1 00:00:06,056 --> 00:00:10,059 (From M1 Patients and Populations at University of Michigan Medical School. Lecture by Gerald Abrams, MD.) You see the title is Disturbances of Growth in Neoplasia. 2 00:00:10,059 --> 00:00:11,769 This is one of the 3 00:00:11,769 --> 00:00:13,099 probably the only time 4 00:00:13,099 --> 00:00:18,004 in the sequence where pathology really meshes with what else is going on. 5 00:00:18,004 --> 00:00:18,829 6 00:00:18,829 --> 00:00:21,039 We will spend 7 00:00:21,039 --> 00:00:25,006 much of the two hours today and then an hour Wednesday 8 00:00:25,006 --> 00:00:28,359 on the subject of neoplasms, that is tumors 9 00:00:28,359 --> 00:00:33,399 this will feed into Dr Gruber's 11 o'clock lecture on Wednesday on the genetics 10 00:00:33,399 --> 00:00:34,041 11 00:00:34,041 --> 00:00:38,073 aspects of neoplasia and then a very interesting MDC in the afternoon, 12 00:00:38,073 --> 00:00:39,089 13 00:00:39,089 --> 00:00:44,071 dealing with some clinical aspects of those same things. 14 00:00:44,071 --> 00:00:46,032 But before we settle down 15 00:00:46,032 --> 00:00:49,086 to the subject of neoplasms, tumors and such, 16 00:00:49,086 --> 00:00:54,071 i want to spend a bit of time giving you a few notions and definitions in visual images 17 00:00:54,071 --> 00:00:55,062 images 18 00:00:55,062 --> 00:00:59,034 dealing with other 19 00:00:59,034 --> 00:01:03,039 abnormalities of growth short of new place, in other words there are some other 20 00:01:03,039 --> 00:01:04,084 some other 21 00:01:04,084 --> 00:01:08,026 disturbances in the size of cells tissues and organs 22 00:01:08,026 --> 00:01:09,055 the 23 00:01:09,055 --> 00:01:13,038 mode of cellular proliferation and even 24 00:01:13,038 --> 00:01:16,008 lead the way that cells mature 25 00:01:16,008 --> 00:01:17,000 and 26 00:01:17,000 --> 00:01:20,009 look at a few of these abnormalities first before we get onto the main 27 00:01:20,009 --> 00:01:21,085 subject 28 00:01:21,085 --> 00:01:23,005 let me begin 29 00:01:23,005 --> 00:01:25,032 very simply with 30 00:01:25,032 --> 00:01:26,059 situations 31 00:01:26,059 --> 00:01:28,079 in which you might 32 00:01:28,079 --> 00:01:32,076 encounter a bunch of cells, a tissue, an organ 33 00:01:32,076 --> 00:01:34,034 smaller than normal 34 00:01:34,034 --> 00:01:37,008 smaller than you expect 35 00:01:37,008 --> 00:01:38,359 and it runs 36 00:01:38,359 --> 00:01:40,027 something like this 37 00:01:40,027 --> 00:01:44,028 it makes pretty good sense that the one way that you could end up with a tissue 38 00:01:44,028 --> 00:01:46,076 that's abnormally small 39 00:01:46,076 --> 00:01:50,066 organized abnormally small is a developmental situation 40 00:01:50,066 --> 00:01:53,063 where it never grew up 41 00:01:53,063 --> 00:01:55,033 sort of a dwarfed tissue 42 00:01:55,033 --> 00:01:56,759 or organ 43 00:01:56,759 --> 00:01:58,002 and on the other hand 44 00:01:58,002 --> 00:01:59,081 there are situations 45 00:01:59,081 --> 00:02:03,036 as i think you're already familiar with 46 00:02:03,036 --> 00:02:08,799 when an organ or tissue reaches a definitive adult size and then shrinks 47 00:02:08,799 --> 00:02:11,086 that process i think you know from Ramsburgh's lecture we call 48 00:02:11,086 --> 00:02:13,629 atrophy 49 00:02:13,629 --> 00:02:15,037 so those are two kinds 50 00:02:15,037 --> 00:02:18,189 situations and i want to run through first 51 00:02:18,189 --> 00:02:21,949 this list of developmental problems 52 00:02:21,949 --> 00:02:26,069 that we have encounter from time to time 53 00:02:26,069 --> 00:02:29,319 the most complete sort of defect 54 00:02:29,319 --> 00:02:33,289 you might encounter is when the embryonic rudiment 55 00:02:33,289 --> 00:02:34,519 of an organ 56 00:02:34,519 --> 00:02:38,012 simply doesn't develop, it's a screw up in embryogenesis 57 00:02:38,012 --> 00:02:40,309 and then there is no organ 58 00:02:40,309 --> 00:02:41,039 laid down 59 00:02:41,039 --> 00:02:42,098 and we referred to that 60 00:02:42,098 --> 00:02:46,589 process as agenesis 61 00:02:46,589 --> 00:02:50,589 there's a slight variation on the theme and that is where the rudiment of the organ 62 00:02:50,589 --> 00:02:51,359 may be 63 00:02:51,359 --> 00:02:53,379 laid down in the embryo, but 64 00:02:53,379 --> 00:02:56,179 the thing never grows 65 00:02:56,179 --> 00:02:58,929 non-descript nubbin' of nothing 66 00:02:58,929 --> 00:03:02,209 and that sometimes is referred to as aplasia 67 00:03:02,209 --> 00:03:05,889 those two terms are essentially synonymous 68 00:03:05,889 --> 00:03:07,689 it's an absence 69 00:03:07,689 --> 00:03:10,069 an absence of the tissue 70 00:03:10,069 --> 00:03:10,939 and I'll 71 00:03:10,939 --> 00:03:15,004 give you an example, a very striking example of this 72 00:03:15,004 --> 00:03:18,006 here's an autopsy specimen, let me orient you to it 73 00:03:18,006 --> 00:03:19,959 this is the urinary bladder down here 74 00:03:19,959 --> 00:03:21,239 here is 75 00:03:21,239 --> 00:03:29,819 a ureter on one side going up and connecting with a very respectable looking kidney 76 00:03:29,819 --> 00:03:32,599 here's the other ureter, boom! 77 00:03:32,599 --> 00:03:33,091 there was nothing outside the 78 00:03:33,091 --> 00:03:36,749 it's not a camera trick, there's nothing outside there, it just ended 79 00:03:36,749 --> 00:03:38,629 that way 80 00:03:38,629 --> 00:03:41,949 now that is an example of the unilateral renal 81 00:03:41,949 --> 00:03:42,999 agenesis 82 00:03:42,999 --> 00:03:47,379 or aplasia, i don't care which word you use 83 00:03:47,379 --> 00:03:50,989 this sort of thing is compatible with long happy life and this is strictly an incidental finding 84 00:03:50,989 --> 00:03:54,199 i don't remember anymore what this individual died of 85 00:03:54,199 --> 00:03:55,048 but it had nothing 86 00:03:55,048 --> 00:03:56,469 relating to the 87 00:03:56,469 --> 00:03:58,209 urinary tract 88 00:03:58,209 --> 00:04:02,289 so it's just a failure on one side for that 89 00:04:02,289 --> 00:04:05,449 kidney to develop. Agenesis or aplasia. 90 00:04:05,449 --> 00:04:07,439 sometimes we see this bilaterally. Both 91 00:04:07,439 --> 00:04:09,399 kidneys are not there 92 00:04:09,399 --> 00:04:11,029 and that 93 00:04:11,029 --> 00:04:16,025 of course is not compatible with life whereas this sort of thing is 94 00:04:16,025 --> 00:04:17,889 now 95 00:04:17,889 --> 00:04:20,819 the next step up from 96 00:04:20,819 --> 00:04:23,013 agenesis or aplasia 97 00:04:23,013 --> 00:04:25,059 is a situation where the 98 00:04:25,059 --> 00:04:28,056 the organ rudiment is laid down in the embryo, and indeed 99 00:04:28,056 --> 00:04:31,229 grows but not 100 00:04:31,229 --> 00:04:33,062 as much as it should 101 00:04:33,062 --> 00:04:35,259 so you end up with something 102 00:04:35,259 --> 00:04:37,047 smaller than normal because of 103 00:04:37,047 --> 00:04:41,569 well we might call it loosely a growth failure, and that we call 104 00:04:41,569 --> 00:04:43,002 hypoplasia 105 00:04:43,002 --> 00:04:45,799 hypo meaning under or less than 106 00:04:45,799 --> 00:04:50,269 and there's an example, let me take you through this one, it's a little bit confusing 107 00:04:50,269 --> 00:04:51,006 here's 108 00:04:51,006 --> 00:04:52,689 the bladder 109 00:04:52,689 --> 00:04:56,559 this happens to be the aorta, forget about that, here's the bladder 110 00:04:56,559 --> 00:04:57,759 the ureter 111 00:04:57,759 --> 00:05:00,499 on one side going up to a very decent looking 112 00:05:00,499 --> 00:05:03,019 kidney 113 00:05:03,019 --> 00:05:06,069 here is the ureter on the other side, sort of stunted 114 00:05:06,069 --> 00:05:08,479 here's 115 00:05:08,479 --> 00:05:10,001 a little shrunken 116 00:05:10,001 --> 00:05:12,639 well, i shouldn't say shrunken, but a tiny, miniature 117 00:05:12,639 --> 00:05:14,899 kidney there 118 00:05:14,899 --> 00:05:16,009 that represents a unilateral 119 00:05:16,009 --> 00:05:22,021 renal hypoplasia 120 00:05:22,021 --> 00:05:25,169 again sort of an embryonic defect 121 00:05:25,169 --> 00:05:26,689 if you will 122 00:05:26,689 --> 00:05:29,013 sometimes we see this bilaterally 123 00:05:29,013 --> 00:05:32,091 and it could be all degrees, it could be something between this and this or something 124 00:05:32,091 --> 00:05:35,919 even less than this and as long as 125 00:05:35,919 --> 00:05:38,003 you put it under the microscope and you see 126 00:05:38,003 --> 00:05:41,649 the structure of kidney, but there's not enough of it, it's too small. that's hypoplasia. 