General > SPN

Evaluation of the Solitary Pulmonary Nodule:

Click here for a discussion of FDG PET imaging in the evaluation of solitary pulmonary nodules

A solitary pulmonary nodule (SPN) is an opacity in the lung parenchyma that measures up to 3 cm in size and that has no associated mediastinal adenopathy or atelectasis [24]. Lesions over 3 cm are classified as masses [24]. In the United States, more than 150,000 new SPN's are identified each year by conventional CXR and an even greater number are detected by CT [28]. The differential for a SPN is quite broad, but a large percentage of these lesions may prove to be malignant (especially if the lesion is larger than 2 cm). In the evaluation of an SPN, only 10-20% of patients with malignancy will have sputum positive for cancer, and up to 30% of patients with negative transthoracic biopsies are ultimately found to have malignancy [1]. Growth rate assessment is an important and cost-effective step in the evaluation of the indeterminate solitary pulmonary nodule [16]. Generally, nodules are followed for at least a two year period. Although many people quote that lesion stability over a two year period indicates that the nodule is benign, this statement was taken out of content from the original article in which it appeared [16]. Caution must be used when applying this criteria to pulmonary nodules- particularly ground glass or subsolid nodules [8,40]. In fact, no growth over a two year period has a positive predictive value for benignity of only 65% (sensitivity is 40%, and specificity is 72%). All two year stability implies is that the lesion has a doubling time of at least 730 days (most malignant lesions have doubling times between 20 and 400 days). Indolent neoplasms such as bronchalveolar cell carcinoma can have doubling times in excess of 490 days and may be incorrectly classified as benign if studied only for a two year period [19,27]. For sub-solid nodules, the median volume doubling time for noninvasive adenocarcinoma has been suggested to be 939 days (range 588-1563 days) and for invasive adenocarcinoma 678 days (range 392-916 days) [63]. For nodules with volumes between 100-300 mm3, a doubling time of less than 400 days has been associated with a lung cancer risk of 9.9%, between 400-600 days with a 4% risk, and over 600 days with a 0.8% risk [55]. None-the-less, experience suggests that most solid nodules greater than 1 cm in diameter that are stable in size for at least a two year period are benign [16].

One point to remember is that subtle increases in volume may not be appreciated on CT imaging- particularly for small nodules. A doubling in volume manifests as a 26% increase in diameter [52]. Volumetic doubling of a 6 mm lesion results in a 1.6 mm increase in diameter- this small difference in size may easily go undetected on CT [2]. Importantly, a lesion may also grow asymmetrically in the Z-axis and such growth is not readily appreciated on axial CT images [17,27]. 3D volumetric measurements for growth of the lesion are a more accurate way to assess for enlargement [17,27,49]. However, even volumetric measurements can demonstrate variability- in one study of patients scanned 3 times in the same session, the interscan volumetric variation was +/- 20% [40]. The variability is greatest for small (less than 1 cm nodules), ground glass nodules, and those with spiculated or irregular borders. Sources of error include cardiac and respiratory motion, varying scan slice thickness, and nodule location [29]. Juxtapleural and juxtavascular nodules have been shown to have greater variability in volume measurements compared to completely intra-parenchymal nodules [29]. Measurements obtained when using a bone algorithm are larger than those obtained when using a standard algorithm [33]. The use of IV contrast can also result in an increase in the measured volume of a nodule (median increased of 4-7% [46]) [33,46]. As such, it is recommended that nodule volume be measured from the same type of scan (contrast or no contrast) at follow-up [46]. At least one study has demonstrated that there is no fairly good nodule volume determination even when using reduced dose imaging parameters and iterative reconstruction in a phantom model [49].

NOTE- rarely a malignant nodule may show an initial decrease in size on followup imaging [52]. This transient decrease in size may be related to the development of a fibrous component and subsequent collapse of the fibrosis [52]. Accordingly, a decrease in nodule size still requires followup to confirm long-term stability [52].

