Diagnostic Evaluation and Management of The Solitary Pulmonary Nodule

06-04-2015
Diagnostic evaluation and management of the solitary pulmonary nodule
Official reprint from UpToDate

www.uptodate.com 2015 UpToDate

Author
Steven E Weinberger, MD
Section Editors
Nestor L Muller, MD, PhD
Talmadge E King, Jr, MD
James R Jett, MD
Deputy Editor
Geraldine Finlay, MD
Disclosures: Steven E Weinberger, MD Nothing to disclose. Nestor L Muller, MD, PhD Nothing to disclose. Talm adge E King,
Jr, MD Consultant/Advisory Boards: InterMune [pulmonary fibrosis (pirfenidone)]; ImmuneWorks [pulmonary fibrosis]; Boehringer
Ingelheim [IPF (nintedanib)]; GlaxoSmithKline [pulmonary fibrosis]; Daiichi Sankyo [pulmonary fibrosis]. Jam es R Jett, MD
Grant/Research/Clinical Trial Support: Oncimmune Inc [Biomarkers of cancer (Early CDT lung)]. Geraldine Finlay, MD Nothing to
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 <10 mm) on a single scan that are often small and nonspecific (<4 mm). In this setting, a
SPN can refer to one dominant nodule among many when a single lesion is larger than others, appears to have
malignant characteristics (eg, spiculated), or is growing. (See "Differential diagnosis and evaluation of multiple
pulmonary nodules".)
DIFFERENTIAL DIAGNOSIS The causes of a solitary pulmonary nodule (SPN) can be categorized as benign or
malignant (table 1). The estimated frequency of each etiology varies substantially among studies, reflecting
differences in the population studied and the methodology used to establish a diagnosis [5-11]. Nonetheless,
screening studies of smokers who are at high risk of malignancy suggest that the vast majority of nodules identified
on computed tomography (CT) are benign. As an example, in the Pan-Canadian Early Detection of Lung Cancer
and the British Columbia Cancer Agency studies, among the 12,029 nodules found, only 144 (1 percent) were
malignant [12].
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Malignant etiologies Common causes of a malignant SPN include primary lung cancer, lung metastases, and
carcinoid tumors.
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".)
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).
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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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.
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].
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 years (65
versus 33 percent) [6]. Another study stratified the percentage of nodules that were malignant according to
age [8]:
35 to 39 years: 3 percent
40 to 49 years: 15 percent
50 to 59: 43 percent
60 years: >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".)
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)'.)
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 <5 mm: <1 percent
Nodules 5 to 9 mm: 2 to 6 percent
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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 (<20 days) or is stable for a prolonged 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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(813 days), ground glass with a solid component (457 days), and solid (149 days) [52]. Thus, purely subsolid
lesions may be less readily detected as actively growing by CT scan, and follow-up for three years,
occasionally longer, to determine stability is probably warranted in that population.
Border The risk of malignancy is lower in SPNs with smooth borders (20 percent) and higher in those with
irregular borders: scalloped (60 percent), spiculated (90 percent) (image 11), corona radiata (95 percent)
(image 12) [21,53,54].
Calcification Asymmetric calcification, also known as "eccentric" calcification (image 13), should raise
concern for malignancy, particularly for carcinoma arising in an old granulomatous lesion (ie, a "scar"
carcinoma) (image 14). In contrast, popcorn (image 5), laminated (concentric), central (image 15 and image
16), and diffuse/homogeneous (image 17) patterns of calcification may suggest that a SPN is benign.
Although specific patterns of calcification are associated with benign or malignant etiologies, none are
diagnostic.
Location Although malignant nodules can be found in any lobe of the lung, those that are located in the
upper lobe have an increased probability of being malignant [12,24]. In one study of over 7000 nodules, among
the 102 that were subsequently found to be malignant, almost two-thirds were located in the upper lobes [12].
In addition, among the 77 perifissural nodules observed on CT, none were reported as malignant [12].
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:
Intermediate probability (5 to 65 percent) solid SPN >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 [5562].
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 (<5 percent) solid SPN and subsolid SPNs Although true positive PET scans can occur in
patients with solid nodules 8 mm and subsolid nodules, the high false-negative rate and low sensitivity in this
population (47 to 89 percent) do not support its routine use [2,63-74]. The lack of sensitivity partially relates to
the limited resolution of PET for the detection of small nodules and the poor uptake of fluorodeoxyglucose
(FDG) by tumors such as carcinoid, or tumors likely to present as a subsolid nodule (eg, lepidic or minimally
invasive adenocarcinoma) [64,73,74]. Although of unproven value, PET is often performed for the evaluation of
larger, persistent, part-solid SPNs (>10 to 15 mm), which are considered to have greater malignant potential
compared with smaller, purely subsolid nodules.
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, <2.5) can be malignant [75]. One prospective study of 344 patients demonstrated a
graded range of probability for the risk of malignancy based upon FDG-avidity, such that tumors with low SUV were
less likely to be malignant than those with high SUV [76]. However, in most studies that examine sensitivity, a
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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:
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].
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]:
Low probability (<5 percent)
Intermediate probability (5 to 65 percent)
High probability (>65 percent)
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]:
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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(calculator 1). Additional tools are available on the following site:

http://www.brocku.ca/cancerpredictionresearch.
Unlike other models, this model considers nodule attenuation (solid, subsolid, part-solid) as a variable that
can affect the risk of malignancy [12]. The increased incidence of adenocarcinoma, which is more likely to
present as a subsolid and part-solid nodule, gives this model a distinct advantage over the others. However,
this model only estimated the probability of malignancy in a population at high risk for lung cancer (current or
ex-smokers). It is not validated, and therefore could potentially overestimate the probability of cancer in low
risk populations (eg, nonsmokers).
Another clinical predictive model (Veterans Administration Cooperative) was derived using data from CT
and/or PET in 375 veterans (current or former smokers) with SPNs measuring 7 to 30 mm [25]. Independent
predictors of malignant SPNs included the following: smoking history (odds ratio [OR] 7.9), older age (OR 2.2
per 10-year increment), larger nodule diameter (OR 1.1 per 1 mm increment), and time since quitting smoking
(OR 0.6 per 10-year increment). This model showed excellent agreement between the predicted probability
and the observed frequency of malignant SPNs. While this model may be useful in high risk populations, it
has not been validated in a nonsmoking/low risk population.
Two additional older models derived data mostly from chest radiographic findings to estimate the probability of
malignancy in a SPN:
One model (Mayo Clinic model) identified six independent predictors of malignancy: older age, smoking
history, history of cancer, nodule diameter, spiculation, and upper lobe location [24]. The prediction for
malignancy is calculated using the equation in the table (table 2). The addition of nodule volume to the
equation may increase the proportion of nodules correctly identified as malignant [36].
Another model used likelihood ratios (LRs) to estimate the probability that a nodule is malignant [37].
LRs are first determined for a number of factors including nodule size, patient age, smoking history, and
overall prevalence of malignancy in the population (table 3 and table 4) [37,87]. The odds of malignancy
are then calculated by multiplying the LRs (figure 1). Finally, the probability of malignancy is calculated
from the odds of malignancy (figure 1).
These older models are likely to accurately reflect the estimated risk of malignancy in the general population.
However, they are based upon estimates from chest radiographic findings (not CT) and do not include nodule
attenuation as a variable.
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 (<1 percent) and therefore prefer a more aggressive
surgical approach [49,94-96]. However, we and others agree with the initial management strategy outlined below
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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]:
The probability of malignancy (low [<5 percent], intermediate [5 to 65 percent] or high [>65 percent]) (see
'Assessing the risk of malignancy' above)
Nodule characteristics (eg, size, attenuation, stability)
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):
A nodule that has a low probability (<5 percent) of being malignant can be followed with serial CT scans. CT
scans should be performed at 3 to 6, 9 to 12, and 18 to 24 months if the nodule remains unchanged. (See 'CT
surveillance' below and 'Assessing the risk of malignancy' above.)
A nodule that has an intermediate probability (5 to 65 percent) of being malignant should be evaluated by
positron emission tomography (PET).
Nodules that are positive on PET should be biopsied or excised. (See 'Nonsurgical biopsy' below and
'Surgical biopsy' below.)
If PET is unavailable, negative, or indeterminate (eg, low standardized uptake value [SUV <2.5]), the
optimal diagnostic strategy is unknown. In this setting, management should be individualized for each
case with a strong reliance upon clinical suspicion for malignancy and a low threshold for biopsy [2].
For example, in patients with a negative PET in whom the suspicion for malignancy is relatively high (eg,
65 percent), a short period of CT surveillance with a low threshold to biopsy may be justified. This
justification is based upon the observation that in patients with early stage lung cancer, the degree of
fluorodeoxyglucose (FDG) uptake on PET correlates with survival [77,100-102]. In this population, the
prognosis may still be favorable even when therapy is delayed by a period as long as eight months
[77,100-102]. In contrast, if PET is unavailable and the clinical suspicion for malignancy is relatively high
(eg, 65 percent), then biopsy may be preferred. (See 'CT surveillance' below and 'Nonsurgical biopsy'
below and 'Surgical biopsy' below.)
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A nodule that has a high probability (>65 percent) of being malignant is preferably excised. Although PET
