AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Background

Worldwide, bronchogenic carcinoma is the most common cause of cancer death in both men and in women. In the US, approximately one third of cancer deaths occur as a consequence of lung cancer, and approximately 170,000 new cases of lung cancer occur annually. The 5-year survival rate is 14%, and it has largely remained unchanged for decades. Lung cancer kills more people than colorectal, breast, and prostate cancers combined. Approximately 45% of lung cancer cases occur in women, and, in North America, the number of deaths resulting from lung cancer has recently surpassed the number of deaths resulting from breast cancer.

For the purpose of treatment and prognosis, lung cancer is divided into 2 categories: small-cell lung cancer and non–small cell lung cancer.

Approximately 20% of malignant tumors of the lung are due to small cell carcinoma. At presentation, small cell lung cancer is almost always metastatic to the mediastinal lymph nodes or distantly; therefore, the treatment is combination chemotherapy.

Non–small cell cancer requires meticulous staging, because the treatment and prognosis vary widely depending on the stage. In non–small cell lung cancer, surgical resection offers patients the best chance for survival. Surgery may be curative for stage I and stage II disease; however, these subgroups only a minority of patients (20-25%) have disease at these stages. Patients with stage IIIA disease may be candidates for surgical resection. In patients with stage IIIB disease, the tumors usually are considered unresectable. Patients with stage IV disease have distant metastases and are offered nonsurgical treatment, with the exception of rare cases of resectable solitary metastasis in a patient who also has a resectable primary lesion.

Most patients with stage I and stage II disease require preoperative or intraoperative mediastinal dissection for accurate staging prior to lung resection. The overall surgical mortality rate following lung resection is 3.7%. The mortality rate is higher (6-9%) in patients requiring pneumonectomy and in patients older than 70 years. The overall 5-five year survival rate may depend on whether the tumor is stage T1 or stage T2. The overall 5- and 10-year survival rates are 75% and 67%, respectively, in patients who undergo resection for stage I disease.

Patients with stage IA (T1 N0) disease have a significantly higher survival rate (82% at 5 y) compared with those with stage IB (T2 N0) disease (68% at 5 y and 60% at 10 y) (Martini, 1995). Patients with stage IIA (T1 N1) tumors have a survival rate of approximately 50% at 5 years, whereas patients with stage IIB (T2 N1 and T3 N0) tumors have 40% survival rate. Patients with stage IIIA (T1 or T2 N2) tumors have been reported to have a 5-year survival rate of 29%. The 5-year survival rate in patients with complete resection of stage IIIB tumors is 49% in T3 N0 disease, 27% in T3 N1 disease, and 15% in T3 N2 tumors. For patients with stage IV disease, the median survival is 8.5-21 weeks, and the 1-year survival rate is 10%.

The overall 5-year survival rate is grim because most patients with non–small cell lung cancer present with locally advanced or metastatic disease. Approximately 65-80% of patients present with unresectable disease. At present, the National Cancer Institute and other medical associations and regulatory bodies do not recommend early screening for lung cancer as part of a periodic health examination.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Lung Cancer, Bronchoscopy, Understanding Lung Cancer Medications, and Non-Small-Cell Lung Cancer.

Pathophysiology

Bronchogenic carcinoma is the most common cancer and the most common cause of cancer-related death in both men and women. Risk factors for lung cancer include the following:

• Cigarette smoking: Smoking increases the risk of bronchogenic carcinoma by 4-120 times. In some patients, the risk may return to normal levels 15 years after they stop smoking, but most patients continue to have a lifelong risk than that of individuals who do not smoke.
• Exposure to asbestos: Asbestos exposure increases the risk 4- or 5-fold, or as much as 100-fold if the exposed individual is also a smoker.
• History of interstitial lung disease: As many as 6-12% of patients with idiopathic pulmonary fibrosis develop bronchogenic carcinoma (adenocarcinoma).
• Exposure to toxic agents: Agents such as arsenic, nickel (squamous cell carcinoma), chromium, and chloromethyl ether (small cell carcinoma) increase the risk.
• Exposure to uranium or radon: Exposure to breakdown products of uranium increases the risk of non–small cell compared to small-cell moreso than the risk of small-cell carcinoma of the lungs.
• Prior lung cancer: Approximately 10-32% of patients who survive resection for lung cancer may develop a second primary lung tumor.
• Lung disease: The presence of concomitant chronic obstructive pulmonary disease is a risk factor for lung cancer.
• HIV infection: In patients with HIV infection the risk of non–small cell lung carcinoma is increased by 6.5 times. Patients with HIV infection and a history of smoking may develop bronchogenic carcinoma at a relatively young age ( <50 y).

Frequency

United States

Lung cancer is the most common cancer in both men and women. In 1999, approximately 171,600 new cases of lung cancer were diagnosed (94,000 new cases in men and 77,600 new cases in women; Landis, 1999). The age-adjusted incidence rates for 1996 were 54.2 cases per 100,000 men and women.

For the general population, the lifetime risk of developing cancer is 8.1% for men and 5.7% for women. The lifetime risk of lung cancer among male smokers is 14.6%, and among female smokers, it is 8.3%.

