database&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Tissue fragments were fixed in formalin&#44; routinely processed and stained with haematoxylin and eosin&#46; All cases that were not optimal for review were excluded&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Histopathological features</span><p id="par0075" class="elsevierStylePara elsevierViewall">Specific features analyzed by Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> were included in our analysis&#58;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Upward spread of intraepidermal melanocytes or pagetoid spread &#40;100&#37; melanocytes at the dermoepidermal junction&#44; 75&#37; up to 100&#37; melanocytes at the dermoepidermal junction&#44; 50&#37; pagetoid spread&#44; &#62;50&#37; pagetoid spread&#41;&#44; nest formation of intraepidermal melanocytes &#40;no nests&#44; &#60;25&#37; melanocytes in nests&#44; 25&#37; up to 50&#37; melanocytes in nests&#44; &#62;50&#37; melanocytes in nests&#41;&#44; pigmentation of melanocytes &#40;absence&#44; slight&#44; moderate&#44; high&#44; very high&#41;&#44; epidermal contour &#40;atrophic&#44; thinned&#44; normal&#44; thickened&#44; hypertrophic&#41;&#44; lateral circumscription &#40;discontinuous&#44; gradual but continuous&#44; abrupt&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We also included some additional features given their potential interest&#58;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Pattern of growth &#40;expansive vs infiltrative&#41;&#44; solar elastosis &#40;categorized in two ways&#58; 1 &#8211; absence&#44; minimum&#44; moderate&#44; and high&#59; and 2 &#8211; low vs high&#41;&#44; presence of ulceration &#40;absence vs presence&#41;&#44; type of ulceration &#40;expansive vs infiltrative&#41;&#44; polypoid shape &#40;absence vs presence&#41;&#44; regression &#40;absence&#44; &#8804;50&#37;&#44; &#62;50&#37;&#41;&#44; presence of necrosis &#40;absence vs presence&#41;&#44; and presence of pleomorphism &#40;absence vs presence&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Their definitions are described in detail in the <a class="elsevierStyleCrossRef" href="#sec0050">supplementary data</a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Results were exported to an Excel table&#46; When a feature or an entire case could not be evaluated for whatever reasons&#44; it was considered as non-applicable&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Agreement among the two groups was assessed using Cohen&#39;s kappa coefficient statistic &#40;<span class="elsevierStyleItalic">&#954;</span>&#41;&#44; which is a known index for measuring chance corrected agreement on a nominal or ordinal scale&#46; According to Landis and Koch&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> values &#62;0&#46;75 represent excellent agreement beyond chance&#44; values between 0&#46;75 and 0&#46;40 represent fair to good agreement beyond chance&#44; and values &#60;0&#46;40 represent poor agreement beyond chance&#46; A <span class="elsevierStyleItalic">&#954;</span> value close to one means almost perfect agreement&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In the case of ordinal variables&#44; we used Cohen&#39;s weighted kappa &#8211; a modification of the original kappa statistic &#8211; proposed for nominal variables in the presence of two observers&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">For each characteristic considered&#44; a 2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2 diagnostic table was built using dichotomous categories&#44; and specific <span class="elsevierStyleItalic">&#954;</span> values were calculated&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">The first 60 consecutive cases diagnosed in the IVO Dermatology service from January 2004 through December 2004 were selected&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Five cases were excluded&#44; four of them because they could not be interpreted due to their small size and one because of duplication &#40;two sections of the same case&#41;&#46; So&#44; eventually 55 valid cases were considered to stablish kappa values&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The study population included 55 patients&#44; 28 &#40;50&#46;9&#37;&#41; men and 27 &#40;49&#46;1&#37;&#41; women&#44; with a mean age at diagnosis of 58&#46;9 years &#40;range&#44; 23&#8211;82 years&#41;&#46; Data on the location of the primary tumor&#44; the histological type and the tumor stage are shown in <a class="elsevierStyleCrossRef" href="#sec0050">Table 1 of the supplementary data</a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">General concordance was moderate &#40;median kappa value&#44; 0&#46;5&#41;&#46; Maximum values were for presence of polypoid shape &#40;0&#46;8&#41;&#44; pigmentation &#40;0&#46;7&#41;&#44; presence of ulceration &#40;0&#46;7&#41; elastosis &#40;high CSD&#47;low CSD&#41; 0&#46;7&#44; and degree of elastosis &#40;0&#46;7&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The most discordant values were the presence of pleomorphism &#40;0&#46;2&#41; and necrosis &#40;0&#46;3&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the kappa values from different studies&#44; specifically our results and those from the studies conducted by Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and Broekaert et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Finally&#44; we conducted an adjustment of the variables pagetoid spread and formation of intraepidermal nests and assessed the interobserver agreement&#46; Specifically&#44; we reduced the number of categories from 4 down to 2&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">&#954;</span> value for pagetoid spread was 0&#46;7 and the <span class="elsevierStyleItalic">&#954;</span> value for nest formation&#44; 0&#46;4&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">In this study&#44; we examined the reproducibility or interobserver agreement of some characteristics of 60 cases of malignant melanoma&#44; some of them with prognostic implications&#46; The overall concordance was moderate&#46; The highest kappa values were for polypoid shape and solar elastosis &#40;high CSD&#47;low CSD&#41;&#46; On the other hand&#44; the lowest values reported were for necrosis and pleomorphism&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Melanoma is a heterogeneous tumor as it shows different clinical and histopathological characteristics&#44; sometimes making diagnosis challenging&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Former studies have evaluated the interobserver reproducibility of diagnostic criteria in melanoma and other melanocytic lesions with heterogeneous results&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;4&#44;8&#44;9&#44;13&#8211;16</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">These studies often perform the circulation of pathological sections of cutaneous melanomas or melanocytic lesions to different combinations of pathologists and dermatopathologists to categorize multiple histopathological variables&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The