scan is not necessary in this setting for characterization of the SPN, it may be indicated as a staging
modality for suspected lung cancer. (See 'Nonsurgical biopsy' below and "Overview of the initial evaluation,
diagnosis, and staging of patients with suspected lung cancer", section on 'Radiographic staging'.)
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 <5 mm, no nodules grew over a 3 to 24 month follow-up period [35]. In
contrast, another study reported growth in 11 percent of SPNs during a 24-month period when risk factors for
malignancy or extrathoracic malignancies were present [34]. These studies provide the basis for more aggressive
CT surveillance strategies in patients at risk for lung cancer compared with those at low risk. Thus, the frequency
with which CT scans should be performed is determined by the patient's risk for lung cancer as well as by the size
of the SPN (table 5) [2,63]. (See 'CT surveillance' below.)
For nodules 4 mm, serial CT scans are not required if the patient is clinically low risk. Patients who are high
risk should have a CT scan performed at 12 months with no further follow-up if the nodule is unchanged.
For nodules 4 to 6 mm, a CT scan should be performed at 12 months if the patient is clinically low risk, at 6
to 12 months and at 18 to 24 months if the patient is clinically high risk, with no further follow-up if the nodule
is unchanged.
For nodules 6 to 8 mm, a CT scan should be performed at 6 to 12 months and at 18 to 24 months if the
nodule is unchanged and the patient is clinically low risk. Patients who are clinically high risk should have a
CT scan performed at 3 to 6 months, 9 to 12 months, and 24 months if the nodule remains unchanged.
Pure subsolid nodules Most pure subsolid (also known as ground glass) SPNs are subjected to
continued surveillance by serial CT scan (table 6). The rationale for this strategy is that many SPNs in this category
will resolve spontaneously [103]. However, some will grow or develop a solid component (ie, changes that are
worrisome for malignancy) and should prompt biopsy or excision. Our approach to pure subsolid nodules is
determined by size:
A purely subsolid nodule 5 mm does not require any further CT follow-up.
A purely subsolid nodule >5 mm should be reevaluated with a single CT scan at three months. The approach
to patients with a persistent nodule at three months is determined by the size and/or the emergence of a solid
component:
A persistent nodule that is 5 to 10 mm in diameter should be followed by serial CT scans at 12, 24,
and 36 months. If the nodule has not increased in size after 36 months of observation, the need for
further CT monitoring is determined on a case-by-case basis. (See 'CT surveillance' below.)
A persistent nodule that has a newly developed solid component or is >10 to 15 mm in diameter should
prompt consideration for an evaluation for biopsy and/or resection. The resection of pure subsolid lesions
10 to 15 mm is controversial. Many clinicians prefer to await until the SPN is at least 15 to 20 mm. (See
'Nonsurgical biopsy' below and 'Surgical biopsy' below.)
Part-solid nodules Compared with pure subsolid nodules, those with a part-solid component have a
greater likelihood of being malignant. For patients with part-solid SPNs, we agree with the Fleischner Society and
the American College of Chest Physicians (ACCP) that CT scan surveillance at least once at three months should
be performed (table 6).
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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:
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.)
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 followup, 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), bronchoscopictransbronchial needle aspiration (bronchoscopic-TBNA), endobronchial ultrasound-guided sheath transbronchial
biopsy (EBUS-guided sheath TBBx), and endobronchial ultrasound-guided transbronchial needle aspiration (EBUSTBNA). 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, EBUShttp://www.uptodate.com/contents/diagnostic-evaluation-and-management-of-the-solitary-pulmonary-nodule?source=search_result&search=nodulo+pulmonar
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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 a diagnostic sensitivity of 73 to 85 percent for large, centrally-located lesions, which
declines for nodules <2 cm (71 percent), particularly those that are peripherally located (56 percent) [110112]. However, these studies are extrapolated from studies of patients with lung cancer and also included
patients with visible airway lesions (ie, not a true solitary pulmonary nodule [SPN]). The indications and
complications of EBUS and its value in the diagnosis of suspected non-small cell lung cancer are discussed
separately. (See "Endobronchial ultrasound: Indications, advantages, and complications" and "Endobronchial
