Detection of nodular pulmonary amyloid by PET positive scan—Deception for lung cancer

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Extenso envolvimento hipermetabólico da pleura direita suspeito de envolvimento neoplásico maligno, uma massa na porção postero-inferior que invadia a parede torácica adjacente, derrame pleural homolateral suspeito de derrame de origem neoplásica e envolvimento ganglionar secundário mediastínico e bronco-hilar direito." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Santos, F. Gamboa, F. Fradinho, A. Pêgo, L. Carvalho, J. Bernardo" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Santos" ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Gamboa" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Fradinho" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Pêgo" ] 4 => array:2 [ "nombre" => "L." "apellidos" => "Carvalho" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Bernardo" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173511512000267" "doi" => "10.1016/j.rppnen.2012.03.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511512000267?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215912000219?idApp=UINPBA00004E" "url" => "/08732159/0000001800000006/v2_201509041329/S0873215912000219/v2_201509041329/pt/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Case report" "titulo" => "Detection of nodular pulmonary amyloid by PET positive scan—Deception for lung cancer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "299" "paginaFinal" => "303" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A.M. Khan, K. Manzoor, V. Jain, P. Mahadevia, A. Berman" "autores" => array:5 [ 0 => array:4 [ "nombre" => "A.M." "apellidos" => "Khan" "email" => array:1 [ 0 => "dramirkhan@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "K." "apellidos" => "Manzoor" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "V." "apellidos" => "Jain" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Mahadevia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Berman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Pulmonary, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Radiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Detecção de amilóide pulmonar nodular por PET positiva – simulando cancro do pulmão" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 899 "Ancho" => 900 "Tamanyo" => 86067 ] ] "descripcion" => array:1 [ "en" => "CT on presentation showing a pulmonary nodule 2cm×2cm in size." ] ] ] "textoCompleto" => "IntroductionAmyloidosis results from over-expression of specific proteins culminating in the extracellular deposition of insoluble β-pleated sheets of fibers. Initially identified as carbohydrate by Virchow<a class="elsevierStyleCrossRef" href="#bib0005">1</a> in 1854, amyloid deposits are composed of linear arrays of subunit proteins in glucose-aminoglycans and serum amyloid P (SAP).Amyloid deposits occur in systemic and organ-limited forms. In systemic amyloidosis, the composition of subunit proteins in the β-pleated sheets dictates the pattern of organ involvement and disease prognosis. Identifying the type of amyloidosis strongly impacts the diagnostic differential of radiographic abnormalities.Classification of systemic amyloidosis is based on the different subunit proteins, which define organ involvement and disease manifestations. There are four major categories of systemic amyloidosis (“A” for amyloid and a letter indicating the protein involved): (1) primary or immunoglobulin light-chain (AL) disease, (2) secondary or amyloid protein A (AA) disease, (3) hereditary or mutant transthyretin (ATTR) disease, and (4) dialysis-associated or β2-microglobulin (β2M) disease. Other less prevalent forms of amyloid disease exist, locally affecting the pancreas (islet amyloid polypeptide, AIAPP) and brain (β-amyloid precursor protein, Aβ), or genetically transmitted systemic disease (apolipoprotein AI, gelsolin, fibrinogen, lysozyme precursor proteins). Pulmonary manifestations mainly occur from AL disease, this may be local or systemic depending upon the expression of monoclonal protein either just locally in the lung or in the serum/urine. Amyloid lung nodules with PET uptake are rare. We describe a rare case where positron emission tomography (PET) uptake was noticed in pulmonary amyloid nodules. To our knowledge there are six reported cases in the English literature to date<a class="elsevierStyleCrossRefs" href="#bib0010">2–7</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Case reportA 68-year-old male with a past medical history significant for hypertension and osteoarthritis presented with bilateral knee pain worse for the last few months. He was a non-smoker, denied any abuse of alcohol or any other illicit substances. He had no known allergies and his past surgical history was only significant for an appendicectomy several years ago.His general physical and systemic examination except for knee crepitus in both knees was otherwise normal. His laboratory examination including a complete blood count, basic chemistry and liver function tests including a clotting profile was normal. No abnormality was seen on an electrocardiogram and pulmonary function tests. On routine investigation his chest X-ray revealed a pulmonary nodule in the right upper lobe. His CT scan of the chest (see <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>) showed pulmonary nodule 2cm×2cm in size.