Good morning, everyone. I'll be talking about immunoglobulin-4-related disease, specifically the imaging in the head and neck, and also hopefully some of the discussion which might be relevant to the other two speakers as well. So it's a fibroinflammatory condition and it's a truly multisystem disease. It affects multiple organs. On an average, 2.3 organs might be affected in patients. And it's important to note that the organ involvement might be synchronous at the same time or might happen over time in different organ systems. And the head and neck is the second most common site that's affected with this disease. And this is, as a distinct clinical pathological entity, this has only been known for less than 25 years. It was initially described as pancreatitis with elevated levels of serum IgG4 in 2001. But as a distinct entity, it was only described in 2003. No definite etiology is known. An autoimmune etiology has been postulated. No definite pathogenic autoantibody has been identified so far. Many of these patients, almost a third of these patients, might have allergic symptoms. They might have asthma, allergic rhinitis. But most of these patients do not have hypereosinophilia or hyper IgG syndrome. And unlike the hyper IgM and the IgE syndromes, these patients do not get recurrent infections or other immune deficiency features. On pathology, there are certain features which can be frequently seen. There is clonal expansion of B cells, plasma blasts. And there is lymphoplasmicytic infiltrate in the tissues involved. There is storiform fibrosis and obliterative phlebitis. And certain features on pathology tend to speak against the presence of IgG4. You see them more with other conditions that mimic IgG4, things like granulomas, giant cells, necrosis, which you see more frequently in conditions like granulomatous polyangiitis. And different criteria have been proposed. This was back in 2011, where elevated levels of serum IgG4, as well as tissue infiltrate were proposed. Then combining this with the clinical and the histopathological criteria. However, since then, it has been recognized that serum IgG4 levels are not very predictive. Half the patients may not have elevated levels. And it is nonspecific. You can see elevated IgG4 levels in many other conditions as well. So the diagnosis becomes challenging. Radiological imaging is not diagnostic. A lot of mimics can look very similar to IgG4 disease, especially inflammatory infections and neoplastic processes. And hopefully, you'll get to see a lot of cases over the next 40 to 50 minutes. Histopathological diagnosis is often required. Often that means either a core biopsy or a small incision biopsy. FNA might be a good first step to exclude neoplasia. But often, you need core biopsy specimens. And there are some reports which talk about the needle sampling being particularly painful in these patients, similar to what you see with schwannomas. More recently, diagnostic criteria have been proposed, which combine the clinical, the organ system involvement, the histopathological involvement. And it's a scoring system now. So even if the serum IgG4 levels are not elevated, there is a numeric criteria for diagnosis. They have to add up to more than 20 points. That's the natural history. It's not really well understood. Spontaneous remission of this disease has been reported, specifically in certain organ systems. I'm speaking about the head and neck. It's rare in certain head and neck sites. Typically, these patients tend to have very good response to corticosteroids. That can be the relapse rate is, although very high, you can see relapse rates of 24 to 63%. And the relapse may not occur at the same site where it initially manifested, but at a different organ system. And surgery is typically reserved for burnt out fibrotic lesions, where it depends on the organs, especially in the salivary glands. Surgery might result in complete remission. But in other sites in the body, it may not really be an option. And what's the role of imaging? Beyond the initial diagnosis, once the initial diagnosis is made, it's good to do whole-body imaging, either with PET or with diffusion-weighted whole-body MRI, to look for other sites of disease. And this is especially relevant if patients have chest or abdominal disease. You are looking for disease in the neck, which is more superficial and might be more amenable to tissue sampling. And no definite treatment response criteria have been established, although some studies have talked about increased normalization of the ADC values and the PET uptake helping with the treatment response. And again, you'll see examples where it can mimic malignancies. Depending on the organ system, you come up with a reasonable differential. Or other chronic inflammations and infections can look very similar. So deep diving into the organ systems or the tissues that can be involved in the head and neck, the salivary glands are the most common site. You can see involvement in 40% of patients. Often these patients will not present with symptoms of salivary gland disease. There might be some painless swelling. But often these patients, it's an incidental finding, and it's often found on whole-body imaging when you're suspecting IgG4. And two different patterns have been described, the multi-gland involvement that you can see that's classically labeled as the Michaelis disease, and the more focal, more localized disease, the Kuttner's tumor. Michaelis disease was described a long time back, and it was only recognized as an IgG4-related disease in 2005. Since the 1950s, it was considered to be part of the Sjokren's syndrome. And you have bilateral symmetrical involvement of the lacrimal glands, the salivary glands, typically the submandibular glands. And the swelling has to be for more than three months with an elevated levels of serum IgG4. Here's an example from the literature, enlarged submandibular glands. The parotid glands are also bilaterally symmetrically enlarged with level 