1 00:00:05,933 --> 00:00:12,299 >> WELL, WELCOME. 2 00:00:12,299 --> 00:00:15,569 I'M PLEASED TO INTRODUCE YOU TO 3 00:00:15,569 --> 00:00:20,073 ELAINE JAFFE AN INVESTIGATOR AT 4 00:00:20,073 --> 00:00:22,709 THE NATIONAL CANCER INSTITUTE 5 00:00:22,709 --> 00:00:28,816 AND COMPLETED HER TRAINING AT 6 00:00:28,816 --> 00:00:35,889 U-PENN AND WAS AN EDITOR FOR 7 00:00:35,889 --> 00:00:37,658 W.H.O. CLASSIFICATION OF TUMORS 8 00:00:37,658 --> 00:00:40,060 OF LYMPHOID MALIGNANCIES AND WAS 9 00:00:40,060 --> 00:00:43,931 NAMED ONE OF THE MOST HIGHLY 10 00:00:43,931 --> 00:00:46,633 CITED RESEARCHERS IN CLINICAL 11 00:00:46,633 --> 00:00:52,139 ONCOLOGY AND AMONG THE TOP 400 12 00:00:52,139 --> 00:00:55,209 CITED RESEARCHERS. 13 00:00:55,209 --> 00:00:57,544 SHE'S HAD ACHIEVEMENTS IN THE 14 00:00:57,544 --> 00:00:59,046 AMERICAN SOCIETY OF HEMATOLOGY 15 00:00:59,046 --> 00:01:01,248 AND PRESIDENT FOR THE UNITED 16 00:01:01,248 --> 00:01:05,018 STATES AND CANADA ACADEMY OF 17 00:01:05,018 --> 00:01:09,456 PATHOLOGY AND THE SOCIETY FOR 18 00:01:09,456 --> 00:01:09,823 HEMATOPATHOLOGY. 19 00:01:09,823 --> 00:01:13,460 IN 2008 SHE WAS ELECTED TO WHAT 20 00:01:13,460 --> 00:01:14,728 IS NOW KNOWN AS THE NATIONAL 21 00:01:14,728 --> 00:01:17,064 ACADEMY OF MEDICINE. 22 00:01:17,064 --> 00:01:20,400 SHE'S HAD MANY OTHER PRESTIGIOUS 23 00:01:20,400 --> 00:01:24,137 AWARDS INCLUDING THE 24 00:01:24,137 --> 00:01:28,909 DISTINGUISHED PATHOLOGY AWARD IN 25 00:01:28,909 --> 00:01:33,747 2009 AND IN THE INAUGURAL AWARD 26 00:01:33,747 --> 00:01:37,584 FOR OUTSTANDING ACHIEVEMENT IN 27 00:01:37,584 --> 00:01:38,318 PATHOLOGY IN CANCER RESEARCH 28 00:01:38,318 --> 00:01:43,624 FROM AACR AND IN 2023 FROM FASB 29 00:01:43,624 --> 00:01:44,791 RECOGNIZED WITH A LIFE TIME 30 00:01:44,791 --> 00:01:45,459 ACHIEVEMENT AWARD. 31 00:01:45,459 --> 00:01:48,829 I HAVE TO SAY I DID MY CLINICAL 32 00:01:48,829 --> 00:01:50,597 TRAINING HERE AS A MEDICAL 33 00:01:50,597 --> 00:01:55,002 ONCOLOGY FELLOW AND MANY TIMES I 34 00:01:55,002 --> 00:01:59,373 WOULD SIT DOWN WITH THE LYMPHOMA 35 00:01:59,373 --> 00:02:02,075 TEAM AND DR. JAFFE AND SHOW US 36 00:02:02,075 --> 00:02:03,777 UNDER THE MICROSCOPE ON WHY THIS 37 00:02:03,777 --> 00:02:07,114 WAS A GIVEN LYMPHOMA. 38 00:02:07,114 --> 00:02:08,482 SHE'LL TALK ABOUT THE MICROSCOPE 39 00:02:08,482 --> 00:02:09,983 AS A TOOL FOR DISEASE DISCOVERY. 40 00:02:09,983 --> 00:02:18,859 ELAINE, THANK YOU. 41 00:02:18,859 --> 00:02:24,431 >> THE CODE IS 57678 FOR THOSE 42 00:02:24,431 --> 00:02:30,170 LISTENING. 43 00:02:30,170 --> 00:02:30,370 57678. 