Professional Documents
Culture Documents
1165
Review
Article
.:
Pitfalls
John
in the Radiologic
Diagnosis
of Lung Cancer
H. Woodring1
Errors
The generally
accepted
error rate for the detection
of early
lung cancer is between 20% and 50%, and little improvement
has been noted over the last few decades
(Fig. 1) [1 -3]. The
results
of several
studies
designed
specifically
to screen
patients
for the radiologic
detection
of early lung cancer
suggest
that the error rate for subtle lung cancers
may be
much higher. Heelan et al. [4], in a study of 1 68 patients with
incidence
non-small-cell
lung cancers
screened
by yearly
chest radiographs,
detected
102 of the lung cancers by the
routine
annual
screening
process.
Seventy-eight
of these
patients
had had chest radiographs
from the previous
year;
in retrospect,
51(65%)
of these had evidence
of the cancer
on the previous
film. Similarly,
Muhm et al. [5] detected
92
cases of lung cancer by routine
radiologic
screening
at 4month intervals.
In retrospect,
90% of cases with peripheral
lung cancers and 65% of cases with hilar cancers had tumor
of Diagnostic Radiology,
AJR 154:1165-1175,
KY 40536-0084.
WOODRING
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
1166
AJA:154,
June 1990
The majority
of obvious
lung cancers
are detected
with
flash viewing of the radiograph
(0.2 sec) [8, 1 1]. Although
the
detection
of subtle
lung cancers
is impaired
severely
by
reducing
viewing
time to less than 4 sec [1 1 ], prolonged
viewing time is of little or no value. By 1 0 sec, 85% of the
lung is studied,
and all of the nodules
that will be reported
have been seen [8]. If discovery
viewing
time is prolonged
much beyond that length of time, the number of true-positive
readings is unaffected,
whereas
the number of false-positive
readings
increases
[1 0]. Kundel et al. [9] have shown that
areas of the chest radiograph
interpreted
as falsely positive
or suspicious
Fig. 1.-Chest
radiograph
in 41-year-old
man with lower extremity
weakness
for 2 weeks. Do you see an abnormality?
View the image for a
few moments
before proceeding.
There is a 2.5 x 2.5-cm large-cell
carci
noma in the superior pole of the right hilum and a 2.0 x 2.5-cm lung-tolung metastasis
posterior
to the left subciavian
artery. The patient also
had spine, liver, and brain metastases.
This case illustrates
how subtle
even an advanced
case of lung cancer may be.
failure
eye
untrained
observer
views a radiograph,
substantial
portions
of the image are neither searched
nor recognized,
and with
specific
training
the search pattern
is improved
[1 0]. Still,
studies
of well-trained
radiologists
eye movements
during
interpretation
confirm that large areas of the film are never
examined
by foveal vision [6]. Kundel et al. [8] have shown
that the probability
that an observer will detect a subtle nodule
during discovery
scanning
depends
on four factors:
nodule
contrast,
average distance
between
visual fixations,
location
of the
nodule
in the
visual
field
during
a single
fixation,
and
search duration.
Although
it might appear that nodule detection could be improved
by altering the visual search pattern
so that the radiologist
made systematic,
closely spaced visual
sweeps
back and forth across the radiograph
over a prolonged
period of time until the entire film was searched
exhaustively,
studies in human visual scanning
indicate that
this cannot be accomplished
[8]. When humans are searching
for inconspicuous
targets, they try to use the smallest
possible visual field to cover the maximal area in minimal time [8].
As a result, the human visual search pattern is semisystematic
at best with some areas never being studied [8]. It is apparent
that, through
the evolutionary
process,
humans
have been
provided with a visual search system that is best adapted for
scanning in the real World, where reaction time is often crucial
for survival
[8]. In other words,
in human visual scanning,
accuracy has been sacrificed
for speed [8]. Although this realworld situation does not apply to the interpretation
of medical
images, where reaction time is not important,
human scanning
behavior
cannot
be significantly
altered
[8].
receive
prolonged
visual
attention;
more
than
90% of false-positive
decisions
are related to some perturbation in the image that the viewer cannot resolve [9]. Double
reading
of radiographs
by two separate
observers
is very
beneficial in reducing
perceptual
errors, particularly
in forcing
decisions
on areas for which the readers lack confidence
[5,
9]. Although
the results of the lung cancer screening
studies
indicate that a substantial
percentage
of early cancers will still
be missed by double reading [4, 5], comparison
of single and
double reading clearly shows the superiority
of double reading
[5, 9]. The false-negative
rate for detecting
early lung cancer
may be reduced without
an increase in the false-positive
rate
by double reading [5, 9]. A single observer
also may place
the films aside and reinterpret
them at a later time, thus
simulating
double reading [8].
The human decision-making
process
plays a role in the
to detect
movements
subtle
show
lung
cancers.
Studies
that
missed
nodules
quately
scanned
by the
comparison
eye movements,
of radiologists
are often
ade-
fovea,
and then
rescanned
after
before the nodules
are reported
mental
process
not
to perceive
a nodule
[7].
This unconscious
limitation
of nodule perception
may not be
correctable
[7].
Still, evidence
indicates
that intentional
underreading
also
plays a role. Despite the fact that radiologists
often state that
false-negative
errors are more important
than false-positive
errors, their performance
indicates
that they take false-positive errors much more seriously
[7]. This may stem from
subliminal
or overt peer pressure
from other radiologists
and
clinicians
to drive the false-positive
rate for the chest radiograph as low as possible.
Swensson
et al. [6] had a group of
radiologists
interpret
a series
of difficult
chest
radiographs
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
AJR:154,
June
LUNG
1990
CANCER
1167
DIAGNOSIS
identify
calcification
[1 6]. Furthermore,
in the poorly penetrated areas ofthe lung (subpleural,
retrodiaphragmatic,
retrocardiac,
paramediastinal),
the contrast
difference
between
lung nodules and the surrounding
area is low, greatly hindering nodule detection
[2, 3, 1 7, 1 8]. A number of techniques,
although
not used widely, increase
contrast
differences
and
nodule detection,
especially
in these poorly penetrated
areas
of the lung, and improve
detection
of calcification
within
nodules. These include optical unsharp masking [2, 1 5, 18],
scanning
equalization
radiography
[7, 1 9-21],
and digital radiography
of the chest [1 1 1 6, 22-25].
