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701
Review
Evaluation
Radiologic W. Richard
of the Solitary
studies are performed or interpreted, several very important clinical factors should be considered. First, in patients less than 30 years of age, the prevalence of bronchogenic carcinoma is so low that a solitary pulmonary nodule generally should be followed-up radiologically without any further evaluation, unless the patient has a known extrathoracic primary malignancy [4]. In some patients in this age group, needle biopsy is performed before follow-up; biopsy may be requested if the patient is very concerned about the possibility of carcinoma, or has a significant risk factor for carcinoma. Although a history of an extrathoracic primary malignancy suggests that a solitary nodule is a metastasis rather than a lung cancer, this is not always the case [5]. In a patient over 35 with an extrathoracic malignancy and a solitary nodule, the likelihood that the nodule represents a bronchogenic carcinoma depends on the cell type of the extrathoracic tumor. If the extrathoracic malignancy is of squamous cell origin, the nodule is most likely a lung cancer. If the extrathoracic primary is a melanoma or sarcoma, the nodule is probably a metastasis. An extrathoracic adenocarcinoma indicates that the lung nodule has about 50% chance of being lung cancer. Sputum cytology should be obtained in all patients with a solitary pulmonary nodule in whom cancer is considered a possibility. False-positive sputum cytology is rare (07-3%) and a positive sputum cytology is the most reliable preoperative method (except biopsy) for diagnosing a pulmonary malignancy. False-negative cytology is far more common, occurring in 10-30% of all patients with lung cancer and in
Considerations
Clinical and historical data, such as dwelling and travel history, risk factors for carcinoma (e.g., smoking), and skin test results should be considered in the evaluation of any patient with a solitary pulmonary nodule, but these data are not generally specific enough to alter the patent’s diagnostic evaluation or eventual treatment. However, before imaging
Received
Nodule
Webb1
The diagnostic evaluation of a patient with a solitary pulmonary nodule is a common problem in radiologic practice. Although there is no universally accepted definition of a solitary pulmonary nodule, this term is usually used to refer to a lung lesion that is reasonably well defined, round or oval, and less than 5 or 6 cm in diameter. The differential diagnosis of a solitary nodule is extensive, but its radiologic evaluation is primarily directed at distinguishing nodules that are benign, and thus inconsequential, from nodules that are malignant or potentially malignant, and require treatment. The large majority of solitary nodules detected radiographically are benign [1-3]. A variety of radiologic procedures have been used for the examination of patients with a solitary pulmonary nodule. Currently, plain chest radiographs and CT are of most value. Simply stated, the goals of imaging in patients with an undiagnosed lung nodule are (1) to make a specific diagnosis; or (2) if a specific diagnosis cannot be made, to distinguish benign nodules from those that are indeterminate and thus potentiallymalignant; or (3) if benign and malignant cannot be distinguished, to help determine what should be done next.
Clinical
Pulmonary
Article
August
‘Department AJR 154:701-708,
14, 1989;
of Radiology. April
accepted
after revision
November
University
of California,
San Francisco,
1990 0361 -803X/90/1
544-0701
14, 1989.
American
San Francisco, Roentgen
CA 94143-0628.
Ray Society
WEBB
702
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up to 60% of thOSe ative cytology does lesion.
Chest
with peripheral malignancies. Thus, nagnot preclude the presence of a malignant
Radiographs
A number of plain film criteria have been reported to be of some value in diagnosing a lung nodule as benign. These include smallness, regular or round shape, smooth contour, sharp edge definition, the presence of satellite lesions, a slow or very fast doubling time, and absence of cavitation. However, these plain film criteria rarely allow a specific diagnosis of benignity to be made. Even attempts to use computers to aid in diagnosis have not resulted in more than 90% accuracy in distinguishing benign and malignant lesions [6]. The individual patient with a solitary pulmonary nodule cannot be properly managed with this degree of uncertainty as to whether or not a nodule is benign. However, two radiologic features-dense or central calcification and absence of growth-can be used to indicate that a solitary pulmonary nodule is benign, for all practical purposes. In patients with either finding, a solitary pulmonary nodule can be followed with sequential chest radiographs at progressively increasing intervals (2 months at first, increasing to 1 year if the nodule is unchanging), but no other examination is usually necessary.
Calcification Dense central, laminated, or diffuse calcification virtually excludes malignancy (Fig. 1). Although bronchogenic carcinomas (scar carcinomas) may incorporate an adjacent calcified granuloma, resulting in a mass with calcification, the
0 DIFFUSE
CENTRAL
AJR:154,
April 1990
calcification is usually eccentric rather than central (Figs. 1 and 2). In addition, bronchogenic carcinomas may themselves calcify; this calcification is often stippled and is frequently not detectable radiologically (Fig. 1). In a study of 72 patients with malignant solitary pulmonary nodules, calcification was visible on radiographs of the resected specimen in 1 0, but in only one was calcification detectable on standard chest radiographs [7]. In the same study, 67 of 1 35 benign lesions (mostly granulomas and hamartomas) contained calcifications on specimen radiographs; in 46, these calcifications also were visible on standard chest radiographs. Metastatic malignant tumors (particularly osteogenic sarcoma, chondrosarcoma, and thyroid carcinoma) can show stippled or homogeneous calcification, but the nodules are usually multiple. Calcification in a solitary pulmonary nodule is usually best appreciated on low-kilovoltage radiographs, but these are of limited value except in obvious examples. Fluoroscopy can also be of value in projecting a nodule away from overlying densities, therefore allowing calcification to be seen more clearly, but this technique is not routinely used because of relatively poor resolution.
Growth
Rate
The growth rate of a solitary pulmonary nodule (usually quantitated by using doubling time-the time required for a doubling of volume) has been used to determine its likelihood of being malignant [8]. A pulmonary nodule that doubles in volume in less than 1 month or more than 1 8 months is usually benign. However, the overlapping growth rates of benign and malignant lesions, particularly among rapidly growing nodules, makes the use of doubling time hazardous as an absolute indicator of benignity. Nevertheless, it is generally agreed that a solitary pulmonary nodule that does not grow over a 2-year period is benign and does not require resection. Only rare exceptions to this rule have been reported. Therefore, a vigorous search for old films must be the first step in the evaluation of a noncalcified solitary pulmonary nodule. If films 2 years or older show the pulmonary nodule to be unchanged, follow-up radiographs at intervals are all that is usually nec-
essary.
POPCORN
LAMINAR,
CONCENTRIC
0 STIPPLED
ECCENTRIC
B Fig. 1.-A and B, Some patterns of benign (A) and “malignant” (B) calcification seen on plain radlographs or CT scans can be helpful in predicting that a lung nodule is benign. Malignant patterns can be seen with either benign or malignant lesions.
