Acs0405 Solitary Pulmonary Nodule

© 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice
4 THORAX 5 SOLITARY PULMONARY NODULE — 1

5 SOLITARY PULMONARY NODULE
Shamus R. Carr, M.D., and Taine T.V Pechet, M.D., F.A.C.S.
.

Assessment of a Solitary Pulmonary Nodule

The solitary pulmonary cative of severe obstructive ventilatory impairment are also associ-
nodule (SPN) is a common ated with an increased likelihood of malignancy.11 In addition, the
finding that is observed in SPNa is < 1.0 cm

presence of endemic granulomatous disease has been shown to
more than 150,000 persons increase the probability that an SPN is harboring cancer.7
each year in the United Other factors that influence the probability of malignancy in an
States.1 An SPN is defined SPN are based on the findings from CT scanning [see Investigative
as a single radiographically Studies, Imaging, Computed Tomography, below]. The size, con-
visible pulmonary lesion tour, internal characteristics, and growth rate of the nodule are all
that is less than 3 cm in potentially significant indicators of malignant disease [see Table 2].
diameter, is completely sur-
rounded by pulmonary parenchyma, and is not associated with Age
atelectasis or adenopathy.2 Any pulmonary lesion larger than 3 cm Lung cancer is rare before the age of 40 years, but its incidence
is considered a mass and as such has a greater likelihood of being steadily increases from that point until the age of 80.5 Above the
malignant.3,4 SPNs are detected on routine chest radiography at a age of 70, the likelihood that an SPN is malignant increases.8 After
rate of 1 in 500 x-rays, but with the growing use of computed to- the age of 80, the incidence of malignancy in an SPN seems to
mographic scanning, they are now being diagnosed with increas- level off or even decrease.
ing frequency.
The differential diagnosis of an SPN is broad and includes vas- Tobacco Exposure
cular diseases, infections, inflammatory conditions, congenital The link between cigarette smoking and lung cancer has been
abnormalities, benign tumors, and malignancies [see Table 1]. well established since the 1950s, and the incidence of lung cancer
Although most SPNs are benign, as many as one third represent in smokers is directly correlated with the number of pack-years of
primary malignancies, and nearly one quarter may be solitary smoking.12 The Surgeon General’s Report from 2004 states that
metastases.1,5,6 Various approaches have been developed to aid in “the evidence is sufficient to infer a causal relationship between
the characterization and identification of SPNs. Certain clinical smoking and lung cancer.”13
characteristics—such as greater age, history of tobacco use, and
previous history of cancer—have been shown to increase the like- Occupational History
lihood that the SPN is malignant.7 Some authors have attempted Patients with a history of workplace exposure to a radioactive
to use Bayes’s theorem, logistic regression models, or neural net- substance (e.g., uranium or plutonium) are at increased risk for
work analysis to predict the likelihood of malignancy.7-9 Such lung cancer, but this association is not as well documented as the
methods are highly sensitive and specific, but they are cumber- association of lung cancer with tobacco use. Miners of heavy met-
some and of limited practical use in actual clinical evaluation of a als (e.g., nickel, cadmium, and silica) are also at increased risk.
patient with an SPN. There is some evidence to suggest that patients with idiopathic
pulmonary fibrosis and pneumoconiosis are at increased risk for
bronchoalveolar cell carcinoma.14 Radon exposure is the second
Clinical Evaluation leading cause of lung cancer, and cigarette smoking further
Once an SPN has been discovered, the essential task is to deter- increases the risks associated with radon exposure.15 Asbestos
mine whether the lesion is benign or malignant. Evaluation and exposure in combination with cigarette smoking also places
workup should be governed by the dictum “malignant until patients at significantly increased risk for lung cancer.
proven otherwise.” The basis for this initial assumption of malig-
nancy is the observation that the average overall 5-year survival
rate is quite poor—10% to 15%—once a diagnosis of lung cancer Investigative Studies
is made.10 Appropriate evaluation involves careful assessment of SPNa is < 1.0 cm

