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the magnitude of this diagnostic yield increase has barely been reported&#46; Moreover&#44; since CB methods can be time consuming and labor intensive they may not be routine in some centers&#44; only being performed at the discretion of the pathologist or clinician&#46; Our aim was to analyze&#44; in the largest series reported to date&#44; the usefulness of CBs beyond conventional cytological smears in the diagnosis of malignant effusions&#46; Biochemical fluid characteristics predictive of the generation of inappropriate or insufficient CB material were also addressed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">The medical records of all consecutive patients at our institution between October 2010 and June 2016 whose pleural fluids had been sent for conventional cytology and&#47;or CB examination&#44; based on the attending physician&#39;s criterion&#44; were retrospectively reviewed&#46; The local ethics committee approved the study protocol&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Pleural fluid specimens were collected in heparinized tubes&#46; For routine cytology&#44; 5<span class="elsevierStyleHsp" style=""></span>mL of fluid were centrifuged at 2000<span class="elsevierStyleHsp" style=""></span>rpm for 10<span class="elsevierStyleHsp" style=""></span>min&#44; the supernatant discarded&#44; and the glass slides prepared and stained with Papanicolaou stain&#46; For CB preparation&#44; 10<span class="elsevierStyleHsp" style=""></span>mL of material were centrifuged as above&#44; the supernatant decanted&#44; and the cell button obtained &#40;with the addition of molten agar if necessary&#41; fixed in 10&#37; formaldehyde&#44; paraffin embedded and stained with hematoxylin&#8211;eosin&#46; Immunocytochemistry panels on CB sections were applied according to the suspected tumor type and cytomorphology&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">An effusion was categorized as definite malignant if malignant cells were detected upon cytological examination of pleural fluid or biopsy specimens&#46; A diagnosis of probable malignant effusion was made on patients who met the following&#58; &#40;a&#41; a known primary tumor or extrapleural metastases of undetermined origin&#44; and &#40;b&#41; a pleural exudate with negative fluid cytological findings&#44; after ruling out other potential causes of fluid accumulation by clinical data &#40;e&#46;g&#46; negative pleural fluid cultures&#44; low pleural adenosine deaminase levels&#41;&#44; imaging &#40;e&#46;g&#46; CT angiography&#41; and&#44; in selected cases&#44; pleural biopsy&#46; All patients with probable MPE were followed up long enough to determine whether alternative causes of the effusion became clinically apparent&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sensitivity of fluid smears and CBs were calculated&#46; The Kruskal&#8211;Wallis test was used to compare pleural fluid biochemistries &#40;i&#46;e&#46;&#44; red and white blood cell counts&#44; differential white cell count&#44; protein&#44; lactate dehydrogenase &#40;LDH&#41;&#44; glucose&#44; adenosine deaminase&#44; pH and C-reactive protein&#41; between patients with representative and suboptimal CB material&#46; The statistical significance level was set at 0&#46;05 &#40;two-tailed&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">During the study period&#44; 632 cytological smears and 554 CBs from 414 patients &#40;median age 70 years&#44; 56&#37; men&#41; who had malignant effusions were examined&#46; The etiological distribution of the primary tumors is displayed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Also&#44; there were 726 patients eventually diagnosed with a benign pleural condition for whom pleural fluid cytological analyses were ordered &#40;a total of 945 smears and 507 CBs&#41; and yielded negative results&#59; all were excluded for the purpose of the study&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Although all effusions were submitted to a first cytologic examination&#44; CBs were initially obtained from 380 &#40;92&#37;&#41; specimens&#44; but 46 &#40;12&#37;&#41; yielded suboptimal material&#46; Whether a first cytological smear or CB examination was used&#44; both had identical sensitivity for identifying malignancy&#58; 44&#37; &#40;95&#37; CI 39&#8211;50&#37;&#41;&#46; Notably&#44; of 184 cancer patients who had a first negative cytological exam&#44; CB was diagnostic of malignancy in 18 &#40;10&#37;&#44; 95&#37; CI 6&#8211;15&#37;&#41;&#46; Conversely&#44; among the 186 patients with a first negative CB examination&#44; cytological smears were positive in 20 &#40;11&#37;&#44; 95&#37; CI 7&#8211;16&#37;&#41;&#46; If any further cytology and CB assessments in patients with previous negative results were considered&#44; the global discrepancy was as follows&#58; 11&#37; &#40;95&#37; CI 7&#8211;17&#37;&#41; smears negative&#47;CBs positive&#44; and 15&#37; &#40;95&#37; CI 11&#8211;21&#37;&#41; smears positive&#47;CBs negative&#46; Overall&#44; 74 of the 554 CB preparations &#40;13&#37;&#44; 95&#37; CI 11&#8211;16&#37;&#41; resulted in inappropriate material for interpretation or diagnosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Immunocytochemical