Thank you john it's indeed the pleasure and privileged to be here with you all this morning. The quality of the speakers is reflected in the size of our audience. Our first speaker dr Jack Frost. Yes. One of our international leaders in diagnostic cycle pathology and a real soldier in the field. It was just yesterday at five p.m. in Baltimore that he concluded his outstanding tutorial and without even getting supper, he took the plane to Houston Dr Mile. Um And I thank you as well as the people here, Jack. This is the bicentennial year. This is the year of psychopathology. We just, some of us just came back from boston boston. The International Academy of Pathology met there this year. I enjoyed my visit there and taking a little time to see some of our bicentennial sites. I was reminded of our upcoming meeting here this morning. Now we have excellent speakers on our program. We have four outstanding men and one woman. As the first slide there shows you. Yeah, I don't know if Eileen is in the audience but yet, but we've got an outstanding retina here and going back to boston there while I was there. I went to bunker hill. I've never been before to bunker hill and I climbed the monument. There's no Elevator, there's 200 and 90 steps to the top and they had a little panda mom there and the next slide shows you the scene at Bunker hill. And I don't know if we condemn this like sir, but I don't think they can see the slide to with the with the line. But it said with the Jack Frost up there, he said don't find until you can see their nuclear cytoplasmic ratio. Yeah. And then I went to the town hall there and I saw him again in the next slide and he said, I know not what course others may take. But as for me, give me psycho pathology or give me death. And uh with that little brief introduction I'd like to ask dr Frost please come up thank you. Don for introducing the year of the path. Mhm. Okay. Mhm. I believe me, it's a real pleasure to be with you while I boarded the plane without any dinner, I can assure you I had steak aboard so I'm not looking at me. You can see I have no problem keeping the calories. As a matter of fact. One of the registers of course was a reverend reverend, MD. And and one of the registrants took great kick out of saying whenever he passed around some candy or something, he would tell. The other agent said I've had reverend, bless the out of this. And he says, of course that's the same as calories. May I have the first slide please? As a matter of fact, the first two slides and maybe you'd better turn these off. Yes, thank you of the female genital tract Is of course something that one can't even begin to touch in 45 minutes. I'm not going to presume to. And actually your program committee and its wisdom gave me two things to touch the cervix and the endometrium and they said you can touch on anything else you wish also. So I took the liberty of that. Um, I I thought it was important that we looked at some of the, the key highlights that present themselves to us today. Not entirely new things, but the ones that have something new attached to them or things that we don't run into quite so often. Of course, one of the newest in the last five years or so, is that which is represented by by what you will have as your first, as your first kodachrome here on the left from me. Anyway, your first one for me, This is from a 20 year old female nursing student, Hop Hopkins. She had a slight vaginal discharge. She had reddening and roughness of the upper vaginal wall and this is a vaginal wall scraping. It's a Papanikolaou stain. Now this this is a very frightening thing to have to. A note that we have added no carcinoma and we have it and a young girl, obvious with the, with the hormonal patterns out of a young girl. Ah When we look at the criteria, of course there's no problem telling that this is cancer. And particularly when we go a little higher and look at the details of the nuclei, there's there's no problem telling this is cancer. It's an adenocarcinoma. The cytoplasm is foamy. A number of these vacuums have very large pouched out. Secretary features not the very thin walled features of ovarian carcinoma. Such as I think that was I don you had up there blowing bubble gum. His so called bubble gum vacuums of ovarian cancer are lacking here, but there is a tendency for the cells to be in a loop. The loop or probably better call hob nail fashion. And because of this, the lesions at the beginning were called by some measures in africa adenocarcinoma of the vaginal wall. Uhh. Other areas of this are are more cytoplasmic. They have larger amounts of cytoplasm and the pattern in those areas are more abundant cytoplasm, the so called clear cell adenocarcinoma, which is the name by which it goes now in most in most usage, these occur in a young woman About 18-21 or so around there whose mothers took di ethyl still best for all During the first trimester of pregnancy with the patient as a two or 3 month old fetus. These patients are not very frequent, that of all the the mothers who took the athletes to best are all very, very few of them end up with a malignancy, a