IMAGING
the patient’s history and risk factors for malignancy in conjunction
with the results of radiographic studies [see Investigative Studies,
below] to develop an individualized care plan. Chest Radiography
Whereas the prevalence
FACTORS INFLUENCING PROBABILITY OF MALIGNANCY
of lung cancer is low in
Of the various factors that influence the probability that cancer comparison to that of
will be found in an SPN before radiographic evaluation, those breast or prostate cancer,
most strongly associated with lung cancer are age, smoking histo- the mortality for lung cancer exceeds that for breast, prostate, and
ry, and occupational history. Pulmonary function test results indi- colon cancer combined. As noted [see Clinical Evaluation, above],


SPN is seen on chest x-ray or CT scan

Obtain history and perform thorough physical
examination.
Assessment of a Solitary Review previous diagnostic images (if available).
Pulmonary Nodule

SPN is < 1.0SPNa is < 1.0 cmis at low risk
cm and patient SPN is 1.0–3.0 cm

Obtain follow-up CT scan at 3 mo. Assess probability of malignancy on the basis of
salient characteristics (age, smoking history, lesion
size, lesion margin).

Probability of cancer is low

Consider PET.

Risk of surgical complications is high

Consider PET, or obtain tissue diagnosis via TTNB
or bronchoscopy, as warranted by clinical situation.

SPN is unchanged SPN has grown

Consider PET scanning if
nature of lesion is indeterminate.
Otherwise, assume malignancy
and resect lesion via VATS
or thoracotomy after staging Tissue diagnosis is obtained
investigations.

Pathology is indeterminate

Consider PET, or proceed to metastatic evaluation,
as warranted by clinical situation.

PET scan is obtained PET scan is not obtained

PET scan is negative PET scan is positive and
lesion is suspicious

Obtain follow-up CT scans at 3-, 6-, or 12-month intervals.

SPN has remained unchanged for > 2 yr SPN has grown

Lesion is probably benign; treat appropriately. Consider PET scanning if nature of lesion is indeterminate. Otherwise,
assume malignancy and resect lesion via VATS or thoracotomy
after staging investigations.


SPN has arisen or grown since previous images, SPN has remained unchanged for > 2 yr
or no previous images are available for review
Lesion is probably benign; treat appropriately.
Obtain CT scan.

SPN is > 3.0 cm

Lesion is considered a mass and thus is more
likely to be malignant.

Probability of cancer is intermediate Probability of cancer is high

Risk of surgical complications is low

Obtain tissue diagnosis via TTNB or bronchoscopy,
or proceed to metastatic evaluation and resection,
as warranted by clinical situation.

Tissue diagnosis is not obtained

Pathology is malignant

Carry out metastatic evaluation. If results are negative,
resect lesion via VATS or thoracotomy. If results are
positive, treat appropriately.