studies were performed on 157 &#40;34&#37;&#41; CBs&#44; particularly in those regarded as positive by cytomorphology &#40;85&#37; vs 1&#46;7&#37;&#41;&#44; with a median of 3 &#40;25th to 75th percentiles 1&#8211;4&#41; immunostains per case&#46; From a total of 480 immunostainings&#44; the most commonly used&#44; in order of decreasing frequency&#44; were TTF-1 &#40;138&#44; 29&#37;&#41;&#44; estrogen receptor &#40;60&#44; 13&#37;&#41;&#44; CK 7 &#40;47&#44; 47&#37;&#41;&#44; CK 20 &#40;43&#44; 9&#37;&#41;&#44; p63 &#40;30&#44; 6&#37;&#41;&#44; calretinin &#40;25&#44; 5&#37;&#41;&#44; mammaglobin &#40;21&#44; 4&#37;&#41;&#44; WT1 &#40;17&#44; 4&#37;&#41;&#44; and CK 19 &#40;15&#44; 3&#37;&#41;&#44; among others&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The sequential sensitivity of separated pleural fluid smears&#44; CBs or their combination for establishing the diagnosis of malignant pleural effusions is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; In general&#44; cytological studies eventually identified 233 &#40;56&#37;&#44; 95&#37; CI 51&#8211;61&#37;&#41; malignant cases&#46; It was also demonstrated that the yield by sending more than two specimens is negligible&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As compared with the reported positive and negative CBs&#44; suboptimal CB materials exhibited significantly lower median red blood cell &#40;10&#44;250&#47;&#956;L vs 3600&#47;&#956;L vs 2200&#47;&#956;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and leukocyte counts &#40;905&#47;&#956;L vs 1158&#47;&#956;L vs 392&#47;&#956;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Furthermore&#44; higher median LDH levels &#40;732<span class="elsevierStyleHsp" style=""></span>U&#47;L vs 434<span class="elsevierStyleHsp" style=""></span>U&#47;L vs 394<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and decreased pH values &#40;7&#46;42 vs 7&#46;46 vs 7&#46;47&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; were associated with a greater likelihood of obtaining a positive CB result rather than a negative one or an insufficient CB&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">This study suggests that the examination of CBs alongside fluid smears is a valuable first step in the diagnostic workup for any suspected malignant effusion&#46; Conventional pleural fluid cytology is negative for malignant cells in up to 40&#37; of malignant effusions&#44; and in an even greater proportion in mesotheliomas and squamous cell lung carcinomas&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> Although CB is an old methodology for the diagnosis of serous effusions&#44; few studies have suggested its potential diagnostic superiority as compared to cytological smears&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">5&#8211;12</span></a> In brief&#44; they have reported that CBs increase the diagnostic yield for malignancy by 5&#8211;15&#37; over routine cytology&#46; However&#44; the inclusion of a small number of cases &#40;no study recruited more than 60 malignant effusions&#41; limits the validity of the results&#46; Even an earlier report casts doubt on the cost-effectiveness of preparing CBs and advocated for cytology smears alone&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> Of note&#44; a recent survey among last two-year Spanish residents of Pneumology or Internal Medicine showed that only 16&#37; of 139 responders in their clinical practice actively ordered a CB when confronted with a suspected malignant effusion&#44; whereas the remaining either never did &#40;27&#37;&#41; or left the decision to the pathologist discretion &#40;57&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> Therefore&#44; despite clinical guidelines which consider CB techniques to be a useful addition for diagnostic purposes&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">3&#44;15</span></a> it appears that too little attention has been paid to this recommendation&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">CBs have some advantages over cytological smears which may facilitate the diagnosis of malignancy<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a>&#58; &#40;a&#41; a better appreciation of tissue architecture &#40;e&#46;g&#46;&#44; acinar or papillary structures&#44; intracytoplasmatic mucin&#41;&#44; &#40;b&#41; an easier cytomorphological distinction between reactive mesothelial cells and mesothelioma or metastatic adenocarcinoma&#44; and &#40;c&#41; the possibility of processing multiple sections for immunocytochemistry&#46; Of interest&#44; smears and CBs were found to have the same sensitivity &#40;44&#37; on a first specimen&#41;&#44; but discrepant results &#40;i&#46;e&#46;&#44; negative smears and positive CBs&#44; or vice versa in 11&#37; and 15&#37; of cases&#44; respectively&#41; pointed to their complementary value&#46; Therefore&#44; CBs are not a substitute for fluid smears&#44; but rather an additional technique for increasing diagnostic accuracy&#46; It was also found that pleural fluids containing low red blood and&#47;or leukocyte cell counts are likely more unsuitable for CB preparation&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our reported