Between 1992 and 1996, the incidence of lung cancer in men decreased by an average of 3.6% per year, and the mortality rates decreased by 1.7% per year. For the same period, the lung cancer incidence among women declined at an average rate of 0.3% per year, but the mortality rates increased at an average rate of 0.9% per year.

International

Worldwide, lung cancer is the most frequently occurring cancer and the leading cause of cancer mortality. Approximately 1.04 million new cases of lung cancer were diagnosed in 1990, accounting for 12.8% of the worldwide total cancer incidence. The number of new cases is increasing each year; a 16% increase occurred between 1985 and 1990.

Mortality/Morbidity

In 1999, approximately 158,900 lung cancer deaths occurred in the United States. Among men, lung cancer had been the leading cause of death since 1950. Among women, the lung cancer mortality rate exceeded the breast cancer mortality rate in 1987. The 5-year survival rate for all cases of lung cancer from 1989 to 1995 was 14%. Patients with stage I or stage II disease have a 5-year survival rate of approximately 50%; however, only 15% of newly diagnosed cases involve early-stage disease.

Race

In the United States, the highest incidence rates occur among blacks (117 cases per 100,000), and the lowest rate occurs among American Indians (14 cases per 100,000). Hispanics, the Japanese, the Chinese, Philippinos, and Koreans have incidence rates of 42-53 cases per 100,000 population. The Vietnamese, Alaskan natives, Hawaiians, and whites have incidence rates of 71-89 cases per 100,000 population.

Sex

Internationally, trends have shown a marked increase in cancer incidence among women. In 1985-1990, the incidence increased by 4% in men compared with 21% in women.

• Age-adjusted incidence rates for 1996 showed that 68.4 new cases occurred in 100,000 US men, compared with 43.7 cases per 100,000 women. In 1973-1996, the rate in men decreased by 2.5%, but the rate in women increased by 123%.
• Worldwide, lung cancer is more common in men (37.5 new cases per 100,000) than in women (10.8 per 100,000).

Age

Lung cancer is uncommon in those younger than 40 years. The incidence increases with advancing age and peaks between in persons aged 70-80 years. New cases occur in 1.4% of men and 1.1% of women aged 40-44 years, and the incidence is 21.5% for men and 19.8% for women aged 70-74 years.

Anatomy

The relative frequency of lung cancer is 3:2 in the right compared with the left lung and in the upper lobe compared with the lower lobe. Squamous cell carcinomas occur predominantly in a central location, whereas adenocarcinoma presents in approximately 50% of patients as a peripheral lesion. Tumors arising endobronchially are located in segmental or lobar bronchi. Fewer than 4% of cancers arise in the apex of the upper lobes, and fewer than 1% arise from the trachea.

TNM classification

• The primary tumor (T) is classified according to its size and local invasion.
  • T1 - A tumor less than or equal to 3 cm in its greatest dimension, surrounded by lung or visceral pleura, without involvement of the main bronchus
  • T2 - A tumor with any of the following features:
    • Larger than 3 cm in largest dimension
    • Involvement of the mainstem bronchus more than 2 cm from the carina
    • Invades the visceral pleura
    • Associated with atelectasis or postobstructive pneumonitis extending to the hilar region but not involving the entire lung
  • T3 - A tumor of any size with any of the following features:
    • Tumor (including superior sulcus tumors) directly invading the chest wall, diaphragm, mediastinal pleura, or parietal pericardium
    • Tumor in the main bronchus less than 2 cm distal to the carina (but without involvement of the carina)
    • Tumor associated with atelectasis or obstructive pneumonitis of the entire lung
  • T4 - A tumor of any size with any of the following features:
    • Tumor invading the mediastinum, heart, great vessels, trachea, esophagus, vertebral body, or carina
    • Any tumor with a malignant pleural or pericardial effusion
    • Any tumor with satellite tumor nodules within the ipsilateral primary tumor lobe of the lung
  • Additional T descriptions that rarely are used include the following:
    • TX - Inability to assess a primary tumor (presence of malignant cells in sputum or bronchial washings but not visualized by imaging studies or bronchoscopy)
    • T0 - No evidence of a primary tumor
    • TIS - Carcinoma in situ
• The regional lymph node status (N) is also used to classify the tumor.
  • N0 - No regional lymph node metastasis
  • N1 - Ipsilateral peribronchial or hilar nodal metastases or intrapulmonary nodes involved by direct extension of the primary tumor
  • N2 - Ipsilateral mediastinal and subcarinal, midline prevascular, and retrotracheal nodes
  • N3 - Contralateral mediastinal or contralateral hilar nodal metastases, ipsilateral or contralateral scalene or supraclavicular nodes
  • NX - Additional N description rarely used, means regional lymph nodes cannot be assessed
• Distant metastasis (M) descriptions classify the tumor according to location of metastases.
  • M0 - No distant metastasis
  • M1
    • Distant metastasis or separate tumor nodules in other lobes of same lung
    • Tumor nodules in the contralateral lung (considered M1 if of the same histologic cell type as the primary lesion; tumor of different cell type in contralateral lung is considered a synchronous primary lesion)
  • MX - Additional M description in which the presence of distant metastasis cannot be assessed

Staging classification

Clinical staging is shown in Image 10. Preoperative staging is denoted by the prefix c before the TNM designation, whereas prefix p indicates surgical-pathologic staging.