Table 1 Differential Diagnosis of Solitary Advocates of CT scanning for assessment of SPNs base their argu-
Pulmonary Nodule ment on two central points. First, as many as 83% of CT-detect-
ed stage I malignancies are not visible on chest x-ray.22 Second,
non–small cell lung cancer (NSCLC) is the malignancy most
Arteriovenous malformations
Vascular disease Pulmonary artery aneurysm
commonly identified, and the survival rate for stage I NSCLC is
relatively high. In patients whose SPN proves to be NSCLC, the
Tuberculosis 5-year survival rate is 67% for stage IA disease. This figure falls
Mycobacterium avium complex infection rapidly as the disease stage rises: the 5-year survival rate is 55% for
Aspergilloma stage IIA NSCLC and only 10% for stage IIIA NSCLC with
Histoplasmosis
mediastinal nodal metastasis.23
Echinococcosis
Infection Blastomycosis
Numerous studies have evaluated the use of screening CT both
Cryptococcosis in the general population and in at-risk groups consisting of older
Coccidioidomycosis patients with a smoking history.22,24,25 The greatest drawback to
Ascariasis screening CT is the high false positive rate: nodules are identified
Benign
Dirofilariasis on 23% to 66% of all CT scans, depending on the thickness of the
slices,22,26 and nearly 98% of these nodules are eventually deter-
Rheumatoid nodule
Inflammatory Sarcoidosis
mined to be benign. Sequential CT scanning is often required to
condition determine whether an SPN is benign or malignant. In 10% to
Wegener granulomatosis
15% of patients, however, this determination cannot be made even
Congenital when two CT scans are compared. Such patients may be assessed
Foregut duplication cyst
abnormality
with other imaging modalities (e.g., positron emission tomogra-
Rounded atelectasis phy [PET]) or may be referred for transthoracic needle biopsy
Other
Pulmonary amyloidosis (TTNB) or other invasive diagnostic tests.
Hamartoma There is currently some controversy regarding the optimal tim-
Benign tumor Lipoma ing of follow-up CT scanning after initial identification of an SPN.
Fibroma In the literature, the recommended interval between initial CT
scanning and repeat CT scanning has ranged from 1 month to 1
Non–small cell lung cancer
year.22,25,26 These varying recommendations are based on what is
Squamous cell carcinoma
Adenocarcinoma
considered the doubling time for an SPN. In a study from 2000
Large cell cancer that included 13 patients with a known diagnosis and lesions less
Primary lung cancer Bronchoalveolar carcinoma than 10 mm in diameter at initial evaluation, volumetric growth
Small cell lung cancer rates were measured to establish the doubling times of the nod-
Malignant Carcinoid ules.10 The doubling times ranged from 51 days to more than 1
Lymphoma year. For malignant lesions, the average doubling time was less
Colon cancer
than 177 days, whereas for benign lesions, it was more than 396
Testicular cancer days.
Metastatic cancer Melanoma In addition to delineating the size and contours of an SPN, CT
Sarcoma scans provide information on its internal characteristics. Certain
Breast cancer lesion characteristics noted on CT, though not absolutely defini-
tive, point more toward a benign condition, whereas others point
more toward malignancy. For example, although cavitation may
the overall 5-year survival rate for lung cancer patients is dismal, occur in either benign or malignant lesions, SPNs with walls thick-
in part because lung cancer is typically identified at a more er than 16 mm are much more likely to be malignant, whereas
advanced stage than other cancers are. Several trials performed those with walls thinner than 4 mm are much more likely to be
before the advent of CT scanning attempted to employ chest radi- benign.27 As another example, the presence of intranodular fat is
ography for early screening of lung cancer, but they were unable a reliable indicator of a hamartoma (a benign lesion) and is seen
to demonstrate that such screening yielded any better survival in as many as 50% of hamartomas.28 In addition, calcification is
than no screening at all.16-18 One explanation for these disappoint- most commonly associated with hamartomas and other benign
ing results may be that fewer than 10% of lung cancers are stage I nodules. Unfortunately, between one third and two thirds of be-
at presentation.16 nign lesions visualized are not calcified, and as many as 6% of
Although chest radiography is ineffective as a screening tool for malignant lesions are calcified.29-31 Finally, increased enhance-
early-stage lung cancer, it remains a valuable investigative tool in ment (measured in Hounsfield units [HU]) after injection with
the evaluation of SPNs. If an SPN’s appearance on chest x-rays intravenous contrast is strongly suggestive of malignancy. Lesions
has not changed for more than 2 years, the SPN will be benign in that enhance by less than 15 HU are most likely benign (positive
more than 90% of cases. In such cases, only yearly follow-up is predictive value, 99%), whereas lesions that enhance by more than
typically required; additional diagnostic tests are usually unneces- 20 HU are typically malignant (sensitivity, 98%; specificity,
sary.19,20 Therefore, an effort should always be made to obtain old 73%).32 Lesions that enhance by 15 to 20 HU should be consid-
chest radiographs if they are known to exist. ered indeterminate.
Because most SPNs are benign and because the risk of misdi-
Computed Tomography agnosing a malignant lesion is so great, it is important to make use
The advent of CT scanning has led to an increase in the num- of all of the data obtained from CT scanning in the effort to make
ber of SPNs detected21—but of course, it has also led to an cost-effective, logical decisions regarding further evaluation or
increase in the number of SPNs found that prove to be benign. treatment. Careful evaluation of the size, contours, and internal


