Hi, I'm Leslie Quint from the Department of Radiology at the University of Michigan. The topic for today's talk is Subsolid Nodules: Imaging Features, Pathologic Correlates, and Management Strategies. The objectives for today's talk are to define the term subsolid nodule and to review imaging features of subsolid nodules. Along the way, we'll correlate imaging and pathologic features for lesions on the bronchogenic adenocarcinoma spectrum, and we'll review and illustrate follow-up guidelines for subsolid nodules. Let's start out with a pre-lecture question. This image is from a 53-year-old woman with no smoking history. She had this incidental subsolid nodule found on a CT scan that was obtained for unrelated reasons. This is an 11 millimeter diameter subsolid nodule with a four millimeter diameter central solid component. So the question for you is, what would you recommend that we do for this patient? Would you recommend no follow-up, a follow-up scan in three to six months, a follow-up scan in 6-12 months, or a PET scan or a biopsy? Pick your best choice and we'll get back to this at the end of the talk. Okay. So, let's get started. There are two subcategories within subsolid nodules. The first subcategory is the pure ground-glass nodule as illustrated here. These nodules do not obscure the underlying vessels. So, you can see there's hazy opacity here, and there's a vessel running through the nodule over here, and another vessel here, and another vessel here. So, the ground-glass nodule does not obscure the underlying bronchovascular markings. The other subcategory within subsolid nodules is the part-solid nodules. So, in this type of nodule, we see solid components here centrally in this particular nodule, as well as ground-glass components. Subsolid nodules may also have bubble-like lucencies. These are these rounded low attenuation areas in this example and this rounded low attenuation area in this example on your right. What is the differential diagnosis for a subsolid nodule? The differential diagnosis is wide and includes a focus of inflammation or infection, a region of organizing pneumonia, or hemorrhage, or focal fibrosis. Of course, what we're all worried about is neoplasm, in particular, bronchogenic adenocarcinoma. If we see a tiny ground-glass nodule like this one, we also need to think of an entity called atypical adenomatous hyperplasia. This entity represents a region of focal proliferation of atypical epithelial cells along the alveoli and the respiratory bronchioles. These lesions are precursors of bronchogenic adenocarcinoma and in fact, they are the earliest pre-invasive lesions for bronchogenic adenocarcinoma that are visible at CT scanning. These lesions grow very slowly, they're no more than five millimeters in diameter, they're often multiple, and they are pure ground-glass in morphology. Let's talk for a minute about early bronchogenic adenocarcinomas. These lesions used to be called bronchioloalveolar cell carcinomas, but we don't use that terminology anymore. These lesions grow along the alveolar septa without or with very little invasion of the adjacent pulmonary parenchyma. They grow very slowly. So they have an indolent course. They're less commonly associated with smoking compared to other types of non-small cell lung cancers. These lesions also have a higher incidence of multifocality and in fact, about a quarter of these are multifocal. Early bronchogenic adenocarcinomas show a younger age distribution compared to other types of non-small cell lung cancers. The presence of other lung diseases, such as interstitial fibrosis, increases the risk of developing a bronchogenic adenocarcinoma. A new pathologic classification system came out in the year 2011 for early bronchogenic adenocarcinomas. So this classification starts out with atypical adenomatous hyperplasia. It then moves on to adenocarcinoma in situ. These lesions are no more than three centimeters in diameter. Then we have the minimally invasive adenocarcinomas with no more than five millimeters of stromal invasion. Finally, the frankly invasive adenocarcinomas, either non-mucinous or mucinous. The adenocarcinomas in situ and the minimally invasive adenocarcinomas make up the category that we used to call bronchioloalveolar cell carcinoma. What do these lesions look like on CT scanning? The atypical adenomatous hyperplasias are the tiny ground-glass lesions. Adenocarcinoma in situ are usually ground-glass, but there may be a small solid component or bubble-like lucencies. Minimally invasive adenocarcinomas shows up as a ground-glass lesion or a part-solid nodule, and there may be a central solid component that's no more than five millimeters in diameter. That solid component generally corresponds to the invasive component that is seen at histology. Finally, the invasive adenocarcinomas may have a variety of appearances at CT. These lesions may be part-solid or solid. Occasionally, there are ground-glass. There are no hard and fast rules, but in general, as we move from the less invasive lesions to the more invasive lesions, they tend to become more solid on CT scanning. So that then brings us to the question, how do we manage an incidental subsolid nodule that is found on a CT scan? The best way to manage such an incidental subsolid nodule is to use published evidence-based guidelines. Here are a few of these guidelines. There are the Fleischner Society Guidelines, which were revised in 2017, the guidelines from the American College of Chest Physicians, and guidelines from the British Thoracic Society. In our practice, we'll use the Fleischner Society Guidelines. So, here's a question about those guidelines just to see how familiar you are with them. The 2017 Fleischner Society Guidelines for the management of subsolid nodules are based on all of the following except smoking history, nodule size, nodule morphology, or nodule multiplicity. The best answer here is smoking history. Although the guidelines for solid nodules are based on underlying risk, including smoking, the guidelines for subsolid nodules do not take into account smoking history because subsolid nodules often turn out to be bronchogenic adenocarcinomas, and these are not strongly correlated with the smoking history. Okay. So, here are the Fleischner Society Recommendations for the management of Subsolid Pulmonary Nodules. This looks a little complicated, but don't despair, we'll go through this looking at examples. I would first of all like to point out a few features about these guidelines. First of all, when measuring these nodules, we need to measure the average of the long and short axis rounded to the nearest millimeter. The other thing I'd like to point out is that when measuring, we can use diameters as shown here or we can use nodule volumes as shown here. In most practices at the current time, we still use nodule diameters, but we're moving more and more towards for volumetry and in the future, most likely, that will replace