ultrasound: Technical aspects" and "Procedures for tissue biopsy in patients with suspected non-small cell
lung cancer", section on 'Endobronchial ultrasound' and "Transbronchial needle aspiration", section on
'Peripheral nodules or masses'.)
Conventional bronchoscopic TBB or TBNA has a reported sensitivity for the diagnosis of lung cancer that
ranges from 65 to 88 percent, with the highest sensitivity for large, central lesions and lower rates for
peripheral nodules (>2 cm: 63 percent; <2 cm: 34 percent) [113]. Although the less invasive methods of
obtaining tissue (washing, lavage, or brush) can occasionally be diagnostic of malignancy, they are unlikely to
obtain enough material for immunohistochemical or genetic analysis for a benign diagnosis. The indications
and complications of conventional bronchoscopy and its value in the diagnosis of suspected non-small cell
lung cancer are discussed separately. (See "Flexible bronchoscopy: Indications and contraindications" and
"Flexible bronchoscopy: Equipment, procedure, and complications" and "Procedures for tissue biopsy in
patients with suspected non-small cell lung cancer", section on 'Conventional bronchoscopy'.)
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 (<3 cm), ranging from 67 to 82 percent [79,125-127]. Common to all needle techniques, the
diagnostic yield is higher when an on-site cytologist reviews the specimen [128,129]. However, the high falsenegative rates indicate that a negative result is of limited value in excluding malignancy. (See "Procedures for tissue
biopsy in patients with suspected non-small cell lung cancer", section on 'Transthoracic needle biopsy'.)
Needle (core) biopsy techniques are preferred to needle aspiration for both benign and malignant diagnoses
[50,120,122]. This preference is based upon the need for histologic architecture for benign diagnoses and the
observation that although a diagnosis of malignancy can be made on cellular material, larger biopsy samples are
often needed for additional immunohistochemical and mutational analysis.
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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.
Retrospective studies report pneumothorax rates of 10 to 17 percent with higher rates (60 percent) reported
when the visceral pleura is traversed [123,124,130,132]. However, for patients with TTNB-associated
pneumothorax, catheter drainage (ie, chest tube insertion) is only required in approximately half of these
cases, which increases the length of hospital stay and risk for respiratory failure or mechanical ventilation
[130].
The overall incidence of hemorrhage was reported in retrospective analyses as 1 to 7 percent, of which 18
percent required red blood cell transfusion [123,130]. Higher rates of hemorrhage may occur in patients on
antiplatelet therapy [131]. In a retrospective study of 1346 TTNBs, dual antiplatelet therapy (aspirin plus
clopidogrel) was an independent risk factor for hemorrhage (odds ratio [OR] 10.09), along with use of cutting
needles (OR 3.22), small ground glass lesions (OR 1.94), and deeply located lesions (OR 1.17). However, use
of single antiplatelet therapy (aspirin or clopidogrel) that was discontinued before the procedure (mean
discontinuation time 2.6 +/- 2.3 days) was not a risk factor for hemorrhage.
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 <1.1 cm and for specific
pathologies, including low grade or pre-cancerous adenocarcinoma (eg, minimally invasive adenocarcinoma,
adenocarcinoma in situ, atypical adenomatous hyperplasia) and carcinoid [137]. Thus, when frozen section is
initially unrevealing for cancer and subsequently found by routine histology to be definitive for NSCLC, a second
surgery (completion lobectomy) may be required for treatment. (See "Management of stage I and stage II non-small
cell lung cancer".)
VATS is safe in experienced hands and can be performed as a day or short stay (three to five days) procedure at
many centers. In every case for whom surgery is indicated, candidacy for surgery (wedge resection and/or
lobectomy) should be assessed where the benefits of diagnosis and/or therapy are weighed against the associated
risk. (See "Evaluation of preoperative pulmonary risk" and "Preoperative evaluation for lung resection" and "Overview
of video assisted thoracoscopic surgery (VATS)".)
CT surveillance Changes in nodule size and characteristics are more readily detected by computed
tomography than chest radiography. CT imaging of solitary pulmonary nodules 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. CT
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surveillance is most often performed in those at low risk for malignancy (eg, solid nodules <8 mm). In addition, CT
surveillance may be preferred in patients at intermediate or high risk of malignancy who are at high risk of surgical