sensitivity for a first cytological pleural fluid specimen &#40;44&#37;&#41; is on the lower end of the spectrum for malignant effusion diagnoses&#46; However&#44; it is in line with our previous series from the 1993&#8211;2006 period in which the yield of a first cytological analysis among 466 patients with malignant effusions was reported to be 48&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> It should be highlighted that we only send 5<span class="elsevierStyleHsp" style=""></span>mL of pleural fluid for smears preparation&#44; and that the incidence of positive results depends on the volume of pleural fluid submitted &#40;the larger the amount the greater the diagnostic accuracy&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> and other factors such as the number of specimens evaluated &#40;i&#46;e&#46;&#44; more than two specimens do not increase sensitivity sufficiently to be clinically meaningful&#41;&#44; the way in which the specimens are examined &#40;e&#46;g&#46;&#44; CBs along with smears&#44; as this study supports&#41;&#44; the tumor type&#44; and the experience of the cytopathologist&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">This study has limitations&#46; First&#44; it is retrospective&#46; Second&#44; pathologists were not blinded of clinical data and the interpretation of CBs may also have been influenced by the results of cytology smears&#44; which however&#44; is a reflection of daily practice&#46; Finally&#44; in a third of pleural effusions the malignant nature was not confirmed by pleural biopsy&#44; though it was based on solid clinical grounds&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study suggests that clinicians should be encouraged to request&#44; along with the conventional routine cytology&#44; CBs of pleural fluid on which immunocytochemical staining can be performed&#44; in order to increase diagnostic sensitivity and establish a more definitive cytopathological diagnosis&#44; whenever a malignant condition is suspected&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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    "fechaRecibido" => "2016-09-20"
    "fechaAceptado" => "2016-11-09"
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          "clase" => "keyword"
          "titulo" => "Keywords"
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            0 => "Pleural effusion"
            1 => "Cytology"
            2 => "Cell blocks"
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          "palabras" => array:3 [
            0 => "Derrame pleural"
            1 => "Citolog&#237;a"
            2 => "Bloques celulares"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the independent usefulness of pleural fluid smear and cell block &#40;CB&#41; preparations for the diagnosis of malignant effusions&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The diagnostic yield of a first specimen was 44&#37; regardless of whether a smear or CB cytologic examination was performed&#46; The use of subsequent separated specimens increased the identification of malignancy to 56&#37;&#46; Overall&#44; 11&#37; of samples found to be negative by cytologic smears showed malignant cells on CBs&#44; whereas 15&#37; of negative CBs were reported as positive on smear slides&#46; Pleural fluid specimens with low red and&#47;or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">If CBs and smears are prepared and examined&#44; the percentage of positive diagnoses will be greater than if only one method is used&#46;</p></span>"
        "secciones" => array:4 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la utilidad independiente de frotis y bloques celulares &#40;BC&#41; del l&#237;quido pleural para diagnosticar derrames malignos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron retrospectivamente un total de 632 frotis citol&#243;gicos y 554 BC de 414 pacientes consecutivos con derrame pleural maligno&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La sensibilidad diagn&#243;stica de una primera muestra fue del 44&#37;&#44; tanto en frotis como en BC&#46; El an&#225;lisis de muestras separadas ulteriores aument&#243; al 56&#37; la identificaci&#243;n de derrames malignos&#46; Globalmente&#44; el 11&#37; de muestras negativas mediante frotis mostraron c&#233;lulas malignas en los BC&#44; mientras que el 15&#37; de BC negativos resultaron positivos en el estudio del frotis&#46; Los l&#237;quidos pleurales con recuentos bajos de hemat&#237;es o leucocitos produjeron con mayor frecuencia BC insuficientes para diagn&#243;stico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Si se eval&#250;an frotis y BC&#44; el porcentaje de resultados positivos es superior que si se emplean estas t&#233;cnicas de forma aislada&#46;</p></span>"
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            "titulo" => "Resultados"