If no old films are available, or if prior films are not old enough, the diagnostic approach may be based on the patient’s age and the plain radiographic appearance of a lesion. If the patient is less than 30 years of age and the pulmonary nodule appears benign (small, round, sharply defined), followup with standard chest radiographs generally is sufficient. However, if the patient is older, has a history of an extrathoracic tumor, or if the lesion does not appear benign (i.e., it is large, irregular, poorly defined, or spiculated), further diagnostic procedures must be performed. Also, occasionally a patient with an acute process, such as pulmonary embolism or focal pneumonia, can present with a nodular density on chest radiographs. In a patient with acute symptoms, a follow-up radiograph in 1-2 weeks can sometimes show a decrease in the size of a nodule, indicating its benign nature. In some patients without symptoms, repeat
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AJR:14,
SOLITARY
April 1990
PULMONARY
NODULES
703
Fig. 2.-A, Plain radiograph in patient with a nodule in right upper lobe shows eccentric calcification (arrow). Mass is poorly defined and spiculated, suggesting malignancy. B, Conventional CT scan at this level shows nodule and focus of calcification. At surgery, this was a carcinoma engulfing a granuloma. Thus, this tumor may represent a scar carcinoma arising in relation to the inflammatory lesion.
radiographs will show a similar decrease in size, indicating that the lesion is benign. Because of this, one or two followup radiographs at 1- to 2-week intervals are often obtained in a patient with a solitary nodule, usually during examination, to assess the stability of the lesion. However, it is not advisable in most subjects to obtain follow-up radiographs, hoping that a nodule will decrease in size. Furthermore, in some patients with cancer, nodules become less well defined as they grow and can appear smaller.
CT CT is performed in most patients with a solitary pulmonary nodule to define the morphology of the lesion, detect calcification, and help in biopsy planning. It has largely replaced conventional tomography for these indications. Although conventional CT with 1 -cm collimation can provide this information in some cases, CT with thin collimation, and particularly high-resolution CT, is superior to conventional CT in delineating nodule morphology and allowing the detection of calcification. When studying a patient with a solitary nodule by using CT, we typically obtain contiguous high-resolution CT scans through the nodule, monitored by the radiologist, followed by a conventional CT study aimed at evaluating the remainder of the lung parenchyma, mediastinum, and hila.
Confirmation
of a Nodule
and Delineation
of Morphology
When a solitary nodule is suspected on plain radiographs, CT is often used to confirm that a nodule is present and to define its morphologic characteristics. In addition to conventional CT (contiguous 1 -cm collimation), thin-slice, high-resolution CT scans can be quite variable in evaluating focal pulmonary parenchymal lesions [9]. We commonly obtain several contiguous high-resolution scans through the abnormal area in a patient with a lung nodule. A few types of nodular lung lesions have morphologic characteristics typical enough to allow a diagnosis to be made on CT (Fig. 3). These include arteriovenous fistulas, rounded atelectasis, focal consolidation, pleural plaques, fungus balls (Fig. 4), and mucous plugs. Pulmonary malignancies (particularly adenocarcino-
mas) often appear irregular and spiculated on high-resolution CT, and this appearance strongly suggests malignancy (Fig. 5) [10]. Identification with CT of multiple lung nodules in a patient in whom a single nodule is visible on plain films suggests metastases as the likely diagnosis, but lung cancer in association with other causes of lung nodules (e.g., granulomas) must also be considered, particularly if one nodule is dominant. Furthermore, any patient with lung cancer has an increased risk (compared with the general population) of having a second lung cancer synchronous with the first. Thus, if two nodules are visible, both may be primary lung cancers, and both may be resectable. However, this is rare and occurs in less than 1% of patients [1 1 12]. ,
CT Nodule
Densitometry
In 1980, Siegelman et al. [1 3] suggested the use of quantitative CT densitometry for the detection of calcium in lung nodules, thus indicating their benignity. They indicated that calcification invisible on plain radiographs or tomograms could be detected by high CT numbers by using CT with thin collimation. In their initial report [1 3], 91 solitary pulmonary nodules with an uncalcified appearance on conventional tomography were studied with CT. Averaging the highest CT numbers for each nodule, all 45 primary tumors and 13 metastatic nodules were found to have values of less than 1 64 H, whereas 20 of 33 benign nodules were identified as such by a representative CT number of over 1 64 H. Other investigators had difficulty in duplicating their results [14, 1 5], largely because of differences between scanners and image reconstruction algorithms. In general, most benign nodules were found to have representative CT values much less than the 164 H cutoff that has been reported. However, other authors confirmed the potential usefulness of this technique, and the results of Siegelman et al. were subsequently confirmed in a larger series [16-18]. From 22% to 36% of lung nodules that cannot be shown to contain calcium by using conventional tomograms are found to contain calcium by using CT [16-18].
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704
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AJA:154,
Fig. 3.-A
and B, High-resolution
April 1990
CT scans
at
two levels in patient with a poorly defined 1-cm nodule visible on chest radiographs. On highresolution CT, nodule is seen to consist of a number of smaller, well-defined nodular densities. This appearance suggests a granulomatous disease, and CT-guided needle aspiration biopsy resufts showed an atypical Mycobacterlum.
P A
B Fig. 4.-CT scan in patient with usual interstitial pneumonitis and a nodule in right upper lobe. lntracavitary mass strongly suggests the presence of a fungus ball. -4
‘4
“I”
I
4
Fig. 5.-High-resolution CT scan in patient with a nodule in upper lobe. Spiculated mass Is very suspicious for carcinoma. Nodule densitometry is not appropriate with nodules having this appearance on plain films or CT scans, because many represent tumors. An adenocarcinoma was found at surgery.
/
5
Further study of individual scanners, scanner geometry, and reconstruction algorithms emphasized the rather considerable variation in nodule density measurements obtained with different scanners, for nodules of different sizes, in different locations, and in patients of different size and chest wall thickness [1 9]. These variables made the use of CT number criteria applicable to one machine difficult or impossible to use on another. It was a difficult problem. One approach to solving this problem was the development of an anthropomorphic phantom for use in chest CT [20]. This phantom can simulate the shape, dimensions, and density of thoracic structures in most patients. Cylinders of various diameters, made of plastic to correspond to the density of a calcified nodule (described as having a density of 164, 190, and 264 H in different publications [20-22]), serve as the reference density for a solitary pulmonary nodule. In this technique, after a patient with a solitary nodule is studied with thin collimation, the phantom is put together to simulate the same slice level, chest wall thickness, nodule location, and size, and then the phantom is scanned with the identical CT technique that was used in scanning the patient (Fig. 6). Then, the densities of pixels in the patient’s nodule and the phantom nodule are compared. If pixels in the lung nodule are denser than those in the phantom nodule, calcium is considered to be present [21-23]. Thus, this phantom is
assumed to provide a measurement of density independent of equipment-related or patient-related variations. However, as stated above, because lung carcinomas can contain some calcium, not all nodules shown to contain calcium on CT scans can be diagnosed as benign. It has been recommended that in order to call a nodule benign, dense pixels must be diffuse or central within the nodule, account for 1 0% or more of the cross-sectional area, and be visible on more than one scan; in other words, the detectable calcification must be of substantial size and central within the nodule (what would be expected for a benign lesion). Thus, CT nodule densitometry with this phantom is not only quantitative, but is qualitative as well. It can be thought of as being used in a way similar to, but in a more objective fashion than, conventional tomography. Also, in order to reduce the risk of calling a calcified carcinoma benign, it has been recommended that a nodule be lobulated or smooth rather than spiculated if it is to be diagnosed as benign, and less than 2 cm in size [16, 2123]. Large or spiculated nodules are much more likely to be carcinomas than smaller, better defined lesions. Because of this, patients who have nodules that are larger than 2 cm or appear spiculated on plain radiographs should not undergo CT nodule densitometry; with such nodules, densitometry would be of no value.
