Salivary Gland Pathology PDF

So we're going to talk about salivary gland pathology today. And I just thought I would remind you where our salivary glands are located. Right. So we have major glands in our cheeks right on both sides. Bilateral or parotid glands are located there. Remember that that little bump that you notice in...

So we're going to talk about salivary gland pathology today. And I just thought I would remind you where our salivary glands are located. Right. So we have major glands in our cheeks right on both sides. Bilateral or parotid glands are located there. Remember that that little bump that you notice in your patients on their buckle mucosa bilaterally near their first molars is not a benign nodule that you need to excise, right? It is the orifice of Stinson's duct. Right? It's the orifice of the parotid gland duct that you you have bilaterally. You should be milking those ducts in every patient as a part of your intra oral exam to confirm that salivary saliva is flowing freely and normally. Right. Okay. So you have the parotid glands, bilateral buccal mucosa. You have sublingual glands kind of on the floor of the mouth and beneath the tongue you have you have minor salivary glands actually located right in the ventral tongue interestingly. And then you have submandibular glands a little deeper down on both sides bilateral symmetric. And they share this excretory duct called Wharton's duct. Right. That that perforate the floor of the mouth on either side of the lingual freedom. All right. So you're very familiar with the general anatomy. I'm sure, but just by way of review. So in addition to big major salivary glands, now salivary glands produce different kinds of secretions you may remember. Right. So the parotid glands tend to produce serous kind of watery secretions. Some sublingual is more mucus. And submandibular is kind of a mixture. Well the minor salivary glands of which we have hundreds and hundreds of of them in our mouth, tend to produce a thick, viscous mucus, snotty like secretion. Okay, now there is a condition I'm highlighting here just because we're talking pathology. What if I tell you this is a patient is a cigaret smoker? What change do you see on the palate? Do you all remember? You got it. Nicotinic stomatitis. Right? Remember that thermal injury from the heat from cigaret? Smoking causes a keratin ization that causes a white change on the diffuse white change on the hard palate. But the minor salivary gland or a fire are highlighted. They're inflamed. Right. So you see these little polka dots, these red polka dots. Those are the inflamed minor salivary gland excretory ducts. I'm just using that condition today to highlight how many minor salivary glands we have on our palate. And we also have them on our lips, right. Soft palate as well. And ventral tongue. So, you know, I love a good cartoon. This is just a drawing of the cell types that are going to misbehave in our conversation today. So this is a salivary gland unit. All right. So there's the inner element here closest to me. Oh I forgot my pointer salivary gland element closest to me. These are astronaut cells I have to get used to that. There we go. And then these are this is the excretory duct that brings the saliva into the oral cavity. All right. So the cells here at the base are in this case they look like little serous cells. They have little granules. They are producing the secretion. These cool cells around the inner cells are myo epithelial cells. Myo meaning muscle. Right. Their job they have some contractile elements in them, is to actually help squeeze the salivary gland units to help drive the process, to help get the saliva out into the oral cavity. Isn't that cool? And you can even see one here lined along the side of the salivary gland excretory duct. And then you notice that there's some salivary gland excretory ductal cells that are kind of hot pink. And they have these kind of frilly surface on them, these we call striated ducts. And they have some mitochondria in there, which gives them kind of a hot pink look. And then you notice that instead of being one cuboid cell thick, the excretory ducts, as they get closer to our mouth look, they start to layer up. And then what did they turn into? Squamous cells. Right. So as our salivary gland excretory ducts merge with our oral mucosa, the ends of the the salivary units I guess, become squamous sized. Or they, they take on the characteristics of the squamous mucosa, kind of a hardier less specialized cell type. So just showing you generally what, what the cells look like in a cartoon fashion. So then we can see them as they get up to trouble. So this is these are some globules of salivary gland tissue that are normal. You can see these are the this pointer. These are the inner units. And then these guys here are the salivary gland excretory ducts. This is probably one big duct. It's just that like a serpent it's going like this right as it's heading towards the the oral cavity. And we're cutting through one plane. Right. So we're not seeing a nice straight tube. We're seeing the gland captured. The duct captured in a couple of different planes. That's why it looks that way. But you can see the cells that circumscribe the excretory ducts are kind of hot pink, right? Kind of pink cuboid looking cells that go around each of the excretory ducts. And here's a higher power view of the mixed salivary gland. So what do I mean by that? I mean that this salivary gland tissue, normal salivary gland tissue, is composed of both serous cells that make kind of a watery spit, all right. And mucus cells that produce a thicker, more viscous saliva. And so if you look closely, you'll see these are the serous cells. They have these little kind of granular polka dots inside them, kind of a purple dusky looking ascender unit. Whereas the mucus acid I have very pale frothy cytoplasm. Right. And then this is a striated duct. Remember I showed you in that picture those excretory ducts that are hot pink and frilly. They have a lot of mitochondria in them and they tend to have a bright pink look. So this is just a normal mixed salivary gland. All right. So that's just a quick review of what normal glandular tissue looks like so that we can talk about it now when things go wrong. So this is a rare situation. But I did want to mention that some patients are born without a full complement of salivary gland tissue. When that occurs the term is salivary gland a plasma. It is rare, but it usually affects one or more than one major salivary glands. So some syndromes, I believe, can show that as a component. But it can also be sporadic that that you may just be born without a full complement of salivary gland tissue. If it's multiple major glands are absent, then you can expect that the patient would suffer from marked hypo salivation, right? Severe dryness of the mouth, which can lead to caries. Right? Dental complications. Our salivary tissue is really important in protecting us from caries. The tongue would be leathery. The mucosa would be dry. The tongue would stick to the roof of the mouth. It might be difficult for them to say if you were to hand them a cracker, to eat that cracker and swallow it safely without having water beside them to to help get dry foods down so it can be, you know, a safety issue. Patients have to be very careful when they're eating and with food choices. Unfortunately, there isn't great treatment for patients with dry mouth. I'll mention