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            "titulo" => "Conclusiones"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tumor type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Definite malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Probable malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lung&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">183 &#40;44&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Squamous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Small cell&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Non-small cell unspecified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sarcoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Breast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unknown origin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastrointestinal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;6&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ovary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pancreas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kidney&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;2&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mesothelioma&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;1&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31 &#40;7&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">260 &#40;63&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">154 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">414&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183 of 414<br>44&#37; &#40;39&#8211;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">167 of 334<br>50&#37; &#40;45&#8211;55&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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Brief Original
Examination of cytological smears and cell blocks of pleural fluid: Complementary diagnostic value for malignant effusions
Examen del frotis citológico y bloque celular del líquido pleural: valor diagnóstico complementario en los derrames malignos
J.M. Porcela,
Corresponding author
jporcelp@yahoo.es

Corresponding author.
, M. Quirósa, S. Gatiusb, S. Bielsaa
a Pleural Medicine Unit, Arnau de Vilanova University Hospital, Lleida, Spain
b Department of Pathology, Arnau de Vilanova University Hospital, Lleida, Spain
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            "entidad" => "Pleural Medicine Unit&#44; Arnau de Vilanova University Hospital&#44; Lleida&#44; Spain"
            "etiqueta" => "a"
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          1 => array:3 [
            "entidad" => "Department of Pathology&#44; Arnau de Vilanova University Hospital&#44; Lleida&#44; Spain"
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            "identificador" => "aff0010"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Examen del frotis citol&#243;gico y bloque celular del l&#237;quido pleural&#58; valor diagn&#243;stico complementario en los derrames malignos"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cytologic examination of pleural fluid is the easiest and least invasive way to diagnose malignant effusions&#44; although it has limited sensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> The routine cytopreparatory technique consists of sample centrifugation&#44; smearing of the cell deposit and Papanicolau staining&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> Scientific guidelines indicate that preparing cell blocks &#40;CBs&#41; from pleural effusion samples&#44; in addition to smears&#44; to allow for &#8220;microhistology&#8221; of the cellular solid portion may lead to greater diagnostic accuracy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> However&#44; the magnitude of this diagnostic yield increase has barely been reported&#46; Moreover&#44; since CB methods can be time consuming and labor intensive they may not be routine in some centers&#44; only being performed at the discretion of the pathologist or clinician&#46; Our aim was to analyze&#44; in the largest series reported to date&#44; the usefulness of CBs beyond conventional cytological smears in the diagnosis of malignant effusions&#46; Biochemical fluid characteristics predictive of the generation of inappropriate or insufficient CB material were also addressed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">The medical records of all consecutive patients at our institution between October 2010 and June 2016 whose pleural fluids had been sent for conventional cytology and&#47;or CB examination&#44; based on the attending physician&#39;s criterion&#44; were retrospectively reviewed&#46; The local ethics committee approved the study protocol&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Pleural fluid specimens were collected in heparinized tubes&#46; For routine cytology&#44; 5<span class="elsevierStyleHsp" style=""></span>mL of fluid were centrifuged at 2000<span class="elsevierStyleHsp" style=""></span>rpm for 10<span class="elsevierStyleHsp" style=""></span>min&#44; the supernatant discarded&#44; and the glass slides prepared and stained with Papanicolaou stain&#46; For CB preparation&#44; 10<span class="elsevierStyleHsp" style=""></span>mL of material were centrifuged as above&#44; the supernatant decanted&#44; and the cell button obtained &#40;with the addition of molten agar if necessary&#41; fixed in 10&#37; formaldehyde&#44; paraffin embedded and stained with hematoxylin&#8211;eosin&#46; Immunocytochemistry panels on CB sections were applied according to the suspected tumor type and