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Official reprint from UpToDate www.uptodate.com 2015
UpToDate
AuthorSteven E Weinberger, MD
Section EditorsNestor L Muller, MD, PhDTalmadge E King, Jr,
MDJames R Jett, MD
Deputy EditorGeraldine Finlay, MD
Disclosures: Steven E Weinberger, MD Nothing to disclose. Nestor
L Muller, MD, PhD Nothing to disclose. Talmadge E King,Jr, MD
Consultant/Advisory Boards: InterMune [pulmonary f ibrosis
(pirfenidone)]; ImmuneWorks [pulmonary f ibrosis];
BoehringerIngelheim [IPF (nintedanib)]; GlaxoSmithKline [pulmonary
f ibrosis]; Daiichi Sankyo [pulmonary f ibrosis]. James R Jett,
MDGrant/Research/Clinical Trial Support: Oncimmune Inc [Biomarkers
of cancer (Early CDT lung)]. Geraldine Finlay, MD Nothing to
Diagnostic evaluation and management of the solitary pulmonary
nodule
All topics are updated as new evidence becomes available and our
peer review process is complete.
Literature review current through: Mar 2015. | This topic last
updated: Feb 10, 2015.
INTRODUCTION A solitary pulmonary nodule (SPN) is a common
clinical problem, with lung cancer screening
studies of smokers at high risk for malignancy reporting the
prevalence of SPNs as high as 50 percent. The major
question that follows detection of a SPN is the probability of
malignancy, with subsequent management varying
accordingly.
The definition, differential diagnosis, initial evaluation, and
management of a SPN are reviewed here. Radiographic
evaluation of pulmonary nodules and differential diagnosis of
multiple pulmonary nodules is discussed in greater
detail separately. (See "Computed tomographic and positron
emission tomographic scanning of pulmonary
nodules" and "Differential diagnosis and evaluation of multiple
pulmonary nodules".)
DEFINITIONS A solitary pulmonary nodule (SPN) is classically
defined as a single, small (30 mm), usually
well-circumscribed, radiographic lesion that is surrounded
completely by pulmonary parenchyma [1-3]. Patients are
usually asymptomatic, and there are typically no associated
features on imaging (eg, hilar adenopathy, atelectasis,
or pleural effusion) [4,5]. SPNs are further subclassified as
solid or subsolid, as discussed separately. (See
'Computed tomography' below.)
Radiographically, lesions that measure 30 mm are considered
nodules and those >30 mm are considered
masses. The distinction between a SPN and a mass is important
because it determines further work-up. When
patients present with a SPN, the focus of the evaluation is the
assessment of the probability of malignancy and the
selection of patients for computed tomography (CT) scan
surveillance, nonsurgical biopsy, or surgical biopsy. In
contrast, when symptoms or associated imaging abnormalities
occur in patients with a nodule or mass, work-up
should proceed for suspected cancer, as discussed separately.
(See "Overview of the initial evaluation, diagnosis,
and staging of patients with suspected lung cancer".)
The increased use of CT scanning for benign pathologies has led
to the identification of multiple pulmonary nodules
(arbitrarily defined as
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Malignant etiologies Common causes of a malignant SPN include
primary lung cancer, lung metastases, and
carcinoid tumors.
Benign etiologies Common causes of a benign SPN include
infectious granulomas and benign tumors such as
a hamartoma. Less common causes include vascular and
inflammatory lesions (table 1).
Primary lung cancer Adenocarcinoma is the histologic subtype of
primary lung cancer that most commonly
presents as a SPN, followed by squamous cell carcinoma and large
cell carcinoma. Both adenocarcinoma
and large cell carcinoma share a tendency to originate as a
peripheral lesion, whereas squamous cell
carcinoma presents more frequently as a central lesion than as a
peripheral nodule. In one review, most of the
malignant SPNs were adenocarcinoma (50 percent) and squamous
cell carcinoma (20 to 25 percent); each of
the other pathologic categories accounted for less than 10
percent of malignant SPNs [2]. Rarely, primary
extranodal lymphomas can present as a SPN. (See "Overview of the
initial evaluation, diagnosis, and staging
of patients with suspected lung cancer".)
Metastatic cancer Although most metastases present as multiple
pulmonary nodules, some present as a
SPN, including malignant melanoma, sarcoma, and carcinomas of
the colon, breast, kidney, and testicle
(image 1) [13]. In a patient with a history of extrathoracic
malignancy, the probability of metastasis is
approximately 25 percent when a SPN is detected on a chest
radiograph [14].
Carcinoid tumors Although carcinoid tumors are typically
endobronchial, approximately 20 percent present
as a peripheral, well-circumscribed SPN. (See "Bronchial
neuroendocrine (carcinoid) tumors: Epidemiology,
risk factors, classification, histology, diagnosis, and
staging".)
Infectious Infectious granulomas cause approximately 80 percent
of benign nodules [1,9,10]. Endemic fungi
(eg, histoplasmosis, coccidioidomycosis) and mycobacteria
(either tuberculous or nontuberculous
mycobacteria) (image 2) are the most frequently recognized
causes of infectious granulomas presenting as a
SPN. While not pathognomonic, they classically appear as a
well-demarcated and fully-calcified SPN (image
3). However, more frequently, they are not diagnosed until the
lesion is resected as a presumed cancer [15].
Less commonly, infection with abscess-forming bacteria (eg,
Staphylococcus aureus) and Pneumocystis
jirovecii (previously called Pneumocystis carinii) can present
as a SPN, which may cavitate [16-19]. Rarely,
dirofilariasis, a mosquito-borne disease, presents as a SPN.
Injected larvae embolize to the lungs and induce
a granulomatous response, typically resulting in a noncalcified,
pleural-based nodule that is mistaken for
cancer. (See "Miscellaneous nematodes".)
Benign tumors Hamartomas cause approximately 10 percent of
benign nodules found in the lung [1,9,10].
They typically present in middle age, grow slowly over years,
and are histologically heterogeneous. Cartilage
(with scattered calcification), fat, muscle, myxomatous tissue,
and fibroblastic tissue may all exist (picture 1
and picture 2A-B and image 4) [20]. The characteristic
appearance of a hamartoma on a chest radiograph is a
SPN with "popcorn" calcification, although this pattern is
observed in less than 10 percent of cases (image 5).
High-resolution CT scanning of the lesion is particularly useful
because it may demonstrate focal areas of fat,
or calcification alternating with fat, which are virtually
diagnostic of a hamartoma (image 6 and image 7) [21].
Less common benign neoplasms such as fibromas, leiomyomas,
hemangiomas, amyloidoma (image 8), and
pneumocytoma do not have characteristic features on imaging
(image 9) [22].
Vascular Pulmonary arteriovenous malformations (PAVMs) are
common in hereditary hemorrhagic
telangiectasia but can also be idiopathic. A contrast-enhanced
CT scan may demonstrate a feeding artery
and vein, which will distinguish vascular from soft tissue
lesions. If a PAVM is suspected and the feeding
artery diameter is >2 to 3 mm, contrast-enhanced CT and
pulmonary angiography are the imaging modalities
of choice and biopsy should be avoided. Rarer causes of SPNs
that are vascular in nature include pulmonary
infarcts (image 10), pulmonary varices, and pulmonary contusion
or hematoma (table 1). (See "Pulmonary
arteriovenous malformations: Diagnostic evaluation".)
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INITIAL EVALUATION The initial evaluation should use clinical
features, radiographic features, and occasionally
quantitative models to determine the likelihood of malignancy.
The likelihood of malignancy then determines further
management (eg, computed tomography [CT] surveillance or
biopsy).
Clinical features Clinical features associated with an increased
probability of malignancy include advanced
patient age and underlying risk factors. However, young age and
the absence of risk factors do not preclude a
diagnosis of malignancy [23].
Imaging The imaging tools used to evaluate a solitary pulmonary
nodule (SPN) include chest radiography, CT,
and functional imaging (usually positron emission tomography
[PET]). Although the vast majority of SPNs that
present to the clinician for evaluation are incidental findings
on CT, occasionally nodules are detected on the chest
radiograph. While nodule characteristics can be appreciated by
chest radiography, they are better defined by CT
scan. It is important to make every attempt to secure old
imaging studies, including prior CTs and chest
radiographs, because size comparisons can be used to determine
whether the nodule has been stable or growing
over time.