The presence
of superimposed
structures
(anatomic
image
noise) and the complexity
of the area surrounding
a nodule
adversely
affect nodule detection
[1 7, 9, 1 0]; this is particularly true in the apical and perihilar
areas of the lungs [3].
End-on
vessels
and overlapping
vessels
and ribs commonly
are encountered
on chest radiographs
and may simulate
or
camouflage
a nodule [1 6, 7, 9, 1 0]. These opacities
cause
confusion
and compete
for the radiologists
attention
[1 6, 7,
9, 1 0]. If the image contains
a great deal of anatomic
noise,
a nodule is less likely to be perceived
[7]. The radiologist
must decide whether or not to report all questionable
opacities
resembling
a nodule as suspicious
or positive,
resulting
in a
high false-positive
rate, or to ignore such opacities,
resulting
in a high false-negative
rate [6]. Shifted,
stereoscopic,
posteroanterior
films have been shown to improve
overall performance
in nodule detection,
both by clarifying
end-on yessels and overlapping
shadows
and by confirming
true nodules
[3, 7, 9, 26]. The stereoscopic
view does not have to be
viewed
stereoscopically
to be effective
[26] and does not
have to be obtained
simultaneously
with the initial posteroanterior view.
Although
the human eye is capable
of detecting
a single
nodule as small as 3 mm [7], it is quite unusual for a solitary
neoplasm
less than 1 cm in diameter
to be seen [2, 7J.
Although
1 cm has generally
been accepted
as the size
threshold
of detectability
for peripheral
lung cancers [2], HeeIan et al. [4] have suggested
that for the prospective
analysis
of chest radiographs
the threshold
size of detectability
may
be much larger. In their series [4], the size of peripheral
lung
cancers
at the initial time of prospective
detection
during
routine screening
ranged from 0.7 to 9.4 cm, with an average
size of 2.4 cm.
The shape of a nodule also plays a significant
role in its
detectability.
If a peripheral
lung cancer
is spherical
and
sharply marginated,
its edge will be enhanced
by a negative
Mach band [1 0, 27]. The presence
of the negative Mach band
will greatly increase
the detectability
of the nodule [1 0]. In
fact, in the poorly penetrated
areas of the lung, nodules
may
be perceived
solely because
of their associated
negative
Mach band [27]. Unfortunately,
many lung cancers are poorly
defined or spiculated
in nature and cannot
produce
a surrounding
negative
Mach band [10, 27]. Thus, these poorly
defined lung cancers may be difficult or impossible
to perceive
until they become quite large [101.
Although
pitfalls in the detection
of lung cancers
arising in
the hilum have not been studied extensively,
it is apparent
that the detection
of hilar cancers
is hindered
by similar
,
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
1168
technical
and perceptual
limitations
(Fig. 1). Muhm et al. [5]
found that 65% of lung cancers
arising in the hilum were
missed initially during routine screening
and were usually more
than 3 cm in diameter
by the time they were discovered.
Furthermore,
detection
of hilar cancers
frequently
is limited
by a surprising
lack of familiarity
with normal and abnormal
hilar anatomy
on the part of those who interpret
chest radiographs. A number of articles [28-37]
have addressed
plain
film hilar anatomy
and the radiologic
signs of subtle hilar
abnormality
that may greatly improve
the detection
of early
hilar
cancers.
Unfortunately,
early
tumors
that
are
limited
to
the bronchial
lumen and have not caused bronchial
obstruction are usually not detectable
on plain films.
It is apparent
that there are a number of factors that limit
the ability of the radiologist
to detect early or subtle lung
cancers.
Although
faulty search patterns
and carelessness
on the part of the radiologist
are always potential
pitfalls, the
majority of limitations
are either inherent to the human visual
system or decision-making
process,
are related to the limitations of the plain film method
itself, are related to the complexity
of the image of the lungs, or are due to the location
and edge characteristics
of the tumor itself. The radiologist
should take steps to reduce detection
errors whenever
possible; however,
it is obvious that the failure to detect an early
lung cancer on plain radiographs
is well within an accepted,
normal standard
of care and does not constitute
negligence
or malpractice
[5].
Improper
Viewing
By paying
viewing
Conditions
attention
to a few simple precautions
concerning
of the chest radiographs,
the radiologist
can
improve
the detection
of subtle lung cancers.
Chest radiographs should be checked
routinely,
immediately
after processing,
for technical
quality and should be repeated
if necessary [3J. They should always be read in side-to-side
comparison with previous studies when these studies are available
[3]. Preferably,
at least one set of films more remote than the
most recent set of previous radiographs
should also be compared with the current study. Ideally, interpretation
of radiographs should occur in a calm environment
free of constant
interruption
or severe
time pressure
[6]. Light coming from
the view box around the film causes light flooding
of the eye
from intraocular
scattering
and decreases
the sensitivity
of
the eye for detecting
subtle changes in contrast
in the denser
portion of the image [1 0]. This veiling glare should be blocked
out [10]. Viewing
distance
also should be varied routinely
[10]. Routine use of a reducing
lens (Edmund
Scientific
Co.,
Barrington,
NJ) greatly improves
the evaluation
of radiographs
by reducing
the number of visual fixations
needed to search
the image adequately,
enhancing
the visibility of large, poorly
defined lesions, increasing
the luminance
gradient of threshold
images,
allowing
previously
subliminal
images
to be perceived,
and facilitating
comparison
of two films [19, 38].
Increasing
the use of scotopic
vision by glancing
at the
radiograph
from the side also may improve detection
of subtle
lesions [38].
the
WOODRING
Pitfalls Related
to the Analysis
of Solitary
Pulmonary
Opacities
of Solitary
Pulmonary
Opacities
Growth
of a Solitary
Pulmonary
Nodule
Assessment
of the growth
of a solitary pulmonary
nodule
can provide great insight into the nature of the nodule; cornparison with previous
chest radiographs
remains
of fundamental importance
in this task [39, 40]. Unfortunately,
it is
not possible
to assess the growth
of a pulmonary
nodule
accurately
by visual inspection
alone; the growth of a pulmonary nodule always
should
be judged
with the aid of a
measuring
instrument
[1 0]. If it can be shown that no growth
at all has occurred
over a minimum
of 2 years, the nodule is
almost certainly benign [39].