highest concordance rates were achieved for the most important variable in terms of prognostic value for Breslow thickness&#46; This is something predictable as it is a quantitative variable&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;6&#44;9&#44;14&#44;17&#8211;20</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">On the contrary&#44; some other variables with prognostic importance show low or moderate reproducibility as Clark level assessment&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">9&#44;14&#44;19&#44;20</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Our study is based on several variables that were defined in the study by Viros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> This study showed better kappa values for most of the variables tested compared to our results<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Another study undertaken by the same group &#40;Broekaert et al&#46;&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> presented similar kappa values&#44; except for nesting&#44; epidermal contour and circumscription that were lower than the values obtained in the study conducted by Viros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">An explanation for some of the discordances reported may be that melanoma can be a very large lesion and show overt heterogenicity <span class="elsevierStyleItalic">per se</span>&#46; Therefore&#44; when considering nest formation or pagetoid spread&#44; an area with high number of nests or intraepidermal spread can exist followed by another with total absence&#44; which complicates providing a result to quantify this finding&#46; Additionally&#44; some features can be detected only in some glass sections&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Regarding lateral circumscription and epidermal contour&#44; we have detected that often&#44; melanoma can show different transitions from the intraepidermal growth portion of the tumor to normal skin from one to the other side of the glass section&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">It is remarkable that solar elastosis was more reproducible than other variables when assessed in two categories &#40;high CSD&#47;low CSD&#41;&#44; a simpler but valid way of classifying elastosis&#44; first defined by Landi et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> and considered by the World Health Organization &#40;WHO&#41; as a major characteristic that categorizes different types of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Kappa concordance for ulceration was substantial as former studies have stated&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;9&#44;17&#44;19&#44;20</span></a> Assessment of ulceration may be only possible in some histological sections of melanoma&#59; for instance&#44; ulceration may only touch a small portion of melanoma and go unnoticed in some glass sections&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">When there is a focal loss of epidermis&#44; it may be problematic to establish ulceration&#44; as it can be an actual ulceration or a sectioning artifact&#46; Unless there is evidence of a dermal scar or a previous biopsy&#44; it can be troublesome to distinguish between traumatic and non-traumatic ulceration&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Polypoid shape was highly reproducible in our experience as it is easy to assess&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">In terms of regression&#44; in our research&#44; its evaluation showed moderate concordance&#44; with heterogeneous rates being reported in former studies&#46; Most studies that assess several features showed low reproducibility<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a> while others showed higher rates&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> Kang et al&#46; showed better reproducibility for regression in their study&#44; yet we should mention that this study was only focused on regression&#46; It should be expected that a study associated with only one feature should reach higher concordance than studies assessing several variables&#44; especially if there is previous training&#46; Categorization of regression and criteria have changed over time&#44; which can be a cause of variable concordance&#46; In fact&#44; some studies consider early&#44; intermediate or late regression&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> while others only consider two grades &#40;presence or slight&#47;absence&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Literature is scarce on the interobserver reproducibility regarding necrosis and pleomorphism&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The variable pleomorphism is very subjective&#44; and melanoma cells from malignant tumors are pleomorphic in general&#44; particularly in some areas of the tumor&#46; This feature can be problematic as it can be difficult to stablish due to its subjectivity&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Regarding assessment of necrosis&#44; in Urso et al&#46; study&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> interobserver concordance was stablished for 55 cases of melanoma and necrosis was found in one case only&#46; Therefore&#44; since it is a less prevalent feature&#44; it can be a finding only made in a small area and go unnoticed&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Finally&#44; there is a really important fact we should mention which is subjectivity&#44; as it has been confirmed that even in some observations there is intraobserver discordance&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Consistent with this&#44; Elmore et al&#46; showed intraobserver discordance &#40;and logically lower interobserver discordance&#41; for categorizing atypia in melanocytic lesions&#44; especially when categorizing those with values different than the extreme values&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">We propose that&#44; if possible&#44; variables should be redefined and regrouped with fewer categories&#46; For example&#44; pagetoid spread could be categorized into two rather than four groups considering 0&#58; absence or minor pagetoid spread &#40;&#60;25&#37; of the cells&#41; and 1&#58; overt pagetoid spread &#40;&#62;25&#37; of the cells&#41;&#46; Similarly&#44; nest formation could be redefined as having two categories only&#59; 0&#58; non or minimal nest formation &#40;&#60;25&#37; of cells in intraepidermal nests&#41; vs 1&#58; marked nest formation &#40;&#62;25&#37; of cells in of intraepidermal nests&#41;&#46; Shape of cells&#44; epidermal contour and pigmentation could be also simplified in fewer categories&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">On the contrary&#44; there are some variables with low concordance that cannot be adjusted&#44; such as lateral circumscription&#46; Therefore&#44; we will probably not use this variable for this definition in the future&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Any adjustment of the categories of the variable like their regrouping&#44; if