127 00:05:41,649 --> 00:05:44,044 128 00:05:44,044 --> 00:05:49,479 i've shown you urinary tract here, these sorts of defects, agenesis and hypoplasia 129 00:05:49,479 --> 00:05:51,189 occur in 130 00:05:51,189 --> 00:05:52,449 other organs 131 00:05:52,449 --> 00:05:56,399 and organ systems as well, i just happen to have these pictures on hand 132 00:05:56,399 --> 00:06:00,689 one of things you'll encounter when you get over in the hospital because we're sort of 133 00:06:00,689 --> 00:06:03,087 a funnel for odd things 134 00:06:03,087 --> 00:06:05,129 is fairly often 135 00:06:05,129 --> 00:06:07,319 136 00:06:07,319 --> 00:06:11,969 kids born with what we call hypoplastic left heart 137 00:06:11,969 --> 00:06:13,008 and that's the situation 138 00:06:13,008 --> 00:06:17,849 where the chambers of the left side of the heart and even sometimes a portion 139 00:06:17,849 --> 00:06:19,027 of the aorta 140 00:06:19,027 --> 00:06:24,013 simply don't develop properly, and there are little tiny nubbin's on the heart 141 00:06:24,013 --> 00:06:28,006 and this hypoplastic left heart syndrome is lethal unless some pretty fancy 142 00:06:28,006 --> 00:06:32,011 surgery is done to intervene for a while 143 00:06:32,011 --> 00:06:36,349 so you will see that hypoplastic left heart 144 00:06:36,349 --> 00:06:40,011 one more term on that list that i gave you, i just defined it and i want to illustrate it 145 00:06:40,011 --> 00:06:42,669 and that is atresia 146 00:06:42,669 --> 00:06:44,839 a-t-r-e-s-i-a, atresia 147 00:06:44,839 --> 00:06:49,979 which is a situation and again it's a developmental failure where a channel 148 00:06:49,979 --> 00:06:53,028 a normal opening or channel fails 149 00:06:53,028 --> 00:06:55,539 to stay open 150 00:06:55,539 --> 00:06:59,074 fails to form properly so you end up with a closure where you should have 151 00:06:59,074 --> 00:07:02,031 a channel 152 00:07:02,031 --> 00:07:06,169 something let's say along the GI tract or along a duct 153 00:07:06,169 --> 00:07:10,169 where it simply disappears because it never opened up properly. That's atresia. 154 00:07:10,169 --> 00:07:13,036 Now the second situation 155 00:07:13,036 --> 00:07:16,409 i mentioned back on that list 156 00:07:16,409 --> 00:07:19,011 other than developmental is a situation 157 00:07:19,011 --> 00:07:20,009 where the organ has reached 158 00:07:20,009 --> 00:07:25,299 a definitive size and undergoes a process of atrophy 159 00:07:25,299 --> 00:07:28,959 atrophy can come about really in in two ways 160 00:07:28,959 --> 00:07:29,969 first of all 161 00:07:29,969 --> 00:07:34,004 every single cell in the tissue could shrink 162 00:07:34,004 --> 00:07:36,029 by some percentage 163 00:07:36,029 --> 00:07:39,349 and that would produce a smaller tissue, a smaller organ 164 00:07:39,349 --> 00:07:40,012 or 165 00:07:40,012 --> 00:07:43,699 a certain number of cells as they start out with a million cells in the population 166 00:07:43,699 --> 00:07:44,009 and 167 00:07:44,009 --> 00:07:47,909 some of them disappear by apoptosis 168 00:07:47,909 --> 00:07:49,789 and you end up 169 00:07:49,789 --> 00:07:53,024 with eight hundred thousand cells, that's going to be a shrunken tissue 170 00:07:53,024 --> 00:07:54,929 so a tissue can 171 00:07:54,929 --> 00:07:58,719 undergo atrophy with shrinkage of individual cells 172 00:07:58,719 --> 00:08:02,419 sometimes loss of cells or both 173 00:08:02,419 --> 00:08:06,879 but it's a secondary change after the the organ has reached its definitive size 174 00:08:06,879 --> 00:08:09,099 some 175 00:08:09,099 --> 00:08:12,809 examples of atrophy as some of you may know already 176 00:08:12,809 --> 00:08:17,139 is perfectly physiologic in the, let's say, fetus 177 00:08:17,139 --> 00:08:19,319 as various things form and come and go 178 00:08:19,319 --> 00:08:20,008 there's atrophy 179 00:08:20,008 --> 00:08:23,078 there's certainly atrophy of fetal structures 180 00:08:23,078 --> 00:08:25,083 in the neonatal period 181 00:08:25,083 --> 00:08:28,329 umbilical vessels and that sort of thing undergo 182 00:08:28,329 --> 00:08:30,439 atrophy 183 00:08:30,439 --> 00:08:31,056 there are examples 184 00:08:31,056 --> 00:08:34,007 of physiologic atrophy 185 00:08:34,007 --> 00:08:38,081 as one matures into adult life, the tonsils shrink 186 00:08:38,081 --> 00:08:40,169 the thymus shrinks 187 00:08:40,169 --> 00:08:41,011 and so forth 188 00:08:41,011 --> 00:08:44,012 there are these things which are expected and physiologic 189 00:08:44,012 --> 00:08:46,093 when 190 00:08:46,093 --> 00:08:52,001 it comes to pathologic forms of atrophy, there are many reasons why 191 00:08:52,001 --> 00:08:53,097 this can happen, one that Dr 192 00:08:53,097 --> 00:08:57,049 Ramsburgh may have mentioned is ischemia 193 00:08:57,049 --> 00:09:02,047 if you rob a tissue of its blood supply, let's say, not enough to kill it 194 00:09:02,047 --> 00:09:04,068 but really to cut it down, there's 195 00:09:04,068 --> 00:09:07,057 such a thing as ischemic atrophy 196 00:09:07,057 --> 00:09:10,026 and you'll see that in arteriosclerotic 197 00:09:10,026 --> 00:09:14,051 areas where the tissues tend to simply shrink 198 00:09:14,051 --> 00:09:16,028 starvation 199 00:09:16,028 --> 00:09:17,041 you don't 200 00:09:17,041 --> 00:09:20,084 feed a person enough calories, starvation will produce 201 00:09:20,084 --> 00:09:25,038 atrophy. there's a hierarchy of organs which i don't want to go into 202 00:09:25,038 --> 00:09:27,043 for instance, the brain doesn't atrophy 203 00:09:27,043 --> 00:09:28,709 in that situation 204 00:09:28,709 --> 00:09:32,299 but the adipose tissue does, the liver does, and so forth 205 00:09:32,299 --> 00:09:34,008 that's starvation atrophy 206 00:09:34,008 --> 00:09:37,065 in the case of muscular tissues 207 00:09:37,065 --> 00:09:38,069 disuse 208 00:09:38,069 --> 00:09:41,057 just plain old disuse will cause atrophy 209 00:09:41,057 --> 00:09:43,013 it could be very striking 210 00:09:43,013 --> 00:09:47,399 i don't know if any of you have been in this situation, but you have an acute injury 211 00:09:47,399 --> 00:09:48,083 like, oh let's say, 212 00:09:48,083 --> 00:09:53,076 a bad knee, for some reason, just self splinting 213 00:09:53,076 --> 00:09:56,028 not using that leg in the same way 214 00:09:56,028 --> 00:09:58,529 will cause a shrinkage within a few weeks 215 00:09:58,529 --> 00:10:04,027 you can get a loss in circumference of a thigh 216 00:10:04,027 --> 00:10:06,021 i don't know how many of you are skiiers 217 00:10:06,021 --> 00:10:07,099 that have gotten into 218 00:10:07,099 --> 00:10:12,034 trouble and ended up with let's say a cast on an extremity 219 00:10:12,034 --> 00:10:17,017 for a number of weeks and when that cast comes off, you've got a shriveled leg 220 00:10:17,017 --> 00:10:19,011 compared to the other one 221 00:10:19,011 --> 00:10:22,053 that is disuse atrophy 222 00:10:22,053 --> 00:10:26,024 an extreme example of that is something we call neurogenic atrophy, if you cut 223 00:10:26,024 --> 00:10:26,076 the motor 224 00:10:26,076 --> 00:10:29,028 nerve going to a muscle 225 00:10:29,028 --> 00:10:33,022 then that muscle can't work at all and is getting no signals 226 00:10:33,022 --> 00:10:37,099 it'll really shrink, it's a tremendous sort of atrophy 227 00:10:37,099 --> 00:10:39,027 then 228 00:10:39,027 --> 00:10:42,013 well, i'll stop this list with one more 229 00:10:42,013 --> 00:10:45,039 many tissues in the body are 230 00:10:45,039 --> 00:10:48,058 the way they are because they have a certain endocrine support 231 00:10:48,058 --> 00:10:54,028 they depend on a certain level of a particular hormone, and if you withdraw that hormone, the tissue 232 00:10:54,028 --> 00:10:58,067 will undergo atrophy. Morphologically 233 00:10:58,067 --> 00:10:59,048 it's pretty 234 00:10:59,048 --> 00:11:02,319 straight forward, i'm not going to show you much of this 235 00:11:02,319 --> 00:11:02,091 it's simply the tissue 236 00:11:02,091 --> 00:11:04,029 is smaller 237 00:11:04,029 --> 00:11:08,189 you look at it under the microscope and the individual cells are smaller 238 00:11:08,189 --> 00:11:11,095 the number of cells, that's a tougher thing to deal 239 00:11:11,095 --> 00:11:15,096 with, but basically it's a small tissue 240 00:11:15,096 --> 00:11:19,074 sometimes there's partial fibrous replacement as the tissues shrink 241 00:11:19,074 --> 00:11:23,027 we call that fibrous atrophy 242 00:11:23,027 --> 00:11:23,074 sometimes 243 00:11:23,074 --> 00:11:28,011 this seems to be an increase in adipose tissue, marbling