Lung - Cancer TNM 7th edition

IJsbrand Zijlstra, Otto van Delden, Cornelia Schaefer-Prokop and Robin Smithuis

Department of Radiology of the Academical Medical Centre, Amsterdam and the Rijnland Hospital, Leiderdorp, the Netherlands

Publicationdate

At this moment we are working on the update of the 8th edition, which will soon be published

This is an updated version of the 2005 article 'Lung cancer - staging'.
It is adapted to the new guidelines in the 7th Edition of TNM in Lung Cancer of the International Association for the Study of Lung Cancer (IASLC) Staging Committee in 2009.

Lungcancer is classified into two categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
NSCLC is a group of primary lung neoplasms with the same staging system and therapy and can be cured with resection if it is in an early stage.

In this review we will discuss:

  • TNM-classification.
  • T-staging with CT.
  • N- and M-staging with CT and PET-CT.

TNM-overview

New T-staging according to the 7th edition of the TNM-staging of lungcancer

T1
Tumor

T2
Tumor > 3 cm but

  • Involves main bronchus > 2 cm distal to carina
  • Invades visceral pleura
  • Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
  • T3
    Tumor > 7 cm or any of the following:

    • Directly invades any of the following: chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, main bronchus Atelectasis or obstructive pneumonitis of the entire lung
    • Separate tumor nodules in the same lobe

    T4
    Tumor of any size that invades the mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, or with separate tumor nodules in a different ipsilateral lobe.

    In 2009 a new Lung cancer lymph node map was proposed by the International Association for the Study of Lung Cancer (IASLC) in order to reconcile the differences between the Naruke and the MD-ATS maps and refine the definitions of the anatomic boundaries of each of the lymph node stations.

    go to the IASLC lymph node map 2009
    Stages of lung cancer adapted from the 7th Edition of TNM in Lung Cancer

    Stages
    NSCLC includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma and is staged according to the TNM-staging system.
    TNM subsets are grouped into certain stages, because these patients share similar prognostic and therapeutic options.
    For instance all stage IIIA patients have a 5 year-survival of 10%.

    In the table on the left resectable stages are indicated in green and unresectable stages are indicated in red.
    Stage IIIA is possibly resectable, usually after combined-modality therapy consisting of platinum-based chemotherapy and radiation.
    Stage IIIB, i.e. any patient who has T4 or N3 disease is virtually unresectable, but in some countries there are subgroups of patients that will get a resection.
    Evidently all patients with distant metastases (stage IV) are inoperable.

    What is new in 7th edition of TNM

    1. T1 tumors
      • T1 is subclassified in T1a: 2 cm or less and T1b: > 2 cm but 3 cm or less, since they have a different prognosis.
    2. T2 tumors
      • Small T2 tumors (> 3 cm but Large T2 tumors > 5 cm but Large T2 > 7 cm is reclassified as T3.
        T2b N0 M0 cases change from stage IB to IIA.
    3. T3 tumors
      • T3 N0 M0 is reclassified from IB to IIB
      • T3 N1 M0 from IIB to IIIA.
    4. T4 tumors
      • T4 by additional tumor nodules in the lobe of the primary is now downstaged to T3.
        These tumors will be down-staged from stage IIIB to IIIA (if N1 or N2) or to stage IIB (if N0).
      • Those cases with additional tumor nodules in other ipsilateral lobes are downstaged to T4 and not M1.
        They will be down-staged from stage IV to IIIB (if N2 or N3) and to stage IIIA (if N0 or N1).
        Tumors that are T4 due to other features will be down-staged if N0 or N1 from stage IIIB to stage IIIA.
    5. M tumors
      • Tumors associated with pleural or pericardial nodules or effusions become M1a instead of T4 and are consequently up-staged from IIIB to stage IV.
      • M tumors are subclassified into M1a (contralateral lung nodules and pleural dissemination) and M1b (distant metastasis).

    In the table on the left the changes for the new stage grouping in the revised TNM staging system .