characteristics of an SPN on successive CT scans—in conjunction 1.0 cm) may have an SUV lower than 2.5 and still be malignant.
with thoughtful consideration of the patient’s age, smoking histo- The reason is that their small volume causes their true activity
ry, and occupational exposure—provides the framework for ap- concentration to be underestimated, with the result that their SUV
propriate treatment. Because the doubling time is considerably drops below the threshold value for malignancy. In one prospec-
shorter for malignant lesions than for benign lesions, a repeat CT tive study of patients with SPNs, the overall sensitivity of FDG-
scan should be performed 3 months after the initial study. If the PET scanning was 79%, and the overall specificity was 65%.46
lesion is visibly larger on the repeat scan, it is probably malignant, When the SPN was smaller than 1.0 cm, however, all of the scans
and further diagnostic evaluation should be carried out with an were negative, even though 40% of the nodules were malignant.
eye toward resection. If, however, the lesion is still present and has In cases where the SPN is larger than 1.0 cm and no previous
not grown, a follow-up CT scan between 3 months and 12 radiographs or CT scans are available for comparison, PET scan-
months is warranted; the precise timing remains controversial and ning can provide information that may facilitate the decision
should be determined on the basis of individual patient and SPN whether to follow the lesion closely or to proceed with biopsy. PET
characteristics. New volumetric modeling methods have been scanning has a definite place in the evaluation of SPNs, but it is
developed that may be capable of detecting conformational not appropriate for every patient. A study that examined the cost-
changes over much shorter intervals, but at present, they are not effectiveness of PET in the evaluation of SPNs concluded that it
frequently used.33 was cost-effective for patients who had an intermediate pretest
probability of a malignant SPN and who were at high risk for sur-
Positron Emission Tomography gical complications.47 In all other groups, PET was not cost-effec-
PET is an imaging modality that employs radiolabeled isotopes tive, and CT led to similar outcomes (in terms of quality-adjusted
of fluorine, carbon, or oxygen; the most commonly used isotope is life years) and to lower costs.
18F-fluorodeoxyglucose (FDG). The rationale for FDG-PET
BIOPSY
scanning in the evaluation of SPNs is based on the higher meta-
bolic rate of most malignancies and the preferential trapping of If an SPN demonstrates characteristics suggestive of malignan-
FDG in malignant cells.34 However, increased FDG activity can cy, a tissue diagnosis should be obtained. There are several alter-
also occur in benign SPNs,35,36 especially those arising from active native biopsy techniques that may be performed in place of resec-
granulomatous diseases37,38 or inflammatory processes.39 These tion, including TTNB and bronchoscopy.Traditionally, open lung
benign diseases can produce false positive PET scans and thereby biopsy was performed for an SPN, but this approach has the draw-
reduce the sensitivity of the test. Conversely, some malignancies— back of the morbidity associated with a thoracotomy. For periph-
bronchoalveolar carcinoma and carcinoid tumors, in particular— eral lesions, video-assisted thoracoscopic surgery (VATS) has now
have low metabolic activity and commonly produce false negative supplanted thoracotomy as the procedure of choice. For central
PET scans.40-44 Thus, a negative PET scan is not a particularly lesions that cannot be diagnosed by means of less invasive tech-
helpful result, and it is necessary to follow the lesion with serial CT niques, more invasive approaches will still be required.
scans.
Efforts have been made to increase the sensitivity and specifici- Transthoracic Needle Biopsy
ty of PET scanning in the diagnosis of SPNs. One such effort Lesions that are between 1.0 and 3.0 cm in diameter should be
involves the use of the standardized uptake value (SUV), which is considered for TTNB. The diagnostic yield of this procedure for
a numerical indication of the activity concentration in a lesion, SPNs is excellent, reaching 95% in some studies. The reported
normalized for the injected dose.45 In many studies, an SPN is sensitivity ranges from 80% to 95%, and the specificity ranges
considered malignant when its SUV is higher than 2.5. Because of from 50% to 88%.48-50 A study of 222 patients who underwent
the method used to calculate the SUV, however, small tumors (< TTNB for an SPN reported a positive predictive value of 98.6%
and a negative predictive value of 96.6%51; however, several other
studies reported false negative rates ranging from 3% to 29%.48,52
Table 2 Factors Affecting Malignant Probability The complication rate associated with TTNB is relatively high—
of Solitary Pulmonary Nodule8 potentially as high as 30% and rarely lower than 10%, in even the
most experienced hands.49,53 Most commonly, a pneumothorax
Factor Likelihood Ratio for Malignancy results; however, chest tube placement is required only if the
patient becomes symptomatic, a situation that occurs in approxi-
Spiculated margins on CT scan 5.54 mately 50% of cases. In the absence of symptoms, observation
Age > 70 yr 4.16 with serial chest x-rays is generally appropriate. If no increase in
the size of the SPN is observed, the patient can be discharged with
Lesion size 2.1–3.0 cm 3.67
the expectation that the pneumothorax will resolve.
Doubling time < 465 days 3.40 For lesions smaller than 1.0 cm, the risk-to-benefit ratio of
TTNB rises to the point where other techniques are typically pre-
History of smoking 2.27
ferred.The utility of TTNB depends primarily on the characteris-
Age 50–69 yr 1.90 tics of the SPN—in particular, its location. Nodules that are cen-
Lesion size 1.1–2.0 cm
tral or close to the diaphragm or the pericardium are less well suit-
0.74
ed to this technique than those at other sites are.
Lesion size < 1 cm 0.52
Bronchoscopy
Smooth margins on CT scan 0.30
Bronchoscopy has a well-established role in the evaluation of
No history of smoking 0.19 central SPNs, which are amenable to direct visualization and biop-
Doubling time > 465 days 0.01 sy. Most SPNs, however, are not central. Various adjunctive mea-
sures, including transbronchial needle biopsy and cytology brush-