the tissue, we call that fatty atrophy 244 00:11:28,011 --> 00:11:31,001 but basically the business cells of the tissue 245 00:11:31,001 --> 00:11:32,073 are smaller 246 00:11:32,073 --> 00:11:35,009 there's one variation on this theme that 247 00:11:35,009 --> 00:11:40,027 Ramsburgh may have introduced you to and that's 248 00:11:40,027 --> 00:11:43,046 as a cell shrinks 249 00:11:43,046 --> 00:11:45,071 it basically 250 00:11:45,071 --> 00:11:50,042 is undergoing a process of autophagy, it's eating itself, it's digesting 251 00:11:50,042 --> 00:11:52,019 various of its 252 00:11:52,019 --> 00:11:55,003 organelles and so forth 253 00:11:55,003 --> 00:12:00,038 one of the things that happens from this digestive process is that there 254 00:12:00,038 --> 00:12:02,369 may be residual products 255 00:12:02,369 --> 00:12:04,057 left afterwards and 256 00:12:04,057 --> 00:12:05,002 they 257 00:12:05,002 --> 00:12:07,077 tend to be pigmented products which we've 258 00:12:07,077 --> 00:12:10,087 we refer to as lipofuscin 259 00:12:10,087 --> 00:12:13,061 260 00:12:13,061 --> 00:12:18,055 here's a liver where particularly in this area, the central area, the cells 261 00:12:18,055 --> 00:12:20,054 are shrunken and you'll 262 00:12:20,054 --> 00:12:23,085 notice this is not a particularly good photo, but you'll notice they are brown 263 00:12:23,085 --> 00:12:25,037 and that's 264 00:12:25,037 --> 00:12:28,006 because of a relative concentration of lipofuscin there 265 00:12:28,006 --> 00:12:29,829 they've been undergoing 266 00:12:29,829 --> 00:12:31,031 autophagy 267 00:12:31,031 --> 00:12:36,035 and the residual products are piling up and sometimes we refer to this as pigment atrophy 268 00:12:36,035 --> 00:12:38,009 or brown atrophy 269 00:12:38,009 --> 00:12:42,044 and i've seen shrunken livers where there's perhaps half the mass of the usual liver 270 00:12:42,044 --> 00:12:43,001 and they're really 271 00:12:43,001 --> 00:12:44,639 definite 272 00:12:44,639 --> 00:12:46,038 brown 273 00:12:46,038 --> 00:12:47,699 rather than the ordinary 274 00:12:47,699 --> 00:12:48,649 liver color 275 00:12:48,649 --> 00:12:50,869 because of this sort of accumulation 276 00:12:50,869 --> 00:12:53,019 Okay so 277 00:12:53,019 --> 00:12:57,007 much for smaller than normal, let's go to the flip side 278 00:12:57,007 --> 00:13:00,959 and look at situations where the tissue or the organ may be larger 279 00:13:00,959 --> 00:13:02,029 than normal 280 00:13:02,029 --> 00:13:03,048 and this 281 00:13:03,048 --> 00:13:07,004 can come about in two ways 282 00:13:07,004 --> 00:13:11,088 you can have an increase in the size of the cells in the tissue 283 00:13:11,088 --> 00:13:15,008 and we refer to that as hypertrophy 284 00:13:15,008 --> 00:13:19,015 you can have an increase in the number of cells in the tissue, we call that hyperplasia 285 00:13:19,015 --> 00:13:21,007 Now let's go back 286 00:13:21,007 --> 00:13:23,074 up to hypertrophy 287 00:13:23,074 --> 00:13:28,022 let me point out that size increase isn't simply cell swelling, you know 288 00:13:28,022 --> 00:13:32,061 about the phenomenon of cell swelling, which involves a net accumulation of water 289 00:13:32,061 --> 00:13:35,062 that we wouldn't call hypertrophy 290 00:13:35,062 --> 00:13:39,065 in hypertrophy, the cells enlarge because of an increased 291 00:13:39,065 --> 00:13:41,006 synthesis 292 00:13:41,006 --> 00:13:43,048 of cellular components 293 00:13:43,048 --> 00:13:44,779 i'll show you that in a 294 00:13:44,779 --> 00:13:46,012 moment 295 00:13:46,012 --> 00:13:48,002 again hyperplasia 296 00:13:48,002 --> 00:13:51,074 involves an increase in cell number so you'd look 297 00:13:51,074 --> 00:13:55,007 for hyperplasia only in tissues that are capable of 298 00:13:55,007 --> 00:13:57,079 dividing in the adult state 299 00:13:57,079 --> 00:14:00,049 another was a permanent sort of tissue 300 00:14:00,049 --> 00:14:03,083 you're not going to get hyperplasia ordinarily in muscle 301 00:14:03,083 --> 00:14:05,006 you're not going to get 302 00:14:05,006 --> 00:14:11,026 hyperplasia, well muscle is probably the best example. but in other 303 00:14:11,026 --> 00:14:12,093 organs, you may 304 00:14:12,093 --> 00:14:16,052 get hyperplasia along with hypertrophy 305 00:14:16,052 --> 00:14:17,095 but conceptually hypertrophy 306 00:14:17,095 --> 00:14:22,399 is increase in cell size, hyperplasia is increase in cell 307 00:14:22,399 --> 00:14:24,249 number 308 00:14:24,249 --> 00:14:26,072 the 309 00:14:26,072 --> 00:14:33,073 best example of hypertrophy is in muscular tissues 310 00:14:33,073 --> 00:14:35,053 it's a response 311 00:14:35,053 --> 00:14:38,077 hypertrophy in muscle is a response to an overload 312 00:14:38,077 --> 00:14:42,057 or unusual workload or what not 313 00:14:42,057 --> 00:14:46,038 now you need a lot of imagination for this, but imagine i went in for bodybuilding 314 00:14:46,038 --> 00:14:48,032 which i never will 315 00:14:48,032 --> 00:14:51,067 and you know you you pump three hundred pounds like this 316 00:14:51,067 --> 00:14:53,015 and after a while couldn't 317 00:14:53,015 --> 00:14:55,078 get into the lab coat. Bulging 318 00:14:55,078 --> 00:14:59,027 muscles, i told you, imagination. 319 00:14:59,027 --> 00:15:00,042 the 320 00:15:00,042 --> 00:15:03,409 muscles of the bodybuilder 321 00:15:03,409 --> 00:15:06,429 you've all seen pictures of this and maybe some of you are into this sort of sport 322 00:15:06,429 --> 00:15:07,075 this 323 00:15:07,075 --> 00:15:09,689 represents 324 00:15:09,689 --> 00:15:10,047 hypertrophy 325 00:15:10,047 --> 00:15:15,004 of muscle, there isn't any real increase in the number of muscle cells 326 00:15:15,004 --> 00:15:18,078 but any individual muscle cells instead of being this big around is this big around 327 00:15:18,078 --> 00:15:20,009 and it 328 00:15:20,009 --> 00:15:23,001 represents actually a synthesis of more 329 00:15:23,001 --> 00:15:26,007 contractile machinery 330 00:15:26,007 --> 00:15:27,829 in the muscle, it's a response 331 00:15:27,829 --> 00:15:30,034 to the work 332 00:15:30,034 --> 00:15:33,084 now a place where we see this that isn't so trivial 333 00:15:33,084 --> 00:15:35,003 is 334 00:15:35,003 --> 00:15:37,018 is, for instance, heart muscle 335 00:15:37,018 --> 00:15:41,005 that is subjected to an abnormal load 336 00:15:41,005 --> 00:15:44,094 for instance, a left ventricle 337 00:15:44,094 --> 00:15:51,094 having to pump blood in a patient with uncontrolled hypertension 338 00:15:51,094 --> 00:15:55,007 in other words, the systemic blood pressure is elevated, the arteriolar resistance is elevated 339 00:15:55,007 --> 00:15:58,439 and every time that poor old left ventricle 340 00:15:58,439 --> 00:16:02,082 tries to eject blood, it's doing it against an increased head of pressure 341 00:16:02,082 --> 00:16:06,089 those muscles are going to undergo hypertrophy 342 00:16:06,089 --> 00:16:07,097 or 343 00:16:07,097 --> 00:16:11,009 let's say the valve, the so-called aortic valve, which is a valve between 344 00:16:11,009 --> 00:16:17,047 the left ventricle and the aorta, as the blood flows out, if that valve gets narrowed 345 00:16:17,047 --> 00:16:20,011 the poor old ventricle has to squeeze harder to get 346 00:16:20,011 --> 00:16:23,003 the blood out to maintain life, it will undergo hypertrophy 347 00:16:23,003 --> 00:16:24,139 not hyperplasia 348 00:16:24,139 --> 00:16:25,119 but hypertrophy 349 00:16:25,119 --> 00:16:26,059 and the 350 00:16:26,059 --> 00:16:29,037 heart gains weight 351 00:16:29,037 --> 00:16:31,031 the ventricle becomes thick 352 00:16:31,031 --> 00:16:35,092 and the cells become enlarged. I'll illustrate this for you. 353 00:16:35,092 --> 00:16:37,049 here is 354 00:16:37,049 --> 00:16:41,042 don't pay attention to the color, there have been some post-mortem changes here but 355 00:16:41,042 --> 00:16:43,739 this is a bread loaf slice 356 00:16:43,739 --> 00:16:45,041 of a normal heart 357 00:16:45,041 --> 00:16:47,919 you're looking at the right ventricle over here 358 00:16:47,919 --> 00:16:52,209 left ventricle over here ordinarily, this is normal, the right ventricle is very thin 359 00:16:52,209 --> 00:16:57,014 because it pumps against a lesser head of pressure in the pulmonary circuit. The left ventricle 360 00:16:57,014 --> 00:16:59,559 ,that's about normal thickness, 361 00:16:59,559 --> 00:17:01,002 now the next slide 362 00:17:01,002 --> 00:17:05,036 is not a photo trick and again don't worry about the colors, but the next 363 00:17:05,036 --> 00:17:12,021 slide