2 lymph nodes. With relatively preserved parenchyma and vascularity on ultrasound. Because of the location, it's very superficial. Ultrasound tends to have very good utility in initial imaging for these patients. And what you expect to see is multiple hypoaequic nodules, which bulge the contour of the gland with some increased vascularity. But the underlying gland itself has preserved architecture. These patients don't show C. electases otherwise. And this is helpful in differentiating it from Sjokren's syndrome. In Sjokren's syndrome, you expect to see more C. electases. In the chronic phase, you can see atrophy. Other features that are helpful in distinguishing are the sinonasal involvement and lymphadenopathy, which tends to be much more frequent with IgG4 than Sjokren's. Cross-sectional imaging is helpful, not just once you have identified the involvement enlargement of the glands. It's good to look for other sites. So in this case, you have enlargement of the lacrimal gland, also lesion in the parotid gland. CT is particularly helpful if you're looking for erosive or bony destructive disease, which tends to happen more frequently in the sinuses, not so much in the salivary glands. But as a common feature, these patients, the tissue tends to show low signal on T1 and T2 with low ADC values. An FDG PET can be very helpful in differentiating and identifying the different sites of disease, but also in differentiating it from lymphoma, which is not just a differential, but can coexist in these patients. Patients with salivary gland disease, if the symptoms are longstanding, for over two years, they tend to have a lot of fibrosis. The response to medical treatment is not that great, and surgery is usually performed. And as I said before, surgery can result in complete remission in up to 80% of cases if it's isolated to the salivary glands. The relapse rate, even after response to corticosteroids, can be seen in up to a third of patients, and it tends to happen in certain subsets of patients more frequently. Going to the cutness tumor, the chronic sclerosing sialadenitis, it's the more focal form where patients present with firm swelling. Most cases have been described in the submandibular gland, very rare case reports in the parotid. These patients have well-defined geographical areas, and again, the surrounding gland might have preserved architecture and vascularity. Here's a different example in the right submandibular gland. Even on the contrast CT, you can see mild hyperenhancement, more heterogeneous appearance on the T1 and T2. But a common feature for most of these patients is the relatively low ADC values. Cutness tumor is more focal at presentation. Some of these cases can progress to involve the entire gland and subsequently become bilateral. And in this case, the patient responded to treatment, but on follow-up imaging, there was another lesion in the left parotid, as you can see here, showing altered signal in the more superficial portion of the left parotid and showing hyperenhancement. Moving on to the orbits, it tends to affect more older population, the middle-aged, the elderly patients. And unlike idiopathic orbital inflammatory disease, for a long time, this was considered to be part of the spectrum of idiopathic orbital inflammatory disease. What we used to call serotumor, it's now no longer used. Those patients tend to present with pain. IgG4-related disease is often periorbital swelling, but painless. Patients often present with proptosis with or without diplopia, and impaired visual acuity is not very common. The sites of involvement within the orbits could be in the lacrimal gland, could be in the extraocular muscles, or could just be in the intracranial or the extracranial soft tissues. The lacrimal glands are the most frequently involved. Often it's bilateral. When it occurs in isolation, the differential is wider, but when you see it in conjunction with the cerebral glands, one should think of IgG4 disease. And again, tends to show low ADCs, which can help differentiate it from pleomorphic adenomas or idiopathic inflammatory disease, which tends to show facilitated diffusion. Here's another example. Marked enlargement of the bilateral lacrimal glands, showing hyperenhancement, low signal on T2. And this patient also had other lesions, lesion in the left thyroid, mucosal disease in the sinuses, which was presumed to be IgG4 related, although it's hard to establish. You see it very frequently in patients with lacrimal gland enlargement or orbital involvement, but frequently it's not biopsied. This patient had other lesions as well, mediastinal lymph nodes, as well as axillary lymphadenopathy. Different patient with bilateral lacrimal gland enlargement. Again, you can see the low ADC values. You can see these with lymphoma as well. So sometimes it can be very difficult to differentiate from lymphoma. This patient actually also, on the coronal post-contrast images, had a large left parietal lesion, which showed very similar features, low ADCs, and responded well to treatment and did on the acute phase. It's important to look at, if you're doing PET, to do it more acutely before the treatment is started, because post-treatment, the PET uptake might decrease very quickly. Extraocular muscle involvement. Unlike idiopathic orbital inflammatory disease and thyroid, those are the two big thyroid orbitopathy, those are the two big conditions to distinguish. Like thyroid orbitopathy, the muscle belly is involved with relative sparing of the tendinous insertions, but there are a couple of features which help distinguish it from thyroid eye disease. One is the signal on T2. In thyroid eye disease, it tends to be high, whereas in IgG4-related disease, it's low signal on T2 and low ADC values, as you can see here. And lateral rectus involvement. With thyroid eye disease, lateral rectus is probably one of the last extraocular muscles to be involved, unlike IgG4 disease, where it's involved early and very frequently involved. And