At CXR, an SPN is seldom evident until it is at least 9 mm in diameter [26]. Tomosynthesis is a method to improve detection of small nodules on CXR [41,54]. In tomosynthesis, by collecting a number of projection images at different angles with a digital detector, an unlimited number of section images at arbitrary depths can be produced [41]. The section images contain much less of the overlapping anatomy and this results in improved lesion detection [41]. One drawback of tomosynthesis is higher patient radiation exposure [41]. For one tomosynthesis unit, 60 projection low exposure images are collected as the tube moves over an angle of 30 degrees- each with an effective dose to a standard patient of approximately 2 uSv [41,54]. The resulting total effective dose is 0.10-0.12 mSv (range 0.07-0.41 mSv) [41,54]. This dose is approximately 2-3 times higher than for a conventional exam (0.06 mSv [range 0.02-0.19 mSv]), but is still much lower than the radiation dose from a typical CT scan (approximately 4 mSv- which is about 30 times higher than the dose from the tomosynthesis exam) [41,54]. More than 3 times as many nodules can be detected using tomosynthesis compared to conventional CXR [41]. In one study, for nodules 4-6 mm in size- only 7% were detected on CXR, while tomosynthesis detected 51% of these small nodules [41]. One drawback of tomosynthesis is an increase in the number of false positive findings (approximately 50% higher than CXR) [41]. Tomosynthesis has also been shown to be superior to dual-energy chest radiography for nodule detection [54].

Computer-aided detection is also being explored to aid in detection of lung nodules/cancers [42]. CAD has been shown to detect up to 47% of missed lesions [42]. However, the radiologist must still decide if the area being highlighted by the CAD represents a true finding, or a false positive as there are an average of 4 false-positive results per radiograph [42].

Volumetric mutlidetector CT (MDCT) is clearly superior to CXR in the detection of nodules smaller than 1 cm. Using surgical exploration and histologic analysis as the gold standard, the sensitivity of CT to detect pulmonary nodules has been reported to be 100% for nodules greater than 1 cm, 95% for nodules larger than 5 mm, and 66% for nodules 5mm or less in size [30]. From screening studies, the likelihood for malignancy in a nodule less than 5mm in size is under 1% (in a patient with no oncologic history) [22]. However, in a retrospective review of surgically resected nodules smaller than 1 cm, 58% of the lesions were found to represent a malignancy [2]. Although there is certainly a selection bias introduced in a retrospective review, this study obviously shows that even small lesions do have a substantial risk of representing a malignancy. In that study, 41% of small nodules were found to be malignant in patients with no history of prior malignancy; while 82% of resected lesions were malignant in patients with a history of prior malignancy (54% metastatic disease and 29% new primary bronchogenic carcinomas). When more than 2 small nodules were identified in a patient with an underlying malignancy, the likelihood that the lesions represent metastases was 80% (previous studies indicate that such findings can be associated with metastatic disease in up to 97% of cases) [2]. In another somewhat flawed retrospective review of small (under 1 cm) pulmonary nodules, the likelihood for malignancy was 11% (and 90% of the malignant nodules were found in patients with a known primary) [18]. Unfortunately, this study used 2 year stability to define a benign nodule [18]- whereas all this really indicates is a nodule with a slow doubling time. The authors concluded that the risk of malignancy in a small pulmonary nodule in a patient with no risk factors and no known primary "may be" as low as 1% [18]. The author's suggested that follow-up exams may not be necessary in this subgroup of patients [18] (see Fleischner Society guidelines below).

The patients clinical history provides important information in the evaluation of a pulmonary nodule [24]. The likelihood for lung cancer increases if the patient has a smoking history and the risk is directly proportional to the number of pack-years smoked [26]. In fact, for smokers over the age of 44 with another known underlying malignancy, the risk for a solitary pulmonary nodule representing a new bronchogenic carcinoma, rather than a metastasis, is higher [13]. Although the incidence of lung cancer does not increase after smoking cessation, it never equals that for individuals who never smoked [26]. An SPN is unlikely to be a metastasis if the patient has no known oncologic history [26]. However, in patients with a history of melanoma, sarcoma, or testicular cancer, an SPN is 2.5 times more likely to be a metastasis than a primary lung cancer [13,26].