Small Cell Lung Cancer
ings, are employed to improve the yield of bronchoscopy. Newer
techniques, including the use of endobronchial ultrasonography, Small cell carcinoma accounts for approximately 20% of lung
are currently under active investigation. cancers. Typically, it presents as a central mass in association with
For SPNs between 2.0 and 3.0 cm in diameter, the diagnostic significant nodal disease, often accompanied by distant metas-
yield of bronchoscopy ranges from 20% to 80%, depending on the tases.62 Small cell carcinoma typically has a very short doubling
size of the lesion, the incidence of malignancy in the study popu- time. Paraneoplastic syndromes are more common with small cell
lation, and the proximity of the lesion to the bronchial tree.54,55 For lung cancer than with NSCLC.
SPNs smaller than 1.5 cm, the yield drops to 10%.56 Even though
bronchoscopy has a low complication rate (about 5%), its low Pulmonary Carcinoid
diagnostic yield for malignancy limits its utility in the evaluation of Pulmonary carcinoid tumors are uncommon neuroendocrine
SPNs. neoplasms that account for 1% to 2% of lung cancers.63 They are
classified as either typical or atypical, depending on their histol-
Excisional Biopsy ogy.64 Either type of carcinoid may present as an SPN, usually in
The decision whether to proceed to excisional lung biopsy the fifth or sixth decade of life. Typical carcinoid tumors have a
(open or thoracoscopic) must be carefully considered.The risk-to- very long doubling time—up to 80 months—and thus may be mis-
benefit ratio of excisional biopsy is determined by clinical charac- taken for benign lesions.65 Atypical carcinoid tumors have a much
teristics affecting perioperative morbidity and mortality, as well as shorter doubling time and are more likely to show an increase in
by the risk of malignancy. size on serial CT scans.Typical carcinoid tumors have an extreme-
Resection is the definitive diagnostic technique. The morbidity ly low incidence of recurrence and are not usually associated with
associated with VATS is less than that associated with thoracotomy; nodal metastasis.
accordingly, when VATS lung biopsy is technically feasible, it is
preferable to open lung biopsy.The overall morbidity is lower than Metastatic Malignancies
1% for VATS wedge resection, compared with 3% to 7% for the Metastases to the lung frequently appear as smooth, round,
equivalent open procedure.57 Patients who have undergone VATS well-demarcated lesions. They often are multiple and rarely are
lung biopsy experience less pain, have shorter hospital stays, and associated with mediastinal adenopathy. Most pulmonary metas-
recover sooner than those who have undergone open biopsy.57,58 tases derive from the lungs, the colon, the testicles, the breasts,
A technical consideration that must be taken into account when melanomas, or sarcomas. Treatment tends to be palliative, based
VATS is planned is possible conversion to a thoracotomy.The con- on the diagnosis of the primary tumor, but it may be curative in
version rate for VATS to thoracotomy has been reported to be as cases of metastatic sarcoma or testicular carcinoma. In patients
high as 33%, but there is evidence to suggest that this rate can be with these cancers, limited wedge resection of a metastasis to the