If a solitary
pulmonary
nodule grows,
malignancy
is more
likely. Assessment
of the doubling
time of the volume
of a
nodule that is growing
may be of diagnostic
value [39]. It
must be remembered,
however,
that doubling
time refers to
volume and not diameter
[39]; doubling
of the diameter
of a
nodule represents
an eightfold
increase
in volume. The volume of a sphere (Vs) is determined
by the equation,
Vs
4/3#{216}r
r3)
r3,
4.1866
4.1866
(0.5
cm)3
cm)3
0.52
cm3
1.04
cm3.
and
Vs
4.1866(0.63
Assuming
that a nodule
1.26 to obtain the diamdoubled.
The doubling
to be between 30 and
AJR:154,
June 1990
LUNG
CANCER
if the doubling
time falls outside
this range the
likely benign [39].
Still, it is well known that some lung cancers
may change
little in size over a long time only to disseminate
widely in a
short time, or alternatively,
some may show rapid growth and
spread in the first few weeks after initial presentation
[40]. In
addition,
hemorrhage
in or around lung cancer may be associated with dramatic
changes
in the size of the lesion that
may mimic benign disease
(Fig. 2) [39]. Therefore,
absolute
reliance
on measurements
of doubling
time
is not
490
days;
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
nodule is most
recommended
[40].
Cummings
et al. [45] have provided
mathematical
formulas
that may be used to estimate
the likelihood
that a given
nodule is malignant.
By using the likelihood
ratio form of
Bayes theorem
to combine
individual
odds into an overall
estimate
of the odds favoring
malignancy,
they developed
a
simple formula
for estimating
the likelihood
that a solitary
pulmonary nodule is malignant
based on the diameter
of the
nodule, the patients
age and history of cigarette
smoking,
and data on the overall prevalence
of malignancy
in solitary
nodules [45]. This method improves
the accuracy
of estimating the likelihood
of malignancy
for individual
patients
with
solitary pulmonary
nodules and may be very helpful in deciding
how to manage the patient. The article is highly recommended
to anyone interested
in the evaluation
and management
of
solitary
pulmonary
Pitfalls Related
nodules.
to Unusual
Radiologic
Manifestations
of
Lung Cancer
Calcification
Visible calcification
erally is considered
Fig. 2.-Rapid
resolution
within
a solitary
good evidence
of hemorrhage
pulmonary
of a benign
surrounding
lung cancer
mimicking
1169
DIAGNOSIS
calcification
is of the diffuse,
popcorn,
laminated,
or centralcore types [39, 40, 46]. However,
unlike the solitary pulmonary nodule,
the presence
of calcification
within a solitary
pulmonary
mass is not a reliable
sign of benignity
[39].
Although
the presence
of calcification
within lung cancer is
common histologically
[40, 46-48],
demonstration
of such
calcification
on plain
radiographs
or conventional
tomograms
is exceedingly
rare [40].
The demonstration
of calcification
within lung cancer by CT
is apparently
more common
and has been reported
in adenocarcinoma,
bronchioloalveolar
carcinoma,
and large-cell
carcinoma
(Fig. 3) [46-49].
The metastases
from calciumproducing
lung cancers
also may contain
calcium
[46, 48,
49]. CT features
of a calcified
lung nodule
or mass that
suggest
malignancy
include
poorly
defined,
spiculated,
or
lobulated
margins;
size larger than 3 cm; and continued
growth [46].
Thin-Walled
Cavitation
Cavitation
in lung cancer is common
and occurs in 2-16%
of cases [39, 40]. Typically,
the cavity will have thick walls;
nodular extensions
of tumor (mural nodules)
projecting
into
the lumen of the cavity are common
[40, 50-52].
Occasionally, a cavitated
lung cancer will have smooth,
thin walls (Fig.
4) [39, 50-52].
In a retrospective
and prospective
analysis
of
126 patients
with solitary cavities of the lung, Woodring et al.
[50, 51] found that 94% (29 of 31) of solitary cavities with a
maximal wall thickness
of 4 mm or less were benign; however,
two (6%) of 31 were malignant.
These two cases had smooth
walls with a maximal wall thickness
of 2 mm [50, 51]. Carcinoma always should be considered
seriously
in the diagnosis
of any cavitary
lesion of the lung, especially
if the patient is
benign
disease
in a 45-year-old
woman
with
hemoptysis;
symptoms.
A, Radiograph
shows poorly defined
opacity of approxImately
5 x 6 cm in left upper lobe. Skin tests, sputum
bronchoscopy
were negative.
B, Radiograph
obtained
8 days later. Opacity
has decreased
to approximately
3.5 x 5 cm. Hemoptysis
has ceased.
C, Radiograph
obtained
22 days after A. Opacity
has decreased
to 3 x 4 cm, but it appears
more masslike.
differentiated
adenocarcinoma.
cultures,
Surgical
serology,
resection
and
fiber-optic
revealed
poorly
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
1170
WOODRING
Fig. 3.-Adenocarcinoma
of left upper lobe with
intrinsic
calcIfication.
CT scan shows spiculated
mass 4.5 x 7.0 cm in left upper lobe containing
calcification
(cursor
reading
from largest calcification was 515 H). Malignancy
is indicated
by large
size (more than 3 cm) and by splculated
lungtumor interface.
Fig. 4.-Lung
cancer with thin-walled
cavity in asymptomatic
A, Radiograph
shows 3 x 3 cm thin-wailed
cavity (arrows)
in superior segment
of left lower lobe.
B, Radiograph obtained 11 months
later shows more typical
Final diagnosis
was squamous
cell carcinoma.
Cystic
Appearance
Occasionally,
a necrotic
lung
cancer
may
not
develop
communication
with a bronchus.
In this situation,
the necrotic
tumor still will appear as a solid mass on plain films; however,
on CT it will appear as a fluid-filled
mass that may resemble
a bronchogenic
cyst, hydatid cyst, lung abscess,
or infected
bulla [53]. The presence
of thick, lobular walls and a size
larger than 3 cm should suggest the possibility
of carcinoma
in such a cystic lesion [53].