this again, but I salivary substitutes are listed here. One of my favorite ones right now is a product called xylem. I think I may have mentioned those to you before. It's just an over-the-counter product, but I tried them. I wanted to see what they were like. And they they come in a box of about 24 little tablets at my local pharmacy, like CVS or whatever. They sell them where they sell toothpaste, but your patients can also get them on Amazon. So that you put this little tablet in your mouth and one side gets sticky and it sticks to your gums, so you can put one in your upper maxillary posterior facial attached gingiva. And you could put one on each side if you wanted, kind of approximating where Stinson's duct is on your buccal mucosa. So that and during the time that it was in my mouth, my mouth felt very lubricated. It lasts about two hours. And I think that's why these products are better than some some salivary substitutes. You just kind of paint them on your tongue or you spray in your mouth, and they work for a moment and then they're gone. Right. And so the reason I kind of like these, if your patient is investing in a product, at least this lasts a couple hours, and they are technically made to be used while you sleep because they safely dissolve, they don't linger. So the patients who have to wake up a lot in the night to quench their thirst and to lubricate their mouth with water, they they may find these helpful. So I just mentioned them to you so that you can remember they exist in case you encounter patients with dry mouth. I would say it's not an uncommon conversation to have in patient care. So let's talk about a scenario in which usually your minor salivary glands. All right. So we'll think about the salivary glands particularly in the region of your lower lip or even your ventral tongue. Right where I told you underneath the tongue the tip of your tongue, you actually have some minor salivary glands. They're very easy to traumatize these areas of your mouth, right. When you're little and you're learning to walk and you fall and you're, you know, you bite your lower lip or your lower lip strikes, something those minor salivary glands are doing great. They're churning out saliva. Everything's fine. And then when you fall, if you crush or sever that excretory duct, the acid, or you're making the spit, but instead of it going into your mouth through that duct, it is often spilling now into the surrounding connective tissue. And that creates a mucosal or mucus escape reaction. All right. Your body does not appreciate having saliva in the connective tissue. And so you react to it by walling it off with granulation tissue. Very brave cells called macrophages jump in to try and sop up the spit the mucus. We call those phages. When they do that, they get very frothy. But there's way more mucosa secretion than there is the ability. It's way beyond their ability to to sop up the the extra mucus. It is not a true cyst. It is a pseudo cyst. Your body walls off the saliva in this little bubble. And so sometimes patients will you will be able to see a fluid filled vesicle on their lip. It might even look a little blue to you clinically. Because when light passes through a fluid the $10 effect makes it look a little blue. So you will look and examine the patient and see a little blue vesicle, usually on the lower lip, almost never on the upper lip. Mucus seals almost never occur on the upper lip. All right. But mucus seals tend to occur on the lower lip. And patients will sometimes say that it fills in empties all on its own. And so that probably has to do with salivary production. Right. And filling of this kind of cavity. So anyone can have a mucus seal. But they are more common in younger patients who tend to take elbows to the lips during basketball and fall down when they're learning to walk and ride bikes and so forth. They are usually fluctuate, but if they are deeper, they might feel a little firm when you palpate them. You can also see them at other sites where a salivary gland excretory duct could theoretically be obstructed or traumatized. And so I've listed those there. Sometimes if the lesions very superficial, it might rupture and resolve on its own. Occasionally they will spontaneously regress, but it is not unusual for surgical excision to be indicated. In order to expedite resolution completely. The surgeon would need to remove not only the regional tissue, but also the feeder glands that are leading to the problem. Otherwise, the lesion will recur. Here's a cartoon. Okay. Sort of emphasizes what I have discussed. At the very top is surface epithelium. All right. And this is epithelium here. And we're down here in the connective tissue. So this is lobular of minor salivary gland. And this is the excretory duct. And you can see it was supposed to join up here with the surface and bring saliva into my mouth. But instead the duct has been severed secondary to trauma. And now all of the secretions that the salivary gland is making our spilling into my connective tissue. So here's just a nondescript swelling of the lower labial mucosa. It could be a number of things other mesenchymal lesions could present this way. This just happened to be a mucosal. Another example. This one has almost a little bit of a bluish color. I think it actually in this case is an old picture. It looks better on the TV monitor. It looks a little blue to me, which is what I typically expect in a mucosal that's a little closer to the surface. So when you biopsy this you will see the surface epithelium at the top up here. And we're down here in the connective tissue. And all of this pale material is mucus that these salivary glands were producing. But you can see that it's kind of walled off. There's this rim around it. And if we zoom in in this other image the rim is made up of granulation tissue. It is not an epithelial lining. It is just your the patient's body's trying to to wall off the mucus and keep it from going anywhere else. So you produce granulation tissue. We call it a pseudo cyst not a true cyst because it doesn't have an epithelial lining. This is very common. You will most certainly see this in your clinical practice. All right. Any questions about that mucosal. So the counterpart to a mucosal when it occurs in the floor of the mouth we use a different name. Same thing exact same pathology. It's just that a major gland is feeding it like your submandibular gland. And so when that occurs it produces a really large swelling in the floor of the mouth where the saliva is pooling beneath this the mucosa. And you end up with what if you've seen a frog when it does that kind of croak and it gets this full kind of throaty bulge, right? Have you seen that? So the term is supposed to mean like frog belly. But in any case, it I think was chosen this term because it kind of has a similar appearance. So it's mucus escape reaction, same phenomenon, just, you know, trauma or severance or damage to the salivary gland, excretory duct, but of a major gland. So sublingual gland or submandibular gland, it can sometimes even be minor salivary glands in the floor of the mouth. But more commonly it's one of these major glands producing a major problem. You get this blue dome shaped fluctuation, swelling of the floor of the mouth. It's usually larger than mucosal at other sites because these are major glands producing quite a lot of saliva. And so that tends to be a little more dramatic. And the treatment is to