is a Fourth-Year Radiology Resident;
is an Assistant Professor of Radiology; and
is a Professor of Radiology, Residency Program Director, and Vice
Chairman of Education in the Department of Radiology, University
of North Carolina, Chapel Hill, NC. Dr. Molina is also a member
of the Editorial Board of this journal.
Lung cancer is the most frequently diagnosed cancer in the
world, and the leading cause of death from cancer.
Radiology plays a critical role in the initial detection and
diagnosis of thoracic malignancies, as well as in pretreatment
staging, which is important in identifying patients with localized
disease who are likely to benefit from surgical resection.
Chest radiography and computed tomography (CT) have been the
primary imaging modalities used to fulfill these roles. Positron
emission tomography (PET) is rapidly emerging as a clinically
useful noninvasive study that complements conventional radiologic
imaging in the evaluation of patients with lung cancer.
The role of magnetic resonance imaging (MRI) in this regard
generally is limited; it is used primarily for specific
problem-solving issues, such as the determination of chest wall or
Lung cancer is by far the number one cause of cancer death in
the United States, regardless of race or ethnic background. This
disease burden is a fairly recent phenomenon, arising first in
western countries in the 1930s, and rising sharply in subsequent
years. Since 1950, lung cancer mortality has risen 197% in men, and
612% in women. In 1998, 20,000 more women died of lung cancer than
breast cancer. The survival rate is poor, largely because lung
cancer is usually diagnosed at an advanced stage. A cure can only
be achieved by surgery, which is feasible only in patients who
present in an early stage. However, even in this group,
approximately 75% will die of recurrent disease.
Lung cancer is rare before the age of 40, after which age-specific
rates rise sharply. The ages with the greatest incidence are
between 65 and 79.
There are several extrinsic risk factors, but lung cancer is
unique among all malignancies in that a single risk factor accounts
for approximately 90% of the risk, specifically, tobacco smoking.
The smoker is not the only one at risk. There is general agreement
that lung cancer risks are increased by 60% from long-term
environmental tobacco smoke exposure, making second-hand smoke a
significant added risk factor. Other extrinsic factors include
exposure to radon, and occupational exposure to asbestos, arsenic,
and chromium compounds. Radon and asbestos share the distinction of
having a synergistic relationship with cigarette smoking. There is
increasing evidence that genetic factors can contribute to lung
cancer risk. However, research has not yet identified the gene
locus or the mechanism.
Lung cancer is a broad term for cancers arising in epithelial
tissue in the lining of the bronchi, and also in the trachea,
bronchioles, and alveoli. Approximately 90% to 95% of all primary
lung cancers are bronchogenic carcinomas. Histologically, about 20%
of these cancers are small-cell carcinomas. The other 80% are
grouped together as nonsmall-cell lung cancers (NSCLC), which are
divided into three subtypes: (1) adenocarcinoma (30% to 40%), (2)
squamous cell carcinoma (30% to 40%), and (3) large cell
undifferentiated carcinoma (10%). These three subtypes are grouped
together because NSCLCs overall have similar treatment options, as
well as a better prognosis when disease is still localized at
Approximately 90% of small-cell carcinomas are located
centrally, and tend to invade longitudinally along submucosal and
intramural portions of the bronchial walls and in the supporting
tissues and lymphatics.
They are often characterized by extensive, bulky, mediastinal
lymphadenopathy. Small-cell lung cancer is considered a nonsurgical
disease, with the majority of cases presenting in an advanced
The majority of squamous cell carcinomas are also located
centrally, and are more frequently associated with bronchial
obstruction. This is in contrast to large-cell tumors and
adenocarcinomas, which tend to be peripheral.
A specific subtype of adenocarcinoma, known as bronchioalveolar
carcinoma (BAC), can appear as a single nodule, segmental or lobar
consolidation, or as diffuse nodules.
Other, more rare types of lung cancer include carcinoid tumors,
adenoid cystic carcinomas, and mucoepidermoid carcinomas.