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>It was decided to follow up the patient with close monitoring and repeat radiological imaging. He was recalled again in two months. Since progression of the nodules was suspected (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 3 and 4</a>), a PET scan was performed on this occasion to see any uptake (see <a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia>Patient underwent an unremarkable bronchoscopy and a following open wedge resection of the parenchymal lung lesion. Pathology revealed deposit of pink material, double arrows on either side of bronchial cartilage (arrow) under low magnification (see <a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>) and further deposits of amyloid in bronchial and alveolar tissue including vessel walls with areas of dystrophic ossification. No malignant cells were seen (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 7</a> with congo red stain).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>DiscussionWhile the presence of nodular amyloid deposits in systemic AL disease is controversial, the presence of nodular amyloid is well established. Three forms of pulmonary disease exist in localized AL amyloid: (1) nodular opacities, (2) diffuse opacities, and (3) tracheobronchial disease. A 1983 literature review of localized amyloid lung disease identified 126 cases only, 44% having nodular disease, 3% with diffuse opacities, and 53% exhibiting tracheobronchial amyloid.<a class="elsevierStyleCrossRefs" href="#bib0040">8,9</a>Among these the presence of amyloid nodules opacification on chest imaging or histologic sampling almost uniformly indicates localized disease. The incidence of nodular disease is unclear because many are diagnosed incidentally at open lung biopsy or at autopsy. Among 223 autopsies of patients with amyloidosis between 1889 and 1979, only three cases with isolated nodular lung disease were identified.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Utz et al.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> reported seven cases of nodular disease over a 13-year period, whereas Hui et al.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> described 25 patients with lung nodules in the absence of plasma cell dyscrasia. The lesions range from 0.6 to 9cm (mean of 3cm) in size, present as multiple nodules of varying size in 58% of cases, and often appear peripherally in the lower lobes.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a> The amyloid deposit is typically surrounded by plasma cells, lymphocytes, and giant cells; small amounts of amyloid can be found in contiguous blood vessels.<a class="elsevierStyleCrossRefs" href="#bib0050">10,12</a>Dystrophic calcification and bone formation were seen in over one third of lesions.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Amyloid nodules grow slowly, if at all, and can cavitate.<a class="elsevierStyleCrossRefs" href="#bib0065">13–15</a> Unless densely calcified, all nodules should expand at similar rates. Dyssynchronous growth of one lesion warrants investigation to rule out carcinoma. Typically, nodular disease does not impair lung function nor impact survivorship.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>The pathogenesis of organ involvement in AL disease, be it systemic or localized, arises from the deposition of monoclonal κ or λ immunoglobulin (Ig) light chains. In systemic disease, clonally expanded plasma cells residing in the bone marrow secrete excessive quantities of monoclonal Ig, which circulates in blood to target organs. Typically AL deposits are composed of the variable region of λVI or κI light-chains. Less commonly, part or the entire Ig constant region is represented. Genotyping of these two light-chain subgroups suggests that genetic rearrangements may underlie production of amyloidogenic proteins in AL disease. Amyloid deposition is widespread in AL disease, although only specific organs may be clinically involved.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>Amino acid analyses of localized amyloid deposits reveal AL protein with κI and λIII light-chain subgroups predominating.<a class="elsevierStyleCrossRefs" href="#bib0085">17–19</a> In contrast to systemic disease, monoclonal proteins constituting localized amyloid deposits arise from a small number of plasma cells surrounding the lesion. Skin, urethra and urinary bladder, eye, larynx and supraglottic area, tracheobronchial tree, and lung parenchyma are sites most commonly involved by localized amyloid. Monoclonal light-chain does not circulate or deposit outside the target organ.Radiologically among 28 cases of amyloid nodules, 29% calcified and 11% cavitated.<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> Pickford et al.