cytomorphology&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">An effusion was categorized as definite malignant if malignant cells were detected upon cytological examination of pleural fluid or biopsy specimens&#46; A diagnosis of probable malignant effusion was made on patients who met the following&#58; &#40;a&#41; a known primary tumor or extrapleural metastases of undetermined origin&#44; and &#40;b&#41; a pleural exudate with negative fluid cytological findings&#44; after ruling out other potential causes of fluid accumulation by clinical data &#40;e&#46;g&#46; negative pleural fluid cultures&#44; low pleural adenosine deaminase levels&#41;&#44; imaging &#40;e&#46;g&#46; CT angiography&#41; and&#44; in selected cases&#44; pleural biopsy&#46; All patients with probable MPE were followed up long enough to determine whether alternative causes of the effusion became clinically apparent&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sensitivity of fluid smears and CBs were calculated&#46; The Kruskal&#8211;Wallis test was used to compare pleural fluid biochemistries &#40;i&#46;e&#46;&#44; red and white blood cell counts&#44; differential white cell count&#44; protein&#44; lactate dehydrogenase &#40;LDH&#41;&#44; glucose&#44; adenosine deaminase&#44; pH and C-reactive protein&#41; between patients with representative and suboptimal CB material&#46; The statistical significance level was set at 0&#46;05 &#40;two-tailed&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0030" class="elsevierStylePara elsevierViewall">During the study period&#44; 632 cytological smears and 554 CBs from 414 patients &#40;median age 70 years&#44; 56&#37; men&#41; who had malignant effusions were examined&#46; The etiological distribution of the primary tumors is displayed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Also&#44; there were 726 patients eventually diagnosed with a benign pleural condition for whom pleural fluid cytological analyses were ordered &#40;a total of 945 smears and 507 CBs&#41; and yielded negative results&#59; all were excluded for the purpose of the study&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Although all effusions were submitted to a first cytologic examination&#44; CBs were initially obtained from 380 &#40;92&#37;&#41; specimens&#44; but 46 &#40;12&#37;&#41; yielded suboptimal material&#46; Whether a first cytological smear or CB examination was used&#44; both had identical sensitivity for identifying malignancy&#58; 44&#37; &#40;95&#37; CI 39&#8211;50&#37;&#41;&#46; Notably&#44; of 184 cancer patients who had a first negative cytological exam&#44; CB was diagnostic of malignancy in 18 &#40;10&#37;&#44; 95&#37; CI 6&#8211;15&#37;&#41;&#46; Conversely&#44; among the 186 patients with a first negative CB examination&#44; cytological smears were positive in 20 &#40;11&#37;&#44; 95&#37; CI 7&#8211;16&#37;&#41;&#46; If any further cytology and CB assessments in patients with previous negative results were considered&#44; the global discrepancy was as follows&#58; 11&#37; &#40;95&#37; CI 7&#8211;17&#37;&#41; smears negative&#47;CBs positive&#44; and 15&#37; &#40;95&#37; CI 11&#8211;21&#37;&#41; smears positive&#47;CBs negative&#46; Overall&#44; 74 of the 554 CB preparations &#40;13&#37;&#44; 95&#37; CI 11&#8211;16&#37;&#41; resulted in inappropriate material for interpretation or diagnosis&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Immunocytochemical studies were performed on 157 &#40;34&#37;&#41; CBs&#44; particularly in those regarded as positive by cytomorphology &#40;85&#37; vs 1&#46;7&#37;&#41;&#44; with a median of 3 &#40;25th to 75th percentiles 1&#8211;4&#41; immunostains per case&#46; From a total of 480 immunostainings&#44; the most commonly used&#44; in order of decreasing frequency&#44; were TTF-1 &#40;138&#44; 29&#37;&#41;&#44; estrogen receptor &#40;60&#44; 13&#37;&#41;&#44; CK 7 &#40;47&#44; 47&#37;&#41;&#44; CK 20 &#40;43&#44; 9&#37;&#41;&#44; p63 &#40;30&#44; 6&#37;&#41;&#44; calretinin &#40;25&#44; 5&#37;&#41;&#44; mammaglobin &#40;21&#44; 4&#37;&#41;&#44; WT1 &#40;17&#44; 4&#37;&#41;&#44; and CK 19 &#40;15&#44; 3&#37;&#41;&#44; among others&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The sequential sensitivity of separated pleural fluid smears&#44; CBs or their combination for establishing the diagnosis of malignant pleural effusions is shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; In general&#44; cytological studies eventually identified 233 &#40;56&#37;&#44; 95&#37; CI 51&#8211;61&#37;&#41; malignant cases&#46; It was also demonstrated that the yield by sending more than two specimens is negligible&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">As compared with the reported positive and negative CBs&#44; suboptimal CB materials exhibited significantly lower median red blood cell &#40;10&#44;250&#47;&#956;L vs 3600&#47;&#956;L vs 2200&#47;&#956;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and leukocyte counts &#40;905&#47;&#956;L vs 1158&#47;&#956;L vs 392&#47;&#956;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; Furthermore&#44; higher median LDH levels &#40;732<span class="elsevierStyleHsp" style=""></span>U&#47;L vs 434<span class="elsevierStyleHsp" style=""></span>U&#47;L vs 394<span