Lung Cancer



Lung Cancer


Todd M. Blodgett, MD

Carl Fuhrman, MD

Sanjay Paidisetty, BS





Key Facts


Terminology



  • Non-small cell lung cancer (NSCLC), bronchogenic carcinoma (CA), adenocarcinoma (adenocarcinoma), squamous cell carcinoma (SCCA), large cell carcinoma (LCCA), bronchoalveolar carcinoma (BAC)


Imaging Findings



  • Spiculated pulmonary nodule in a smoker


  • Hilar and mediastinal lymphadenopathy


  • Whole body PET/CT is superior to CT or PET alone


  • PET/CT currently best technique for imaging diagnosis of nodal staging in NSCLC


  • PET can identify metastases that would have been occult on conventional workup (e.g., adrenal metastases)


  • Prognostic information from FDG PET: Max SUV > 5.0 suggests aggressive neoplasm, poorer prognosis


Top Differential Diagnoses



  • Pulmonary Infarct, Infection


  • Granulomatous Disease


  • Mediastinal Mass


  • Hamartoma


  • Infection


Pathology



  • > 85% smoke; 50% in former smokers


Diagnostic Checklist



  • Consider PET/CT for all patients with newly diagnosed NSCLC


  • Suspicious FDG PET findings should be biopsied/removed without following growth on CT


  • Suspicious CT morphology should be biopsied even with negative PET






One week after discharge status post right lower lobectomy for NSCLC, coronal PET (A) shows focal FDG activity image. PET/CT (C) localizes the lesion image to the pericardium, without obvious abnormality on the CECT (B). Autopsy confirmed a pericardial metastasis.






Coronal PET (A) and PET/CT (C) from the same PET/CT exam as the previous image show a hepatic lesion image not detected on axial CECT (B). Unsuspected additional lesions were also present image.


TERMINOLOGY


Abbreviations and Synonyms



  • Non-small cell lung cancer (NSCLC)


  • Adenocarcinoma


  • Bronchogenic carcinoma


  • Squamous cell carcinoma (SCCA)


  • Bronchoalveolar carcinoma (BAC)


  • Large cell carcinoma (LCCA)


Definitions



  • Glandular carcinomas of varying histology arising in lung parenchyma


IMAGING FINDINGS


General Features



  • Best diagnostic clue



    • Peripheral irregular spiculated pulmonary nodule in a smoker



      • Malignant in > 90% of patients


    • Hilar and mediastinal lymphadenopathy


    • Bronchial stenosis and associated atelectasis


  • Location



    • Adenocarcinoma: Periphery of upper lobe


    • SCCA: Central


  • Size



    • By time of detection



      • At screening: 8-15 mm


      • Symptomatic: 25 mm


    • Size is not a reliable indicator of nodal involvement



      • 21% of subcentimeter nodes = malignant


      • 40% of nodes > 1 cm = benign


    • LCCA: > 4 cm at diagnosis


  • Morphology



    • Spiculated irregular ill-defined nodule is specific for malignancy



      • Borders may also be lobulated or smooth


Imaging Recommendations



  • Best imaging tool



    • CT for delineating extent of disease


    • PET/CT for prognosis and staging


    • MR for diagnosing neural invasion



      • CNS, Pancoast invasion of brachial plexus


    • No imaging tool is specific enough to defer lymph node biopsy if required for treatment planning



    • Mediastinoscopy most common method for assessing mediastinal lymph nodes


  • Protocol advice



    • CT



      • To include adrenals, image caudally from thoracic inlet to inferior edge of liver


      • Pleural and diaphragmatic tumor spread best imaged with multiplanar reformatting


      • Screening CT studies should be performed without contrast and with the lowest possible mAs


    • FDG PET



      • Serum glucose < 150 mg/dL (reschedule hyperglycemic patients)


      • 90 minute uptake period


    • PET/CT



      • Modified breath-hold techniques employed to reduce misregistration artifact


      • Sensitivity in lower lobes may be minimized without maximal inspiration


CT Findings



  • General findings



    • Current CT does not provide adequate anatomic detail to separate invasion from simple contact between tumor and adjacent organ


