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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The incidence of synchronous primary lung tumors &#40;SPLT&#41; ranges from 0&#46;2 to 20&#37; and has recently increased due to the widespread use of imaging techniques &#40;such as multidetector computed tomography &#91;CT&#93;&#41; and the increasing implementation of lung cancer screening programs with low-dose radiation thoracic CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1&#44;2</span></a> The simultaneous detection of more than one pulmonary nodule in patients with lung cancer raises the clinical and radiological dilemma of whether these lesions represent intrapulmonary metastases or additional SPLT&#46; Although the classic criteria proposed by Martini and Melamed in 1975 for the diagnosis of SPLT are still in use &#40;based on the histologic features of the tumors&#44; location&#44; presence or absence of carcinoma in situ&#44; vascular invasion&#44; etc&#46;&#41; they do not take into account more modern biomarkers such as driver gene mutations and detailed genetic assessments &#40;like comparative genomic hybridization or Next-Generation sequencing&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3&#44;4</span></a> Very few cases of three SPLT involving one single lobe have been described&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">5&#8211;7</span></a> but to our knowledge there are no cases describing three SPLT in the same lung segment&#46; In this document we describe the case of a patient with three different SPLT in one single pulmonary segment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 72-year-old male&#44; active smoker&#44; who complained of progressive dyspnea and cough&#46; A chest radiograph showed a nodular opacity in the left lung&#44; so it was decided to perform a thoracic CT&#44; which confirmed the presence of 3 suspicious lesions in the superior segment of the left lower lobe &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#58; one 16-mm solid nodule in the inferior aspect of the superior segment &#40;lesion 1&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; one 17-mm solid subpleural nodule in the superior and lateral aspect of the superior segment &#40;lesion 2&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#44; and one 11-mm solid subpleural nodule in the superior and medial aspect of the inferior segment &#40;lesion 3&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46; Fluorine-18 fluorodeoxyglucose positron emission tomography&#47;CT &#40;FDG-PET&#47;CT&#41; demonstrated variable standardized uptake values &#40;SUVs&#41; by the three lung nodules&#58; SUV of 4&#46;7 &#40;lesion 1&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>E&#41;&#44; SUV of 4&#46;3 &#40;lesion 2&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#44; and SUV of 2&#46;2 &#40;lesion 3&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>G&#41;&#44; suggesting a different glycolytic metabolism&#46; There were no signs of mediastinal or distant metastases&#46; Endobronchial ultrasound &#40;EBUS&#41; and bronchial brushing did not show malignant cells&#46; A presumed diagnosis of a T3 &#40;lung cancer associated with ipsilobar nodules&#41; tumor was made&#44; and the patient underwent a video-assisted thoracoscopic left lower lobectomy&#46; Pathologic findings revealed a low-grade malignant neuroendocrine tumor &#40;pT1bN0M0&#44; lesion 1&#41;&#44; an invasive acinar-predominant adenocarcinoma &#40;pT1bN0M0&#44; lesion 2&#41;&#44; and another invasive acinar-predominant adenocarcinoma &#40;pT1bN0M0&#41;&#46; Although the microscopic morphology of lesions 2 and 3 were similar&#44; immunohistochemical differences &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; confirmed that they represented two independent primary lung adenocarcinomas&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The simultaneous detection of more than one suspicious lung nodule in the same patient is increasing&#44; due to the widespread use of CTs and the implementation of lung cancer screening programs with low-dose CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1&#44;2</span></a> Distinguishing synchronous primary lung tumors &#40;SPLT&#41; from primary lung cancers with pulmonary metastases has been extensively discussed in the literature&#44; and has implications both on staging and treatment planning&#44; leading to the choice between local therapies for patients with independent primary tumors versus more aggressive systemic therapies for patients with metastatic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3&#44;4</span></a> Recent improvements in imaging technologies and genomic studies have greatly contributed to the delineation of the clinical&#44; pathologic&#44; and molecular characteristics allowing the discrimination between multiple SPLT and pulmonary metastases&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">8&#44;9</span></a> However&#44; few