Computed tomography A CT scan of the chest, preferably with thin
sections (1 mm slice), should be
obtained in all patients. Contrast enhancement is not typically
required when imaging a SPN. CT features that can
be used to predict whether a nodule is malignant include size,
border, calcification, attenuation, and growth. (See
"Computed tomographic and positron emission tomographic scanning
of pulmonary nodules", section on 'Computed
tomography (CT)'.)
Other Inflammatory lesions (granulomatosis with polyangiitis
[formerly known as Wegeners
granulomatosis], rheumatoid arthritis, sarcoidosis, amyloidosis,
rounded atelectasis), perifissural pulmonary
lymph nodes, and developmental lesions (bronchogenic cyst) are
unusual causes of benign nodules (table 1).
The presence of systemic disease elsewhere may increase the
likelihood of an inflammatory nodule, but not
all patients will have such a history since nodules can
occasionally be the initial presenting feature of the
underlying disease. Rarely are SPNs due to artifact such as
pseudotumor (loculated fluid in the interlobar
fissure) or mucoid impaction; simple maneuvers such as diuresis
and cough assistance may result in the
resolution of a SPN due to such entities on follow-up
imaging.
Patient age The probability of malignancy rises with increasing
patient age [6,8,23-26]. One study reported
a higher frequency of malignant nodules in patients >50 years
of age compared with patients 50 percent
Risk factors The probability of malignancy is always higher when
a nodule occurs in a patient with a history
of smoking, especially current smokers, because of the strong
association between cigarette smoking and
lung cancer [27]. Other risk factors for lung cancer including
family history, female sex, emphysema, prior
malignancy, and asbestos exposure should also be considered when
evaluating a patient with a nodule [28].
(See "Overview of the risk factors, pathology, and clinical
manifestations of lung cancer", section on 'Risk
factors' and "Cigarette smoking and other risk factors for lung
cancer".)
Size Consistently among studies, size, usually measured as the
maximum diameter of a nodule, is an
independent predictor for malignancy. Data from retrospective
series and prospective screening trials all
confirm that the risk of malignancy rises with increasing size
as follows [12,24,25,27,29-37]:
Nodules
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Nodules 8 to 20 mm: 18 percent
Nodules >20 mm: >50 percent
Attenuation Nodule attenuation should be classified as solid or
subsolid (pure and part-solid). Solid lesions
are more common, but part-solid lesions have a higher likelihood
of being malignant [12,38,39].
Solid SPNs are typically dense and homogeneous on imaging. Solid
nodules 8 mm (also known as
subcentimeter nodules) are unlikely to be malignant, are
difficult to biopsy, not reliably characterized by
functional imaging, and more likely to be followed by CT scan
surveillance. In contrast, solid nodules >8 mm
have a greater likelihood of malignancy, can be more reliably
characterized by functional imaging, and are
more likely to be successfully diagnosed by biopsy.
Subsolid/non solid nodules have poor attenuation (ie, density)
on imaging such that normal parenchymal
structures, including airways and vessels, can be visualized
through them. They should be further assessed
for the absence (pure subsolid; ground glass nodules) or
presence (part-solid) of a solid component.
Compared with solid nodules, they are often less amenable to
functional imaging and biopsy.
The incidence of subsolid nodules is increasing, likely due to
the rising incidence of adenocarcinoma
worldwide. The most common neoplastic histologies seen with
ground glass morphology are atypical
adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and
minimally invasive adenocarcinoma (MIA)
(picture 3) [40-45]. (See "Pathology of lung malignancies" and
"Bronchioloalveolar carcinoma, including
adenocarcinoma in situ".)
The risk of malignancy in ground glass lesions that persist
beyond three months by CT scan ranges from 10
to 60 percent and depends upon the size and presence of a
part-solid component [2,12,40-43,45,46]. As
examples, malignancy is rare in small (10 mm) SPN that are pure
ground glass and more common (10 to 50
percent) in larger lesions (>10 mm). In contrast, malignancy
will be identified in at least half of ground glass
lesions that have a large (>50 percent) or newly developed
solid component. This higher malignant potential of
part-solid lesions was demonstrated in CT screening studies
where the identification of a solid component of
ground glass lesions was an independent predictor for malignancy
[12].
Formal density measurement of SPNs was at one time considered to
be a promising technique but is no
longer used as part of the routine evaluation of a SPN.
Growth CT is classically used as a diagnostic and management
tool to assess nodule growth or stability. A
SPN that has clearly grown on serial imaging is at high risk for
malignancy, often necessitating a tissue
diagnosis. Conversely, a solid nodule that has been stable for
two years and a subsolid nodule that is stable
for three years are likely to be benign, and immediate tissue
biopsy can be avoided. Consequently, in patients
who present with a SPN, every attempt should be made to obtain
older imaging studies, preferably a CT.
Traditionally, a nodule that remained stable for two years or
longer on a chest radiograph was considered
benign. However, retrospective studies suggest that lack of
appreciable growth on a chest radiograph over a
two-year duration has a poor positive predictive value (65
percent) for a benign lesion [1,47,48]. Compared to
chest radiography, high-resolution CT scan can better appreciate
changes in diameter (0.5 mm change versus
3 to 5 mm) [1]. As such, serial CT is preferred for growth
assessment.
Studies that assess the volume doubling time (VDT) of cancers
have been helpful in predicting the probability
of malignancy in a SPN. Most malignant nodules have a VDT
between 20 and 400 days, with slower VDTs
(>400 days) observed in typical carcinoid and in preinvasive
or low grade adenocarcinoma (eg,
adenocarcinoma in situ [AIS] and minimally-invasive
adenocarcinoma [MIA]) [1,5,49-51]. Thus, a nodule that
has increased in size over a short period of time (two
years) is likely benign. These data largely apply to solid
nodules. In contrast, subsolid nodules are more likely
to be seen with early or low grade adenocarcinoma, which has a
slower average VDT. One retrospective study
reported median VDTs of malignant nodules according to their CT
attenuation characteristics as: ground glass
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Functional imaging Because cancers are more likely to be
metabolically active, functional imaging is often
used to help distinguish benign from malignant nodules. Positron
emission tomography (PET) is the most common
functional imaging modality used. Less common modalities include
dynamic contrast-enhanced CT scan, dynamic
magnetic resonance imaging (MRI), and dynamic single photon
emission CT scan. Although the sensitivity is
similar among all four modalities, PET is the preferred modality
because it is best studied and widely available.
(See "Computed tomographic and positron emission tomographic
scanning of pulmonary nodules", section on
'Positron emission tomography (PET)'.)
The decision to perform a PET depends upon the probability of
malignancy, size, and attenuation:
FDG-avidity is measured by the standardized uptake value (SUV).
The optimal cut-off point that distinguishes
benign from malignant lesions is unknown. The SUV correlates
positively with the likelihood of malignancy and even
nodules with a low SUV (eg, 8 mm PET has a high sensitivity (72
to 94 percent) for
the diagnosis of malignancy and should be used to further
evaluate a SPN in all patients in this category [55-
62].
High probability (>65 percent) solid SPN >8 mm Although
PET scan is unlikely to change the indication for
biopsy in this population, in practice, it is frequently
performed as part of the work-up for suspected cancer.
This is because it has the distinct advantage of confirming the
clinical suspicion for malignancy as well as
acquiring staging data if the nodule is indeed malignant. (See
"Overview of the initial evaluation, diagnosis, and
staging of patients with suspected lung cancer", section on
'Radiographic staging'.)
Low probability (10 to 15 mm), which are considered to have
greater malignant potential
compared with smaller, purely subsolid nodules.
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SUV >2.5 is typically used to distinguish SPNs that have a
high probability of malignancy, reflecting the value
typically used in practice [2].