possible&#44; should be tested for reproducibility again&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">In our experience&#44; after regrouping and studying interobserver concordance of pagetoid spread and nest formation only in pagetoid spread improved&#46; It is an example that the regrouping of categories of variables can sometimes improve their reproducibility or&#44; at least&#44; maintain it&#44; while making sure its relevance remains untouched&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Perhaps it is still too early&#44; but new technologies and A&#46;I&#46; could be a before and after in the histological categorization of melanocytic lesions&#46; For this purpose&#44; it is necessary to generate useful algorithms that should be trained until their diagnostic sensitivity approaches that of an experienced pathologist&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">As a matter of fact&#44; a three-dimensional histology computer model of malignant melanoma has been tested with promising results&#46; It evaluated different tissue levels while avoiding the problem of some features being present in a limited subset of slides&#46; Although these are promising technologies in the field of histopathology diagnosis there are still some limitations that should be addressed&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study showed a median moderate reproducibility of several histopathological features of melanoma&#44; meaning that&#44; if possible&#44; some variables should be redefined and evaluated for interobserver agreement for future research&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Since the field of dermatopathology is not an exact science&#44; it is subject to personal subjectivity&#44; which sometimes causes disagreements on the diagnosis and assessment of some histological features&#46; In the case of melanoma&#44; some variables such as regression are associated with low interobserver agreement&#46; On the contrary&#44; other variables such as the measurement of Breslow thickness show high reproducibility&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods and main results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We conducted an observational and descriptive study at Hospital de Manises&#44; Valencia&#44; Spain&#44; IVO Foundation&#44; Valencia&#44; Spain&#44; and Hospital 12 de Octubre&#44; Madrid&#44; Spain&#46; The mean level of agreement of all study variables was moderate &#40;Cohen&#39;s kappa coefficient statistic<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#41;&#46; The highest agreement corresponded to polypoid morphology&#44; pigmentation&#44; ulceration&#44; and solar elastosis&#46; On the other hand&#44; the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our mean level of agreement was moderate&#44; which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility&#44; reestablished&#46; When conducting a research study&#44; it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature&#46; It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La dermatopatolog&#237;a no es una ciencia exacta estando sujeta a la subjetividad personal&#44; lo que en ocasiones provoca variabilidad interobservador en cuanto al diagn&#243;stico y la valoraci&#243;n de determinadas caracter&#237;sticas histol&#243;gicas&#46; Respecto al melanoma&#44; algunas variables como la regresi&#243;n presentan baja concordancia interobservador&#46; Por el contrario&#44; otras variables como la medici&#243;n del espesor de Breslow muestran una alta reproducibilidad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El principal objetivo de nuestro estudio fue investigar la reproducibilidad interobservador de m&#250;ltiples caracter&#237;sticas sobre un total de 60 casos consecutivos de melanoma&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos y resultados principales</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio observacional y descriptivo en el Hospital de Manises &#40;Manises&#41;&#44; la Fundaci&#243;n IVO &#40;Valencia&#41; y el Hospital 12 de Octubre &#40;Madrid&#41;&#46; La concordancia media de las variables del estudio fue moderada&#46; Las mayores tasas de concordancia se obtuvieron para la morfolog&#237;a polipoide&#44; la pigmentaci&#243;n&#44; la ulceraci&#243;n y la elastosis solar&#46; Por el contrario&#44; la concordancia m&#225;s baja se dio para la presencia de pleomorfismo celular y la necrosis tumoral&#46; Es necesario al realizar un estudio de investigaci&#243;n&#44; analizar las variables de estudio y demostrar su validez para medir o clasificar una determinada caracter&#237;stica&#46; Adicionalmente&#44; es recomendable garantizar que las variables sean reproducibles para poder utilizarlas en otros estudios o en la pr&#225;ctica cl&#237;nica habitual&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestra concordancia media fue moderada&#44; lo que refleja que algunas de las caracter&#237;sticas medidas como el pleomorfismo celular o la presencia de necrosis no pueden ser utilizadas para futuros estudios o&#44; por el contrario&#44; deben ser redefinidas y restablecida su reproducibilidad&#46;</p></span>"
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                  \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">Nesting&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;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">0&#46;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&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">Pigmentation&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;7&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;7&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
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                  \t\t\t\t">0&#46;7&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">Lateral circumscription&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;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">0&#46;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&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">Epidermal contour&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;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">0&#46;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="char" valign="\n
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                  \t\t\t\t">0&#46;4&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">Solar elastosis &#40;4 grades&#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
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                  \t\t\t\t">0&#46;8&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;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="char" valign="\n
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                  \t\t\t\t">0&#46;7&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">Pattern of growth&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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">Elastosis &#40;high CSD&#47;low CSD&#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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&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">Ulceration&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&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">Type of ulceration&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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