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    LEFT: Axial image of tumor near fissure.RIGHT: Coronal reconstruction showing no transfissural growth.

    The goal of imaging is to decide whether the tumor is resectable and whether it should be a lobectomy or a pneumonectomy.

    On the left a patient with a tumor near the fissure.
    On coronal reconstructions it was demonstrated that there was no transfissural growth.
    Lobectomy therefore is a possibilty.

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    Coronal and sagital reconstruction showing transfissural growth.

    Lobectomy is not possible if there is:

    • Transfissural growth.
    • Pulmonary vascular invasion.
    • Invasion of main bronchus.
    • Involvement of upper and lower lobe bronchi.

    Thin collimation and MPR are necessary in order to clearly demonstrate the relation of a tumor with the fissure.

    On the left a case with transfissural growth on both coronal and sagittal reconstructions.
    Lobectomy is not possible.

    T-Staging

    In the Table on the left the new T-staging according to the 7th edition of the TNM-staging of lungcancer.

    T-staging is best done with CT to determine the local extent and to look for satellite nodules.
    There are advantages if CT precedes bronchoscopy and the information from CT is used by the bronchoscopist.
    CT however has important limitations in overall staging.
    Preoperative predictions with CT differ from operative staging in 45% of cases.
    Patients are being both over- and understaged.
    CT staging remains unsatisfactory for detecting hilar (N1) and mediastinal (N2 and N3) lymph node metastases, and for chest wall involvement (T3) or mediastinal invasion (T4), in which sensitivity and specificity can be less than 65%.

    MR is more useful than CT in the following cases:

    • mediastinal ingrowth
    • pancoast tumor
    • vertebral ingrowth

    PET has a limited role in T-staging because of its lack of resolution.
    PET however is of great value in N- and M-staging.

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    T1 tumor

    T1 - tumor

    • Diameter of 3 cm or smaller and surrounded by lung or visceral pleura or
    • endobronchial tumor distal to the lobar bronchus
    • T1A= T1B= 2 cm - 3 cm

    On the left a typical T1 tumor.

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    T2 tumor

    T2 - tumor

    • Greater than 3 and smaller than 7 cm
    • T2a= 3 cm - 5 cm
    • T2b= 5 cm - 7 cm
    • Invasion of the visceral pleura
    • Atelectasis or obstructive pneumopathy involving less than the whole lung
    • Tumor involving the main bronchus 2 cm or more distal to the carina.

    On the left a typical T2 tumor with obstructive infiltrate of the left lower lobe.
    The tumor is located in the main bronchus, but the distance is more than 2 cm from the carina.

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    T3 tumor with invasion of the chest wall.

    T3 - tumor

    • Tumor with atelectasis or obstructive pneumonitis of the entire lung
    • Tumor in the main bronchus within 2 cm of the carina but not invading it
    • Tumor of any size with invasion of non-vital structures such as the chest wall, mediastinal pleura, diaphragm, pericardium.
    • Separate tumour nodules in the same lobe as the primary tumor.

    Chest pain usually indicates chest wall invasion (i.e.T3).
    A Pancoast tumor is a tumor that involves the superior sulcus and the chest wall is almost always involved in these patients (i.e. T3).
    Local chest wall invasion can be treated with en-bloc resection.

    On the left a typical T3 tumor.

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    T4 tumor. Coronal reconstruction at the level of the carina.

    T4 - tumor

    • Invasion of vital mediastinal structures: fat, heart, trachea, esophagus, great vessels, recurrent laryngeal nerve, carina.
    • Invasion of vertebral body.
    • Separate tumour nodule(s) in a different ipsilateral lobe to that of the primary tumor.

    On the left an endobronchial tumor of the left main bronchus within 2 cm of the carina.
    This means that it is at least a T3 tumor.
    There is also invasion of the mediastinum (blue arrow) and invasion of the pulmonary artery (small yellow arrow), indicating that this is a T4-tumor.