diameters. Okay. So, let's look at some examples and see what the guidelines would suggest we do. We'll start with the small pure ground-glass nodules less than six millimeters in diameter as in this example. If these lesions are persistent on a follow-up exam, they most likely represent foci of atypical adenomatous hyperplasia. These lesions are extremely common. Only about 10 percent of them grow, and the ones that do grow grow very slowly. One published study found that only about one percent of these lesions develop into invasive or minimally invasive adenocarcinomas. Because of that, the guidelines suggest that no routine follow-up is recommended. Okay. Well, what about part-solid nodules less than six millimeters in diameter? In practice, part-solid nodules cannot be defined as such until they're six millimeters in diameter or larger. So, if I show you this lesion, you might say it's a ground-glass nodule or you might say maybe there's a small solid component. But in practice, it's very hard to tell when the nodules are this small and therefore, the guidelines treat these just the same as definitively pure small ground-glass nodules and no routine follow-up is recommended. Okay, let's now move on to the larger pure Ground Glass nodules, six millimeters in diameter or larger as in these two examples. The guidelines suggest that we get a follow-up scan in 6-12 months to see if the nodule goes away because it's likely that such a nodule represents a focus of inflammation or infection. If it doesn't go away, then the guidelines suggest that we get a follow-up scan every two years to establish for stability up until five years. In other words, so we can establish long-term stability. These lesions probably represent foci of Adenocarcinoma In-Situ or possibly Minimally Invasive Adenocarcinoma. What about part solid nodules that are six millimeters in diameter or larger? The guidelines suggest that we get a follow-up scan in 3-6 months to evaluate for resolution. If the nodule is stable and if the solid component is less than six millimeters in diameter, we should then get annual CT scans for five years to establish long-term stability. These types of lesions likely represent Adenocarcinoma In-Situ or Minimally Invasive Adenocarcinoma. If we have a part solid nodule that's larger than or equal to six millimeters in diameter, and if there's a persistent solid component that's six millimeters in diameter or larger, we need to be highly suspicious that that lesion represents an early bronchogenic adenocarcinoma. So, it's that central solid component that is key and once that gets to be six millimeters in diameter we have to be very suspicious. For these types of lesions, we should consider biopsy or resection and it is likely that these lesions represent Adenocarcinoma In-Situ, Minimally Invasive Adenocarcinoma, or frankly invasive adenocarcinoma. Here's an example of a lesion we followed along for three years. On the initial scan, we see that it's mostly ground glass with a small central solid component. At the one-year mark, the lesion had grown a little bit. At the two-year mark, the central solid component had grown and looks rather speculated, and at the three-year mark, the central solid component has exceeded that six millimeter diameter threshold. So, the patient was taken to surgery after three years and this was a Minimally Invasive Adenocarcinoma. So, you can see how indolent these lesions are. One caveat that I'd like to point out is that there is substantial intra and interobserver disagreement regarding the size and the presence of a solid component. So, if I show you this lesion, many of you might say this is a pure ground glass nodule, and others might say, well, I think I see a small solid component. So, keep in mind when using these management guidelines that there is some disagreement regarding ground glass and solid components, and that can affect how you use the guidelines. Okay, here's another question. Malignant correlates for subsolid nodules include all of the following. Would you choose increase in size, development of a solid component, increase in overall attenuation, or development of calcification. The best answer here is development of calcification. That does not correlate with malignancy but in fact all of these other factors do correlate with malignancy. So, let's look at some examples. In this patient, there's a small left upper lobe ground-glass nodule. This was not found prospectively but it was seen in retrospect scan obtained four years later shows a larger ground glass nodule. This is just a blood vessel running through it that's not a solid component. So, this lesion grew, and it was taken to surgery and resected. This turned out to be an Adenocarcinoma In-Situ. In another patient, we see a ground glass nodule on the baseline scan. This patient was lost to follow up and came back four years later. At this point, we see the nodule has grown, but more importantly, there's a large central solid component. So, that's quite worrisome. The solid component is larger than six millimeters in diameter. This patient was also taken to surgery. This was an Invasive Adenocarcinoma. Finally, we'll look at another example. This patient had a small ground glass nodule on a baseline scan. These are but just blood vessels running through and nearby the nodule. One year later, the nodule is slightly increased in attenuation without a definite solid component and at the three-year mark, the lesion has grown more and we can see that is also increased in attenuationm, but I would say there's no definite solid component. The patient went to surgery at this point in time, and this was resected. It was a Minimally Invasive Adenocarcinoma. So just to summarize, malignant correlates for subsolid nodules include increase in size, development of a solid component and increase in overall attenuation without a frank solid component. So, that brings us back to our initial question. Here we have an example of a nodule from a 53-year-old woman with no smoking history, an incidental nodule was found on a CT obtained for unrelated reasons, we see an 11 millimeters subsolid nodule with a four millimeter central solid component. So, what would you recommend for this patient? Would you recommend no follow-up, a follow-up CT in 3-6 months, a follow-up scan in 6-12 months or a PET scan or a biopsy. So, what would you recommend for this patient? The best answer would be a follow-up CT scan in 3-6 months, and if the lesion is stable then we would follow the patient with annual scans out to five years. That brings us to our take home points. Early lung adenocarcinomas may grow very slowly, and because of that we need to follow these for a long period of time. Our guidelines recommend follow-up for five years for apparently stable subsolid nodules in order to detect indolent growth, and we should intervene when the solid component gets to be greater than or equal to six millimeters in diameter. Thank you for your attention.