Air-Crescent
Sign
Rarely, a meniscus
or air-crescent
sign may be seen in
association
with a cavitated
lung cancer (Fig. 5) [40]. This
may occur because of an intracavitary
tumor mass, aspergilloma, or other formed
debris
within
the cavity
[40, 54].
Unfortunately,
such a lesion may be mistaken
for a fungus
ball in a preexisting
benign cavity. The presence
of thick,
nodular cavity walls; size larger than 3 cm; continued
growth;
or lack of a preexisting
benign
cavity
should
suggest
malignancy.
Air-Space
Filling
AJR:154,
43-year-old
with maximal
thick-walled
man.
wail thickness
cavity
June 1990
of 2 mm
with air-fluid
level.
on radiographs
(Fig. 6) [40, 55-61].
This occurs because the
tumor may grow and spread within the lumen of the distal air
spaces, using the existing stroma of the peripheral lung tissue
as its support
[59, 60]. Bronchioloalveolar
carcinoma
may
present as focal segmental
or nonsegmental
consolidation,
lobar consolidation,
or a diffuse air-space
filling process
that
may involve
both lungs extensively
[55, 56, 58-60].
The
alveolar consolidation
produced
by bronchioloalveolar
carcinoma usually is chronic [57] but may show rapid progression
and mimic acute air-space
diseases
such as pneumonia,
edema, or hemorrhage
[56, 60]. Air bronchogram
formation
is common
(Fig. 6) [40, 55, 58]. Im et al. [58] have shown
that CT of lobar bronchioloalveolar
carcinoma
may show
stretching,
spreading,
and uniform narrowing
of the involved
bronchi without obstruction.
This is the CT equivalent
of the
classic bronchographic
features
of bronchioloalveolar
carcinoma reported
by Zheutlin
et al. [62] in 1954. The air-filled
bronchi
in chronic
pneumonic
consolidation
usually
show
some degree of tortuosity
and ectasia because of fibrosis and
atelectasis
of the involved lung [58]. These bronchial
findings
then would differ from those of bronchioloalveolar
carcinoma
[58].
Unfortunately,
the characteristic
bronchial
findings
of
bronchioloalveolar
carcinoma
on CT may be absent (Fig. 6).
Kuriyama
et al. [43] have shown
that air bronchograms
frequently
are identified
in small peripheral
lung cancers
on
thin-section
CT. Although
the presence
of air bronchograms
within a solitary pulmonary
opacity on plain radiographs
classically has been considered
as evidence
against lung cancer,
their presence
within peripheral
lung nodules on thin-section
CT should not be used as evidence
of benign disease.
Pattern
Satellite
Multiple
proximity,
Nodules
small pulmonary
often in association
nodules
clustered
together
in
with a larger peripheral
nodule,
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
AJR:154,
June 1990
LUNG
CANCER
are termed
satellite
nodules
[63]. These nodules
often are
said to be characteristic
of inflammatory
disease, particularly
tuberculosis,
and have been reported
in about 1 0% of cases
of tuberculoma
and 8% of cases of tuberculosis
[63]. Unfortunately,
satellite
nodules also have been reported
in 1% of
cases of primary lung cancer [63].
Bronchial
Abnormalities
Focal bronchial
wall thickening
is an early sign of lung
cancer that may precede
the development
of an obvious
mass lesion by several years [33, 39, 64]. The bronchial
cuff
sign, also termed the anterior bronchus
sign, consists
of two
components:
(1) an increase
in the thickness
of the soft-tissue
compartment
surrounding
an end-on
bronchus,
often with
partial or complete
obliteration
of the normal curvilinear
demarcation
of the bronchial
wall; and (2) partial or complete
envelopment
of the adjacent
artery by the increased
softFig. 5.-Intracavitary
cus sign in a 44-year-old
tumor
mass
with
1171
DIAGNOSIS
tissue component,
causing partial or complete
obscuration
of
the artery [39]. On plain films the sign is seen best in the endon perihilar bronchi,
particularly
the anterior segmental
bronchi of the upper lobes (Fig. 7) [33, 39]. Early endobronchial
tumor occasionally
may be identified on CT as focal thickening
of the bronchial
wall limited to the lumen of the involved
bronchus
(Fig. 8) [64].
Obstructive
hyperinflation
is an uncommonly
imaged manifestation
of lung cancer. Obstruction
of the larynx or trachea
by tumor can act as a check valve and can result in obstructive
hyperinflation
of both lungs [40, 65]. The lungs become
markedly
overinflated;
both diaphragms
are low; respiratory
excursion
is diminished
markedly
on expiration;
and the heart,
which
may appear
small on expiration,
paradoxically
will
enlarge
on inspiration
[40, 65]. A history
of stridor should
evoke close scrutiny
of the trachea
and larynx on the chest
radiograph.
Obstructive
hypennflation
also may develop distal
to obstructing
tumors
of the main bronchi
(Fig. 9), lobar
bronchi,
or segmental
bronchi
[65].
A history
of unilateral
menis-
onset
of massive
hemoptysis.
Chest radiograph
shows
oval cavity of 4.5 x 6.0 cm with Irregular walls In
anterior segment
of right upper lobe. Mass is present Inferiorly
In cavity,
causing
meniscus
sign.
Surrounding
lung Is opaclfied by pulmonary
hemorrhage.
Surgical
resection
revealed cavitary adenocarcinoma
containing
necrotic
tumor tissue.
Fig. 6.-CT
scan
shows bilateralair-space
opacification
from bronchioloalveolar
carcinoma.
Note prominent
air bronchogram
in iinguia of left
upper lobe (arrowheads).
,.k.
A
Fig. 7.-Anterior
bronchus sign of hilar cancer.
A, Radiograph
shows soft tissue (arrowheads)
surrounding
and extending
laterally
to anterior
segmental
bronchus (arrow)
of left upper lobe.
B, CT scan shows how anterior
bronchus
sign is formed:
a cuff of tumor tissue
(arrowheads)
completely
surrounds anterior segmental
bronchus (arrow)
of left upper lobe. Biopsy revealed
poorly
differentiated
non-small-cell
carcinoma.