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                  \t\t\t\t">Polypoid shape&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&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">Regression&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">N&#47;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">N&#47;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="char" valign="\n
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                  \t\t\t\t">0&#46;5&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
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                  \t\t\t\t">Necrosis&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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                  \t\t\t\t">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&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">Pleomorphism&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                    0 => array:2 [
                      "titulo" => "Modern concepts in melanocytic tumors"
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                            0 => "A&#46; Fernandez-Flores"
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                      "titulo" => "Improving melanoma classification by integrating genetic and morphologic features"
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                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "A&#46; Viros"
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                            2 => "J&#46; Bauer"
                            3 => "K&#46; Lasithiotakis"
                            4 => "C&#46; Garbe"
                            5 => "D&#46; Pinkel"
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                    0 => array:2 [
                      "doi" => "10.1371/journal.pmed.0050120"
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                        "tituloSerie" => "PLoS Med"
                        "fecha" => "2008"
                        "volumen" => "5"
                        "paginaInicial" => "e120"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18532874"
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                      "titulo" => "Histopathologic recognition and grading of dysplastic melanocytic nevi&#58; an interobserver agreement study"
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                          "etal" => false
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                            2 => "J&#46;A&#46; Bruijn"
                            3 => "H&#46;R&#46; Byers"
                            4 => "M&#46;C&#46; Mihm"
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                        "tituloSerie" => "J Invest Dermatol"
                        "fecha" => "1993"
                        "volumen" => "100"
                        "paginaInicial" => "318S"
                        "paginaFinal" => "321S"
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                      "titulo" => "Interobserver variation in the histopathologic reporting of key prognostic parameters&#44; particularly Clark level&#44; affects pathologic staging of primary cutaneous melanoma"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
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                    0 => array:2 [
                      "doi" => "10.1097/SLA.0b013e31819ed973"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Surg"
                        "fecha" => "2009"
                        "volumen" => "249"
                        "paginaInicial" => "641"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
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Original Article
Interobserver Variability in the Histopathological Evaluation of Melanoma: Analysis of 60 Cases
Variabilidad interobservador en el análisis histológico del melanoma: análisis de 60 casos
V. Sanz-Motilvaa, A. Martorella, E. Manrique-Silvab, L. Terradez-Masc, C. Requenab, V. Travesd, O. Sanmartínb, J.L. Rodríguez-Peraltoe, E. Nagoreb,
Corresponding author
eduardo.nagore@ucv.es

Corresponding author.
a Department of Dermatology, Hospital de Manises, Valencia, Spain
b Department of Dermatology, Fundación Instituto Valenciano de Oncología, Valencia, Spain
c Department of Pathology, Hospital Clínico Universitario de Valencia, Valencia, Spain
d Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain
e Department of Pathology, Hospital Universitario 12 de Octubre, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Multiple morphological features are often used in the histopathological diagnosis of cutaneous melanoma&#46; These can be categorized into two major types such as architectural &#40;pagetoid infiltration and solar elastosis&#41; and cytological features &#40;melanocytic atypia and rate of mitoses&#44; among others&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Several features have prognostic implications&#44; the most important being the presence of ulceration and Breslow thickness&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Molecular biology is changing the way we see and classify melanocytic lesions&#44; and there have been interesting advances in this field over the past few years&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Moreover&#44; it is remarkable how heterogeneous melanoma can be in terms of its histopathological appearance&#46; Although this is probably due to multiple factors&#44; mutational status is gaining interest as it might determine some clinical and histopathological features such as the degree of pagetoid spread or the shape and size of melanoma cells&#46; In a previous study&#44; Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> defined some histopathological features associated with the presence of BRAF mutations&#46; BRAF mutated melanomas displayed an increased upward migration and nest formation of intraepidermal melanocytes&#44; a sharper demarcation towards the surrounding skin&#44; thickening of the involved epidermis&#44; rounder&#44; larger and more pigmented melanoma cells&#44; and thickening of the involved epidermis&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Histopathological reports of tumor characteristics are subject to interobserver variability&#44; so diagnosis and description of melanoma can often be problematic&#46; In melanocytic lesions&#44; several studies have reported a low level of agreement for some semi-quantitative features&#44; such as lymphocytic infiltration or regression&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">3&#8211;6</span></a> In addition&#44; the differential diagnosis between dysplastic nevi and early-stage invasive melanoma can sometimes be challenging