44 00:02:30,370 --> 00:02:30,804 YOU'RE ON. 45 00:02:30,804 --> 00:02:32,639 >> TODAY I'LL TRY TO CONVINCE 46 00:02:32,639 --> 00:02:36,376 YOU THE MICROSCOPE IS NOT AN 47 00:02:36,376 --> 00:02:37,511 OBSOLETE PIECE OF EQUIPMENT IN 48 00:02:37,511 --> 00:02:40,013 THE LABORATORY BUT STILL HAS A 49 00:02:40,013 --> 00:02:43,784 ROLE IN DISEASE DISCOVERY. 50 00:02:43,784 --> 00:02:47,788 SO WHY DO WE CLASSIFY TUMORS? 51 00:02:47,788 --> 00:02:51,825 WELL, WE CLASSIFY TO DELINEATE 52 00:02:51,825 --> 00:02:52,659 DISEASE ENTITIES. 53 00:02:52,659 --> 00:02:54,328 I'M GOING DISEASE DEFINITION IS 54 00:02:54,328 --> 00:02:55,295 ESSENTIAL FOR ONGOING STUDIES OF 55 00:02:55,295 --> 00:02:59,666 PATHOGENESIS. 56 00:02:59,666 --> 00:03:07,908 COMPARISON OF CLINICAL TRIALS, 57 00:03:07,908 --> 00:03:09,242 EPIDEMIOLOGICAL STUDIES AND THE 58 00:03:09,242 --> 00:03:16,049 CORRECT THERAPY OF THE 59 00:03:16,049 --> 00:03:17,718 INDIVIDUAL PATIENT. 60 00:03:17,718 --> 00:03:22,422 WILL THE FATHER OF SURGICAL 61 00:03:22,422 --> 00:03:23,724 PSYCHOLOGY COINED TERMS MORE 62 00:03:23,724 --> 00:03:26,026 THAN 100 YEARS AGO. 63 00:03:26,026 --> 00:03:29,229 WE HAVE OTHER TOOLS TO DIAGNOSE 64 00:03:29,229 --> 00:03:30,731 DISEASE BUT THE MICROSCOPE STILL 65 00:03:30,731 --> 00:03:36,236 HAS AN IMPORTANT PLACE IN THE 66 00:03:36,236 --> 00:03:37,671 MEDICAL ARMAMENTARIUM. 67 00:03:37,671 --> 00:03:41,408 WHEN I STARTED IN PATHOLOGY WE 68 00:03:41,408 --> 00:03:43,443 USED THE RAPPAPORT SYSTEM OF 69 00:03:43,443 --> 00:03:45,946 LYMPHOMA CLASSIFICATION. 70 00:03:45,946 --> 00:03:50,250 IT WAS A PRETTY PRIMITIVE 71 00:03:50,250 --> 00:03:50,517 APPROACH. 72 00:03:50,517 --> 00:03:54,588 THEY WERE BASED ON CELL SIZE 73 00:03:54,588 --> 00:03:58,125 WITH HISTOCYTES BEING LARGE. 74 00:03:58,125 --> 00:04:01,895 THIS WAS NOT BIO LOGICALLY 75 00:04:01,895 --> 00:04:05,732 CORRECT AND ALSO CLAIMED MOST 76 00:04:05,732 --> 00:04:16,243 LYMPHOMAS COULD NODULEAR AND 77 00:04:21,715 --> 00:04:23,016 CAREFUL STUDIES WERE STARTED OF 78 00:04:23,016 --> 00:04:27,988 THE LYMPHOID SYSTEM UNDER THE 79 00:04:27,988 --> 00:04:28,288 MICROSCOPE. 80 00:04:28,288 --> 00:04:30,791 IN THE EXEMPTION OF GERMINAL 81 00:04:30,791 --> 00:04:34,094 CENTERS HE CHARACTERIZED THE 82 00:04:34,094 --> 00:04:37,664 CELL TYPES AND DESCRIBED 83 00:04:37,664 --> 00:04:41,601 CENTROBLASTS AND CENTROCYTES AND 84 00:04:41,601 --> 00:04:43,470 THOSE WITH A PATTERN WERE 85 00:04:43,470 --> 00:04:45,372 DERIVED FROM THE GERMINAL 86 00:04:45,372 --> 00:04:45,605 CENTER. 87 00:04:45,605 --> 00:04:48,008 THIS HAD BEEN REFUTED BY 88 00:04:48,008 --> 00:04:49,943 RAPPAPORT'S EARLIER WORK. 89 00:04:49,943 --> 00:04:53,346 WHEN I STARTED AS A RESIDENT 90 00:04:53,346 --> 00:04:55,682 BACK IN 1970, THE STARS WERE 91 00:04:55,682 --> 00:04:58,185 REALLY ALIGNED FOR THE 92 00:04:58,185 --> 00:05:01,221 REVOLUTION OF LYMPHOMA 93 00:05:01,221 --> 00:05:02,289 DIAGNOSIS. 