idiopathic orbital inflammatory disease is more painful, as I said. It also tends to involve the tendinous insertions, so that helps to distinguish the two. Here's an example. You can see the marked enlargement of the extraocular muscles. And more at the orbital apex, the medial rectus shows a big, almost mass-like lesion, which is showing low T2, restricted diffusion, and very avid enhancement. Different patient. This patient presented with visual symptoms, actually. You can see the thickening of the lateral rectus, but the inflammatory changes extend beyond along the lateral orbital wall. And on the coronal post-contrast images, you can see it extending. Even the retroanteral fat pad is effaced on the left side. And there is fat stranding and contrast enhancement along the optic nerve. This patient had other sites of disease, the nasal pharynx, the splenius capitis. This was actually biopsied to establish the diagnosis. Different patient who presented with just a mass at the orbital apex, extending into the superior orbital fissure on the left side. Patient had some improvement with the initial treatment, but two months later had a relative increase in the enhancing mass. Fortunately, this patient did have disease at other sites, and that was confirmed to be IgG-4-related disease. There are case reports of the infraorbital nerve being involved, the second division of the trigeminal nerve. This can be very challenging to distinguish from perineural spread in cases with, say, head and neck cancers. So, it's very important to look for a primary site of disease to distinguish the two. In the adnexa eyelids, it can be diffuse thickening or multiple nodular areas of enhancement. When it's bilateral, it's more helpful. Again, the differentials are lymphoma, thyroid eye disease, and other infections. Sinonasal disease tends to have two different patterns. So, there could be diffuse involvement where there is mucosal disease, sinonasal obstructive pattern, which, again, can be very difficult to distinguish from chronic rhinosinusitis. And these patients can have bony sclerosis as well in the chronic phase. But when you see something which is more destructive, mass-like, one has to think about infection, especially invasive fungal sinusitis, because the treatment for IgG-4, when you start steroids, it can make it significantly worse. So, it's important to exclude infection before starting any treatment, assuming it's IgG-4. And it's important to get tissue sampling and confirm the diagnosis. A different case, more focal form, involving the nasal vestibule, and this is the area, the markers showing enhancing mass and showing the typical features of low ADCs. This patient actually already carried a diagnosis, had a lung mass which had been biopsied previously, and post-treatment showed a very good response, nearly completely disappeared. Lymph node involvement is very common. Again, it's usually discovered when imaging for other sites or organs of involvement, because clinical presenting features are very uncommon because of the nodal disease. On imaging, it can be very nonspecific. It can look like benign or malignant lymph nodes. They do show activity, increased uptake on the PET scans. And sometimes can be challenging to distinguish from conditions like Rosi-Dorfman, because they can also have very similar imaging findings. And again, histopathology is important to distinguish the two conditions. There are certain features that help to distinguish. The nodes tend to be smaller. And systemic symptoms are often absent in patients with IgG-4 lymphadenopathy. Thyroid involvement can be, again, of two different types. The Riedel's thyroiditis, where there is extensive fibrosis, which extends into the adjacent tissues, versus the sclerosing, the fibrosing subtype of the Hashimoto's thyroiditis, where there is no extension. And most of these thyroid cases, there tends to be diffuse enlargement of the gland with low echogenicity on ultrasound, reduced density on CT. And Riedel's thyroiditis, because of the fibrosis which extends, it can present with tracheal compression and vocal cord paralysis. Hashimoto's is a very rare condition. Only a few case descriptions are there in the literature. There is an enlarged gland. And again, there is no extension into the adjacent tissues. And the main complication is lymphomatous transformation. Very rare case reports, we had this case of a patient who was treated for auto mastoiditis. The interesting feature, or the main distinguishing feature, is if you look at the tissue, it's a low signal on T2. In this case, it looks like any infection, a bad case of auto mastoiditis with intracranial extension. But this was IgG4-related disease. And there is more involvement of the otic capsule. But again, a key feature to recognize is the low signal on T2 and the ADC values. Rare case reports of idiopathic, can look very similar to idiopathic pachymeningitis have been reported. And last but not least, when looking at the CNS, some cases, in this case, we had a patient with hypophysitis, thickening of the stock, which was not initially recognized. And on follow-up, you can see the stock thickening increased. And subsequently, this was diagnosed. In the last, what's the goal of treatment? The goal of treatment is to reduce the inflammatory response, to keep the disease in remission, and to preserve the organ function. Disease monitoring criteria have been proposed. I apologize for this big slide. But this is relatively recent on how do we monitor these patients and their response to treatment. In the end, it's a challenging diagnosis. It can mimic many other conditions. Ultrasound is a good first step, especially in the head and neck, because of the superficial involvement. But MRI and PET are helpful to look for this multi-system involvement. And often, these patients need imaging-guided biopsy. Thank you. Good morning, everybody. So I'm moving down. I'm moving from the CNS to the chest. And the chest involves both lungs and