The role of chest radiography
The detection and diagnosis of lung cancer usually begins with a
chest radiograph, either in a symptomatic patient or in a patient
undergoing a chest radiograph for an unrelated reason. The
appearance of lung cancer is variable, and can range from a subtle
finding, to the dramatic, depending on location, stage at
presentation, and associated findings.
Central tumors may be visible on the chest radiograph as an
abnormal convexity or density in the hilar region. In many cases,
however, the major radiographic abnormality is abnormal parenchymal
opacification due to atelectasis or postobstructive pneumonitis,
which may obscure the central tumor. The distribution of
parenchymal findings depends on the tumor location, and can range
from subsegmental atelectasis to the collapse of an entire lobe or
lung (Figure 1).
Occasionally, the cancer remains identifiable as a central contour
bulge, and if it obstructs the right upper lobe bronchus, it may
result in the S-sign of Golden. The peripheral concave portion of
the S is formed by the interface between the collapsed right upper
lobe and the remaining hyperinflated lung. The more central convex
portion of the S represents the tumor itself. Other, less
frequently seen manifestations of a central tumor include mucoid
impaction, air trapping, and pulmonary vascular occlusion or reflex
vasoconstriction leading to oligemia or infarction.
Often, the first indication that a cancer exists is the finding
of a solitary pulmonary nodule (SPN) on a chest radiograph. The SPN
is usually defined as a single round or oval opacity in the
pulmonary parenchyma, measuring <3 cm in diameter. The SPN is
one of the most common radiographic abnormalities detected, seen in
up to 1 in 500 chest radiographs, with an estimated malignancy rate
between 20% and 40%.
With studies of good quality, a SPN larger than 1 to 2 cm is
usually not difficult to detect, but can be overlooked easily in
certain locations, such as the lung apices, the parahilar and
paramediastinal regions, below the domes of the diaphragm, and
overlying the spine. As many as 90% of small peripheral lung
cancers have been reported to be visible retrospectively on prior
chest radiographs, and missed lung cancer is a leading cause of
malpractice litigation against radiologists.
Bronchogenic carcinoma is most often located in the upper lobes,
particularly the right upper lobe, and not surprisingly, most
missed cancers are in the right upper lobe (Figure 2). A 1991 study
of 93 patients with SPNs found 63% to be in the upper lobes, with
the right lower lobe being the next most common site.
Once discovered, certain characteristics of an SPN, such as
size, calcification, shape, edge characteristics, cavitation, and
growth rate can help differentiate between a benign and malignant
lesion. The size of a lesion is not only important in terms of its
visibility, but also because of the relationship of size to
malignancy. Once a nodule reaches a size >3 cm, it is more
likely to be malignant. However, the incidence of primary
malignancy in smaller lesions, even in those <1.5 cm, is
substantial enough that size alone is insufficient for
Certain types of radiographically visible calcification, such as
lamellated or central calcification in granulomas, and the popcorn
pattern in hamartomas, are highly specific for benignity. Caution
must be exercised, however, as a growing lung cancer may surround a
calcified granuloma. In addition, dystrophic calcifications may
rarely be seen in both primary and metastatic tumors, and a
minority of carcinoid tumors also calcify.
The margin of a lesion can also provide useful information.
Lobulation of a nodule is a worrisome feature that suggests uneven
growth, and supports malignancy. Lobulations are thought to be
caused by contraction or differential growth rates within the
tumor. Spiculations, defined as linear strands extending from the
nodule into the lung parenchyma, are of even greater concern, and
are thought to represent a desmoplastic response to local tumor
Cavitation is seen in a minority of lung cancer, mostly squamous
cell carcinoma, but also occasionally in adenocarcinoma or large
cell types (Figure 3). Usually, the cavity wall is thick (>5 mm)
and may demonstrate a nodular internal margin. A maximum wall
thickness <4 mm is unlikely to be malignant, but rare cases do
exist with thin walls simulating bullae.
Growth correlates with doubling time, which is a measure of
volumetric growth, not diameter. The natural history of lung
malignancy is to double its volume 40 times before death occurs.