Clinical Details

Squamous cell carcinoma

Squamous cell carcinoma accounts for 30-40% of cases of bronchogenic carcinoma, and it has a strong association with smoking. The lesion is usually located centrally, and among all bronchogenic carcinomas, it is most likely to cavitate. Squamous cell carcinomas grow intraluminally and are least likely to metastasize distantly (<20% of cases at presentation). The mode of spread is direct extension to the local lymph nodes. Squamous cell carcinomas are commonly associated with clubbing and hypertrophic osteoarthropathy. Hypercalcemia is also commonly observed secondary to a parathormone-like peptide created by the tumor. Tumors of squamous histology can sometimes elicit a sarcoid reaction in nodes, resulting in nodal enlargement without metastatic spread.

Adenocarcinoma

Adenocarcinoma occurs with a frequency of 30-40%, which has surpassed the incidence of squamous cell carcinoma. The lesion is located peripherally in approximately one half of cases, and it is associated with smoking. Adenocarcinoma may arise from a previous scar, it rarely cavitates, and an eccentric pattern of calcification may be evident. An early propensity is noted of metastases to the lymph nodes, pleura, adrenal glands, central nervous system (CNS), and bone.

Bronchoalveolar cell carcinoma

Bronchoalveolar cell carcinoma is a subtype of adenocarcinoma that accounts for as many as 5% of bronchogenic carcinomas. Although an association with smoking has not been established, a substantial percentage of patients have a significant smoking history. The incidence of bronchoalveolar cell carcinoma is increased in patients who have underlying interstitial lung disease, parenchymal scaring, and exogenous lipoid pneumonia.

Bronchoalveolar cell carcinoma is classified as mucinous and nonmucinous on the basis of histopathologic features. The mucinous variety is most common (80%) and arises from columnar mucous containing cells. The mucinous variety is likely to be multicentric, it occasionally appears with bronchorrhea, and it has a worse prognosis. The nonmucinous form arises from type II pneumocytes or Clara cells, it is more likely to be localized, and it has a better prognosis. Bronchoalveolar carcinoma may spread to other sites or the other lung by means of transbronchial spread called aerogenous spread. These tumors can also demonstrate growth along the pulmonary interstitium without destroying lung architecture. This is called lepidic growth. In comparison, both types of growth are associated with a worse prognosis.

Bronchoalveolar carcinoma may appear in a variety of ways, including a solitary pulmonary nodule (45%), multiple nodules (25%), and consolidation (30%). Presentation as a solitary pulmonary nodule is associated with the best prognosis. Nodules can be sharp or poorly defined, and they may be cavitated. In 30% of patients, an associated pleural effusion is noted, as well as hilar or mediastinal lymphadenopathy.

Large cell carcinoma

Large cell carcinomas account for only 5-10% of bronchogenic carcinomas and are strongly associated with cigarette smoking. The lesion occurs peripherally and grows rapidly, with early metastases and a poor outcome. A subtype of large cell carcinoma is giant cell carcinoma. This is highly malignant and associated with a poor prognosis.

Clinical manifestations

The symptoms of non–small cell carcinoma can be secondary to the following:

• Local bronchopulmonary disease – Cough and hemoptysis
• Spread of tumor to adjacent structures – Chest pain
• Distant metastases - Bone pain, jaundice, seizures, or neurologic symptoms
• Constitutional effects – Fatigue, anorexia, and weight loss
• Paraneoplastic syndromes

Paraneoplastic syndromes associated with bronchogenic carcinoma

• Hypercalcemia
• Ectopic adrenocorticotropic hormone production
• Syndrome of inappropriate secretion of antidiuretic hormone
• Eaton-Lambert syndrome (peripheral neuropathy with myasthenia-like symptoms)
• Acanthosis nigricans
• Hypertrophic osteoarthropathy

Superior sulcus or Pancoast tumor may involve the subclavian vein, the phrenic or vagus nerve, the subclavian artery, the recurrent laryngeal nerve, and/or the sympathetic chain. The symptoms may depend on the structure involved and include arm pain, weakness of the shoulder and arm, arm swelling, and Horner syndrome. Constitutional symptoms can include malaise, weakness, fever, and weight loss.

International staging system for lung cancer

The international staging system for lung cancer provides a common framework for treatment options and prognostication in patients with bronchogenic carcinoma. The staging system is derived from the TNM classification scheme in which T indicates the primary tumor, N indicates the regional lymph nodes, and M indicates the distant metastasis; the 4 stage groups I-IV.