heart. The heart is in the chest, contrary to what some people believe. So you're going to hear a few things that my colleague also said, because contrary to that, we work together. We don't see each other at work. So we know that IgG4-related disease, so IgG4RD, is a very new disease. So when I went to medical school, I didn't know about this. I knew about autoimmune pancreatitis. And this turns out to be part of the IgG4. And we'll hear from our astute colleague later. But furthermore, it's an unexpected disease. It's not something that you go in, you have a clinical scenario, and you are prepared to make the diagnosis of IgG4-related disease. It's a multi-station and a multi-organ disease, as we heard before. And this is a publication that was already mentioned, that autoimmune pancreatitis is not simply a pancreatitis. So it is an involvement with IgG4. And some very smart people 22 years ago in Japan identified that it's not just one entity, but it's part of a bigger picture that we are now so fortunate to call IgG4 disease and know that we can have to address the entire system and not just that particular problem. If you look at common pathohistologic feature, and this is, you know, radiology is an imaging-based as we all know, it's an imaging-based entity, but pathology is as well. And so I always like to give the pathohistologic correlation. It has diffuse lymphoplasmatic infiltrates and abundant IgG4 positive plasma cells and extensive fibrosis. So this is what our pathologists are looking for. Those are the hallmark features. Sometimes there are tumor swellings, eosinophilia, and obliterated phlebitis. And as we heard before that the polyclonal elevations of IgG4 is in most, but not in all patients. So if you don't have that, it doesn't mean that it cannot be IgG4-related disease. So keep that in mind. And the opposite is also true. If you have elevated IgG4, serum IgG4, it doesn't have to be IgG4-related disease. Pictures, right? So where does it go? We've heard about the meninges, the orbits, the lacrimal glands, salivary glands. And this is in an order of from top to top down, so to speak. Lungs, pancreas, kidneys, bile duct, and last but not least, cardiovascular. And this is just an anti-IgG4 antibody staining with IgG4 positive plasma cells. And so you can see that there's an abundance of cells that actually label with that stain, making the diagnosis of IgG4 possible. And that's why tissue is actually critical to be obtained before we can make that final diagnosis. We heard about this. And this is the pathohistologic diagnosis, how it is made about. And they are defining it or dividing it into highly suggestive, probable, and insufficient based on pathohistologic assessments. And so there is these features. And I apologize. It's extremely busy. And you can look it up online. You have to have two or more of the histopathological features and IgG4 and plasma cells that have more than 50 per high field. You also have to have a ratio between IgG4 and the normal IgG and the plasma cells that is more than 40%. So if you have that constellation of findings in your pathohistologic report, that is highly suggestive of IgG4-related disease. As you go down, you can see that the features become less prominent. So you only have to have one list from the findings. You have to have less, more than 50 cells. And you have to have a serum IgG4 concentration of greater than 2. So it's not a slam dunk. It's not something like an adenocarcinoma where you look, you look at your adenocarcinoma cells, it stains, it has its tumor markers, and you're done. This is a completely different entity and much more complex to diagnose, not just for us, but also for our colleagues in pathology. Now, if you're looking at cardiovascular and thoracic IgG4 disease, you have three big entities that are affected. You have the heart, you have the vasculature, and you have the lungs, per se. And they can be affected individually or all of them. It doesn't say anything of the more likelihood if you have all of them affected or if you just have one affected. The only thing that you have to do, as we heard from my astute colleague, is you have to look everywhere. If you have something in the chest that looks like it, you have to look at the entire body because it is likely that you will find more. And I have a bunch of cases that I'm sharing with you. So this is a 60-year-old lady who came in with a fever and cough. And obviously, we didn't start out with the PET. But just for completeness, I'm showing you the PET. We started out with the chest X-ray, and she had this opacity in her left lower lobe. Eventually, she got a chest CT. With contrast, and lo and behold, she had this consolidation in her posterior left lower lobe. If you see that without any clinical information, you diagnose a left lower lobe pneumonia, you put her on antibiotics, and you send her away, which is exactly what was done. Unfortunately, the patient didn't get any better. She continued to have a fever and a cough. At that point, people became a little bit suspicious that maybe this could be a vasculitis. You know, is this GPA? Is this eGPA? We don't know. She was just not doing well. And before, just giving her steroids, our colleague in rheumatology were like, no, we need tissue. And this was PET positive, because obviously, it was a big mass, so people were also concerned that this may be a tumor. But it was not very FTG-avid. It had a little bit of FTG-avidity. She didn't have any lymph nodes. And as you can see, she has a bit of a pericardial effusion, also something that you want to pick up, not a pleural effusion, which you would expect in this size of a pneumonia, a little bit of a pleural irritation. But no, a pericardial effusion. She came back two weeks later. And two weeks later, this looked like this. But then all in a sudden, she had a contralateral focus that was equally FTG-avid. And at that point, she was biopsied. And the diagnosis was made of IgG4-related disease. So you