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> reported CT figures of five patients with localized nodular AL; 60% had one nodule, 20% had two nodules, and 20% had 10 nodules. A separate series observed multiple nodules in 67% of the cases.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Eighty percent of the nodules had smooth contours and were located in the subpleural region of the midzone; 20% of the nodules were spiculated. No associated adenopathy or pleural disease was detected. With diffuse variety of AL disease reticular and reticulonodular patterns are reported,<a class="elsevierStyleCrossRef" href="#bib0060">12</a> although peripheral alveolar opacities occur as well. Despite reports of reticulonodular opacities in localized AL, this X-ray pattern should prompt thorough investigations for primary systemic (AL) disease. With tracheobronchial variety of AL disease chest X-rays are normal in 50% of cases. Findings in other cases include atelectasis or lobar collapse, calcified extraluminal amyloid deposits, bronchiectasis, or hilar adenopathy.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> CT, unlike bronchoscopy, demonstrates the full extent of disease: (a) airway wall thickening, (b) irregular narrowing of airway lumen, and (c) heterotopic calcification of amyloid deposits in airway walls.<a class="elsevierStyleCrossRefs" href="#bib0110">22–25</a> Additionally, CT depicts airways beyond critical narrowing, affording full assessment of the airway.PET imaging is a useful diagnostic and staging tool in the evaluation of suspected or known carcinoma. FDG (18 F- fluorodeoxyglucose) enters tumor cells as a consequence of increased cellular and metabolic activity. As with other diagnostic modalities, false positives can occur in cases of tuberculosis, aspergillosis, histoplasmosis and inflammatory disorders. Even though all agree the rate of false positive is low one should be aware of other possible clinical entities that can complicate the specificity of PET scanning.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> We acknowledge that FDG as a radiotracer may be insensitive to detecting amyloid which would explain the above rare finding. Furthermore, one could speculate that radiotracers used specifically to detect amyloid e.g. C11-PIB, may have clinched the diagnosis but their current use is restricted to research settings only.The published data addressing prognosis and treatment of amyloid localized to the lung are anecdotal. Nodular disease may slowly progress, with increasing size or number of lesions, but does not impact on lung gas exchange or patient survival. Diffuse parenchymal involvement can impair lung physiology and lead to death. Rubinow et al.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> reported on four patients with diffuse lung involvement, three of whom died of respiratory failure. Corticosteroids had no effect on the course of disease in two of these patients. Systemic chemotherapy is not advocated for treatment of localized disease; however, diffuse parenchymal involvement may warrant consideration of aggressive therapy given its inexorable course.Supportive care should be directed at minimizing mucous production, which may further compromise airway lumen caliber. Antibiotics, regular nebulizer use, and occasional courses of oral or inhaled glucocorticoids are useful adjuncts to airway debridement." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xres547642" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec565522" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres547643" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec565523" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-11-16" "fechaAceptado" => "2012-01-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec565522" "palabras" => array:6 [ 0 => "Amyloidosis" 1 => "Nodular" 2 => "Local" 3 => "PET scan" 4 => "Tracheobronchial amyloidosis" 5 => "Lung diseases" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec565523" "palabras" => array:6 [ 0 => "Amiloidose" 1 => "Nodular" 2 => "Local" 3 => "Tomografia de emissão positrónica (TEP)" 4 => "Amiloidose traqueobrônquica" 5 => "Doenças pulmonares" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Amyloidosis results from proteins being deposited as insoluble β-pleated sheets and disrupting organ function. Each precursor protein induces a separate spectrum of organ involvement, and different disease manifestations within the lung. Although autopsy findings often demonstrate amyloid deposits in various compartments of the lung, few are manifested pathologically. Amyloid lung nodules with positron emission tomography (PET) uptake are rare. We describe a rare case where PET uptake was detected in a pulmonary amyloid nodule. To our knowledge there are six previously reported cases in the English literature.This review also focuses on amyloid derived from immunoglobulin light-chain protein (AL disease), which most frequently involves the lung in both systemic and localized forms of the disease. Manifestations of AL-related lung disease range from nodules identified on incidental chest films to diffuse alveolar and septal deposition mimicking malignancy and or diffuse alveolar damage." ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "A amiloidose é causada por proteínas depositadas como lâminas β insolúveis e que interferem com o funcionamento dos órgãos. Cada proteína precursora induz um espectro diferenciado de envolvimento dos órgãos, e diferentes manifestações de doença no pulmão. Apesar dos achados de autópsias revelarem frequentemente depósitos de amilóide em vários compartimentos do pulmão, poucos se manifestam patologicamente. A captação de nódulos de amilóide do pulmão na tomografia de emissão de positrões (PET) é rara. Descrevemos um caso raro em que foram detectados nódulos de amiloidose pulmonar através do PET. Que seja do nosso conhecimento, existem seis casos registados anteriormente na literatura Inglesa.Esta análise também se centra na amiloidose derivada da proteína de cadeia leve de imunoglobulina (doença de AL – Amiloidose primária), que frequentemente envolve o pulmão tanto em formas localizadas como sistémicas da doença. As manifestações da doença pulmonar relacionadas com a AL variam desde nódulos identificados em incidências de raio-X do tórax até à deposição septal, simulando malignidade, e/ou em danos difusos alveolares." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 899 "Ancho" => 900 "Tamanyo" => 86067 ] ] "descripcion" => array:1 [ "en" => "CT on presentation showing a pulmonary nodule 2cm×2cm in size." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 903 "Ancho" => 900 "Tamanyo" => 84229 ] ] "descripcion" => array:1 [ "en" => "CT on presentation. Another level." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 707 "Ancho" => 900 "Tamanyo" => 72101 ] ] "descripcion" => array:1 [ "en" => "Follow-up CT scan showing the nodule increase in size and with spiculation." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 707 "Ancho" => 900 "Tamanyo" => 67158 ] ] "descripcion" => array:1 [ "en" => "Follow-up CT scan same level as <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>." ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1979 "Ancho" => 2917 "Tamanyo" => 380187 ] ] "descripcion" => array:1 [ "en" => "PET scan: figure showing uptake corresponding to the nodule seen on CT of the chest." ] ] 5 => array:7 [ "identificador" => "fig0030" "etiqueta" => "Figures 6 and 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6v7.jpeg" "Alto" => 1368 "Ancho" => 900 "Tamanyo" => 191805 ] ] "descripcion" => array:1 [ "en" => "Histology showing congo red staining confirming diagnosis of amyloid. For interpretation of the references to color in this figure legend, the reader is referred to the web version of the article.)" ] ] 6 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "r/o: rule out, na: not available." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <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">Paper \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">Year of publication \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">Age/gender \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">Etiology of further workup \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">Further intervention \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1. Currie et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73 female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r/o ca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Video-assisted thorascopic wedge biopsy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2. Ollenberger et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">85 male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r/o ca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Upper lobe segmentectomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3. Umeda et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r/o ca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Video-assisted thorascopic biopsy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4. Kung et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">68 female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r/o ca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lung lobectomy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5. Yadav et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">55 male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">r/o ca \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Wedge excision \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6. Grubstein et al. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">59 female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">na \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">na-comment: described 2 other cases of lymphoma \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884601.png" ] ] ] ] "descripcion" => array:1 [ "en" => "PET positive cases with amyloid described in the literature." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ueber einem Gehirn und Rueckenmark des Menschen aufgefundene Substanz mit chemischen reaction der Cellulose" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "V.R. 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Case report