    • NECT adequate for evaluation of primary tumor, but less sensitive for vascular invasion and liver metastases


    • CECT can reveal small endobronchial lesions and better elicit small mediastinal nodes



      • Particularly hilar nodes that may otherwise missed due to proximity to vessels


    • Bronchial obstruction with lobar collapse or post-obstructive pneumonitis


    • Peripheral lesions



      • SCCA more likely to demonstrate cavitation


      • Peripheral adenocarcinoma may be solid, mixed solid/ground-glass, or ground-glass


  • Staging



    • CT has not demonstrated improved staging accuracy with the advent of multislice detectors


    • Malignant potential and degree of contrast enhancement may be related due to increased vascularity of lung cancer lesions


  • Lymph nodes



    • Upper size limits for suspicion of malignancy



      • > 5 mm hilum and > 10 mm mediastinum


    • Size criteria are insensitive, as normal-sized nodes often harbor malignancy



      • Sensitivity 41-54%


      • Combined PET/CT may correct 81% of false negatives on CT


    • Measurement errors inherent with borderline node size of 5 mm


    • Mediastinal and hilar nodal metastasis is not predicted by characteristics of primary tumor



      • Size, margins, necrosis, bronchovascular thickening


    • Best predictor of mediastinal nodal metastasis is peak enhancement of malignant lung nodules



      • > 100 HU or > 60 HU of net enhancement in stage T1 NSCLC


      • Mediastinoscopic biopsy recommended in the setting of these findings whether FDG PET is positive or not


    • Supraclavicular nodal sensitivity of 67-85%



      • Area often obscured by beam-hardening artifacts


      • Delayed scans may improve detection


      • Transverse scan may not accurately depict short-axis measurement of nodes


    • Normal structures that mimic lymph nodes



      • External/internal jugular veins


      • Vertebral veins


      • Common carotids


      • Scalene and longus colli muscles


  • Metastatic disease



    • High resolution CT to detect lymphangitic carcinomatosis


    • Look for metastasis to non-tumor lobe


    • CECT can demonstrate pleural metastases in pleural effusion


    • Adrenal evaluation complicated by insensitivity of morphologic criteria for presence of malignancy




      • May be evaluated with NECT


      • 17% of normal-appearing adrenals may harbor malignancy


      • Overall, fewer than half of adrenal masses in patients with lung cancer will be due to metastasis


Nuclear Medicine Findings



  • PET/CT



    • Central to initial and post-treatment evaluation and management of NSCLC


    • Depicts response to treatment accurately and predicts prognosis


    • Influences management by demonstrating occult disease


    • Provides high contrast between tumor and adjacent structures like mediastinum, chest wall, atelectasis


    • Helps determine cause of pleural effusion


  • Normal uptake



    • Low level in thyroid, breast, and mediastinal blood pool


    • Talking can cause laryngeal uptake


    • Anxiety may be manifested as uptake in the SCM


    • Brown fat in neck, paravertebral, mediastinal, and axillary regions


    • Also seen in esophagus, spleen, liver, and bowel


  • Initial diagnosis


  • FDG PET criteria for malignancy (less specific than sensitive)



    • FDG uptake > background mediastinal uptake


    • Max SUV ≥ 2.5; however wide overlap of SUVs between benign and malignant processes


    • Any activity above background levels in lesion < 1-1.5 cm


  • For SPN larger than 1.0 cm, PET has sensitivity and specificity of 95-98% and 73-85% respectively



    • Same predictive value as observation of nodule growth on CT


  • Nodules < 2.5 cm may be misinterpreted as non-FDG-avid due to partial volume averaging on PET



    • Recovery coefficient helps correct SUV in smaller nodules for purposes of quantitative determinations


  • Tumor with low metabolic rate (low grade adenocarcinoma, BAC, carcinoid)


  • Subtypes may show low FDG uptake despite aggressiveness



    • BAC, carcinoid, low grade adenocarcinoma


  • Staging


  • Detection of disease



    • PET can identify metastases that would be occult on conventional workup (e.g., adrenal metastases)