class="elsevierStyleHsp" style=""></span>U&#47;L&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; and decreased pH values &#40;7&#46;42 vs 7&#46;46 vs 7&#46;47&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; were associated with a greater likelihood of obtaining a positive CB result rather than a negative one or an insufficient CB&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">This study suggests that the examination of CBs alongside fluid smears is a valuable first step in the diagnostic workup for any suspected malignant effusion&#46; Conventional pleural fluid cytology is negative for malignant cells in up to 40&#37; of malignant effusions&#44; and in an even greater proportion in mesotheliomas and squamous cell lung carcinomas&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> Although CB is an old methodology for the diagnosis of serous effusions&#44; few studies have suggested its potential diagnostic superiority as compared to cytological smears&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">5&#8211;12</span></a> In brief&#44; they have reported that CBs increase the diagnostic yield for malignancy by 5&#8211;15&#37; over routine cytology&#46; However&#44; the inclusion of a small number of cases &#40;no study recruited more than 60 malignant effusions&#41; limits the validity of the results&#46; Even an earlier report casts doubt on the cost-effectiveness of preparing CBs and advocated for cytology smears alone&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> Of note&#44; a recent survey among last two-year Spanish residents of Pneumology or Internal Medicine showed that only 16&#37; of 139 responders in their clinical practice actively ordered a CB when confronted with a suspected malignant effusion&#44; whereas the remaining either never did &#40;27&#37;&#41; or left the decision to the pathologist discretion &#40;57&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> Therefore&#44; despite clinical guidelines which consider CB techniques to be a useful addition for diagnostic purposes&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">3&#44;15</span></a> it appears that too little attention has been paid to this recommendation&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">CBs have some advantages over cytological smears which may facilitate the diagnosis of malignancy<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a>&#58; &#40;a&#41; a better appreciation of tissue architecture &#40;e&#46;g&#46;&#44; acinar or papillary structures&#44; intracytoplasmatic mucin&#41;&#44; &#40;b&#41; an easier cytomorphological distinction between reactive mesothelial cells and mesothelioma or metastatic adenocarcinoma&#44; and &#40;c&#41; the possibility of processing multiple sections for immunocytochemistry&#46; Of interest&#44; smears and CBs were found to have the same sensitivity &#40;44&#37; on a first specimen&#41;&#44; but discrepant results &#40;i&#46;e&#46;&#44; negative smears and positive CBs&#44; or vice versa in 11&#37; and 15&#37; of cases&#44; respectively&#41; pointed to their complementary value&#46; Therefore&#44; CBs are not a substitute for fluid smears&#44; but rather an additional technique for increasing diagnostic accuracy&#46; It was also found that pleural fluids containing low red blood and&#47;or leukocyte cell counts are likely more unsuitable for CB preparation&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Our reported sensitivity for a first cytological pleural fluid specimen &#40;44&#37;&#41; is on the lower end of the spectrum for malignant effusion diagnoses&#46; However&#44; it is in line with our previous series from the 1993&#8211;2006 period in which the yield of a first cytological analysis among 466 patients with malignant effusions was reported to be 48&#46;5&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> It should be highlighted that we only send 5<span class="elsevierStyleHsp" style=""></span>mL of pleural fluid for smears preparation&#44; and that the incidence of positive results depends on the volume of pleural fluid submitted &#40;the larger the amount the greater the diagnostic accuracy&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> and other factors such as the number of specimens evaluated &#40;i&#46;e&#46;&#44; more than two specimens do not increase sensitivity sufficiently to be clinically meaningful&#41;&#44; the way in which the specimens are examined &#40;e&#46;g&#46;&#44; CBs along with smears&#44; as this study supports&#41;&#44; the tumor type&#44; and the experience of the cytopathologist&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">This study has limitations&#46; First&#44; it is retrospective&#46; Second&#44; pathologists were not blinded of clinical data and the interpretation of CBs may also have been influenced by the results of cytology smears&#44; which however&#44; is a reflection of daily practice&#46; Finally&#44; in a third of pleural effusions the malignant nature was not confirmed by pleural biopsy&#44; though it was based on solid clinical grounds&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion&#44; this study suggests that clinicians should be encouraged to request&#44; along with the conventional routine cytology&#44; CBs of pleural fluid on which immunocytochemical staining can be performed&#44; in order to increase diagnostic sensitivity and establish a more definitive cytopathological diagnosis&#44; whenever a malignant condition is suspected&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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          "titulo" => "References"