excise the lesion and the feeder gland just as before. So this is the patient's tongue is kind of pushed to the side. But you can see this huge swelling in the floor of the mouth that is taking up most of the patient's right side of the floor of the mouth and pressing the tongue up. And that's kind of got that bluish coloration. So again, that's a regular it's a mucus seal a mucus escape reaction is just we use a different term when it involves the floor of the mouth, because it can sometimes have some complications. If the mucus escape occurs below the musculature of the floor of the mouth, it can you can get what's called a plunging granuloma, which can cause some swelling in the neck. And that can be a little bit serious with regard to some airway complications. So. So sometimes when mucus escape reactions occur in the floor of the mouth, that can be a little more problematic. Did you have a question. So the differential diagnostic for mucosal and. Ranelagh. It's just the location or and the. Because on these slides for Newcastle it's also saying that it has a little more of a mouth. So regular. I'm sorry. Let me back up. Confused. What? Idea for the mall. Most common locations. The. It's it. Right? Yeah. So so we use that term usually for size of the lesion and the feeder gland. Right. So if it's a pretty large robust lesion on the floor of the mouth, we usually assume that it's probably being fed by a major gland. And so we usually use the term regular in that case. So if you see a mucous escape reaction on the floor of the mouth, we usually use the term granular. And if we see a mucus escape reaction elsewhere in the oral cavity being fed by one of these minor salivary gland clusters, we call it a mucosal. And in either instance they are both mucous escape reactions. And neither is wrong okay. It's just a terminology change. And then I would say I think granular kind of acknowledges that it could be a little more serious, right. It could be a little more significant because if it's being fed by a major gland, then you're more likely to have complications. All right. So we talked about a mucus seal when we said that that is not a true sift cyst. Right. Granulation tissue surrounds this mucus that's spilling into the connective tissue. Well, there's another scenario where a true cyst can occur. Salivary ducts are much more common on the upper lip, interestingly. And it is a true cyst line by epithelium. And it could be developmental in nature where there is a true cystic lesion that developed in the salivary gland tissue. Or you could get a cyst like dilatation of a salivary gland excretory duct if it is obstructed. All right. So let me show you the scenario. All right. We're back to our cartoon. So here's the surface epithelium. Connective tissue. Here's my minor salivary glands producing saliva were in the duct. And you can see that the duct still connects to the surface. But what if there's a little obstruction. Maybe it's a life like it is, in this case, a little stone, a salivary gland calculus, if you will. Or what if it could just be a plug of Inc. mucus dried up mucus plug. Something that's preventing the saliva from getting out of my salivary gland, excretory duct. So the saliva stays within the duct. It's just synthetically dilated. Okay. We call that a salivary duct cyst. And again, it's often that the saliva is being prevented from exiting the duct. The gland is healthy. It's producing saliva. It's moving down the duct but it can't go anywhere. So the duct just gets very full. Again, we're just looking at a nondescript soft tissue swelling here in the kind of retro molar Trigun area. Could be any number of things. This just happened to be a salivary duct cyst. So what does it look like under the microscope? Everyone wants to know I know. So you have this overlying surface epithelium down here in the connective tissue. I see some of that new coiled material. But instead of granulation tissue at the edge there's a true epithelial lining. And it's kind of a cuboid or bilayer cuboid lining like I would expect in a salivary gland excretory duct. And here you see it again a different these are inflamed minor glands, obstructive scientists. The glands are trying to produce saliva, but they're quite angry and upset because the spits not going anywhere. So here's the saliva pooled mucin and surrounded by this cystic epithelial lining. So that is a salivary duct cyst. And again the difference location. Much more common in the upper lip. And then the effect essentially is that when you look at the specimen instead of the extrapolated mucosa material being out into the connective tissue, it's contained within the lining of this cystic dilated excretory duct. All right. That's the difference. Now we mentioned just now that sometimes you can get a little calcified concretion in your salivary glands. And they aren't always little, quite frankly, just like you can imagine having developing a kidney stone. You can get salivary stones. We call them cialis sile. It can occur in any gland. But it's much more common in the glands of the upper lip. So minor salivary glands in the upper lip area, we sometimes see them in the vestibule. And then certainly our submandibular gland has a very tortuous excretory duct. And it is a known fact that that particular duct and its anatomy makes it a troublemaker, a magnet, if you will, for for developing these salivary stones. They start with a nice of something. It could just be a little insisted. Insisted. Beads kind of dried, right? Insisted McCoy material. And then over time, the mineralized products from our saliva as the saliva flows over this little nubbin. Right. This is mucus, muses. Mucus. Mucus? Well, just like the rings of a tree, you'll get layers and layers of mineralization around this nidus, and you will develop a stone that is composed when you cut into it histopathological. It really does look laminated like the rings of a tree. So these are calcified structures within salivary gland excretory ducts. We tend to see them, say post-surgery. Or if you are on medications that diminish your salivary flow or if you're dehydrated, things of that nature, anything that reduces salivary flow will mean give your. Not only will it thicken your secretions and give you a greater chance of having a little noticed from which the stone can build upon, but it also slows salivary flow, and so the saliva tends to thicken and pool, and then the mineralized components can develop and contribute to the development of salivary gland stones. All right. So I think we went over all of that and. Oh yeah, of course, at meal time when you sit down to think about dinner or you're eating, your salivary glands are stimulated to produce saliva. And so patients with obstructive silence will often endorse discomfort that's associated with meal time or round meal time. Palpably firm, and if you do imaging, you might be able to see the stone as a radial mass in an excretory duct. This is kind of an old picture, but we're looking at the swollen, if you will, dilated Horton's duct here. But this is, I think, a nicer picture. So this is an old fashioned occlusal film right. Occlusal radiograph. And you can appreciate the stone the lith it's sort of an ovoid calcification in the floor of the mouth. This is right near Horton's duct. This is the lesion when it was excised. And then remember I told you under the microscope you just see these layers of mineralized material, kind of amorphous