Bayesian analysis incorporates clinical history with imaging findings and is an important tool in the assessment of the patient with a solitary indeterminate pulmonary nodule [16]. By using Bayesian analysis a more precise determination for the probability of a nodule representing a malignancy (pCa) can be performed [16]. Bayesian analysis has been shown to be superior to evaluation by experienced radiologists in the stratificaton of benign and malignant nodules [16]. Bayesian analysis applies likelihood ratios to clinical and radiographic variables- the likelihood ratio (LR) is defined as (number of malignant nodules with a specific feature/number benign nodules with a specific feature) [16]. A likelihood ratio (LR) of 1.0 indicates a 50% chance of malignancy, while a ratio of less than 1.0 is more indicative of benign disease [16]. The odds of malignancy are then calculated based upon the produce of all the LR's: 

LRprior is the likelihood of malignancy in all nodules based upon local prevalence

Odd of cancer= LRprior x LRsize x LRsmoking hx x LRedge x LRcalcif  

The probability of cancer (pCa) is calculated by the formula:  Oddsca/(1+ Oddsca). The most cost effective strategy for a nodule is observation when the pCa is low (less than 0.05 [5%]) [16]. Surgical resection should be performed when the pCa is greater than or equal to 0.60 (60%) [16]. Biopsy or further evaluation with PET or nodule enhancement characteristics should be performed when the pCa is between 0.05 and 0.60 (5-60%) [16].

Below are some LR's for selected radiologic and clinical variables [16]:

Characteristic LR
Spiculated margin 5.54
Size over 3 cm 5.23
Patient age over 70 years 4.16
Malignant growth rate 3.40
Smoker 2.27
Upper lobe location 1.22
Size less than 1 cm 0.52
Smooth margins 0.30
30-39 years of age 0.24
Never smoked 0.19
20-29 years of age 0.05
Benign calcification 0.01
Benign growth rate 0.01

Morphologic findings that can be used to guide proper management of lung nodules:

When describing a pulmonary nodule it is important to describe its location (parenchymal, fissural, or pleural), attenuation, enhancement, and morphology. Based upon their appearance, nodules should be characterized as low, intermediate, or high risk for malignancy.

- Lesion margins:

The margins of the lesion should be evaluated and determined to be sharp, ill-defined, lobulated, or spiculated. Coarse spiculation occurs with a significantly higher frequency among malignant nodules than among benign nodules- approximately 90-97% of spiculated masses are neoplastic [15,21,26]. The spiculation correlates pathologically with a desmoplastic response incited by the tumor that results in fibrotic strands radiating into the surrounding lung parenchyma; or it can also be due to direct infiltration by the tumor into the surrounding bronchovascular sheaths, or localized lymphangetic extension [15]. Ragged margins (about 90% malignant) and lobulated margins (indicating uneven nodule growth - 40-80% malignant) are also associated with an increased risk for malignancy [26,40]. Smooth/sharp margins do not always ensure a benign etiology as 20-31.5% of lesions with smooth margins may be malignant [40,52].

Some peripheral carcinomas can incite a desmoplastic reaction and demonstrate a connection to the pleura. Retraction of the visceral pleura towards the lesion by this reaction and a small quantity of fluid within the space formed between the visceral and parietal pleura produce a pyramidal soft-tissue opacity between the lesion and the pleural surface. A "pleural tail" is a thin line extending from the lesion to the pleural surface and is likely secondary to tumor-induced thickening of the interlobular septa [3], however, pleural tags can also be seen in association with benign lesions. Although these findings are characteristic of carcinomas, they are not specific between 21-33% of malignant nodules can have smooth borders (particularly metastatic lesions) [21,26].

- Nodule location:

One study has suggested that fissural/perifissural non-calcified nodules (PFN's) have a very low likelihood for malignancy and may represent small intrapulmonary lymph nodes [44,48]. These small nodules typically measure less than 10 mm, have an oval/lenticular or triangular configuration with a homogeneous solid appearance, and sharp/smooth margins [44,48,59]. It has been suggested to refer to these nodules as "juxtapleural nodules with benign features " [59]. PFN's may enlarge over time, but one study has suggested that even enlarging PFN's carry a very low risk for malignancy [48]. It is important to remember that a juxtapleural location is not always indicative of benignancy and irregular nodules and nodules that abut a fissure, but are rounded on only one side do not meet the criteria of a PFN and should be considered atypical [48,60]. In one study population, 7% of all cancers were attached to a fissure and 21% were attached to the pleura [59].