PET can have false-positive and false-negative findings:
Other functional imaging modalities are rarely used. Combined
imaging with CT and PET (integrated PET/CT)
increases the amount of ionizing radiation exposure from 5 to 7
mSv (PET) to 10 to 25 mSv (PET/CT) [2,78-81].
Although earlier studies suggested that CT scan with dynamic
contrast enhancement had a sensitivity of 98
percent, the high false-negative rate demonstrated in later
studies has discouraged its use [2,82-84]. Despite
reports of high sensitivity for dynamic MRI and dynamic
single-photon emission CT scan (94 and 95 percent,
respectively), they are poorly studied and not widely available
[2,78].
Assessing the risk of malignancy The probability of malignancy
in a SPN should be assessed either clinically
or by quantitative predictive models as the following [2]:
Many physicians estimate the probability of malignancy
intuitively. Studies that have compared the accuracy of
clinician judgment with quantitative prediction models report
modest to excellent agreement in estimating the
probability of malignancy, suggesting that clinical assessment
and prediction models may be complementary
[85,86].
Although no single quantitative predictive model is superior,
they all combine clinical and radiographic features to
estimate the probability of malignancy [24,25,37,86-90]. They
are most useful for nodules that are 8 to 30 mm to
facilitate patient discussion and guide management choices [2].
Typically, nodules >30 mm are resected because
these lesions have such a high likelihood of malignancy that the
benefit of resection outweighs the associated risk
of surgery. In contrast, nodules 8 mm (without documented
growth) are usually followed by serial CT scan
because these lesions have a low likelihood of malignancy such
that the benefits of resection do not justify the risk
of a technically-difficult resective surgery
[2,27,29,35,40-43,46]. Thus, estimating the probability of
malignancy in
both of these settings is unlikely to change the diagnostic
strategy. However, the risk of malignancy and diagnostic
options are widely variable in nodules that are 8 to 30 mm.
Thus, estimating the pretest probability of malignancy in
that setting will facilitate the selection and interpretation of
subsequent diagnostic tests.
Quantitative predictive models that have been validated for use
include the following [12,24,25,36,37]:
False-positive findings occur with infectious and inflammatory
conditions, in particular, pneumonia,
mycobacterial disease, rheumatoid nodules, and sarcoidosis.
False-negative results can occur with less metabolically active
tumors (adenocarcinoma in situ, minimally
invasive adenocarcinoma, mucinous adenocarcinoma, and carcinoid
tumors) and uncontrolled hyperglycemia
(high serum glucose levels retard FDG uptake). In addition,
smaller lesions (eg, 8 mm) and subsolid lesions
may be falsely negative on PET because a critical mass of
metabolically active malignant cells is required for
detection by PET [2,62-64,77].
Low probability (65 percent)
A full and simplified version of one model was derived using
data collected from the Pan-Canadian Early
Detection of Lung Cancer screening study and validated using
data from the British Columbia Cancer Agency
study [12]. Predictors of cancer were identified in 2961
patients with nodules found on first screening CT and
included the following: older age, female sex, family history of
lung cancer, emphysema, larger nodule size,
location of the nodule in the upper lobe, part-solid nodule
type, lower nodule count, and spiculation. Both full
and simplified versions of the model showed excellent
discrimination between benign and malignant nodules,
even when applied to nodules typically difficult to characterize
(SPN 10 mm). While the negative predictive
value of this model was consistently high (99 percent), the
sensitivity ranged from 60 to 86 percent when
different cut-off thresholds were used. The probability of
malignancy can be calculated using the calculator
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The use of biomarkers (eg, carcinoembryonic antigen, alpha-1
antitrypsin, squamous cell carcinoma antigen) to
stratify risk of malignancy in patients with SPNs has been
reported but is not yet validated for use [91].
Measurement of biomarkers of benign diseases (eg, angiotensin
converting enzyme, connective tissue disease
markers) has not been tested in the general setting of SPN but
can be considered on a case-by-case basis.
Assessing nodule volume to increase the proportion of nodules
correctly identified as malignant has been reported
but is not yet validated for routine use [36,92].
MANAGEMENT STRATEGY The optimal approach to a solitary pulmonary
nodule (SPN) is unknown and the
approaches used in practice are often inconsistent with
guidelines [93]. However, there is consensus that the
management be individualized to each patient.
Aggressive approaches that surgically remove nodules are more
likely to result in the diagnosis of early stage lung
cancer, which is potentially curable and associated with a
five-year survival of 70 to 80 percent [1,46,49,94-96].
However, they also result in the unnecessary removal of benign
nodules of uncertain clinical significance. In
contrast, less aggressive approaches that leave most benign
nodules intact will miss some cases of potentially
curable lung cancer, which may no longer be curable after
progression. Many clinicians place a high value on
diagnostic certainty in the context of low operative mortality
(
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[2,63]. This approach maximizes the detection of early
resectable lung cancer while minimizing the harm
associated with an excessively aggressive surgical approach and
takes into consideration patient values and
preferences.
Selection of strategy Management options for SPNs include
computed tomography (CT) surveillance and
nodule sampling or resection. Despite variation among
institutions regarding optimal management strategy for
nodules, there is consensus that the management be
individualized to each patient after consideration of the
following [2,63,97-99]:
Once this information is known, a strategy can be selected that
is optimized to meet patient preferences (eg, for
diagnosis and safety) and institutional-related expertise. (See
'Values and preferences' below.)
Patients with adequate prior imaging This group of patients
includes those in whom prior imaging is
sufficient for the assessment of growth or stability.
Growing nodule A solid or subsolid nodule that has clearly grown
on serial imaging tests has a high
likelihood of being malignant and should be evaluated
pathologically with excision or biopsy. This is discussed in
more detail separately. (See 'Surgical biopsy' below.)
Stable nodule Experts agree that the vast majority of solid SPNs
that are unchanged on serial CT scan
over a two-year period and subsolid SPNs unchanged over a
three-year period are likely benign and do not need
further diagnostic evaluation. Occasionally, patients in this
category may require extended periods of CT
surveillance to ensure stability, especially if low grade
adenocarcinoma or carcinoid is suspected.
Patients without adequate prior imaging This group of patients
includes those in whom prior imaging is
insufficient for the assessment of growth or stability.
Solid nodules >8 mm In patients with solid SPNs >8 mm for
which growth or stability cannot be
adequately determined, there is a consensus of opinion on the
following (algorithm 1):
The probability of malignancy (low [65 percent]) (see
'Assessing the risk of malignancy' above)
Nodule characteristics (eg, size, attenuation, stability)
A nodule that has a low probability (
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Solid nodules 8 mm A solid nodule 8 mm can be followed by serial
CT scan. The rationale for this
strategy is based upon the low prevalence of malignancy as well
as the procedural difficulty and high risk of tissue
biopsy in this population. Any increase in nodule size should
prompt redirection of the management strategy toward
biopsy or excision.
Studies that report growth for nodules found on CT suggest that
the detection of growth is dependent upon the
presence of risk factors in the study population. One
retrospective review reported that in patients with no risk
factors for lung cancer who had SPNs
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The optimal management of persistent part-solid nodules is
uncertain. Regardless of disagreement among
societies, the common goal is the selective removal of nodules
at greater risk of being malignant, while avoiding the
removal of those that are more likely to be benign. For example,
the Fleischner Society suggests management
based upon size of the solid component: CT surveillance when the
solid component is 5 mm, surgical removal
when the solid component is >5 mm, and PET scanning for
persistent part-solid nodules >10 mm. However, we
agree with the ACCP that suggests management based upon size of
the part-solid nodule:
Multiple nodules The increased use of CT surveillance has led to
the frequent identification of multiple
nodules of uncertain significance on serial imaging. Prospective
studies of patients during evaluation for lung cancer
and screening studies suggest that the vast majority of these
nodules are benign [29,30,104-109]. This suggests
that benign and malignant nodules can coexist in the same
patient. Although one nodule may be dominant (size,
growth characteristics, PET avidity), each nodule should be
assessed individually for the probability of malignancy
and followed by CT surveillance or biopsied accordingly [2]. As
an alternative approach, the Fleischner Society has
developed detailed guidelines for the management of multiple
nodules based upon size and appearance (table 6).
