 Another session of oral medicine and radiology series, today we will be dealing with leukoplakia. Leukoplakia is derived from two different words, leuko which means white and plaqueia which means patch. So simply put together it means a white patch. Leukoplakia was earlier considered to be an oral remalignant lesion but now it comes under oral potentially malignant disorders. So when we look into the history part, we see that it was earlier called as smoker's patch. So this clearly points out to the role of tobacco or smoking as one of the causes for leukoplakia. So this term leukoplakia that we still continue to use today was coined by Swarmer in 1877. Coming to the definition, I've added two definitions, one by WHO in 1984 which is pretty self-explanatory and this is the more recent one. Coming to the definition, it goes like this, a white patch or plaque that cannot be characterized clinically or pathologically as any other disease in which it's not associated with any physical or chemical agent except the use of tobacco. So it clearly points out towards tobacco being the causative agent for leukoplakia. And this is the more recent one. It goes like this, a predominantly white lesion of the oral myocosa that cannot be characterized as any other definable lesion, some oral leukoplakia will transform into cancer. Coming to the etiology. So etiology can broadly divide into local, systemic and videopathic. Coming to the local factors, it includes tobacco, alcohol, chronic irritation, UV rays, chemicals like sanguinaria, electrogalvanic reactions, candidiasis, viruses like maybe HPV, serostomia. And then under systemic, we have syphilis, nutrition deficiencies like vitamin B12, polygaphyde, vitamin AN, endorphins, endorphins. And then you have hormones or hormonal variations in the energy, especially that involved with P53 gene, the mutation of P53 gene. So now let's delve into the details. Coming to tobacco, both the smokeless form of tobacco as well as the form of tobacco which can be smoked, both of them are attributed towards leukoplakia formation. However, smoking forms of tobacco are more prone to produce tobacco, especially when you have forms like BD, where you don't have filter when compared to cigarette. Here you have more of a generalized appearance of leukoplakia, whereas in smokeless forms of tobacco, you have a more localized form of leukoplakia or a particular lesion because here you actually place it in the vestibular or a particular area where here, whereas in smoking forms you actually hold the smoke in your mouth for some time. So it is more generalized and here just localized. Coming to alcohol, though alcohol doesn't directly produce leukoplakia, it has a synergistic effect. By that I mean that it works along with tobacco and potentiates the role of tobacco. It actually increases the chances for leukoplakia formation when tobacco is used yellow. When compared to when tobacco is used yellow. So when you are using alcohol, it actually dehydrates the mucosa and makes it more permeable and porous so that the same toxins that we see here can be absorbed by the oral mucosa more easily. And another factor which has been considered to promote this plastic feature, promote malignant transformation is that in long time alcoholism, your liver is damaged and hence the capacity of liver to detoxify or remove toxins from the body is again compromised and hence we have more tendency towards malignant. That has also been discussed. Coming to chronic irritation like ill-fitting dentures, sharp broken teeth, jacked ends or sharp edges of dentures or roots or pieces of teeth, all these can be, or even malocclusion can be positive factors. Candidia acids can be associated with leukoplakia. It is called as Candidia leukoplakia and this particular type of leukoplakia or this particular combination is more deadlier than leukoplakia alone. It has more malignant transformation rate than leukoplakia alone. It is because when there is leukoplakia, the mucosa becomes slightly more rough and it is not as smooth as normal mucosa. So there is colonization of Candidia. And then when nitrosamines are produced that actually prolongs the leukoplakia or increases the duration of leukoplakia and even increases the malignant tendency or the transformation rate of leukoplakia. Then there is electrogalbinism. So this particular thing was a thing of the past because earlier we used to have different metal crowns. So there was always possibility of electrogalbinism. But now since we use ceramic or siliconia, we don't have this problem. In ultraviolet radiation again some exposed areas like lower lip and vermilion water please burn more. Sanguinaria again this is also a little bit outdated. In traditional American medicine this particular perineal flowering plant sanguinaria was used for serious treatment. So that was associated with white blood formation in the whole cavity especially your vestibular area. So now that's just no more of importance. And viruses like HPV especially 16 and 18 subjects are also associated with leukoplakia. Coming to nutrition deficiencies like vitamin A, B complex and polycarcin and endocrine C. All these have also been attributed