somewhat higher proportion. End up with with vaginal a gnosis. How the usual uhh tumor of the vagina is, of course, epidermal carcinoma, highly characterized, usually, That occurs in the older patient, 40 plus 50, 60. The adenocarcinoma we're speaking of now is is relatively rare, not rare, but relatively rare in the older patient at it occurs in Barcelona's glands, peri urethral glands and such as that but occurring in the vaginal wall uh is relatively rare in the older patient, but is that which is occurring now in these young patients? These are in the vaginal wall up near the the portion of the wall near the servings. Now a larger number of them whose mothers took to ethel's to best Raul don't have adenocarcinoma but have a diagnosis. Abner sis has been known for many, many years, but it was a rarity because the vaginal epithelium does not have mucous glands and to find mucous glands in the vaginal epithelium was an abnormality and was called vaginal a gnosis. Actually, the the appearance of the vaginal wall with the fairly extensive a diagnosis that some of these young women have tend to be fairly typical when it's relatively extensive. Now this is light spots, these brilliant areas, or light spots in the areas which are significant are these pale white areas. And the more normal areas are the reddened areas. But the pale white areas of the areas that are significant. It's under the epithelium. In these areas that one has the ab no sis. The putting on of this of iodine. So called schiller's iodine nicely outlines the areas that normally the darker areas that have normal glycogen, and then the lighter areas that are are less normal in that the overlying epithelium of this of this lesion. This is the overlying epithelium and this is the lesion of the diagnosis that the overlying epithelium does not have the amount of glycogen that the normal epithelium has, and therefore we see areas which are devoid of the of the eid and staining. We therefore are not staining the abdiasis were actually not staining the overlying epithelium. Now, it's important from the point of view of psychology that the the lesion, the ad Nanosys, they usually lies underneath the surface, and the very small neck of the gland sometimes comes to the surface, but very frequently will not cover the surface. In order to obtain the the psychologic evidence that we do have a diagnosis. One has to a fairly briskly uh scrape the vaginal wall in that area. So this is actually to make the diagnosis a localized vaginal vaginal wall scraping, not just a non descript lateral vaginal wall, such as we do to obtain a good side of hormonal pattern, which is about this area, the vaginal wall. Uh This is not for the side of hormonal pattern. This is in an area where there is a lesion and the lesions usually run up around near the cervix. I want to make a couple of points at this point, because the our types of cells we get from the A diagnosis, not the adenocarcinoma, but from the A diagnosis looked just like very reactive, very pro plastic endo cervical cell degenerating, regenerating and those cervical cells. And so if we were to take a cervical scraping, we'd expect sell something like that in the presence of service itis there's somewhat active and sometimes fairly active. It is very important therefore, that we know from the clinician that he took this as a as a local um local specimen from a lesion on the vaginal wall. Or we don't have to know it's a lesion but he took it as a vaginal wall specimen. Now another thing that may be a tip off, if the if the clinician doesn't tell us where he took it, we don't have the vaginal component with this. We don't have the mucus stream that that almost always accompanies the vaginal component. These are not coming the cervical, I'm sorry, we don't have the cervical component with this. We don't have the cervical component. The cervical mucus isn't there? And if these were cervical cells and the cervical cells that were very reactive, we would expect to find a lot of Polly's and a lot of inflammatory to bring in the background and we don't. So these occur not in the cervical component but they occur in the nondescript vaginal component which tends to be more watery and of as you know from experience, you can tell the background from the cervical material as it sits in the vaginal pool from the material that comes from the vaginal wall as it sits in the vaginal pool. These cells tend to be associated with that type of a background of the vaginal wall. So number one, they're very reactive. # two, they are not in the cervical component. And number three, if we have a clinician who who understands the other importance of giving us good history, he will tell us this is a a vaginal wall scraping and so he won't think it's as usual, whatever he takes a combined faster a pan cervical or a pool or something else. Okay, I want to briefly go into the lesions on the cervix, which are of the epidermal I. Type and we begin with the Petipa's and work up to the invasive cancers rapidly because this is not a a session on the epidermal lesions on the cervix exclusively. And as you know, one could