can see, again, this is not multi-organ, but it's multi-station. And it's with metachrinous foci, right? So they show up at different times across the patient's timeline. Now she has a little bit of a pleural effusion on that. Her pericardial effusion still remained. And she was still febrile. And then once the initiation of this corticosteroid therapy was started, she was feeling better fairly quickly. And all the opacities and the consolidation and even the pericardial effusion disappeared over time. So a unusual presentation. And the classic treatment started with no effect, at which point then it was prompted to look a little bit further. Next case. This is a 42-year-old male who comes in with a palpable mass. This is a well-built person who is working out quite a bit, but all of a sudden he was palpating something here in his axilla under his pectoralis muscle, and of course he was concerned. And as we can all see, there's this enlarged lymph node that lost his fatty hilum, doesn't have this classic grainy form shape anymore. There's not much peri-fat stranding, so it's not really like an inflammatory lymph node that you think or you might think. He may have injured himself, maybe has like an infection in his hand. It didn't have any of this. And since this was so easily accessible, a biopsy was planned. But before the biopsy, they did the PET, which is the wise thing to do because you don't want to do a PET right after a biopsy because it might be positive simply from your manipulation from the needle. And lo and behold, the PET was positive. So there was quite a bit of FTG avidity in that lymph node, and you can see in the adjacent lymph node as well. And the biopsy, again, was positive for IgG4-related disease. So this was unistation and not multifocal. And they scanned him from tip to toe, and that was all he had. So it can be quite exquisite, and it can be ubiquitous. The next patient presented with chest pain. And as you can see here, he has this very prominent lymph node on the left side. There are no lymph nodes on the right side. And this lymph node is clearly abnormal in size, abnormal in shape, lost his fatty hyaline. So all about this lymph node is concerning. If you see this in a woman, you would think, does she have a breast cancer? In a man, you would think, does he have melanoma? So you're looking for a primary tumor that is draining through that lymph node if you experience this. But they did this, and the IgG subclass was 170. As I said, this is not diagnostic, but this may be a hint to look further. And he ended up having steroid treatment, and it went down, but then it came back. So he also was diagnosed with IgG4. And again, this is just in the lymph nodes. The hint was the elevated IgG4, but ultimately, the diagnosis was made by tissue sampling. This is a middle-aged woman also, again, presenting with cough. This was the initial exam and the follow-up, right? Initial up, follow-up looked OK. But when she came back again, you could see that there is multistation disease here on our chest CT. They're very subtle. But then on the PET, you can see there are the internal mammary lymph nodes that are lighting up. There's a little bit of nodularity in the anterior left upper lobe. And there's quite a bit of FTG uptake in the posterior left lower lobe. And all you're seeing on the CT, and I don't know if that projects well enough. You know, chest X-rays and CTs don't project, as we all know. There's a bit of ground glass in the area of the FTG avidity. And last but not least, there is avidity in both axillary lymph nodes. And obviously, the easiest access point was the axillary lymph node, was biopsied, and was proven IgG4 disease. And again, I'm making the point that if you see this without any context, you wouldn't make the diagnosis of IgG4-related disease as first choice. In your list of differential diagnoses, that's not the first choice that you're pulling. But it shouldn't be outside of your choices. I think that's the point that I'm trying to make, is that if you have something that simply doesn't fit or something that looks weird, consider IgG4-related disease. Because it is more common than we think. It is heavily underdiagnosed because people don't have it on their internal checklist when they read those cases. This is something that I should have given my colleague, but I couldn't hesitate because I needed a case. Either way, this is a child. So it also happens in children. It's rare, but it does. And we see this T2-weighted MRI here with this fluid attenuation or high T2 signal mass here in the lower neck, which reflects to this mass here on the T1. And this was also biopsied because obviously, on a child, you're worried with all sorts of other things. Just for reference, this is another here, the parotid, also quite hyper-intense. This is a 65-year-old man. If you look at this, you would think, well, does he have sarcoid, right? You have bilateral hyaluronidase disease. You have middle mediastinal disease. But this was, in fact, actually IgG4-related disease. So 10 days later, the lymph nodes became quite a bit prominent, FTG-AVID, and biopsies were obtained. It's a great mimicker of other things. Of course, you wouldn't entertain this as a first thing. You would go to lymphoma and sarcoidosis, maybe. But if those come back negative, then you probably should say, hey, have you looked for IgG4-related disease? Because you are often the one who has to think about that. This is, I'm having a video here, and I hope it plays. So this is a 70-year-old male who comes in with a chronic dyspnea of unclear etiology. And this was one of the cases where the residents were like, OMG. And I'm just showing you the stills here for time's sake. So you can see that there is a very, very massive soft tissue attenuation focus next to the circumflex coronary artery here in an axial view, and then here in a multiplanar reconstruction. The circumflex coronary artery looks a little bit unhappy, squished, and attenuated. But it's