Fig. 8.-Lung
cancer limited
CT scan through
right-lower-lobe
origin of superior
segmental
small squamous
cell carcinoma
lumen of bronchus and causing
bronchial
lumen.
to bronchial lumen.
bronchus
below
bronchus
shows
(arrow)
limited to
focal narrowing
of
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
1172
WOODRING
AJR:154,
June
1990
tumor through
a fissure to obstruct
a major bronchus
in an
adjacent
lobe, carcinoma
in one lobe and inflammatory
disease in another,
variations
in bronchial
anatomy,
and a channel situated
through the bronchial
tumor so that the lumen to
one lobar bronchus
is patent while the other lobar bronchi are
occluded
[40].
Pleural
Involvement
Pleural involvement
in primary lung cancer is not uncommon, occurring
in about 8-1 5% of cases [68]. Usually this is
manifested
by pleural effusion.
Typically
a hilar or parenchymal mass is visible on the radiograph;
however,
a subtle hilar
mass or small peripheral
tumor may be relatively
inapparent
on the initial radiographs,
especially
when the effusion is large,
leaving the impression
that the pleural effusion is an isolated
finding [68]. It has been my experience
that the majority
of
massive,
unilateral
pleural effusions
ultimately
are proved to
be malignant
(lymphoma,
lung cancer, mesothelioma,
or metastatic disease).
However,
the presence
of smaller unilateral
or bilateral pleural effusions,
with a normal-sized
heart, should
always raise the possibility
of a malignant
process
[68].
Fig. 9.-Radiograph
shows postobstructive hyperinflation of left lung
associated with endobronchial
tumor in left main bronchus causing checkvalve-type
obstruction.
Left lung is enlarged,
fused compared
with right.
hyperlucent,
and underper-
is highly suggestive
of the condition
[40]. The
may be missed on full inspiration;
an expiratory
view is often necessary
to demonstrate
the air trapping
[65].
Mucoid impaction
of bronchi refers to the accumulation
of
inspissated
secretions
within the bronchial
lumen usually associated with bronchial dilatation
or bronchiectasis
[40, 66,
67]. Lung cancer is by far the most common
cause of mucoid
impaction
caused by bronchial obstruction
[66, 67]. Radiologically, mucoid impaction
of the bronchi distal to an obstructing
tumor often is obscured
by postobstructive
pneumonia
or
collapse.
However,
if collateral
ventilation
occurs, so that the
lung distal to the obstruction
remains aerated, mucoid impaction may be visible on plain films or CT scans [40, 66, 67].
The plain film or CT appearance
of mucoid impaction
usually
consists
of one or more fusiform,
branching
structures
with
their long axes directed
toward the hilum [40, 66, 67]. If the
tumor obstructing
the bronchus
is large enough,
a central
tumor mass may be identified
proximal
to the mucoid impacwheezing
hyperinflation
tion;
however,
if the obstructing
tumor
is small
and
limited
Pulmonary
Artery
Involvement
the tumor
the infarct
and
the peripheral
mass
representing
an approach
for percutaneous
needle biopsy is planned in such a case, the central lesion
representing
the tumor should be sampled
rather than the
more easily accessible
peripheral
infarct [39].
Esophageal
Involvement
Dysphagia
the presenting
symptom
in pa70]. Metastatic
enlargement
of
the subcarinal
or posterior
mediastinal
lymph
nodes may
compress
the esophagus,
or lung cancer
may invade the
esophagus
directly, causing dysphagia
[39, 70]. The extrinsic
pressure
effect of the lung tumor on the esophagus
may be
subtle and may be easily missed on chest radiographs,
barium
studies, or endoscopy
[70].
tients
with
is occasionally
lung
cancer
[39,
to
the bronchial
lumen, mucoid impaction
may be the only radiologic indication of an obstructing
bronchial tumor (Fig. 10) [40,
66, 67]. Visible mucoid
impaction
commonly
is seen in lung
cancer obstructing
a segmental
bronchus
[66] and may be
seen distal to carcinoma
of a lobar or main bronchus
[67].
The double
lesion
sign,
considered
strong
evidence
against lung cancer, is defined as lobar or segmental
atelectasis in two different
lobes that cannot be explained
easily by
a single bronchial
abnormality
[40]. The sign does fail rarely,
and the exceptions
have various explanations,
including
multiple primaries,
atelectasis
in one lobe from a primary tumor
and in another
from a metastasis,
extension
of the primary
Pericardial
and Cardiac
Involvement
Approximately
8-1 0% of lung tumors
metastasize
to the
heart [71]. Metastatic
disease to the heart may follow three
pathways:
hematogenous
or lymphangitic
spread to the per-
icardium
or myocardium,
direct
invasion
across
the pleura
and pericardium,
or extension
into the right or left atrium by
continuity
through
the vena cava or pulmonary
veins [7174]. Pericardial
effusion is the most common
manifestation
of
metastatic
lung cancer and may be the presenting
feature of
the disease;
generalized
or localized
neoplastic
pericardial
thickening
or nodular masses also may be seen [73].
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
Fig. 10.-CT
scan shows mucold impaction
of
right-lower-lobe
bronchi caused
by obstructing
endobronchial
adenocarcinoma
of right-lowerlobe bronchus.
Note branching
V- and V-shaped
opacity
(arrowheads)
representing
inspissated
mucus in distended
bronchi distal to tumor. No
central mass effect was evident on higher cuts.
L = apex of liver.
Pancoast
LUNG
CANCER
DIAGNOSIS
1173
Fig. 11.-Radiograph
shows poorly
defined
squamous
cell carcinoma
of 4.5 x 5.0 cm arising
In left hilum (straight
arrow).
Invasion
of left
pulmonary
artery by this tumor resulted
in peripheral
pulmonary
infarct
in left upper
lobe
(curved
arrow).
This produces
typical dumbbellshaped
opacity seen in this condition.
Syndrome
Pancoast
syndrome
is caused by a tumor, usually primary
to the lung, occurring
at the extreme
lung apex, that invades
the neck, brachial plexus, and shoulder,
causing
pain in the
distribution
ofthe eighth cervical and first and second thoracic
nerves,
wasting
of the muscles
of the hand, and Horner
syndrome
[75, 76]. Radiologically,
Pancoast
described
small
homogeneous
shadows
at the extreme
lung apex associated
with more or less rib destruction
and often with vertebral
infiltration
[77]. In retrospect,
it is now apparent
that all of
Pancoasts
cases were diagnosed
at a late, advanced
stage
of disease;
most patients
diagnosed
today have only one or
two components
of the syndrome,
and Homer syndrome
now
is quite rare [75-77].