Once a nodule has reached the reliably detectable size of 9 mm, it
has already undergone 30 doublings. Most tumors have a doubling
time of between 30 and 490 days (mean value 120 days), and doubling
times that are either shorter or longer suggest a benign etiology.
A 9-mm SPN with a doubling time of 100 days will measure 1.1 cm at
3 months and 1.4 cm at 6 months, making accurate measurement
critical. Discovery of an SPN on a chest radiograph should prompt
every effort to obtain more remote films for comparison. The
absence of growth over a 2-year period is the most reliable
indicator of benignity.
Unfortunately, making a firm diagnosis for all pulmonary nodules,
especially for small nodules ¾ 1 cm, remains problematic, as
evidenced by a high rate for resection of benign nodules.
Cancers arising in the lung apex, known as superior sulcus or
Pancoast tumors, are a distinct subgroup because of their
characteristic location and constellation of symptoms (Figure 4).
Radiographic findings can be quite subtle and are frequently
obscured by, or misinterpreted as, overlying musculoskeletal
structures, brachiocephalic vessels, or benign pleural thickening.
Findings suggestive of malignancy include an apical cap >5 mm,
asymmetry of apical caps >5 mm, an apical mass, and adjacent
Clinical symptoms of arm pain (secondary to involvement of the
brachial plexus) and a Horner's syndrome (meiosis, ptosis, and
anhydrosis, secondary to involvement of the stellate ganglion) are
classically associated with a Pancoast tumor. CT and MRI are
superior to chest radiography in evaluating the lung apex,
particularly MRI, because of its ability to image directly in
multiple planes and visualize the brachial plexus.
Lung cancer occasionally takes the form of focal or multifocal
consolidation, typically with bronchioalveolar carcinoma (BAC).
Although the most common appearance of BAC is as a SPN (43%),
consolidation is the second most common radiographic pattern (30%).
This pattern is caused by tumor growth along the framework of
peripheral airways and alveoli, combined with mucoid secretions.
Air bronchograms and air alveolograms are characteristic, but not
specific, features. A pattern of focal or multifocal nodularity can
result from involvement of one or more acini, and when confluent,
can resemble non-neoplastic conditions, such as pneumonia,
aspiration, or edema (Figure 5). However, the clinical course of
bronchioalveolar carcinoma is more chronic, and without signs and
symptoms of infection. The consolidative pattern has a poorer
prognosis than the solitary nodular pattern. Bronchorrhea (copious
white mucoid or watery expectoration), once considered the clinical
hallmark of this disease, is an unusual and late manifestation seen
only with diffuse bronchioalveolar carcinoma.
Hilar and/or mediastinal adenopathy is sometimes the sole
manifestation of lung cancer. Small-cell carcinoma tends to have
bulky, central adenopathy with a relatively inconspicuous separate
primary lung parenchymal site, but all cell types can have
metastatic spread centrally. Careful inspection of the normal
contours, lines, and stripes that classically define the
mediastinum may reveal enlargement of the aortopulmonary window,
right paratracheal thickening or soft-tissue density, a double
density adjacent to the aortic knob, or an abnormal convexity in
the azygoesophageal recess, all of which are frequent findings of
mediastinal metastasis of lung carcinoma.
The lateral film can be especially helpful in the evaluation of
suspicious increased hilar or mediastinal density.
Intrathoracic spread of lung carcinoma is not limited solely to
mediastinal and hilar adenopathy. The pleura, chest wall, heart,
great vessels, diaphragm, and nerves are additional structures that
can be involved secondarily. Such involvement significantly impacts
tumor staging, treatment, and prognosis. Pleural involvement
usually manifests as a pleural effusion, with or without pleural
masses. Pleural effusion (either free-flowing or loculated) implies
seeding by tumor, but a nonmalignant effusion can result from
central lymphatic obstruction, or a coincidental benign cause, such
as pneumonia, congestive heart failure, or pulmonary embolus.
