neuroendocrine ( ne ) tumors of the lung , arising from kulchitzky cells of the bronchial mucosa , can be categorized into typical carcinoid , atypical carcinoid , large cell neuroendocrine carcinoma ( lcnec ) , and small cell lung carcinoma ( sclc ) . the prognosis and behavioral features of these ne tumors worsen as the grade of malignancy increases . it is reported that positron emission tomography ( pet ) with fluorine-18 fluorodeoxyglucose ( fdg ) increases diagnostic accuracy when differentiating benign and malignant lesions . in addition , it is shown to improve identification of lymph node and extrathoracic metastasis in pulmonary neoplasms . pulmonary carcinoid tumors have been known to exhibit little activity on pet scans and usually have less fdg uptake than expected for malignant tumors . as much as it is used to evaluate non - small cell carcinoma of the lung , fdg pet has also been studied for the evaluation of sclc . fdg pet was found to be highly sensitive in detecting sclc and useful for evaluating prognosis and tumor stage . in this review , we describe the spectrum of integrated pet / ct findings on ne tumors of the lung . we also describe the usefulness of this imaging modality in patients with known or suspected ne tumors of the lung . neuroendocrine tumors of the lung share ne morphologic features such as organoid nesting , palisading , rosettes , and a trabecular growth pattern . in 1991 , travis et al . proposed the following classification of pulmonary ne tumors : low - grade malignancy , namely , typical carcinoid tumors ; medium - grade malignancy , which includes atypical carcinoid tumors ; and high - grade malignancy , such as lcnec and sclc ( fig . photomicrograph shows small nests of uniform cells without mitotic or necrotic features ( h&e , 40 ) . photomicrogra ph shows nuclear pleomorphism and mitosis ( arrow ) ( h&e , 400 ) . photomicrograph shows a neuroendocri ne appearance with peripheral palisading and rosettes ( h&e , 4 0 ) . photomicrograph shows high cellularity ; the small round cells have scanty cytoplasm and coarse chromatin . also note frequent mitoses ( h&e , 200).\ histopathologic features of pulmonary neuroendocrine tumor of the lungs . photomicrograph shows small nests of uniform cells without mitotic or necrotic features ( h&e , 40 ) . photomicrogra ph shows nuclear pleomorphism and mitosis ( arrow ) ( h&e , 400 ) . photomicrograph shows a neuroendocri ne appearance with peripheral palisading and rosettes ( h&e , 4 0 ) . photomicrograph shows high cellularity ; the small round cells have scanty cytoplasm and coarse chromatin . these tumors represent a broad clinicopathologic spectrum with variable morphologic features and biologic behaviors . in terms of histologic features predictive of prognosis , typical carcinoid tumors show no evidence of necrosis and less than 2 mitoses per 10 high power fields ( hpfs ) ( or 2  mm ) of viable tumor ( fig . 1a ) , whereas atypical carcinoid tumors have areas of necrosis or 210 mitoses per 10 hpfs ( fig . 1b ) . the histopathologic diagnostic criteria for lcnec proposed by the world health organization ( who ) in 1999 is as follows : ( 1 ) ne morphologic features ( organoid nesting , palisading , rosettes , or trabecular growth pattern ) ; ( 2 ) high mitotic rate ( > 10 per 10 hpfs ) ; ( 3 ) necrosis ( often large zones ) ; ( 4 ) cytologic features different from sclc ( large cell size , polygonal , low nuclear / cytoplasmatic ratio , finely granular eosinophilic cytoplasm , coarse nuclear chromatin , and frequent nucleoli ) ; ( 5 ) positive immunohistochemical staining for one or more ne markers including chromogranin a , synaptophysin and neural cell adhesion molecule ( ncam / cd56 ) ( fig . therefore , the prognosis and tumor biology of these ne tumors worsen as the grade of malignancy increases ( fig . therefore , imaging studies show a well - defined hilar or perihilar mass as an isolated finding or with associated distal parenchymal changes of atelectasis or obstructive pneumonia ( fig . the tumors appear at ct as a spherical or ovoid nodule or mass with well - defined and slightly lobulated border . they are typically located close to central bronchi , often near the bifurcation area . on ct scans , calcification or ossification can be seen in up to 30% of tumors , and manifests as punctate or diffuse . therefore , observation of a central tumor that causes a bronchus to be narrowed , deformed or obstructed and that displays punctate or diffuse calcification should suggest the diagnosis of bronchial carcinoids ( fig . 2 ) . they occasionally present with a small nodule entirely located within the lumen of a bronchus . even a small nodule , located beyond the origin of a subsegmental bronchus , may be noticed abutting a subsegmental bronchus or displaying a small endoluminal component of tumor at thin - section ct . peripheral carcinoids may manifest as a well - defined , lobulated nodule or mass without ct evidence of a bronchial relationship . typical and atypical carcinoid tumors show high enhancement , more than 30 hu of net enhancement . ( b ) transverse unenhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the level of the left lower lobar bronchus demonstrates the upper portion of the tumor involving the distal bronchus intermedius with an intrabronchial component of the tumor ( arrow ) . ( c ) mediastinal window image of a transverse ct scan ( 1.0-mm section thickness , 120  mas ) obtained at the level of the inferior pulmonary vein shows a large mass containing nodular calcifications ( arrows ) within the lesion in the right middle lobe . ( a ) and ( c ) are reproduced with permission from chong et al .. 