It is now also known that the radiologic
findings of a Pancoast
tumor may be quite subtle, consisting
of only slight asymmetric
apical thickening
with or without
bone destruction
[77]. In the series reported
by OConnell
et
al. [77], old films in two-thirds
of the patients
in whom they
were available
showed
evidence
of apical thickening
on the
side of abnormality
before the development
of clinical signs
and symptoms,
a finding
that carries
considerable
significance. Certainly,
any degree of apical asymmetry
in a symptomatic patient should raise the suspicion
of a superior sulcus
cancer and elicit an appropriate
workup
[77]. An asymptomatic patient who has not received prior cervical lymph-node
irradiation,
with a unilateral
or asymmetric
apical cap of
greater than 5 mm, or a patient with an enlarging
apical cap,
merits further
investigation
[77]. Unfortunately,
because
of
the vague nature of the shoulder
and arm pain, and the
similarity
with other clinical conditions,
Pancoast
tumor may
not be suspected
clinically and the radiologic
workup may be
focused on the cervical spine or shoulder
(Fig. 12).
Fig. 12.-Pancoast
tumor. Cervical
radiograph
in 47-year-old
man with weakness
In right upper
extremity
for 2 weeks
shows subtle, asymmetric
opacity
(arrow)
12 mm thick at extreme
lung apex
on right. Subsequent
needle
biopsy
revealed
large-cell
carcinoma
of lung.
Conclusions
Perceptual
missed
limited
problems
lung cancers.
to a certain
account
Although
extent
by the
for
a large
it is apparent
inherent
proportion
that we
limitations
of
are
of the
clarify
questionable
opacities,
also
will
improve
our
performance.
Still, the radiologist
may perceive
a nodule or mass, report
its presence,
and misinterpret
the radiologic features of the
cancer as indicating
benign disease.
Any solitary pulmonary
opacity larger than 3 cm in size should be viewed as malignant. Pulmonary
nodules
less than 3 cm in size should
be
considered
malignant
if the pretest
probability
of cancer
is
high; if they grow; or if their edge is spiculated,
notched,
or
there is a pleural tail sign. Assessment
of nodule
growth
should be made with the assistance
of a measuring
device,
and calculation
of doubling
time should consider
doubling
of
the volume of the nodule rather than doubling
of the diameter
of the nodule. The presence of calcification
within a pulmonary
opacity,
especially
one larger than 3 cm, should
not be
considered
evidence of benignancy.
Occasionally
lung cancer
WOODRING
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
1174
pulmonary
infarction,
dysphagia,
and pericardial
effusion
Pancoast
tomatic patients
and may be suspected
unilateral or asymmetric
apical thickening
Any patient with a growing
apical cap,
signs of Pancoast
syndrome,
should be
harboring
a superior
sulcus
of asymp-
by the presence
of
of 5 mm or greater.
or any patient with
viewed as possibly
carcinoma.
It is hoped
that
through
increased
awareness
of the growth patterns
of lung
cancer and of some of the more uncommon
manifestations
oflung cancer, radiologists
may escape some of the avoidable
pitfalls in the detection
and diagnosis
of lung cancer.
REFERENCES
1 . Revesz G, Kundel HL. Psychophysical studies of detection errors in chest
radiology.
Radiology
1977;123:559-562
2. Sorenson
JA, Mitchell CR, Armstrong
JD II, et al. Effects
of improved
contrast
on lung-nodule
detection:
a clinical ROC study. Invest Radio!
1987;22: 772-780
3. Hayabuchi N, Russell WJ, Murakami J, Nishitani H. Screening
for lung
cancer in a fixed population
by biennial
chest radiography.
Radiology
1983;148:369-373
4. Heelan RT, Flehinger BJ, Melamed MA, et al. Non-small-cell
results
program.
Radiology
lung cancer:
1984;151
:289-293
cancer
detected
dunng
a screening
program
radiographs.
Radiology
1983;148:609-615
using
four-month
chest
faulty
between
viewing
12. Christensen
EE, Dietz GW, Murry AC, Moore JG, Stokely EM. Effect of
nodules in a chest phantom. AJR
1977;128:789-793
13. Herman PG, Drummey J, Swensson AG, Hessel SJ, Balikian JP. 350 kV
chest radiography has no diagnostic advantage: a comparison with 140
kV technique.
AJR 1982:138:485-489
kilovoltage on detectabilityof pulmonary
14.
on diagnostic
AJR:154,
15.
Sorenson
JA, Mitchell
contrast
enhancement
275-281
June 1990
CR. Evaluation
of optical
unsharp
masking
and
of low-scatter
chest radiographs.
AJR 1987;149:
517-521
radiography.
AJR 1985;145:979-983
dual-energy
subtraction chest
radiography:
dinical evaluation
of film images.
23. Shemer RH, Chiles C, Wilkinson WE, Johnson GA, Ravin CE. Effects of
image
processing
on nodule
detection
rates in digitized
chest
radiographs:
1988;166:447-450
radiography
of the chest:
clinical
experience
with a prototype
unit. Radiology
1983;148:
1-5
AG, Sanders
C, Barnes GT, et al. Digital imaging of the chest.
Radiology 1989;171 :297-307
26. Kelsey CA, Moseley AD Jr, Mettler FA Jr, Bnscoe DE. Cost-effectiveness
of stereoscopic
radiographs in detection
of lung nodules.
Radiology
1982;142:61
1-613
27. Lane EJ, Proto Av, Phillips TW. Mach bands and density perception.
Radiology
1976;121 :9-17
28. Vix VA, Klatte EC. The lateral chest radiograph
in the diagnosis
of hilar
and mediastinal masses. Radiology
1970;96:307-316
25. Fraser
29. Chang CH(J), Zinn TW. Aoentgen recognition of enlarged hilar lymph
nodes: an anatomical review. Radiology
1976;120:291-296
30. Schnur MJ, Winkler B, Austin JHM. Thickening of the posterior wall of the
bronchus
intermedius:
a sign on lateral chest radiographs
of congestive
heart failure, lymph node enlargement,
and neoplastic
infiltration.