Detection of nodular pulmonary amyloid by PET positive scan—Deception for lung cancer

Detecção de amilóide pulmonar nodular por PET positiva – simulando cancro do pulmão

A.M. Khana,

Corresponding author

dramirkhan@hotmail.com

Corresponding author.

, K. Manzoora, V. Jainb, P. Mahadeviac, A. Bermana

a Department of Pulmonary, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA

b Department of Radiology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA

c Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA

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which define organ involvement and disease manifestations&#46; There are four major categories of systemic amyloidosis &#40;&#8220;A&#8221; for amyloid and a letter indicating the protein involved&#41;&#58; &#40;1&#41; primary or immunoglobulin light-chain &#40;AL&#41; disease&#44; &#40;2&#41; secondary or amyloid protein A &#40;AA&#41; disease&#44; &#40;3&#41; hereditary or mutant transthyretin &#40;ATTR&#41; disease&#44; and &#40;4&#41; dialysis-associated or &#946;<span class="elsevierStyleInf">2</span>-microglobulin &#40;&#946;<span class="elsevierStyleInf">2</span>M&#41; disease&#46; Other less prevalent forms of amyloid disease exist&#44; locally affecting the pancreas &#40;islet amyloid polypeptide&#44; AIAPP&#41; and brain &#40;&#946;-amyloid precursor protein&#44; A&#946;&#41;&#44; or genetically transmitted systemic disease &#40;apolipoprotein AI&#44; gelsolin&#44; fibrinogen&#44; lysozyme precursor proteins&#41;&#46; Pulmonary manifestations mainly occur from AL disease&#44; this may be local or systemic depending upon the expression of monoclonal protein either just locally in the lung or in the serum&#47;urine&#46; Amyloid lung nodules with PET uptake are rare&#46; We describe a rare case where positron emission tomography &#40;PET&#41; uptake was noticed in pulmonary amyloid nodules&#46; To our knowledge there are six reported cases in the English literature to date<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;7</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case report</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 68-year-old male with a past medical history significant for hypertension and osteoarthritis presented with bilateral knee pain worse for the last few months&#46; He was a non-smoker&#44; denied any abuse of alcohol or any other illicit substances&#46; He had no known allergies and his past surgical history was only significant for an appendicectomy several years ago&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">His general physical and systemic examination except for knee crepitus in both knees was otherwise normal&#46; His laboratory examination including a complete blood count&#44; basic chemistry and liver function tests including a clotting profile was normal&#46; No abnormality was seen on an electrocardiogram and pulmonary function tests&#46; On routine investigation his chest X-ray revealed a pulmonary nodule in the right upper lobe&#46; His CT scan of the chest &#40;see <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a>&#41; showed pulmonary nodule 2<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>cm in size&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">It was decided to follow up the patient with close monitoring and repeat radiological imaging&#46; He was recalled again in two months&#46; Since progression of the nodules was suspected &#40;<a class="elsevierStyleCrossRefs" href="#fig0015">Figs&#46; 3 and 4</a>&#41;&#44; a PET scan was performed on this occasion to see any uptake &#40;see <a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Patient underwent an unremarkable bronchoscopy and a following open wedge resection of the parenchymal lung lesion&#46; Pathology revealed deposit of pink material&#44; double arrows on either side of bronchial cartilage &#40;arrow&#41; under low magnification &#40;see <a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41; and further deposits of amyloid in bronchial and alveolar tissue including vessel walls with areas of dystrophic ossification&#46; No malignant cells were seen &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 7</a> with congo red stain&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">While the presence of nodular amyloid deposits in systemic AL disease is controversial&#44; the presence of nodular amyloid is well established&#46; Three forms of pulmonary disease exist in localized AL amyloid&#58; &#40;1&#41; nodular opacities&#44; &#40;2&#41; diffuse opacities&#44; and &#40;3&#41; tracheobronchial disease&#46; A 1983 literature review of localized amyloid lung disease identified 126 cases only&#44; 44&#37; having nodular disease&#44; 3&#37; with diffuse opacities&#44; and 53&#37; exhibiting tracheobronchial amyloid&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Among these the presence of amyloid nodules opacification on chest imaging or histologic sampling almost uniformly indicates localized disease&#46; The incidence of nodular disease is unclear because many are diagnosed incidentally at open lung biopsy or at autopsy&#46; Among 223 autopsies of patients with amyloidosis between 1889 and 1979&#44; only three cases with isolated nodular lung disease were identified&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Utz et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reported seven cases of nodular disease over a 13-year period&#44; whereas Hui et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> described 25 patients with lung nodules in the absence of plasma cell dyscrasia&#46; The lesions range from 0&#46;6 to 9<span class="elsevierStyleHsp" style=""></span>cm &#40;mean of 3<span class="elsevierStyleHsp" style=""></span>cm&#41; in size&#44; present as multiple nodules of varying size in 58&#37; of cases&#44; and often appear peripherally in the lower lobes&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> The amyloid deposit is typically surrounded by plasma cells&#44; lymphocytes&#44; and giant cells&#59; small amounts of amyloid can be found in contiguous blood vessels&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Dystrophic calcification and bone formation were seen in over one third of lesions&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Amyloid nodules grow slowly&#44; if at all&#44; and can cavitate&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a> Unless densely calcified&#44; all nodules should expand at similar rates&#46; Dyssynchronous growth of one lesion warrants investigation to rule out carcinoma&#46; Typically&#44; nodular disease does not impair lung function nor impact survivorship&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The