 figure 3a 58-year - old man with typical carcinoid . mediastinal window images of transverse ct scans before ( left ) and 60  s after ( right ) contrast medium injection show enhancing nodules ( arrows ; 37 hu on unenhanced scan and 76 hu on enhanced scan ) in the right middle lobe . a 24-year - old man with typical carcinoid . ( b ) transverse unenhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the level of the left lower lobar bronchus demonstrates the upper portion of the tumor involving the distal bronchus intermedius with an intrabronchial component of the tumor ( arrow ) . ( c ) mediastinal window image of a transverse ct scan ( 1.0-mm section thickness , 120  mas ) obtained at the level of the inferior pulmonary vein shows a large mass containing nodular calcifications ( arrows ) within the lesion in the right middle lobe . ( a ) and ( c ) are reproduced with permission from chong et al .. a 58-year - old man with typical carcinoid . mediastinal window images of transverse ct scans before ( left ) and 60  s after ( right ) contrast medium injection show enhancing nodules ( arrows ; 37 hu on unenhanced scan and 76 hu on enhanced scan ) in the right middle lobe . imaging findings of lcnecs are similar to those of other common non - small cell lung cancers . approximately 80% of lcnecs appear as a peripheral mass or nodule , whereas 20% of the tumors present with a central mass and attendant atelectasis or distal mucus plugging . most sclcs are located centrally and appear with mediastinal ( 92% ) or hilar ( 84% ) lymphadenopathy with displacement or narrowing of the tracheobronchial trees ( 68% ) or major vessels ( 68% ) . other intrathoracic ct findings are major ( at least lobar ) atelectasis ( 30% ) , a non - contiguous parenchymal mass ( 41% ) , and pleural effusion ( 38% ) . in 510% of cases , in carcinoids and lcnecs , tumor stages are determined by the tnm and american joint committee on cancer staging systems as in non - small cell lung cancers . however , sclc is usually classified using a two - stage system , i.e. , limited ( ld ) or extensive disease ( ed ) . ld is defined as a tumor confined to one hemithorax including regional mediastinal and supraclavicular lymph nodes , whereas ed is defined as disease beyond these boundaries . however , the veterans administration lung study group ( valg ) definition of ld , primary tumor and nodal involvement limited to one hemithorax , is widely used . in a few studies about the pet findings of carcinoid tumors , it has been initially reported that typical carcinoid tumors do not exhibit increased activity during pet and usually have less fdg uptake than expected for malignant tumors ( fig . however , subsequent reports described that typical carcinoid tumors show variable uptake according to mitotic figures and tumor proliferation . atypical carcinoid tumors also show variable fdg uptake ( fig . 5 ) . according to a report , three ( 60% ) of five atypical carcinoids had higher than mediastinal uptake ( maximum suv , 4.07.1 ) . therefore , both typical and atypical carcinoid tumors show variable fdg uptake according to mitotic figure and tumor proliferation . ( a ) transverse unenhanced ct scan ( 5-mm section thickness , 40  mas ) obtained at the level of the right inferior pulmonary vein shows a 42-mm - sized mass ( arrow ) in the right lower lobe . ( b),(c ) fdg pet ( b ) and integrated pet / ct ( c ) scans show little fdg uptake ( arrow ) within the tumor ( suvmax , 3.4 ) . ( a ) lung window image of a transverse unenhanced ct scan ( 5-mm section thickness , 40  mas ) obtained at the level of the right inferior pulmonary vein shows a 25-mm - sized nodule ( arrow ) in the right middle lobe . ( b ) integrated pet / ct scan shows high fdg uptake ( arrow ) within the tumor ( suvmax , 7.1 ) . a 56-year - old man with typical carcinoid ( t2n0m0 , ib ) . ( a ) transverse unenhanced ct scan ( 5-mm section thickness , 40  mas ) obtained at the level of the right inferior pulmonary vein shows a 42-mm - sized mass ( arrow ) in the right lower lobe . ( b),(c ) fdg pet ( b ) and integrated pet / ct ( c ) scans show little fdg uptake ( arrow ) within the tumor ( suvmax , 3.4 ) . ( a ) lung window image of a transverse unenhanced ct scan ( 5-mm section thickness , 40  mas ) obtained at the level of the right inferior pulmonary vein shows a 25-mm - sized nodule ( arrow ) in the right middle lobe . ( b ) integrated pet / ct scan shows high fdg uptake ( arrow ) within the tumor ( suvmax , 7.1 ) . in the pet / ct analysis study of lcnecs , all tumors had homogeneously high fdg uptake with their maximum suvs ranging from 3.9 to 25.6 ( mean 12.0 , median 10.7 ) ( fig . , the tumors showed high fdg uptake with their suvs ranging from 6.1 to 17.3 ( mean 11.6 , median 11.7 ) ( fig . therefore , the maximum suvs of ne