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AJR:154,
SOLITARY
April 1990
PULMONARY
NODULES
705
Fig. 6.-A, Thin, collimated CT scan reconstructed with standard algorithm In patient with a small nodule in right lung. B, CT phantom has been constructed to simulate same slice level, nodule size, and location, and phantom has been scanned by using Identical technical factors. C, CT numbers recorded from nodule include many pixels exceeding 100 H and some exceedleg 200 H. D, Numbers recorded from phantom nodule are considerably lower. Thus, lung nodule Is calcified.
B NX
126
127
128
129
130
131
132
133
134
NX__117
118
119
120
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202
-839
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284
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-126
-64
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203
-627
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204
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-64
286
-192
-81
5
-279
205
-265
287
-118
-23
41
-25
-326
205
-241
288
-187
-77
-88
-419
20’
-339
289
-354
-183
-221
-554
205
-533
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209
-765
-464
-226
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210
-921
-799
-623
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-473
2
-579
291
-
-3% -654
2 -55 -228 -538
18
82
94
38
87
141
118
85
161
205
135
85
184
227
1%
52
146
1%
-103 -433
3 -337
72
42
-92
-301
-375
2
-405 -563
-6% -751
C
-241
121
283
-205
122
123
124
125
-283
-477
-742
-919
-13
-146
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-782
-1%
-613
12
30
32
35
38
27
-1
13
35
33
31
19
23
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-482
24
33
33
31
21
35
-52
-461
-9
50
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28
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-2
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-113
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-562
-714
-880
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D
B
C
Fig. 7.-A, Conventional CT scan with 1-cm collimation at level of a nodule in right lung. B, With medlastinal window for this slIce, nodule Is InvIsible and no evIdence of calcification C, Thin, collimated scan shows nodule Is densely calcified. Measured CT numbers exceeded
In a cooperative study [21 ]of this phantom, 298 pulmonary nodules were evaluated. Of 69 nodules determined to contain substantial calcification, 68 were benign and one was malignant. Of the 229 remaining patients who had nodules that did not contain substantial calcification (indeterminate nodules), 176 had malignant nodules.
Is shown. 400 H.
It must be emphasized that the thin-section (1 .5-mm) technique is necessary when using CT for the diagnosis of nodule calcification. Calcium easily diagnosable on thin-section CT is sometimes invisible with 1-cm collimation (Fig. 7). Also, in regard to the study reporting the use of the chest phantom for nodule densitometry [21], in approximately half of the
WEBB
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706
cases in which a nodule could be called benign, calcium was easily visible within the lesion on the thin-section scans, and the phantom itself was unnecessary. Furthermore, concurrent improvements in scanner technology allow more accurate density measurements with CT, obviating a phantom in many cases. Some current scanners appear to be better densitometers, and less susceptible to variations in CT number measurement, than the scanners that prompted the invention of this phantom [24]. In our institution we routinely perform nodule densitometry using a GE 9800 machine, without using a nodule phantom. Although varying technical factors (kVp, mA, reconstruction algorithm) can be used in performing nodule densitometry with adequate results, we prefer using relatively high-kVp settings (because of decreased image noise and a more linear relationship between CT number and calcium content) and a high-spatial-frequency algorithm (GE bone), which improves spatial resolution and may be slightly more sensitive than the standard algorithm for detecting small amounts of calcium [24]. Nodules with visible calcification on the thin-section scans will generally have CT number values of about 400 H on the GE 9800 (Fig. 7). We regard nodules with CT numbers of more than 200 to contain calcium (Fig. 6) [24]. CT with thin collimation can also be valuable in diagnosing pulmonary hamartomas. In one study [25], 30 of 47 patients with a hamartoma were correctly diagnosed with CT because of visible fat, either focal or diffuse (CT numbers ranging from -40 to -120 H); fat and calcification; or diffuse calcification (Fig.
8).
Dual-Energy It has in a lung scanning (calcium) different beam at amount
Techniques
been suggested that the amount of calcium present nodule can be quantified by using a dual-energy CT technique [26]. Elements with high atomic numbers exhibit different degrees of X-ray absorption at energies. By noting the attenuation of the X-ray different energies, one can accurately quantify the of calcium in an area of interest. However, because
AJR:154,
April 1990
of technical difficulties, this technique has not yet been used clinically in a large series. Replicating the exact same level on the two different scans obtained with different energies is the primary difficulty with this technique. Preliminary experiments with dual-energy digital radiography with the two energy measurements obtained simultaneously have been reported recently [27]. Because there is exact correspondence of the dual-energy images, the problems of misregistration occurring with CT have been avoided. With this technique, measurements of calcium in simulated lung nodules in a phantom have been quite accurate. However, as with dual-energy CT, digital radiography techniques remain experimental.
Use of Imaging
to Guide
Biopsies
If plain radiography and CT do not allow a specific diagnosis to be made, and no calcification is visible within the nodule, a biopsy may be necessary. Depending on the clinical situation, and the prejudices of the patient’s physician, several options are available. These may include needle lung biopsy, bronchoscopy, mediastinoscopy, or thoracotomy. To some degree, imaging studies can be valuable in making this choice.
Aspiration
Lung Biopsy
or Bronchoscopy?
Aspiration needle biopsy has become firmly established in the investigation of peripheral solitary pulmonary nodules suspected of being neoplastic [28, 29]. Biopsies can be performed on lesions as small as 1 cm, although the minimum size varies with the skill of the operator. Confirmation of the tip of the needle within the lesion must be obtained. Biplane fluoroscopy is the most conventional method, but single-plane fluoroscopy and CT may also be used. Needle biopsy of the lung is a safe procedure. Although pneumothorax occurs in about 20% of patients, intercostal tube evacuation is required in only a few percent. In patients with carcinoma, hemorrhage and death are uncommon; dis-
Fig. 8.-A, High-resolution CT scans with lung window settings in patient with a small nodule detected on plain films. B, With mediastinal window settings, nodule (arrow) appears to be of a density similar to that of subcutaneous fat. C, CT numbers measured from this nodule indicate It is entirely or almost entirely fat. Hamartomas can have this appearance. up with plain radiographs and remained unchanged in size.