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    "fechaRecibido" => "2016-09-20"
    "fechaAceptado" => "2016-11-09"
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          "clase" => "keyword"
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          "palabras" => array:3 [
            0 => "Pleural effusion"
            1 => "Cytology"
            2 => "Cell blocks"
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          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec818231"
          "palabras" => array:3 [
            0 => "Derrame pleural"
            1 => "Citolog&#237;a"
            2 => "Bloques celulares"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the independent usefulness of pleural fluid smear and cell block &#40;CB&#41; preparations for the diagnosis of malignant effusions&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 632 cytological smears and 554 CBs from 414 consecutive patients with malignant effusions were retrospectively evaluated&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The diagnostic yield of a first specimen was 44&#37; regardless of whether a smear or CB cytologic examination was performed&#46; The use of subsequent separated specimens increased the identification of malignancy to 56&#37;&#46; Overall&#44; 11&#37; of samples found to be negative by cytologic smears showed malignant cells on CBs&#44; whereas 15&#37; of negative CBs were reported as positive on smear slides&#46; Pleural fluid specimens with low red and&#47;or white blood cell counts more frequently resulted in the generation of suboptimal CB preparations&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">If CBs and smears are prepared and examined&#44; the percentage of positive diagnoses will be greater than if only one method is used&#46;</p></span>"
        "secciones" => array:4 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la utilidad independiente de frotis y bloques celulares &#40;BC&#41; del l&#237;quido pleural para diagnosticar derrames malignos&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se evaluaron retrospectivamente un total de 632 frotis citol&#243;gicos y 554 BC de 414 pacientes consecutivos con derrame pleural maligno&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La sensibilidad diagn&#243;stica de una primera muestra fue del 44&#37;&#44; tanto en frotis como en BC&#46; El an&#225;lisis de muestras separadas ulteriores aument&#243; al 56&#37; la identificaci&#243;n de derrames malignos&#46; Globalmente&#44; el 11&#37; de muestras negativas mediante frotis mostraron c&#233;lulas malignas en los BC&#44; mientras que el 15&#37; de BC negativos resultaron positivos en el estudio del frotis&#46; Los l&#237;quidos pleurales con recuentos bajos de hemat&#237;es o leucocitos produjeron con mayor frecuencia BC insuficientes para diagn&#243;stico&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Si se eval&#250;an frotis y BC&#44; el porcentaje de resultados positivos es superior que si se emplean estas t&#233;cnicas de forma aislada&#46;</p></span>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tumor type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Definite malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Probable malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">All malignant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lung&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">183 &#40;44&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Adenocarcinoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Squamous&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Small cell&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Non-small cell unspecified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sarcoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Breast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46 &#40;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Unknown origin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">32 &#40;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastrointestinal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27 &#40;6&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ovary&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pancreas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kidney&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;2&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mesothelioma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;1&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Others&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31 &#40;7&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">260 &#40;63&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">154 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">414&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Etiology of