Values and preferences It is prudent to assess a patients desire
for an extensive work-up as well as for
treatment in the eventuality that a nodule is cancer. Some
individuals prefer no treatment or suboptimal therapy,
especially those with life-limiting comorbid conditions. For
others who are risk averse, particularly to curative
lobectomy, discussion of alternative suboptimal therapies for
lung cancer is reasonable. For patients who prefer no
therapy, monitoring clinically or with CT surveillance may be
preferred for palliative purposes. In contrast, surgical
excision may be preferred by those who have a strong desire for
diagnostic certainty, are noncompliant with follow-
up, and are willing to accept the risks associated with
surgery.
Nonsurgical biopsy Nonsurgical biopsy can be performed by
sampling the nodule through the airway
(bronchoscopic techniques) or through the chest wall
(transthoracic needle biopsy). Nonsurgical biopsy is preferred
in patients who have a nodule at intermediate risk (5 to 65
percent) for malignancy or in patients who are at high
risk (>65 percent) who are not surgical candidates.
Additional indications may include patients in whom a benign
diagnosis is suspected that requires therapy (eg, mycobacterial
disease) or rarely, for patients at low risk of
malignancy who place a high value on diagnostic certainty.
The choice of sampling procedure varies according to the size
and location of the nodule, the availability of the
procedure, and local expertise. Typically, bronchoscopic
techniques (endobronchial ultrasound [EBUS] and
conventional bronchoscopy) are preferred for large,
centrally-located lesions, and transthoracic needle biopsy
techniques are preferred for more peripheral lesions.
EBUS-guided sheath transbronchial biopsy may also be used
in centers with expertise for peripheral nodules. Navigational
tools (eg, virtual bronchoscopy or electromagnetic
navigation) hold promise as modalities that increase the
diagnostic yield of bronchoscopy for small peripheral
nodules; their use depends on equipment availability and
institutional expertise.
Bronchoscopic techniques The main bronchoscopic techniques that
are used to obtain diagnostic material
from pulmonary nodules include conventional bronchoscopic-guided
transbronchial biopsy (TBB), bronchoscopic-
transbronchial needle aspiration (bronchoscopic-TBNA),
endobronchial ultrasound-guided sheath transbronchial
biopsy (EBUS-guided sheath TBBx), and endobronchial
ultrasound-guided transbronchial needle aspiration (EBUS-
TBNA). Because these modalities biopsy nodules via the airway
and are performed under conscious sedation, they
are preferred for patients who have nodules that are close to a
patent airway and for those in whom the risk of
complications from surgery or transthoracic needle biopsy is
high. Among the bronchoscopic modalities, EBUS-
A part-solid nodule 8 mm can be followed by CT surveillance at
3, 12, and 24 months. If the nodule or the
solid component is unchanged after 24 months of observation and
clinical suspicion for low grade
adenocarcinoma or carcinoid exists, further CT yearly for an
additional one to three years is preferred [2]. (See
'CT surveillance' below.)
A part-solid nodule >8 mm (especially those >15 mm) or
those with a solid component >8 mm can be further
evaluated by PET, and when feasible, biopsy or surgical
resection can be considered. (See 'Nonsurgical
biopsy' below and 'Surgical biopsy' below.)
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TBNA or EBUS-guided sheath TBBx are the preferred procedures,
when local expertise is available. Conventional
bronchoscopic-TBNA or TBB are alternatives when EBUS is not
available.
EBUS-TBNA has been shown to surpass flexible bronchoscopy for
the diagnosis of lung malignancies [110-112].
Its comparative performance for specific benign diagnoses is
unknown but likely to also be superior to conventional
bronchoscopy. However, for both procedures, high operator
proficiency and multiple passes with rapid onsite
cytologic evaluation (ROSE) may enhance the diagnostic accuracy
[114-119].
The low negative predictive values for TBNA-associated
techniques emphasize that a nondiagnostic or negative
finding does not rule out the possibility of malignancy. In such
cases, when nonsurgical biopsy findings are
nondiagnostic, selecting a strategy that weighs the benefits of
diagnostic certainty against the risks of surgical
resection is preferred.
Transthoracic needle biopsy Transthoracic needle biopsy (TTNB)
is performed by passing a needle
percutaneously through the chest wall into the target nodule,
usually under CT guidance. The needle frequently
traverses pleura and lung to either aspirate or biopsy tissue.
Typically, the diagnostic yield of TTNB is >88 percent
for benign and malignant nodules [50,120-124]. However, the high
diagnostic accuracy of TTNB should be weighed
against the risk of pneumothorax. The risk-benefit ratio is
increased in patients with concomitant emphysema,
bullous disease, or chronic respiratory failure. Thus, TTNB is
the preferred modality for biopsy of peripheral nodules
that are located close to the chest wall or for deeper lesions
where fissures do not need to be traversed and are
without surrounding bullous disease.
One meta-analysis of 46 studies of TTNB detected malignant
solitary pulmonary nodules (SPNs) with a sensitivity
and false negative rate of 90 and 22 percent, respectively
[113]. However, the diagnostic sensitivity of TTNB is lower
for smaller SPNs (2 cm: 63 percent;
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The most common complication of TTNB is pneumothorax (10 to 60
percent), with hemorrhage occurring less
commonly (1 to 9.5 percent) [123,124,130-132]. The risk of
complications appears to be greatest in smokers, older
patients (>60 years), patients with chronic obstructive
pulmonary disease or emphysema, and possibly in those
with ground glass nodules.
Surgical biopsy Surgical excision is the gold standard for the
diagnosis of malignant SPNs. It is also the
definitive treatment for most malignant nodules, especially
non-small cell lung cancer and carcinoid. For patients
that are surgical candidates, a diagnostic wedge resection by
video-assisted thoracic surgery (VATS) is the
preferred procedure for SPNs at high risk of malignancy (>65
percent) or SPNs of intermediate risk when
nonsurgical biopsy is nondiagnostic or suspicious for malignancy
[133,134]. Additional indications may include
patients in whom a benign diagnosis is suspected that requires
therapy (eg, mycobacterial disease) in whom
nonsurgical biopsy was nondiagnostic or rarely for patients who
place a high value on a diagnostic certainty.
During VATS, nodules targeted for resection are usually located
by visual inspection, such that VATS is best
utilized for SPNs located close to the pleural surface
[133,134]. However, for deeper lesions, digital palpation or
localization techniques can be performed to increase the
diagnostic yield during thoracoscopy. Localization
techniques include preoperative placement of a hook wire and
percutaneous injection of methylene blue or
microcoils; or intraoperative imaging with technetium-99
radioguidance, ultrasound, or fluoroscopy [135,136].
The diagnosis is typically established intraoperatively by
frozen section analysis after wedge resection of the SPN.
When the diagnosis is consistent with non-small cell carcinoma
(NSCLC), the surgery is preferably converted to a
VATS lobectomy with mediastinal node sampling, which is the
optimal treatment for early stage NSCLC. The
advantage of this approach is that for SPNs that are malignant,
diagnosis, staging, and therapy are performed in a
single operative procedure. However, frozen section pathology is
less reliable for lesions
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surveillance is most often performed in those at low risk for
malignancy (eg, solid nodules
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REFERENCES
1. Ost D, Fein AM, Feinsilver SH. Clinical practice. The
solitary pulmonary nodule. N Engl J Med 2003;
recommend diagnostic evaluation with surgical excision or
nonsurgical biopsy rather than CT surveillance.
(See 'Growing nodule' above and 'Computed tomography'
above.)
For patients with solid SPNs that have been stable over two
years and subsolid SPNs stable over three years
on serial imaging, we suggest no further diagnostic testing.
(See 'Stable nodule' above and 'Computed
tomography' above.)
For patients with a solid SPN >8 mm for which growth or
stability cannot be determined, we suggest that the
diagnostic evaluation be determined by the probability of
malignancy (algorithm 1). A SPN that has a low
probability (65 percent) of being malignant should be biopsied
or surgically excised
rather than followed with serial CT. (See 'Solid nodules >8
mm' above.)