    • Detects bone metastases with equal sensitivity to and greater specificity than bone scintigraphy


    • False positives with benign inflammatory disease > 1.0 cm


    • False negatives in subcentimeter lesion with limited cancer invasion


    • Low sensitivity of 47% for stage T1 NSCLC


    • 100% PPV and high NPV for mediastinal nodal metastasis


    • Brain metastases may be overlooked due to high background FDG avidity


    • Necrotic metastases may be negative (e.g., adrenal masses)


  • Influence on management



    • PET more sensitive than clinical exam for supraclavicular lymphadenopathy



      • Significant indicator of inoperable disease


      • Confirmation by histopathology is mandatory when positive PET/CT would deny patient chance for potentially curative treatment


    • High NPV of 93% helps avoid invasive procedures like fine needle aspiration (FNA) when there is no FDG uptake



      • Microscopic disease may be present, and mediastinal surgical staging may still be indicated


    • Thoracotomy



      • PET has greater than 90% NPV for nodal disease


      • Patients with negative mediastinal nodes may proceed directly to thoracotomy without need for mediastinoscopy


      • PET may also avoid non-therapeutic thoracotomy in 20% by detecting previously occult distant disease


    • PET/CT may alter 50% of radiotherapy gross tumor volume estimation compared to targeting with CT alone



      • Clinical impact yet to be determined


      • Gross tumor volume (GTV) shown to include all pathologically involved mediastinal lymph nodes


      • More positive lymph nodes are detected by PET/CT compared to CT alone


  • Prognosis



    • FDG PET may provide information on prognosis independent from standard staging algorithms


    • Primary tumor with SUV ≥ 5.0



      • Associated with significant increase in post-operative relapse in early stage lung cancer


    • Intense uptake in bone marrow also associated with poorer outcome


  • Response to treatment


  • Decrease in FDG avidity of malignant lesion by 60% following 2-3 cycles of chemotherapy



    • May indicate good response and be predictive of improved survival


  • Some tumors may show falsely decreased SUV post-therapy (“stunned”) but still represent threat of recurrence


  • False positives



    • Nonmalignant metabolically active conditions



      • Active inflammation, infection, granulomatous disease


    • Pattern of physiologic muscle uptake typically



      • Bilateral, symmetric, fusiform, or elongated; seldom confused with presence of malignancy


      • Asymmetric uptake can occur


    • Increased glycolysis in leukocytes, lymphocytes, macrophages



      • Produce uptake in areas of infection, inflammation


    • Examples of benign processes that may mimic malignancy



      • Atherosclerotic plaque


      • Reflux esophagitis



      • Tuberculous caseating granuloma


      • Sarcoidosis


      • Wegener granulomatosis


      • Amyloidosis


      • Pulmonary infarction


      • Pulmonary embolus


      • Pulmonary hamartomas


      • Needle biopsy site


      • Mediastinoscopy


      • Talc pleurodesis, which may remain FDG positive for several years


      • Empyema


      • Pneumonias usually produce low grade uptake but avid uptake can occur


      • Organizing pneumonia as a single focus of consolidation can mimic lung cancer


  • Patients with false positives on PET/CT often have comorbid pulmonary complications, such as



    • Obstructive pneumonia


    • Chronic bronchitis


    • Interstitial pneumonia


    • Bronchiectasis


    • Silicosis


    • Previous pulmonary tuberculosis


DIFFERENTIAL DIAGNOSIS


Metastases



  • Usually less spiculated than primary pulmonary malignancies


  • Variably FDG avid


Infection



  • Pneumonia may show intense focal uptake and is easily mistaken for malignancy


  • Repeat PET to rule out presence of underlying malignancy


Granulomatous Disease



  • Mediastinal and hilar adenopathy generally symmetrical and FDG avid


  • Predominantly in upper lobes


  • Calcification is common


Pulmonary Infarct



  • Early following infarct, may show intense FDG activity


  • Usually becomes less intense over time


  • Distribution of occluded artery


Hamartoma



  • Generally noninflammatory with little FDG uptake


  • “Popcorn” calcifications


PATHOLOGY


General Features



  • General path comments: Sputum analysis is insensitive, with false negative in 40% of cases