Direct invasion of the pleura is also possible, but cannot be
distinguished on a chest radiograph. Bone involvement is common,
and can be due to direct extension or metastatic spread. Pancoast
tumors are typically associated with direct extension to ribs or
vertebral bodies, but this can also occur with other peripheral
cancers. Metastatic disease may also involve other bones on the
chest radiograph, as evidenced by bony destruction or lytic lesions
in the humerus, sternum, clavicle, and scapula. Bronchogenic
carcinoma can also involve the heart, either by direct extension or
by manifesting as a malignant pericardial effusion, seen as an
enlarging cardiac silhouette on serial radiographs. Elevation of
the diaphragm may indicate phrenic nerve involvement by tumor, or
be mimicked by a subpulmonic effusion. A history of hoarseness can
be secondary to tumor involvement of the recurrent laryngeal nerve
in the aortopulmonary window.
The chest radiograph plays a critical role in the detection and
evaluation of the protean appearances and manifestations of lung
cancer. However, once the suspected tumor is identified, additional
important information is often necessary that cannot be provided by
the chest radiograph. Therefore, the next step in the diagnostic
work-up of lung cancer is computed tomography.
The role of computed tomography
Thoracic CT scanning plays several vital roles in the evaluation
of patients with known or suspected lung cancer. One is to further
characterize a suspicious abnormality seen on a chest radiograph,
and to provide a more complete evaluation of a primary neoplasm. A
second and indispensable role is that of pretreatment or pre-
operative staging, for which CT is the primary imaging modality.
Additionally, chest CT helps provide a roadmap for other staging
procedures such as bronchoscopy, mediastinoscopy, transthoracic
needle biopsy, and video-assisted thorocoscopy.
Most, if not all, of the various manifestations of lung cancer
described for chest radiography can be better evaluated with CT.
Cross-sectional imaging can help further clarify a tumor's
location, whether in a central or peripheral location, and
delineate its relationship to pleura, chest wall, and mediastinal
structures. The level and degree of obstruction by central tumors
leading to atelectasis and postobstructive pneumonitis can be
visualized easily with cross-sectional imaging (Figure 6). Squamous
cell cancers arise in the cells lining the mainstem, lobar, or
segmental bronchi, and are frequently associated with this pattern
Trapped secretions distal to an obstructing lesion can produce the
so-called mucous bronchogram.
Imaging features used to characterize an SPN on a chest
radiograph are equally as useful on CT, including size and growth
rate, calcification, shape and margins, and cavitation, along with
the additional characteristics of density and contrast enhancement.
As with chest radiography, increasing size, especially >3 cm,
correlates with an increasing chance of malignancy. CT enjoys the
added advantage of more accurate measurement of a nodule's size to
better detect and quantify interval growth.
CT can better detect and evaluate calcifications within a nodule.
The distribution of calcium, rather than its presence alone, is a
more important diagnostic consideration. Thin layers of calcium in
a lamellar pattern are indicative of a granuloma, and popcorn
calcifications with associated fat density, are associated with a
A smooth peripheral margin on CT is associated more frequently
with benign lesions. As with chest radiographs, lobulations and
spiculations are worrisome findings. In addition, the finding of a
pleural tag, defined as a linear area of high attenuation,
surrounded by aerated lung, originating from the edge of the mass
and extending peripherally to contact the pleural surface, is also
associated more frequently with malignant lesions. As with
spiculations, a pleural tag correlates with a desmoplastic
The wall thickness of a cavitary lesion can be measured more
accurately with CT. One study found that the majority (94%) of
cavitary solitary pulmonary nodules with a wall thickness ¾ 4 mm
were benign, and the majority (95%) with a wall thickness >= 15
mm were malignant. Lesions with wall thicknesses between 5 and 15
mm were almost equally divided between benign and malignant. CT
also has the added advantage of better evaluating the contour of a
cavity's wall. A smooth inner wall is more commonly associated with
a benign etiology, while a nodular internal margin reflects focal
Several other characteristics of an SPN can be evaluated with
CT, such as attenuation and contrast enhancement. Homogeneous
attenuation has been found to be associated more often with a
benign, rather than a malignant lesion. Thin collimation CT is more
sensitive than standard CT for assessment of attenuation.