too&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand&#44; some prognostic features generally have high interobserver reproducibility&#44; such as Breslow thickness and the presence of ulceration&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;6&#44;9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The main objective ot the study was to evaluate the concordance between the two groups for each pathologic feature assessed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Clinician panel and review procedure</span><p id="par0040" class="elsevierStylePara elsevierViewall">Our study was conducted by two groups of researchers&#44; the first one included two dermatopathologists from the same institution &#40;IVO&#41; and the second&#44; one pathologist &#40;HUDO&#41; and one dermatologist &#40;HM&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The dermatologist performed the histological assessment always under supervision and accompanied by the pathologist and had experience in dermatopathology &#40;held a 4-month internship in the dermatopathology unit at Hospital Universitario 12 de Octubre&#44; Madrid&#44; Spain and a 15-day short internship in Ackerman Academy&#44; New York City&#44; NY&#44; United States&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study was conducted in two stages&#46; Stage &#35;1 was the pre-selection of the histologic features to be studied&#44; as well as their definitions&#46; This was done considering previous literature&#44; specifically Viros et al&#46; research work&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and preliminary meetings of the research group in which a subset of 40 samples with different mutational status was examined&#46; We decided to include some extra features based on their prevalence&#46; This stage also included an assessment of the level of agreement in a training set of 10 samples to identify and resolve discrepancies in the assessment of the definitive variables&#46; This assessment was performed separately by each of the two groups&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Finally&#44; the last stage was performed the same way but with the final sample set on which the present study was conducted&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cases studied</span><p id="par0060" class="elsevierStylePara elsevierViewall">The histological sections were obtained consecutively from IVO pathology files from January 2004 through December 2004&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Demographic data including age&#44; sex&#44; location&#44; type of melanoma&#44; Breslow thickness and Clark level were retrieved from the IVO Melanoma Database&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Tissue fragments were fixed in formalin&#44; routinely processed and stained with haematoxylin and eosin&#46; All cases that were not optimal for review were excluded&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Histopathological features</span><p id="par0075" class="elsevierStylePara elsevierViewall">Specific features analyzed by Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> were included in our analysis&#58;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Upward spread of intraepidermal melanocytes or pagetoid spread &#40;100&#37; melanocytes at the dermoepidermal junction&#44; 75&#37; up to 100&#37; melanocytes at the dermoepidermal junction&#44; 50&#37; pagetoid spread&#44; &#62;50&#37; pagetoid spread&#41;&#44; nest formation of intraepidermal melanocytes &#40;no nests&#44; &#60;25&#37; melanocytes in nests&#44; 25&#37; up to 50&#37; melanocytes in nests&#44; &#62;50&#37; melanocytes in nests&#41;&#44; pigmentation of melanocytes &#40;absence&#44; slight&#44; moderate&#44; high&#44; very high&#41;&#44; epidermal contour &#40;atrophic&#44; thinned&#44; normal&#44; thickened&#44; hypertrophic&#41;&#44; lateral circumscription &#40;discontinuous&#44; gradual but continuous&#44; abrupt&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We also included some additional features given their potential interest&#58;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Pattern of growth &#40;expansive vs infiltrative&#41;&#44; solar elastosis &#40;categorized in two ways&#58; 1 &#8211; absence&#44; minimum&#44; moderate&#44; and high&#59; and 2 &#8211; low vs high&#41;&#44; presence of ulceration &#40;absence vs presence&#41;&#44; type of ulceration &#40;expansive vs infiltrative&#41;&#44; polypoid shape &#40;absence vs presence&#41;&#44; regression &#40;absence&#44; &#8804;50&#37;&#44; &#62;50&#37;&#41;&#44; presence of necrosis &#40;absence vs presence&#41;&#44; and presence of pleomorphism &#40;absence vs presence&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Their definitions are described in detail in the <a class="elsevierStyleCrossRef" href="#sec0050">supplementary data</a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0100" class="elsevierStylePara elsevierViewall">Results were exported to an Excel table&#46; When a feature or an entire case could not be evaluated for whatever reasons&#44; it was considered as non-applicable&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Agreement among the two groups was assessed using Cohen&#39;s kappa coefficient statistic &#40;<span class="elsevierStyleItalic">&#954;</span>&#41;&#44; which is a known index for measuring chance corrected agreement on a nominal or ordinal scale&#46; According to Landis and Koch&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> values &#62;0&#46;75 represent excellent agreement beyond chance&#44; values between 0&#46;75 and 0&#46;40 represent fair to good agreement beyond chance&#44; and values &#60;0&#46;40 represent poor agreement beyond chance&#46; A <span class="elsevierStyleItalic">&#954;</span> value close to one means almost perfect agreement&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In the case of ordinal variables&#44; we used Cohen&#39;s weighted kappa &#8211; a modification of the original kappa statistic &#8211; proposed for nominal variables in the presence of two observers&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">For each characteristic considered&#44; a 2<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2 diagnostic table was built using dichotomous categories&#44; and specific <span class="elsevierStyleItalic">&#954;</span> values were calculated&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0120" class="elsevierStylePara elsevierViewall">The first 60 consecutive cases diagnosed in the IVO Dermatology service from January 2004 through December 2004 were selected&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Five cases were excluded&#44; four of them because they could not be interpreted due to their small size and one because of duplication &#40;two sections of the same case&#41;&#46; So&#44; eventually 55 valid cases were considered to stablish kappa values&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The study population included 55 patients&#44; 28 &#40;50&#46;9&#37;&#41; men and 27 &#40;49&#46;1&#37;&#41; women&#44; with a mean age at diagnosis of 58&#46;9 years &#40;range&#44; 23&#8211;82 years&#41;&#46; Data on the location of the primary tumor&#44; the histological type and the tumor stage are shown in <a class="elsevierStyleCrossRef" href="#sec0050">Table 1 of the supplementary data</a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">General concordance was moderate &#40;median kappa value&#44; 0&#46;5&#41;&#46; Maximum values were for presence of polypoid shape &#40;0&#46;8&#41;&#44; pigmentation &#40;0&#46;7&#41;&#44; presence of ulceration &#40;0&#46;7&#41; elastosis &#40;high CSD&#47;low CSD&#41; 0&#46;7&#44; and degree of elastosis &#40;0&#46;7&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The most discordant values were the presence of pleomorphism &#40;0&#46;2&#41; and necrosis &#40;0&#46;3&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the kappa values from different studies&#44; specifically our results and those from the studies conducted by Viros et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> and Broekaert et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0150" class="elsevierStylePara elsevierViewall">Finally&#44; we conducted an adjustment of the variables pagetoid spread and formation of intraepidermal nests and assessed the interobserver agreement&#46; Specifically&#44; we reduced the number of categories from 4 down to 2&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">&#954;</span> value for pagetoid spread was 0&#46;7 and the <span class="elsevierStyleItalic">&#954;</span> value for nest formation&#44; 0&#46;4&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">In this study&#44; we examined the reproducibility or interobserver agreement of some characteristics of 60 cases of malignant melanoma&#44; some of them with prognostic implications&#46; The overall concordance was moderate&#46; The highest kappa values were for polypoid shape and solar elastosis &#40;high CSD&#47;low CSD&#41;&#46; On the other hand&#44; the lowest values reported were for necrosis and pleomorphism&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Melanoma is a heterogeneous tumor as it shows different clinical and histopathological characteristics&#44; sometimes making diagnosis challenging&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Former studies have evaluated the interobserver reproducibility of diagnostic criteria in melanoma and other melanocytic lesions with heterogeneous results&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">2&#44;4&#44;8&#44;9&#44;13&#8211;16</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">These studies often perform the circulation of pathological sections of cutaneous melanomas or melanocytic lesions to different combinations of pathologists and dermatopathologists to categorize multiple histopathological variables&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The highest concordance rates were achieved for the most important variable in terms of prognostic value for Breslow thickness&#46; This is something predictable as it is a quantitative variable&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">4&#44;6&#44;9&#44;14&#44;17&#8211;20</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">On the contrary&#44; some other variables with prognostic importance show low or moderate reproducibility as Clark level assessment&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">9&#44;14&#44;19&#44;20</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Our study is based on several variables that were defined in the study by Viros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> This study showed better kappa values for most of the variables tested compared to our results<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Another study undertaken by the same group &#40;Broekaert et al&#46;&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> presented similar kappa values&#44; except for nesting&#44; epidermal contour and circumscription that were lower than the values obtained in the study conducted by Viros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">An explanation for some of the discordances reported may be that melanoma can be a very large lesion and show overt heterogenicity <span class="elsevierStyleItalic">per se</span>&#46; Therefore&#44; when considering nest formation or pagetoid spread&#44; an area with high number of nests or intraepidermal spread can exist followed by another with total absence&#44; which complicates providing a result to quantify this finding&#46; Additionally&#44; some features can be detected only in some glass sections&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Regarding lateral circumscription and epidermal contour&#44; we have detected that often&#44; melanoma can show different transitions from the intraepidermal growth portion of the tumor to normal skin from one to the other side of the glass section&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">It is remarkable that solar elastosis was more reproducible than other variables when assessed in two categories &#40;high CSD&#47;low CSD&#41;&#44; a simpler but valid way of classifying elastosis&#44; first defined by Landi et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a> and considered by the World Health Organization &#40;WHO&#41; as a major characteristic that categorizes different types of melanoma&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Kappa concordance for ulceration was substantial as former studies have stated&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;9&#44;17&#44;19&#44;20</span></a> Assessment of ulceration may be only possible in some histological sections of melanoma&#59; for instance&#44; ulceration may only touch a small portion of melanoma and go unnoticed in some glass sections&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">When there is a focal loss of epidermis&#44; it may be problematic to establish ulceration&#44; as it can be an actual ulceration or a sectioning artifact&#46; Unless there is evidence of a dermal scar or a previous biopsy&#44; it can be troublesome to distinguish between traumatic and non-traumatic ulceration&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">9</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Polypoid shape was highly reproducible in our experience as it is easy to assess&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">In terms of regression&#44; in our research&#44; its evaluation showed moderate concordance&#44; with heterogeneous rates being reported in former studies&#46; Most studies that assess several features showed low reproducibility<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">6&#44;19&#44;20</span></a> while others showed higher rates&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> Kang et al&#46; showed better reproducibility for regression in their study&#44; yet we should mention that this study was only focused on regression&#46; It should be expected that a study associated with only one feature should reach higher concordance than studies assessing several variables&#44; especially if there is previous