tumors are significantly different , listed in increasing order , in carcinoids , lcnecs and sclcs . figure 6a 70-year - old man with a large cell neuroendocrine cell carcinoma ( t1n0m0 , ia ) . ( a ) mediastinal window image of a transverse contrast - enhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the level of the left upper divisional bronchus shows a 19-mm - sized peripheral nodule ( arrow ) in the left lower lobe . ( b ) integrated pet / ct scan shows high fdg uptake ( arrow ) within the tumor ( suvmax , 10.7 ) . figure 7a 39-year - old woman with small cell lung carcinoma ( limited disease ) . ( a ) a mediastinal window image of a transverse contrast - enhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the subcarinal area shows an enlarged lymph node in the subcarinal and left hilar areas ( arrows ) . ( b ) integrated pet / ct scan shows high fdg uptake ( arrows ) within the nodes ( suvmax , 15.7 ) . a 70-year - old man with a large cell neuroendocrine cell carcinoma ( t1n0m0 , ia ) . ( a ) mediastinal window image of a transverse contrast - enhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the level of the left upper divisional bronchus shows a 19-mm - sized peripheral nodule ( arrow ) in the left lower lobe . ( b ) integrated pet / ct scan shows high fdg uptake ( arrow ) within the tumor ( suvmax , 10.7 ) . a 39-year - old woman with small cell lung carcinoma ( limited disease ) . ( a ) a mediastinal window image of a transverse contrast - enhanced ct scan ( 5-mm section thickness , 130  mas ) obtained at the subcarinal area shows an enlarged lymph node in the subcarinal and left hilar areas ( arrows ) . ( b ) integrated pet / ct scan shows high fdg uptake ( arrows ) within the nodes ( suvmax , 15.7 ) . as for the relationship between the maximum suvs of pulmonary ne tumors and tumor stages , chong et al . reported that there is no significant positive correlation between the maximum suv of primary tumors and tumor stage of carcinoids and lcnecs . in addition , the difference in maximum suv between limited and extensive stages of sclcs is not statistically significant . therefore , the estimation of maximum suvs in pulmonary ne tumors seems to be not helpful in the initial differentiation of early from advanced stages of disease . chong et al . found a significant negative correlation between the initial maximum suvs of lcnecs and sclcs and patients survival . for example , a maximum suv greater than 13.7 suggests relatively shorter survival time for patients with lcnec and those with sclc . pandit et al . reported that pet of patients with sclc is useful for predicting prognosis , especially among treated patients . after - treatment survival in pet - positive cases is significantly worse than in pet - negative cases . accurate tumor staging , particularly accurate detection of n1n3 metastatic lesions or extrathoracic tumor involvement is a determining factor in treatment modality and patient prognoses . according to a report , in lcnec , integrated pet / ct and standalone ct both showed similar and high accuracy in predicting the presence of n1 and n2 metastasis . however , pet / ct was more effective for identifying n3 ( supraclavicular ) disease and extrathoracic ( bone ) metastasis . patients with limited disease are treated with chemoradiation therapy , whereas those with extensive disease usually receive chemotherapy alone . pet has been considered valuable for initial tumor staging and for treatment planning of sclc . stage evaluation using pet is accurate and it usually concurs with the final clinical stage determined by conventional methods . carcinoids show variable fdg uptake at pet depending on their mitotic figures and the extent of tumor proliferation . the maximum suvs of ne tumors are significantly different for carcinoids , lcnecs and sclcs ( listed in order of increasing value ) . integrated pet / ct is more accurate than standalone ct or conventional staging methods in detecting extrapulmonary metastatic lesions especially in lcnecs and sclcs . moreover , the maximum suvs in lcnecs and sclcs appear to be related to patient survival . thus , integrated pet / ct is useful not only in characterizing and staging of pulmonary ne tumors but also in predicting patient prognoses in these tumors .
abstractpositron emission tomography ( pet ) with fluorine-18 fluorodeoxyglucose ( fdg ) has been known to increase diagnostic accuracy in differentiating benign and malignant lung lesions and to improve identification of lymph node and extrathoracic metastasis in pulmonary neoplasms . in this review , 
 the authors describe the spectrum of integrated pet / ct findings on neuroendocrine ( ne ) tumors of the lung . 
 we also demonstrate the usefulness of this imaging modality in patients with known or suspected ne tumors of the lung .