Radiologic Findings by Tumor Histologic Type

Patients with limited chest wall invasion and no evidence of distant metastases are considered potentially curable (stage IIIA). MRI may be slightly more accurate than CT in determining the extent of chest wall invasion. The treatment of choice is radiation therapy followed by surgery or radiation therapy alone for patients with unresectable lesions. The following criteria usually indicate an unresectable lesion:

• Tumor invasion of the great vessels at the thoracic inlet (most commonly the subclavian artery because of its location)
• Phrenic or recurrent laryngeal nerve paralysis
• Invasion of the vertebral bodies, trachea, or esophagus

Preoperative radiation therapy is used to reduce tumor size 3-6 weeks prior to surgery. Surgery involves en block resection of the chest wall.

Preferred Examination

In a malignancy such as bronchogenic carcinoma, early detection can lead to surgical resection of the lesion and cure. Unfortunately, to date, the use of radiologic modalities has not proven successful in reducing mortality rates. For screening of non–small cell carcinoma of the lung, chest radiography may result in improved survival, although a mortality benefit cannot be demonstrated.

On the basis of results from the Mayo Lung Project and a Czechoslovakian study, the American Cancer Society does not recommend routine mass screening for the detection of lung cancer. However, early stage detection, resectability, and survival improve with chest radiographic screening in high-risk populations. More recently, preliminary studies have shown that low-dose helical CT scan of the thorax may detect lesions at an earlier stage and, therefore, potentially may improve resectability, survival, and mortality rates. A large randomized study is currently underway at the Mayo Clinic.

Radiologic manifestations of bronchogenic carcinoma include obstructive pneumonitis or atelectasis, lung nodule or mass, apical mass, cavitated mass, nodule or mass associated with lymphadenopathy, unilateral hilar, or mediastinal lymphadenopathy alone. Chest radiography is a readily available, inexpensive, and useful imaging modality in the workup of patients with non–small cell carcinoma. Therefore, chest radiography is used most often as an initial investigation.

Invariably, other investigations such as CT scanning are required for better delineation of the abnormality detected on plain radiographs. CT can also be helpful in excluding a benign lesion and in preoperative staging. CT of the chest is an important informative tool that helps in detailed imaging of the primary tumor and its anatomic relationship to other structures, and it provides information with respect to the size of mediastinal lymph nodes and the status of the pleural space. However, CT criteria for adenopathy are based on size alone and do not always accurately reflect the presence or absence of tumor metastases. CT can best be thought of as a technique that provides a roadmap for more accurate surgical staging.

The role of MRI and positron emission tomography (PET) scan are not as well defined, MRI is not used routinely. MRI may be superior to CT in the assessment of the chest wall invasion by apical tumors. The use of PET scanning is expanding rapidly.

PET scanning may be useful in the assessment of solitary pulmonary lung nodules. Several studies indicate that PET scanning appears to be valuable in deciding whether a nodule is benign or malignant as well as in staging locoregional and distant metastatic disease. In some centers, PET/CT scanners are available to allow more precise anatomic localization.

Limitations of Techniques

Chest radiography remains the primary means of radiographic assessment of lung carcinoma. However, 12-30% of lung cancers are missed on chest radiographs (Miller, 1990). A nodule smaller than 2-3 mm may not be detected by using chest radiographs, and overlapping soft tissue opacities may hide small endobronchial lesions. Chest radiographs depict indirect signs of endobronchial lesions such as obstructive pneumonia or atelectasis. These signs may well be secondary to benign tumors or mucus plugging or foreign body. In a solitary lung nodule, probability of malignancy is approximately 40% overall; therefore, a nodule identified on a chest x-ray requires further diagnostic workup to exclude lung cancer.

The advantage of CT scan in non–small cell lung cancer is that it can be used to distinguish tumor from surrounding atelectatic lung. CT scans may be helpful in demonstrating superior vena cava compression, pericardial effusion, and lymphangitic dissemination in several other conditions. A major limitation of CT scan is the inability to distinguish invasion from simple approximation to adjacent structures.

In staging of non–small cell carcinoma, CT has several limitations. Normal-sized mediastinal lymph nodes may contain microscopic metastatic deposits that are subsequently identified on thoracotomy in as many as 20% of patients. Similarly, enlarged inflammatory nodes may be falsely characterized as metastases in as many as 20% of patients.

The sensitivity and specificity of CT in detecting metastatic mediastinal lymph node involvement is in the range of 70-80%. CT scan may have further limitations in distinguishing stage IIIA disease from stage IIIB disease. In a peripheral TI lesion, CT probably does not contribute, because chest radiography appears to be sufficient. CT is also limited in evaluating the extent of endobronchial abnormalities. CT may also be limited in evaluating and staging apical lung tumors.

DIFFERENTIALS

Section 3 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Other Problems to be Considered

Lung abscess

RADIOGRAPH

Section 4 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

On chest radiography, the findings of non–small cell lung carcinomas are varied and considered in the differential diagnosis of many disorders. The most common findings are described below.