pathogenesis of organ involvement in AL disease&#44; be it systemic or localized&#44; arises from the deposition of monoclonal &#954; or &#955; immunoglobulin &#40;Ig&#41; light chains&#46; In systemic disease&#44; clonally expanded plasma cells residing in the bone marrow secrete excessive quantities of monoclonal Ig&#44; which circulates in blood to target organs&#46; Typically AL deposits are composed of the variable region of &#955;VI or &#954;I light-chains&#46; Less commonly&#44; part or the entire Ig constant region is represented&#46; Genotyping of these two light-chain subgroups suggests that genetic rearrangements may underlie production of amyloidogenic proteins in AL disease&#46; Amyloid deposition is widespread in AL disease&#44; although only specific organs may be clinically involved&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Amino acid analyses of localized amyloid deposits reveal AL protein with &#954;I and &#955;III light-chain subgroups predominating&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;19</span></a> In contrast to systemic disease&#44; monoclonal proteins constituting localized amyloid deposits arise from a small number of plasma cells surrounding the lesion&#46; Skin&#44; urethra and urinary bladder&#44; eye&#44; larynx and supraglottic area&#44; tracheobronchial tree&#44; and lung parenchyma are sites most commonly involved by localized amyloid&#46; Monoclonal light-chain does not circulate or deposit outside the target organ&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Radiologically among 28 cases of amyloid nodules&#44; 29&#37; calcified and 11&#37; cavitated&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> Pickford et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> reported CT figures of five patients with localized nodular AL&#59; 60&#37; had one nodule&#44; 20&#37; had two nodules&#44; and 20&#37; had 10 nodules&#46; A separate series observed multiple nodules in 67&#37; of the cases&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Eighty percent of the nodules had smooth contours and were located in the subpleural region of the midzone&#59; 20&#37; of the nodules were spiculated&#46; No associated adenopathy or pleural disease was detected&#46; <span class="elsevierStyleItalic">With diffuse variety of AL disease</span> reticular and reticulonodular patterns are reported&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> although peripheral alveolar opacities occur as well&#46; Despite reports of reticulonodular opacities in localized AL&#44; this X-ray pattern should prompt thorough investigations for primary systemic &#40;AL&#41; disease&#46; <span class="elsevierStyleItalic">With tracheobronchial variety of AL disease</span> chest X-rays are normal in 50&#37; of cases&#46; Findings in other cases include atelectasis or lobar collapse&#44; calcified extraluminal amyloid deposits&#44; bronchiectasis&#44; or hilar adenopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> CT&#44; unlike bronchoscopy&#44; demonstrates the full extent of disease&#58; &#40;a&#41; airway wall thickening&#44; &#40;b&#41; irregular narrowing of airway lumen&#44; and &#40;c&#41; heterotopic calcification of amyloid deposits in airway walls&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;25</span></a> Additionally&#44; CT depicts airways beyond critical narrowing&#44; affording full assessment of the airway&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">PET imaging is a useful diagnostic and staging tool in the evaluation of suspected or known carcinoma&#46; FDG &#40;18 F- fluorodeoxyglucose&#41; enters tumor cells as a consequence of increased cellular and metabolic activity&#46; As with other diagnostic modalities&#44; false positives can occur in cases of tuberculosis&#44; aspergillosis&#44; histoplasmosis and inflammatory disorders&#46; Even though all agree the rate of false positive is low one should be aware of other possible clinical entities that can complicate the specificity of PET scanning&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> We acknowledge that FDG as a radiotracer may be insensitive to detecting amyloid which would explain the above rare finding&#46; Furthermore&#44; one could speculate that radiotracers used specifically to detect amyloid e&#46;g&#46; C11-PIB&#44; may have clinched the diagnosis but their current use is restricted to research settings only&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The published data addressing prognosis and treatment of amyloid localized to the lung are anecdotal&#46; Nodular disease may slowly progress&#44; with increasing size or number of lesions&#44; but does not impact on lung gas exchange or patient survival&#46; Diffuse parenchymal involvement can impair lung physiology and lead to death&#46; Rubinow et al&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> reported on four patients with diffuse lung involvement&#44; three of whom died of respiratory failure&#46; Corticosteroids had no effect on the course of disease in two of these patients&#46; Systemic chemotherapy is not advocated for treatment of localized disease&#59; however&#44; diffuse parenchymal involvement may warrant consideration of aggressive therapy given its inexorable course&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Supportive care should be directed at minimizing mucous production&#44; which may further compromise airway lumen caliber&#46; Antibiotics&#44; regular nebulizer use&#44; and occasional courses of oral or inhaled glucocorticoids are useful adjuncts to airway debridement&#46;</p></span></span>"
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          "identificador" => "xpalclavsec565522"
          "titulo" => "Keywords"
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          "identificador" => "xres547643"
          "titulo" => "Resumo"
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          "titulo" => "Palavras-chave"
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          "titulo" => "Introduction"
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          "titulo" => "Case report"
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        6 => array:2 [
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          "titulo" => "Discussion"
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    "tienePdf" => true
    "fechaRecibido" => "2011-11-16"
    "fechaAceptado" => "2012-01-31"
    "PalabrasClave" => array:2 [
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Amyloidosis"
            1 => "Nodular"
            2 => "Local"
            3 => "PET scan"
            4 => "Tracheobronchial amyloidosis"