This lesion
was followed
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AJR:154,
SOLITARY
April 1990
PULMONARY
semination of malignant cells from an aspiration biopsy may occur rarely. Needle aspiration will yield malignant cells in more than 90% of neoplastic nodules. This percentage can be optimized by having a cytologist on hand at the time of the biopsy, and repeating the biopsy if specimens are negative. Cytologic determination of cell type is good for squamous cell carcinomas and adenocarcinomas, but poor for undifferentiated tumors. A bacterial diagnosis can be made in almost 70% of infectious nodules. The diagnosis of a benign nodule (e.g., hamartoma) can also be made, though this usually requires a larger aspirate than for the diagnosis of malignancy. The indications for needle aspiration biopsy vary between institutions, often determined at least in part by the preference of the surgeon. I think an argument can be made for reserving needle biopsy for those patients with solitary pulmonary nodules who are not candidates for thoracotomy because of age, complicating illness, or because the lesion is suspected of being a metastatic deposit. Because of the relatively high false-negative rate (up to 1 0%) in patients with carcinoma, a negative biopsy cannot be taken to mean that no tumor is present. If a patient can tolerate surgery, a solitary pulmonary nodule that could represent a malignancy is often resected without a preliminary needle biopsy. In patients suspected of having a benign nodule because of its appearance or growth rate or the patient’s age, needle biopsy can be used to make a specific diagnosis of a benign lesion or to increase the likelihood of a benign process prior to radiologic follow-up. It is important to note that the role of needle biopsy in patients with a solitary nodule can vary considerably from one institution to the next. CT can be helpful in planning a needle aspiration biopsy [30], even if CT is not used for the biopsy itself. First, CT can indicate the depth of the lesion, and the needle can be marked for the appropriate depth. Second, CT can help in planning the biopsy approach. If bullae lie in the path of the needle, or the needle must cross a fissure to reach the lesion, the risk
F,
j
I
Fig. 9.-CT scan in patient with a small nodule In right lung shows nodule (large arrow) is closely related to posterior segmental bronchus of right upper lobe (small arrow). Because of this, it was approached bronchoscopically rather than with a percutaneous biopsy; brush cytology findings were positive.
NODULES
707
of pneumothorax is increased, and a different approach might be used. Bronchoscopy is most accurate in diagnosing central masses with an endobronchial component, whereas needle biopsy is best for peripheral lesions. Thus, the location of the lesion can be important in choosing the biopsy procedure. CT can be quite valuable in this regard. If an endobronchial lesion is detected with CT, or bronchial narrowing at the site of a hilar mass is visible, bronchoscopy directed to the proper level is most appropriate (Fig. 9) [31]. In some patients, CT will show an endobronchial lesion beyond the visibility of the bronchoscope, and thus guide the biopsy attempt.
CT for Staging
Cancer
in Patients
with a Solitary
Nodule
If a patient with a lung nodule is known to have a carcinoma from needle aspiration biopsy or cytology, or is strongly suspected of having a malignant lesion, then the radiologic examination, particularly with CT, has an additional goalspecifically to determine the resectability of the tumor. However, the use of CT for staging cancer in patients with solitary nodules is controversial. Because of the relatively low likelihood of mediastinal node metastases in patients with solitary lung nodules who do not have evidence of hilar or mediastinal mass on plain radiographs, a number of surgeons perform thoracotomy on patients with a potentially malignant nodule without further biopsy or staging procedures (including CT). For example, in a recent survey of thoracic surgeons [32], only 1 5% of surgeons would obtain a CT scan preoperatively to evaluate the extent of the disease in a patient with a peripheral nodule. Furthermore, the value of CT in staging cancer in patients with Ti lesions (peripheral nodules :3 cm in diameter) has not been clearly established, and some investigators believe it may provide misleading information regarding the status of mediastinal nodes [33-35]. In patients with a solitary nodule, if mediastinal node metastases are found at surgery, they may be resectable with a reasonable chance of cure if they are ipsilateral [36], and particularly if they are low in the mediastinum and the primary tumor is squamous cell. Some thoracic surgeons believe that positive lymph nodes found at mediastinoscopy rule out effective surgery treatment of lung cancer [37, 38]; in several studies, patients with positive findings on mediastinoscopy had a relatively poor survival rate after surgical resection, compared with patients in whom mediastinoscopy showed negative results but positive nodes were found at surgery. Because of this, these surgeons perform mediastinoscopy in all lung cancer patients, including those with a solitary nodule. Recently, two studies [37, 38] found mediastinoscopy and CT to have the same reasonably high sensitivity for detecting mediastinal node metastases. However, as would be expected, mediastinoscopy was 100% specific (no normal cases were called abnormal), whereas CT had a specificity of 50-65%. Despite this, these authors recommend that CT (in addition to mediastinoscopy) be performed in evaluating patients with solitary nodules. In their opinion, if CT shows abnormal lymph nodes, it should be used to guide mediastinoscopy and
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708
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biopsy. However, it is also pointed out that biopsy should not be limited to nodes that appear abnormal on CT; other nodes may be the ones involved by tumor.
AJR:154,
CT measurements of solitary pulmonary nodules. J Comput Assist Tomogr 1982;6: 1075-1 087 Zerhouni EA, Boukadoum M, Siddiky MA, et al. A standard phantom for
20.
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24. 25. 26.
27.
28. 29. 30. 31
32.
33. 34. 35. 36.
37.
38.
April 1990
.