• Bronchial stenosis
  • Bronchial stenosis and poststenotic changes are commonly because most non–small cell carcinomas demonstrate intraluminal growth. Narrowing of the main bronchi or a complete cutoff can be identified on chest radiographs.
  • Endobronchial lesion commonly leads to partial or complete atelectasis and is the most common sign of bronchogenic carcinoma. Complete endobronchial obstruction can sometimes produce distal mucoid impaction, which may be visible on plain radiographs as a tubular or branching opacity.
    • Atelectasis of a segment, a lobe, or an entire lung may occur.
    • Radiographic signs include patchy irregular or homogeneous opacities in a lobar or segmental distribution.
    • A loss of lung volume may be seen, as well as displacement of interlobar fissures, mediastinum, diaphragm, and the ribs.
    • Postobstructive pneumonia may be identified in a segmental or lobar distribution. In patients with recurrent pneumonia, bronchogenic carcinoma is suggested unless proven otherwise.
• Regional hyperlucency
  • An endobronchial lesion reduces the ventilation despite normal or increased air volume.
  • As a result, hypoxic vasoconstriction reduces perfusion, and attenuation is seen as hyperlucency on chest radiography. In partially atelectatic areas of the lung, hyperlucency rather than opacity may be evident.
• Hilar mass
  • Central bronchogenic carcinomas manifest added opacity in the hilar region.
  • In the early stage, the tumor may fill the lateral concavity of the hilar shadow, and in the advanced stage, all hilar structures are obliterated.
  • Infiltration of lymphatics with bronchogenic carcinomas may be demonstrated as linear opacities radiating from the hilar mass into the lung periphery.
• Solitary pulmonary nodule
  • A solitary pulmonary nodule may be relatively well marginated and appears as a rounded lung opacity.
  • Reportedly, a solitary pulmonary nodule is benign in as many as 60% of patients in some series. All patterns of calcification except eccentric or scattered punctate (stippled) calcification are associated with a benign lesion.
  • Procuring and identifying the lesion on previous chest radiographs is extremely important. This may help establish the doubling time interval for the nodule. A doubling time of 30-365 days commonly is associated with a malignancy.
  • Other possible signs of malignancy include the following:
    • Diameter more than 3 cm
    • Ill-defined or spiculated margin
    • Rigler notch sign (a notch on the nodule corresponding to the vascular supply)
    • Radial striated markings at the nodular margin (termed corona radiata)
    • Thick-walled cavity
    • Eccentric calcification
• Nonresolving pneumonia
  • An ill-defined homogeneous or patchy consolidation in a segmental or nonsegmental distribution may be an indication of bronchogenic carcinoma. Patients with these findings often are treated initially for pneumonia; the lack of response to antibiotic therapy suggests the diagnosis of a malignancy.
  • The opacity may contain air bronchograms and air alveolograms. This presentation is often seen with adenocarcinoma and bronchoalveolar carcinoma.
• Indirect signs of involvement of contiguous structures also may be found. Bronchogenic carcinoma may involve the surrounding thoracic structures, which often indicates that the tumor is not resectable. Findings include the following:
  • Osteolytic lesions and pathologic fractures of rib and vertebra
  • Phrenic nerve involvement causing diaphragmatic paralysis and exhibiting ipsilateral elevation of involved diaphragm
  • Pleural effusion secondary to visceral pleural involvement or lymphatic obstruction (confirm the presence of a malignant effusion using thoracentesis)
• Mediastinal lymph node enlargement: Metastases to paratracheal, tracheobronchial, peribronchial, aortopulmonary, and subcarinal lymph nodes may be identified on chest radiographs. The radiographic signs include a widened mediastinum, an increase in the right paratracheal stripe, a convex margin of the mediastinum, an absence of concavity in the aortopulmonary window, and splaying of carina.

Degree of Confidence

Lung cancer screening with chest radiographs has improved the 5-year survival rates, but a mortality benefit has not been demonstrated.

CT SCAN

Section 5 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

CT scanning of the thorax plays multiple roles in evaluation of patients with bronchogenic carcinoma. These include lung cancer screening, evaluation of a solitary pulmonary nodule, and staging.

Using CT to detect lung cancer

A few trials have used low-dose helical CT to screen patients at risk for lung cancer. CT depicted noncalcified nodules, although a small number were found to be malignant. Although these studies looked promising, they lacked control groups. Further clinical trials to evaluate outcome in patients screened for lung cancer by using CT scan are underway. Hopefully, CT scan will become a worthwhile modality for use in the early detection of lung cancer.