wax on this for days and yet not have the answers out. There are so many. But I want to point out that a few of the major features to me in assessing these lesions lie in the nuclei and lie in the cytoplasm. This sounds obvious, but I want to break them up into those two compartments in the nuclei. We run into what papa nickel out called disk keratosis and which so many people associate that if you see that you must have cancer and he never meant that it's associated with cancer. It, however, is associated with the early lesions of cancer with the early pre cancerous lesions and with the early early lesions which aren't even cancer at the present time but are very, very active. And we noticed even in them very minor, a tip is in the healing a tip. Use of the service. We'll find these types of changes that the nuclei become large. This is something that that occurs even by looking at the cell, crosswise cross eyed. The nuclei tend to become a little large cytomegalovirus occurs with the minimal uh part of, of irritation. The minimal uhh types of a chip to have seen Ahmed ali. Now, if we have an epithelium that in addition to being uh being somewhat atypical is a minor a tibia. And so the cells as they reach the surface or are are all able to become carry a pick. Not IQ. We then add to the huge nuclei, we add to it. We had the features of the area. Pick no sis namely darkness. In other words hyper from asia. But we also have blurry. Now this is the hyper chrome asia of a blurring degenerated nucleus, which is not a type of hypericum asia that is valuable to us. And so we must discount that as far as the severity of the lesion. And so we end up really with only one thing, we have large nuclei carrie omega lee and the other thing that we have in this lesion in the minor lesion is the ability of the cells to mature. Which we see in the sight of pleasant mature squamous type cells. Another thing we note in this particular minor lesion is that there's this very peculiar of perry nuclear clearing which leo costs referred to as coil oh psychosis. Which one season the cells which has no significance at all as far as cancer but is found much more frequently in the minor and in the moderate platypus than in any of the others. And these are features going along with a minor inflammatory tapia showing kylo psychosis. Now if if we move to the utopias that are more severe that we see that the more that the moderate Petipa's shed cells much the same as the previous ones. But they also shed cells whose nuclei a party whose cytoplasm is less mature and is not able to flatten out. Yeah. This is a flat screen of cytoplasm as is that one. But this is a less mature cytoplasm not flattening out. And this is not only not flattening out but it's not making much cytoplasm and we get more of what we refer to as a moderate it's a moderately mature disk idiotic cell with the moderate a tip is but we yet get some whose cytoplasm is able to mature. And and we're just picking up more of the less mature ones. Now when we have the very grave a tapia's we then get more of these unable to mature. We get more of these very very immature ones and we'll note the nuclear changes are now getting worse too. We're now getting hyper chrome asia. But this is hyper cremation, a well preserved nucleus which is not blurry. Which is not degenerative for this. Hyper chrome asia means something. This isn't the hyper chrome asia curio prognosis or cell degeneration and this means that we have increased activity and we're very worried about it. So we're getting to major changes in nuclei with the more severe lesions tend to be more severely disc erotic and the cytoplasm with the more severe lesions, a higher percentage of them are not able to mature. Now when we get insight to carcinoma, we can still have shed from insight to carcinoma. Many cells with moderately abundant cytoplasm. But we also have some and in certain side of in certain lesions, very few of them with a very scanty side of pleasant. Sometimes it's just just enough to make a diagnosis. Other times, practically every cell shed from inside a carcinoma has. This very scanty cytoplasm is completely unable to mature and is more typical of the classical, non characterizing insight. A carcinoma in service. Now I want to go to case for which I know you don't have but you will have And this is the section of tissue of a 38, year old army wife with who had a slight vaginal discharge. And the cervix had a ridden area At about 12:00 which bled very easily. A cervical smear in a biopsy was taken. This is the cervical smear. This is the biopsy and this is the cervical smear. That's your number three and # four. Mhm. Now this was seen by a board certified pathologist at an army hospital and he felt this was carcinoma inside too and sent her to a larger hospital to walter reed actually for a therapy. But the biopsy was sent through channels and at the area laboratory. The not only the biopsy was looked at but also the cervical smear was looked at and one can see that we do have carrier meagley large nuclei but it's pale and it's able to mature and we also have quite a bit of