quantitative analysis of pulmonary nodules by computed tomography. Radiology 1983;149:767-773 Zerhouni EA, Stitik FP, Siegelman SS, et al. CT of the pulmonary nodule: a cooperative study. Radiology 1986;160:319-327 Khouri NF, Meziane MA, Zerhouni EA, Fishman EK, Siegelman SS. The solitary pulmonary nodule; assessment, diagnosis, and management. Chest 1987;91 :128-133 Zerhouni EA, Stitik FP. Controversies in computed tomography of the thorax: the pulmonary nodule-lung cancer staging. Radio! Clin North Am 1985;23:407-426 Im J-G, Gamsu G, Gordon D, et al. CT densitometry of pulmonary nodules in a frozen human thorax. AIR 1988;150:61-66 Siegelman SS, KhOUn NF, Scott WW Jr, et al. Pulmonary hamartoma: CT findings. Radiology 1986;160:313-317 Cann CE, Gamsu G, Bimberg FA, et al. Quantification of calcium in solitary pulmonary nodules using single- and dual-energy CT. Radiology 1982; 145:493-496 Hickey NM, Niklason LT, Sabbagh E, Fraser RG, Barnes GT. Dual-energy digital radiographic quantification of calcium in simulated pulmonary nodules. AiR 1987;148: 19-24 Herman PG, Hessel SJ. The diagnostic accuracy and complications of closed lung biopsies. Radiology 1977;125: 11-14 Khouri NF, Stitik FP, Erozan YS, et al. Transthoracic needle aspiration biopsy of benign and malignant lung lesions. AIR 1985;144:281-288 vanSonnenberg E, Casola G, Ho M, et al. Difficult thoracic lesions: CTguided biopsy experience in 150 cases. Radiology 1988;167:457-461 Naidich DP, Sussman R, Kutcher WL, Aranda CP, Garay SM, Ettenger NA. Solitary pulmonary nodules: CT-bronchoscopic correlation. Chest 1988;93:595-598 Epstein DM, Stephenson LW, Getter WB, et al. Value of CT in the preoperative assessment of lung cancer: a survey of thoracic surgeons. Radiology 1986;161 :423-427 Pearlberg JL, Sandier MA, Beute GH, et al. Ti NO MO bronchogenic carcinoma: assessment by CT. Radiology 1985;1 57:187-190 Heavey LR, Glazer GM, Gross BH, et al. The role of CT in staging radiographic Ti NO MO lung cancer. AIR 1982;146:285-290 Conces DJ Jr, Klink JF, Tarver RD. Moak GD. Ti NO MO lung cancer: evaluation with CT. Radiology 1989;170:643-646 Martini N, Flehinger BJ, zaman MB, et al. Results of resection in non-oat cell carcinoma of the lung with mediastinal lymph node metastases. Ann Surg 1983;198:386-396 Ratto GB, Mereu C, Motta
G. The prognostic
significance
of preoperative
assessment of mediastinal lymph nodes in patients with lung cancer. Chest 1988;93:807-813 Staples CA, Muller NL, Miller RR, Evans KG, Nelems B. Mediastinal nodes in bronchogenic carcinoma: comparison between CT and mediastinoscopy. Radiology 1988;167:367-372
701
Review
Evaluation
Radiologic W. Richard
of the Solitary
studies are performed or interpreted, several very important clinical factors should be considered. First, in patients less than 30 years of age, the prevalence of bronchogenic carcinoma is so low that a solitary pulmonary nodule generally should be followed-up radiologically without any further evaluation, unless the patient has a known extrathoracic primary malignancy [4]. In some patients in this age group, needle biopsy is performed before follow-up; biopsy may be requested if the patient is very concerned about the possibility of carcinoma, or has a significant risk factor for carcinoma. Although a history of an extrathoracic primary malignancy suggests that a solitary nodule is a metastasis rather than a lung cancer, this is not always the case [5]. In a patient over 35 with an extrathoracic malignancy and a solitary nodule, the likelihood that the nodule represents a bronchogenic carcinoma depends on the cell type of the extrathoracic tumor. If the extrathoracic malignancy is of squamous cell origin, the nodule is most likely a lung cancer. If the extrathoracic primary is a melanoma or sarcoma, the nodule is probably a metastasis. An extrathoracic adenocarcinoma indicates that the lung nodule has about 50% chance of being lung cancer. Sputum cytology should be obtained in all patients with a solitary pulmonary nodule in whom cancer is considered a possibility. False-positive sputum cytology is rare (07-3%) and a positive sputum cytology is the most reliable preoperative method (except biopsy) for diagnosing a pulmonary malignancy. False-negative cytology is far more common, occurring in 10-30% of all patients with lung cancer and in
Considerations
Clinical and historical data, such as dwelling and travel history, risk factors for carcinoma (e.g., smoking), and skin test results should be considered in the evaluation of any patient with a solitary pulmonary nodule, but these data are not generally specific enough to alter the patent’s diagnostic evaluation or eventual treatment. However, before imaging
Received
Nodule
Webb1
The diagnostic evaluation of a patient with a solitary pulmonary nodule is a common problem in radiologic practice. Although there is no universally accepted definition of a solitary pulmonary nodule, this term is usually used to refer to a lung lesion that is reasonably well defined, round or oval, and less than 5 or 6 cm in diameter. The differential diagnosis of a solitary nodule is extensive, but its radiologic evaluation is primarily directed at distinguishing nodules that are benign, and thus inconsequential, from nodules that are malignant or potentially malignant, and require treatment. The large majority of solitary nodules detected radiographically are benign [1-3]. A variety of radiologic procedures have been used for the examination of patients with a solitary pulmonary nodule. Currently, plain chest radiographs and CT are of most value. Simply stated, the goals of imaging in patients with an undiagnosed lung nodule are (1) to make a specific diagnosis; or (2) if a specific diagnosis cannot be made, to distinguish benign nodules from those that are indeterminate and thus potentiallymalignant; or (3) if benign and malignant cannot be distinguished, to help determine what should be done next.
Clinical
Pulmonary
Article
August
‘Department AJR 154:701-708,
14, 1989;
of Radiology. April
accepted
after revision
November
University
of California,
San Francisco,
1990 0361 -803X/90/1
544-0701
14, 1989.
American
San Francisco, Roentgen
CA 94143-0628.
Ray Society
WEBB
702
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up to 60% of thOSe ative cytology does lesion.
Chest
with peripheral malignancies. Thus, nagnot preclude the presence of a malignant
Radiographs
A number of plain film criteria have been reported to be of some value in diagnosing a lung nodule as benign. These include smallness, regular or round shape, smooth contour, sharp edge definition, the presence of satellite lesions, a slow or very fast doubling time, and absence of cavitation. However, these plain film criteria rarely allow a specific diagnosis of benignity to be made. Even attempts to use computers to aid in diagnosis have not resulted in more than 90% accuracy in distinguishing benign and malignant lesions [6]. The individual patient with a solitary pulmonary nodule cannot be properly managed with this degree of uncertainty as to whether or not a nodule is benign. However, two radiologic features-dense or central calcification and absence of growth-can be used to indicate that a solitary pulmonary nodule is benign, for all practical purposes. In patients with either finding, a solitary pulmonary nodule can be followed with sequential chest radiographs at progressively increasing intervals (2 months at first, increasing to 1 year if the nodule is unchanging), but no other examination is usually necessary.
Calcification Dense central, laminated, or diffuse calcification virtually excludes malignancy (Fig. 1). Although bronchogenic carcinomas (scar carcinomas) may incorporate an adjacent calcified granuloma, resulting in a mass with calcification, the
0 DIFFUSE
CENTRAL
AJR:154,
April 1990
calcification is usually eccentric rather than central (Figs. 1 and 2). In addition, bronchogenic carcinomas may themselves calcify; this calcification is often stippled and is frequently not detectable radiologically (Fig. 1). In a study of 72 patients with malignant solitary pulmonary nodules, calcification was visible on radiographs of the resected specimen in 1 0, but in only one was calcification detectable on standard chest radiographs [7]. In the same study, 67 of 1 35 benign lesions (mostly granulomas and hamartomas) contained calcifications on specimen radiographs; in 46, these calcifications also were visible on standard chest radiographs. Metastatic malignant tumors (particularly osteogenic sarcoma, chondrosarcoma, and thyroid carcinoma) can show stippled or homogeneous calcification, but the nodules are usually multiple. Calcification in a solitary pulmonary nodule is usually best appreciated on low-kilovoltage radiographs, but these are of limited value except in obvious examples. Fluoroscopy can also be of value in projecting a nodule away from overlying densities, therefore allowing calcification to be seen more clearly, but this technique is not routinely used because of relatively poor resolution.