- Vascular relationship:

It is also important to identify vascular relationships- is there a feeding artery or draining vein to suggest that the lesion represents an arterio-venous malformation. Converging vessels are an indication of malignancy as the cicatrical features of small carcinomas may cause surrounding vessels to converge on the mass.

- Nodule size:

The larger the nodule, the more likely it is to be malignant [26,40,52]. Available data from lung cancer screening studies indicate that fewer than 1% of nodules under 5 mm in size in patients without an oncologic history demonstrate malignant behavior [22]. The likelihood of malignancy base upon size is 0.2% for nodules smaller than 3mm, 0.9% for nodules between 4-7mm, 18% for nodules between 8-20mm, and for 50% for nodules larger than 2 cm [22]. Larger nodules over 300 mm3 at baseline have a much higher for malignancy (16.9% in one study) [55]. In the Early Lung Cancer Action Project, only 8% of lesions smaller than 1 cm in diameter were malignant [26].

- Cavitation:

Cavitation occurs in both infectious and malignant nodules, as well as vasculitis and infarction [52]. Smooth thin walls are typically associated with benign lesions and thick irregular walls with malignancy [52]. It has been reported that 95% of cavitary nodules with a wall thickness greater than 15 mm are malignant; 92% with a wall thickness less than 5 mm are benign; and for a wall thickness between 5-15 mm-  51% were benign and 49% were malignant [52].

Solitary cystic lesions that should be considered suspicious for lung cancer have the following features- non-uniform cyst walls, sepatation(s) within the cyst, wall nodule(s), GGO around the cyst, irregular margins, and gradual expansion over time [61]. Benign lung cysts typically have thin, symmetric walls without nodularity [61].

- Air bronchogram/bronchiologram (Bronchus sign):

Connection to bronchi or air-bronchograms should be evaluated for as small, peripheral bronchogenic carcinomas (particularly bronchoalveolar cell carcinoma or pulmonary lymphoma) may demonstrate one or more bronchi protruding into the mass confirming an endobronchial component suggestive of primary bronchogenic carcinoma [10]. Air bronchograms can be seen in up to 30% of malignant nodules, but in only 6% of benign nodules [26]. Bubble-like lucencies secondary to airway distortion associated with a tumor desmoplastic reaction are seen in up to 55% of bronchoalveolar cell caricnomas [26].

- Lesion attenuation/calcification:

Lesion density is another variable to be considered. It is important to remember that assessment of lesion density requires the use of thin sections (1.5-2 mm) and no IV contrast (contrast enhancement may mimick calcification). Important findings to look for are the presence of fat or calcification within the lesion. Fat within the lesion confirms it is benign and about one-third of hamartomas contain fat.

Regarding calcification - up to 13% of lung cancers have some calcification (often stippled or eccentric [40]), but this is true of only 2% of lung cancers smaller than 3 cm in diameter [26]. Target (focal central), lamellar (suggesting a healed granuloma), pop-corn (chondroid), or diffuse all suggest a benign lesion [21]. Focal, eccentric peripheral calcification is indeterminate with regards to malignancy as it can be seen in association with malignant lesions- particularly a scar carcinoma which engulfs the adjacent calcification. However, granulomas and other benign lesions may sometimes calcify eccentrically as well, and therefore eccentric calcification does not confirm malignancy. It has been reported that 77% of nodules smaller than 7 mm visualized on CXR are calcified [40]. Very small nodules that are visible on CXR therefore have a higher probability of representing calcified granulomas [40]. Note, however, that up to 7% of nodules (over 5 mm) felt to be "definitely calcified" on CXR, were not calcified at CT [14]. Without documentation of long-term stability, a low threshold to recommend CT may be appropriate to better characterize a nodule seen on CXR [14].

Nodule densitometry has been used to aid in distinguishing benign from malignant lesions based upon a pixel analysis of the lesion using thin cuts to detect the presence of fat or calcium within the nodule. Visible calcification or high CT numbers (greater than 15% of contiguous pixels greater than 150-200 HU) imply the lesion is benign (granuloma or hamartoma). However, there is about a 10% false-negative rate due to the presence of calcification within a malignancy [NYU Course, Dec 95]. Thus, although high pixel values suggest a benign lesion, other factors such as lesion margins, the pattern of calcification, and interval growth must all be considered when evaluating a nodule. Densitometry is more reliable when performed on helical CT. Remember- do not use a high spatial frequency algorithm image when measuring nodule density.