• Solitary pulmonary nodule: CT plays a significant role in workup of solitary pulmonary nodules.
  • CT scans may help establish a specific diagnosis in some patients.
  • CT densitometry may help in differentiating between benign and malignant lesions.
  • CT scans may help in the diagnosis of arteriovenous fistulas, rounded atelectasis, fungus balls, mucoid impaction, and lung infarcts. CT scans may also help in identifying a fungus ball that is not well delineated on a chest radiograph.
  • A peripheral nodule with ill-defined, irregular, and spiculated border is malignant in more than 90% of patients.
  • Air bronchogram findings and pseudocavitation (focal lucency) are seen more commonly in malignant nodules.
  • Cavitation may be a feature of both malignant and benign lesions.
  • The thickness of the wall cavity may be helpful in distinguishing benign from malignant lesions. A wall of less than 1 mm indicates a benign lesion in 95% of patients, and a wall thickness of more than 15 mm indicates a malignant lesion in more than 80% of patients.
• CT densitometry: CT densitometry is useful in detecting the presence and distribution of calcification and fat within solitary nodules.
  • CT scan is more sensitive than chest radiography for detecting the presence of calcification. Approximately one third of indeterminate nodules found on chest radiography can be demonstrated to have calcium on CT scans. CT numbers can be obtained by placing a cursor over the lesion; a value of more than 200 HU indicates calcification.
  • The presence of fat, detected either from direct visualization or from CT numbers ranging from –40 to –120 HU, is diagnostic for hamartoma.
• Contrast-enhanced CT: Enhanced scans may help in distinguishing between malignant and benign lesions.
  • Malignant lesions enhance to a greater degree than do benign lesions after the administration of a contrast material; however, active granulomas or other infectious lesions can also enhance.
  • A measurement of CT numbers during enhancement is useful. An increase of 20 HU or more indicates a sensitivity for lung cancer of 98% and a specificity of 73% (Swensen, 1996). Contrast enhancement may be used in patients who do not have characteristic findings of either malignant or benign lesions. The nonenhancing nodules may be monitored as long as other features suggesting malignancy are not present.

Using CT to stage lung cancer

• Primary tumors: CT scans may be useful in evaluating primary tumors. Although the size of the tumor, whether the lesion is T1 or T2, may not change the surgical approach, the site of the tumor is important to identify.
• CT scans may be helpful in determining tumor extension across the major fissure.
• CT scans are useful in assessing local invasion of the chest wall, mediastinum, mainstem bronchus, central veins, and arteries.
  • Signs of chest wall invasion include bone destruction, tumor extension into the chest wall, pleural thickening, and loss of extra pleural fat plane.
  • Identification of mediastinal invasion with CT usually is unreliable. In addition, minimal mediastinal fat invasion may be resectable in many cases.
  • Tumor invasion of the central arteries and veins may be identified by using CT, which indicates that a pneumonectomy is required.
  • Tumor invasion of the mainstem bronchus can also be visualized on CT scans. This is a useful finding for planning the surgical procedure.
• Hilar and mediastinal lymph node metastases: CT is a useful radiologic modality for noninvasive anatomic evaluation of the hila and mediastinum.
  • The indication of metastasis primarily is based on size criteria. A lymph node with a short-axis diameter of more than 1 cm is defined as enlarged.
  • Although the probability of metastasis increases with increasing lymph node size, CT scanning is not helpful in differentiating a metastasis from a benign lesion.
• Microscopic metastasis: CT may be useful in assessing metastases.
  • Normal-sized lymph nodes have been reported in 7-33% of patients undergoing CT staging. In addition, controversy exists over whether the short-axis or the long-axis diameters should be used in imaging. Another limitation may be interobserver variability in the interpretation of imaging studies.
  • Despite the limitations, CT provides useful staging information to the surgeon. Noting enlargement in a specific location may help surgeons in planning procedures, including mediastinoscopy, mediastinotomy, or percutaneous needle aspiration biopsy.
  • CT is useful in demonstrating extrathoracic metastases. Distant metastases demonstrated with CT include metastases to the adrenal glands, brain, bones, liver, and soft tissues.
  • Chest CT should include the upper abdomen to assess the liver, upper abdominal lymph nodes, and adrenal glands. However, on needle biopsy, most adrenal masses are shown to be adenomas rather than metastases.

Degree of Confidence

On contrast-enhanced CT scans, increased attenuation of 20 HU or more is 98% sensitivity and 73% specific for lung cancer (Swensen, 1996).

MRI

Section 6 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

MRI is an imaging modality with several advantages, including a lack of ionizing radiation, the ability to image vascular structures without contrast media, the ability to image in any plane, and superior contrast resolution. MRI is not useful as an initial imaging tool, but it may be superior to CT in the evaluation of local invasion and detection of hilar lymphadenopathy.

In particular, MRI is useful in the evaluation of superior sulcus tumors. Invasion of the brachial plexus, subclavian vessels, and adjacent vertebral bodies can be demonstrated with MRI. Compared with other techniques, MRI may be slightly more accurate in detecting extranodal tumor extension into the mediastinum.

The multiplanar capability of MRI enables a more accurate evaluation of hilar lymph nodes, aortopulmonary window lymph nodes, and subcarinal region lymph nodes, compared with that of CT.

Degree of Confidence

MRI depends on size criteria for the detection of mediastinal metastases. MRI is limited in detecting small lymph nodes containing microscopic deposits. MRI can be used as an imaging modality for apical or superior sulcus lung tumors. MRI is superior in detecting invasion of the chest wall, vertebral body, subclavian vessels, and brachial plexus. For the detection of chest wall invasion, a sensitivity of approximately 90% and a specificity of 96-100% has been reported.

NUCLEAR MEDICINE

Section 7 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Findings

Bone scanning

In patients who have biochemical or physical evidence of bone metastasis, a bone scan is required as part of the preoperative workup. A routine bone scan is usually not recommended in asymptomatic patients.