an extravascular mass. It's not in a vascular mass. It's outside in the pericoronary soft tissues. And if you look here, you can see this is in the effect. This is the LAD. So you can see that there's this pericoronary mass outside of the LAD with long soft tissue along the entire LAD causing quite a bit of attenuation. The patient had elevated troponins. The patient was obviously not doing well. His EKG was highly abnormal. But this is not atherosclerotic disease. So the diagnosis or the differential diagnosis was, is this lymphoma or is this another vasculitis? We then scanned him tip to toe, and lo and behold, he had this periodic soft tissue stranding and also stranding around his SMA that involved the left renal artery ostium. And just to give you two multiplanar reformats of the LAD and the CERG, here you can see the extent of the tissue and the resultant stenosis. So you can imagine why this gentleman had elevated troponins, wasn't feeling well, had his chest pain. But the key was to give him steroids, which they did, and it melted away, and a week later it was gone. It was literally gone. And that's the other kicker that, obviously, we didn't biopsy this. Nobody sticks a needle in the pericoronary mass. That sort of, I haven't found someone crazy enough to do that, and I've done a lot of crazy things in biopsies. So this is obviously a diagnosis of exclusions, but the sheer fact that we gave him steroids and it disappeared makes it very, very likely, and we believe that this is. And his IgG4 levels were also highly elevated. And then just to give you a companion case to tell you that it's not always IgG4-related disease. This is an elderly woman presenting with weakness. Her ESR was 45, her CRP 19, her white blood count was 12.5. And you can see that there's concentric mural thickening, both in the ascending and the descending aorta. We have an FTG PET, and it shows this hyperintensity, sorry, FTG uptake around concentric. And here, this is just a rendition of the entire abdominal aorta. You can see that there's a lot of FTG avidity. And this ended up being temporal arteriosclerosis biopsy, and this was giant cell arteritis. Everything that has involvement of the large vessels, obviously, is IgG4-related disease. I don't want you to walk out here and think, okay, so I have to diagnose this on every weird-looking vascular case. But my take-home points are, think about IgG4-related disease. That's the most important thing. Have it on your differential. If you see abnormal perivascular soft tissue and masses and multistation disease, think about it even more. Recommend a PET CT early, before they initiate therapy, because the abnormality will vanish within days, meaning it will not be FTG avid after they initiated the corticosteroid therapy. And that's very important. It can melt it away, image early, and remind people about it. And with that, I thank you for your attention. Wow. Those were two wonderful presentations, laying a great foundation for me. So before we begin, let's see two unknown cases. And we have this case on the left. What do you think is going on with the gallbladder here? That's case number one. Unknown case number two is we see this structure. What do you think this structure is? So hold on to those thoughts, and we will revisit these cases in a bit. I'm Yashant from University of Iowa, and we will talk about IgG4 in the abdomen today. In next 16 minutes or so, we are going to be talking about a little bit of introduction about IgG4. We'll skip pathology. We'll talk difference between pathologic, sorry, we'll talk difference between classification criteria and diagnostic criteria. We'll talk about autoimmune pancreatitis, particularly IgG4. We'll digress a little bit, and we'll talk about autoimmune pancreatitis as a whole. We'll come back to IgG4, and we'll talk about other organs, which is bile duct, kidney, ureter. And in interest of time, we'll talk about aorta on the fly. And then finally, we'll summarize. So IgG4, as we just learned, is an immune-mediated disorder. And one fact which I want to emphasize enough that it is multifocal, multifocal, and multifocal, which can be synchronous or metachronous. Let's reemphasize this fact again. So say if a patient comes to us, and if we see on abdomen that the pancreatic pattern looks like autoimmune pancreatitis, look for CBD, because that will be involved. Look for salivary glands, and also look for lacrimal glands. Conversely, if the patient has enlargement of bilateral salivary glands, bilateral lacrimal glands, always look for lung involvement, pancreatic involvement, as well as kidney involvement. And again, emphasizing the same fact. If you see a pancreas versus sausage, at least 60% of those guys will have sclerosing cholangitis, and at least a quarter will have renal involvement. So multifocal, multifocal, multifocal, that's the key. Now let's talk about, I think we can skip pathology. Let's talk about the criteria. We have classification as well as diagnostic criteria. Classification, C for classification, C for clinical trials. So that's something we do not use. What I use as a radiologist on a day-to-day practice is diagnostic criteria, D for diagnostic, D for day-to-day. Interestingly enough, classification criteria alone will not suffice the diagnosis. And if you want to learn more about it, catch me in the hallway. So now we have laid emphasis on diagnostic criteria. So what are those diagnostic criteria? So those were revised from 2011 in 2020, and they are combination of clinical and serological, radiological and pathological. And a various combination of these will make the diagnosis definitive, probable, or possible. Now let's talk about organ involvement in the abdomen. Starting with pancreas, which as we know is the most common organ involved in the abdomen. Commonly presents as obstructive jaundice and has good response to steroids. It has at least three patterns. So this is the pattern that we know which is sausage pancreas, may or may not