- Satellite nodules:

Satellite nodules are tiny 1 to 4 mm nodules which surround a larger nodule. If identified, the presence of satellite nodules indicate that the large nodule is very likely benign (about 90% likely) [21,26]. Satellite nodules are found in association with about 5% of granulomas.

- Solid versus non-solid nodules:

Ground glass nodules are defined as focal lesions with increased attenuation through which normal parenchymal structures such as vessels and interlobular septa can be seen [43]. Pure ground glass nodules can be seen with benign processes such as inflammation, organizing pneumonia, focal hemorrhage, and interstitial fibrosis; with the precancerous lesion atypical adenomatous hyperplasia (AAH); with pulmonary lymphoproliferative disorder; and with adenocarcinoma in site (AIS- previously bronchoalveolar cell carcinoma- BAC) and in AIS the ground glass opacity is felt to be related to the lepidic growth of the tumor without invasion [32,34,47,52].

Atypical adenomatous hyperplasia (AAH) occurs in about 3% of the general population and in 6.6% of the population over the age of 60 years [32]. The lesion is found in 10-23% of patients with pulmonary adenocarcinoma [32]. AAH is typically a pure ground glass nodule that measures less than 1 cm [52]. AIS is typically a pure ground glass nodule that measures less than 3 cm [52]. Both AAH and AIS are usually homogeneous and round or oval [62]. When minimally invasive adenocarcinoma or invasive adenocarcinoma present as pure ground glass nodules, they are typically larger (over 10.5 mm or have a volume of mroe than 86.5 mm2), irregular/spiculated, heterogeneous or of a higher attenuation value, associated with pleural indentation, or contain dilated or distorted vessels [62].

According to ELCAP data, 18% of nodules with pure ground glass opacity were malignant and these lesions are usually bronchoalveolar cell carcinomas [31,32]. However, up to 75% of persistent or enlarging ground-glass nodules can be caused by BAC [34]. Both aytpical adenomatous hyperplasia and BAC may persist without an interval change for a period of greater than 2 years (with doubling times for low grade BAC as long as 1,346 days [40]) [35]. The mean doubling time for lung cancer presenting as a pure ground glass nodule is 813-880 days (+/- 375 days) [37,47]. Other authors have reported volume doubling times of 988 days +/- 470 for AAH, 567 days +/- 168 for BAC, and 384 days +/- 212 for mixed subtype adenocarcinoma [43]. Hence, the previous concept that lack of growth over a 2 year follow-up indicates a benign etiology does not apply to subsolid nodules [43]. Guidelines have been suggested for the management of ground-glass nodules [43].

Partially solid nodules are more likely to be malignant [26]. In one study, 63% of semi-solid nodules (with a ground-glass component) were found to be malignant [21]. Minimally invasive adenocarcinoma (MIA) may be seen as a ground glass or part solid nodule [52]. MIA is defined as a predominantly lepidic lesion that demonstrates no necrosis or invasion of lymphatic, blood vessels, or pleura; measures less than 3 cm; and has an invasive component that measures no more than 5 mm in any one location [52].

For ground glass and subsolid nodules, in addition to increase in size, other changes over time that raise concern for malignancy include increase in attenuation or development of a solid component [52].

Ground-glass attenuation or a "halo sign" refers to the presence of a hazy area of ground glass density about the lesion. In an immune competent patient this finding is concerning for the presence of lepidic tumor growth. This finding has also been described in association with aspergillus infection in immune compromised patients.