nuclear is tippy a here of perhaps this curiosity type and it's moderately hyper chromatic, but it's a little blurry and one doesn't know how much of that is due to degeneration or how much of that hyper from asIA is actually due to the increased activity of these cells. Uh all in all, it was not felt to represent a cancer either on cells or on tissue. It's a very severe borderline gravy tapia. And if one looked at the smear a little farther, one ran into this. Now this of course, is typical of herpes. Herpes, Simplex, genitals, type two herpes multi multiple nuclei packed in there like the seeds in the pomegranate or the stones in the gallbladder Moulay, not just lying there loose but molding around each other, yet having a fairly intact and compact cytoplasm. Not a lot of it, but it's intact and it tends to be very criminal. Filic, got a lot of protein. It's a very criminal Felix cytoplasm and the nuclei show a certain amount of degeneration. Well, first we see the multi new creation which is which is self stimulation and this happens first, that's the reason that we've had this. This is epithelial stimulation. There have been quite a few articles in the literature, a sighting lesions that have been called insight to carcinoma tissue and others citing lesions that have been called carcinoma in sight to on cells in the early days. The early stages of of herpes. Now the early stages are a proliferated stage and many times we'll see nuclei still retaining a a granular chromosome pattern of paps, disc neurosis. However, now they begin to degenerate in the second phase is out of a nondescript degeneration plus a very specific type of degeneration. And one looks around in herpes for nuclear inclusions. This is about the best that one had, but one doesn't need nuclear inclusion and herpes. If you have what I refer to as a gelatin, what I feel. The word gelatinous tends to describe it better than ground glass because it's not finally divided Granules. It's more of a uniform gelatinous appearance just like the nucleus was was pumped up with a syringe of jell O. And this very gelatinous appearances as diagnostic to me as is a nuclear inclusion. Well, this is herpes. This is this is a herpetic lesion which when one took the biopsy, what you recall was this biopsy and one was to cut the block down farther. one then got uhh ran into an ulcer which was not present on the original section of the block. and in the edge of that Ulcer one ran into cells like this which are right down here, the multi new created cells right on the edge of the ulcer. These not only the herpetic viral infection usually affects the cells of the screams epithelium, but it doesn't have to, it can also affect the endo cervical Colombia ourselves. Now this is another lesion and this is our classical non characterizing insight to carcinoma from the basement membrane. The cells remain the same basically all the way up to the surface. There's a little bit of serum on the surface, but there's no maturation on the surface. A very, very high nuclear cytoplasmic ratio is present, giving when we get the cells exfoliated a very high nuclear cytoplasmic ratio. Once again with the nuclei that Papanikolaou characterizes, disc periodic very hyper chromatic. The nuclear membranes wavy chrome button, coarsely granular perico martin somewhat cleared but uniformly distributed amongst the chromosome Granules and this extremely high nuclear cytoplasmic ratio. But the cytoplasm is intact and must be intact for our diagnosis. I now note that there are no nuclear ally, rarely under one of pure non characterizing insight. A carcinoma does one get nuclear line and the nuclear I tend to be perfectly round. They don't tend to elongate and the nuclear outline is that of of away venous of an undulation, not that of the nuclear regularity of of invasive cancer. And these cells don't functionally differentiate. The one thing that could possibly be said to be a functioning differentiation is a very harsh cytoplasm, the very crisp cytoplasmic border at times one gets in these cells, but not always When one does begin to get functional differentiation, one then worries about invasion. And here we get here we have a characterizing Granules in the cytoplasm and the lady in granule or granule that looks like a lady in, we'll get tadpoles. We have cytoplasmic differentiation now it's become invasive. It can differentiate the insight who sell finds it very difficult to uh to uh to differentiate with the exception of those inciting carcinomas which occur out near the ecto cervix. And they tend to differentiate more. But the major mostly insightful carcinomas of the cervix are of the more, more classical type that we've discussed. Note also were beginning to develop nuclear ally were beginning to develop large areas of pair of Cormack and clearing. Which you're not university are not uniformly dispersed here we have Peric Roma and clearing, but it's uniformly dispersed throughout the cytoplasm. Throughout the nucleus. Here it is not. There are large areas of clearing here. It's not clear over here. The nuclear membrane tends to be wavy, just like the disk