In 1980, an early study with CT reported that benignity was
correlated with high Hounsfield units (>164), but further
studies have demonstrated that the CT numbers of an SPN cannot be
viewed as an absolute value, but rather are a relative indication
of attenuation, dependent on scanner and patient variables.
These studies resulted in the introduction in the 1980s of a
reference phantom that could be used as a standard with which the
attenuation of a pulmonary nodule could be compared. Although there
is controversy regarding the use of a reference phantom versus
thin-section CT alone, a 1991 study found that a phantom is useful
if the initial thin-slice CT is indeterminate. Also, if the
attenuation of the nodule in question exceeds the attenuation of
the phantom by 10%, it has a high probability of being benign.
A newer technique for the assessment of the SPN is based on
differential nodule enhancement with IV contrast material, as
measured with thin-slice CT. It relies on qualitative and
quantitative differences in the blood supply to benign and
malignant nodules. Results from a 1992 study suggest that malignant
nodules tend to enhance significantly more (20 HU increase) than
benign nodules, with the most diagnostically important measurement
made at 2 minutes postinjection.
One additional CT finding that may be helpful in the evaluation
of lobar consolidation and the clinical suspicion of
bronchioalveolar cell carcinoma is the CT angiogram sign (Figure
7). This is defined as branching pulmonary vessels extending >3
cm in the midst of completely consolidated pulmonary parenchyma
that is of diffusely homogeneous lower attenuation than that of
muscle. This finding has been noted to be present in a large
majority of cases of BAC, but is a nonspecific finding and can be
seen in pneumococcal or tuberculous pneumonia, pulmonary
infarction, and even lymphoma.
Of all newly diagnosed cases of lung cancer, approximately 80%
are NSCLC. Surgical resectability, chemotherapy and radiation
options, and survival rates are all related to the stage of
disease. Small-cell lung cancer remains a nonsurgical disease, with
the majority of patients presenting in advanced stages. The
intrathoracic and extrathoracic staging of lung cancer involves
assessment of the primary tumor and potential sites for metastases.
The TNM staging system (Table 1), most recently revised in 1997, is
the most widely accepted and utilized classification for
preoperative staging. Accurate and reproducible staging is crucial
in the clinical management of this disease. Since the development
of CT scanning, this modality has become the mainstay in radiologic
staging of chest malignancies.
With CT, the primary tumor is evaluated for initial size and
location, as well as possible extension beyond the lung parenchyma.
The primary tumor may involve the pleura, chest wall, mediastinal
structures, or vertebral bodies. Hilar tumors may invade the
trachea or carina. Metastatic sites include mediastinal lymph
nodes, as well as distant sites such as liver, adrenals, brain,
bone, and soft tissue.
Approximately 5% to 10% of patients who present with lung cancer
have a pleural effusion. Unfortunately, diagnostic thoracentesis
has a high (65%) false-negative rate of cytology for malignant
The CT hallmark for a malignant effusion is soft-tissue nodularity
along the pleural surface accompanying the effusion. Pleural
nodularity or fissural thickening without an effusion can also be a
sign of pleural metastasis. Pleural tumor dissemination is
classified as T4 disease, and is usually considered unresectable.
Approximately 5% of all lung cancers invade the parietal pleura
and chest wall (Figure 8). CT has demonstrated a wide range of
results when assessing for chest wall invasion by tumor.
Sensitivity ranges from 38% to 87%, and specificity ranges from 40%
to 90%, depending on the study.
The best criterion for diagnosing chest-wall invasion with CT is
bony destruction, with or without tumor extension into the chest
wall. Other, less reliable signs of chest-wall invasion include
pleural thickening, loss of the extra-pleural fat plane, an obtuse
angle between the mass and the chest wall, and >3 cm of contact
between the mass and the chest wall. Chest-wall invasion does not
necessarily exclude resection, but there is increased morbidity and
mortality associated with en bloc resection and chest-wall
reconstruction in this setting.