Growth
Rate
The growth rate of a solitary pulmonary nodule (usually quantitated by using doubling time-the time required for a doubling of volume) has been used to determine its likelihood of being malignant [8]. A pulmonary nodule that doubles in volume in less than 1 month or more than 1 8 months is usually benign. However, the overlapping growth rates of benign and malignant lesions, particularly among rapidly growing nodules, makes the use of doubling time hazardous as an absolute indicator of benignity. Nevertheless, it is generally agreed that a solitary pulmonary nodule that does not grow over a 2-year period is benign and does not require resection. Only rare exceptions to this rule have been reported. Therefore, a vigorous search for old films must be the first step in the evaluation of a noncalcified solitary pulmonary nodule. If films 2 years or older show the pulmonary nodule to be unchanged, follow-up radiographs at intervals are all that is usually nec-
essary.
POPCORN
LAMINAR,
CONCENTRIC
0 STIPPLED
ECCENTRIC
B Fig. 1.-A and B, Some patterns of benign (A) and “malignant” (B) calcification seen on plain radlographs or CT scans can be helpful in predicting that a lung nodule is benign. Malignant patterns can be seen with either benign or malignant lesions.
If no old films are available, or if prior films are not old enough, the diagnostic approach may be based on the patient’s age and the plain radiographic appearance of a lesion. If the patient is less than 30 years of age and the pulmonary nodule appears benign (small, round, sharply defined), followup with standard chest radiographs generally is sufficient. However, if the patient is older, has a history of an extrathoracic tumor, or if the lesion does not appear benign (i.e., it is large, irregular, poorly defined, or spiculated), further diagnostic procedures must be performed. Also, occasionally a patient with an acute process, such as pulmonary embolism or focal pneumonia, can present with a nodular density on chest radiographs. In a patient with acute symptoms, a follow-up radiograph in 1-2 weeks can sometimes show a decrease in the size of a nodule, indicating its benign nature. In some patients without symptoms, repeat
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AJR:14,
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NODULES
703
Fig. 2.-A, Plain radiograph in patient with a nodule in right upper lobe shows eccentric calcification (arrow). Mass is poorly defined and spiculated, suggesting malignancy. B, Conventional CT scan at this level shows nodule and focus of calcification. At surgery, this was a carcinoma engulfing a granuloma. Thus, this tumor may represent a scar carcinoma arising in relation to the inflammatory lesion.
radiographs will show a similar decrease in size, indicating that the lesion is benign. Because of this, one or two followup radiographs at 1- to 2-week intervals are often obtained in a patient with a solitary nodule, usually during examination, to assess the stability of the lesion. However, it is not advisable in most subjects to obtain follow-up radiographs, hoping that a nodule will decrease in size. Furthermore, in some patients with cancer, nodules become less well defined as they grow and can appear smaller.
CT CT is performed in most patients with a solitary pulmonary nodule to define the morphology of the lesion, detect calcification, and help in biopsy planning. It has largely replaced conventional tomography for these indications. Although conventional CT with 1 -cm collimation can provide this information in some cases, CT with thin collimation, and particularly high-resolution CT, is superior to conventional CT in delineating nodule morphology and allowing the detection of calcification. When studying a patient with a solitary nodule by using CT, we typically obtain contiguous high-resolution CT scans through the nodule, monitored by the radiologist, followed by a conventional CT study aimed at evaluating the remainder of the lung parenchyma, mediastinum, and hila.
Confirmation
of a Nodule
and Delineation
of Morphology
When a solitary nodule is suspected on plain radiographs, CT is often used to confirm that a nodule is present and to define its morphologic characteristics. In addition to conventional CT (contiguous 1 -cm collimation), thin-slice, high-resolution CT scans can be quite variable in evaluating focal pulmonary parenchymal lesions [9]. We commonly obtain several contiguous high-resolution scans through the abnormal area in a patient with a lung nodule. A few types of nodular lung lesions have morphologic characteristics typical enough to allow a diagnosis to be made on CT (Fig. 3). These include arteriovenous fistulas, rounded atelectasis, focal consolidation, pleural plaques, fungus balls (Fig. 4), and mucous plugs. Pulmonary malignancies (particularly adenocarcino-
mas) often appear irregular and spiculated on high-resolution CT, and this appearance strongly suggests malignancy (Fig. 5) [10]. Identification with CT of multiple lung nodules in a patient in whom a single nodule is visible on plain films suggests metastases as the likely diagnosis, but lung cancer in association with other causes of lung nodules (e.g., granulomas) must also be considered, particularly if one nodule is dominant. Furthermore, any patient with lung cancer has an increased risk (compared with the general population) of having a second lung cancer synchronous with the first. Thus, if two nodules are visible, both may be primary lung cancers, and both may be resectable. However, this is rare and occurs in less than 1% of patients [1 1 12]. ,
CT Nodule
Densitometry
In 1980, Siegelman et al. [1 3] suggested the use of quantitative CT densitometry for the detection of calcium in lung nodules, thus indicating their benignity. They indicated that calcification invisible on plain radiographs or tomograms could be detected by high CT numbers by using CT with thin collimation. In their initial report [1 3], 91 solitary pulmonary nodules with an uncalcified appearance on conventional tomography were studied with CT. Averaging the highest CT numbers for each nodule, all 45 primary tumors and 13 metastatic nodules were found to have values of less than 1 64 H, whereas 20 of 33 benign nodules were identified as such by a representative CT number of over 1 64 H. Other investigators had difficulty in duplicating their results [14, 1 5], largely because of differences between scanners and image reconstruction algorithms. In general, most benign nodules were found to have representative CT values much less than the 164 H cutoff that has been reported. However, other authors confirmed the potential usefulness of this technique, and the results of Siegelman et al. were subsequently confirmed in a larger series [16-18]. From 22% to 36% of lung nodules that cannot be shown to contain calcium by using conventional tomograms are found to contain calcium by using CT [16-18].
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AJA:154,
Fig. 3.-A
and B, High-resolution
April 1990
CT scans
at
two levels in patient with a poorly defined 1-cm nodule visible on chest radiographs. On highresolution CT, nodule is seen to consist of a number of smaller, well-defined nodular densities. This appearance suggests a granulomatous disease, and CT-guided needle aspiration biopsy resufts showed an atypical Mycobacterlum.
P A
B Fig. 4.-CT scan in patient with usual interstitial pneumonitis and a nodule in right upper lobe. lntracavitary mass strongly suggests the presence of a fungus ball. -4
‘4
“I”
I
4
Fig. 5.-High-resolution CT scan in patient with a nodule in upper lobe. Spiculated mass Is very suspicious for carcinoma. Nodule densitometry is not appropriate with nodules having this appearance on plain films or CT scans, because many represent tumors. An adenocarcinoma was found at surgery.