malignant pleural effusions&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cytological smears&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cell blocks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Smears plus cell blocks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">First specimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183 of 414<br>44&#37; &#40;39&#8211;49&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">143 of 334<br>44&#37; &#40;39&#8211;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">200 of 414<br>48&#37; &#40;44&#8211;53&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Second specimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">211 of 414<br>51&#37; &#40;46&#8211;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">167 of 334<br>50&#37; &#40;45&#8211;55&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">231 of 414<br>56&#37; &#40;51&#8211;61&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third or subsequent specimens&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">214 of 414<br>52&#37; &#40;47&#8211;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">179 of 360<br>50&#37; &#40;45&#8211;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">233 of 414<br>56&#37; &#40;51&#8211;61&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Sequential cumulative sensitivity &#40;95&#37; CI&#41; of pleural fluid smears&#44; cell blocks&#44; and their combination for labeling malignancy in 414 patients&#44; based on the number of processed specimens&#46;</p>"
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      "titulo" => "References"
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          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current controversies in the management of malignant pleural effusions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Azzopardi"
                            1 => "J&#46;M&#46; Porcel"
                            2 => "C&#46;F&#46; Koegelenberg"
                            3 => "Y&#46;C&#46; Lee"
                            4 => "E&#46;T&#46; Fysh"
                          ]
                        ]
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                    0 => array:2 [
                      "doi" => "10.1055/s-0034-1395795"
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              "identificador" => "bib0095"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effusion cytology&#46; A practical guide to cancer diagnosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "P&#46; Ganjei-Azar"
                            1 => "M&#46; Jord&#224;"
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                  "host" => array:1 [
                    0 => array:1 [
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            2 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Investigation of a unilateral pleural effusion in adults&#58; British Thoracic Society Pleural Disease Guideline 2010"
                      "autores" => array:1 [
                        0 => array:3 [
                          "colaboracion" => "BTS Pleural Guideline Group"
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Hooper"
                            1 => "Y&#46;C&#46; Lee"
                            2 => "N&#46; Maskell"
                          ]
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                  "host" => array:1 [
                    0 => array:2 [
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                      "Revista" => array:8 [
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                        "numero" => "Suppl&#46; 2"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20696692"
                            "web" => "Medline"
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                        "itemHostRev" => array:3 [
                          "pii" => "S0002937809020900"
                          "estado" => "S300"
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            3 => array:3 [
              "identificador" => "bib0105"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Etiolog&#237;a del derrame pleural&#58; an&#225;lisis de m&#225;s de 3&#46;000 toracocentesis consecutivas"
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                          "etal" => false
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                            0 => "J&#46;M&#46; Porcel"
                            1 => "A&#46; Esquerda"
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            4 => array:3 [
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                        0 => array:2 [
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                            0 => "A&#46; Dekker"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/364975"
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            5 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic utility of the cell block method versus the conventional smear study in pleural fluid cytology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "U&#46; Shivakumarswamy"
                            1 => "S&#46;U&#46; Arakeri"
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