is taken from an individual with high blood pressure 364 00:17:12,021 --> 00:17:15,015 now that first heart probably weighed 365 00:17:15,015 --> 00:17:18,819 oh in the neighborhood of three hundred, three hundred and twenty five grams 366 00:17:18,819 --> 00:17:20,045 this heart weighed closer 367 00:17:20,045 --> 00:17:24,022 to the six or seven hundred grams, i don't remember precisely, but 368 00:17:24,022 --> 00:17:28,005 it kind of speaks for itself, there is more muscle there 369 00:17:28,005 --> 00:17:31,099 and again this is not hyperplasia, this is hypertrophy 370 00:17:31,099 --> 00:17:36,045 and it looks something like this. i know you don't know much of this histology 371 00:17:36,045 --> 00:17:37,088 but just 372 00:17:37,088 --> 00:17:41,046 think of these as cross-sections of these cylindrical muscle cells 373 00:17:41,046 --> 00:17:42,086 and this is 374 00:17:42,086 --> 00:17:44,091 a normal myocardium 375 00:17:44,091 --> 00:17:45,063 and 376 00:17:45,063 --> 00:17:50,052 let's just cast your eyeballs around and look at the approximate 377 00:17:50,052 --> 00:17:54,083 average diameter 378 00:17:54,083 --> 00:17:55,057 the next slide 379 00:17:55,057 --> 00:17:58,059 is taken with the same optics in the microscope 380 00:17:58,059 --> 00:18:04,006 from a hypertrophic heart, now you got this? 381 00:18:04,006 --> 00:18:04,071 The point 382 00:18:04,071 --> 00:18:08,809 those cells are really increased in diameter, don't worry about this, I don't expect you to 383 00:18:08,809 --> 00:18:11,049 pick this up on the quiz 384 00:18:11,049 --> 00:18:13,007 but just to show you 385 00:18:13,007 --> 00:18:14,003 the increase 386 00:18:14,003 --> 00:18:19,019 and what this represents really is an increase, a very striking increase 387 00:18:19,019 --> 00:18:21,058 in the myofibrillar contractile machinery 388 00:18:21,058 --> 00:18:24,079 of these cells 389 00:18:24,079 --> 00:18:28,679 so this is clearly an adaptive 390 00:18:28,679 --> 00:18:30,052 phenomenon 391 00:18:30,052 --> 00:18:33,056 and it works very well up to a point 392 00:18:33,056 --> 00:18:38,092 the heart can't keep getting more and more and more hypertrophic 393 00:18:38,092 --> 00:18:40,069 i've never seen a heart 394 00:18:40,069 --> 00:18:42,081 weigh much more than a kilogram 395 00:18:42,081 --> 00:18:44,309 and that's rare 396 00:18:44,309 --> 00:18:45,049 but beyond that 397 00:18:45,049 --> 00:18:46,809 it doesn't work 398 00:18:46,809 --> 00:18:51,299 and one of the reasons that it doesn't work is that the vascularity of the blood supply 399 00:18:51,299 --> 00:18:53,008 of the heart 400 00:18:53,008 --> 00:18:56,017 muscle doesn't keep up 401 00:18:56,017 --> 00:18:59,038 with too much hypertrophy and pretty soon 402 00:18:59,038 --> 00:19:03,067 the muscle to capillary ratio is unfavorable 403 00:19:03,067 --> 00:19:06,095 and it plateaus, it can't go any further 404 00:19:06,095 --> 00:19:12,012 and then what you get is the onset of apoptosis in cells and actually some 405 00:19:12,012 --> 00:19:17,001 fibrous replacement of the myocardium so it doesn't work indefinitely 406 00:19:17,001 --> 00:19:17,061 actually some 407 00:19:17,061 --> 00:19:19,084 of the proteins that are formed 408 00:19:19,084 --> 00:19:22,081 are not necessarily normal either 409 00:19:22,081 --> 00:19:23,089 so hypertrophy 410 00:19:23,089 --> 00:19:30,045 is nice and adaptive up to a point, but beyond that 411 00:19:30,045 --> 00:19:33,091 i might mention that before we leave hypertrophy that this also goes on in other types of 412 00:19:33,091 --> 00:19:35,067 of muscle 413 00:19:35,067 --> 00:19:36,009 as you may 414 00:19:36,009 --> 00:19:40,043 know for instance, the wall of the urinary bladder is muscle but 415 00:19:40,043 --> 00:19:43,061 this kind of muscle is what we call smooth muscle 416 00:19:43,061 --> 00:19:46,051 but if there is a chronic obstruction to bladder outflow 417 00:19:46,051 --> 00:19:48,066 you get a very thick muscular bladder 418 00:19:48,066 --> 00:19:51,066 the same kind of response 419 00:19:51,066 --> 00:19:55,048 hypertrophy of the muscle cells 420 00:19:55,048 --> 00:19:57,077 we return to hyperplasia 421 00:19:57,077 --> 00:19:59,919 lots of examples i can give you 422 00:19:59,919 --> 00:20:00,044 of increased 423 00:20:00,044 --> 00:20:02,004 in 424 00:20:02,004 --> 00:20:02,098 the number of cells 425 00:20:02,098 --> 00:20:05,001 in the tissue 426 00:20:05,001 --> 00:20:07,096 and a nice example i think you've all been there 427 00:20:07,096 --> 00:20:09,012 one way or another 428 00:20:09,012 --> 00:20:11,015 there's a callus that forms 429 00:20:11,015 --> 00:20:13,001 in the skin 430 00:20:13,001 --> 00:20:14,059 if you have a 431 00:20:14,059 --> 00:20:17,016 ill-fitting pair of shoes and something is rubbing 432 00:20:17,016 --> 00:20:18,023 on the spot 433 00:20:18,023 --> 00:20:21,077 or God forbid if you have to do manual labor 434 00:20:21,077 --> 00:20:26,024 some concerted length of time 435 00:20:26,024 --> 00:20:29,659 you develop calluses. You've all had this happen. This is an example of 436 00:20:29,659 --> 00:20:31,062 hyperplasia 437 00:20:31,062 --> 00:20:33,023 It's a response to this overwork stimulus 438 00:20:33,023 --> 00:20:35,075 which increases 439 00:20:35,075 --> 00:20:40,046 or leads to an increase in number of cells in the system 440 00:20:40,046 --> 00:20:42,001 let me illustrate this 441 00:20:42,001 --> 00:20:44,079 give you a little histology 442 00:20:44,079 --> 00:20:47,082 this is basically normal skin 443 00:20:47,082 --> 00:20:49,011 on the palmar surface of the hand 444 00:20:49,011 --> 00:20:50,078 this is the dermis, the connective tissue part 445 00:20:50,078 --> 00:20:51,088 this is the 446 00:20:51,088 --> 00:20:56,038 epidermis, the epithelial portion 447 00:20:56,038 --> 00:20:58,065 now this is a renewing 448 00:20:58,065 --> 00:21:00,659 cell system 449 00:21:00,659 --> 00:21:01,025 normally 450 00:21:01,025 --> 00:21:06,023 a certain number of cells are mitosing down here in the basal layer 451 00:21:06,023 --> 00:21:08,086 and daughter cells are moving out and maturing 452 00:21:08,086 --> 00:21:13,007 as they move on out 453 00:21:13,007 --> 00:21:16,016 and this upper layer where you see no nuclei is the 454 00:21:16,016 --> 00:21:18,038 so-called stratum corneum 455 00:21:18,038 --> 00:21:20,003 it's like a layer of shingles on the roof 456 00:21:20,003 --> 00:21:23,064 these cells undergo progressive changes 457 00:21:23,064 --> 00:21:26,052 in armor plate there 458 00:21:26,052 --> 00:21:30,018 so the normal palmar skin is set with a certain cell population 459 00:21:30,018 --> 00:21:31,419 and a certain 460 00:21:31,419 --> 00:21:36,017 balance where certain cells come and go 461 00:21:36,017 --> 00:21:38,075 i'll show you the callus 462 00:21:38,075 --> 00:21:41,048 keep this picture in mind 463 00:21:41,048 --> 00:21:44,007 and this represents the hyperplasia of the callus 464 00:21:44,007 --> 00:21:47,000 now you've got 465 00:21:47,000 --> 00:21:49,009 a much thicker cell population 466 00:21:49,009 --> 00:21:51,057 it's still a very orderly cell population 467 00:21:51,057 --> 00:21:55,008 the cells are being born down here and are maturing up here 468 00:21:55,008 --> 00:21:56,055 there's actually 469 00:21:56,055 --> 00:21:58,095 so much thickening going on here that I couldn't 470 00:21:58,095 --> 00:22:00,032 get it all on one picture 471 00:22:00,032 --> 00:22:02,061 at the same magnification 472 00:22:02,061 --> 00:22:03,095 here is the beginning of the stratum 473 00:22:03,095 --> 00:22:05,006 corneum 474 00:22:05,006 --> 00:22:07,929 there's the rest of it 475 00:22:07,929 --> 00:22:10,077 and that is a callus 476 00:22:10,077 --> 00:22:12,022 So you see there is a tremendous 477 00:22:12,022 --> 00:22:16,031 hyperplasia here in response to this mechanical stimulus 478 00:22:16,031 --> 00:22:18,069 Now the nice thing 479 00:22:18,069 --> 00:22:25,001 about hyperplasia, and also applies to hypertrophy, if you get rid of 480 00:22:25,001 --> 00:22:28,007 the noxious stimulus, 481 00:22:28,007 --> 00:22:29,419 things pretty much 482 00:22:29,419 --> 00:22:32,074 wind back to normal. You can't always do that, but 483 00:22:32,074 --> 00:22:34,028 if you can, if you quit 484 00:22:34,028 --> 00:22:37,073 raking the ground or whatever you're doing, 485 00:22:37,073 --> 00:22:39,086 pretty soon those hands will be the ones you know and love. 486 00:22:39,086 --> 00:22:41,061 The calloused thins out 487 00:22:41,061 --> 00:22:45,069 and you go back to normal. Now 488 00:22:45,069 --> 00:22:46,081 I could give you 489 00:22:46,081 --> 00:22:52,017 other happier examples, maybe, I'll give you one. 490 00:22:52,017 --> 00:22:53,086 In a hormone sensitive 491 00:22:53,086 --> 00:22:55,071 tissue that responds 492 00:22:55,071 --> 00:22:58,034 that response with hyperplasia 493 00:22:58,034 --> 00:23:00,066 here is a normal 494 00:23:00,066 --> 00:23:03,041 lobule. This is kind of a potential 495 00:23:03,041 --> 00:23:04,095 secretory unit, 496 00:23:04,095 --> 00:23:07,076 a normal lobule of an adult female breast. 