towards leukoplakia formation increased propensity of leukoplakia. Then we have hormonal variations especially in women. So you know women are for female sex is more prone for malignant transformation than male sex even though males are more prone to leukoplakia formation because they use or they smoke more than women or they are considered to smoke more than women. They are people who have more chance for getting leukoplakia however the female sex is associated with more malignant transformation. Then coming to genetic factors the P53 gene which is a tumor suppressor gene is you know because of mutations on P53 gene you have propensity towards leukoplakia formation or malignant transformation. Then there is an idiopathic form where you know the vet is not associated with leukoplakia formation. I myself had a patient where the patient was or had never used the vet but still he had leukoplakia. So he was very resistant towards normal treatment. Even this type of leukoplakia is more prone to malignant transformation than when compared to the forms we have more of a fetus tuberculosis. Coming to the classification of leukoplakia there are various classification of leukoplakia but basically all these classification involve mainly two forms that is homogeneous and non-homogeneous. Homogeneous type of leukoplakia means the lesion is more or less uniform and you know one part of the lesion appears almost similar or you know is almost uniform compared to the other part of the lesion. But in non-homogeneous types you see that you know one particular part of the lesion is not exactly like the other part. You may have a thicker aspect there or maybe a mix of red there. So that is the non-homogeneous part. And again non-homogeneous leukoplakia can be subdivided into various types. So here we have another classification based on etiology and clinical adherence. In etiology it is a leukoplakia. And tuberculosis is a leukoplakia. And clinical again homogeneous and non-homogeneous. And under non-homogeneous we have rosacea, nodular and varicose types. And this is a more recent one where again you have similar non-homogeneous and homogenous types. Here you have the erythrole leukoplakia type which comes again under non-homogeneous type where it is a mixture of both the leukoplakia as well as erythroplakia or white in this first week. Coming to the clinical features of leukoplakia, you see that males are more affected than females maybe because of habitat smoking or tobacco usage. And then age you can have right from the young age. Maybe you can come around 40. 40 is the age where you can see leukoplakia. Coming to the location you can see leukoplakia occur in the buckling mucosa, the commissary mucosa, allular mucosa, tongue, heart pallet and soft pallet, vertebrum, mouth and gendiva. All these point more towards smoked forms of tobacco and eras in sorry smoked forms of tobacco usage. Whereas in non-smoked forms, smokeless forms of tobacco you have more in the vegetable level. So buckling mucosa is the most commonly associated area. Whereas these both areas, floor of the mouth and lateral part of the tongue are danger areas also. Those areas are more prone to malignant transformation. So when you have leukoplakia or leukoplakia associated with the lateral part of the tongue or the floor of the mouth you need to be extra cautious, extra careful. Coming to the clinical appearance, we have a lot of clinical appearances. The classic appearance is called as crack mud appearance or ride mud appearance. That is usually seen in the buckling mucosa or the tongue. Whereas this particular pattern, ebbing tide type, for the ebbing tide pattern or appearance is usually seen in the floor of the mouth. There you have different grooves or furrows, usually associated with the receding tide. You know the markings you see on the sand when the tide recedes. So that is called as ebbing tide pattern and that is usually seen in the floor of the mouth. Coming to the various stages, this particular stage or pre-lucoplakia stage is when you have a thin white phylloenic kind of appearance, not exactly a homogenous appearance, a small thin appearance, a thin coating as you can tell. That is called as a pre-lucoplakic or a smooth-lucoplakic stage, pre-lucoplakic stage. This is the proper, you know, classic appearance, what you see. It is called as homogenous appearance or a fissured lucoplakia. So here you see the classic sign of lucoplakia, the classic sign of, also the classic appearance of homogenous lucoplakia, which is called as a cracked mud appearance. So this appearance is quite similar to that of dried mud. The cracks that you see on the fields after it completely dries. That is called as a cracked mud appearance. You can see that this particular area is very similar to this particular area and for that matter, this particular area. So it is called uniform too. So this is called as homogenous appearance. Here also you can see, this particular appearance is almost similar to that of here. So you can see that it is almost uniform. So that is why it is called as a homogenous appearance. So coming to the non-homogenous forms. We have nodular or vandal forms. So here you can see where