features are definitive for accurately differentiating intrapulmonary metastasis from SPLT&#59; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification&#46; Therefore&#44; careful review by a multidisciplinary tumor board considering all available information &#40;clinical&#44; imaging&#44; and histopathological findings&#41; is always recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">10&#44;11</span></a> We have only found three reports of three SPLT involving the same lobe&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">5&#8211;7</span></a> One of them described two lung cancers in the left upper lobe &#40;one corresponded to a squamous cell cancer and the other one to a combined small cell lung cancer&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> other report described three lesions in the right upper lobe &#40;two invasive lung cancers &#91;one squamous and one adenocarcinoma&#93; and one preneoplastic lung cancer lesion &#91;atypical adenomatous hyperplasia&#93;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> and another report described three lung cancers in the right lower lobe &#40;one squamous cell cancer&#44; one adenocarcinoma&#44; and one small cell lung cancer&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Our patient had three primary lung cancers &#40;one typical carcinoid tumor and two invasive adenocarcinomas&#41; in the superior segment of the left lower lobe&#44; but this was only confirmed after thorough immunohistochemical and genetic assessments&#46; The different SUV uptake on FDG-PET&#47;CT by the three lung lesions along with the different expression of p53 and PD-L1 by the 2 lung adenocarcinomas confirmed the independent nature of each lung lesion&#46; Long-term survival after resection for patients with SPLT has been reported to be better than that of patients with higher stages &#40;for reasons other than synchronous tumors&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> Considering this observed survival advantage&#44; surgical resection is presumed to offer the best chance for prolonged survival in these patients&#59; however&#44; controversies related to diagnosis and patient selection for surgical resection still exist&#46; The previously published reports with three SPLT were all surgically treated &#40;lobectomy&#41;&#59; in our case&#44; since the presurgical diagnosis suggested a T3 tumor &#40;lung cancer with secondary satellite nodules within the same lobe&#41;&#44; a lobectomy was performed&#46; Although a segmentectomy of the superior segment of the left lower lobe could have been attempted&#44; the resection margins for the carcinoid tumor would have been suboptimal&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Synchronous lung cancers in the same &#40;or different&#41; lobe are likely to be underdiagnosed&#44; as it is not always possible to make a histological diagnosis of every lung lesion before treatment initiation &#40;especially if the patient is not a surgical candidate&#41;&#46; Multidisciplinary diagnostic evaluation &#40;and comprehensive evaluation of the CT and FDG-PET&#47;CT images&#41; can be very helpful in these cases&#44; because a correct diagnosis will determine the best treatment for the patient and&#44; consequently&#44; a better prognosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Con&#64258;ict of Interests</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors state that they have no con&#64258;ict of interests&#46;</p></span></span>"
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Scientific Letter
Three synchronous Lung Cancers in the Same Lung Segment: Triple Trouble?
Luis Gorospea,
Corresponding author
luisgorospe@yahoo.com

Corresponding author.
, Miguel Ángel Gómez-Bermejoa, Patricia Paredes-Rodríguezb, Rosa Mariela Mirambeaux-Villalonac, Sara Fra-Fernándezd, Gemma María Muñoz-Molinad, Amparo Benito-Berlinchese
a Department of Radiology, Hospital Universitario Ramón y Cajal, Madrid, Spain
b Department of Nuclear Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain
c Department of Respiratory Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain
d Department of Thoracic Surgery, Hospital Universitario Ramón y Cajal, Madrid, Spain