497 00:23:07,076 --> 00:23:08,098 I don't want to go into detail, but 498 00:23:08,098 --> 00:23:11,053 just to show you the little terminal 499 00:23:11,053 --> 00:23:15,013 units forming this lobule. During pregnancy 500 00:23:15,013 --> 00:23:16,799 and lactation, 501 00:23:16,799 --> 00:23:17,005 this tremendous 502 00:23:17,005 --> 00:23:19,094 hormonal stimulus to these cells 503 00:23:19,094 --> 00:23:20,096 makes them undergo 504 00:23:20,096 --> 00:23:22,033 hyperplasia 505 00:23:22,033 --> 00:23:23,419 and that lobule 506 00:23:23,419 --> 00:23:24,062 , take a look 507 00:23:24,062 --> 00:23:26,035 at the size there 508 00:23:26,035 --> 00:23:27,051 enlarged 509 00:23:27,051 --> 00:23:30,007 couldn't even get the whole lobule on the screen there 510 00:23:30,007 --> 00:23:33,002 This is a lactating mammary gland 511 00:23:33,002 --> 00:23:34,063 there's a tremendous 512 00:23:34,063 --> 00:23:38,012 increase in the number of cells, actually some hypertrophy 513 00:23:38,012 --> 00:23:40,044 in individual cells, but basically 514 00:23:40,044 --> 00:23:41,087 a whole lot of hyperplasia 515 00:23:41,087 --> 00:23:44,032 there, and it responds to 516 00:23:44,032 --> 00:23:46,071 the hormone. 517 00:23:46,071 --> 00:23:51,056 When the hormonal stimulus is withdrawn at the end of lactation, things pretty much 518 00:23:51,056 --> 00:23:55,002 go back to normal, plus or minus a little stretching of the connective tissue 519 00:23:55,002 --> 00:23:57,002 but the epithelial 520 00:23:57,002 --> 00:24:02,299 population goes back to normal. 521 00:24:02,299 --> 00:24:06,007 That's hyperplasia, tends to be reversible 522 00:24:06,007 --> 00:24:09,068 under very nice elegant control 523 00:24:09,068 --> 00:24:11,091 in some situations 524 00:24:11,091 --> 00:24:13,083 got to throw this in. Not all good news. 525 00:24:13,083 --> 00:24:15,093 In some situations, the hyperplasia 526 00:24:15,093 --> 00:24:17,038 527 00:24:17,038 --> 00:24:18,073 isn't necessarily 528 00:24:18,073 --> 00:24:22,053 adaptive and good. We see 529 00:24:22,053 --> 00:24:25,047 examples of hyperplasia, I'll show two of them. 530 00:24:25,047 --> 00:24:28,012 531 00:24:28,012 --> 00:24:29,062 They're probably responses 532 00:24:29,062 --> 00:24:34,075 to the subtly abnormal endocrine stimulation, somehow 533 00:24:34,075 --> 00:24:36,045 we don't exactly know. 534 00:24:36,045 --> 00:24:40,065 but, i think one for the guys, one for the girls 535 00:24:40,065 --> 00:24:43,062 this is something that is going to afflict about 536 00:24:43,062 --> 00:24:46,071 forty nine percent of us in the room, one way or the other. 537 00:24:46,071 --> 00:24:48,005 and this is 538 00:24:48,005 --> 00:24:50,084 a cross cut of the prostate 539 00:24:50,084 --> 00:24:51,065 and the 540 00:24:51,065 --> 00:24:54,035 prostate normally is about the size 541 00:24:54,035 --> 00:24:56,013 of a golf 542 00:24:56,013 --> 00:24:59,048 ball, a walnut, a good sized walnut 543 00:24:59,048 --> 00:25:00,082 and it's right at the base 544 00:25:00,082 --> 00:25:08,000 the bladder and the urethra. The outflow tract goes through the prostate. 545 00:25:08,000 --> 00:25:08,034 You're looking at a cross-section there 546 00:25:08,034 --> 00:25:10,046 and you see the urethra there. 547 00:25:10,046 --> 00:25:11,096 The normal prostate would be 548 00:25:11,096 --> 00:25:15,019 nice and smooth across the cut surface. 549 00:25:15,019 --> 00:25:15,095 Here you see 550 00:25:15,095 --> 00:25:21,001 a bunch of lumps and this represents 551 00:25:21,001 --> 00:25:23,004 hyperplasia of 552 00:25:23,004 --> 00:25:26,031 glandular and muscular tissue, glandular tissue undergoes tremendous hyperplasia. 553 00:25:26,031 --> 00:25:29,041 we don't know why, and the 554 00:25:29,041 --> 00:25:31,044 problem with 555 00:25:31,044 --> 00:25:33,059 is not simply walk around with a tennis ball 556 00:25:33,059 --> 00:25:39,018 there instead of a walnut, but it rests on the base of the bladder 557 00:25:39,018 --> 00:25:41,072 and urethra and can cause outflow problems. 558 00:25:41,072 --> 00:25:46,027 and also urinary tract problems. 559 00:25:46,027 --> 00:25:49,053 I'll give you a little tidbit that's absolutely useless. 560 00:25:49,053 --> 00:25:53,039 Eunuchs don't get prostatic hyperplasia, 561 00:25:53,039 --> 00:25:58,052 but it's not a very popular preventative measure. 562 00:25:58,052 --> 00:26:02,095 so there's an example, it's not a neoplasm, it's strictly hyperplasia, but it's out of 563 00:26:02,095 --> 00:26:05,039 kilter and not good. 564 00:26:05,039 --> 00:26:07,007 for 565 00:26:07,007 --> 00:26:07,096 the rest of you 566 00:26:07,096 --> 00:26:09,044 we'll talk about 567 00:26:09,044 --> 00:26:11,035 a very common condition 568 00:26:11,035 --> 00:26:13,078 called fibrocystic change in the breast 569 00:26:13,078 --> 00:26:15,029 now this is 570 00:26:15,029 --> 00:26:18,062 a non-descript looking piece of tissue 571 00:26:18,062 --> 00:26:19,047 but if it were perfectly normal 572 00:26:19,047 --> 00:26:20,094 mostly 573 00:26:20,094 --> 00:26:23,061 it would be a yellowish background 574 00:26:23,061 --> 00:26:25,062 because the breast is largely fatty tissue 575 00:26:25,062 --> 00:26:27,022 and not 576 00:26:27,022 --> 00:26:30,073 those big yawning things there. So what's happened in this breast 577 00:26:30,073 --> 00:26:34,028 it's, first of all, increase in fibroblast 578 00:26:34,028 --> 00:26:38,039 fibrous connective tissue, see these white streaks 579 00:26:38,039 --> 00:26:39,096 and this represents part of the duct system. 580 00:26:39,096 --> 00:26:42,000 where the cells increase in number 581 00:26:42,000 --> 00:26:44,559 and fluid is accumulated in 582 00:26:44,559 --> 00:26:45,095 what we call cysts, 583 00:26:45,095 --> 00:26:46,076 a cyst 584 00:26:46,076 --> 00:26:48,058 is a hollow space filled with fluid 585 00:26:48,058 --> 00:26:51,089 lined with epithelium 586 00:26:51,089 --> 00:26:54,076 and so we call this fibrocystic change. 587 00:26:54,076 --> 00:26:56,064 In and of itself, it's very 588 00:26:56,064 --> 00:27:00,016 common, in and of itself it's no big deal. 589 00:27:00,016 --> 00:27:01,052 I'll show you 590 00:27:01,052 --> 00:27:04,094 what happens conceptually, here again here's the 591 00:27:04,094 --> 00:27:09,029 normal breast, this is a lobule like I showed you before and this is 592 00:27:09,029 --> 00:27:15,046 part of the duct system leading to that lobule. That's normal. Now in a fibrocystic 593 00:27:15,046 --> 00:27:17,012 change, what you see 594 00:27:17,012 --> 00:27:17,045 is 595 00:27:17,045 --> 00:27:19,559 this little garbled 596 00:27:19,559 --> 00:27:20,097 Here's a lobule 597 00:27:20,097 --> 00:27:22,061 that has undergone 598 00:27:22,061 --> 00:27:26,097 hyperplasia, pretty evident 599 00:27:26,097 --> 00:27:28,559 and the duct system, the lining is also 600 00:27:28,559 --> 00:27:35,085 undergone hyperplasia, the ducts are dilating and eventually form cysts. 601 00:27:35,085 --> 00:27:38,047 and again we don't know exactly why 602 00:27:38,047 --> 00:27:43,025 this happens, but it represents hyperplasia 603 00:27:43,025 --> 00:27:48,058 gone wrong. 604 00:27:48,058 --> 00:27:59,037 All right, moving right along, what I'm doing is just ticking off these concepts. You can follow this in your reading too. 605 00:27:59,037 --> 00:28:09,037 I want to move on to proliferation and maturation of cells within a population. 606 00:28:09,037 --> 00:28:12,005 I'm talking about two particular situations here 607 00:28:12,005 --> 00:28:13,041 we'll talk first about 608 00:28:13,041 --> 00:28:17,077 metaplasia and then dysplasia. 