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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The World Health Organization classification of lung cancer categorizes diffuse idiopathic neuroendocrine cell hyperplasia as a premalignant lesion&#46; This entity presents with clinical and radiological manifestations&#44; such as cough and pulmonary nodules&#44; that are so non-specific that they present a diagnostic challenge for clinicians&#46; We report 2 cases of this disease and describe our diagnostic experience&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 1</span>&#58; A 66-year-old woman with ductal carcinoma in situ of the breast with positive hormonal receptors&#44; treated with lumpectomy&#44; radiation therapy and adjuvant hormone therapy&#46; She developed chronic pericardial effusion associated with radiation therapy requiring evacuation&#46; In a follow-up computed tomography &#40;CT&#41;&#44; pulmonary nodules were observed that were subsequently evaluated&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">She had a history of chronic cough for many years&#46; Lung function tests showed forced vital capacity of 1820<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span> &#40;80&#46;5&#37;&#41; and a forced expiratory volume in 1 second of 1120<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span> &#40;59&#46;6&#37;&#41;&#44; ratio 61&#46;33&#37;&#46; CT revealed multiple nodules of different sizes distributed throughout both lung fields&#46; Six months later&#44; the number and size of the nodules had increased &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Positron emission tomography &#40;PET&#41;-CT revealed solid nodules measuring between 8 and 14<span class="elsevierStyleHsp" style=""></span>mm&#44; with maximum SUV of 3&#46;88&#46; Others showed no uptake&#46; Three enlarged lymph nodes were also observed with maximum SUV of 6&#46;8&#8211;8&#46;0<span class="elsevierStyleHsp" style=""></span>mm in the right cervical and retromandibular region&#46; Bronchoscopy provided no significant information&#44; with the exception of <span class="elsevierStyleItalic">Aspergillus fumigatus</span> growth in the bronchial aspirate which subsequently became negative&#46; Two months later&#44; a video-assisted thoracoscopy with wedge resections of the middle and lower right lobe showed diffuse idiopathic neuroendocrine cell hyperplasia associated with tumorlets and peripheral typical carcinoid tumors &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2</span>&#58; A 29-year-old woman with bilateral breast prostheses&#44; with a diagnosis of extrinsic bronchial asthma presented with a complaint of chronic cough&#46; Spirometry&#44; chest radiograph&#44; and paranasal sinuses were normal&#46; Bilateral pulmonary micronodules with a residual appearance were seen on chest CT&#46; Nine months later&#44; multiple pulmonary nodules were detected in the patient&#39;s mother and removed with wedge resection of the middle lobe and right lower lobe&#46; The pathology report described peripheral typical carcinoid tumor associated with tumorlets and diffuse idiopathic neuroendocrine cell hyperplasia&#46; Resected mediastinal nodes were normal&#46; A more detailed study revealed a multifocal proliferation of neuroendocrine cells consisting of at least 2 tumor lesions larger than 5<span class="elsevierStyleHsp" style=""></span>mm&#44; and more than 7 lesions smaller than 5<span class="elsevierStyleHsp" style=""></span>mm&#44; and others in the form of intraepithelial neuroendocrine cell hyperplasia&#46; Less than 2 mitosis&#47;10 HPF were observed&#46; Chromogranin&#44; synaptophysin and CD 56 were positive&#44; and the calcitonin study was negative&#46; Given these results in a first-degree relative&#44; we requested a follow-up CT in our patient that provided a more detailed report of multiple pulmonary nodules less than 1<span class="elsevierStyleHsp" style=""></span>cm in diameter&#44; with a mean diameter of about 3<span class="elsevierStyleHsp" style=""></span>mm&#44; bilateral&#44; diffuse rounded&#44; with no calcification in the interior&#59; in number&#44; about 25 in the right lung and 15 in the left lung&#46; Bronchoscopy detected direct signs of neoplasm in the bronchus of the lingula&#46; Biopsy revealed a well-differentiated typical carcinoid lesion&#46; Scintigraphy with fluorine-18-L-dihydroxyphenylalanine &#40;18F-DOPA&#41; revealed 3 nodules in the right lower lobe&#44; the largest of which was 9<span class="elsevierStyleHsp" style=""></span>mm&#44; with a maximum SUV of 1&#46;09 &#40;parenchymal SUV 0&#46;49&#41;&#44; and 4 nodules in the left lung&#44; of which 2 