complications, have poor prognosis from comorbid conditions, or have a strong, well-informed preference for no
procedural intervention. (See 'Selection of strategy' above.)
Typically, differences in size are measured manually by changes in the maximum cross-sectional diameter of the
SPN. Limitations of this method include poor accuracy for small nodules <5 mm and poor inter- and intra-observer
agreement for differences in diameter in nodules <1.5 mm [138-143]. In addition, all methods of growth assessment
have false-positive and false-negative rates. For example, when using thin-slice CT with 1 mm sections, small
changes within 1 mm should be interpreted with caution. To overcome these errors, some institutions use methods
that measure the three-dimensional volume of SPNs. Although volumetric assessment holds promise for the
evaluation of nodule growth over time, further validation of this method will be needed before it is routinely used to
assess nodule growth [36,138,144,145].
One of the caveats of CT surveillance is that during follow-up, approximately 10 percent of patients develop new
nodules over a one-year period [29,104]. Each nodule should be individually assessed when they arise, frequently
necessitating further additional surveillance and radiation exposure. (See 'Multiple nodules' above.)
Informing the patient of the benefits and risks of CT surveillance is important when choosing this strategy. The
purpose of surveillance is the avoidance of unnecessary invasive procedures in patients with a benign nodule for
which no therapy is indicated. This benefit is weighed against the risk of a delayed or missed diagnosis of cancer
and excessive radiation. (See 'Values and preferences' above.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and
Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given condition. These
articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the
Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the
10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with
some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these
topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on
patient info and the keyword(s) of interest.)
Basics topic (see "Patient information: Single pulmonary nodule (The Basics)")
SUMMARY AND RECOMMENDATIONS
A solitary pulmonary nodule (SPN) is a lesion that is surrounded by pulmonary parenchyma. It is typically 30
mm and not associated with additional radiographic features such as hilar adenopathy, atelectasis, or pleural
effusion. (See 'Definitions' above.)
The majority of SPNs, particularly those found on screening or incidentally, are benign. Infectious granulomas
and hamartomas are the most common causes of a benign SPN. The most common causes of a malignant
SPN are primary lung cancer, lung metastases, and carcinoid tumors. (See 'Differential diagnosis' above.)
For every patient with a SPN we recommend a noncontrast, thin slice (1 mm) computed tomography (CT) of
the chest for the optimal evaluation of nodule characteristics. When available, old imaging studies, chest
radiograph and/or CT, should be reviewed to determine stability or growth. (See 'Imaging' above.)
Clinical features, radiographic features (CT with or without functional imaging), and occasionally quantitative
models are used to determine the likelihood of malignancy. The risk of malignancy is assessed as high (>65
percent), intermediate (5 to 65 percent), or low (<5 percent). (See 'Initial evaluation' above.)
For patients with solid and subsolid SPNs that have clear evidence of growth on serial imaging studies, we
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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 (<5 percent) of being malignant can be followed with non enhanced serial CT scans rather than
biopsy. A nodule that has an intermediate probability (5 to 65 percent) of being malignant should be evaluated
with positron emission tomography (PET); nodules that are positive on PET should be biopsied or excised. A
nodule that has a high 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.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

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Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

(calculator 1). Additional tools are available on the following site:

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

pulmonary nodules. Respirology 2007; 12:856.

Diagnostic evaluation and management of the solitary pulmonary nodule

Thorac Cardiovasc Surg 1981; 82:70.

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

Diagnostic evaluation and management of the solitary pulmonary nodule

adenocarcinoma subtypes. Diagn Cytopathol 2012; 40:380.

Diagnostic evaluation and management of the solitary pulmonary nodule

with serial volumetric CT measurements. Radiology 2006; 241:554.

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