For patients with a solid SPN 8 mm for which growth or stability
cannot be determined, we suggest non
enhanced serial CT scans rather than biopsy (table 5). The
frequency of CT scanning depends upon the
individuals risk for cancer and nodule size. (See 'Solid nodules
8 mm' above.)
For patients with a pure subsolid (ground glass) SPN 5 mm, we
suggest no additional diagnostic testing.
For patients with a pure subsolid SPN >5 mm, we suggest that
a follow-up non enhanced CT scan be
performed at three months (table 6). A persistent nodule at
three months that is 5 to 10 mm can be followed
by yearly CT for three years. A persistent nodule at three
months that is >10 to 15 mm is preferably excised
or biopsied. (See 'Pure subsolid nodules' above.)
For patients with part-solid nodules, we suggest CT surveillance
once at three months (table 6). For
persistent part-solid lesions, CT surveillance (non enhanced) is
preferred for small SPNs (eg, 8 mm, solid
component 5 mm). For larger persistent part-solid SPNs (eg,
>8 mm or with solid component >8 mm), a
more aggressive strategy that incorporates PET scan and a low
threshold for biopsy or excision is preferred.
(See 'Part-solid nodules' above.)
For patients with a SPN who are subsequently found to have
multiple nodules on imaging on serial CT scan,
each nodule should be assessed individually for the probability
of malignancy and followed by additional CT
surveillance or biopsied accordingly. (See 'Multiple nodules'
above.)
Considerable variation in strategies occurs among clinicians.
However, there is consensus that the
management be individualized and that patient values be assessed
when discussing the advantages and
disadvantages for each management strategy. (See 'Values and
preferences' above.)
The choice of sampling procedure (nonsurgical biopsy or surgical
biopsy) varies according to the probability
of malignancy, size and location of the nodule, local expertise,
and patient values. (See 'Nonsurgical biopsy'
above and 'Surgical biopsy' above.)
For patients in whom surveillance is chosen, CT imaging should
be noncontrast, thin slice (1 mm),
contiguous sections, using a low-dose radiation technique
[2,63]. Any increase in size or character of the
nodule is concerning for malignancy and warrants evaluation for
tissue biopsy or excision, when feasible.
Informing the patient of the risks and benefits of CT
surveillance is important when choosing this strategy.
(See 'CT surveillance' above.)
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
15/21
348:2535.
2. Gould MK, Donington J, Lynch WR, et al. Evaluation of
individuals with pulmonary nodules: when is it lungcancer?
Diagnosis and management of lung cancer, 3rd ed: American College
of Chest Physicians evidence-based clinical practice guidelines.
Chest 2013; 143:e93S.
3. Tuddenham WJ. Glossary of terms for thoracic radiology:
recommendations of the Nomenclature Committeeof the Fleischner
Society. AJR Am J Roentgenol 1984; 143:509.
4. Lillington GA, Caskey CI. Evaluation and management of
solitary and multiple pulmonary nodules. Clin ChestMed 1993;
14:111.
5. Midthun DE, Swensen SJ, Jett JR. Approach to the solitary
pulmonary nodule. Mayo Clin Proc 1993; 68:378.
6. Toomes H, Delphendahl A, Manke HG, Vogt-Moykopf I. The coin
lesion of the lung. A review of 955 resectedcoin lesions. Cancer
1983; 51:534.
7. Ost D, Fein A. Management strategies for the solitary
pulmonary nodule. Curr Opin Pulm Med 2004; 10:272.
8. Trunk G, Gracey DR, Byrd RB. The management and evaluation of
the solitary pulmonary nodule. Chest1974; 66:236.
9. Higgins GA, Shields TW, Keehn RJ. The solitary pulmonary
nodule. Ten-year follow-up of veteransadministration-armed forces
cooperative study. Arch Surg 1975; 110:570.
10. Ray JF 3rd, Lawton BR, Magnin GE, et al. The coin lesion
story: update 1976. Twenty years' experience withthoracotomy for
179 suspected malignant coin lesions. Chest 1976; 70:332.
11. Rubins JB, Rubins HB. Temporal trends in the prevalence of
malignancy in resected solitary pulmonarylesions. Chest 1996;
109:100.
12. McWilliams A, Tammemagi MC, Mayo JR, et al. Probability of
cancer in pulmonary nodules detected on firstscreening CT. N Engl J
Med 2013; 369:910.
13. Seo JB, Im JG, Goo JM, et al. Atypical pulmonary metastases:
spectrum of radiologic findings.Radiographics 2001; 21:403.
14. Cahan WG, Shah JP, Castro EB. Benign solitary lung lesions
in patients with cancer. Ann Surg 1978;187:241.
15. Gribetz AR, Damsker B, Bottone EJ, et al. Solitary pulmonary
nodules due to nontuberculous mycobacterialinfection. Am J Med
1981; 70:39.
16. Barrio JL, Suarez M, Rodriguez JL, et al. Pneumocystis
carinii pneumonia presenting as cavitating andnoncavitating
solitary pulmonary nodules in patients with the acquired
immunodeficiency syndrome. Am RevRespir Dis 1986; 134:1094.
17. Nicholson CP, Allen MS, Trastek VF, et al. Dirofilaria
immitis: a rare, increasing cause of pulmonary nodules.Mayo Clin
Proc 1992; 67:646.
18. Asimacopoulos PJ, Katras A, Christie B. Pulmonary
dirofilariasis. The largest single-hospital experience.Chest 1992;
102:851.
19. Echeverri A, Long RF, Check W, Burnett CM. Pulmonary
dirofilariasis. Ann Thorac Surg 1999; 67:201.
20. Gjevre JA, Myers JL, Prakash UB. Pulmonary hamartomas. Mayo
Clin Proc 1996; 71:14.
21. Siegelman SS, Khouri NF, Scott WW Jr, et al. Pulmonary
hamartoma: CT findings. Radiology 1986; 160:313.
22. Shin SY, Kim MY, Oh SY, et al. Pulmonary Sclerosing
Pneumocytoma of the Lung: CT Characteristics in aLarge Series of a
Tertiary Referral Center. Medicine (Baltimore) 2015; 94:e498.
23. Bourke W, Milstein D, Giura R, et al. Lung cancer in young
adults. Chest 1992; 102:1723.
24. Swensen SJ, Silverstein MD, Ilstrup DM, et al. The
probability of malignancy in solitary pulmonary nodules.Application
to small radiologically indeterminate nodules. Arch Intern Med
1997; 157:849.
25. Gould MK, Ananth L, Barnett PG, Veterans Affairs SNAP
Cooperative Study Group. A clinical model toestimate the pretest
probability of lung cancer in patients with solitary pulmonary
nodules. Chest 2007;131:383.
26. Yonemori K, Tateishi U, Uno H, et al. Development and
validation of diagnostic prediction model for solitary
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
16/21
pulmonary nodules. Respirology 2007; 12:856.
27. Gohagan J, Marcus P, Fagerstrom R, et al. Baseline findings
of a randomized feasibility trial of lung cancerscreening with
spiral CT scan vs chest radiograph: the Lung Screening Study of the
National Cancer Institute.Chest 2004; 126:114.
28. Neifeld JP, Michaelis LL, Doppman JL. Suspected pulmonary
metastases: correlation of chest x-ray, wholelung tomograms, and
operative findings. Cancer 1977; 39:383.
29. MacMahon H, Austin JH, Gamsu G, et al. Guidelines for
management of small pulmonary nodules detectedon CT scans: a
statement from the Fleischner Society. Radiology 2005; 237:395.
30. Midthun, DE, Swensen, SJ, Jett, JR, et al. Evaluation of
nodules detected by screening for lung cancer withlow dose spiral
computed tomography. Lung Cancer 2003; 41:40S.
31. Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung
cancer with low-dose spiral computed tomography.Am J Respir Crit
Care Med 2002; 165:508.
32. Henschke CI, Yankelevitz DF, Naidich DP, et al. CT screening
for lung cancer: suspiciousness of nodulesaccording to size on
baseline scans. Radiology 2004; 231:164.