have a halo. It can be unifocal or it can be multifocal. Now let's digress into autoimmune pancreatitis. It is at least of three types. The one that we are trying to discuss today is type 1, which is IgG4 mediated. This is type 2, which is seen in young males, does not have an IgG correlation, and it may have ulcerative colitis. Recently, there is a described entity which is type 3 autoimmune pancreatitis, and that is because of checkpoint inhibitor. Let's see imaging. So in type 1, type 2, and type 3, we do not see much difference. This is sausage pancreas, some halo, again sausage, and then some contour abnormality, but then a lot of halo here. So virtually we cannot distinguish. Similarly, we can have just focal pattern of type 1, type 2, and type 3. And what really helps us diagnose is the histopathology and the clinical context. Now I said that if we have a unifocal lesion, is it always autoimmune pancreatitis? We have to consider a differential of the more common entity, which is pancreatic adenocarcinoma. So let's see how will we differentiate. So on the left, I have chosen a case which is multifocal IgG4. And if we see that the pancreas is... That's the sausage in the body and tail. And then there's another focus here in the head. Now what is more interesting here is that's the pancreatic duct, in which this size of a mass, it's not massively distended or dilated. So that's the key. Versus if you see pancreatic adenocarcinoma, first of all, the pancreas itself is very atrophic. The duct is extremely dilated. And there is abrupt duct cut off and we see the tiny mass here. So the dilatation of pancreatic duct is disproportionate to the size of pancreatic mass. So that is pancreatic ductal adenocarcinoma. Now, before we close this section on pancreas, let's see how the imaging is on post-treatment changes. So this again... So in this patient, we have again sausage pancreas. And after three years of treatment, the pancreas is atrophic. The patient developed diabetes and the pancreas has gathered a lot of calcification. Next, let's talk about bile duct, which is the second most common organ affected. Again, multifocal thing. 96% of patients with IgG4-related sclerosing cholangitis will have autoimmune pancreatitis. So the association is so strong. So always try and look for it. Always try to look for other clues to narrow down your differential. It can have multiple patterns. The most common is distal CBD involvement, but it can be a combination of distal CBD, hyler or intrahepatic patterns. How does it look on imaging? Just like any other regular cholangitis. And there is just thickening. But then is there any imaging pattern which is specific for IgG4 cholangitis? Yes, there is. And that is this long segment of distal biliary duct involvement. Versus we have differential of PSC, primary sclerosing cholangitis, and we see short segment structure. The duct in between is dilated. So it looks beaded. Now I have purposefully given two images because I want to lay emphasis on the fact that PSC most common pattern is extrahepatic as well as intrahepatic. Whereas IgG4 most common pattern is distal. Now IgG4-related sclerosing cholangitis is such a big name. So big or long segment involvement. PSC is a short name, short segment structures. The other differential to consider is cholangiocarcinoma. Let's see the imaging. So again, long segment structure for IgG4, short segment structure for cholangiocarcinoma. And if you remember, we saw pancreatic ductal dilation with cancer was massive. And similarly, upstream biliary dilation here is massive. And IgG4 is more located distally. Cholangiocarcinoma is more common at the hilum. And finally, if we see the distal CBD, it is concentric and smooth thickened. Versus if we see cholangiocarcinoma, so that's the bile duct and there is eccentric thickening. So the thickening in cholangiocarcinoma is eccentric versus thickening in IgG4 is going to be concentric and smooth. And let's see about post-treatment imaging. So this guy had obstructive jaundice and long segment narrowing. And after two years of steroids as well as balloon dilatation therapy, the CBD does not look that bad. Okay, before moving to kidney, let's do our unknown case number one. So in this case, we had massive thickening of the gallbladder wall. Let's see this case again from the top and what other things this guy has. So the spleen has this plaque at the outer surface. Look at the pancreas. Some subtle absence of the nodularity, some sausage appearance here. Look at the CBD distally. There is thickening as well as there is enhancement of the CBD. And further distally, if I go, I see that there is peri-aortic soft tissue. So in the entire clinical context, this thickening of gallbladder is also because of IgG4 and ultimately it was proven as IgG4. Let's talk about kidneys. Kidneys are the most common GU organ and they also show good response to steroids. So what are the renal patterns of IgG4? So each time I think of IgG4 in kidney, I think of lymphomine kidney because those are virtually the same patterns. So which is multifocal bilateral involvement, solitary, perinephric rind, unilateral or bilateral, something like Erdheim-Chester or unilateral or bilateral, something like Erdheim-Chester or unilateral or bilateral soft tissue at the hilum, something like Roseidorfman. Okay, so a lot of differentials in kidneys, starting with multifocal as well as those can be round or those can be wedge-shaped. So we see this wedge-shaped lesions here on corticomedullary phase. The seeping little bit of contrast become isotope, slightly hypotopic cortex versus, let's see infarct. So infarct again will be wedge-shaped and hypotenuating. But if we do delayed, the infarct will seep in the contrast. This is the flip-flop pattern of enhancement, pretty specific for infarct. Another differential for multifocal involvement. Okay, so the interesting part here is I've not given you any pretty images because diffusion weighted images are not like, you