it is, you know, pink finger-like projections or, you know, nodular appearances, lot of furrows, I think, bulbous appearances. But here you have a little more thinner sections. You can see that, you know, it is not very homogenous. It is not uniform. It has different appearances at different sections or different places. So that is why it is called as a non-homogenous lookable. This is another type of non-homogenous lookable. They are one of the dangerous types. Apart from vertical lookable, this type of lookable. This is called as PVEL or tolerative varicose lookable. So you have a lot of finger-like projections or tolerable or like projections. It is actually called as finger-like projections. Kind of 40 or something like that. Again here also you can see that it is not very homogenous. Here we have finger-like projections. This is called as a varicose lookable. This is very dangerous. This is more prone towards malignant transformation. And if you find a patient with this kind of appearance, you need to act fast. It is better to surgically treat this patient than stick on the medical limit to it. Okay. This is another very dangerous form of lookable. Here it is called a spectral lookable. Here it is called a ellipsoid lookable. So we have a white ellipsoid lookable. Okay. The mix of red and white is called as a spectral lookable. PVEL or tolerative varicose lookable and spectral lookable are the most dangerous forms of lookable. Both of these come under non-homogenous lookable. According to the staging of lookable. So you can stage lookable based on the size or the extent of lookable. You can figure the site or the areas involved. The clinical aspect of the clinical appearance and then the histopathological appearance. So based on the size, it can range from L1 to L3 or LX. L1 less than or equal to 2 cm, L2 2 to 4 cm, L3 greater than 4 cm. So the size is not specified. And then site S1 to S2. S1 all sites excluding the floor of the mouth and the tongue. And S2 is floor of the mouth and the tongue is also removed. So you can see that these are the dangerous areas. Not the whole of the tongue but the lateral movement of the tongue. So that is the dangerous area and then the floor of the mouth. And Sx is not specified. And then clinical aspect, homogeneous, non-homogeneous and Px is not specified. Coming to histopathology features, you have P12, P4 where P1 is, you have no dysplasia. P2 means mild. P3 means moderate dysplasia. P4 means severe dysplasia. And Px means it is not specified. So you can stage lookable as stage 1, 2, 3 and 4 based on various combinations of these subsets. Based on various combinations of the size, site, clinical appearance and the histopathological appearance. These are the histological features. I have included these because a little bit later we will be dealing with something which is called a chair set investigations where, you know, if you look at these, that might sound a little more easier for you to understand. So I have included all these things here. These are the histological features. A small glance at this. So you have hyper or ortho paracarotosis. Sorry, hyper, ortho or paracarotosis. Acandosis and ballooning of cells and dysplastic features that you need to be careful about are basal cell hydroplasia, loss of basal cell polarity, cellular pleomorphism, loss of stratification, enlarged or increased nuclear cytoplasmic ratio, increased mitotic activity of normal mitotic activity, hypochromatic nuclei, dyscarotosis, bulbous or tear drop shape epiphex or epithelial ridges, keratin or epithelial pearls, loss of typical epithelial cell cohesiveness or loss of attachment between cells. And in connective tissue, you have sub-epithelial lymphocytes in plasma cells, inflammatory cell infiltrates. All these are the dysplastic features we need to be careful about. Various degrees of dysplasia can range from mild, moderate, severe and carcinoma in CT. Coming to the differential diagnosis, you have a lot of topics. So it thinks entities under differential diagnosis. Leukodema is another normal variant. It is just the palestin hue of the orenuposa, which, you know, slightly resembles Leukoplegia. However, when stretching, you see that Leukodema is completely disappearing or it has vanished. So it has no, you know, relation to Leukoplegia. It is just a normal variant and it has no association with tubar. Plexigene keratosis, again, Plexigene keratosis can resemble Leukoplegia, but you always see that there is a sharp edge on a jagged border or any projecting part which is in contact with that area and that area will be a little bit localized. And there is just no association with that. Coming to smokeless tobacco lesions, you have tobacco quick lesions, tobacco pouch keratosis where again you have a localized lesion. And even sometimes the burns or the caustic, you know, burns of slaker line while using VBT for chewing. All those can also resemble your Leukoplegia at certain state. So that can also be different. Then you have lighting plants. This particular lesion is very different from that of Leukoplegia. Leukoplegia has a homogenous or non-homogenous effect. That is why we have a striallet here. So this happens is