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* From the Dana-Farber Cancer Institute, Boston, MA.
Correspondence to: Kitt Shaffer, MD, PhD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: kitt_shaffer{at}dfci.harvard.edu
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Abstract |
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 TOP Abstract IntroductionImagingBiopsySummaryReferences |
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Introduction |
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Imaging |
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Nodule Characterization
Once a nodule has been detected, CT can also be used to
characterize the nodule and help estimate the likelihood of malignancy.
Detection of calcification is particularly important, since certain
patterns of calcification are associated with a very high likelihood
that the nodule is benign. Organized patterns of calcification, such as
"popcorn" (seen in hamartomas), lamellar concentric rings of
calcium, central calcification, or homogeneous dense calcification all
carry an extremely low likelihood of malignancy. However, not all
nodules that contain calcification are benign. Certain patterns of
calcification are considered radiologically "indeterminate,"
meaning that they do not increase or decrease the likelihood of
malignancy compared to a noncalcified nodule. These indeterminate
patterns include stippled fine calcification and eccentric
calcification. Detection of calcification when only a small amount is
present is not always easy, even with CT. Reference phantoms have been
developed to assist in detection of low levels of
calcification,6
but these are expensive and cumbersome to
use. Dual-energy CT allows detection of low levels of calcification
without use of a phantom.7
Presence of fat density within
a nodule is also specifically indicative of hamartoma.
The role of IV contrast in the evaluation of SPN is changing. In routine practice, IV contrast is not needed for nodule detection, since nodules inherently stand out from surrounding aerated lung. However, for characterization of nodules, quantitation of degree of enhancement may be useful. This must be done in a controlled manner, with time-activity curves calculated for the nodules to allow comparison between precontrast and postcontrast images, and to allow quantitation of the percentage change in density with IV contrast. Studies of this technique have shown it to be fairly specific in distinguishing between benign and malignant nodules.8 9 Gadolinium-enhanced MRI of SPN may offer similar information.10
Another imaging modality with promise for discriminating between benign and malignant SPN is positron emission tomography (PET). PET scanning has been studied in the setting of SPN and shows good specificity for benign vs malignant etiologies.11 False-positives, however, can occur in SPN with inflammatory components, such as anthrosilicotic nodules and some infectious nodules.12 PET is still an expensive procedure and not readily available, but it may play a larger role in future nodule evaluation. While PET is expensive, if it prevents unnecessary surgery it may actually be cheaper in the long run.13 14
Detection of Small Nodules
As CT technology has improved, smaller nodules are now more easily
detected. We are now faced with the common occurrence of very tiny
subpleural nodules, sometimes called "ditzels," which would
probably not have been visible on older CT scans. Many of these are
benign in etiology, such as granulomas or intrapulmonary lymph
nodes.15
Most typically, intrapulmonary lymph nodes are 1
to 2 mm in diameter and are located in the posterior basal subpleural
portions of the lungs. Biopsy is not cost-effective for all of these
lesions. However, since they are so small, they are generally
indeterminate in terms of imaging criteria, with no detectable
calcification, and they are too small to be imaged with PET or sampled
by percutaneous biopsy. This is a management dilemma with no
clear solution. Several studies have shown that a significant
proportion of these ditzels are metastatic disease in patients with
known malignancies.16
17
This suggests that management of
ditzels must be tempered by consideration of the patient’s history of
any malignancy with propensity to metastasize to the lung. With the
advent of video-assisted thoracoscopic techniques, sampling of these
lesions is much easier for patients than in the past.
Differential Diagnosis of SPN
The differential diagnosis of SPN is usually between malignancy,
benign tumor, and infection. In most studies, the incidence of
malignancy in SPN ranges from 50%18
19
to
75%.20
Among patients with initial imaging suggesting
cancer who were later found to have an infectious diagnosis, almost all
had SPN as an initial imaging finding. Overall, in a 3-year
retrospective study, only 1% of patients with SPN ultimately had an
infectious final diagnosis (mainly fungal infections followed by
mycobacterial or other bacterial infections).21
These
percentages may be altered in areas endemic for fungal infections or
tuberculosis.22
Noninfectious benign etiologies for SPN
include rheumatoid nodules,23
hamartoma, plasma cell
granuloma, anthrosilicotic nodule, and sarcoidosis. Unusual causes
include parasitic infections, intrapulmonary Castleman’s
disease,24
and inflammatory pseudotumor.