know, really anatomic images. They do not give you that anatomical detail. The reason here is because I want to emphasize the fact that IgG4 also does cause diffusion restriction and so is the case with pilonephritis. Yes, IgG4 is more common bilateral, pilonephritis is more common unilateral, but the real distribution factor here is the clinical scenario of the patient. Multifocal, next set of differentials. Again, IgG4, it can look like lymphoma. So you have to biopsy. At times, we can see lymph nodes, but regardless, you have to biopsy to typify the subtype of lymphoma as well. What if there are thickening at the higher level? It can be unilateral or bilateral. Again, lymphoma is a differential. You may or may not have lymph nodes. Again, the answer here is biopsy. And finally, perinephric rind. So you can see it in IgG4, look for other organ involvement. It can be in lymphoma, look for lymph nodes. It can be in Arthritis. Look for other classic findings like sclerosis at the knee level. And finally, what is the post-treatment imaging in kidneys? So this guy had those multifocal involvement of the kidney. And after six years of image, we are seeing those cortical scars. So one pattern that we did not describe in detail was the solitary pattern. So let's see that as a case. So this patient presented with this incidental renal mass. This is cortical based, looks more like wedge-shaped or maybe oval. I don't know of a renal cell carcinoma which is oval. They are round, they are infiltrative, they are ugly looking. Okay, but that does not negate that it cannot be RCC. But let's go further inferiorly. And again, I see this periaotic soft tissue. So in that context, again, I'm not saying we are replacing biopsy. We are just narrowing down the differentiation. And it turned out to be IgG4. Okay, so patterns in the ureter. So ureter is affected at least in four different ways. So the first pattern is pretty nonspecific. We can have fibrous pseudotumor. Second pattern is segmental urethelial thickening. It is difficult to differentiate this pattern from a third pattern, which is periureteral fibrosis. And a fourth pattern in which the ureters can be affected is retroperitoneal fibrosis. So let's see example for the polyploid mass. And let's see example for retroperitoneal fibrosis. So this is the case. Again, there's absolutely no way on imaging for me to think of IgG4 in this case. But luckily in this case, the very first slide showed some soft tissue around the right side of the paravertebral area. I said, let's get a CT chest done. We got a CT chest done. And we see this band of soft tissue. Now this band of soft tissue on the right side at the level TA2 to T11 is pretty specific for IgG4. And it turned out this was biopsied and it turned out to be IgG4. And this mass was excised. And again, this also turned out to be IgG4. Okay, the another pattern for ureteral involvement, as we said, is retroperitoneal fibrosis. And this is our unknown case number two. So let's see, we have bilateral hydronephrosis, hydroureteronephrosis, more on the right side. Let's focus on the right side. So we have the ureter and there is ureterial thickening. Ureter is not exactly anterior to the psoas, which is fine. Let's follow the ureter. Ureter is retroperitoneal and should be on psoas, but the ureter is going far lateral. Let's follow the ureter. Now ureter is so lateral that it is lateral to the ascending colon. And that's the fold of pectoralis. And that's the fold of peritoneum. So ureter is in the right paracolic gutter, which means ureter from being retroperitoneum has gone into intraperitoneal. And that actually is the treatment for liberating ureters of the retroperitoneal fibrosis. This is known as intraperitonealization of the ureters. And that's a treatment for liberating the ureters. And this guy had normal appendix. That's the normal appendix. So that structure, that unknown structure that we saw adjacent to the colon was actually the ureter. Okay, so we learned aorta on the fly. My previous speaker did an excellent job showing circumferential thickening around the aorta. That's one pattern of aortic involvement. Another specific, more specific pattern is if you see both these, these are two different patients. If you see there is thickening around the aorta, anterior or anterolateral, but there's virtually no thickening posteriorly. Again, another patient, anterior and anterolateral and no thickening posteriorly. So that pattern is specific for IgG4. And I did mention almost all cases that good response to steroid, good response to steroid. With aorta, if this is the patient, I will see good response to steroid. But if I see aortic aneurysm, especially for IgG4, steroids are contraindicated because this has risk of rupture. So we have to keep that in mind. And with that, I would just like to summarize. IgG4 is a fibroinflammatory disorder. It's multifocal. So always look for other associations. And if I have time, I can show one more case. Okay, so this patient, 63-year-old male, has bladder cancer. Two years later, comes with this lesion in the pelvis. Again, urethral cancer is also multifocal, either synchronous or metachronous. So is it really urethral cancer? Again, final answer lies in biopsy. But let's see the imaging two years later. So in two years, this patient has sausage pancreas, halo around the pancreas, thickening of CBD. And it turns out that this urethral thickening and this polyploid mass in the ureter was IgG4 in the right clinical context. So again, I'm not saying that we are dismissing the fact that biopsy is important. It is definitely important. But as radiologists, we can narrow down the differential diagnosis. And if one thing that you want to carry from this talk is multifocal, multifocal, and multifocal, thank you. Thank you.

IgG4-related disease

fibroinflammatory condition

multiple organs

histopathological confirmation

corticosteroids

autoimmune pancreatitis

multisystem involvement

differential diagnoses

biopsies