acellular calcified material. And you can see again how it's kind of laid down in layers. So that's a nice salivary stone silo. Lith this one was big. So they can get quite large. And of course there can be discomfort associated with that now when salivary glands are obstructed, when there's been trauma secondary to misadventures, if there is an infection, things of that nature, you can develop selenium, which is just inflammation of salivary gland tissue. So as I mentioned you can have both infectious and non infectious causes. Infectious causes could be viral. We've talked about mumps already in the course CMV I told you you don't have to know that under the microscope. But we did talk about how it was trophic for salivary glands and endothelial cells right. CMV if you remember, was the usually an immune compromised patient just a non healing ulcer that you will biopsy. But if you remember it was the viral inclusion. Looks like an ally looking back at you. Yeah. So that one tends to be trophic or thrive in salivary gland tissue. Bacterial infections sometimes from ductal obstruction. So post surgery if you are we are given medications when we go undergo general anesthesia. That helps slow our secretions to protect us. Right. And so it is not uncommon for post-surgical complications to include silent itis because of stasis. Right. So our salivary glands are not cleansing. They're not flushing the system. And so bacterial organisms can kind of retrograde, find their way into orifice. And you can develop, you know, complications from that certainly decreased salivary flow for other reasons to polypharmacy and inadequate hydration, things of that nature. Obstructive phenomena that we've discussed can also cause silent nights and then noninfectious causes. We've actually talked about sarcoidosis before in the course. Remember when we talked about granulomatous inflammation? I told you there is a very particular kind of inflammation where you get these collections of epithelial adhesive sites, if you remember, and we said you could see them in Crohn's. And the other thing was sarcoidosis. Sarcoidosis like salivary gland tissue. So that's a form of an inflammatory condition that is not infectious. At least we don't think we don't know. But it's a very particular inflammatory condition Chagrin syndrome we're going to talk about now. It's an autoimmune silent itis. So your own immune system inappropriately targets your salivary gland tissue. And then, of course, if you've ever undergone radiation therapy and your salivary glands were in the field of radiation. So this isn't terribly common. But just for sake of completeness, we'll talk briefly about celebrities that's caused from bacterial causes. It most commonly affects the parotid gland. And unfortunately, about a quarter of the time patients have bilateral involvement. Patients develop pain and swelling of the affected glandular tissue. And because this is an infection, they will develop a low grade fever. When you milk these glands, you know how to do that, right? You dry the Wharton's ducts, the papilla with gauze. Always. You must dry it, otherwise it doesn't work. You have to dry the gland and then reflect the buckle mucosa and just kind of palpate from posterior to anterior. And you will be able to express saliva from the stetson's ducts and, and Wharton's ducts as well. And the floor of the mouth, just to make sure that saliva is flowing freely. When you do that, pus often comes out instead of saliva. So that's also a very helpful sign that there's an infection. And so pushing fluids is important in these patients to help flush the glands and make sure that they are not state, they're not dealing with stasis. And then of course systemic antibiotics. So here's a patient with a just large swelling of the submandibular gland area as a result. As a consequence I should say of a bacterial psyllid notice and all of the signs that you would expect in that situation, the what is it, dolore ruber? You know, you go through all of your signs of inflammation, pain, swelling, redness, heat, loss of function. All of those things would be expected in a bacterial side notice. Yes. Any anything related with mumps also that you can. Uh, think it's mumps instead of selenite. So, you know, one thing I will say about mumps is that it it tends to affect multiple glands, including genital glandular tissue. And whereas acute bacterial itis also when you. Milk the ducks in mumps, you would not expect to see pus. So this bacterial infections tend to lead to the formation of pus, whereas the viral. Infections do not. So then a chronic bacterial notice. But I don't discount your point that there is some overlap. Certainly chronic bacterial meningitis is kind of disagreeable because these patients have multiple either multiple episodes or kind of an on and off again issue with disorders related to bacterial infection of their salivary glands. And sialic acid is a known troublemaker. So if you have obstructive silentnight as a result of salivary stones, then you may develop chronic bacterial meningitis as a result. And patients will endorse, you know, whenever they're getting ready to have a meal, they have pain and swelling because of the obstruction. So proximal to the area obstruction, the salivary gland excretory duct is markedly ecstatic, right. It's dilated because it's trying to force saliva past. And so you may be able to see that on imaging studies both major and minor glands can be affected. Although I would say certainly when it's a bacterial itis I usually think of major glands. And then certainly if you can remove the obstruction, push fluids, antibiotics, things of that nature, patients usually tend to have a good outcome. There is kind of an uncommon phenomenon that is an inflammatory condition of the minor glands of the lips. It is called colitis, glandular, and it is usually in patients who have severe sun damage of the lips. That's generally the most common cause that's associated with that, although I listed the other factors that are mentioned in your textbook as plausible etiologies. So it's a very rare, but nevertheless you should know about it. Patients develop inflammation of the minor glands, usually of the lower lip, and it causes the lower lip to swell and avert. And you can actually see the horrify of the minor salivary gland excretory ducts. They kind of ooze. And certainly patients have pain and irritation, if you will, at the site. So here's a patient just demonstrating kind of diffuse fullness of the lips. And you can see here a little punctuate area of ulceration or irritation. I don't know if that is from their own kind of traumatizing the area because it's bothersome. But usually patients will endorse kind of salivary secretions on their lips. Now again, that's fairly uncommon, but just mentioned it for completeness sake. But this is not uncommon for Estonia, which is an oral sensation of oral dryness. It's the the sense that you have dry mouth is actually very common. I'm sure many of your patients will comment with regard to the lubrication in their mouth, because most often it is because of medications they take and need. There obviously a long list of medications that are list hypo salivation or stoma is a side effect in their side effect profile. However, you know that just taking multiple medications, even if dry mouth, is not associated as one of the side effects, that certainly can also cause hypo salivation. So the more medicine