Mediastinal structures that can be invaded by tumor extension
include the trachea and carina, esophagus, mediastinal vessels,
heart and pericardium, and vertebral bodies (Figure 9). Disease
involving these mediastinal structures is classified as T4.
Although gross mediastinal invasion by bronchogenic cancer can be
diagnosed confidently on CT, attempts to distinguish subtle
mediastinal invasion from mere mediastinal contiguity have met with
However, there are certain CT criteria that suggest technically
feasible resectability. These include tumor contact of ¾ 3 cm with
the mediastinum, less than 90š of contact with the aorta, and the
presence of mediastinal fat between the mass and mediastinal
structures. Unfortunately, the opposite findings (>3 cm contact
with mediastinum, >90š of contact with the aorta, and
obliteration of fat planes) are unreliable signs of either invasion
CT is the preferred imaging technique for evaluating adenopathy.
The accurate localization of abnormal lymph nodes, whether
peribronchial, hilar, mediastinal, scalene, or supraclavicular, is
important in determining the N classification of the disease. The
American Thoracic Society's mediastinal nodal stations are used by
most surgeons, radiologists, oncologists, and pathologists to
describe sites of nodal metastases in thoracic malignancies
Lymph nodes are generally identified on CT as nonenhancing
soft-tissue densities surrounded by mediastinal fat. Several
studies have shown that the short axis diameter is the best
predictor of actual nodal volume.
In practice, increased nodal size is the only useful criterion for
malignancy, and a node measuring >1 cm is generally considered
abnormal. Increased nodal size is not an absolute indicator of
malignant disease, however, as nodes <1 cm in size may contain
microscopic metastases, and enlarged nodes may represent benign
reactive adenopathy to an unrelated process in the chest. Central
low density can represent fat in a normal node, or necrosis in a
The accurate description of abnormal nodal location is essential
information in assisting the surgeon, bronchoscopist, or
radiologist in planning a more invasive staging procedure.
Estimates of the overall prevalence of extrathoracic metastases
(M1 classification and therefore stage 4 disease) range from 18% to
The most frequent sites of hematogenous metastases are bone, brain,
contralateral lung, liver, adrenals, soft tissue, and skin. Distant
metastatic disease implies surgical unresectability, and the median
survival once distant metastases are diagnosed ranges from weeks to
months, with few patients surviving beyond 1 year. At most
institutions, a chest CT in patients with suspected lung cancer is
extended inferiorly to include the superior portion of the liver
and the adrenal glands.
A careful review of bone windows is also necessary in these
circumstances, to exclude metastatic deposits in ribs, the sternum,
the scapula, and the vertebral column.
The role of MRI
It is well accepted that CT is the imaging modality of choice
for staging patients with lung cancer. Compared with MRI, CT is
faster, less expensive, has better spatial resolution, offers
superior evaluation of the lung parenchyma, and is more sensitive
in detecting calcification. However, in certain circumstances, MRI
may play a complementary role to CT because of its superior tissue
contrast, multiplanar imaging capability, and superb delineation of
There are areas of the chest where the geometry of the structures
of interest are better imaged with MRI. Perhaps the best example is
the evaluation of Pancoast tumors, in which direct coronal and
sagittal imaging with MRI facilitates assessment of invasion of the
chest wall, brachial plexus, subclavian vessels, vertebral bodies,
and neural foramina
The superior contrast resolution of MRI suggests an advantage
over CT in detecting subtle mediastinal invasion, but its poorer
spatial resolution limits this advantage. The replacement of high
signal intensity mediastinal fat by lower signal intensity tumor on
T1-weighted MR images suggests the presence of mediastinal
invasion, but one study comparing CT and MRI for this purpose
showed similar accuracies of 56% and 50%, respectively. Some
investigators have shown MRI to be superior to CT in detecting
mediastinal extension when there is associated vessel involvement.
MRI is also believed to be more accurate in establishing superior
vena caval patency or obstruction, which may be due to thrombus,
compression by soft-tissue mass, or direct invasion.