were in the lingula&#44; the largest measuring 13<span class="elsevierStyleHsp" style=""></span>mm with maximum SUV of 0&#46;78 &#40;parenchymal SUV 0&#46;37&#41; and another measuring 9<span class="elsevierStyleHsp" style=""></span>mm with maximum SUV of 0&#46;79&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Diffuse idiopathic neuroendocrine cell hyperplasia &#40;DIPNECH&#41; is an entity that every year becomes more common in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> It comprises a generalized&#44; extensive overgrowth of neuroendocrine cells in the peripheral airway and is considered a premalignant lesion&#46; Clinical presentation can be asymptomatic&#44; as was the case of our second patient&#39;s mother&#44; or can involve cough&#44; dyspnea&#44; and wheezing&#44; all of which are manifestations of such prevalent diseases as asthma or bronchiolitis&#46; Consequently&#44; this entity is infrequently suspected or investigated&#44; so its true prevalence is unknown&#46; Lung function tests can range from normal to an obstructive or mixed pattern&#46; In the imaging tests&#44; the most common presentation in a bilateral nodular pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> In our second case&#44; we did not have a larger sample&#44; as recommended for the diagnosis of this disease&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> but the family history of diffuse idiopathic neuroendocrine cell hyperplasia&#44; the patient&#39;s own clinical history&#44; and the radiological changes&#44; along with the biopsy results&#44; led to a reinterpretation of the lesions that initially were interpreted as residual&#46; We are unaware of any reports of familial accumulation of this disease&#46; Gorschtein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> did not find any relationship among any of the 11 cases in their series&#46; On other occasions&#44; radiological images show air trapping or mosaic attenuation pattern&#44; which could go unnoticed if expiratory CT is not performed&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Standard PET-CT with glucose is not sensitive for carcinoid tumors&#44; due to their small size and sparse mitotic activity&#46; Markers such as octreotide or 18F-DOPA amino acid analog are used&#46; Overall prognosis is good&#44; although some exceptional cases may progress poorly if distant metastases occur&#46;</p></span>"
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Scientific Letter
Diffuse Idiopathic Neuroendocrine Cell Hyperplasia, Tumorlets and Typical Carcinoid Tumors
Hiperplasia idiopática difusa de células neuroendocrinas, tumorlets y carcinoides típicos
Jorge Lima Álvareza,
Corresponding author
, Javier Muñoz Gutiérreza, Antonio J. Cruz Medinaa, Nuria Reyes Núñeza, Enrique Rodríguez Zarcob
a Unidad de Gestión Clínica de Neumología, Hospital Universitario Virgen de Valme, Sevilla, Spain
b Unidad de Gestión Clínica de Anatomía Patológica, Hospital Universitario Virgen Macarena, Sevilla, Spain
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pulmonary nodules were observed that were subsequently evaluated&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">She had a history of chronic cough for many years&#46; Lung function tests showed forced vital capacity of 1820<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span> &#40;80&#46;5&#37;&#41; and a forced expiratory volume in 1 second of 1120<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span> &#40;59&#46;6&#37;&#41;&#44; ratio 61&#46;33&#37;&#46; CT revealed multiple nodules of different sizes distributed throughout both lung fields&#46; Six months later&#44; the number and size of the nodules had increased &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Positron emission tomography &#40;PET&#41;-CT revealed solid nodules measuring between 8 and 14<span class="elsevierStyleHsp" style=""></span>mm&#44; with maximum SUV of 3&#46;88&#46; Others showed no uptake&#46; Three enlarged lymph nodes were also observed with maximum SUV of 6&#46;8&#8211;8&#46;0<span class="elsevierStyleHsp" style=""></span>mm in the right cervical and retromandibular region&#46; Bronchoscopy provided no significant information&#44; with the exception of <span class="elsevierStyleItalic">Aspergillus fumigatus</span> growth in the bronchial aspirate which subsequently became negative&#46; Two months later&#44; a video-assisted thoracoscopy with wedge resections of the middle and lower right lobe showed diffuse idiopathic neuroendocrine cell hyperplasia associated with tumorlets and peripheral typical carcinoid tumors &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Case 2</span>&#58; A 