609 00:28:17,077 --> 00:28:23,022 all right, what about metaplasia? We define this as 610 00:28:23,022 --> 00:28:30,091 a change in the cell population, in which one normal mature special 611 00:28:30,091 --> 00:28:34,071 cell, I'll clarify this in a moment, but one 612 00:28:34,071 --> 00:28:37,799 cell type is replaced by another 613 00:28:37,799 --> 00:28:39,019 normal cell type, 614 00:28:39,019 --> 00:28:41,007 except it doesn't belong 615 00:28:41,007 --> 00:28:43,096 there, in other words, it's changed 616 00:28:43,096 --> 00:28:52,063 that particular location. Now this isn't just a substitution, where this cell 617 00:28:52,063 --> 00:28:54,003 changes into another cell 618 00:28:54,003 --> 00:28:56,067 what this is, rather, 619 00:28:56,067 --> 00:29:02,057 is change in the maturation of stem cells in the population. We've got a proliferating cell population 620 00:29:02,057 --> 00:29:09,081 where ordinarily the cells mature in this direction, and metaplasia represents 621 00:29:09,081 --> 00:29:30,061 a switch, under some influence, where they mature in that direction. 622 00:29:30,061 --> 00:29:36,067 They become more resistant than the normal one and that represents metaplasia. 623 00:29:36,067 --> 00:29:40,809 Let me illustrate this, try to make sense out of it. 624 00:29:40,809 --> 00:29:43,056 Here is the lining 625 00:29:43,056 --> 00:29:45,022 of the 626 00:29:45,022 --> 00:29:46,017 what we call 627 00:29:46,017 --> 00:29:49,033 the endocervical canal 628 00:29:49,033 --> 00:29:54,539 this is the canal that goes up into the uterus. Now normally 629 00:29:54,539 --> 00:29:56,021 what's going on 630 00:29:56,021 --> 00:30:00,299 here is that there are certain number of, well, call them stem cells 631 00:30:00,299 --> 00:30:02,049 or reserved cells that are proliferating 632 00:30:02,049 --> 00:30:02,051 all the 633 00:30:02,051 --> 00:30:05,001 time, but they mature 634 00:30:05,001 --> 00:30:06,044 into these tall 635 00:30:06,044 --> 00:30:07,036 what we call columnar 636 00:30:07,036 --> 00:30:09,056 cells, they are 637 00:30:09,056 --> 00:30:11,091 tall and columnar and they've got 638 00:30:11,091 --> 00:30:15,083 very pale cytoplasm because they're full of mucus. 639 00:30:15,083 --> 00:30:22,001 So normally this endocervical canal is lined by this mucus secreting epithelium, very 640 00:30:22,001 --> 00:30:23,029 slight stimulus 641 00:30:23,029 --> 00:30:24,065 is all it takes 642 00:30:24,065 --> 00:30:26,019 and there may be a change 643 00:30:26,019 --> 00:30:29,001 here you see the normal, here you see a plaque 644 00:30:29,001 --> 00:30:31,149 of cells that looks a little bit different 645 00:30:31,149 --> 00:30:33,088 and these cells 646 00:30:33,088 --> 00:30:35,018 are, well, they're 647 00:30:35,018 --> 00:30:39,049 odd shapes here, they're maturing into these 648 00:30:39,049 --> 00:30:43,007 flat cells that we saw on top of the epidermis, and we call this 649 00:30:43,007 --> 00:30:44,047 these are columnar 650 00:30:44,047 --> 00:30:47,098 cells, these are squamous cells, we call this squamous 651 00:30:47,098 --> 00:30:48,079 metaplasia 652 00:30:48,079 --> 00:30:51,026 very very 653 00:30:51,026 --> 00:30:52,759 common, some of you 654 00:30:52,759 --> 00:30:54,539 in this room have this, it's a trivial change 655 00:30:54,539 --> 00:30:56,023 practically 656 00:30:56,023 --> 00:31:00,017 ubiquitous in the adult females in the 657 00:31:00,017 --> 00:31:01,068 endocervix 658 00:31:01,068 --> 00:31:06,039 it can become quite extreme. Look at this. 659 00:31:06,039 --> 00:31:14,086 this whole area should be lined by these columnar cells that look this, and instead what we've got here is squamous 660 00:31:14,086 --> 00:31:20,033 epithelium, looks a lot like the epidermis, doesn't it? 661 00:31:20,033 --> 00:31:24,015 I would emphasize a couple things 662 00:31:24,015 --> 00:31:27,073 this is perfectly orderly, you look at this 663 00:31:27,073 --> 00:31:32,024 and I know you haven't become histologic experts yet 664 00:31:32,024 --> 00:31:33,008 but that is a perfectly orderly 665 00:31:33,008 --> 00:31:37,149 squamous epithelium, nothing unusual about it except 666 00:31:37,149 --> 00:31:38,097 it doesn't belong there. 667 00:31:38,097 --> 00:31:41,031 So that's an example 668 00:31:41,031 --> 00:31:43,034 of metaplasia 669 00:31:43,034 --> 00:31:44,159 in and of itself 670 00:31:44,159 --> 00:31:45,089 trivial 671 00:31:45,089 --> 00:31:47,042 or even protective. 672 00:31:47,042 --> 00:31:49,019 Let's say 673 00:31:49,019 --> 00:31:52,084 chemical workers were exposed to fumes might develop 674 00:31:52,084 --> 00:31:53,006 this kind of 675 00:31:53,006 --> 00:31:59,033 metaplasia in the lining of their trachea and bronchi, that makes them more resistant to whatever they're 676 00:31:59,033 --> 00:32:02,007 inhaling, smokers develop 677 00:32:02,007 --> 00:32:03,078 this sort of thing. Now, this could go on 678 00:32:03,078 --> 00:32:05,047 and something 679 00:32:05,047 --> 00:32:07,072 else might happen, and this might 680 00:32:07,072 --> 00:32:09,012 lead to bad 681 00:32:09,012 --> 00:32:10,071 things, but 682 00:32:10,071 --> 00:32:12,073 in and of itself, metaplasia 683 00:32:12,073 --> 00:32:14,061 is perfectly innocent. 684 00:32:14,061 --> 00:32:16,003 Not so 685 00:32:16,003 --> 00:32:17,061 with dysplasia. 686 00:32:17,061 --> 00:32:19,054 D-y-s-p-l-a-s-i-a 687 00:32:19,054 --> 00:32:23,079 Now morphologically, 688 00:32:23,079 --> 00:32:42,096 dysplasia is a 689 00:32:42,096 --> 00:32:45,062 variation, abnormal variation 690 00:32:45,062 --> 00:32:48,055 in 691 00:32:48,055 --> 00:32:50,006 the size 692 00:32:50,006 --> 00:32:51,006 of the cells, the shape of the cells 693 00:32:51,006 --> 00:32:53,093 the arrangement of the 694 00:32:53,093 --> 00:32:54,058 cells 695 00:32:54,058 --> 00:32:57,022 and the maturation of the cells 696 00:32:57,022 --> 00:32:59,041 too much variation 697 00:32:59,041 --> 00:33:01,009 in other words 698 00:33:01,009 --> 00:33:04,034 something very well controlled like this 699 00:33:04,034 --> 00:33:06,057 this epithelium is very well controlled 700 00:33:06,057 --> 00:33:08,008 with all the cells down here proliferating 701 00:33:08,008 --> 00:33:10,062 at a certain rate and maturing gradually 702 00:33:10,062 --> 00:33:12,002 and so forth 703 00:33:12,002 --> 00:33:19,025 all of this gets screwed up in dysplasia. 704 00:33:19,025 --> 00:33:21,029 Here again is a normal squamous 705 00:33:21,029 --> 00:33:23,028 epithelium, this isn't palmar 706 00:33:23,028 --> 00:33:28,021 or skin now, this is let's say the lining of the vagina or 707 00:33:28,021 --> 00:33:32,025 covering of the cervix, one of those, this happens to be cervix 708 00:33:32,025 --> 00:33:35,034 perfectly normal squamous epithelium, notice how orderly 709 00:33:35,034 --> 00:33:36,085 it is, it's like a 710 00:33:36,085 --> 00:33:37,084 kind of like 711 00:33:37,084 --> 00:33:41,059 a parade where you have cells in 712 00:33:41,059 --> 00:33:44,006 a certain type down here, they all resemble one another 713 00:33:44,006 --> 00:33:46,034 in this layer, cells here 714 00:33:46,034 --> 00:33:49,094 resemble one another, and then there's this maturation 715 00:33:49,094 --> 00:33:53,046 these flattened out cells, that's occurring in a very orderly 716 00:33:53,046 --> 00:33:57,086 step fashion. In dysplasia 717 00:33:57,086 --> 00:34:00,098 of the epithelium, everything gets 718 00:34:00,098 --> 00:34:08,409 screwed up. All right, 719 00:34:08,409 --> 00:34:10,329 this is dysplasia. 720 00:34:10,329 --> 00:34:14,379 and we can see where 721 00:34:14,379 --> 00:34:18,619 there's a shadow of what you looked at in the preceding slide, but now some things have 722 00:34:18,619 --> 00:34:20,069 happened, there's more 723 00:34:20,069 --> 00:34:22,829 variation in any 724 00:34:22,829 --> 00:34:23,079 layer. In other words, 725 00:34:23,079 --> 00:34:24,049 726 00:34:24,049 --> 00:34:29,219 if you look down here, these cells are more variable than those cells were in the basal layer 727 00:34:29,219 --> 00:34:31,359 in the normal. You look here 728 00:34:31,359 --> 00:34:33,339 where in the 729 00:34:33,339 --> 00:34:36,949 preceding slide, every cell in the intermediate zone is perfectly 730 00:34:36,949 --> 00:34:38,979 like every other cell, there's variation 731 00:34:38,979 --> 00:34:43,419 here, there's big cells and small cells, round cells and elongated cells 732 00:34:43,419 --> 00:34:45,009 cells with 733 00:34:45,009 --> 00:34:48,639 very dark nuclei, cells with lighter nuclei 734 00:34:48,639 --> 00:34:50,949 and so forth 735 00:34:50,949 --> 00:34:51,078 and gradually, though, despite 736 00:34:51,078 --> 00:34:53,539 this mess, there is 737 00:34:53,539 --> 00:34:54,999 slight 738 00:34:54,999 --> 00:34:56,009 maturation 739 00:34:56,009 --> 00:35:01,959 you can see here how this jumble of cells gradually becomes organized 740 00:35:01,959 --> 00:35:04,689 up here, so what have we got 741 00:35:04,689 --> 00:35:07,079 we've got abnormal 742 00:35:07,079 --> 00:35:07,939 variations 743 00:35:07,939 --> 00:35:11,579 in the size of the cells, the shape of the cells, the arrangement 744 00:35:11,579 --> 00:35:15,709 of the cells, this is out of order. It's not in a nice, neat, locked set. 745 00:35:15,709 --> 00:35:16,098 And it's not 746 00:35:16,098 --> 00:35:21,219 maturing quite properly until it gets to the very top. 747 00:35:21,219 --> 00:35:23,439 Actually, 748 00:35:23,439 --> 00:35:28,799 this is trivial for you now, but we grade dysplasia as slight, moderate, severe depending on how much 749 00:35:28,799 --> 00:35:30,369 normal 750 00:35:30,369 --> 00:35:32,809 there might be there. But when you see 751 00:35:32,809 --> 00:35:36,269 this degree of variation, that's a very 752 00:35:36,269 --> 00:35:39,019 bad thing. There's one other thing 753 00:35:39,019 --> 00:35:42,499 that's abnormal here, it's a little more subtle, ordinarily 754 00:35:42,499 --> 00:35:44,969 mitosis occurs only down in this 755 00:35:44,969 --> 00:35:47,064 basal layer. But these cells 756 00:35:47,064 --> 00:35:51,519 are goofy enough that they forget about that and they do something very impolite. 