  • Genetics



    • NSCLC associated with amplification of oncogenes (e.g., ras family) in 30% of cases



      • Also inactivation of tumor suppression genes


      • Portends worse prognosis


    • Genetic predisposition plays role in vulnerability to risk factors (e.g., smoking)


  • Etiology



    • Tobacco is the cause of lung cancer in ˜ 90% of cases



      • Disease was practically unknown prior to the rise of cigarette smoking in the 1920s


      • 15% of lung cancer in patients who do not smoke is caused by passive smoke


    • Asbestos exposure in a patient who smokes confers 80-90x increased risk of lung cancer


    • Radon accounts for 2-3% of lung cancer and is a byproduct of uranium decay (miners)


  • Epidemiology



    • In USA: 170,000 new cases/year (90k in men and 80k in women); 150,000 deaths/year


    • Estimated 1 million new cases/year worldwide


    • NSCLC accounts for ˜ 80% of all lung cancers


  • Associated abnormalities: COPD


Gross Pathologic & Surgical Features



  • Cavitation is common in SCCA


Microscopic Features



  • Adenocarcinoma: Forms glands and produces mucin, which can be identified with mucicarmine or PAS staining


  • SCCA: Large irregular nuclei, coarse nuclear chromatin, large nucleoli



    • Presence of intercellular bridging among cells arranged in sheets is pathognomonic


  • LCCA: Large cells with prominent nucleoli in the absence of mucin production or intercellular bridging


Staging, Grading, or Classification Criteria



  • Primary lesion (T)



    • Tx: Tumor cannot be assessed, + sputum/washings


    • T0: No evidence of primary tumor


    • Tis: Carcinoma in situ


    • T1: < 3 cm, completely surrounded by lung; no main bronchi invasion


    • T2: > 3 cm, involving main bronchus > 2 cm from the carina, visceral pleura; atelectasis/pneumonitis extending to hila


    • T3: Invading chest wall, diaphragm, mediastinal pleura, parietal pericardium, main bronchus < 2 cm from the carina



      • Total atelectasis of whole lung


    • T4: Invading the mediastinal structures, vertebrae, carina; separate tumor nodules in same lobe; malignant pleural effusion


  • Mediastinal and hilar lymph nodes (N)



    • N1: Hilar lymph nodes at vessel branch point


    • N2: Ipsilateral to primary tumor (subcarinal lymph node is ipsilateral)


    • N3: Contralateral lymph node, supraclavicular fossa


  • Stages



    • 0 (TisN0M0)


    • 1A (T1N0M0)


    • IB (T2N0M0)


    • IIA (T1N1M0)


    • IIB [(T2N1M0), (T3N0M0)]


    • IIIA [(T1-3 N2M0), (T3N1M0)]



    • IIIB [(any T, N3M0), (T4, any N, M0)]


    • IV (any T, any N, M1)


CLINICAL ISSUES


Presentation



  • Most common signs/symptoms



    • Central primary tumor



      • Cough, dyspnea, wheezing, and hemoptysis


      • Atelectasis and post-obstructive pneumonia


    • Peripheral primary tumor may cause the above



      • ± Pleural effusion and pain related to pleural and chest wall invasion


    • Locoregional spread may cause SVC obstruction and nerve infiltration



      • Leads to hoarseness, diaphragm paralysis, and Horner syndrome, as well as brachial plexus neuropathy


    • Paraneoplastic symptoms may include hypercalcemia and PTHrP production


  • Other signs/symptoms



    • Recurrent pneumonia in same lobe


    • Metastasis to supraclavicular lymph node



      • Indicator of inoperable disease


      • Palpation of supraclavicular lymph nodes is unreliable for detection


Demographics



  • Age: > 50 years


  • Gender



    • M:F approaching 1:1 in USA


    • M > F worldwide


    • Mortality higher in males, increasing in females


  • Ethnicity: African-American:Caucasian:Native American = 1.5:1:0.2


Natural History & Prognosis



  • Most patients present with advanced disease


  • Adenocarcinoma has worse prognosis per stage than SCCA (except T1N0)


