CT shows a case of minimally invasive adenocarcinoma, with a total size of 17 mm and solid component size of 7 mm. 

Context in source publication

Context 1

... of a granuloma, whereas a classic “popcorn” pattern is most often seen in hamartomas ( Figure 2 ) (24). In approximately half the cases of hamartoma, high-resolution CT can show a definitive pattern of fat and cartilage (29). Fat content suggests a hamartoma or occasionally a lipoid granuloma or lipoma (30). Calcification patterns that are stippled or eccentric have been associated with cancer. Another benign entity is rounded atelectasis. Diagnosis for rounded atelectasis can be made as it has specific diagnostic morphological features including subpleural location, curved course of blood vessels into the opacity, and evidence of pleural disease ( Figure 3 ) (31). When nodules considered as benign no further investigation is necessary. SPNs with irregular, spiculated margins, or lobulated contours, are typically associated with malignancy. Two patterns of the margins of a nodule are relatively specific for cancer. One is the corona radiata sign, consisting of very fine linear strands extending 4 to 5 mm outward from the nodule; they have a spiculated appearance on plain radiographs ( Figures 4,5 ). A scalloped border is associated with an intermediate probability of cancer. Although most SPNs with smooth, well-defined margins are benign, these features are not diagnostic of benignity. A total of 21% of malignant nodules had well-defined margins (29). For a single nodule, upper lobe location increases the likelihood of malignancy, because primary lung cancers are more common in the upper lobes (32). On the other hand, small, irregular, benign subpleural opacities, presumably due to scarring, are extremely common in the apical areas in older patients. Triangular or ovoid circumscribed nodules 3-9 mm in diameter adjacent to pleural fissures commonly represent intrapulmonary lymph nodes (33). In general, purely linear or sheetlike lung opacities are unlikely to represent neoplasms and do not require follow-up (34). When SPN is considered to be indeterminate in the initial exam, the risk factor of the patients should be evaluated. Increasing patient age generally correlates with increasing likelihood of malignancy. On the other hand, lung cancer is uncommon in patients younger than 40 years and is rare in those younger than 35 years (<1% of all cases) (35). The relative risk for developing lung carcinoma in male smokers was about 10 times that in nonsmokers (36). For heavy smokers, the risk was 15-35 times greater (37). Also, the cancer risk for smokers increases in proportion to the degree and duration of exposure to cigarette smoke (38). Other established risk factors include exposure to asbestos, uranium, and radon (39-41). A history of lung cancer in first-degree relatives is also a risk factor, and strong evidence for a specific lung cancer susceptibility gene has been discovered recently (42,43). A history of cancer can greatly increase the likelihood of a nodule being malignant (44). Low-risk individuals are <50 years old and have <20 pack-year smoking history. Moderate-risk group is defined as age >50 and >20 pack-year smoking history or second hand exposure, and no additional risk factor (random exposure, occupational exposure, cancer history, family history, or lung cancer). The positive relationship of lesion size to likelihood of malignancy has been clearly demonstrated (10-15). The standard size value used is an average of the largest and smallest cross-sectional diameters of the most representative area of the nodule. In a meta-analysis of eight large screening trials, the prevalence of malignancy depended on the size of the nodules, ranging from 0% to 1% for nodules 5 mm or smaller, 6% to 28% for those between 5 and 10 mm, and 64% to 82% for nodules 20 mm or larger. Even in smokers, the percentage of all nodules smaller than 4 mm that will eventually turn into lethal cancers is very low (<1%), whereas for those in the 8-mm range the percentage is approximately 10-20%. The 2005 Fleischner Society guideline ( Table 1 ) stated that at least 99% of all nodules 4 mm or smaller are benign and because such small opacities are common on thin-section CT scans, follow-up CT in every such case is not recommended; in selected cases with suspicious morphology or in high-risk subjects, a single follow-up scan in 12 months should be considered (45). This protocol could result in a few indolent cancers being missed, the number of such instances would be extremely small relative to the reduction in the number of unnecessary studies (45). The increased use of CT screening for lung cancer led to an increase in identification of early lesions such as adenocarcinoma in situ (AIS, histopathologically ≤ 30 mm, noninvasive lepidic growth, which at CT is usually nonsolid; Figure 6 ) and minimally invasive adenocarcinoma (MIA, histopathologically ≤ 30 mm and predominantly lepidic growth that has 5-mm or smaller invasion, which at CT is