significantly reduced with careful patient selection and increasing lung has been shown to confer a survival advantage; this measure
experience in minimally invasive techniques.59,60 may also be beneficial for patients with metastatic colon or head
Peripheral SPNs more than 1.0 cm in diameter are the lesions and neck cancer and, occasionally, for those with metastatic
best suited to VATS excision. As SPNs become smaller and more melanoma.66
central, they become harder to identify, and the rate of conversion
BENIGN LESIONS
to thoracotomy rises. A wide variety of techniques have been
employed to improve the identification of SPNs for VATS, ranging
from radioisotope use through guide-wire localization. None of Pulmonary Hamartoma
these techniques have achieved wide acceptance, and most sur- Pulmonary hamartomas are the most common benign pul-
geons rely on simple finger palpation through one of the port sites. monary tumors and the third most common cause of SPNs over-
all. Most (90%) arise in the periphery of the lung, but endo-
bronchial hamartomas are seen as well. Because they are most
Differential Diagnosis common in the periphery, hamartomas are usually asymptomatic.
When a potential hamartoma appears as an SPN on a chest x-ray,
MALIGNANT LESIONS
CT scanning is warranted for further evaluation.
Certain typical CT findings suggest that the SPN is likely to be
Non–Small Cell Lung Cancer a hamartoma. One such finding is a particular pattern of calcifica-
As noted, NSCLC is the malignancy most frequently identified tion. Calcification is more common in benign lesions than in
in an SPN. Most lung cancer patients are asymptomatic, and those malignant tumors. There are four patterns of calcification that are
who are symptomatic usually have advanced disease, including considered benign: central, diffuse, laminated, and “popcornlike.”
mediastinal lymph node involvement. Arterial invasion has also The first three patterns are most commonly associated with an
been shown to have an adverse effect on survival in patients with infectious condition (e.g., histoplasmosis or tuberculosis). The
early-stage NSCLC.61 The most common sites of metastases are popcornlike pattern, however, indicates that the lesion is probably
the lungs, the brain, the bones, and the adrenal glands. a hamartoma. Unfortunately, calcification is present in only about
Accordingly, it is essential to perform a metastatic workup that 50% of benign lesions, and only about 50% of hamartomas are
focuses on these areas to identify metastatic disease before pro- calcified.29 It is important to remember that pulmonary carcinoid
ceeding with resection. tumors and metastases to the lung (especially those from osteosar-
Bronchoalveolar carcinoma is a subtype of NSCLC that is well comas, chondrosarcomas, or synovial cell sarcomas) may also have
differentiated and has a prolonged doubling time. Because of its calcifications.
slow growth rate, it may be missed by PET scanning.42 Broncho- Another reliable marker of a hamartoma is the finding of fat
alveolar carcinoma may present as an SPN, as airspace disease, or within the lesion on a CT scan; however, fewer than 50% of
as multiple nodules. hamartomas demonstrate this characteristic.