you take in certain medications can cause dry mouth. Other causes. Dehydration. Many of us do not drink enough water. All I've had today is a cup of coffee, so I'm pretty sure I have dry mouth right now and then autoimmune, which I'll mention in a moment. Smoking can cause hypo salivation or at least contribute to it. Certainly radiation therapy damages the very delicate salivary gland elements. Mouth, breathing and other things can contribute. Um. It's not uncommon when you are examining a patient with hypo salivation to notice that your mirror sticks to the mucosa. Have you noticed that when you're examining patients? I have even had a patient whose saliva was so thick and ropey that when I. And this is a true story, not exaggerating. When I put my mirror in their mouth, the saliva was so thick it kind of clung to my mirror, and I twirled my mirror and the saliva stayed on like spaghetti. It was just so thick. And mukasey and so the viscosity of the salivary, the saliva can change in patients who are very dry. The tongue looks very dry. They have difficulty swallowing, especially dry foods. Always counsel your patients to have water with them when they are eating, especially if hypo salivation is a real issue for them. Our saliva protects us from trouble, right? And so caries incidence goes up. And also fungal opportunistic fungal infections. Right. Patients who are carriers for Candida. We talked about candidiasis. Patients who are carriers for Candida will have exacerbations in the context of hypo salivation. Because IGA are our own. Antibodies tend to protect us in our own flora, kind of help to protect us and keep those organisms from overgrowing. And they will take advantage of the situation in the setting of dry mouth. So again, you'll see that the. Remedies are kind of disagreeable. Quite frankly. We have to use over-the-counter salivary substitutes. I again recommend. I think they're pretty darn good. Certainly, you can also recommend sugar free chewing gum and patients who do not have TMJ. Contraindications. Because mechanical stimulation of chewing that stimulates salivary flow. Sour flavors are best, and certainly they can suck on sour flavor sugar free candies. That's also helpful. And then the last thing are silo dogs. These are systemic medications like pillow carping, that patients can be prescribed before they will take just before a meal, and it will force the salivary glands to produce saliva. They are very good and they are sometimes absolutely necessary. I just encourage you to prescribe them with caution. All medicines have side effects and side effects of silent dogs include a racing heart, sweating and peeing, and sometimes patients dislike those things. All right. So we do need to talk about one other inflammatory concept with regard to salivary gland tissue. And I just want to caution you against over diagnosing Sjogren's or over suspecting Sjogren's in your patients. The thing we just talked about, medication related hypo salivation or dehydration, because we don't drink enough water, that's really common. You're going to see that all the time. Not every patient in your practice is going to have shoguns just because they have dry mouth. Okay. It's good to keep it on your radar and certainly not unreasonable to consider it in a differential, but I just remind you that common things occur commonly. All right. Sjogren's syndrome is a chronic autoimmune condition where patients develop autoantibodies that attack glandular tissue, not only salivary gland tissue, but also lacrimal lacrimal glandular tissue. So easy for me to say. So patients will develop dry mouth and dry eyes. Now we're heading into winter and it's colder out and the air is dry. And you don't all have Sjogren's just because your mouth is dry right now and your eyes are dry, you know, it's very easy to kind of say, oh, do I have Sjogren's? And it's often associated with other autoimmune diseases, especially lupus and rheumatoid arthritis. So if a patient has RA and they're complaining of hypo salivation and ocular dryness, and their tongue is stuck to the roof of their mouth in the morning and it's really bad, then I would say consultation with their physician to look for some autoantibodies for Sjogren's would be really important. The etiologies enigmatic. We don't know what causes Sjogren's, but it is more commonly seen in middle aged women and managed by rheumatologists. And then all those salivary substitute things because they that there really isn't a great treatment. Right. So in addition to dry mouth, patients can get enlargement of the glandular tissue kind of a swelling or enlargement of the usually the prodded we do the blood tests that we do. We look for rheumatoid factor and we look for SSR, which is an autoantibody for Sjogren's and anti SSB. And if those are very elevated as well as ana antinuclear antibodies, then that may support the interpretation of Sjogren's. Sometimes biopsies of the lower lip salivary gland tissue are done. And we look for clusters of lymphocytes in otherwise normal glandular tissue. And that sort of supports our thinking. The reason we need to get this right is that this patients who really do have Sjogren's syndrome do have an increased risk of malignancy, particularly lymphoma. And you'll see that's 40 times over those of us who do not have Sjogren's. So it's an important diagnosis because it can bring to their attention more frequent screenings and things of that nature for lymphoma, proliferative disease. But as far as treating it, it's just supportive. So here's a patient with bilateral parotid swelling. And she has been diagnosed with Sjogren's syndrome. So you can see this kind of chronic enlargement painless enlargement of the salivary glands. There is one more kind of uncommon thing you should know about. It's a non inflammatory disorder not caused by inflammation. But you still develop chronic enlargement of the salivary gland tissue. It's mostly the carotid gland. And it's more commonly seen in patients who have diabetes, in patients who are malnourished and patients who are have alcohol use disorder. And in bulimia microscopically we see. Enlargement of of the asana units in the gland. So they they take on this kind of enlarged appearance or the glandular tissue is infiltrated by adipocytes, fat cells. And so it just causes this kind of diffuse enlargement. The etiology is uncertain. If you treat the underlying disorder, then the enlargement tends to improve. But for some patients, certainly that is not the case. You're left with kind of an enlargement. Now we're kind of heading gently towards salivary gland issues that can be a little more significant. And there is one entity that you need to know about that is very interesting. All right. This is a condition in which your patient will say, the roof of my mouth was tender and it got very swollen. And then a big chunk of my palate fell out. That sounds pretty dramatic, right? That would get my attention. But interestingly it is it is a condition called necrotizing plasma, and it is likely the result of ischemia and ischemia event vasoconstriction or vaso disruptive situation in which some salivary gland globules become necrotic. And then your body, once your salivary gland tissue is no longer viable, recognizes it as foreign and it exfoliates. All right. So the clinical scenario is like this. It's usually involving the palate. Palatal salivary glands usually seen in middle aged adults. Patients will get this