periodic cells. And all of a sudden there's a sharp point, a sharp point up there, a sharp point out there. And for no reason at all, we get the nuclear membrane irregularities that we associate with cancer. And so thus with the with the micro invasive tumor which we have here, we have going from bottom to top many of the same type cells we had with the insight who carcinoma, namely perhaps disc periodic cells. But we do also in addition have cells in tissue, in tissue with the same nuclear characteristics we've talked about. The pere chromosome begins to clear, the chromosome begins to clump. The nuclei become very irregular and also in tissue. Now we we again pick up the ability for the cells to functionally differentiate but very atypically and it's usual for the history pathologist to look at the tongues of these little things for these little pearls down at the base of the tongue. Here's one that hasn't gotten done quite so far, but it's a long way from the surface and it's a typical functional differentiation. Now the type of cells that we've shed will show the same thing as the cells and the tissues certainly, and one doesn't need any more evidence in this day and age that the cells were looking at in cytology are identical with the cells we have in tissue. And an appreciation of what we see exfoliated gives us a better appreciation of what lies in the tissue. And when we get invasive carcinoma, we then pick up, we pick up the nuclear changes of nuclear ally of massive chromosome clumping of pere chroma and clearing and of a typical lengthening abnormal shapes. And then in the cytoplasm we now see a cell that can begin to differentiate. The insight of carcinoma is not able to differentiate and the less than inside to differentiates. Normally typically like the dysplasia but the invasive more than inside to then differentiates. But it differentiates a typically it can also differentiate typically, but it begins to pick up more more of the atypical differentiations. Tadpoles, many atypical ecto endo plas. Ums this elongated nucleus. It's a so called fiber type cell spindle cell and this one looks like a typical fiber cell. But this one has made a large bowl showing us the ecto plasm very typical characterization. The large amount of ectoplasm here and then a little thin room of ectoplasm, the end of plasm going between the nucleus and the tail. the nucleus and the tail thrown into of curls and spirals gave me the typical herk heimer spiral, so called february apparatus. These are all types of functional differentiation which are not typical and which one finds with with invasive carcinoma. Now with micro invasive carcinoma, we begin to pick these changes up and so the major difference between insight to micro invasion is we begin to pick up on nuclear ally, we begin to pick up chromosome clumping. We begin to pick up irregular perico McCann clearing. We begin to pick up a typical functional differentiation, lengthening, very macabre shapes etcetera. And as you know, Alan Ng has in a very, very fine study, has been able to actually in a very high degree of accuracy predict from psychology the length of micro invasion that he will run into in tissue. Now this is not to say and please don't misinterpret what I'm saying. This is not to say that we rule out invasion from psychology. No more than to say we rule out invasion from histology. Neither of them are perfect. But it is to say that if that if the histology fails to show invasion, we should get very adequate psychologic um material psychologic specimens to be sure there is no evidence for invasion. So one needs to use both histology and cytology to rule out invasion in the times when it's very important, such as the lady who's pregnant. I'd like to just show in addition to this, which is a large cell characterizing cancer. This is a large cell non characterizing the bud, Wentz and Jim Regan and this one has a better prognosis. And then the one with the poorest prognosis, of course is the is a small sound non characterizing. I want to say a fast word about the location of these lesions. The earliest lesions, which is the ones were mainly interested in because these when we catch them are Are able to be almost 100% curable. And the early lesions of the cervix. If we go back about 20 years ago from a series by Marsh, she took cervical lesions about 300 cases and and he pulled out what, according to his definition were so called early cervical cancer. His definition was they were confined to either above the external loss or below the external loss. And if they involve both of them, he threw them out. So it's very, very early and that they're very restricting. He got 44 out of that group. And it's amazing that when one looks at his group of that, 44, were combined, were confined above the external loss. This tells us something. This tells us that if we have a perfectly normal appearing cervix and if if it's not spatulas were not able to get up even in Capasa copy to see very high. If it's spatulas, one can with with proper cervical speculate, get up and look up the wall, but but not very high. Sometimes it's hard to see