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Commentary |
1 Department of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Unit 371, 1515 Holcombe Blvd., Houston, TX 77030.
Received November 26, 2007; accepted after revision December 1, 2007.
Address correspondence to E. M. Marom
(emarom{at}di.mdacc.tmc.edu).
Keywords: CT • lung • nodule
Since the introduction of chest radiography, radiologists have been struggling to distinguish between benign and malignant pulmonary nodules on imaging. Surgically removing all suspicious nodules is not only impractical because of their prevalence in the population but also because of the associated risk because the mean postoperative mortality rate after lung cancer resection in the United States is 5% [1].
CT revolutionized the workup of solitary pulmonary nodules by markedly improving the detection rate compared with chest radiography and linear tomography and by allowing radiologists to objectively measure the internal characteristics of nodules. However, neither of these advantages was apparent in the early days of CT use.
The use of CT in chest imaging initially encountered some reluctance because of radiography's high quality in imaging pulmonary nodules, secondary to the natural contrast, air. CT was eagerly embraced by those imaging the brain and abdomen, but not the chest [2]. In the late 1970s, CT detection of pulmonary nodules was proven to be superior to chest radiography and linear tomography [3]. Improved detection led to more nodules detected, which made it more important to distinguish benign from malignant nodules.
The ability of chest radiography to discern between malignant and benign pulmonary nodules was and still is limited. Numerous studies in the 1940s and 1950s attempted to address this issue as the use of chest radiography exponentially increased. Before the advent of CT, positive preoperative diagnoses were seldom made of asymptomatic solitary pulmonary nodules; early exploratory tho raco tomy was strongly urged for these nodules [4, 5]. Two methods of distinguishing between benign and malignant nodules were developed, both of which became popular over the years: stability of the nodule over a period of 2 years and benign-appearing calcifications. However, both methods were problematic. Stability was not robustly and scientifically found to be reliable, with the original data from the 1950s suggesting a positive predictive value of 65% for benignity [6]. Identifying benign calcifications was subjective on radiography, as found in a later study [7].
Siegelman et al. [8] were the first to apply the ability of CT to measure soft tissues to pulmonary nodules. It was a breakthrough in the evaluation of the internal characteristics of pulmonary nodules: for the first time, an objective criterion was used to determine whether a nodule was dense enough to be considered calcified. By studying 91 nodules in 88 patients, Siegelman et al. found a Hounsfield unit (H) threshold of 164 H, above which nodules were considered calcified and thus presumably benign. The reasoning used for this threshold was that nodules that were sufficiently dense to be identified by chest radiography were believed to be benign because ma lig nancies with calcifications in them had been identified in < 1% of patients on radiography [9–11]. They assumed the increased sensitivity of CT would lead to the identification of an increased number of benign nodules, with no false-negatives and that this would lead to fewer futile thoracotomies.
Several studies tested this threshold method, which was perfected by using phantom pulmonary nodules with a specific density to overcome machine-dependent factors that could influence specific Hounsfield measurements. More than 10% of nodules that had been evaluated with a threshold of 185 H (above which nodules should be benign) were malignant. Thus, this threshold was abandoned because it did not reliably distinguish between benign and malignant nodules [12]. However, the use of CT for documentation of obviously calcified nodules by visual inspection and the characterization of the calcification was and still is used today for establishing benignancy with a few caveats that were discussed in a comprehensive follow-up study by Siegelman et al. [13]. For a nodule to be considered benign, it was shown that it should have benign-type calcifications either of the popcorn type or dense central or diffuse. If calcifications were eccentric or if a nodule was bilobed, irregular, or spiculated, it should not be considered benign despite the presence of benign-appearing calcifications.
The Siegelman et al. [8]
study remains a turning point, even though it did not stand up to the test of
time. As Alexander Graham Bell best phrased it, "When one door closes
another door opens." The method of Siegelman et al. of evaluating the
Hounsfield measurement of a pulmonary nodule can still be used to reliably
identify some benign pulmonary nodules, thus decreasing unnecessary
intervention. Pulmo nary nodules containing fat on the basis of their
Hounsfield measurement are considered to be hamartomas, with no need for
follow-up [14,
15]. The vessels supplying
tumors differ both quantitatively and qualitatively from those supplying
benign growths and tend to be more "leaky." This inherent
difference between malignant and benign blood supplies can be shown by changes
in Hounsfield values in the pulmonary nodule after IV contrast injection. This
method was perfected by Swensen et al.
[16,
17], who showed that the
absence of significant lung nodule enhancement (
15 H) at CT is suggestive
of benignity. Although it is not 100% accurate in separating benign from
malignant nodules, it does have high sensitivity, and this method can be used
to guide followup or intervention. The method of Hounsfield value changes
after contrast enhancement is also currently used to evaluate the effects of
novel chemotherapeutic agents on tumor vascularity.
Radiologists must not only use each new imaging technique but also cautiously test it. An open, innovative mind is important in these evaluations; we must allow ourselves to make mistakes. Repeated testing will show us which methods are best for the practice of medicine and may hopefully benefit mankind.
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