training&#46; Categorization of regression and criteria have changed over time&#44; which can be a cause of variable concordance&#46; In fact&#44; some studies consider early&#44; intermediate or late regression&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a> while others only consider two grades &#40;presence or slight&#47;absence&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">19&#44;20</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Literature is scarce on the interobserver reproducibility regarding necrosis and pleomorphism&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">The variable pleomorphism is very subjective&#44; and melanoma cells from malignant tumors are pleomorphic in general&#44; particularly in some areas of the tumor&#46; This feature can be problematic as it can be difficult to stablish due to its subjectivity&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Regarding assessment of necrosis&#44; in Urso et al&#46; study&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> interobserver concordance was stablished for 55 cases of melanoma and necrosis was found in one case only&#46; Therefore&#44; since it is a less prevalent feature&#44; it can be a finding only made in a small area and go unnoticed&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Finally&#44; there is a really important fact we should mention which is subjectivity&#44; as it has been confirmed that even in some observations there is intraobserver discordance&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Consistent with this&#44; Elmore et al&#46; showed intraobserver discordance &#40;and logically lower interobserver discordance&#41; for categorizing atypia in melanocytic lesions&#44; especially when categorizing those with values different than the extreme values&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">8</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">We propose that&#44; if possible&#44; variables should be redefined and regrouped with fewer categories&#46; For example&#44; pagetoid spread could be categorized into two rather than four groups considering 0&#58; absence or minor pagetoid spread &#40;&#60;25&#37; of the cells&#41; and 1&#58; overt pagetoid spread &#40;&#62;25&#37; of the cells&#41;&#46; Similarly&#44; nest formation could be redefined as having two categories only&#59; 0&#58; non or minimal nest formation &#40;&#60;25&#37; of cells in intraepidermal nests&#41; vs 1&#58; marked nest formation &#40;&#62;25&#37; of cells in of intraepidermal nests&#41;&#46; Shape of cells&#44; epidermal contour and pigmentation could be also simplified in fewer categories&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">On the contrary&#44; there are some variables with low concordance that cannot be adjusted&#44; such as lateral circumscription&#46; Therefore&#44; we will probably not use this variable for this definition in the future&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Any adjustment of the categories of the variable like their regrouping&#44; if possible&#44; should be tested for reproducibility again&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">In our experience&#44; after regrouping and studying interobserver concordance of pagetoid spread and nest formation only in pagetoid spread improved&#46; It is an example that the regrouping of categories of variables can sometimes improve their reproducibility or&#44; at least&#44; maintain it&#44; while making sure its relevance remains untouched&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Perhaps it is still too early&#44; but new technologies and A&#46;I&#46; could be a before and after in the histological categorization of melanocytic lesions&#46; For this purpose&#44; it is necessary to generate useful algorithms that should be trained until their diagnostic sensitivity approaches that of an experienced pathologist&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a></p><p id="par0285" class="elsevierStylePara elsevierViewall">As a matter of fact&#44; a three-dimensional histology computer model of malignant melanoma has been tested with promising results&#46; It evaluated different tissue levels while avoiding the problem of some features being present in a limited subset of slides&#46; Although these are promising technologies in the field of histopathology diagnosis there are still some limitations that should be addressed&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a></p><p id="par0290" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study showed a median moderate reproducibility of several histopathological features of melanoma&#44; meaning that&#44; if possible&#44; some variables should be redefined and evaluated for interobserver agreement for future research&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Since the field of dermatopathology is not an exact science&#44; it is subject to personal subjectivity&#44; which sometimes causes disagreements on the diagnosis and assessment of some histological features&#46; In the case of melanoma&#44; some variables such as regression are associated with low interobserver agreement&#46; On the contrary&#44; other variables such as the measurement of Breslow thickness show high reproducibility&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The main objective of our study was to investigate multiple features of 60 consecutive cases of melanoma to establish interobserver reproducibility&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods and main results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We conducted an observational and descriptive study at Hospital de Manises&#44; Valencia&#44; Spain&#44; IVO Foundation&#44; Valencia&#44; Spain&#44; and Hospital 12 de Octubre&#44; Madrid&#44; Spain&#46; The mean level of agreement of all study variables was moderate &#40;Cohen&#39;s kappa coefficient statistic<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#41;&#46; The highest agreement corresponded to polypoid morphology&#44; pigmentation&#44; ulceration&#44; and solar elastosis&#46; On the other hand&#44; the lowest level agreement was reached for the presence of cellular pleomorphism and tumor necrosis&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Our mean level of agreement was moderate&#44; which reflects that some of the measured characteristics such as cellular pleomorphism or the presence of necrosis cannot be used for future studies or must be redefined and their reproducibility&#44; reestablished&#46; When conducting a research study&#44; it is necessary to analyze the study variables to demonstrate their validity to measure or classify a certain feature&#46; It is also advisable to warrant that that the variables are reproducible to be able to use them for other studies or in the routine clinical practice&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La dermatopatolog&#237;a no es una ciencia exacta estando sujeta a la subjetividad personal&#44; lo que en ocasiones provoca variabilidad interobservador en cuanto al diagn&#243;stico y la valoraci&#243;n de determinadas caracter&#237;sticas