called victim striage on a tree slate. Here we have periods of interleaving, whites, vertebrates, wild striage. And again, this is again a immune mediatrist. Leukoplegia is again on tobacco enlist. So again, these three cases are going to be here. And we have Candidia. These forms of Candidia. Again, for Candidia is to occur, you either need to have a poor oral hygiene or your immune team needs to be compromised. Again, these forms of Candidia can be straight up. And they are not resemble. You don't have a history of tobacco in history. Again, history and coherence. And history will be lost here. White-point fever is again something that is related more to third degree. For third degree causes than tobacco. In white-point fever, you always have your parents or different parents having this particular lesion. And you have this at a very end. More generalized appearance and all that. Here is Leukoplegia. You can always associate it with smoking or use of tobacco. Here is Leukoplegia. Again, it usually appears on the lateral borders of the channel. But it is not a tobacco in this lesion. It is not Leukoplegia for that matter. Actually, a lesion is caused by steam-bar virus, which is just white. And it may be a little bit like Leukoplegia at certain stage. But it can easily be differentiated by history as well as the proper diagnosis. Again, Harry Leukoplegia with steam-bar virus lesions can also occur in patients who have poor immune system. Then, Vedicca vulgaris. Sorry, Vedicca vulgaris. It is more of a generalized lesion. You have more king lesions than oral lesions. And again, oral lesions are more red or watery kind of in appearance. Whereas in Leukoplegia, you have more homogenous or non-homogenous. You do not have this typical vorty at the end. Vorty at the end. You have more of whites and red. Coming to DLE, Oral Discord Leukoceratometrocyl. This is actually predominantly a king lesion than oral lesion. And it is immune-mediated rather than tobacco induced. And again, in DLE, you have red lesion for a red pore. It is surrounded by white. And then, try radiating from that. Whereas in Leukoplegia, you have a homogenous appearance or a crackment appearance. Or even for that matter, if you consider an erythro-leukoplegia, you have white and red in this first. You do not have this particular red pore with white striated appearance. You can distinguish that appearance. And again, maybe the history part. It is a diacrososacea and the enamel. And the skin relations. All those can be used to roll out DLE. Coming to the diagnosis, proper history and the proper clinical examination is very necessary. History involves asking the patient regarding his habits, especially those associated with the use of tobacco. Smokeless as well as those with smoke. So you need to ask that. And when he says that he has this particular habit, you need to ask about the type, the frequency, the duration, any other symptoms of signs, any other treatment. Whether he has a substance from that or still is using it. All those need to be done. And clinical examination, you need to examine all those areas. Not exactly, only the buccal methods. But you need to examine the root of the mouth, the lateral root of the tongue, and all those areas which might escape fast for a quick examination. Because those are the areas which are more prone to malignant transformation. So those areas need to be examined with great observation. Coming to chair side investigation. So earlier I happened to tell about this plastic pages. So these are the investigations which can be performed when you have a small suspicion regarding any malignant transformation. So this particular investigation can be done just prior to your biopsy. Many a time when the patient comes to you, he is almost afraid of the word biopsy. So just before doing a proper biopsy, you can actually test for any displastic changes. Usually you cannot identify dysplasia by naked eye. Usually no, you cannot identify dysplasia by naked eye. So you need to do a biopsy for proper cold standard analysis. However, this particular step can be used as a preceding step, just a step before proper biopsy. So if you find dysplasia here, then you can proceed to a biopsy. But if you do not find dysplasia in the particular relation side, then you may actually delay biopsy for some more time or you may observe the patient until he recovers or for any other change towards malignant for that matter, any displastic changes. So these are the various chair side investigations. One is vital staining. So you can use tolding blue or lukal siding. Tolding blue is again the most commonly used method and then you have lukal siding too. And tolding blue, actually the dysplastic area or the cells or the area of the lesion which undergoes dysplastic changes will retain the blue dye even when there is acetic acid decolourization done. So even when you ask the patient to, you know, when you do the decolourization using acetic acid, this particular area where dysplasia is set in that retains the blue colour dye. And this points out towards dysplasia. And then in lukal siding, you can use it separately or in combination tolding blue. So in lukal siding what we have