            5 => "Lung diseases"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:6 [
            0 => "Amiloidose"
            1 => "Nodular"
            2 => "Local"
            3 => "Tomografia de emiss&#227;o positr&#243;nica &#40;TEP&#41;"
            4 => "Amiloidose traqueobr&#244;nquica"
            5 => "Doen&#231;as pulmonares"
          ]
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Amyloidosis results from proteins being deposited as insoluble &#946;-pleated sheets and disrupting organ function&#46; Each precursor protein induces a separate spectrum of organ involvement&#44; and different disease manifestations within the lung&#46; Although autopsy findings often demonstrate amyloid deposits in various compartments of the lung&#44; few are manifested pathologically&#46; Amyloid lung nodules with positron emission tomography &#40;PET&#41; uptake are rare&#46; We describe a rare case where PET uptake was detected in a pulmonary amyloid nodule&#46; To our knowledge there are six previously reported cases in the English literature&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This review also focuses on amyloid derived from immunoglobulin light-chain protein &#40;AL disease&#41;&#44; which most frequently involves the lung in both systemic and localized forms of the disease&#46; Manifestations of AL-related lung disease range from nodules identified on incidental chest films to diffuse alveolar and septal deposition mimicking malignancy and or diffuse alveolar damage&#46;</p></span>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A amiloidose &#233; causada por prote&#237;nas depositadas como l&#226;minas &#946; insol&#250;veis e que interferem com o funcionamento dos &#243;rg&#227;os&#46; Cada prote&#237;na precursora induz um espectro diferenciado de envolvimento dos &#243;rg&#227;os&#44; e diferentes manifesta&#231;&#245;es de doen&#231;a no pulm&#227;o&#46; Apesar dos achados de aut&#243;psias revelarem frequentemente dep&#243;sitos de amil&#243;ide em v&#225;rios compartimentos do pulm&#227;o&#44; poucos se manifestam patologicamente&#46; A capta&#231;&#227;o de n&#243;dulos de amil&#243;ide do pulm&#227;o na tomografia de emiss&#227;o de positr&#245;es &#40;PET&#41; &#233; rara&#46; Descrevemos um caso raro em que foram detectados n&#243;dulos de amiloidose pulmonar atrav&#233;s do PET&#46; Que seja do nosso conhecimento&#44; existem seis casos registados anteriormente na literatura Inglesa&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Esta an&#225;lise tamb&#233;m se centra na amiloidose derivada da prote&#237;na de cadeia leve de imunoglobulina &#40;doen&#231;a de AL &#8211; Amiloidose prim&#225;ria&#41;&#44; que frequentemente envolve o pulm&#227;o tanto em formas localizadas como sist&#233;micas da doen&#231;a&#46; As manifesta&#231;&#245;es da doen&#231;a pulmonar relacionadas com a AL variam desde n&#243;dulos identificados em incid&#234;ncias de raio-X do t&#243;rax at&#233; &#224; deposi&#231;&#227;o septal&#44; simulando malignidade&#44; e&#47;ou em danos difusos alveolares&#46;</p></span>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">CT on presentation showing a pulmonary nodule 2<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;2<span class="elsevierStyleHsp" style=""></span>cm in size&#46;</p>"
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">CT on presentation&#46; Another level&#46;</p>"
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Follow-up CT scan same level as <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PET scan&#58; figure showing uptake corresponding to the nodule seen on CT of the chest&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Histology showing congo red staining confirming diagnosis of amyloid&#46; For interpretation of the references to color in this figure legend&#44; the reader is referred to the web version of the article&#46;&#41;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">r&#47;o&#58; rule out&#44; na&#58; not available&#46;</p>"
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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">Paper&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">Year of publication&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">Age&#47;gender&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">Etiology of further workup&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">Further intervention&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" title="table-entry  " align="left" valign="top">1&#46; Currie et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73 female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">r&#47;o ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Video-assisted thorascopic wedge biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&#46; Ollenberger et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">85 male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">r&#47;o ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Upper lobe segmentectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&#46; Umeda et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">60 female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">r&#47;o ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Video-assisted thorascopic biopsy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4&#46; Kung et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68 female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">r&#47;o ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lung lobectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5&#46; Yadav et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55 male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">r&#47;o ca&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Wedge excision&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6&#46; Grubstein et al&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">59 female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">na&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">na-comment&#58; described 2 other cases of lymphoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">PET positive cases with amyloid described in the literature&#46;</p>"
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                      "titulo" => "Ueber einem Gehirn und Rueckenmark des Menschen aufgefundene Substanz mit chemischen reaction der Cellulose"
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                          "etal" => false
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                        "tituloSerie" => "Virchows Arch Pathol Anat"
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Article information