Radiology
1981;139:551
-559
31 . Don C, Hammond
Dl. The vascular converging
points of the right pulmonary
hilus and their diagnostic
significance.
Radiology
1985;155:295-298
32. Webb WA. Aadiologic imaging of the pulmonary hila. Postgrad
Radio!
1986;6: 145-1 68
33. Spizamy DL, Cavanaugh
B. The anterior bronchus
sign: a new clue to hilar
abnormality. AJR 1985:145:265-267
34. Genereux
GP. Conventional
tomographic
hilar anatomy
emphasizing
the
pulmonary
veins. AJR 1983;141 :1241-1257
35. Chasen MH, Ynzarry JM. Tomography
of the pulmonary
hili: anatomical
reassessment of the conventional 55#{176}
posterior
oblique view. Radiology
1983;149:365-369
36. Proto AV, Speckman
Photogr
radiograph
of the chest.
Med
but underused
tool.
1980:56:38-64
lens: an important
39. Fraser AG, Pare JAP, Pare PD, Fraser AS, Genereux GP. Diagnosis
of
diseases of the chest, vol. II, 3rd ed. Philadelphia: Saunders, 1989:13671442
Roentgenol
1977;12:
165-1
of carcinoma
correlations:
74
AJR:154,
45.
46.
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
47.
48.
49.
50.
51 .
52.
53.
June 1990
Cummings
SR,
LUNG
Liilington
GA,
Richard
RJ. Estimating
CANCER
of
the probabilify
malignancy
in solitary pulmonary
nodules:
a bayesian
approach.
Am Rev
Respir Dis 1986:134:449-452
Kelly RB, Mahoney PD, Johnson JF. A calcified carcinoma
of the lung and
intracerebral
metastasis.
J Comput Tomogr 1987;1 1:389-391
Goldstein MS. Rush M, Johnson P, Sprung CL. A calcified adenocarcinoma
of the lung with very high CT numbers. Radiology
1984;150:785-786
Melons WMC, Nijhuis-Heddes JMA. Bakker W. Calcified lymph node
metastases
in bronchioloalveoiar
carcinoma.
Radiology
1986;161:
103-104
Austin JHM, Grimes MM, Carberry
D. CT detection of calcified nodal
metastases of lung adenocarcinoma.
J Comput
Assist
Tomogr
1988;
12:314-316
WoodringJH,
Fiied AM, Chuang VP. Sofitarycavifies
ofthe lung: diagnostic
implications
of cavity wall thickness. AiR 1980;135:1269-1271
Woodnng
JH, Fried AM. Significance
of wall thickness in solitary cavities
of the lung: a follow-up study. AJA 1983;140:473-474
Good CA, Holman CB. Cavitary carcinoma
of the lung: roentgenologic
features in 19 cases. Dis Chest 1960;37:289-293
Hebert C, George RB. Large fluid-filled thoracic
mass in a young man.
within
carcinoma.
a malignant
correlations,
changing
62.
2nd
ed.
St.
Zheuthn
pleomorphic
63.
64.
65.
66.
67.
68.
69.
70.
73.
74.
75.
76.
77.
EC, Rigler
AiR
1983;140:657-664
abnOrmalitieS
in alveolar
1954:25:
542-549
Fraser AG, Pare JAP, Pare PD. Fraser AS, Genereux
GP. Diagnosis of the
chest, vol I, 3rd ed. Philadelphia: Saunders, 1988:578
Foster WL Jr, Roberts L Jr, McLendon
RE, Hill AC. Localized peribronchial
thickening:
a CT sign of occult brOnchOgenic
carcinoma.
AiR
1985;
144:906-908
Rabin CB, Baron MG. Radiology of the chest, 2nd ed. Baltimore:
Williams
& Wilkins, 1980:128-132
Falcon B. Muccid impaction(inspissated
secretions)in
segmental
bronchial
obstruction. Radiology
1979;133:9-16
Woodnng
JH, Bemardy MO, Loh FK. Muccid impaction
of the bronchi.
Australas
Radio! 1985:29:234-239
Fraser AG, Pare JAP. Diagnosis
of diseases
of the chest, vol. iii, 2nd ed.
Philadelphia:
Saunders,
1979:1759
MarriOtt AE, Weisbrod
G. Bronchogenic
carcinoma
associated
with pulmonary infarction.
Radiology
1982;145:593-597
Heater K, Macmahon H, Vyborny CJ. Occult lung carcinoma
presenting
with dysphagia:
the value of computed
tomography.
Clln Imaging
1989;
13: 122-1 26
71 . Dore A, Alerci
72.
character.
LG. Bronchographic
of the lung: a new diagnostic
N, Lesser
cell carcinoma
Semin
cell card-
1175
DIAGNOSIS
M, DAndrea
F, Di Giuiio G, Do Agostini
A, volpato
G.
Intracardiac
extension
of lung cancer via pulmonary
veins: CT diagnosis.
J Comput Assist Tomogr 1988;12:565-568
Koo BC, Woldenberg
LS, Kim C-T. Pulmonary vein tumor thrombosis
and
left atrial extension
in lung carcinoma.
J Comput Tomogr 1984;8:331-336
Posniak HV, Olson MC, Moncada A. Pericardial
diseases:
still a radiologists province? Postgrad Radiol 1988:8:122-136
Borts Fr, Rohatgi PK, Sehgal E. Bronchogenic
cavoattial
tumor thrombus:
CT demonstration. J Comput Assist Tomogr 1985;9: 111-1117
Johnson
DH, Hainsworth
JD, Greco FA. Pancoasts
syndrome
and small
cell lung cancer. Chest 1982:82:602-606
Aockoff
SD. Apical lung cancer masquerading
as a Pancoast
tumor. AJR
1982;139:163-165
OConnell
AS, McLoud
TC, Wilkins
EW. Superior
sulcus tumor:
radiographic diagnosis
and workup.