histol&#243;gicas&#46; Respecto al melanoma&#44; algunas variables como la regresi&#243;n presentan baja concordancia interobservador&#46; Por el contrario&#44; otras variables como la medici&#243;n del espesor de Breslow muestran una alta reproducibilidad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El principal objetivo de nuestro estudio fue investigar la reproducibilidad interobservador de m&#250;ltiples caracter&#237;sticas sobre un total de 60 casos consecutivos de melanoma&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos y resultados principales</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un estudio observacional y descriptivo en el Hospital de Manises &#40;Manises&#41;&#44; la Fundaci&#243;n IVO &#40;Valencia&#41; y el Hospital 12 de Octubre &#40;Madrid&#41;&#46; La concordancia media de las variables del estudio fue moderada&#46; Las mayores tasas de concordancia se obtuvieron para la morfolog&#237;a polipoide&#44; la pigmentaci&#243;n&#44; la ulceraci&#243;n y la elastosis solar&#46; Por el contrario&#44; la concordancia m&#225;s baja se dio para la presencia de pleomorfismo celular y la necrosis tumoral&#46; Es necesario al realizar un estudio de investigaci&#243;n&#44; analizar las variables de estudio y demostrar su validez para medir o clasificar una determinada caracter&#237;stica&#46; Adicionalmente&#44; es recomendable garantizar que las variables sean reproducibles para poder utilizarlas en otros estudios o en la pr&#225;ctica cl&#237;nica habitual&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nuestra concordancia media fue moderada&#44; lo que refleja que algunas de las caracter&#237;sticas medidas como el pleomorfismo celular o la presencia de necrosis no pueden ser utilizadas para futuros estudios o&#44; por el contrario&#44; deben ser redefinidas y restablecida su reproducibilidad&#46;</p></span>"
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            "titulo" => "Introducci&#243;n"
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          0 => array:4 [
            "apendice" => "<p id="par0305" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article&#58;<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>"
            "etiqueta" => "Appendix A"
            "titulo" => "Supplementary data"
            "identificador" => "sec0055"
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        ]
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">Viros et al&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a>&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
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Broekaert et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Our study&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Spread&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  " align="left" valign="\n
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                  \t\t\t\t">0&#46;7&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
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                  \t\t\t\t">0&#46;7&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  " align="char" valign="\n
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                  \t\t\t\t">0&#46;5&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
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                  \t\t\t\t">Nesting&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  " align="left" valign="\n
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                  \t\t\t\t">0&#46;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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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  " align="char" valign="\n
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                  \t\t\t\t">0&#46;5&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">Pigmentation&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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                  \t\t\t\t">0&#46;7&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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                  \t\t\t\t">0&#46;7&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
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                  \t\t\t\t">0&#46;7&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">Lateral circumscription&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;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">0&#46;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&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">Epidermal contour&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;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">0&#46;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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">Solar elastosis &#40;4 grades&#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">0&#46;8&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;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&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">Pattern of growth&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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">Elastosis &#40;high CSD&#47;low CSD&#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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&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">Ulceration&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;7&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">Type of ulceration&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;4&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">Polypoid shape&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;8&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">Regression&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;5&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">Necrosis&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">N&#47;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">N&#47;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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&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">Pleomorphism&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">N&#47;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
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                  \t\t\t\t">N&#47;A&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                    0 => array:2 [
                      "titulo" => "Modern concepts in melanocytic tumors"
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                            0 => "A&#46; Fernandez-Flores"
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                      "doi" => "10.1016/j.ad.2023.01.001"
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                        "tituloSerie" => "Actas Dermosifiliogr"
                        "fecha" => "2023"
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Original language: English
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