ISSN: 08732159
Original language: English

DOI:10.1016/j.rppneu.2012.01.007

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Year/Month	Html	Pdf	Total

2024 November	10	8	18
2024 October	54	37	91
2024 September	63	27	90
2024 August	88	43	131
2024 July	72	39	111
2024 June	57	28	85
2024 May	49	35	84
2024 April	41	25	66
2024 March	56	30	86
2024 February	60	23	83
2024 January	33	19	52
2023 December	34	29	63
2023 November	42	36	78
2023 October	38	29	67
2023 September	44	31	75
2023 August	46	29	75
2023 July	37	24	61
2023 June	40	16	56
2023 May	66	30	96
2023 April	39	14	53
2023 March	60	25	85
2023 February	49	17	66
2023 January	37	24	61
2022 December	52	46	98
2022 November	55	37	92
2022 October	61	31	92
2022 September	33	36	69
2022 August	44	34	78
2022 July	43	44	87
2022 June	41	31	72
2022 May	65	33	98
2022 April	69	40	109
2022 March	61	46	107
2022 February	56	34	90
2022 January	33	36	69
2021 December	26	43	69
2021 November	37	37	74
2021 October	44	39	83
2021 September	56	37	93
2021 August	27	34	61
2021 July	34	25	59
2021 June	30	22	52
2021 May	53	30	83
2021 April	85	65	150
2021 March	72	15	87
2021 February	66	14	80
2021 January	40	20	60
2020 December	63	9	72
2020 November	62	17	79
2020 October	50	16	66
2020 September	82	31	113
2020 August	103	20	123
2020 July	116	26	142
2020 June	118	31	149
2020 May	119	19	138
2020 April	82	16	98
2020 March	84	11	95
2020 February	114	21	135
2020 January	115	21	136
2019 December	103	18	121
2019 November	121	12	133
2019 October	111	26	137
2019 September	93	15	108
2019 August	248	23	271
2019 July	276	21	297
2019 June	321	16	337
2019 May	297	17	314
2019 April	298	26	324
2019 March	404	15	419
2019 February	346	10	356
2019 January	306	16	322
2018 December	253	8	261
2018 November	112	0	112
2018 October	134	7	141
2018 September	89	4	93
2018 August	105	30	135
2018 July	85	25	110
2018 June	93	13	106
2018 May	132	20	152
2018 April	195	24	219
2018 March	249	16	265
2018 February	213	18	231
2018 January	154	20	174
2017 December	313	14	327
2017 November	126	22	148
2017 October	54	25	79
2017 September	61	17	78
2017 August	59	14	73
2017 July	60	19	79
2017 June	59	14	73
2017 May	66	19	85
2017 April	46	7	53
2017 March	56	11	67
2017 February	34	9	43
2017 January	28	6	34
2016 December	47	24	71
2016 November	91	12	103
2016 October	72	17	89
2016 September	76	7	83
2016 August	55	11	66
2016 July	23	15	38
2016 June	0	12	12
2016 April	95	2	97
2016 March	136	17	153
2016 February	136	14	150
2016 January	117	16	133
2015 December	110	11	121
2015 November	108	6	114
2015 October	108	15	123
2015 September	117	10	127
2015 August	97	5	102
2015 July	119	9	128
2015 June	72	5	77
2015 May	97	9	106
2015 April	125	18	143
2015 March	123	8	131
2015 February	162	4	166
2015 January	101	13	114
2014 December	99	8	107
2014 November	130	11	141
2014 October	141	13	154
2014 September	130	13	143
2014 August	142	6	148
2014 July	154	11	165
2014 June	105	11	116
2014 May	391	9	400
2014 April	192	13	205
2014 March	240	20	260
2014 February	228	17	245
2014 January	217	18	235
2013 December	209	13	222
2013 November	170	29	199
2013 October	113	25	138
2013 September	90	28	118
2013 August	94	27	121
2013 July	89	31	120
2013 June	80	19	99
2013 May	91	26	117
2013 April	124	36	160
2013 March	75	28	103
2013 February	86	26	112
2013 January	108	30	138
2012 December	92	44	136
2012 November	90	42	132

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