e Department of Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Coronal CT image &#40;lung window&#41; shows 3 suspicious lung nodules in the superior segment of the left lower lobe&#46; &#40;B&#41; Axial CT image &#40;lung window&#41; shows one solid nodule in the inferior region of the superior segment &#40;arrow&#44; lesion 1&#41;&#46; &#40;C&#41; Axial CT image &#40;lung window&#41; shows one subpleural nodular opacity in the lateral aspect of the superior segment &#40;arrow&#44; lesion 2&#41;&#46; &#40;D&#41; Axial CT image &#40;lung window&#41; shows one small solid nodule in the medial aspect of the superior segment &#40;arrow&#44; lesion 3&#41;&#46; &#40;E&#8211;G&#41; Axial fused PET&#47;CT images corresponding to lesions shown on Figs&#46; B&#44; C&#44; and D&#44; respectively&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The incidence of synchronous primary lung tumors &#40;SPLT&#41; ranges from 0&#46;2 to 20&#37; and has recently increased due to the widespread use of imaging techniques &#40;such as multidetector computed tomography &#91;CT&#93;&#41; and the increasing implementation of lung cancer screening programs with low-dose radiation thoracic CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1&#44;2</span></a> The simultaneous detection of more than one pulmonary nodule in patients with lung cancer raises the clinical and radiological dilemma of whether these lesions represent intrapulmonary metastases or additional SPLT&#46; Although the classic criteria proposed by Martini and Melamed in 1975 for the diagnosis of SPLT are still in use &#40;based on the histologic features of the tumors&#44; location&#44; presence or absence of carcinoma in situ&#44; vascular invasion&#44; etc&#46;&#41; they do not take into account more modern biomarkers such as driver gene mutations and detailed genetic assessments &#40;like comparative genomic hybridization or Next-Generation sequencing&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3&#44;4</span></a> Very few cases of three SPLT involving one single lobe have been described&#44;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">5&#8211;7</span></a> but to our knowledge there are no cases describing three SPLT in the same lung segment&#46; In this document we describe the case of a patient with three different SPLT in one single pulmonary segment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 72-year-old male&#44; active smoker&#44; who complained of progressive dyspnea and cough&#46; A chest radiograph showed a nodular opacity in the left lung&#44; so it was decided to perform a thoracic CT&#44; which confirmed the presence of 3 suspicious lesions in the superior segment of the left lower lobe &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#58; one 16-mm solid nodule in the inferior aspect of the superior segment &#40;lesion 1&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#44; one 17-mm solid subpleural nodule in the superior and lateral aspect of the superior segment &#40;lesion 2&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#44; and one 11-mm solid subpleural nodule in the superior and medial aspect of the inferior segment &#40;lesion 3&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D&#41;&#46; Fluorine-18 fluorodeoxyglucose positron emission tomography&#47;CT &#40;FDG-PET&#47;CT&#41; demonstrated variable standardized uptake values &#40;SUVs&#41; by the three lung nodules&#58; SUV of 4&#46;7 &#40;lesion 1&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>E&#41;&#44; SUV of 4&#46;3 &#40;lesion 2&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41;&#44; and SUV of 2&#46;2 &#40;lesion 3&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>G&#41;&#44; suggesting a different glycolytic metabolism&#46; There were no signs of mediastinal or distant metastases&#46; Endobronchial ultrasound &#40;EBUS&#41; and bronchial brushing did not show malignant cells&#46; A presumed diagnosis of a T3 &#40;lung cancer associated with ipsilobar nodules&#41; tumor was made&#44; and the patient underwent a video-assisted thoracoscopic left lower lobectomy&#46; Pathologic findings revealed a low-grade malignant neuroendocrine tumor &#40;pT1bN0M0&#44; lesion 1&#41;&#44; an invasive acinar-predominant adenocarcinoma &#40;pT1bN0M0&#44; lesion 2&#41;&#44; and another invasive acinar-predominant adenocarcinoma &#40;pT1bN0M0&#41;&#46; Although the microscopic morphology of lesions 2 and 3 were similar&#44; immunohistochemical differences &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; confirmed that they represented two independent primary lung adenocarcinomas&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The simultaneous detection of more than one suspicious lung nodule in the same patient is increasing&#44; due to the widespread use of CTs and the implementation of lung cancer screening programs with low-dose CT&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">1&#44;2</span></a> Distinguishing synchronous primary lung tumors &#40;SPLT&#41; from primary lung cancers with pulmonary metastases has been extensively discussed in the literature&#44; and has implications both on staging and treatment planning&#44; leading to the choice between local therapies for patients with independent primary tumors versus more aggressive systemic therapies for patients with metastatic disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">3&#44;4</span></a> Recent improvements in imaging technologies and genomic studies have greatly contributed to the delineation of the clinical&#44; pathologic&#44; and molecular characteristics allowing the discrimination between multiple SPLT and pulmonary