Inflammatory Nodules
rupture could result in an anaphylactic reaction to the highly anti-
Sarcoidosis is known as the great mimicker, but it rarely presents genic contents. Patients may be treated with anthelmintic agents,
as an SPN.67 Most commonly, it presents as hilar and mediastinal but the incidence of persistent or recurrent disease is high. Accord-
lymphadenopathy and diffuse parenchymal involvement. When it ingly, surgical resection should be considered.
does present as an SPN, it is almost invariably a solid lesion, hard-
ly ever a cavitary one. The incidence of sarcoidosis is highest in OTHER CONSIDERATIONS
African-American women between 20 and 40 years of age. If sar- Pulmonary amyloidosis may present in either a diffuse or a
coidosis is suspected during the evaluation of an SPN, an elevated nodular form.The prognosis is most favorable when it presents as
angiotensin-converting enzyme level supports the diagnosis, but a an asymptomatic SPN. Typically, the nodule is well defined and
normal level does not exclude it. If a biopsy is performed, the pres- between 2 and 4 cm in diameter. Unless the patient exhibits sys-
ence of noncaseating granulomas on pathologic evaluation estab- temic manifestations of amyloidosis, the diagnosis can be con-
lishes the diagnosis. firmed only by biopsy of the nodule.35
Pulmonary rheumatoid nodules are present in fewer then 1% of Rounded atelectasis usually presents as a pleura-based nodular
patients with rheumatoid arthritis.68 They are usually associated density that occurs secondary to pleural scarring and thickening.
with rheumatoid nodules in other parts of the body but may pre- An effort should be made to look for associated pleural plaques
cede any systemic manifestations of the disease. Pulmonary resulting from asbestos exposure. The CT scan usually demon-
rheumatoid nodules, though generally asymptomatic in them- strates an SPN with a “comet tail.” Biopsy is not required unless
selves, arise from underlying rheumatoid activity.When the under- mesothelioma is strongly suspected or the SPN is seen to have
lying disease is active, the nodules may grow, simulating malignan- grown on successive CT scans.75
cy. An elevated serum rheumatoid factor level is typical and helps
confirm the diagnosis.
Wegener granulomatosis is a necrotizing vasculitis that affects Management
both the upper and the lower respiratory tract, as well as the kid- Currently, there are no evidence-based guidelines that fully
neys. It presents with an SPN in approximately 20% of patients.69 delineate a recommended approach to the workup and manage-
If vasculitis is suspected during evaluation of an SPN, laboratory ment of SPNs.76 The following is a summary of our preferred
studies should include testing for cytoplasmic antineutrophil cyto- approach.
plasmic antibodies (c-ANCA); a positive result on this test is high- The ultimate aim in the evaluation of an SPN is to classify the
ly suggestive of Wegener granulomatosis. Treatment includes the lesion as either benign or malignant.The first step toward that end
cytotoxic drug cyclophosphamide, either alone or in combination is to compare current chest x-rays or CT scans with any previous
with corticosteroids. images that are available. An SPN whose size has been stable for
Infectious Nodules 2 years on diagnostic images will be benign 90% to 95% of the
time. If no previous images are available for comparison, the
An SPN can also represent an infectious granuloma caused by
patient should undergo a complete evaluation as if the nodule
tuberculosis, atypical mycobacterial diseases, histoplasmosis, coc-
were an early-stage NSCLC. This evaluation must be individual-
cidioidomycosis, or aspergillosis. Such granulomas normally have
ized according to the characteristics of the patient and the lesion.
a cavitary appearance on CT scans. Occasionally, an upright chest
On the basis of the patient’s age and smoking history, the size of
x-ray taken with the patient in the lateral decubitus position shows