painful swelling that rapidly ulcer rates. You must biopsy it because we're getting ready to talk about tumors. And an ulcerative lesion on the palate should put you in a differential for salivary gland tumors. So you must biopsy it. But under the microscope all we see are normal salivary gland shapes. But they're ghost images of themselves because they're all necrotic. And the ducts that bring this spit into the oral cavity instead of being cute. Little cuboid cells are squamous. They look a lot like surface. And it's meta plasma. When glandular tissue goes from being very sophisticated, very specialized and refined to a hardier type, we call that meta plasma. And so that's where the name comes from. Once you make the diagnosis, it will heal on its own. So here is a patient presenting with a very dramatic lesion on the left kind of initial presentation. And then you're watching a biopsy was performed to confirm the diagnosis. And you're kind of watching the progression to resolution. It went from being quite large to slowly getting better. So what did the what does it look like under the microscope when you biopsy it? I've zoomed in here. These are the sorry I keep forgetting I have this these are the residual Asner units. But instead of being cells with nice nuclei it's just a ghost of itself. The the assignee, the cells at the very back end of that structure, that cartoon that we we showed at the beginning, they're very delicate. It does not take much for them to get upset and just die. The ducks, interestingly, are a little hardier and they are harder to kill off. All right. So we see the salivary gland maintaining globule shapes of salivary gland globules. It's just that the cells have died. And so you just see little ghost images of where the cells used to be. That's called necrosis. All right. So necrotizing Siloam and apologia keep that on your radar. It would present acutely so patients were fine two weeks ago. And then all of a sudden this came on. So that makes a tumor less likely. Salivary gland tumors don't just pop up over the course of a few to several days. Patients will say there's pain swelling almost always on the palate. It can even be bilateral. I've seen a bilateral example on the palate. Very weird. But we think either trauma or maybe ischemia leads to suboptimal perfusion. And so those very delicate elements die and then you reject it. All right. And then once the biopsy is performed the diagnosis is confirmed. Then you just follow the patient to healing. All right. All right, so this is the end of my presentation. I told you, we're going to talk through it. All right. Just because we don't have two too much to go. But we are going to now learn. Five, I think five salivary gland tumors. And you are responsible for these because they are the most common benign. There are two and the most common malignant three salivary gland tumors. There are a ton load of salivary gland tumors and they can be very tricky. I will tell you that I even rely on an expert in salivary gland pathology. And in Texas, sometimes he and I will. I will send him a case every now and then if it's really tricky. So salivary gland tumors can be very challenging. But I do think it's appropriate for you in there are many way beyond the scope of this course, many salivary gland tumors. I'm just asking you to learn the two most common benign ones and three or some of the most common malignant ones, so that that way you generally know the most common salivary gland tumors you're going to run into. And yes, you will probably encounter some that are not on this list, but they will be few and far between. All right. So salivary gland tumors are uncommon, but they're not rare. It is very possible that you will encounter a salivary gland tumor in your practice lifetime. The list is long for both benign and malignant salivary gland tumors, and both major glands and minor glands can develop neoplasms. The very most common benign salivary gland tumor is a tumor called the playa morphic adenoma. All right. So you're responsible for that one. I actually saw one today. Oh I could take a picture of that for you. I saw that today in my practice. It presented as a swelling in the right maxillary vestibule. And the clinician said it was firm and mobile and it was a morphic adenoma, a very beautiful tumor. The most common malignant salivary gland tumor is a tumor called micro epidermal carcinoma. All right. So you now have learned the most common benign the most common malignant. We'll talk about this benign salivary gland tumor. It's a little odd. It's called the Wharton's tumor. And you see that only in the periodic glands it doesn't occur anywhere else. And then we'll talk about two other malignant salivary gland tumors. There is a typo here I need to draw your attention to I think I changed it moving forward I missed this one. Adenoid cystic carcinoma. And then the other one is called now polymorphous adenocarcinoma. We don't say low grade. It's really hard for me to change. I learned it as a as a student. Polymorphous low grade adenocarcinoma, low grade is now taken away from us. We just call it polymorphous adenocarcinoma pack. So I want you to learn it as a pack. Polymorphous adenocarcinoma not low grade. Low grade is something you you get to decide after you've looked at it under the microscope, whether it's a low or high grade lesion. Most of these tumors are still low grade tumors, but there are some that misbehave. So we have to they're all malignant, but some are better actors than others. So microscopically they're made up of their constituent parts. So salivary gland tumors. That little cartoon we started with today constituent cells misbehave just like in in a Donna genic tumors. Right. And then those salivary those atypical cells differentiate towards that cell type. And so salivary gland tumors are made up of cells that come from either the ductal elements, my epithelial cells, those ones that squeeze that can be part of it as inner cells can become neoplastic. So it's anywhere in between. How we decide whether it's benign or malignant cancer or not is. Has to do with the way the cells look. Certainly, if we see a lot of mitosis and ATP and play a morphism, that's worrisome necrosis, things of that nature. But it's also what it's doing to the surrounding tissue, how it's treating the neighbor cells. All right. And so how it's behaving actually plays a big role in salivary gland pathology. Even more so than sometimes the cells can look a little bland but still be up to no good. So all right. So let's let's stay focused. Just a few more minutes. We'll get through these few tumors. And you're going to just love them I know you will. So the first one is the plea morphic adenoma the most common benign salivary gland tumor. No it love it. It can happen anywhere. You can have it in minor or major glands. It is a neoplasm that is composed of ductal elements in the salivary glands, the things that form the little excretory ducts, and those myo epithelial cells that help squeeze the spit. All right. So these cell types come together to produce a very interesting tumor. And you notice the name says polymorphic clea morphic. Rather clea morphic means it can look like a lot of different things. Sorry. So it has a little bit not no two tumors look exactly the same, which is nice. They're very individual. But don't worry, you will recognize them by key features I'm going to teach you today. You must see them to make the