metastases&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">8&#44;9</span></a> However&#44; few features are definitive for accurately differentiating intrapulmonary metastasis from SPLT&#59; many commonly used characteristics are suggestive but associated with a substantial rate of misclassification&#46; Therefore&#44; careful review by a multidisciplinary tumor board considering all available information &#40;clinical&#44; imaging&#44; and histopathological findings&#41; is always recommended&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">10&#44;11</span></a> We have only found three reports of three SPLT involving the same lobe&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">5&#8211;7</span></a> One of them described two lung cancers in the left upper lobe &#40;one corresponded to a squamous cell cancer and the other one to a combined small cell lung cancer&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> other report described three lesions in the right upper lobe &#40;two invasive lung cancers &#91;one squamous and one adenocarcinoma&#93; and one preneoplastic lung cancer lesion &#91;atypical adenomatous hyperplasia&#93;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> and another report described three lung cancers in the right lower lobe &#40;one squamous cell cancer&#44; one adenocarcinoma&#44; and one small cell lung cancer&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> Our patient had three primary lung cancers &#40;one typical carcinoid tumor and two invasive adenocarcinomas&#41; in the superior segment of the left lower lobe&#44; but this was only confirmed after thorough immunohistochemical and genetic assessments&#46; The different SUV uptake on FDG-PET&#47;CT by the three lung lesions along with the different expression of p53 and PD-L1 by the 2 lung adenocarcinomas confirmed the independent nature of each lung lesion&#46; Long-term survival after resection for patients with SPLT has been reported to be better than that of patients with higher stages &#40;for reasons other than synchronous tumors&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> Considering this observed survival advantage&#44; surgical resection is presumed to offer the best chance for prolonged survival in these patients&#59; however&#44; controversies related to diagnosis and patient selection for surgical resection still exist&#46; The previously published reports with three SPLT were all surgically treated &#40;lobectomy&#41;&#59; in our case&#44; since the presurgical diagnosis suggested a T3 tumor &#40;lung cancer with secondary satellite nodules within the same lobe&#41;&#44; a lobectomy was performed&#46; Although a segmentectomy of the superior segment of the left lower lobe could have been attempted&#44; the resection margins for the carcinoid tumor would have been suboptimal&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Synchronous lung cancers in the same &#40;or different&#41; lobe are likely to be underdiagnosed&#44; as it is not always possible to make a histological diagnosis of every lung lesion before treatment initiation &#40;especially if the patient is not a surgical candidate&#41;&#46; Multidisciplinary diagnostic evaluation &#40;and comprehensive evaluation of the CT and FDG-PET&#47;CT images&#41; can be very helpful in these cases&#44; because a correct diagnosis will determine the best treatment for the patient and&#44; consequently&#44; a better prognosis&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Con&#64258;ict of Interests</span><p id="par0025" class="elsevierStylePara elsevierViewall">The authors state that they have no con&#64258;ict of interests&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Coronal CT image &#40;lung window&#41; shows 3 suspicious lung nodules in the superior segment of the left lower lobe&#46; &#40;B&#41; Axial CT image &#40;lung window&#41; shows one solid nodule in the inferior region of the superior segment &#40;arrow&#44; lesion 1&#41;&#46; &#40;C&#41; Axial CT image &#40;lung window&#41; shows one subpleural nodular opacity in the lateral aspect of the superior segment &#40;arrow&#44; lesion 2&#41;&#46; &#40;D&#41; Axial CT image &#40;lung window&#41; shows one small solid nodule in the medial aspect of the superior segment &#40;arrow&#44; lesion 3&#41;&#46; &#40;E&#8211;G&#41; Axial fused PET&#47;CT images corresponding to lesions shown on Figs&#46; B&#44; C&#44; and D&#44; respectively&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">TTF-1&#58; TTF1&#44; thyroid transcription factor-1&#59; p53&#58; p53 tumor suppressor gene&#59; PD-L1&#58; programmed death ligand 1&#59; ALK&#58; anaplastic lymphoma kinase&#59; KRAS&#58; Kirsten rat sarcoma virus&#59; ROS1&#58; ROS Proto-Oncogene 1&#44; receptor tyrosine kinase&#59; EGFR&#58; epidermal growth factor receptor&#59; SUV&#58; standardized uptake value&#59; PET&#47;CT&#58; positron emission tomography&#47;computed tomography&#46;</p>"
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