Positron emission tomography

Although not universally available, PET holds promise in the evaluation of bronchogenic carcinoma. PET can be used to determine the metabolic activity rather than the morphologic features of the lesions. Bronchogenic carcinoma is associated with an increased rate of glucose metabolism. PET uses deoxyglucose linked to fluorine 18 (a positron emitter). The agent, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG), competes with glucose for transport into the cells and after phosphorylation accumulates in tumor cells. Lung tumor cells have increased glucose metabolism; however, this is not specific for tumors and may occur in infectious or inflammatory processes.

FDG PET scan has been used to differentiate benign from malignant pulmonary nodules. PET scans also may be useful in detecting distant metastases when whole-body imaging is performed. Because of the false-positive rate, invasive staging procedures may still be required before potentially curative surgical management is denied.

Degree of Confidence

PET imaging has higher sensitivity, specificity, and accuracy than CT in staging mediastinal disease. Published studies have demonstrated a sensitivity of 80%, an overall specificity of 92%, and an accuracy of 92%, with a positive predictive value of 90% and a negative predictive value of 93%.

False Positives/Negatives

False-negative studies can occur in patients with carcinoid syndrome, bronchoalveolar carcinomas, and bronchogenic carcinoma measuring less than 10 mm. False-positive findings are known to occur in infectious or inflammatory disorders such as tuberculosis, histoplasmosis, and rheumatoid nodules.

INTERVENTION

Section 8 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Percutaneous transthoracic needle biopsy (PTNA) is used for the diagnosis of lung cancer.

Technique

The patient is prepared for percutaneous transthoracic needle biopsy prior to the procedure, and informed consent is obtained. Prothrombin time and platelet count tests are performed within the 2 weeks prior to the procedure. The relative contraindications for PTNA include patient inability to hold breath, patient inability to maintain certain body positions, underlying coagulopathy (internal normalized ratio >1.3, platelet count <50,000/cm³), severe chronic obstructive pulmonary disease, required mechanical ventilation, vascular lesion, pulmonary arterial hypertension, and bullae near the lesion.

The biopsy room should be equipped with oxygen, suction and oral and nasal airway machines, an AmbuBag, a Pleurovac, and a crash cart. An intravenous line is inserted in the patient, and blood pressure monitors (during and after the procedure), electrocardiogram leads, and an oxygen saturation monitor are attached. After localization of the lesion, the biopsy needle is introduced over the rib, and the specimen is obtained while the patient holds his or her breath. A core biopsy may also be performed with a cutting needle through the same puncture site.

Results

Expert support from a cytopathologist is essential for the preparation of samples and the interpretation of findings. The diagnostic yield is increased if quick on-site pathologic analysis is available at the time of biopsy to confirm the adequacy of the sample. Many investigators have reported a sensitivity of 90-95% with PTNA for the diagnosis of cancer. The accuracy is 100% in differentiating non–small cell carcinoma from small cell carcinoma. The yield for accurate diagnosis is lower for smaller and deeply situated lesions.

A negative result is unsatisfactory unless a specific benign diagnosis is established. Benign diagnoses include hamartoma, granuloma, an infectious organism, or fibrogranulation tissue. Patients who receive a benign diagnosis usually require periodic follow-up monitoring. Unfortunately, fewer than 40% of needle biopsies indicate a specific benign diagnosis.

Complications

The incidence of pneumothorax after needle biopsy has been reported to be 15-30%. Most pneumothoraces occur within the first hour after biopsy; however, a 4-hour chest radiograph must be obtained. Chest tube drainage is required in a minority ( <15%) of patients.

Hemorrhage may occur in patients in 1-10% of transthoracic needle biopsy procedures. Hemorrhage is almost always self-limiting. Patients are cautioned to lay on the side of the hemorrhage to avoid spilling blood into the unaffected lung.

Systemic air embolism is an extremely rare complication of needle biopsy occurs when air enters the pulmonary vein directly from the open needle. Rarely, placement of the needle may create a fistula between the alveolus and the vein. This is an extremely rare complication (0.012%) of transthoracic needle biopsy.

Postbiopsy management

Chest radiographs are recommended at 1- and 4-hour intervals after the biopsy is performed, unless the patient appears to be hypoxemic or unstable, in which case, chest radiography should be performed immediately.

A small or asymptomatic pneumothorax may be followed at an interval of 2-4 hours with repeat chest radiography. If the pneumothorax remains stable and patient is asymptomatic, chest tube drainage is not required. In an enlarging pneumothorax (15-30% pneumothorax) or a symptomatic patient, a pneumothorax drainage catheter should be placed and connected to a Heimlich valve or Pleurovac system.