  • Staging criteria include



    • Histologic type


    • Tumor size


    • Regional lymph node involvement


    • Presence of metastatic disease


  • Mediastinal lymph node metastasis is found in 16-21% of patients with stage T1 NSCLC


  • Metastatic relapse occurs in up to 20% of patients who have undergone surgery


Treatment



  • Stages 1 & 2: Patients with no metastatic lymph nodes (N0 disease) or with only intrapulmonary or hilar lymph nodes (N1 disease)



    • Resection with adjuvant chemo in selected cases


  • Stage 3A: Neoadjuvant chemoradiation, then surgery in selected


  • Stage 3B: Chemoradiation, then surgery in selected T4N0


  • Stage 4: Chemotherapy, palliative radiation in selected



    • Solitary brain mets: Resection of brain met and primary if possible


  • Radiation or RFA: Symptomatic inoperable lesions



    • Some patients with inoperable NSCLC can be cured with radiotherapy


DIAGNOSTIC CHECKLIST


Consider



  • Suspicious CT morphology should be biopsied even with negative PET


  • Suspicious FDG PET findings should be biopsied/removed without following growth on CT


  • Consider PET/CT for ALL patients with newly diagnosed NSCLC



SELECTED REFERENCES

1. Bryant AS et al: Differences in outcomes between younger and older patients with non-small cell lung cancer. Ann Thorac Surg. 85(5):1735-9; discussion 1739, 2008

2. Cerfolio RJ et al: Survival of patients with unsuspected N2 (stage IIIA) nonsmall-cell lung cancer. Ann Thorac Surg. 86(2):362-6; discussion 366-7, 2008

3. Decker RH et al: Advances in radiotherapy for lung cancer. Semin Respir Crit Care Med. 29(3):285-90, 2008

4. Hampton T: New studies target lung cancer prevention, imaging, and treatment. JAMA. 300(3):267-8, 2008

5. Hanin FX et al: Prognostic value of FDG uptake in early stage non-small cell lung cancer. Eur J Cardiothorac Surg. 33(5):819-23, 2008

6. Hart JP et al: Radiation pneumonitis: correlation of toxicity with pulmonary metabolic radiation response. Int J Radiat Oncol Biol Phys. 71(4):967-71, 2008

7. Higaki F et al: Preliminary retrospective investigation of FDG-PET/CT timing in follow-up of ablated lung tumor. Ann Nucl Med. 22(3):157-63, 2008

8. Kased N et al: Prognostic value of posttreatment [18F] fluorodeoxyglucose uptake of primary non-small cell lung carcinoma treated with radiation therapy with or without chemotherapy: a brief review. J Thorac Oncol. 3(5):534-8, 2008

9. Lima CG Jr et al: Is there a definitive answer to the question of involved-field radiotherapy for inoperable non-small-cell lung cancer? J Clin Oncol. 26(13):2235; author reply 2235-6, 2008

10. Ohno Y et al: Non-small cell lung cancer: whole-body MR examination for M-stage assessment—utility for whole-body diffusion-weighted imaging compared with integrated FDG PET/CT. Radiology. 248(2):643-54, 2008

11. Yi CA et al: Non-small cell lung cancer staging: efficacy comparison of integrated PET/CT versus 3.0-T whole-body MR imaging. Radiology. 248(2):632-42, 2008

12. Poettgen C et al: Correlation of PET/CT findings and histopathology after neoadjuvant therapy in non-small cell lung cancer. Oncology. 73(5-6):316-23, 2007

13. Decoster L et al: Complete metabolic tumour response, assessed by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET), after induction chemotherapy predicts a favourable outcome in patients with locally advanced non-small cell lung cancer (NSCLC). Lung Cancer. (In Press)

14. Wilson DO et al: The Pittsburgh Lung Screening Study (PLuSS): Outcomes within 3 years of a first CT Scan. Am J Respir Crit Care Med. (In Press)


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Sep 22, 2016 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Lung Cancer

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