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    T4 tumor with invasion of the mediastinum

    In many cases T4-tumors do not pose a diagnostic dilemma.
    On the left we see a large mass that invades the mediastinum.
    There is complete obliteration of the superior vena cava with collaterals in the para-aortic and paraspinal regions.
    The aortic arch is partially surrounded by tumor.

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    T4 tumor constricting the right pulmonary artery (blue arrow)

    T4 - tumor (2)
    On the left another straight forward case.
    The tumor invades the mediastinum and surrounds and narrows the right pulmonary artery.

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    Tumor with possible invasion of the mediastinum

    T4 - tumor (3)- mediastinal invasion
    In many cases it is not certain whether there is mediastinal invasion.
    These are patients with a mass that is not clearly invading the mediastinum but that do not have an intervening fat-plane (Figure).

    In the case on the left there is an intimate relationship of the tumor with the right brachiocephalic vein.
    This should be dagnosed as 'indeterminate mediastinal invasion'.
    This patient should be given the benefit of the doubt and get an operation, since that is the only chance for definitive cure.
    At surgery the tumor fell away from the mediastinum and was subsequently succesfully resected.

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    'Staging' pneumothorax (Courtesy Robert C. Hoch, M.D. Minnesota Lung Center (11)

    On the left an odd case, that was recently published in the NEJM, to illustrate the difficulty of determining mediastinal invasion (11).

    A CT showed a mass in the right upper lobe, closely associated with the paratracheal soft tissues, indicating possible mediastinal invasion.
    A needle biopsy of the mass resulted in a pneumothorax.
    Repeat CT imaging with the patient in a right decubitus position revealed that the mass had moved with the lung and had separated completely from the trachea and mediastinum.
    Evidently this is not a T4-tumor, but a T2-tumor.
    The patient underwent resection of the right upper lobe.

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    CT demonstrates satellite nodule in ipsilateral lobe (arrow) next to tumor in lower lobe. PET demonstrates FDG-uptake only in large tumor.

    T3/T4 - tumor (4)- Satellite nodules
    In patients with NSCLC the presence of satellite metastatic nodules may be considered a contraindication to surgical treatment.
    However the use of multidetector CT has led to the detection of a considerable number of indeterminate satellite lesions.
    Obtaining a differential diagnosis of these lesions is extremely important in defining the therapeutic strategy (12).

    In many institutions T3/T4-tumors due to satellite metastatic nodules in the ipsilateral lung will be resected, since these patients have a slightly better prognosis than other T4-patients and have a chance of completeness of resection.

    PET scan is of limited value in the detection and differentiation of satellite nodules.
    Many nodules are not detected by PET because of their small size (figure).

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    CT and PET demonstrate second nodule in right upper lobe in a patient with lungcancer in left upper lobe.

    On the left a patient with a lungcancer in the left upper lobe.
    In the right upper lobe a second nodule is seen.
    Both lesions show FDG-uptake.

    A malignant node in another lobe can either be a metastasis or a synchronous primary tumor.
    In this case, if it is a metastasis, this means stage IV disease, which is not resectable, because it is not in the ipsilateral lung.
    If it is a synchronous primary tumor, it is possibly resectable.

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    T4 tumor with invason of the left atrium (arrow)

    T4 - tumor (6) - resectability
    There is some controversy concerning the resectability of certain T4-tumors.
    As mentioned above in some institutions T4-tumors due to ipsilateral satellite nodules will be resected.
    In some institutions even limited invasion of the vertebral body or the heart is no contraindication for surgery.

    On the left a T4 tumor with invason of the left atrium.
    The invasion is usually through the pulmonary veins.

    Pancoast tumor

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    Pancoast tumor in the right upper lobe with displacement of the superior mediastium and trachea.