Medical/Legal Pitfalls

• The role of chest radiography in screening for lung cancer remains unanswered. Three large randomized trials demonstrated a decreased lung cancer mortality rate in the screening group, but none of these three centers had an untested control group.
• Presently, the decision whether to observe the lesion, perform biopsy, or resect an indeterminate nodule remains unclear. Contrast-enhanced CT and PET scanning with FDG may improve the sensitivity and specificity in identifying malignant nodules.
• CT scans are used extensively for staging non–small cell lung cancer; however, CT staging leads to either overestimated or underestimated in approximately 40% of patients. MRI can be helpful in identifying the relationship of the tumor to the central pulmonary artery, aorta, carina, and main bronchi.
• MRI can better delineate invasion or abutment of the superior vena cava, central pulmonary arteries, pericardium, and heart.
• Variability in interpretation is common, even among experienced radiologists.
• Advantages of MRI over CT are such that it may be easier to distinguish lymph nodes from blood vessels due to their different signal intensities or attenuations, respectively. Enlargement of aortal pulmonary and subcarinal nodes may be better detected by using MRI scanning.
• MRI is not able to depict calcification. Blood vessels with low flow may be misdiagnosed as lymph nodes or masses. Respiratory or other motion may cause blurring of images, leading to a missed diagnosis of lymphadenopathy.
• Prevalence of mediastinal lymph node involvement with T1 lesion is 22% or less.

See also the Medscape topic Medical Malpractice and Legal Issues.

Special Concerns

• Postpneumonectomy complications
• • After pneumonectomy, accumulation of pleural fluid gradually replaces the air in the surgical bed over time. Most of the air is reabsorbed within 2 weeks after pneumonectomy; residual air may persist for months or occasionally years.
  • Multiple air-fluid levels may also be seen within a few days following pneumonectomy and reflect loculation of fluid. Over time, ipsilateral shift of the mediastinum occurs, with elevation of the diaphragm, and the space is filled with fluid as well as some degree of fibrothorax. If shift occurs too rapidly, compromise of vascular or bronchial structures can lead to respiratory or circulatory instability.
  • Contralateral mediastinal shift may occur secondary to accumulation of air or fluid and may suggest one of several diagnoses, depending on the postpneumonectomy interval. Absence of a continuous rise in the air-fluid level in postpneumonectomy space suggests bronchial stump air leak. A decrease in the air-fluid level after an initial rise may indicate thoracentesis, chest tube drainage, leakage of fluid through dehiscence of thoracic incision, bronchial stump leak, or leak into the abdominal cavity through a diaphragmatic tear.
  • Pneumonectomy has a high mortality rate (5-10%). The causes of death include pneumonia, respiratory failure, pulmonary embolism, myocardial infarction, bronchopleural fistula, and empyema. The incidence of postpneumonectomy empyema varies from 2-5% and is often associated with bronchopleural fistula. Early postoperative empyema may be caused either by a preoperative pleural sepsis or by intraoperative contamination, while delayed onset of empyema connotes bronchopleural or bronchoesophageal pleural fistula.
• Pancoast tumor
• • A Pancoast tumor (superior sulcus tumor) is a rare form (1%) of bronchogenic carcinoma that arises in the superior sulcus of the lung apex.
  • The most common tissue type is squamous cell carcinoma, but adenocarcinoma also may occur at this site.
  • These tumors often lead to invasion of the pleura and rib, producing shoulder pain that is often treated as musculoskeletal pain.
  • Involvement of the lower roots of brachial plexus cause arm pain and paresthesias in ulnar nerve distribution.
  • The tumor may spread to the symptomatic ganglion, leading to Horner syndrome, which manifests as ipsilateral enophthalmos, miosis, partial ptosis, and anhidrosis.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

Media file 1:  Non–small cell lung cancer. Bronchoscopy. A large central lesion was diagnosed as non–small cell carcinoma.
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Media file 2:  Non–small cell lung cancer. Left pleural effusion and volume loss secondary to non–small cell carcinoma of the left lower lobe. The pleural effusion was sampled and found to be malignant; therefore, the lesion is inoperable.
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Media file 3:  Non–small cell lung cancer. Left upper collapse is almost always secondary to endobronchial bronchogenic carcinoma.
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Media file 4:  Non–small cell lung cancer. Complete left lung collapse secondary to bronchogenic carcinoma of left mainstem bronchus.
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Media file 5:  Non–small cell lung cancer. A cavitating right lower lobe squamous cell carcinoma.
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Media file 6:  Non–small cell lung cancer. CT scan shows cavitation and air-fluid level (same patient as in Image 5).
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Media type:  CT

Media file 7:  Non–small cell lung cancer. Patient has right lower lobe opacity. This is not well circumscribed and was found to be a squamous cell carcinoma.
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Media type:  X-RAY

Media file 8:  Non–small cell lung cancer. Right upper lobe lesion diagnosed as adenocarcinoma on percutaneous biopsy.
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Media file 9:  Non–small cell lung cancer. Right upper lobe collapse with the S sign of Golden secondary to underlying non–small cell carcinoma of the bronchus.
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Media type:  X-RAY

Media file 10:  Non–small cell lung cancer. Comparative characteristics of the primary tumor are shown in the vertical columns. Horizontal columns refer to lymph node involvement. The different stages are color coded and can be found at the intersection of appropriately matched horizontal and vertical columns. Stages with unique characteristics, such as stages 0 and IV, are defined in separate boxes. Courtesy of Lababede et al (Chest 1999; 115(1): 233-5).
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Media type:  Image

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Nuclear Medicine
• Intervention
• Multimedia
• References

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Article Last Updated: Aug 10, 2005