Contrast Enhancement CT in the Evaluation of the Solitary Pulmonary Nodule:

Thin cut helical CT with contrast enhancement has also been evaluated for use in distinguishing benign from malignant small, (less than 3 cm) parenchymal nodules. The study can be performed using 100 ml of 60% iodinated contrast injected at 2 ml/minute. Other authors have advocated using 30% iodinated contrast and a total iodine dose based upon patient weight (420mg/kg) [4,11]. The scan is performed using 3 mm collimation, pitch 1:1, 120 kVp, 280 mA, and a 2 mm reconstruction interval [11]. A baseline non-contrast exam is performed and then the nodule is scanned every 60 seconds for a 5 minute period beginning one minute following initiation of the infusion. Most malignant nodules will obtain maximal enhancement within 5 minutes of contrast administration, however, some malignant nodules (up to 8%) may require a longer period of time [23]. Standard reconstruction algorithms (not high spatial frequency) are used. It is important to ensure adequate vascular enhancement for accurate assessment of the degree of lesion enhancement. Regions of interest should be drawn on the image closest to the nodule equator and should be drawn on the mediastinal window setting (to minimize partial-volume averaging) [11]. The sensitivity for this procedure has been reported to be as high as 98-100%, with a specificity of 29-77%, positive predictive value of 65-90%, and a negative predictive value of 100%. A meta-analysis found an overall sensitivity of 93%, a specificity of 76%, a PPV of 80%, and an NPV 95% [36]. The same meta-analysis did not note any significant difference between dynamic CT and FDG PET for distinguishing benign from malignant nodules [36]. About 10% of benign lesions (such as organizing pneumonia's and active granulomas) will demonstrate enhancement greater than 20 HU. A higher cut-off (30HU) may be required when imaging patients using a multidetector CT scanner [20].

CT enhancement should be determined only in nodules with relatively spherical shape and homogeneous attenuation (no evidence of cavitation or necrosis) [52]. A lesion that enhances greater than 10 HU should be considered suspicious for malignancy and should be biopsied, while enhancement of less than 10 HU indicates a benign lesion [11]. Some authors advocate using 15 HU as the criteria for abnormal lesion enhancement [12], however, some primary and metastatic malignant lesions may not enhance to this level [10]. I personally use the following criteria: A lesion that enhances less than 10 HU is considered benign. A lesion that enhances greater than 20 HU is considered suspicious for malignancy and should be biopsied or surgically removed. Lesions that enhance between 10-20 HU are indeterminate and require serial evaluation. When images are acquired on a multi-detector CT, higher peak enhancement may be achieved compared to single-detector scans and thus higher attenuation cutoff values may be required (i.e.: 25 or 30 HU rather than 20 HU) [23,24]. Remember- despite what the literature implies, no exam is 100% sensitive. Some malignant lesions may not enhance. CECT provides one additional piece of information in the evaluation of a solitary pulmonary nodule. Always fully evaluate all characteristics of each lesion and a patients clinical risk factors for malignancy to determine optimal patient managment.

Although homogeneous enhancement is common, some lesions demonstrate variable enhancement patterns. The particular pattern of lesion enhancement may provide useful information regarding its nature. Ring enhancement has been described in association with non-calcified tuberculomas and this is most likely secondary to central necrosis within the lesion. Although there may be some overlap with malignant lesions, most bronchogenic carcinomas less than 3 cm in size do not have significant necrosis. [5,7]. Contrast enhanced CT is limited in it's ability to evaluate lesions under 8-10 mm in size, cavitary lesions, lesions with central necrosis, and for lesions which lack well defined borders [21]. One must also consider the radiation dose received by the patient as multiple scans are performed through the lesion. Finally, the exams low specificity can lead to overall increased costs and morbidity due to unnecessary biopsies and surgical interventions [28 ,38].

The amount of enhancement may also aid in predicting the likelihood for nodal metastases [25]. For T1 lesions, peak enhancement of 110HU or greater or net enhancement of 60HU or greater has been shown to be associated with an increased likelihood for hilar and mediastinal nodal metastases [25]. This may be related to an increased number of intratumoral microvessels within densely enhancing lesions [25].

Case 1: Example of enhancement of a carcinoid tumor

Contrast Enhanced MR in the Evaluation of the Solitary Pulmonary Nodule:

Dynamic contrast enhanced MR measurements of the rate of lesion enhancement during the first transit of contrast material (and generation of time activity curves) can be used to determine if a lesion is benign or malignant with sensitivites from 52-100%, specificities from 17-100%, and accuracies from 58-96% [51]. The absolute increase in signal intensity alone, however, is not sufficient to make this determination as there is considerable overlap between benign, inflammatory, and malignant lesions [6,38].