    A Pancoast tumor is a tumor of the superior pulmonary sulcus characterized by pain due to invasion of the brachial plexus, Horner's syndrome and destruction of bone due to chest wall invasion.
    MR is superior to CT for local staging due to its superior soft tissue contrast.
    Sagittal T1WI will best demonstrate ingrowth into thoracic and cervical nerves.
    Axial MR will best demonstrate ingrowth into mediastinum and vertebral canal.
    Pancoast tumors are staged at least as T3, because there is almost always chest wall invasion.
    When there is ingrowth into a vertebral body or vital mediastinal structures, the tumor is staged as T4.
    Nodes in pancoast tumors are treated differently than in other tumors.
    Ipsilateral supraclavicular nodes (N3) are potentially resectable with en bloc resection, while mediastinal nodes (N2) are not.
    In 20% of patients there will be N2 nodes, so all patients with a pancoast tumor should undergo mediastinoscopy with sampling of mediastinal nodes before surgery.

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    Pancoast tumor seen on AP-film of cervical spine

    On the left a detail of an AP-film of the cervical spine of a patient with pain in the neck and shoulder.
    A mass is seen in the apex of the left lung.
    This proved to be a Pancoast with ingrowth in the brachial plexus.

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    On the left the chest film of the same patient.
    Notice how difficult it is to depict the tumor.
    We will continue with the MR-images.

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    Pancoast tumor. Scroll through the images by clicking on the arrows.

    On the left sagittal T1-weighted images after the administration of Gadolinium.
    Scroll through the images by clicking on the arrows.
    Notice how the tumor grows through the chest wall and invades the structures of the neck.
    Only a small part of the tumor is actually within the lung.

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    Operable Pancoast tumor. Sagittal contrast-enhanced T1-weighted image. The tumor abuts the root T1 (long arrow), but the other roots of the brachial plexus are not involved. A = subclavian artery, ASM = anterior scalene muscle. (Courtesy of Wouter van Es, MD. St. Antonius Hospital Nieuwegein, The Netherlands)

    Pancoast tumors are potentially resectable if only one of the following occurs:

    1. Rib destruction.
    2. Limited vertebral body involvement
    3. T1 nerve involvement.

    Patients are nowadays treated with a trimodality approach.
    First they undergo preoperative radiotherapy and chemotherapy (chemoradiation), followed by restaging and finally en-bloc resection of the upper lobe and the chest wall if there is no evidence of progressive disease.

    On the left a Pancoast tumor.
    The tumor abuts the root T1 (long white arrow), but the other roots of the brachial plexus are free in the interscalene triangle (green arrow).
    This patient is operable.

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    Inoperable Pancoast tumor. Sagittal contrast-enhanced T1-weighted image. Invasion of brachial plexus (white arrow). Encasement of the subclavian artery (A). (Courtesy of Wouter van Es, MD. St. Antonius Hospital Nieuwegein, The Netherlands)

    Pancoast tumors are unresectable if one of the following occurs:

    1. Brachial plexus involvement above T1 (Ingrowth of C8 or higher level).
    2. Elevated diaphragm (i.e. ingrowth of nerves C3-4-5).
    3. Esophageal or tracheal involvement (i.e. vital mediastinal structures).
    4. Vertebral body involvement > 50%.
    5. N2 (mediastinal) or N3 (contralateral).
    6. Distant metastases.

    On the left another patient with a Pancoast tumor.
    The tumor is seen as an enhancing mass and invades the interscalene triangle, where the roots and trunks of the brachial plexus are located.
    There is encasement of the subclavian artery (A).

    N - Staging

    Adapted from the American Thoracic Society mapping scheme

    Regional Lymph Node Classification System

    Lymph node staging is done according to the American Thoracic Society mapping scheme.

    Supraclavicular zone (1)

    • 1. Low cervical, supraclavicular and sternal notch nodes

    Superior Mediastinal Nodes (2-4)

    • 2. Upper Paratracheal: above the aortic arch, but below the clavicles.
    • 3A. Pre-vascular: these nodes are not adjacent to the trachea like the nodes in station 2, but they are either anterior to the vessels.
    • 3P. Pre-vertebral: these nodes are not adjacent to the trachea like the nodes in station 2, but they are behind the esophagus, which is prevertebral (3P).
    • 4. Lower Paratracheal (including Azygos Nodes): below upper margin of aortic arch down to level of main bronchus.