757 00:35:51,519 --> 00:35:53,489 They reproduce out 758 00:35:53,489 --> 00:35:59,039 in public and you find mitotic figures at all levels of such an epithelium. 759 00:35:59,039 --> 00:36:00,799 So morphologically, 760 00:36:00,799 --> 00:36:07,379 this represents a lot of variation. 761 00:36:07,379 --> 00:36:13,959 This is a serious change because these cells 762 00:36:13,959 --> 00:36:26,749 are in a sense losing control. They're losing control of proliferation and maturation. 763 00:36:26,749 --> 00:36:28,067 Any number of mutations 764 00:36:28,067 --> 00:36:38,809 that occur in the cell population, this reflects genetic change in the cell, somatic cell 765 00:36:38,809 --> 00:36:56,069 any number of these mutations and this happens. This I want you to remember for the rest of your lives, dysplasia 766 00:36:56,069 --> 00:36:58,419 in other words, I can't tell you 767 00:36:58,419 --> 00:37:12,729 that epithelium absolutely for sure will become cancer, it depends I suppose on the last garbled 768 00:37:12,729 --> 00:37:38,109 mild degree of dysplasia sometimes don't necessarily progress, while very severe degrees of dysplasia can. 769 00:37:38,109 --> 00:37:39,041 Here is a squamous epithelium 770 00:37:39,041 --> 00:37:40,889 with what we call severe 771 00:37:40,889 --> 00:37:42,859 dysplasia, and you can see close 772 00:37:42,859 --> 00:37:45,139 up what's going on here 773 00:37:45,139 --> 00:37:48,579 This basal layer is increased in thickness, a lot of variation 774 00:37:48,579 --> 00:37:49,489 in these cells, 775 00:37:49,489 --> 00:37:51,299 here is 776 00:37:51,299 --> 00:37:56,049 a cell dividing, as they say, out in public and there is an absolute total 777 00:37:56,049 --> 00:37:57,859 jumble 778 00:37:57,859 --> 00:38:01,379 in terms of how these cells are arranged with respect to one another. 779 00:38:01,379 --> 00:38:03,094 We call that a loss of polarity. 780 00:38:03,094 --> 00:38:05,309 And in this instance 781 00:38:05,309 --> 00:38:16,249 it occurred all the way, full thickness of this epithelium. 782 00:38:16,249 --> 00:38:20,149 and we now know, from a lot of experience, severe dysplasia 783 00:38:20,149 --> 00:38:22,089 really is 784 00:38:22,089 --> 00:38:23,989 tantamount to cancer 785 00:38:23,989 --> 00:38:27,029 that perhaps hasn't 786 00:38:27,029 --> 00:38:28,007 yet invaded. Now that'll 787 00:38:28,007 --> 00:38:34,459 make sense when we talk about what cancer really is. Without 788 00:38:34,459 --> 00:38:40,179 any evidence of invasion or anything else that cancers usually do 789 00:38:40,179 --> 00:38:43,849 when dysplasia is this severe, we can say this is like carcinoma-in-situ 790 00:38:43,849 --> 00:38:46,599 which means an 'in-place' cancer 791 00:38:46,599 --> 00:38:48,239 pre-invasive 792 00:38:48,239 --> 00:38:51,069 cancer because we know 793 00:38:51,069 --> 00:38:51,809 if this sort of 794 00:38:51,809 --> 00:38:54,649 dysplasia is left alone, probably close 795 00:38:54,649 --> 00:38:56,229 to 100% will 796 00:38:56,229 --> 00:39:02,048 evolve into a cancer if the patient lives long enough. 797 00:39:02,048 --> 00:39:07,609 While I've got this on the screen, I'll point out some cytologic changes that are very important in making 798 00:39:07,609 --> 00:39:09,019 this decision. First of all 799 00:39:09,019 --> 00:39:09,098 you'll notice 800 00:39:09,098 --> 00:39:13,009 there's a lot of variation in size of nuclei. We call that 801 00:39:13,009 --> 00:39:15,209 nuclear pleomorphism. 802 00:39:15,209 --> 00:39:16,469 p-l-e-o 803 00:39:16,469 --> 00:39:18,769 that's a bad sign 804 00:39:18,769 --> 00:39:19,539 and none of these 805 00:39:19,539 --> 00:39:23,339 is absolute, but it's a bad sign. 806 00:39:23,339 --> 00:39:28,669 Some of the nuclei are very dark as you cast your eye around here. 807 00:39:28,669 --> 00:39:32,889 We would call that nuclear hyperchromatism. Too much 808 00:39:32,889 --> 00:39:36,749 colored material in the nucleus. 809 00:39:36,749 --> 00:39:37,119 The nuclei 810 00:39:37,119 --> 00:39:43,759 are very unusually shaped and sometimes 811 00:39:43,759 --> 00:39:44,989 you can't see it, but 812 00:39:44,989 --> 00:39:47,959 sometimes the mitotic figures are themselves 813 00:39:47,959 --> 00:39:51,319 are even abnormal, may see a tripolar mitotic figure 814 00:39:51,319 --> 00:39:53,269 or something like that. 815 00:39:53,269 --> 00:40:01,579 These are all signs of badness in a cell population. 816 00:40:01,579 --> 00:40:13,319 If something like this is left alone, it will proceed to an invasive cancer. Instead of carcinoma-in-situ, we call it invasive. 817 00:40:13,319 --> 00:40:18,039 Put a line underneath all of this and now we turn to the main topic -- Neoplasia. 818 00:40:18,039 --> 00:40:47,559 Spend the rest of this morning and Wednesday morning on this topic. It's ultimately 819 00:40:47,559 --> 00:40:49,339 more cells than there ought to be, it's an increase in cells 820 00:40:49,339 --> 00:40:52,189 it's a lump basically 821 00:40:52,189 --> 00:40:56,219 and these are proliferating cells, they're not just sitting there, they're 822 00:40:56,219 --> 00:41:01,799 they're dividing and making new cells. And, they're cells that have somehow 823 00:41:01,799 --> 00:41:23,219 become autonomous 824 00:41:23,219 --> 00:41:25,279 they don't obey the same start and stop signals 825 00:41:25,279 --> 00:41:28,159 that normal cells do. Their growth 826 00:41:28,159 --> 00:41:34,329 tends to be excessive and uncoordinated with the needs of the host. 827 00:41:34,329 --> 00:41:37,229 In other words, this thing is taking off on its own! 828 00:41:37,229 --> 00:41:45,899 It's kind of rebellious, I'm going to grow, I don't give a damn about what's going on over here, I'm not going to listen to your signals. 829 00:41:45,899 --> 00:41:59,729 You want to think teleologically, serves no useful purpose, it's not adaptive. 830 00:41:59,729 --> 00:42:04,459 Once the neoplasm is formed, it's off and running, 831 00:42:04,459 --> 00:42:22,849 which is different from hypertrophy and hyperplasia, where once you remove the stimulus, it goes back to normal. 832 00:42:22,849 --> 00:42:31,289 In some countries, it's the word tumor, which now is practically synonymous with neoplasm. 833 00:42:31,289 --> 00:42:38,039 It's also one of the cardinal signs of inflammation, the old meaning of tumor simply means swelling. But 834 00:42:38,039 --> 00:42:48,849 when you say a patient has a tumor, you don't mean swelling, you mean neoplasm. So tumor, neoplasm, same thing. 835 00:42:48,849 --> 00:43:04,092 'oma' usually denotes a neoplasm of some sort, there are exceptions, hematoma is a lump of blood. 836 00:43:04,092 --> 00:43:07,769 Different types of neoplasms are distinguished by their behavior, 837 00:43:07,769 --> 00:43:21,359 which, I think you all know, is benign and malignant. Cancer is a general term which refers only to malignant neoplasms. I don't want to insult you, but 838 00:43:21,359 --> 00:43:30,709 just so we're on the same page, there are many neoplasms that are not cancer. Only the malignant ones we refer to as cancer. 839 00:43:30,709 --> 00:43:51,016 Looking at all of these characteristics, they are very different from hyperplasia and hypertrophy, which are generally adaptive. 