33. Suzuki K, Nagai K, Yoshida J, et al. Video-assisted
thoracoscopic surgery for small indeterminate pulmonarynodules:
indications for preoperative marking. Chest 1999; 115:563.
34. Benjamin MS, Drucker EA, McLoud TC, Shepard JA. Small
pulmonary nodules: detection at chest CT andoutcome. Radiology
2003; 226:489.
35. Piyavisetpat N, Aquino SL, Hahn PF, et al. Small incidental
pulmonary nodules: how useful is short-terminterval CT follow-up? J
Thorac Imaging 2005; 20:5.
36. Mehta HJ, Ravenel JG, Shaftman SR, et al. The utility of
nodule volume in the context of malignancyprediction for small
pulmonary nodules. Chest 2014; 145:464.
37. Cummings SR, Lillington GA, Richard RJ. Estimating the
probability of malignancy in solitary pulmonarynodules. A Bayesian
approach. Am Rev Respir Dis 1986; 134:449.
38. Henschke CI, Yankelevitz DF, Mirtcheva R, et al. CT
screening for lung cancer: frequency and significance ofpart-solid
and nonsolid nodules. AJR Am J Roentgenol 2002; 178:1053.
39. Li F, Sone S, Abe H, et al. Malignant versus benign nodules
at CT screening for lung cancer: comparison ofthin-section CT
findings. Radiology 2004; 233:793.
40. Kim HY, Shim YM, Lee KS, et al. Persistent pulmonary nodular
ground-glass opacity at thin-section CT:histopathologic
comparisons. Radiology 2007; 245:267.
41. Kodama K, Higashiyama M, Takami K, et al. Treatment strategy
for patients with small peripheral lunglesion(s): intermediate-term
results of prospective study. Eur J Cardiothorac Surg 2008;
34:1068.
42. Mun M, Kohno T. Efficacy of thoracoscopic resection for
multifocal bronchioloalveolar carcinoma showingpure ground-glass
opacities of 20 mm or less in diameter. J Thorac Cardiovasc Surg
2007; 134:877.
43. Nakata M, Sawada S, Saeki H, et al. Prospective study of
thoracoscopic limited resection for ground-glassopacity selected by
computed tomography. Ann Thorac Surg 2003; 75:1601.
44. Ohtsuka T, Watanabe K, Kaji M, et al. A clinicopathological
study of resected pulmonary nodules with focalpure ground-glass
opacity. Eur J Cardiothorac Surg 2006; 30:160.
45. Lim HJ, Ahn S, Lee KS, et al. Persistent pure ground-glass
opacity lung nodules 10 mm in diameter at CTscan: histopathologic
comparisons and prognostic implications. Chest 2013; 144:1291.
46. Allen MS, Darling GE, Pechet TT, et al. Morbidity and
mortality of major pulmonary resections in patientswith early-stage
lung cancer: initial results of the randomized, prospective ACOSOG
Z0030 trial. Ann ThoracSurg 2006; 81:1013.
47. GOOD CA, HOOD RT Jr, McDONALD JR. Significance of a solitary
mass in the lung. Am J RoentgenolRadium Ther Nucl Med 1953;
70:543.
48. Yankelevitz DF, Henschke CI. Does 2-year stability imply
that pulmonary nodules are benign? AJR Am JRoentgenol 1997;
168:325.
49. Williams DE, Pairolero PC, Davis CS, et al. Survival of
patients surgically treated for stage I lung cancer. J
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
17/21
Thorac Cardiovasc Surg 1981; 82:70.
50. Ost D, Fein A. Evaluation and management of the solitary
pulmonary nodule. Am J Respir Crit Care Med2000; 162:782.
51. Song YS, Park CM, Park SJ, et al. Volume and mass doubling
times of persistent pulmonary subsolidnodules detected in patients
without known malignancy. Radiology 2014; 273:276.
52. Hasegawa M, Sone S, Takashima S, et al. Growth rate of small
lung cancers detected on mass CTscreening. Br J Radiol 2000;
73:1252.
53. Zerhouni EA, Stitik FP, Siegelman SS, et al. CT of the
pulmonary nodule: a cooperative study. Radiology1986; 160:319.
54. Rigler LG. An overview of cancer of the lung. Semin
Roentgenol 1977; 12:161.
55. Grgic A, Yksel Y, Grschel A, et al. Risk stratification of
solitary pulmonary nodules by means of PET
using(18)F-fluorodeoxyglucose and SUV quantification. Eur J Nucl
Med Mol Imaging 2010; 37:1087.
56. Kagna O, Solomonov A, Keidar Z, et al. The value of
FDG-PET/CT in assessing single pulmonary nodules inpatients at high
risk of lung cancer. Eur J Nucl Med Mol Imaging 2009; 36:997.
57. Mizugaki H, Shinagawa N, Kanegae K, et al. Combining
transbronchial biopsy using endobronchialultrasonography with a
guide sheath and positron emission tomography for the diagnosis of
small peripheralpulmonary lesions. Lung Cancer 2010; 68:211.
58. Mori T, Nomori H, Ikeda K, et al. Diffusion-weighted
magnetic resonance imaging for diagnosing malignantpulmonary
nodules/masses: comparison with positron emission tomography. J
Thorac Oncol 2008; 3:358.
59. Ohba Y, Nomori H, Mori T, et al. Is diffusion-weighted
magnetic resonance imaging superior to positronemission tomography
with fludeoxyglucose F 18 in imaging non-small cell lung cancer? J
Thorac CardiovascSurg 2009; 138:439.
60. Cronin P, Dwamena BA, Kelly AM, Carlos RC. Solitary
pulmonary nodules: meta-analytic comparison ofcross-sectional
imaging modalities for diagnosis of malignancy. Radiology 2008;
246:772.
61. Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of
positron emission tomography for diagnosis ofpulmonary nodules and
mass lesions: a meta-analysis. JAMA 2001; 285:914.
62. Vansteenkiste JF, Stroobants SS. PET scan in lung cancer:
current recommendations and innovation. JThorac Oncol 2006;
1:71.
63. Naidich DP, Bankier AA, MacMahon H, et al. Recommendations
for the management of subsolid pulmonarynodules detected at CT: a
statement from the Fleischner Society. Radiology 2013; 266:304.
64. Casali C, Cucca M, Rossi G, et al. The variation of
prognostic significance of Maximum Standardized UptakeValue of
[18F]-fluoro-2-deoxy-glucose positron emission tomography in
different histological subtypes andpathological stages of
surgically resected Non-Small Cell Lung Carcinoma. Lung Cancer
2010; 69:187.
65. Divisi D, Di Tommaso S, Di Leonardo G, et al. 18-fluorine
fluorodeoxyglucose positron emission tomographywith computerized
tomography versus computerized tomography alone for the management
of solitary lungnodules with diameters inferior to 1.5 cm. Thorac
Cardiovasc Surg 2010; 58:422.
66. Herder GJ, Golding RP, Hoekstra OS, et al. The performance
of( 18)F-fluorodeoxyglucose positron emissiontomography in small
solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004;
31:1231.
67. Nomori H, Watanabe K, Ohtsuka T, et al. Fluorine 18-tagged
fluorodeoxyglucose positron emissiontomographic scanning to predict
lymph node metastasis, invasiveness, or both, in clinical T1 N0 M0
lungadenocarcinoma. J Thorac Cardiovasc Surg 2004; 128:396.
68. Nomori H, Watanabe K, Ohtsuka T, et al. Evaluation of F-18
fluorodeoxyglucose (FDG) PET scanning forpulmonary nodules less
than 3 cm in diameter, with special reference to the CT images.
Lung Cancer 2004;45:19.
69. Chun EJ, Lee HJ, Kang WJ, et al. Differentiation between
malignancy and inflammation in pulmonary ground-glass nodules: The
feasibility of integrated (18)F-FDG PET/CT. Lung Cancer 2009;
65:180.