/
5
Further study of individual scanners, scanner geometry, and reconstruction algorithms emphasized the rather considerable variation in nodule density measurements obtained with different scanners, for nodules of different sizes, in different locations, and in patients of different size and chest wall thickness [1 9]. These variables made the use of CT number criteria applicable to one machine difficult or impossible to use on another. It was a difficult problem. One approach to solving this problem was the development of an anthropomorphic phantom for use in chest CT [20]. This phantom can simulate the shape, dimensions, and density of thoracic structures in most patients. Cylinders of various diameters, made of plastic to correspond to the density of a calcified nodule (described as having a density of 164, 190, and 264 H in different publications [20-22]), serve as the reference density for a solitary pulmonary nodule. In this technique, after a patient with a solitary nodule is studied with thin collimation, the phantom is put together to simulate the same slice level, chest wall thickness, nodule location, and size, and then the phantom is scanned with the identical CT technique that was used in scanning the patient (Fig. 6). Then, the densities of pixels in the patient’s nodule and the phantom nodule are compared. If pixels in the lung nodule are denser than those in the phantom nodule, calcium is considered to be present [21-23]. Thus, this phantom is
assumed to provide a measurement of density independent of equipment-related or patient-related variations. However, as stated above, because lung carcinomas can contain some calcium, not all nodules shown to contain calcium on CT scans can be diagnosed as benign. It has been recommended that in order to call a nodule benign, dense pixels must be diffuse or central within the nodule, account for 1 0% or more of the cross-sectional area, and be visible on more than one scan; in other words, the detectable calcification must be of substantial size and central within the nodule (what would be expected for a benign lesion). Thus, CT nodule densitometry with this phantom is not only quantitative, but is qualitative as well. It can be thought of as being used in a way similar to, but in a more objective fashion than, conventional tomography. Also, in order to reduce the risk of calling a calcified carcinoma benign, it has been recommended that a nodule be lobulated or smooth rather than spiculated if it is to be diagnosed as benign, and less than 2 cm in size [16, 2123]. Large or spiculated nodules are much more likely to be carcinomas than smaller, better defined lesions. Because of this, patients who have nodules that are larger than 2 cm or appear spiculated on plain radiographs should not undergo CT nodule densitometry; with such nodules, densitometry would be of no value.
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AJR:154,
SOLITARY
April 1990
PULMONARY
NODULES
705
Fig. 6.-A, Thin, collimated CT scan reconstructed with standard algorithm In patient with a small nodule in right lung. B, CT phantom has been constructed to simulate same slice level, nodule size, and location, and phantom has been scanned by using Identical technical factors. C, CT numbers recorded from nodule include many pixels exceeding 100 H and some exceedleg 200 H. D, Numbers recorded from phantom nodule are considerably lower. Thus, lung nodule Is calcified.
B NX
126
127
128
129
130
131
132
133
134
NX__117
118
119
120
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202
-839
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284
-648
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-177
-126
-64
-24
-147
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203
-627
-279
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285
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-11’
-35
-24
-319
204
-399
-64
286
-192
-81
5
-279
205
-265
287
-118
-23
41
-25
-326
205
-241
288
-187
-77
-88
-419
20’
-339
289
-354
-183
-221
-554
205
-533
-163
209
-765
-464
-226
-109
-86
210
-921
-799
-623
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-473
2
-579
291
-
-3% -654
2 -55 -228 -538
18
82
94
38
87
141
118
85
161
205
135
85
184
227
1%
52
146
1%
-103 -433
3 -337
72
42
-92
-301
-375
2
-405 -563
-6% -751
C
-241
121
283
-205
122
123
124
125
-283
-477
-742
-919
-13
-146
-446
-782
-1%
-613
12
30
32
35
38
27
-1
13
35
33
31
19
23
-74
-482
24
33
33
31
21
35
-52
-461
-9
50
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26
28
43
-2
34
37
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-113
-549
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-722
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-714
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D
B
C
Fig. 7.-A, Conventional CT scan with 1-cm collimation at level of a nodule in right lung. B, With medlastinal window for this slIce, nodule Is InvIsible and no evIdence of calcification C, Thin, collimated scan shows nodule Is densely calcified. Measured CT numbers exceeded
In a cooperative study [21 ]of this phantom, 298 pulmonary nodules were evaluated. Of 69 nodules determined to contain substantial calcification, 68 were benign and one was malignant. Of the 229 remaining patients who had nodules that did not contain substantial calcification (indeterminate nodules), 176 had malignant nodules.
Is shown. 400 H.
It must be emphasized that the thin-section (1 .5-mm) technique is necessary when using CT for the diagnosis of nodule calcification. Calcium easily diagnosable on thin-section CT is sometimes invisible with 1-cm collimation (Fig. 7). Also, in regard to the study reporting the use of the chest phantom for nodule densitometry [21], in approximately half of the
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706
cases in which a nodule could be called benign, calcium was easily visible within the lesion on the thin-section scans, and the phantom itself was unnecessary. Furthermore, concurrent improvements in scanner technology allow more accurate density measurements with CT, obviating a phantom in many cases. Some current scanners appear to be better densitometers, and less susceptible to variations in CT number measurement, than the scanners that prompted the invention of this phantom [24]. In our institution we routinely perform nodule densitometry using a GE 9800 machine, without using a nodule phantom. Although varying technical factors (kVp, mA, reconstruction algorithm) can be used in performing nodule densitometry with adequate results, we prefer using relatively high-kVp settings (because of decreased image noise and a more linear relationship between CT number and calcium content) and a high-spatial-frequency algorithm (GE bone), which improves spatial resolution and may be slightly more sensitive than the standard algorithm for detecting small amounts of calcium [24]. Nodules with visible calcification on the thin-section scans will generally have CT number values of about 400 H on the GE 9800 (Fig. 7). We regard nodules with CT numbers of more than 200 to contain calcium (Fig. 6) [24]. CT with thin collimation can also be valuable in diagnosing pulmonary hamartomas. In one study [25], 30 of 47 patients with a hamartoma were correctly diagnosed with CT because of visible fat, either focal or diffuse (CT numbers ranging from -40 to -120 H); fat and calcification; or diffuse calcification (Fig.
8).
Dual-Energy It has in a lung scanning (calcium) different beam at amount
Techniques
been suggested that the amount of calcium present nodule can be quantified by using a dual-energy CT technique [26]. Elements with high atomic numbers exhibit different degrees of X-ray absorption at energies. By noting the attenuation of the X-ray different energies, one can accurately quantify the of calcium in an area of interest. However, because
AJR:154,
April 1990
of technical difficulties, this technique has not yet been used clinically in a large series. Replicating the exact same level on the two different scans obtained with different energies is the primary difficulty with this technique. Preliminary experiments with dual-energy digital radiography with the two energy measurements obtained simultaneously have been reported recently [27]. Because there is exact correspondence of the dual-energy images, the problems of misregistration occurring with CT have been avoided. With this technique, measurements of calcium in simulated lung nodules in a phantom have been quite accurate. However, as with dual-energy CT, digital radiography techniques remain experimental.