diagnosis. The pallet is a great spot. It will present kind of nondescript. Like many things. It's not a surface problem, right? It's a down in the underlying connective tissue. So it will present as a swelling. Anyone can get a morphic adenoma after early childhood. And you treat this with surgical excision sometimes. The one I saw today had a nice capsule around it. Now because this is a benign tumor, it can get very large. There's an archival image I have of this gentleman with enormous tumor, and it had gotten so large he was like shaving it because it's benign, right? You can live with it sometimes for a bit. So this patient is showing you the tumor on the palate. And then I think we can see with the arrow there you can see the tail of the parotid. This is another example of a plea of morphic adenoma here. This this enlargement there. All right. So just a nondescript swelling. Certainly. You'll biopsy that, right. Now, here are the features. All right. It is usually well circumscribed. It's benign. So it it usually will have this fibrous capsule. There is a caveat to that. I have to be honest. When it's on the palate it's squished. It doesn't have anywhere it can go. And so it can sometimes look a little like it's insinuating. And that is just because it has nowhere to go on the palate. Right? But in places where it can do what it wants, it will often have this little wall of fibrous tissue around and it will shell out fairly easily. It is made up of ducts and myo epithelial cells, and you need to see both to make the diagnosis. So at low power, I see all these little holes here that are filled with this pink goop. All right. Those are ducts. All right. And then if you notice you see some areas where it's kind of hot pink in the background. That's interesting. Right. The stroma the soup can do different things in some areas it can be Hellenized or very sclerotic and pink and other areas like down here, it can be kind of snotty and kind of loosey goosey with lots of ground substance. It can even have a little bit of a cartilaginous look like cartilage. So we say that the stroma can be variably high, lionized. Where it's hot pink, it can be mixed like this. But always you want to look for these structures here. Ducts. Now, normally a salivary gland duct has a row of luminal cells that goes around it. That's one row of cuboid cells. What's interesting, this one also has this extra layer. You see that we say that is a duct that has been cuffed by myo epithelial cells, ducts with cuffing classic feature for amorphous adenoma. So you're going to be looking for these donut holes with two layers of nuclei around them. So I've said that's a feature. Now let's go over here I'm sorry to I know how I know I have that pointer, but I feel like I really need to get in here. So you see here duct and another row of nuclei around it. Those are the myo epithelial cells ducts with cuffing. And then look for the soup the stroma to be there B hot pink and Hellenized kind of sclerotic fibrous. And or it can have both in one tumor like this one does these kind of loose, snotty, sweaty areas. Often in that soup you'll just see some cells peeling off, hanging out here in the stroma. These are these myo epithelial cells, the ones that squeeze. They just kind of float off in the in the soup. All right. Plea and morphic adenoma, the most common benign salivary gland tumor. All right. This one's very pretty. And it's easy. You won't have any problem with this one, because it only occurs in the product land and has a very distinct look under the microscope. But I wanted to mention it to you because it's such a weird tumor. It's the second most common benign tumor. All right. Occurs almost exclusively in the product and almost always in smokers okay. Can be bilateral. Look at the smoking association eight times over non smokers. And it's made up of the ductal cells the excretory ducts. And then you get all these lymphocytes to help tumor associated lymphoid proliferation. To help that that find their way into the the surrounding tissue. And so it's very pretty very pink and blue. So here's a gentleman with the carotid swelling. None of us will miss the lesion. Right. We see it. And then you get this kind of tortuous cyst like tumor. It's a tumor. But it makes these kind of cyst like spaces line by epithelial cells. Now if you go to the zoomed in version I'll use my pointer this time. We've let's say picked this little area right here and zoomed in on it. You see these hot pink cells at the edge. Those are the oncolytic sort of lining cells. And then in the wall you just have all these small round blue cells. Those are the lymphocytic cells that are a part of it. So it tends to have this tortuous kind of cystic structure lined by cells that are hot pink. Those are the acidic sort of duct like structures, a duct like cells rather. And then you have all these lymphocytes in the wall. And that's characteristic must see in order to make the diagnosis of a dense tumor. All right. So those are your two benign. Now you just have three malignant and we're out of here. All right. No problem. All right. The most common malignant salivary gland tumor is micro epidermal carcinoma. MC MC epidermal carcinoma can happen in any age range. We see it in children. And interestingly, we see it in the jawbones too in our mandible. Great spot for mucosa. They either because of residual vestigial salivary gland tissue that's entrapped in our mandible during embryogenesis. There's a lot of hand-waving about how it occurs, but it does occur. And this is the most common central salivary gland tumor, by the way as a central mucosa. I mentioned over the wide age range products most common site. But you can see it anywhere. You can have it in minor glands two including the palate. Great spot for salivary gland tumors in general, but it can happen anywhere, anywhere where you have salivary gland tissue. You can have a salivary gland tumor. And I already mentioned that part. The that you can see this one in the jawbone. So kind of interesting. Right. So here we are on the upper lip. Now I told you a little bit ago mucous seals almost always occur where on the lower lip. So you should not have mucus seal honestly in your differential. We did a big just like in house little quick and dirty study just to see we could not find maybe one example of a mucosal in the upper lip. It is very rare. So reactive benign inflammatory lesions lower lip upper lip gets a side eye. For me I worry about the upper lip. It could be a salivary duct cyst with the stone. I told you those those can be up there. That's fine and it can be trouble. So just keep that in mind. Little something to carry around with you as you do your clinical exams on patients. Upper lip. Think about it might not be a good thing, but don't think about mucosal here. We just don't see them there. So it is bluish kind of like a mucus seal. The problem interestingly is that mucus epidermal carcinoma, the low grade ones have lots of cystic spaces filled with mucin. And so that's why it can mimic a mucosal clinically okay. So in order to make the diagnosis of mucosal epidermal carcinoma, you need to see mucosa and epidermis. I know that may sound silly, but stick with me, all right? I'm not. You're all brilliant. I'm not watering it down for you. But I do think it sometimes when you're learning a lot, keeping it simple is is important. So you need to see mucus cells. This is a tumor of both epidermis cells. Cells