    Aortic Nodes (5-6)

    • 5. Subaortic (A-P window): nodes lateral to ligamentum arteriosum. These nodes are not located between the aorta and the pulmonary trunk, but lateral to these vessels.
    • 6. Para-aortic (ascending aorta or phrenic): nodes lying anterior and lateral to the ascending aorta and the aortic arch.

    Inferior Mediastinal Nodes (7-9)

    • 7. Subcarinal.
    • 8. Paraesophageal (below carina).
    • 9. Pulmonary Ligament: nodes lying within the pulmonary ligaments.

    Hilar, Interlobar, Lobar, Segmental and Subsegmental Nodes (10-14)

    • 10-14. N1-nodes: these are located outside of the mediastinum.
      They are all N1-nodes.
    go to the IASLC lymph node map 2009
    • .

    N1 - Nodes

    N1-nodes are ipsilateral nodes within the lung up to hilar nodes.
    N1 alters the prognosis but not the management.
    A T1-tumor without positive nodes within the lung has a 5-y survival of 61%.
    The same T1-tumor with N1-nodes has a 5-y survival of only 34%.

    On the left a T2 tumor (> 3cm) in the right lower lobe with ipsilateral hilar node (N1).

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    T4N2-tumor

    N2 - Nodes

    Although we all have learned, that N2-nodes are resectable, there is only a subset of patients with N2 disease that benefits from resection.
    Those are the patients who, after a negative mediastinoscopy, are found to have microscopic metastatic disease at the time of thoracotomy.
    Those patients have a better prognosis.
    Patients however with bulky N2-nodes on CT and FDG-PET will not undergo surgery.
    They are treated with neo-adjuvant therapy followed by definitive locoregional treatment, which may consist of either radiotherapy or surgery.

    On the left a tumor in the right upper lobe with progression into the mediastinum (T4) with ipsilateral mediastinal N2 nodes in station 4R.

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    On the left a patient with a lungcancer and hilar nodes (N1), right paratracheal (station 4R = N2) and a prevascular node (station 3A = N2).

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    N3-stage disease.

    N3 - Nodes

    N3-nodes are clearly unresectable.
    These are contralateral mediastinal or contralateral hilar nodes or any scalene or supraclavicular nodes.

    On the left a central tumor in the right lung.
    Lymphadenopathy all the way up to the lower paratracheal station on the left (i.e. station 4L).
    This is N3-stage due to contralateral mediastinal nodes.

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    Two patients with N3-disease.

    On the left two patients with lungcancer in the right lung.
    Both have contralateral nodes.
    If these lymph nodes contain tumor cells, this means inoperable stage IIIB-disease.

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    On the left another patient with lungcancer.
    Scroll through the images.

    There is possible ingrowth into the mediastinum.
    Notice the extensive spread into the mediastinal lymph nodes up to the station 1 level, i.e. N3.
    The next step should be US-guided FNA.

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    CT vs PET-CT in N-staging

    Regardless of the threshold size of lymph node chosen, CT findings in isolation can not be taken as clear evidence of malignant nodal involvement.
    20% of all nodes deemed malignant on CT criteria will be benign.
    Size alone cannot be an exclusion criterion and proof is needed by biopsy or resection that a node is indeed malignant.

    It is now well established that PET is a much better technique than CT in the determining the lymph node status in patients with NSCLC.
    In the Table on the left a list of studies that clearly demonstrated the superiority of PET over CT.
    False-positive mediastinal nodal scans occur in sarcoid, tuberculosis and other infections.

    In normal-sized mediastinal lymph nodes PET has a sensitivity and specificity of 74 and 96%, respectively, for detecting metastasis.
    This means that if the PET is positive in these normal-sized nodes, there is almost always a lymph node metastasis.
    Only in 4% of cases PET is false negative.