the anterior wall even in good Capasa copy with the spatula cervix. And while Capasa copy is the best tool the clinician has now for these early lesions, is it a grave a tip here? Is it an early cancer? It is not perfect And one can have very normal exhaust cervix. And yet on opening that Uterus one will see a Luca plastic sarah pigeon. This area going up that canal which had a higher power will reveal that this is the lesion, a very irregular syrup. Indigenous lesion, virtually nothing on on the outside. And this brings to mind one of arthur heard IX and Don Mackay's pictures of about 20 years ago. This of course is using the boston terminology of anna pleasure rather than dysplasia and it matches it very very nicely A lesion that is not one lesion. In other words if we took a biopsy in this in this particular lesion this would be in sight to this was mainly incited carcinoma with quite a bit of dysplasia. But there was an area of invasive cancer which which lay around there somewhere. And of course if one doesn't take the proper tissue, he's not gonna miss, he's gonna miss it. If one doesn't take the proper cytology, he's gonna miss it too. And this is one of the big reasons we don't like the word cervical scraping. We prefer the word pen, cervical scraping because pan cervical scraping to us means not only the ecto cervix, the wage earners, their first described cervical scraping. And he said, you put the point of the cervical spatula in the oss and using that as a fulcrum. You then rotated 360°. of course. That's an ecto cervical scraping. And this unfortunately is what so many of our clinicians are giving us now and they're calling it a cervical scraping and it's only an extra cervical scraping, but to get as high up the end a cervical canal as possible. Is is of the utmost importance to get these very earliest lesions. There are other ways, of course, rather than this, there's the cotton swab. The cotton swab causes the cells to draw. And more so in the more disease cervix, a higher percentage of the cells will show so called drying artifact, even though one works real fast on it and gets it into fixative right away. And if one uses a cotton swab, I feel it should be a non observant cotton and it should be dipped into normal saline beforehand. But even then, there's a much higher percentage of unsatisfactory. And of course, the, the Western Reserve technique of walter scott to put in a a an aspirating cannula into the end of cervix and aspirate. That material is very fine, wonderful material in the hands of the Western Reserve group. But I don't know why other people just cannot do it so well. We get a very high unsatisfactory percentage in our material. And uh and even stand patent when he went up to buffalo gave up the under cervical aspiration because his clinician just couldn't do it right. It's a superb technique when one gets people like the Western Reserve group who are so interested that they get a very, very fine, simple uhh The average clinician is able to take a very refined pan cervical scraping as long as he knows he should get up as high as he can. Now the vaginal pool material we feel is very important. Also, we feel it's important. From two major points with the vaginal pool mature, we can find the portion that is the vaginal wall portion, the vaginal wall component of the vaginal pool material. And we can therefore do a hormonal evaluation on it which at times will detect cancer. At times it'll detect hormonal abnormalities. One cannot do, one cannot do an accurate hormonal evaluation on surgical material. This will lead you down the primrose path and won't even tell you that it's misleading you. On the other hand, when there's something wrong with vaginal pool material, namely when it's inflammatory and it's not accurate, it'll tell you, but that's not true of cervical material. One can make an evaluation, but its value is in question. You don't know whether it's good or not. And the other thing about vaginal pool is you get material from the endometrium, you get material from the tubes, material from the ovaries And it does pick up endometrial, it picks up cells in 75-80% and then it picks up a typical cells and atypical hormonal patterns in another 15-20% and one can get over 80%, about 83% in our series of, of endometrial carcinoma detections, you find the cells in about 75%. Then I'll go through that and the ovarian tumors utilizing vaginal pool. One can find the sales and about a third of the cases, Not only a third, but a third is better than nothing. And you don't find them in India cervical aspirants only very rarely or with cervical scrapings. You do find them with endometrial aspirations. But in in vaginal pool you find about a third and you also get another third In women over the age of 65 who have an atypical hormonal pattern that will help you pick up or help you detect that you have ovarian. So we prefer a vaginal pool and we prefer putting them together on a single slide. Getting first the vaginal pool because this has mucus and when you have service site, a cervical material does not protect the cells well. And of course when we have