29-year-old woman with bilateral breast prostheses&#44; with a diagnosis of extrinsic bronchial asthma presented with a complaint of chronic cough&#46; Spirometry&#44; chest radiograph&#44; and paranasal sinuses were normal&#46; Bilateral pulmonary micronodules with a residual appearance were seen on chest CT&#46; Nine months later&#44; multiple pulmonary nodules were detected in the patient&#39;s mother and removed with wedge resection of the middle lobe and right lower lobe&#46; The pathology report described peripheral typical carcinoid tumor associated with tumorlets and diffuse idiopathic neuroendocrine cell hyperplasia&#46; Resected mediastinal nodes were normal&#46; A more detailed study revealed a multifocal proliferation of neuroendocrine cells consisting of at least 2 tumor lesions larger than 5<span class="elsevierStyleHsp" style=""></span>mm&#44; and more than 7 lesions smaller than 5<span class="elsevierStyleHsp" style=""></span>mm&#44; and others in the form of intraepithelial neuroendocrine cell hyperplasia&#46; Less than 2 mitosis&#47;10 HPF were observed&#46; Chromogranin&#44; synaptophysin and CD 56 were positive&#44; and the calcitonin study was negative&#46; Given these results in a first-degree relative&#44; we requested a follow-up CT in our patient that provided a more detailed report of multiple pulmonary nodules less than 1<span class="elsevierStyleHsp" style=""></span>cm in diameter&#44; with a mean diameter of about 3<span class="elsevierStyleHsp" style=""></span>mm&#44; bilateral&#44; diffuse rounded&#44; with no calcification in the interior&#59; in number&#44; about 25 in the right lung and 15 in the left lung&#46; Bronchoscopy detected direct signs of neoplasm in the bronchus of the lingula&#46; Biopsy revealed a well-differentiated typical carcinoid lesion&#46; Scintigraphy with fluorine-18-L-dihydroxyphenylalanine &#40;18F-DOPA&#41; revealed 3 nodules in the right lower lobe&#44; the largest of which was 9<span class="elsevierStyleHsp" style=""></span>mm&#44; with a maximum SUV of 1&#46;09 &#40;parenchymal SUV 0&#46;49&#41;&#44; and 4 nodules in the left lung&#44; of which 2 were in the lingula&#44; the largest measuring 13<span class="elsevierStyleHsp" style=""></span>mm with maximum SUV of 0&#46;78 &#40;parenchymal SUV 0&#46;37&#41; and another measuring 9<span class="elsevierStyleHsp" style=""></span>mm with maximum SUV of 0&#46;79&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Diffuse idiopathic neuroendocrine cell hyperplasia &#40;DIPNECH&#41; is an entity that every year becomes more common in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> It comprises a generalized&#44; extensive overgrowth of neuroendocrine cells in the peripheral airway and is considered a premalignant lesion&#46; Clinical presentation can be asymptomatic&#44; as was the case of our second patient&#39;s mother&#44; or can involve cough&#44; dyspnea&#44; and wheezing&#44; all of which are manifestations of such prevalent diseases as asthma or bronchiolitis&#46; Consequently&#44; this entity is infrequently suspected or investigated&#44; so its true prevalence is unknown&#46; Lung function tests can range from normal to an obstructive or mixed pattern&#46; In the imaging tests&#44; the most common presentation in a bilateral nodular pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> In our second case&#44; we did not have a larger sample&#44; as recommended for the diagnosis of this disease&#44;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> but the family history of diffuse idiopathic neuroendocrine cell hyperplasia&#44; the patient&#39;s own clinical history&#44; and the radiological changes&#44; along with the biopsy results&#44; led to a reinterpretation of the lesions that initially were interpreted as residual&#46; We are unaware of any reports of familial accumulation of this disease&#46; Gorschtein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a> did not find any relationship among any of the 11 cases in their series&#46; On other occasions&#44; radiological images show air trapping or mosaic attenuation pattern&#44; which could go unnoticed if expiratory CT is not performed&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> Standard PET-CT with glucose is not sensitive for carcinoid tumors&#44; due to their small size and sparse mitotic activity&#46; Markers such as octreotide or 18F-DOPA amino acid analog are used&#46; Overall prognosis is good&#44; although some exceptional cases may progress poorly if distant metastases occur&#46;</p></span>"
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ISSN: 15792129
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