is in dysplastic cells, it doesn't take up the stain. There is non-dysplastic areas, or the areas which are normal, they turn brown or brownish black. So that is because there are those kinds of tissues or those kinds of cells that glycogen. Whereas dysplastic cells don't have glycogen or glycogen is depleted in them. So that doesn't take up the stain. So this can be used for taking dysplasia. Then you have exfoliative cytology and oral blood pressure where you actually agitate or, you know, rub against the epithelial cells. So you rub against the epithelium or the bacterial mucosa for that matter. And if there is dysplasia, you have, you know, the thing that we discussed earlier, the loss of cohesiveness or the reduction in cohesiveness between cells. So what happens is when you agitate the cells, these cells get shed off. When they are taken as a smear and examine, you can see that there are various dysplastic cells. So this is also okay. Easy method. It is non-invasive and it is painless procedure. And, you know, patients are more willing to do these procedures than biopsies. Okay. So there are, again, advanced cancer investigations where there is micronucleus test and vasylate. Okay, micronucleus test is, you know, when you test the smear or maybe the gargle or whatever for that matter for micronucleus. So these are small fragments or particles of nucleus or nuclear fragments. It's actually mean that there are more number of dysplastic cells there or that epithelium is dysplastical. This is not only done for leucoblake. It can be done for OSM or for leicinclinus. All these patients, it can be done. And then we have chemoluminescent illumination, especially vizilite system. So here what you do is you ask the patient to use acetic acid or gargle with acetic acid and then you shine a particular light of a particular frequency. This particular light is called as a vizilite. So the normal epithelium, it takes up this light or it absorbs the light whereas the dysplastic epithelium takes up a lot of nucleus. Because there are a lot of cells there, there are a lot more nucleus and there is more reflection of light. So you have a particular appearance which is called as an acetyl white appearance. So that you see here. And then all these other side investigations yield or point towards dysplasia, you need to take a proper biopsy so that you can confirm. Because all these things just point out towards dysplasia. It doesn't give a confirmatory diagnosis. The confirmation is always done by oral pathological investigation. Biopsy. So biopsy is the gold standard here. Coming to the management of leukoplecia, first and foremost is patient education and motivation. You need to educate the patient on the ill effects of smoking and motivate the patient to fit the habit. Or else even whatever medication or treatment you do will be of no use. Then you need to identify and remove any pre-discussing factors. Maybe if there are sharp edges or jagged borders, you need to correct those. Any teeth which are not in proper occlusion which are causing trouble, that also should be corrected. And maybe if there is any candida, that will be the next point. Okay, antifungal agents like clotrimazole may be used to reduce candida infection. So that is like two weeks of antifungal agents or topical clotrimazole can actually reduce the lesion size. So you might wonder why tobacco-induced lesion will be treated by antifungal agents like clotrimazole. It's not very surprising. Totally before about a condition called a candida leukoplacic. So that is proper candida leukoplacic. But even a normal leukoplacic lesion is also rough in surface. Okay, so you can have colonization of candida over there. When there is candida, that is always nitrosamine production. And even if you treat, the treatment is not going to act properly when there is the presence of candida over there. So the first and foremost thing would be to treat that candida first. So when you actually treat that candida or remove that candida, we can see the leukoplacic actually responds faster to medication. And for that matter even without using the normal medication just with the antifungal agents also it can reduce itself. That is also seen in many cases. You need to treat with antifungal agents for almost 2 weeks. Now coming to periodic observation, that has to be done. So you need to first see for any dysplastic changes and observe the patient for at least 6 months. And then yearly once. Every month for 6 months nearly once you need to hold a patient. And then when you see that it has reduced, you can actually stop observing the patient. So you need to observe for any increase in the size of the lesion or change in the appearance of the lesion. This indicates that there is a small tendency towards malignant transformation or evolution of lesion towards malignant. So you need to do a historical examination. You might attempt a clinical research investigation before that if you need. But otherwise you can just do a historical examination. So if you observe dysplastic changes go forth especially when you have pVL and alkylucopia. So dysplastic changes if you see, you need to aggressively treat it. The medical line