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Biopsy |
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TOPAbstractIntroductionImagingBiopsySummaryReferences |
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Technical Concerns
Certain technical limitations must be kept in mind when
considering image-directed biopsy or fine-needle aspiration (FNA) of
lung nodules. In order to minimize the risk of pneumothorax, which is
the main complication of FNA, the smallest possible gauge of needle
should be used (generally 21 gauge or 22 gauge). Larger-caliber core
biopsy needles can also be used for lung lesions, particularly those
abutting pleura.30
Many FNA needles have compartments
along their distal side walls that are designed to allow collection of
the maximum amount of tissue while aspirating through the needle and
moving it back and forth within the lesion. This aspiration technique
will not work if the lesion is so small that the needle side wall
compartment cannot be kept within the lesion while the needle is being
moved. Overall, diagnostic success is low in lesions < 1 cm in
diameter.31
32
The risk of pneumothorax is also increased
with increased lesion depth from pleura and decreased lesion
size.33
The location of the solitary pulmonary nodule can affect the likelihood of success with FNA. Lesions that are nearer the pleura are generally easier to sample.31 Lesions that are in the lower lobes may be harder to sample if the patient is unable to hold his or her breath in a consistent manner, particularly for CT-guided FNA, since the basilar portions of the lungs move the most with breathing. This is less of a limitation for fluoroscopically guided FNA. The risk of pneumothorax increases when a fissure must be crossed in order to reach a lesion. Thus, certain nodules positioned such that the only possible needle path crosses the major or minor fissure may have a high risk of associated pneumothorax. Lesions surrounded by bullae carry the same high risk of pneumothorax. In fact, COPD has been associated with an overall increased risk of pneumothorax during FNA. This risk increased as the FEV1 decreased in one study,34 although results are controversial.35 Some lesions may be inaccessible due to overlying bony structures. It is also important to keep in mind that overall complications from lung biopsy are generally higher than for liver or adrenal biopsy, so that if a biopsy is being considered in a patient with lung and liver/adrenal masses, it is safer to biopsy the abdominal disease rather than the lung disease in most cases.
Clinical Concerns
Certain clinical conditions should also be kept in mind when
considering image-guided FNA of lung lesions. Patients who are taking
aspirin should have bleeding time checked before the procedure, and if
prolonged, the risk of serious bleeding may necessitate other measures,
such as delay of the procedure until the effects of the aspirin are
reversed. Routine CBC count, prothrombin time, and partial
thromboplastin time are sometimes checked before FNA to detect
unsuspected clotting disorders or anemia, although this may not be
necessary in patients with no history of bleeding problems. FNA may not
be possible in patients who are extremely dyspneic or uncooperative.
For CT-guided biopsies, patients must be able to hold still on the CT
table in a supine, prone, or decubitus position for up to 30 min, and
be able to cooperate in terms of breath-holding instructions. Local
anesthesia is used to infiltrate the skin and subcutaneous tissues,
followed by a small skin nick and insertion of the biopsy needle. It is
important during the procedure to suspend respiration at all times when
the needle is being moved, to minimize the size of the pleural tear
that is produced and to decrease the risk of pneumothorax.
On-Site Cytology
The utility of on-site cytologic examination is somewhat
controversial. Initial studies suggested that having a cytologist
examine the specimen immediately could increase the success rate for
the procedure.36
Other articles have suggested that this
is not necessary if enough samples are collected.37
However, more samples require a longer procedure, more discomfort for
the patient, and a higher risk of pneumothorax. At our institution, a
cytologist is routinely on site during the procedure, and a quick-prep
slide is examined after each pass to determine the adequacy of the
sample and whether more tissue will be needed. The cytologist also
helps with slide preparation, which may also ensure that the most
information is obtained from each sample.36
It is
important to plan prior to the procedure exactly what specimens are
needed, since some techniques (eg, immunohistochemical
studies) may require slightly different specimen
handling.20
In addition, if microbiologic culture is
needed, some of the specimen must be added to various culture media in
a sterile manner before preparation of the cytologic slides.
Technical Advances
Some new technical advances may lead to more accurate FNA
diagnoses. The addition of core biopsy with an automated biopsy device
to routine FNA may increase specific benign diagnoses. In a study of 50
patients, the accuracy of benign diagnoses increased from 31% with FNA
alone to 69% with core biopsy, although the addition of core samples
did not increase the accuracy of malignant diagnoses.38
Role of FNA
The role of FNA is best examined as part of a multimodality
approach to patient management, and decisions about FNA should be
discussed with the radiologist and other caregivers to determine if the
procedure will be cost-effective and safe in each individual patient.
Many surgeons do not require preoperative FNA diagnosis before planned
resection of a solitary pulmonary nodule, since a nondiagnostic result
will not prevent resection, and a malignant result will not alter the
surgical approach. In fact, in patients with no contraindication to
surgery, resection may be cheaper overall than initial bronchoscopy or
FNA.39
Rarely, a specific benign diagnosis may be made
(eg, hamartoma) that may preclude surgery, but in most
cases, the results are nonspecific. Since the sample is usually
cytologic rather than a core of tissue, architectural histologic
information is not available from an FNA sample and may further limit
the ability to reach a specific benign diagnosis. The role of FNA is
also unclear in cases of multiple pulmonary nodules, where
determination of the primary site may have important effects on further
treatment options, but may also require larger tissue samples for
immunohistochemical analysis than can be easily obtained with FNA.
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Summary |
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TOPAbstractIntroductionImagingBiopsySummaryReferences |
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Footnotes |
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References |
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This article has been cited by other articles:
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  B. L. Partik, A. N. Leung, M. R. Muller, M. Breitenseher, F. Eckersberger, G. Dekan, T. H. Helbich, and V. Metz Using a Dedicated Lung-Marker System for Localization of Pulmonary Nodules Before Thoracoscopic Surgery Am. J. Roentgenol., March 1, 2003; 180(3): 805 - 809. [Abstract] [Full Text] [PDF]
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