70. Raz DJ, Odisho AY, Franc BL, Jablons DM. Tumor
fluoro-2-deoxy-D-glucose avidity on positron emissiontomographic
scan predicts mortality in patients with early-stage pure and mixed
bronchioloalveolarcarcinoma. J Thorac Cardiovasc Surg 2006;
132:1189.
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
18/21
71. Heyneman LE, Patz EF. PET imaging in patients with
bronchioloalveolar cell carcinoma. Lung Cancer 2002;38:261.
72. Yap CS, Schiepers C, Fishbein MC, et al. FDG-PET imaging in
lung cancer: how sensitive is it forbronchioloalveolar carcinoma?
Eur J Nucl Med Mol Imaging 2002; 29:1166.
73. Maeda R, Isowa N, Onuma H, et al. The maximum standardized
uptake values on positron emissiontomography to predict the Noguchi
classification and invasiveness in clinical stage IA
adenocarcinomameasuring 2 cm or less in size. Interact Cardiovasc
Thorac Surg 2009; 9:70.
74. Okada M, Tauchi S, Iwanaga K, et al. Associations among
bronchioloalveolar carcinoma components,positron emission
tomographic and computed tomographic findings, and malignant
behavior in small lungadenocarcinomas. J Thorac Cardiovasc Surg
2007; 133:1448.
75. Sim YT, Goh YG, Dempsey MF, et al. PET-CT evaluation of
solitary pulmonary nodules: correlation withmaximum standardized
uptake value and pathology. Lung 2013; 191:625.
76. Fletcher JW, Kymes SM, Gould M, et al. A comparison of the
diagnostic accuracy of 18F-FDG PET and CTin the characterization of
solitary pulmonary nodules. J Nucl Med 2008; 49:179.
77. Nair VS, Barnett PG, Ananth L, et al. PET scan
18F-fluorodeoxyglucose uptake and prognosis in patientswith
resected clinical stage IA non-small cell lung cancer. Chest 2010;
137:1150.
78. Brix G, Lechel U, Glatting G, et al. Radiation exposure of
patients undergoing whole-body dual-modality 18F-FDG PET/CT
examinations. J Nucl Med 2005; 46:608.
79. Chang CY, Tzao C, Lee SC, et al. Incremental value of
integrated FDG-PET/CT in evaluating indeterminatesolitary pulmonary
nodule for malignancy. Mol Imaging Biol 2010; 12:204.
80. Kim SK, Allen-Auerbach M, Goldin J, et al. Accuracy of
PET/CT in characterization of solitary pulmonarylesions. J Nucl Med
2007; 48:214.
81. Jeong SY, Lee KS, Shin KM, et al. Efficacy of PET/CT in the
characterization of solid or partly solid solitarypulmonary
nodules. Lung Cancer 2008; 61:186.
82. Swensen SJ, Viggiano RW, Midthun DE, et al. Lung nodule
enhancement at CT: multicenter study.Radiology 2000; 214:73.
83. Yamashita K, Matsunobe S, Tsuda T, et al. Intratumoral
necrosis of lung carcinoma: a potential diagnosticpitfall in
incremental dynamic computed tomography analysis of solitary
pulmonary nodules? J ThoracImaging 1997; 12:181.
84. Li Y, Yang ZG, Chen TW, et al. First-pass perfusion imaging
of solitary pulmonary nodules with 64-detectorrow CT: comparison of
perfusion parameters of malignant and benign lesions. Br J Radiol
2010; 83:785.
85. Swensen SJ, Silverstein MD, Edell ES, et al. Solitary
pulmonary nodules: clinical prediction model versusphysicians. Mayo
Clin Proc 1999; 74:319.
86. Balekian AA, Silvestri GA, Simkovich SM, et al. Accuracy of
clinicians and models for estimating theprobability that a
pulmonary nodule is malignant. Ann Am Thorac Soc 2013; 10:629.
87. Gurney JW, Lyddon DM, McKay JA. Determining the likelihood
of malignancy in solitary pulmonary noduleswith Bayesian analysis.
Part II. Application. Radiology 1993; 186:415.
88. Herder GJ, van Tinteren H, Golding RP, et al. Clinical
prediction model to characterize pulmonary nodules:validation and
added value of 18F-fluorodeoxyglucose positron emission tomography.
Chest 2005; 128:2490.
89. Isbell JM, Deppen S, Putnam JB Jr, et al. Existing general
population models inaccurately predict lungcancer risk in patients
referred for surgical evaluation. Ann Thorac Surg 2011; 91:227.
90. Schultz EM, Sanders GD, Trotter PR, et al. Validation of two
models to estimate the probability ofmalignancy in patients with
solitary pulmonary nodules. Thorax 2008; 63:335.
91. Patz EF Jr, Campa MJ, Gottlin EB, et al. Biomarkers to help
guide management of patients with pulmonarynodules. Am J Respir
Crit Care Med 2013; 188:461.
92. Ko JP, Berman EJ, Kaur M, et al. Pulmonary Nodules: growth
rate assessment in patients by using serial CTand three-dimensional
volumetry. Radiology 2012; 262:662.
93. Wiener RS, Gould MK, Slatore CG, et al. Resource use and
guideline concordance in evaluation of
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
19/21
pulmonary nodules for cancer: too much and too little care. JAMA
Intern Med 2014; 174:871.
94. Mountain CF. A new international staging system for lung
cancer. Chest 1986; 89:225S.
95. Naruke T, Goya T, Tsuchiya R, Suemasu K. Prognosis and
survival in resected lung carcinoma based on thenew international
staging system. J Thorac Cardiovasc Surg 1988; 96:440.
96. Gail MH, Eagan RT, Feld R, et al. Prognostic factors in
patients with resected stage I non-small cell lungcancer. A report
from the Lung Cancer Study Group. Cancer 1984; 54:1802.
97. Cummings SR, Lillington GA, Richard RJ. Managing solitary
pulmonary nodules. The choice of strategy is a"close call". Am Rev
Respir Dis 1986; 134:453.
98. Wiener RS, Gould MK, Woloshin S, et al. What do you mean, a
spot?: A qualitative analysis of patients'reactions to discussions
with their physicians about pulmonary nodules. Chest 2013;
143:672.
99. Kaplan SH, Gandek B, Greenfield S, et al. Patient and visit
characteristics related to physicians' participatorydecision-making
style. Results from the Medical Outcomes Study. Med Care 1995;
33:1176.
100. Berghmans T, Dusart M, Paesmans M, et al. Primary tumor
standardized uptake value (SUVmax) measuredon fluorodeoxyglucose
positron emission tomography (FDG-PET) is of prognostic value for
survival in non-small cell lung cancer (NSCLC): a systematic review
and meta-analysis (MA) by the European Lung CancerWorking Party for
the IASLC Lung Cancer Staging Project. J Thorac Oncol 2008;
3:6.
101. Cheran SK, Nielsen ND, Patz EF Jr. False-negative findings
for primary lung tumors on FDG positronemission tomography: staging
and prognostic implications. AJR Am J Roentgenol 2004;
182:1129.
102. Marom EM, Sarvis S, Herndon JE 2nd, Patz EF Jr. T1 lung
cancers: sensitivity of diagnosis withfluorodeoxyglucose PET.
Radiology 2002; 223:453.
103. Zhao YR, Heuvelmans MA, Dorrius MD, et al. Features of
resolving and nonresolving indeterminate pulmonarynodules at
follow-up CT: the NELSON study. Radiology 2014; 270:872.
104. Swensen SJ. CT screening for lung cancer. AJR Am J
Roentgenol 2002; 179:833.
105. Kunitoh H, Eguchi K, Yamada K, et al. Intrapulmonary
sublesions detected before surgery in patients withlung cancer.
Cancer 1992; 70:1876.
106. Keogan MT, Tung KT, Kaplan DK, et al. The significance of
pulmonary nodules detected on CT staging forlung cancer. Clin
Radiol 1993; 48:94.
107. Henschke CI, McCauley DI, Yankelevitz DF, et al. Early Lung
Cancer Action Project: overall design andfindings from baseline
screening. Lancet 1999; 354:99.
108. Henschke CI, Naidich DP, Yankelevitz DF, et al. Early lung
cancer action project: initial findings on repeatscreenings. Cancer
2001; 92:153.