disease in the cervix, we have serum and it doesn't protect the cells well. So we like to get the vaginal pool first, we put it on the slide as a puddle and don't spread it and then get the pan cervical scraping, getting as high as we can all the way around, mixing it with that vaginal pool and then moving over to the bottle of fixative, making the cell spread and dropping it in. And this is very critical, immediate wet fixation. If one is going to use this an aerosol spray, that's fine too. As long as it's poised and ready to go, it's an immediate fixation. One man can't do it, make the cells spread and then pick up and adjust the aerosol spray. By that time many of the cells have dried and the pathologists are scratching their head wondering why they're not able to make diagnoses. They wish they could like to say one fast word about this lesion. This lesion is obviously cancer. There's a huge nuclear list. There is a nucleus with no nuclear lie and here's a nucleus that has about 10 nuclear lie multiple nuclear ally varying in a tissue fragment the number of varying tissue fragment. Another thing. Note how round in the secular these nuclei are. I think of a physical like a florentine flask. It's under pressure. It's sort of a bloated nucleus. It's under pressure. And note the amount of cytoplasm here with the nuclei down at one side. So it's calumnies are oriented. It's got abundant cytoplasm, it's got particular nuclei and it makes a Luminal border and it has moderately prominent nuclear life. And this has a lot to recall with regard to endo cervical cells. They are vesicular nuclei. They have abundant cytoplasm that's calumnies are in form and has Luminal borders. Mhm. Mhm. And the only problem is these frequently in the cervical adenocarcinoma frequently looks like a very reactive and a cervical cell. Now the big difference that helps me there is that the very reactive endo cervical cells have a background of service itis. In the end of cervical adenocarcinoma can very frequently be found the void of the cervical mucus and avoid of any real service itis no real evidence why those reactive cells should be there. And then one really gets interested and looks at the nuclear lion by golly rather than all of them having one or two or three nuclear lie. One has no nuclear lion. One has nine to clear line. Now that is another major malignant criteria. That is a good malignant criteria. Many times when it occurs solution how a point about endo cervical adenocarcinoma is that it is found higher up the cervical canal. It's able to go up as high as the internal loss or it can go as low as the external loss in origin. And so the early in the, early in the cervical canal tumors are able to hide above even a good cervical scraping. But the important thing is they hide above the office biopsy of the physician. And when he takes a biopsy of the cervix and he thinks the cervical cancer, he's going to take the usual cervical cancer biopsy and he'll miss the end of cervical adenocarcinoma as that is unless you point out that this is an indo cervical adam. Of course, no mind of course, a cone or some people like DNC, I'm sorry. And a cervical cure ratings uh of Mhm. Is the way to detect that you do have the tumor. Now, this is your case # two. And you see these are somewhat irregular nuclei on some of them, but there are many that are large and pouched out bloated, so called vesicular type. And we have an epithelial Luminal border along here with abundant cytoplasm in the nuclei oriented towards the base. We have a columnar type cell which is malignant. It is not in a very inflammatory background. It's not a real massively massively inflamed chronic service side us. It's it's a background that makes us worried with regard to the APL asia. But it doesn't give us an excuse that it is an inflamed cervix that's shedding very reactive in the cervical cells. There is a section of the indo cervical adenocarcinoma from that case. Now let's go briefly to the endometrium and remember this, we pick up mainly by the pool material. Now the classical endometrial cells show a lot of good malignant criteria. This is grade four, grade three Regan ending, showed that beautifully in there fast. Ical that the later grade show beautiful malignant criteria. The earlier grades, however, show many other uh many minor criteria and a lot of features of other type cells. Take this beautiful little history site for instance, it actually is not a history site. When you look carefully, you see there's a biophysics cytoplasm. The outside of the cytoplasm tends to be a little pale and history sites tend to do that. And then the nuclear I have irregularities and they have irregularities opposite where history site should. And these anti Hoff irregularities can be a key that you're not dealing with. Just a very active history site. And note also the background is that it has superficial cells in the background. It has a shift to the right. These ladies past the age of 65 should have only 10% superficial or thereabouts. Now, this is a history side looking sell. But look at that the outside side of Plasm and this one is a