PET FDG imaging of the pulmonary nodule (See discussion in lung cancer section)

Followup of incidentally solid nodules at non-screening CT:

The following recommendations were proposed by the Fleischner Society [22] and subsequently revised [56] for incidentally detected lung nodules in patients over the age of 35 years [22,60]. The Fleischner society feels that nodules less than 6 mm in low risk patients have a less than 1% chance of malignancy [56]. The patient's age and the presence of comorbid conditions should also influence management recommendations [22]. The present recommendations refer to incidentally detected non-suspicious, well-circumscribed, non-calcified lung nodules at non-screening CT in adults who are at least 35 years old [56]. Followup studies can be performed with adjustment to the scanning parameters based upon the patients weight in order to decrease patient radiation exposure (i.e.: 70 mAs for a 70 kg patient) [27]. A 2 mm increase in dimension threshold has been suggested for documented nodule growth [57].

Nodule size

Low risk patient

High risk patient

Less than 6 mm No followup needed
Followup at 12 months
6 mm to 8 mm Initial followup at 6-12 months, then consider at 18-24 months if no change Initial followup at 6-12 months, then at 18-24 months if no change.
Over 8 mm Followup CT at 3 months, PET/CT, PET, and/or biopsy Followup CT at 3 months, PET/CT, PET, and/or biopsy

Multiple nodules- use most suspicious nodule as guide to management
Nodule size
Low risk patient
High risk patient
Less than 6 mm
No routine followup
Followup at 12 months
6mm to 8 mm
CT at 3-6 months, then consider 18-24 months
CT at 3-6 months, then 18-24 months
Over 8 mm
CT at 3-6 months, then consider 18-24 months
CT at 3-6 months, then 18-24 months


Low risk patient: Minimal or absent history of smoking and or other known risk factors

High risk patient: Smoking history or other known risk factors

Suggested followup of incidentally detected subsolid and ground glass nodules at CT [43]:

Some authors suggest that because isolated lesions smaller than 5 mm in size with pure GGO represent foci of atypical adenomatous hyperplasia (AHH) sufficiently often, that follow-up CT studies are not required- especially in the elderly [43]. The authors, however, state that this guideline needs to be interpreted in light of the individual clinical history [43]. For pure GGO nodules between 5-10 mm in size, a follow-up CT in 3-6 months should be performed to document that the lesion did not resolve spontaneously (or following antibiotic therapy) [43]. Between 37-70% of ground glass nodules resolve at short term follow-up [47]. If the lesion persists, then long term follow-up is likely preferable to surgical resection, although a small percentage of these lesions will prove to be invasive adenocarcinoma [43]. Follow-up surveillance should probably extend for 3 to 5 years, although the optimal duration for follow-up has yet to be determined [43]. Ideally, follow-up studies should be performed with the lowest possible exposure techniques to minimize radiation exposure (mAs as low as 80) [43]. However, a low tube current may hinder visualization of pure GGO nodules due to excessive noise and should be at least 50 mAs of greater [47].

If biopsy is deemed necessary, core needle biopsy is preferred [43]. The diagnostic yield for FNA of ground glass nodules can be as low as 51% if the lesion is more than 50% ground glass, while core biopsy has a sensitivity of 92% and a specificity of 90% [47]. Pure GGO nodules larger than 10 mm may be resected provided that persistence or growth of the lesion has been established over a 3-6 month period [43]. As mentioned previously, biopsy prior to resection is of limited value due to low yield from sampling error [43]. A limited wedge resection may be adequate in patients with small ground glass nodules [47]. In patients with multiple pure GGO nodules measuring less than 5 mm in size, a follow-up CT scan in one year should be performed as these patients may be at greater risk for developing cancer [43]. Follow-up CT surveillance should be performed in patients with multiple small (5-10 mm) pure GGO nodules as these most likely represent multifocal AAH or in smokers, respiratory bronchiolitis [43]. When a GGO nodule increases in size or if a solid component develops, it should be resected [45,47]. Interobserver agreement on the presence of a solid component has been shown to be improved by viewing the nodule in thin 1 mm slices on mediastinal window settings [58]. The detection of a visible solid portion to the nodule on mediastinal windows aids in confirmation of a part solid lesion [58].