that resemble epidermis or squamous cells and cells that produce mucin. It's that kind of thick secretion. You've got to see both cell types in order to really cinch the diagnosis. So we'll look at this one. You have the overlying surface epithelium here. And then the tumor is down here in the connective tissue. We see these nests or islands of cells that have this kind of epithelial appearance. They sort of remind me of the surface epidermis okay. And then there are all these frothy blue cells. Do you see all of them here. Can you see them in the back? Okay. I just want to make sure you can see them, because you've got to be able to see these cells to make these diagnoses. And I'm counting on that. You can see what I'm pointing to. And then often in mucus, it's not unusual to get these cyst like spaces filled with pools of mucin. And here we've zoomed in. These frothy cells are all mucus cells. And these cells here are either intermediate or epidermal cells. So you need to see both parts in order to make the diagnosis. Now epidermal carcinoma can be a little trickier than what I'm laying it out to be. They're sort of low grade ones that have this sort of cyst like spaces and lots of mucin and higher grade ones that can look a little nasty and can be a little trickier to diagnose. But for our purposes, I will be careful. If I want you to make a diagnosis of a carcinoma, I will use an example that is appropriate. All right. I'm not going to put some really hard one that you know, it should be straightforward. I want to make sure you can see the cell types. Why. Because this is an important tumor. Micro epidermal carcinoma is something you really might see in your clinical practice. And being able to dialog with your patients about its biologic behavior is helpful. Here's a gentleman presenting with a large lesion. It's caused facial asymmetry. And on imaging you can see that it's kind of got a cyst like quality to it. That's not unusual for a well a low grade mucosa to have lots of cystic spaces. And then look the biopsy is just what you expected right. You're already thinking about it. You've got these mucus cells here cyst like spaces with mucin. And then these cells here are those epidermal cells. They remind us of squamous epithelial cells. You have to see all of that in order to make the diagnosis. All right, let's do two more malignant ones, and then we're good. All right, this next one's kind of a bad actor. I'll be honest. Adenoid cystic carcinoma is not a good tumor. It's nasty. It's fairly common. It does have a propensity to involve minor salivary glands. And you can get an ad cystic anywhere. But minor salivary glands are not unusual. And often the palate. It's a slow growing mass, but it's typically associated with pain. And that is because this tumor has a tendency for what we call peripheral spread or perineal invasion. The tumor cells tend to track along nerve fibers, probably to get from one place to another. And so they do have a tendency to cause pain. So here we are zoomed in. This looks really close to me, but for some reason I see it better on that little TV. But you see this. We're on the palette and you just see the swelling on the palette. Now, we've learned salivary gland tumors are now in our differential, our collective differential for a palatal swelling for sure. And but as I mentioned it can occur in any salivary gland site. It's just very the palate is a great spot for it. So just nondescript palatal swelling. Could this be a mucosa. Absolutely. It's just it wasn't a biopsy now. A biopsy. Adenoid cystic carcinoma is often especially the form type, which is the type I would most likely expect you to know because it's a common pattern. We say it looks like Swiss cheese. Okay, you have these many tubular or ductal structures in adenoid cystic carcinoma and they form lots of donut holes. But there's so many. This is one of these form structures right here. Do you see this little nest here with all these little donut holes in there? That's what we mean when we say crib or form. It reminds us of kind of a Swiss cheese like appearance. Now, I was also taught that in adenoid cystic the tumor cells are very dark, angular and angry. Okay. So the tumor nuclei are very dark blue, has a very angular look if you zoom in on the cell specifically. So like down here, when you look at the individual cells they tend to be a little pointy triangular. And then the tumor islands tend to be pretty cleanly separated from the surrounding soup. So I got so excited here that the tumors islands tend to cling to each other and not peel off quite to the extent they do in poorly morphic adenoma. That benign tumor we learned I was taught like, okay, so like if you were to roll out cookie dough and you cut the cookie dough with cookie cutter, the tumor island, stay away from the stroma will make the dough the stroma. And the thing you cut out are the tumor islands. It's clean there. There isn't a lot of spillover of loose cells in the stroma. There might be a few. Sure. You know, maybe some of these guys here, but generally speaking, it's a pretty clean, crisp. Tumor cells, they form these nests that stick together with lots of donut holes, dark, angry looking, angular nuclei. All right. Adenoid cystic carcinoma pain is not unusual because of the perennial spread. Oh, and one last thing. I heard someone point out to me this blue goo. Sometimes within these little donut holes, these little duct like spaces and ductile structures, you see this kind of amorphous blue stuff, blue goo, we call it. We actually call it blue goo. That is not unusual in adenoid cystic carcinoma. So for what it's worth, I mentioned that to you. Last one. The new name pack polymorphous adenocarcinoma pack pack. I apologize if I accidentally say plaga or something like that. I am trying very hard to break that habit. It's just a reflex. This is a minor salivary gland tumor. I just actually saw one again just a couple of weeks ago. So they really are out there. They really do show up anywhere. That one was from the upper lip so you can see them anywhere. They are often on the palate slow growing mass. Any of these malignant tumors, even benign tumors, if left to sit a bit, can ulcer rate. So it's not unusual to have a lesion ulcer rate. But here again we're just looking at a couple different ulcerative swellings of the palate. Nonspecific okay. But at biopsy that's where the answer lies. Now polymorphous adenocarcinoma has a very deceptively bland nuclear appearance. The tumor cells every tumor nucleus looks just like its neighbor. They have these oval nuclei with just this very pale, finely dispersed chromatin. They tend to form streaming chords. We say single file. So you can see the tumor cords tend to kind of stream. This one also can do the quiver forming unfortunately. But this is a much messier tumor than adenoid cystic. You won't confuse it because look at the mess it makes. It just tends to be streaming these cords where we said adenoid cystic is like cookie cutter, very clean. It respects the stroma. This one also can do Perry neural invasion. And I wanted you to see what that looks like under the microscope in the middle is a nerve. And all around it is tumor. So this tumor also has a tendency for a very neural invasion. All right. So I would encourage you to, to use your textbook after this discussion today to read on those five salivary gland tumors. You learned, because there are great textbook examples. And