840 00:43:51,016 --> 00:44:20,279 A neoplasm is a living, proliferating cell and 841 00:44:20,279 --> 00:44:27,129 we call this neoplastic transformation, basically, and when speaking of transformed cells, we speak of cells that have acquired 842 00:44:27,129 --> 00:44:30,479 a set of these new characteristics 843 00:44:30,479 --> 00:44:45,017 that define them as neoplastic and, as you will hear, usually 844 00:44:45,017 --> 00:44:48,079 the wrong mutations. We talk about the clonal origin 845 00:44:48,079 --> 00:45:00,299 of neoplasms, in other words, a neoplasm is a clonal proliferation of a transformed cell. 846 00:45:00,299 --> 00:45:03,889 This transformed cell has a lot of characteristics 847 00:45:03,889 --> 00:45:11,499 and behaviors that are quite abnormal and we can see this in vitro when we culture it. 848 00:45:11,499 --> 00:45:13,699 Malignant cells, for instance, 849 00:45:13,699 --> 00:45:31,939 they've often lost control of movement that they display on the surface of a plate. There's 850 00:45:31,939 --> 00:45:55,429 loss of, ordinarily there's control in a cell population where proliferation reaches a certain size, not so with cancer cells. I could go on, there are many different things that occur 851 00:45:55,429 --> 00:46:11,449 in vitro and in vivo, in the host, it manifests a non-equilibrium growth, at some point, and keeps on growing. 852 00:46:11,449 --> 00:46:28,679 You will learn that 853 00:46:28,679 --> 00:46:42,149 there's a difference between benign and malignant. I think this cartoon sums it up well. 854 00:46:42,149 --> 00:46:52,579 As the neoplasm grows, the number of cells gradually increases, they tend to be cohesive 855 00:46:52,579 --> 00:46:58,004 there's not any reason for this, just they tend to be cohesive, so as the neoplasm 856 00:46:58,004 --> 00:47:00,639 grows, and it may grow to a very large 857 00:47:00,639 --> 00:47:02,489 size, it tends to grow 858 00:47:02,489 --> 00:47:07,549 by a centrifugal expansion. Now it's not a perfect circle, but 859 00:47:07,549 --> 00:47:13,039 it tends to grow by expansion. As it expands, 860 00:47:13,039 --> 00:47:14,909 it frequently will pick up 861 00:47:14,909 --> 00:47:15,499 a 862 00:47:15,499 --> 00:47:18,078 condensed capsule of connective tissue as it pushes out 863 00:47:18,078 --> 00:47:20,169 causes atrophy of surrounding tissues 864 00:47:20,169 --> 00:47:25,579 and will accumulate a kind of capsule almost and anyway 865 00:47:25,579 --> 00:47:26,219 at any rate 866 00:47:26,219 --> 00:47:32,719 it stays local, its size, and it doesn't invade 867 00:47:32,719 --> 00:47:38,038 adjacent tissues, just pushes them out of the way, or it may press up, but it's like blowing up a 868 00:47:38,038 --> 00:48:04,479 balloon in the thing. On the average, 869 00:48:04,479 --> 00:48:07,029 this is not as cohesive as this suggests 870 00:48:07,029 --> 00:48:11,619 it grows, the cells have a great tendency of invading 871 00:48:11,619 --> 00:48:12,829 what we call the primary, 872 00:48:12,829 --> 00:48:16,659 they tend to drift 873 00:48:16,659 --> 00:48:20,939 away and don't obey the stop and start signals. 874 00:48:20,939 --> 00:48:22,046 They have a very different relationship 875 00:48:22,046 --> 00:48:25,091 with the cellular matrix and basically 876 00:48:25,091 --> 00:48:27,039 they have 877 00:48:27,039 --> 00:48:32,909 the ability, this is the primary difference, to cut their way 878 00:48:32,909 --> 00:48:35,519 through 879 00:48:35,519 --> 00:48:36,066 the adjacent stroma 880 00:48:36,066 --> 00:48:39,519 and actually invade as clumps of cells, 881 00:48:39,519 --> 00:48:43,069 lines of cells, individual cells, 882 00:48:43,069 --> 00:48:44,349 Invasion is one 883 00:48:44,349 --> 00:48:47,042 of the defining 884 00:48:47,042 --> 00:48:55,289 characteristics of malignancy. When I said the malignant ones tend to grow faster than benign ones, that's not a defining difference. 885 00:48:55,289 --> 00:49:03,709 They have to be invasive to be malignant. 886 00:49:03,709 --> 00:49:05,075 One other, well this sums it up, 887 00:49:05,075 --> 00:49:08,519 cohesive, expansile, circumscribed, localized 888 00:49:08,519 --> 00:49:13,119 that's benign. Malignant is poorly circumscribed, invasive, metastasizing. 889 00:49:13,119 --> 00:49:13,659 That means 890 00:49:13,659 --> 00:49:21,099 it can spread to distant foci, we'll talk about that in just a moment. But it's invasion 891 00:49:21,099 --> 00:49:32,399 and metastasis that define malignancy. Benign neoplasms do not metastasize. 892 00:49:32,399 --> 00:49:37,579 Here's a uterus 893 00:49:37,579 --> 00:49:41,429 cut sort of in 894 00:49:41,429 --> 00:49:43,769 sagittal sections, this is the cervix 895 00:49:43,769 --> 00:49:47,013 down here, this is a normal one half 896 00:49:47,013 --> 00:49:48,919 this is the cavity here, here is a 897 00:49:48,919 --> 00:49:52,729 neoplasm. 898 00:49:52,729 --> 00:49:57,379 Benign or malignant? See, it works. 899 00:49:57,379 --> 00:49:58,031 This is what you 900 00:49:58,031 --> 00:49:59,619 probably grew up hearing, a fibroid. 901 00:49:59,619 --> 00:50:01,088 Uterine fibroid. 902 00:50:01,088 --> 00:50:04,809 That's a misnomer, because it isn't 903 00:50:04,809 --> 00:50:08,779 a fibrous tumor, it's a muscular tumor 904 00:50:08,779 --> 00:50:10,459 one we call a leiomyoma. 905 00:50:10,459 --> 00:50:13,629 But you can see it's got, just like the cartoon, pushing at the edges. 906 00:50:13,629 --> 00:50:15,719 You look at that microscopically, 907 00:50:15,719 --> 00:50:16,619 same sort of thing 908 00:50:16,619 --> 00:50:18,159 here's a 909 00:50:18,159 --> 00:50:20,059 tumor, here's the 910 00:50:20,059 --> 00:50:24,179 edge along here, no invasion. 911 00:50:24,179 --> 00:50:28,089 Can see it just pushing, pressing along that adjacent line. 912 00:50:28,089 --> 00:50:31,329 Here's a breast 913 00:50:31,329 --> 00:50:32,989 that's been 914 00:50:32,989 --> 00:50:33,819 taken off 915 00:50:33,819 --> 00:50:37,549 a mastectomy specimen and it's been cut in this plane, 916 00:50:37,549 --> 00:50:39,539 a section where you can see 917 00:50:39,539 --> 00:50:41,669 the skin out here, and this is the neoplasm 918 00:50:41,669 --> 00:50:43,039 very very hard 919 00:50:43,039 --> 00:50:45,008 to define and circumscribe. 920 00:50:45,008 --> 00:50:47,209 It's going out in little 921 00:50:47,209 --> 00:50:48,669 sites in the adjacent 922 00:50:48,669 --> 00:50:49,589 tissue, even 923 00:50:49,589 --> 00:50:51,051 way beyond this microscopically 924 00:50:51,051 --> 00:50:54,013 there are lines of cells that you couldn't see here. 925 00:50:54,013 --> 00:50:57,229 That's invasion. A benign neoplasm 926 00:50:57,229 --> 00:50:59,559 wouldn't look like that. 927 00:50:59,559 --> 00:51:01,419 Here's one that's a little deceptive at first. 928 00:51:01,419 --> 00:51:02,004 This is a colon cancer, 929 00:51:02,004 --> 00:51:06,009 we've opened the colon and washed it off. You might 930 00:51:06,009 --> 00:51:08,519 say, at first, gee that's circumscribed, 931 00:51:08,519 --> 00:51:10,989 isn't it? Well, not exactly. 932 00:51:10,989 --> 00:51:13,179 What I did here is 933 00:51:13,179 --> 00:51:14,093 fix this in formaldehyde 934 00:51:14,093 --> 00:51:17,539 and then made a cut 935 00:51:17,539 --> 00:51:21,069 across it, and it looks like 936 00:51:21,069 --> 00:51:23,269 this. Now this doesn't look so 937 00:51:23,269 --> 00:51:25,599 awful, but it really is. 938 00:51:25,599 --> 00:51:30,067 Here's the normal mucous membrane up here, this layer we call sub-mucosa, 939 00:51:30,067 --> 00:51:33,569 this is the muscular wall of the colon here. 940 00:51:33,569 --> 00:51:36,509 Here is that mushroom 941 00:51:36,509 --> 00:51:39,679 and you can see this whitish tissue, this is neoplasm, invade 942 00:51:39,679 --> 00:51:41,349 all the way through that muscular layer. 943 00:51:41,349 --> 00:51:44,729 This is invasion. 944 00:51:44,729 --> 00:51:49,919 This is what it looks 945 00:51:49,919 --> 00:51:52,639 like microscopically, don't worry about this. 946 00:51:52,639 --> 00:51:55,269 duct cells, hyperchromatic, pleomorphic nuclei, 947 00:51:55,269 --> 00:51:58,529 and so forth. 948 00:51:58,529 --> 00:52:03,459 These cancer cells are cutting right through the colonic wall, it's not that simple, 949 00:52:03,459 --> 00:52:05,579 but they're cutting right through that colonic wall 950 00:52:05,579 --> 00:52:08,729 and invading. That constitutes 951 00:52:08,729 --> 00:52:13,015 the evidence 952 00:52:13,015 --> 00:52:18,369 that this is a malignant neoplasm. 953 00:52:18,369 --> 99:59:59,999 Let's take a break.