AJR 1983;140:25-30
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
22. Tan-Lucien H. Mohammed, Charles S. White, Robert D. Pugatch. 2005. The imaging manifestations of lung cancer. Seminars
in Roentgenology 40:2, 98-108. [CrossRef]
23. Laurence Monnier-Cholley, Fabrice Carrat, Bernard P. Cholley, Jean-Michel Tubiana, Lionel Arriv. 2004. Detection of Lung
Cancer on Radiographs: Receiver Operating Characteristic Analyses of Radiologists, Pulmonologists, and Anesthesiologists
Performance. Radiology 233:3, 799-805. [CrossRef]
24. L N Gomersall, S Olson. 2004. Imaging in lung cancer. Imaging 16:1, 1-9. [CrossRef]
25. Marios Froudarakis, Pierre FournelPleural Effusion in Lung Carcinoma 439-455. [CrossRef]
26. G. Coppini, S. Diciotti, M. Falchini, N. Villari, G. Valli. 2003. Neural networks for computer-aided diagnosis: detection of lung
nodules in chest radiograms. IEEE Transactions on Information Technology in Biomedicine 7:4, 344-357. [CrossRef]
27. Leonard Berlin. 2003. Failure to Diagnose Lung Cancer: Anatomy of a Malpractice Trial. American Journal of Roentgenology
180:1, 37-45. [Citation] [Full Text] [PDF] [PDF Plus]
28. Feng Li, Shusuke Sone, Hiroyuki Abe, Heber MacMahon, Samuel G. Armato, Kunio Doi. 2002. Lung Cancers Missed at LowDose Helical CT Screening in a General Population: Comparison of Clinical, Histopathologic, and Imaging Findings. Radiology
225:3, 673-683. [CrossRef]
29. Jannette Collins, Ella A. Kazerooni, Joan Lacomis, H. Page McAdams, Ann N. Leung, Maria Shiau, Janice Semenkovich, Robert
B. Love. 2002. Bronchogenic Carcinoma after Lung Transplantation: Frequency, Clinical Characteristics, and Imaging Findings.
Radiology 224:1, 131-138. [CrossRef]
30. Mitsuko Tsubamoto, Keiko Kuriyama, Shoji Kido, Jun Arisawa, Nobuaki Kohno, Takeshi Johkoh, Noriyuki Tomiyama, Osamu
Honda, Chikazumi Kuroda. 2002. Detection of Lung Cancer on Chest Radiographs: Analysis on the Basis of Size and Extent of
Ground-Glass Opacity at Thin-Section CT. Radiology 224:1, 139-144. [CrossRef]
31. Maryellen Giger, Kunio Doi, Samuel Armato, Heber MacmahonComputerized Detection of Lung Nodules . [CrossRef]
32. JohnE. Heffner, Gerard Silvestri. 2002. CT Screening for Lung Cancer. American Journal of Respiratory and Critical Care
Medicine 165:4, 433-434. [CrossRef]
33. L.G.B.A. Quekel, R. Goei, A.G.H. Kessels, J.M.A. van Engelshoven. 2001. Detection of lung cancer on the chest radiograph.
Journal of Clinical Epidemiology 54:11, 1146-1150. [CrossRef]
34. J R C Ellis, F V Gleeson. 2001. Lung cancer screening. The British Journal of Radiology 74:882, 478-485. [CrossRef]
35. Z-G Yang, S Sone, F Li, S Takashima, Y Maruyama, T Honda, M Hasegawa. 2001. Visibility of small peripheral lung cancers
on chest radiographs: influence of densitometric parameters, CT values and tumour type. The British Journal of Radiology 74:877,
32-41. [CrossRef]
36. Giampaolo Gavelli, Emanuela Giampalma. 2000. Sensitivity and specificity of chest x-ray screening for lung cancer. Cancer 89:S11,
2453-2456. [CrossRef]
37. Leonard Berlin. 2000. Alliterative Errors. American Journal of Roentgenology 174:4, 925-931. [Citation] [Full Text] [PDF] [PDF
Plus]
38. Young Hi Choi, Ann N. Leung, Santiago Miro, Charles Poirier, Sharon Hunt, James Theodore. 2000. Primary Bronchogenic
Carcinoma After Heart or Lung Transplantation: Radiologic and Clinical Findings. Journal of Thoracic Imaging 15:1, 36-40.
[CrossRef]
39. Edith M. Marom, Edward F. Patz, Stephen J. Swensen. 1999. Radiologic findings of bronchogenic carcinoma with pulmonary
metastases at presentation. Clinical Radiology 54:10, 665-668. [CrossRef]
40. Ryutaro Kakinuma, Hironobu Ohmatsu, Masahiro Kaneko, Kenji Eguchi, Tsuguo Naruke, Kanji Nagai, Yutaka Nishiwaki, Akira
Suzuki, Noriyuki Moriyama. 1999. Detection Failures in Spiral CT Screening for Lung Cancer: Analysis of CT Findings.
Radiology 212:1, 61-66. [CrossRef]
41. Lorentz G.B.A. Quekel, Alphons G.H. Kessels, Reginald Goei, Joseph M.A. van Engelshoven. 1999. Miss Rate of Lung Cancer
on the Chest Radiograph in Clinical Practice. Chest 115:3, 720-724. [CrossRef]
42. Akihiko Arakawa, Tetsuya Matsukawa, Mitsuko Kira, Seiji Tomiguchi, Mutsumasa Takahashi, Osamu Kawano. 1997. Value of
ultrasound-guided core-needle biopsy for peripheral intrathoracic and mediastinal lesions. Computerized Medical Imaging and
Graphics 21:1, 23-28. [CrossRef]
43. Lorenzo Bonomo, Cesario Ciccotosto, Alessandro Guidotti, Maria Luigia Storto. 1996. Lung cancer staging: the role of computed
tomography and magnetic resonance imaging. European Journal of Radiology 23:1, 35-45. [CrossRef]
44. Hiroshi Soda, Shigeru Kohno, Mikio Oka, Hiroshi Tomita. 1993. Limitation of annual screening chest radiography for the
diagnosis of lung cancer. A retrospective study. Cancer 72:8, 2341-2346. [CrossRef]
Downloaded from www.ajronline.org by 112.215.175.66 on 11/11/16 from IP address 112.215.175.66. Copyright ARRS. For personal use only; all rights reserved
45. Glen A. Lillington. 1991. Management of solitary pulmonary nodules. Disease-a-Month 37:5, 269-318. [CrossRef]