MRI may also demonstrate chest wall invasion better, with one
study reporting a sensitivity of 90% and a specificity of 86%.
Signs of chest-wall invasion on MRI include loss of the subpleural
fat stripe and visualization of soft-tissue tumor extension into
the chest wall. Some early data suggest that MRI can also
differentiate benign (low signal intensity) pleural nodules from
malignant (high signal intensity) pleural nodules with T2-weighted
and proton density weighted images with a specificity of 87%.
In early studies it was initially thought that tumor within
lymph nodes would generate differential signal changes with respect
to normal nodes, leading to increased sensitivity and specificity
of MRI when compared with CT. However, several studies comparing
these modalities for detection of mediastinal nodal metastases
report similar sensitivities and specificities of MR and CT. A
significant disadvantage of MRI is its poorer spatial resolution,
which can lead to adjacent nodes on CT appearing as an enlarged
mass on MRI, resulting in the mistaken diagnosis of abnormal nodal
The role of PET
CT and MR imaging of the chest provides valuable information
about the morphology of a lesion. However, morphologic information
alone may not offer all the information necessary to direct proper
clinical management. Many lesions are indeterminate as to whether
they are benign or malignant by morphologic imaging techniques,
such as CT and MRI, and further investigation is warranted.
Patients may require an invasive biopsy procedure for further
evaluation. Depending on the size and location of the lesion,
CT-guided fine needle aspiration biopsy, transbronchial biopsy,
mediastinoscopy, video-assisted thorocoscopy, or even thoracotomy
may be considered to determine the nature of the lesion. There are
risks associated with these procedures and some will be
nondiagnostic. Also, >50% of radiographically indeterminate
lesions that are thoracoscopically resected are found to be benign.
One of the more recent advances in oncologic imaging that has
generated a renewed interest in diagnosis, staging, and response to
therapy is positron emission tomography (PET). PET imaging with
[2-18F]fluoro-2-deoxy-D-glucose (F-18 FDG) allows for the
evaluation of the relative level of metabolic activity of a lesion
compared with other tissues. PET imaging with F-18 FDG is based on
the principle that there is increased utilization of glucose in
malignant cells compared with most normal tissues.
The mechanism for the increase in F-18-FDG uptake is thought to be
the result of an increase in the number of glucose transporters in
There is also an increase in the glycolytic rate as a result of
increased hexokinase activity.
When F-18 FDG is administered intravenously, it competes with
glucose for transport into cells. Once intracellular, it also
competes with glucose for phosphorylation by hexokinase to F-18
FDG-6-phoshate. However, F-18 FDG-6-phosphate is not a substrate
for glycolysis and is not further metabolized. Thus, it becomes
trapped in the cancer cells, and the resultant accumulation of F-18
FDG-6-phosphate reflects glucose metabolism and allows for imaging.
Malignant lesions demonstrating increased metabolism will appear as
abnormal focal areas of increased radiotracer accumulation (ie,
focal areas of hypermetabolism) (Figure 12).
F-18 FDG PET imaging has been shown to be an accurate,
noninvasive imaging test for the assessment of pulmonary nodules
and larger mass lesions. A comprehensive meta-analysis by Gould et
of 40 eligible studies, including 1474 focal pulmonary lesions of
any size, found the mean sensitivity and specificity for detecting
malignancy were 96.0% and 73.5%, respectively. However, in this
analysis, there was little data for nodules <1 cm in
When a lung mass is shown to be malignant, it is important to
stage the extent of disease accurately. Appropriate clinical
management depends on whether there is mediastinal involvement
and/or distal disease. Several studies have shown that PET is more
accurate than CT for the staging of NSCLC. A tabulated summary of
FDG PET literature in lung cancer from 1993 through June 2000
showed PET to have a sensitivity of 96% for the diagnosis of
malignancy versus 67% for CT. For NSCLC staging, the sensitivity
and specificity for PET were 83% and 91%, respectively, versus 64%
and 74% for CT.