    In enlarged mediastinal lymph nodes (short axis diameter of 10 mm or more) PET has a sensitivity and specificity of 95 and 76%, respectively.
    This means that PET depicts almost all the metastases, but is false positive due to reactive nodes in 24%.

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    On the left a patient who during follow up for obstructive pulmonary disease presented with a mass in the left upper lobe.
    On the chest film enlarged nodes are seen in the AP-window (i.e. station 5 nodes).

    The next diagnostic step was a PET-CT which clearly depicted the tumor, many positive mediastinal nodes, but also nodes in the neck on the left side (i.e. N3-disease).
    This indicates stage IIIB, non-operable.
    The PET also showed activity in the right upper lung, which can be a metastasis or a synchronous tumor.

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    Enlarged lymph node lateral to the carotid artery.

    There were no palpable nodes in the neck region, but ultrasound depicted the nodes that were PET-positive.
    Fine needle aspiration was performed and the diagnosis of NSCLC was made (i.e. N3-disease).

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    FDG-uptake in solitary pulmonary nodule, but no evidence of nodal disease or distant metastases.

    On the left a patient with a solitary pulmonary nodule.
    There is FDG-uptake in the nodule, but not in the mediastinaum or elsewhere in the body.
    This is probably a T1N0M0 tumor (Stage I)

    Classification of disease as stage I on the basis of a clinical examination and negative results from CT and PET examinations appears sufficient to exclude mediastinal disease.
    In this case there is no need for mediastinoscopy, because the accuracy of PET-CT is as high as it is.

    Classification of stage II and III diseases is more controversial.
    The negative predictive value of PET decreases in relation to the size of the metastases, the presence of centrally located primary disease or N1 nodes, and the avidity of the primary tumor for 18F-FDG.
    In addition, the presence of hypermetabolic central tumors or hilar lymph nodes can decrease the detectability of mediastinal lymph nodes and thus the negative predictive value of mediastinal PET.
    For stage II and III diseases, the incidence of false-negative results is still greater with PET than with mediastinoscopy (respectively 11.7% and 3%).
    Mediastinoscopy likely will remain part of the standard protocol for mediastinal staging for stage II and III diseases.

    M-Staging

    • M0: No distant metastasis
    • M1: Distant metastasis
      • M1a: Separate tumour nodule(s) in a contralateral lobe or tumour with pleural nodules or malignant pleural or pericardial effusion.
      • M1b Distant metastasis

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    PET-CT

    Distant metastases are very common in patients with lung cancer.
    Almost every organ may be involved but the extra-thoracic sites posing common clinical problems are brain metastases, bone metastases, sometimes with cord compression, nodal spread, adrenal and liver involvement.

    On the left a CT- and corresponding PET image of a tumor in the right lung.

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    PET-CT is extremely helpful in the detection of distant metastases.
    In a study of 100 patients PET was compared with conventional imaging, which consisted of CT of chest and upper abdomen, bone scintigraphy, brain-CT or MR (3).
    PET had superior sensitivity and specificity in the lung, liver, adrenals and bone.
    Not suprisingly PET was only less sensitive in the brain due to the high glucose uptake in the normal brain.
    In this study 9% of patients had metastases demonstrated by PET that were not found with conventional imaging, whereas 10% of patients suspected of having metastases because of conventional imaging findings were correctly shown with PET not to have metastases.

    Because of the high negative predictive value, PET scanning should be performed in all patients with no evidence of metastatic disease on CT who are considered candidates for surgery.

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    PET-image demonstrates FDG-uptake in mediastinal nodes, but also in the liver (yellow arrows) and the spine (red arrow) indicating distant metastases.

    M1a-tumor and pleural effusion
    Malignant pleural effusion has a poor prognosis.
    These patients usually die within 3 months.
    In patients with malignant pleural effusion aspiration will yield a false negative results in about a third of the cases.
    If the cytology is negative, you can either do another thoracocenthesis or do a VATS-procedure (video assisted thoracoscopy) and obtain pleural biopsies.