of treatment involves antioxidants like vitamin A and systemic and topical also. And this vitamin A therapy involves both natural as well as synthetic radians also. It's called vitamin E. Combination of antioxidants, vitamin A and B. Lycopene has been giving very promising results. Green tea all these things. Vitamin A is very useful because it helps in proper characterization of the epithelium. However, this should be used with a little bit caution because in non-homogeneous conditions especially where you have spectrolocoplate, if you give this vitamin A it can actually give more trouble. It's a kind of a double-edged sort. It can change this particular condition towards malignant condition. That can also be seen. So you need to weigh the outcome. You need to judge the case properly go for only homogeneous cases. If you see non-homogeneous cases don't go for vitamin A. You need to weigh the outcome. And then there are other anti-cancer chemotherapy things like gliomycin, interferon, FIFU, cisplatin, etc. And when you have human papillomavirus association you can go for antiviral also. In surgery you can use scalpel, cryosurgery, electrocutory, laser ablation. And you have this particular modality for photodynamic therapy where you inject a particular dye into the body into the bloodstream and it gets concentrated at the site of the lesion and you actually assign a particular light, a particular frequency on the lesion and this dye disintegrates into certain by-products and that by-products treat or help in reducing the leukoplagia. This method has also been tried and a lot of promising results have been received from various researchers. Coming to the pre-malignant nature and malignant potential, almost 4 to 6 percent of leukoplagia undergo malignant transformation and most of this is non-homogeneous state. It's almost all non-homogeneous states. So malignant transformation it depends on the phase or clinical appearance of leukoplagia. As I told you, pre-lucoplagia or the earlier homogenous stages don't point towards malignant transformation whereas the non-homogeneous types are more prone to malignant transformation. Degree of dysplasia again more than mild. You have severe dysplasia going into malignancy faster. In sight the lateral border of the tongue as well as the flow of the mouth are more prone for malignant transformation and compared to other areas. Six, as I told you, female six due to probably due to the hormonal influence causes more tendency towards transformation malignant transformation than males. Duration again this has been a big controversial. Short duration leukoplagia has also been transformed into malignancy even a long standing one you know after observation for a long long time can suddenly change. So this again is a controversial thing. Habit again depends on what particular type of form of tobacco you are using as I told you beauty can cause more you know malignancy than smoke less form or cigarette for that matter. Then as I told you before you know Habit associated or tobacco associated leukoplagia is less prone than non-tobacco associated leukoplagia towards malignancy. This is because you know in tobacco associated malignancy we actually know the etiology and the reason we can actually stop the habit and then decrease the malignant potential whereas in non-tobacco associated leukoplagia you don't actually know what is the real cause of the etiology for leukoplagia formation. So we don't have any stop or control over that. So there is more chance for that to undergo malignant transformation and respond to giving less response to our treatment and then size size also when a small relation can undergo malignant transformation or a large relation but however a large relation can have homogenous as well as areas. So there are more tendency for large relations to undergo malignant transformation than small relations. Clinical features of malignant transformation you need to be you know careful about. So this is what you need to look for when the patient comes to you for recall visits. So development of erythematous or indurated areas. Erythematous means reddish areas and indurated means hardened area thickened area. This is called induration. So you need to both visualize as well as help it. Alceration with induration areas of speckling mix of red and white. Nodular areas in relation. So more than a homogenous or smooth or thin area if you have nodules or bulbous areas that is more come to this plastic. Roll Borders. This is again very dangerous sign. Roll Borders. Enlargement of change in the pre-existing lesion. So you might observe the lesion being or appearing the same for maybe or five or six months. But suddenly next or the next month you can see this certain enlargement. So that time you need to be very careful. It might be a small sign which points towards malignant transformation. So these are the points you need to be very careful and you need to know to prevent malignant transformation. So this is the stage when we need to look out for a biopsy and then surgical treatment. Okay. So with that I will wrap up this session on leukoplakia. Thank you so much for your patient hearing. Stay safe, stay enlightened.