PET appears to be more accurate than CT in detecting metastatic
mediastinal lymphadenopathy. In one retrospective study of 96
patients, 66 with histologically proven malignant tumors and 30
with benign masses, the sensitivity and specificity of PET for
detecting malignancy in the pulmonary lesions was 97% and 89%,
In this study, 111 surgically sampled sites were from lymph nodes.
The accuracy of FDG PET in predicting malignancy of nodes was 91%
compared with 64% for CT. The sensitivity and specificity of FDG
PET in detecting metastatic mediastinal lymph nodes was 98% and
Imaging with PET was more accurate than CT for diagnosis of both
mediastinal and distant metastases.
Valk et al
conducted a prospective study in 76 patients of PET imaging for
staging of NSCLC in which mediastinal PET and CT findings were
compared with the results of surgical staging. They reported the
sensitivity and specificity for the diagnosis of N2 mediastinal
nodal disease were 83% and 94% for PET and 63% and 73% for CT,
In another prospective study by Pieterman et al,
a logistic regression analysis was used to evaluate the ability of
PET and CT to identify malignant mediastinal lymph nodes and
distant sites in 102 patients with resectable NSCLC. The
sensitivity and specificity of PET for the detection of mediastinal
metastases were 91% and 86%, respectively.
PET improves the rate of detection of local and distant
metastases in patients with NSCLC. Detection of unsuspected
metastatic disease by PET may permit reduction in the number of
thoracotomies performed for nonresectable disease (Figure 13). For
broad groupings of NSCLC stage, 10% of cases were downstaged and
33% upstaged after PET. Staging that incorporated PET provided a
more accurate prognostic stratification than did staging with
In NSCLC, PET may reduce the need for mediastinoscopy when the
primary lesion standard uptake value is <2.5 and the mediastinum
is PET negative.
The high negative predictive value of PET suggests that lesions
that are negative on PET are benign, biopsy is not needed and
radiographic follow-up is recommended.
After potentially curative therapy of NSCLC, abnormalities or
symptoms suggesting recurrence can be difficult to characterize.
Early detection is important because salvage therapies are
available for localized recurrence. PET better assesses the status
of disease and stratifies prognosis than does conventional staging,
effects patient management, and should be incorporated into
paradigms for suspected recurrence of NSCLC.
Though there is much excitement about the use of PET in
oncology, the technique has its limitations. False-positive FDG PET
scans can occur with infectious or inflammatory processes.
Abnormally increased FDG uptake can be seen with sarcoidosis,
tuberculosis, histoplasmosis, cryptococcosis, aspergillosis, and
False-negative FDG PET scans have been seen with pulmonary
False-negative scans have also been reported with
bronchioloalveolar lung carcinoma.
False-negative PET imaging is also a problem if the lesion is too
small for the resolution of the machine. This is most worrisome for
lesions <1 cm in diameter.
In a study by Valk et al, a decision tree sensitivity analysis
was used to assess the cost-effectiveness of a PET-based strategy
for staging of NSCLC. They considered CT alone versus CT with
thoracic PET. The CT plus PET strategy in the conservative decision
tree showed a saving of $1154 per patient without a loss of life
Another decision tree sensitivity analysis by Gambhir et al
demonstrated that a strategy using PET plus CT is more economical
and has a marginal increase in patient life expectancy compared
with the conventional strategy of staging patients with CT alone.
Lung cancer is an extremely prevalent disease that most
radiologists will encounter on a frequent basis. Familiarity with
the various manifestations of lung cancer on chest radiography may
help suggest the initial diagnosis, especially in an older patient
with a history of cigarette smoking. Once a suspicious abnormality
is detected, CT is the next step in the diagnostic work-up. This is
necessary to help confirm the diagnosis by identifying CT features
of an abnormality that would more likely suggest cancer, and to
stage the disease.
The emerging role of PET offers an exciting new diagnostic tool
that can quantify the metabolic activity of a tumor or node, and
can reveal additional sites of disease unsuspected on CT, thereby
increasing the accuracy of the staging process. The role of MRI
generally is limited to specific problem-solving areas, or when CT
findings are equivocal or indeterminate.