mainly nonsolid but may have a central solid component of up to approximately 5 mm; Figure 7 ) (22). These lesions should not be regarded as conventional invasive adenocarcinomas and can be observed rather than surgically resected (22). When the nodule is 5-9 mm in diameter, approximately 6% of cases showed interval nodule growth detectable on 4-8 month follow-up scans (11). For these nodules the best strategy is surveillance. The timing of these control examinations is given in Table 1 . This varies according to the nodule size (4-6, or 6-8 mm) and type of patients, specifically at low or high risk of malignancy concerned. Noncalcified nodules larger than 8 mm diameter can bear a substantial risk of malignancy ( Figure 8 ) (46). In the case of nodules larger than 8 mm, additional options such as contrast material-enhanced CT, positron emission tomography (PET), percutaneous needle biopsy, and thoracoscopic resection or videoassisted thoracoscopic resection can be considered (13). A common aspect of invasive adenocarcinoma of the lung is metastasis to the brain (47,48). Its probability is a function of the size of the primary tumor, at least for tumors in the 20-60 mm size range. For node-negative invasive adenocarcinoma of the lung, a 20 mm primary lesion has been found to show a 14% probability of brain metastatic disease, progressing nearly linearly to a 60 mm primary node-negative lesion showing a 64% probability of brain metastatic disease (47). In certain clinical settings, such as a patient presenting with neutropenic fever, the presence of a nodule may indicate active infection, and short-term imaging follow-up may be appropriate. Previous CT scans, chest radiographs, and other pertinent imaging studies should be obtained for comparison whenever possible, as they may serve to demonstrate either stability or interval growth of the nodule in question. In a patient with known primary malignancy, lung nodules, regardless of being solitary or multiple, would be deemed suspicious for metastases. Pertinent factors will include the site, cell type, and stage of the primary tumor and whether early detection of lung metastases will affect care. The volume doubling time (DT) for malignant bronchogenic tumors is rarely less than a month or more than a year. A nodule that was not present on a radiograph obtained less than two months before the current image is therefore not likely to be malignant. The “doubling time” (DT) of a nodule can be calculated using the following formula: DT = (t.ln2)/ln(Vf/Vi) Where Vi is the initial volume of the nodule, Vf the final volume, t the time interval between observations and ln the logarithmic value. This formula is based on an exponential model of nodule growth (23). Note that a 5-mm nodule with a DT of 60 days will reach a diameter of 20.3 mm in 12 months, whereas a similar nodule with a DT of 240 days would reach a diameter of only 7.1 mm in the same period. It has been considered that stability of nodule size for over 2 years for solid pulmonary nodules suggest benign nature. Recently, the radiologic-pathologic correlation of pure ground-glass attenuation nodules and mixed attenuation nodules with the histologic spectrum of pulmonary adenocarcinoma was described (49). Small purely ground-glass opacity (nonsolid) nodules that have malignant histopathologic features tend to grow very slowly, with a mean volume DT on the order of two years (50). Solid cancers, on the other hand, tend to grow more rapidly, with a mean volume DT on the order of 6 months. The growth rate of partly solid nodules tends to fall between these extremes, and this particular morphologic pattern is predictive of adenocarcinoma (46,51,52). Bronchoalveolar cell carcinomas and typical carcinoids occasionally appear to be stable for two or more years (53). Longer follow-up intervals are appropriate for nonsolid (ground-glass opacity) and very small opacities (50,51). Even if malignant, a nonsolid nodule that is smaller than 6 mm will probably not grow perceptibly in much less than 12 months (50,51). Currently, though the dictum that two-year stability on plain-film radiography indicates a benign process should be used with caution (54), it is still reasonable to use two-year stability on high-resolution CT as a practical guideline for predicting a benign process. Hasegawa et al. (50) reported an analysis of the growth rates of small lung cancers detected during a 3-year mass screening program. They classified nodules as ground-glass opacity, as ground-glass opacity with a solid component, or as solid. Mean volume DTs were 813, 457, and 149 days, respectively. In addition, the mean volume DT for cancerous nodules in nonsmokers was significantly longer than that for cancerous nodules in smokers. Authors of a number of other series have confirmed similar findings and have estimated the median tumor DTs, assuming a constant growth rate to be in the 160-180-day range (55,56). Authors of all of these reports, however, recognize wide variations, and in one study 22% of tumors had a volume ...