Use of Imaging
to Guide
Biopsies
If plain radiography and CT do not allow a specific diagnosis to be made, and no calcification is visible within the nodule, a biopsy may be necessary. Depending on the clinical situation, and the prejudices of the patient’s physician, several options are available. These may include needle lung biopsy, bronchoscopy, mediastinoscopy, or thoracotomy. To some degree, imaging studies can be valuable in making this choice.
Aspiration
Lung Biopsy
or Bronchoscopy?
Aspiration needle biopsy has become firmly established in the investigation of peripheral solitary pulmonary nodules suspected of being neoplastic [28, 29]. Biopsies can be performed on lesions as small as 1 cm, although the minimum size varies with the skill of the operator. Confirmation of the tip of the needle within the lesion must be obtained. Biplane fluoroscopy is the most conventional method, but single-plane fluoroscopy and CT may also be used. Needle biopsy of the lung is a safe procedure. Although pneumothorax occurs in about 20% of patients, intercostal tube evacuation is required in only a few percent. In patients with carcinoma, hemorrhage and death are uncommon; dis-
Fig. 8.-A, High-resolution CT scans with lung window settings in patient with a small nodule detected on plain films. B, With mediastinal window settings, nodule (arrow) appears to be of a density similar to that of subcutaneous fat. C, CT numbers measured from this nodule indicate It is entirely or almost entirely fat. Hamartomas can have this appearance. up with plain radiographs and remained unchanged in size.
This lesion
was followed
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AJR:154,
SOLITARY
April 1990
PULMONARY
semination of malignant cells from an aspiration biopsy may occur rarely. Needle aspiration will yield malignant cells in more than 90% of neoplastic nodules. This percentage can be optimized by having a cytologist on hand at the time of the biopsy, and repeating the biopsy if specimens are negative. Cytologic determination of cell type is good for squamous cell carcinomas and adenocarcinomas, but poor for undifferentiated tumors. A bacterial diagnosis can be made in almost 70% of infectious nodules. The diagnosis of a benign nodule (e.g., hamartoma) can also be made, though this usually requires a larger aspirate than for the diagnosis of malignancy. The indications for needle aspiration biopsy vary between institutions, often determined at least in part by the preference of the surgeon. I think an argument can be made for reserving needle biopsy for those patients with solitary pulmonary nodules who are not candidates for thoracotomy because of age, complicating illness, or because the lesion is suspected of being a metastatic deposit. Because of the relatively high false-negative rate (up to 1 0%) in patients with carcinoma, a negative biopsy cannot be taken to mean that no tumor is present. If a patient can tolerate surgery, a solitary pulmonary nodule that could represent a malignancy is often resected without a preliminary needle biopsy. In patients suspected of having a benign nodule because of its appearance or growth rate or the patient’s age, needle biopsy can be used to make a specific diagnosis of a benign lesion or to increase the likelihood of a benign process prior to radiologic follow-up. It is important to note that the role of needle biopsy in patients with a solitary nodule can vary considerably from one institution to the next. CT can be helpful in planning a needle aspiration biopsy [30], even if CT is not used for the biopsy itself. First, CT can indicate the depth of the lesion, and the needle can be marked for the appropriate depth. Second, CT can help in planning the biopsy approach. If bullae lie in the path of the needle, or the needle must cross a fissure to reach the lesion, the risk
F,
j
I
Fig. 9.-CT scan in patient with a small nodule In right lung shows nodule (large arrow) is closely related to posterior segmental bronchus of right upper lobe (small arrow). Because of this, it was approached bronchoscopically rather than with a percutaneous biopsy; brush cytology findings were positive.
NODULES
707
of pneumothorax is increased, and a different approach might be used. Bronchoscopy is most accurate in diagnosing central masses with an endobronchial component, whereas needle biopsy is best for peripheral lesions. Thus, the location of the lesion can be important in choosing the biopsy procedure. CT can be quite valuable in this regard. If an endobronchial lesion is detected with CT, or bronchial narrowing at the site of a hilar mass is visible, bronchoscopy directed to the proper level is most appropriate (Fig. 9) [31]. In some patients, CT will show an endobronchial lesion beyond the visibility of the bronchoscope, and thus guide the biopsy attempt.
CT for Staging
Cancer
in Patients
with a Solitary
Nodule
If a patient with a lung nodule is known to have a carcinoma from needle aspiration biopsy or cytology, or is strongly suspected of having a malignant lesion, then the radiologic examination, particularly with CT, has an additional goalspecifically to determine the resectability of the tumor. However, the use of CT for staging cancer in patients with solitary nodules is controversial. Because of the relatively low likelihood of mediastinal node metastases in patients with solitary lung nodules who do not have evidence of hilar or mediastinal mass on plain radiographs, a number of surgeons perform thoracotomy on patients with a potentially malignant nodule without further biopsy or staging procedures (including CT). For example, in a recent survey of thoracic surgeons [32], only 1 5% of surgeons would obtain a CT scan preoperatively to evaluate the extent of the disease in a patient with a peripheral nodule. Furthermore, the value of CT in staging cancer in patients with Ti lesions (peripheral nodules :3 cm in diameter) has not been clearly established, and some investigators believe it may provide misleading information regarding the status of mediastinal nodes [33-35]. In patients with a solitary nodule, if mediastinal node metastases are found at surgery, they may be resectable with a reasonable chance of cure if they are ipsilateral [36], and particularly if they are low in the mediastinum and the primary tumor is squamous cell. Some thoracic surgeons believe that positive lymph nodes found at mediastinoscopy rule out effective surgery treatment of lung cancer [37, 38]; in several studies, patients with positive findings on mediastinoscopy had a relatively poor survival rate after surgical resection, compared with patients in whom mediastinoscopy showed negative results but positive nodes were found at surgery. Because of this, these surgeons perform mediastinoscopy in all lung cancer patients, including those with a solitary nodule. Recently, two studies [37, 38] found mediastinoscopy and CT to have the same reasonably high sensitivity for detecting mediastinal node metastases. However, as would be expected, mediastinoscopy was 100% specific (no normal cases were called abnormal), whereas CT had a specificity of 50-65%. Despite this, these authors recommend that CT (in addition to mediastinoscopy) be performed in evaluating patients with solitary nodules. In their opinion, if CT shows abnormal lymph nodes, it should be used to guide mediastinoscopy and
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708
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biopsy. However, it is also pointed out that biopsy should not be limited to nodes that appear abnormal on CT; other nodes may be the ones involved by tumor.
AJR:154,
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