Any semi-solid (i.e. GGO with mixed solid components) 10 mm or larger in size represents malignancy with sufficient likelihood that further evaluation should be performed [43]. PET or biopsy can be considered, but may not aid in the ultimate decision to resect the nodule [43].

The Fleischner Society has published new recommendations for the management of ground-glass and sub-solid nodules [50]. Although smokers have a greater likelihood of developing cancer, they note that there is insufficient data to support the use of different management guidelines based solely on smoking history [50]. However, the guidelines must be interpreted in light of an individuals clinical history [50]. Furthermore, thin-slice 1mm images are recommended to document that the nodule is truly ground glass as volume averaging on thicker slices can cause a solid nodule to appear ground glass [50]. The development of a solid component in a ground glass nodule over time is also strong evidence of an invasive adenocarcinoma- although, if the solid component is 5mm or less in size, the lesions frequently prove to be with adenocarcinoma in situ or minimally invasive adenocarcinoma [50]. Note also that pure ground glass nodules larger than 10mm, atypical sub-solid nodules with spiculated contours, "bubbly" appearance or reticulation, or part solid nodules with initial solid components smaller than 5mm that demonstrate interval change in size or attenuation, should be interpreted with a high degree of suspicion for carcinoma [50]. It is recommended that followup studies be performed with a consistent low-dose technique [50].

Although the Fleischner Society suggests that no followup is required for GG nodules less than 6 mm (which are felt to most likely represent atypical adenomatous hyperplasia), this may not be the case for patients that undergo lung cancer screening CT exams [56]. In one study, 10% of GG nodules less than 5 mm on lung screen CTs eventually demonstrated growth over time, and 1% developed into minimally invasive/invasive adenocarcinomas [53]. The mean period between baseline screening and the appearance of solid components was 3.6 years (mean volume doubling time was 864 days) [53].

For management of incidentally detected ground glass and part solid nodules - the chart below is from Radiology 2017; MacMahon H, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner Society 2017. 284: 1-16

Nodule type

Management Recommendations

Addtional Remarks
Solitary GG < 6 mm No routine follow-up required
Obtain contiguous 1mm thick sections to confirm nodule is truly a pure GG nodule. Also- for certain suspicious nodules < 6 mm consider followup at 2 and 4 years. If solid components or growth develops, consider resection.
Solitary GGO equal or greater than 6 mm Followup at 6-12 months to confirm persistence, then CT every two years until 5 years
FDG PET is of limited value and not recommended for this type of nodule. Persistent  GG nodules prove to be benign in up to 20% of cases [50]. Surveillance CT to detect interval growth in these cases should not have an adverse effect in patient outcomes [50]. Followup CT should include contiguous 1 mm thick sections and use of a low-dose technique [50].
Solitary part-solid nodule
Initial followup at 3-6 months to confirm persistence. If persists and solid component is < 6 mm, then yearly surveillance for a minimum of 5 years. If persists and solid component is equal or more than 6 mm should be considered highly suspicious (biopsy or surgical resection). PET/CT may be considered for part solid nodules > 10mm. These nodules have a greater likelihood of being malignant (up to 63% for part-solid nodules in one study of high-risk patients using screening CT) [50].
Multiple pure GG nodules < 6 mm in size
Obtain initial followup at 3- 6 months. If stable, consider followup at 2 and 4 years Consider alternate causes for multiple GG nodules. Multiple < 6mm pure GG nodules are usually benign, but consider followup in selected patients at high risk at 2 and 4 years
Multiple GG nodules, at least one of which is equal to or larger than 6 mm
Initial followup at 3-6 months to confirm persistence, then annual surveillance by CT for a minimum of 5 years

Multiple subsolid nodules with a dominant nodule(s) with part-solid or solid component
Initial followup CT at 3-6 months to confirm persistence. Subsequent management based on most suspicious nodule(s). If persistent, biopsy or surgical resection is recommended, especially for lesions with  > 6 mm solid component
The dominant lesion should determine further management. Consider lung-sparing surgery for patients with dominant lesion(s) suspicious for lung cancer

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