the SPN, and the characteristics of the lesion’s borders, an SPN
shifting of the position of the cavity’s contents or a crescent of air
for which no previous diagnostic images are available can be ini-
around the mass (the Monod sign).70 This radiographic finding is
tially classified as having a low, intermediate, or high probability
characteristic of a mycetoma, usually aspergilloma. Depending on
the circumstances—in particular, on whether there has been sig- of cancer [see Table 3].7,77,78 This classification governs the subse-
nificant hemoptysis and whether pulmonary function is reasonably quent workup. Whereas a patient with a high-probability SPN
well preserved—many of these lesions are best treated by means of needs a complete workup, with the goal being resection, the same
resection. Others are best diagnosed by noninvasive techniques workup would not be cost-effective for a patient with a low-prob-
and treated with antibiotics. ability SPN. It is important not to subject a patient with a high-
Pulmonary dirofilariasis is a rare but well-attested cause of probability SPN to studies that will not change clinical manage-
SPNs that is the consequence of infestation of human lungs by the ment or outcome: doing so will delay diagnosis and treatment
canine heartworm Dirofilaria immitis.This organism is transmitted unnecessarily.
to humans in larval form by mosquitoes that have ingested blood At this point in the evaluation, if the nature of the SPN is still
from affected dogs.71 Because humans are not suitable hosts for
this organism, the larvae die and embolize to the lungs, where they
initiate a granulomatous response.Typically, these lesions are pleu- Table 3 Initial Assessment of Probability
ra based, and the diagnosis is made at the time of resection.72 Once of Cancer in Solitary Pulmonary Nodule
the diagnosis is made, no further therapy is required.
Echinococcosis is a hydatid disease caused by the tapeworm Characteristics of Probability of Cancer
Echinococcus granulosus. It is endemic to certain areas of the world Patient or Lesion Low Intermediate High
where sheep and cattle are raised. Normally, it is ingested inciden-
tally; the parasite penetrates the bowel wall and travels to the lungs Patient age < 40 yr 40–60 yr > 60 yr
in 10% to 30% of cases.73,74 A complete blood count usually de-
Patient smoking history Never smoked < 20 pack-years ≥ 20 pack-years
monstrates peripheral eosinophilia. If echinococcosis is suspected, a
hemagglutination test, which has a sensitivity of 66% to 100% and Lesion size < 1.0 cm 1.1–2.2 cm ≥ 2.3 cm
a specificity of 98% to 99% for Echinococcus, should be performed. Lesion margin Smooth Scalloped Spiculated
TTNB should not be performed, because there is a risk that cyst


indeterminate and the lesion is larger than 1.0 cm, there may be a vals for a minimum of 2 years. The rationale for this approach is
role for PET scanning. If PET scanning yields negative results, the based on the difficulty of identifying these lesions with VATS, the
SPN is probably benign, and follow-up with CT scanning is low likelihood of establishing a diagnosis with TTNB, and the pos-
appropriate. If PET scanning yields positive results and the patient sibility that the lesion may be benign. If the lesion has grown visi-
is a high surgical risk,TTNB may be performed to establish a diag- bly between scans, it is probably malignant, and proceeding with
nosis. If, however, the patient is a reasonable surgical risk, pro- resection for diagnosis and treatment is appropriate.The likelihood
ceeding directly to VATS resection (and, potentially, to lobectomy) that nodal metastases will develop in a closely followed SPN small-
offers the best chance of a cure. er than 1.0 cm is low.60 If the SPN proves to be malignant, scan-
For patients with SPNs smaller than 1.0 cm, the optimal ning at 3-month intervals is unlikely to alter the eventual
approach may be to perform serial CT scanning at 3-month inter- outcome.

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