very, very dark reactive cell. And once again with the outside type side of plaza. But the nuclear regularities over here and over here just don't go along with those of history site. Very early adenocarcinoma. Grade one or so called grade one half. Depending on who's Terminology one uses. This is another very early grade one adenocarcinoma. These look like little folded over history sites. A very active history sites are to be a very concerning to us. This is case number six of yours. And this is a higher power of that cell. Way down at the bottom. Now on on her whole material, on her whole material. This is all we had on her whole material. And this is a lady who was 78 years of age and she had about 18% superficial cells. And she had very early, very early great one adenocarcinoma. This is the time to find the adenocarcinoma for cure. One should not hesitate to go up into the endometrial cavity by either aspiration or by brushing. And and there are other techniques. Also. The elaborate technique is a very fine one. And the so called jet washing is a good one. But uh keep your criteria high. If it's unsatisfactory or less than satisfactory, tell the clinician that don't make him think that he's doing a good job. Now the the I. U. D. Is a subject I want to just touch on briefly. And here is your number eight a vaginal smear that we've noted in the last 2.5 years and patients who have I. E. Ds. Having in their material little sulfur type Granules. You go down on them. They may or may not have neutral files around them. Typical of what we like to call sulfur Granules. But you can see this is a pap Nicholaus staying. You can see parallel rods. Put your branching and put your granular And this is action. Oh my sees, this is a gram stain of it. We never saw it before. Now we began to see it about as I say 234 years ago We now have 140 cases everyone associated with i. e. DS. And this is this is a fluorescent down the body. Uhh this is for acting to my season pass qalandia. It was negative for acting like action of mrs. Israeli. We do not have one traction to mice is bogus, but this is the organism of acting to mrs and surrounding of this group. It's interesting that now we found it in 12 cases in tissue one on the DNC. Seven on tubo. Ovarian abscess is one of following a hysterectomy with the I. U. D. In place in which you're not able to see the organisms only. But we could also see them on section. And we we're also able to do a fluorescent antibody work on it. And it and on one case who died of pneumonia following a DNC. A laparotomy um um with bilateral tubal abscesses and had the organism in there. Uhh this is from a a paper coming out of our lab Gupta And of 140. That's the way they went. We are not able to pin any particular type of an I. u. d. and and after the missus has been found as little as three months after the insertion of the I. U. D. Or as long as seven years after the insertion of the I. U. D. Now one fast thing about ovarian cancer that these cells can go down the tubes. They will drop off even before uh the host is able to accept them. So you don't have to have implants in order to have these things go down the tubes in order to then see them in the vaginal pool. Now note that the that the background is very clear and this is the background of two things of ovarian tumor. In the background of metastatic tumor. This is a primary and the breast metastatic to the vaginal smear. This is primary ovarian with this bubble gum type of pouched out back. You'll hear it is with papillary. Another feature of Bulgarian. Uh huh. Papillary can be endometrial also. But it's very common with ovarian. And of course the finding of Sanoma bodies. It can be endometrium but it's very common with ovarian and at times one gets a very peculiar perry nuclear clearing the house and halo, which is much more common with ovarian than it is with the endometrium and others. And as I mentioned a third of them, one gets cells that are shed Able to be diagnosed. Another third one gets in a typical hormonal pattern of women over the age of 45, which you can only pick up on the vaginal component and then another third we missed completely and one has to think in terms of a cola synthesis. Now this is your last case number seven And this is not a very clean background. But this was a lady who was in her 70s and she has about an 18% superficial cells which is much higher than one should have. And I blow up of this, it did have a perry nuclear clearing and was a primary ovarian adenocarcinoma. Well I'm afraid Don that I I run awfully fast and I've left many many things and said, but it's been a real pleasure to be with you today. Okay. Yeah. Thank you, Jeff, ladies and gentlemen, is are there any questions from the audience? We neglected to say that there is one microphone in the audience. We had two but one of them is not working. However, Miss Dues right there has a microphone and if there's a question we'd be glad to hear it. No questions for dr Frost. If there aren't then I have a few announcements to make one. There are restrooms available immediately to the right. Their room 102 for the ladies.