109. Swensen SJ, Jett JR, Hartman TE, et al. CT screening for
lung cancer: five-year prospective experience.Radiology 2005;
235:259.
110. Herth F, Becker HD, Ernst A. Conventional vs endobronchial
ultrasound-guided transbronchial needleaspiration: a randomized
trial. Chest 2004; 125:322.
111. Paone G, Nicastri E, Lucantoni G, et al. Endobronchial
ultrasound-driven biopsy in the diagnosis of peripherallung
lesions. Chest 2005; 128:3551.
112. Steinfort DP, Khor YH, Manser RL, Irving LB. Radial probe
endobronchial ultrasound for the diagnosis ofperipheral lung
cancer: systematic review and meta-analysis. Eur Respir J 2011;
37:902.
113. Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis
of lung cancer: Diagnosis and management oflung cancer, 3rd ed:
American College of Chest Physicians evidence-based clinical
practice guidelines.Chest 2013; 143:e142S.
114. Travis WD, Brambilla E, Noguchi M, et al. International
association for the study of lung cancer/americanthoracic
society/european respiratory society international
multidisciplinary classification of lungadenocarcinoma. J Thorac
Oncol 2011; 6:244.
115. Nakajima T, Yasufuku K, Takahashi R, et al. Comparison of
21-gauge and 22-gauge aspiration needle duringendobronchial
ultrasound-guided transbronchial needle aspiration. Respirology
2011; 16:90.
116. Loukeris K, Vazquez MF, Sica G, et al. Cytological cell
blocks: Predictors of squamous cell carcinoma and
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
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adenocarcinoma subtypes. Diagn Cytopathol 2012; 40:380.
117. Ost DE, Ernst A, Lei X, et al. Diagnostic yield of
endobronchial ultrasound-guided transbronchial needleaspiration:
results of the AQuIRE Bronchoscopy Registry. Chest 2011;
140:1557.
118. Oki M, Saka H, Kitagawa C, et al. Randomized Study of
21-gauge Versus 22-gauge EndobronchialUltrasound-guided
Transbronchial Needle Aspiration Needles for Sampling Histology
Specimens. JBronchology Interv Pulmonol 2011; 18:306.
119. Yarmus LB, Akulian J, Lechtzin N, et al. Comparison of
21-gauge and 22-gauge aspiration needle inendobronchial
ultrasound-guided transbronchial needle aspiration: results of the
American College of ChestPhysicians Quality Improvement Registry,
Education, and Evaluation Registry. Chest 2013; 143:1036.
120. Rivera MP, Mehta AC, American College of Chest Physicians.
Initial diagnosis of lung cancer: ACCPevidence-based clinical
practice guidelines (2nd edition). Chest 2007; 132:131S.
121. Loubeyre P, Copercini M, Dietrich PY. Percutaneous
CT-guided multisampling core needle biopsy of thoraciclesions. AJR
Am J Roentgenol 2005; 185:1294.
122. Choi SH, Chae EJ, Kim JE, et al. Percutaneous CT-guided
aspiration and core biopsy of pulmonary nodulessmaller than 1 cm:
analysis of outcomes of 305 procedures from a tertiary referral
center. AJR Am JRoentgenol 2013; 201:964.
123. Lee SM, Park CM, Lee KH, et al. C-arm cone-beam CT-guided
percutaneous transthoracic needle biopsy oflung nodules: clinical
experience in 1108 patients. Radiology 2014; 271:291.
124. Takeshita J, Masago K, Kato R, et al. CT-guided fine-needle
aspiration and core needle biopsies ofpulmonary lesions: a
single-center experience with 750 biopsies in Japan. AJR Am J
Roentgenol 2015;204:29.
125. Larscheid RC, Thorpe PE, Scott WJ. Percutaneous
transthoracic needle aspiration biopsy: a comprehensivereview of
its current role in the diagnosis and treatment of lung tumors.
Chest 1998; 114:704.
126. Kothary N, Lock L, Sze DY, Hofmann LV. Computed
tomography-guided percutaneous needle biopsy ofpulmonary nodules:
impact of nodule size on diagnostic accuracy. Clin Lung Cancer
2009; 10:360.
127. Ng YL, Patsios D, Roberts H, et al. CT-guided percutaneous
fine-needle aspiration biopsy of pulmonarynodules measuring 10 mm
or less. Clin Radiol 2008; 63:272.
128. Schreiber G, McCrory DC. Performance characteristics of
different modalities for diagnosis of suspected lungcancer: summary
of published evidence. Chest 2003; 123:115S.
129. Santambrogio L, Nosotti M, Bellaviti N, et al. CT-guided
fine-needle aspiration cytology of solitary pulmonarynodules: a
prospective, randomized study of immediate cytologic evaluation.
Chest 1997; 112:423.
130. Wiener RS, Schwartz LM, Woloshin S, Welch HG.
Population-based risk for complications aftertransthoracic needle
lung biopsy of a pulmonary nodule: an analysis of discharge
records. Ann Intern Med2011; 155:137.
131. Song YS, Park CM, Park KW, et al. Does antiplatelet therapy
increase the risk of hemoptysis duringpercutaneous transthoracic
needle biopsy of a pulmonary lesion? AJR Am J Roentgenol 2013;
200:1014.
132. Zwischenberger JB, Savage C, Alpard SK, et al. Mediastinal
transthoracic needle and core lymph nodebiopsy: should it replace
mediastinoscopy? Chest 2002; 121:1165.
133. Allen MS, Deschamps C, Lee RE, et al. Video-assisted
thoracoscopic stapled wedge excision forindeterminate pulmonary
nodules. J Thorac Cardiovasc Surg 1993; 106:1048.
134. Bernard A. Resection of pulmonary nodules using
video-assisted thoracic surgery. The Thorax Group. AnnThorac Surg
1996; 61:202.
135. Shennib H. Intraoperative localization techniques for
pulmonary nodules. Ann Thorac Surg 1993; 56:745.
136. Zaman M, Bilal H, Woo CY, Tang A. In patients undergoing
video-assisted thoracoscopic surgery excision,what is the best way
to locate a subcentimetre solitary pulmonary nodule in order to
achieve successfulexcision? Interact Cardiovasc Thorac Surg 2012;
15:266.
137. Marchevsky AM, Changsri C, Gupta I, et al. Frozen section
diagnoses of small pulmonary nodules: accuracyand clinical
implications. Ann Thorac Surg 2004; 78:1755.
138. Jennings SG, Winer-Muram HT, Tann M, et al. Distribution of
stage I lung cancer growth rates determined
-
06-04-2015 Diagnostic evaluation and management of the solitary
pulmonary nodule
http://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
21/21
with serial volumetric CT measurements. Radiology 2006;
241:554.
139. Revel MP, Bissery A, Bienvenu M, et al. Are two-dimensional
CT measurements of small noncalcifiedpulmonary nodules reliable?
Radiology 2004; 231:453.
140. Winer-Muram HT, Jennings SG, Meyer CA, et al. Effect of
varying CT section width on volumetricmeasurement of lung tumors
and application of compensatory equations. Radiology 2003;
229:184.
141. Mayo JR, Aldrich J, Muller NL, Fleischner Society.
Radiation exposure at chest CT: a statement of theFleischner
Society. Radiology 2003; 228:15.
142. Rusinek H, Naidich DP, McGuinness G, et al. Pulmonary
nodule detection: low-dose versus conventional CT.Radiology 1998;
209:243.
143. Diederich S, Lenzen H. Radiation exposure associated with
imaging of the chest: comparison of differentradiographic and
computed tomography techniques. Cancer 2000; 89:2457.
144. Revel MP, Merlin A, Peyrard S, et al. Software volumetric
evaluation of doubling times for differentiatingbenign versus
malignant pulmonary nodules. AJR Am J Roentgenol 2006; 187:135.
145. de Hoop B, Gietema H, van de Vorst S, et al. Pulmonary
ground-glass nodules: increase in mass as an earlyindicator of
growth. Radiology 2010; 255:199.
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