94 00:05:02,289 --> 00:05:05,725 THERE WERE NEW ADVANCES IN THE 95 00:05:05,725 --> 00:05:09,096 TREATMENT AND ADVANCES IN 96 00:05:09,096 --> 00:05:11,098 IMMUNOLOGY AND NEW INSIGHTS INTO 97 00:05:11,098 --> 00:05:15,869 THE NATURE OF IMMUNE CELLS AND 98 00:05:15,869 --> 00:05:17,304 EMERGING TECHNIQUES TO 99 00:05:17,304 --> 00:05:24,845 CHARACTERIZE LYMPHOCYTES AND 100 00:05:24,845 --> 00:05:25,378 HISTIOCYTES. 101 00:05:25,378 --> 00:05:30,250 I WAS LUCKY TO BECOME A FELLOW 102 00:05:30,250 --> 00:05:32,252 WITH MOST THE LYMPHOMA DIAGNOSIS 103 00:05:32,252 --> 00:05:34,488 AT THAT POINT AND HAD THE GOOD 104 00:05:34,488 --> 00:05:39,459 FORTUNE TO WORK WITH THREE 105 00:05:39,459 --> 00:05:42,729 IMMUNOLOGISTS IN NIAID, IRA 106 00:05:42,729 --> 00:05:51,104 GREEN, DR. FRANK AND ETHAN 107 00:05:51,104 --> 00:05:53,340 SHEVACH THEY WERE DEVELOPING 108 00:05:53,340 --> 00:05:56,076 TOOLS TO IDENTIFY B CELLS AND T 109 00:05:56,076 --> 00:05:58,145 CELLS AND IT WAS KNOWN T CELLS 110 00:05:58,145 --> 00:06:01,248 HAD RECEPTORS FOR COMPLEMENT. 111 00:06:01,248 --> 00:06:04,718 NOW WE KNOW THAT ANTIGEN IS CD 112 00:06:04,718 --> 00:06:10,423 21 AND DETECTED BY WHAT WAS 113 00:06:10,423 --> 00:06:14,761 CALLED EAC CELLS CODED WITH 114 00:06:14,761 --> 00:06:17,597 ANTIBODY IN COMPLEMENT AND BIND 115 00:06:17,597 --> 00:06:19,633 TO CELLS WITH THE CD 21 116 00:06:19,633 --> 00:06:20,000 RECEPTOR. 117 00:06:20,000 --> 00:06:22,435 SO I UNDERTOOK AN ATTEMPT TO TRY 118 00:06:22,435 --> 00:06:26,039 AND USE THIS TECHNIQUE TO LOOK 119 00:06:26,039 --> 00:06:28,608 AT TISSUE SECTIONS. 120 00:06:28,608 --> 00:06:30,010 DEVELOPED WHAT WE CALL THE 121 00:06:30,010 --> 00:06:32,779 HANGING DROP TECHNIQUE IN WHICH 122 00:06:32,779 --> 00:06:36,016 WE CUT FROZEN SECTIONS ON 123 00:06:36,016 --> 00:06:36,917 MICROSCOPIC SLIDES. 124 00:06:36,917 --> 00:06:42,189 WE LOADED THE EAC RED CELLS IN A 125 00:06:42,189 --> 00:06:45,659 MICROCULTURE CHAMBER AND 126 00:06:45,659 --> 00:06:49,629 INCUBATED THE SECTION WITH THE 127 00:06:49,629 --> 00:06:52,065 EAC RED CELLS. 128 00:06:52,065 --> 00:06:55,502 AFTER GENTLE TAPPING THE SLIDE 129 00:06:55,502 --> 00:06:57,504 WAS DETACHED AND WE LOOKED UNDER 130 00:06:57,504 --> 00:07:01,908 THE MICROSCOPE TO SEE WHERE THE 131 00:07:01,908 --> 00:07:05,178 EAC CELLS HAD BOUND. 132 00:07:05,178 --> 00:07:07,147 LO AND BEHOLD WE SAW BINDING TO 133 00:07:07,147 --> 00:07:14,020 THE REACTIVE FOLLICLES IN LYMPH 134 00:07:14,020 --> 00:07:14,387 NODE SECTION. 135 00:07:14,387 --> 00:07:22,529 I USED THE TECHNIQUE TO LOOK AT 136 00:07:22,529 --> 00:07:27,667 NODULAR LYMPHOMA AND FOUND THE 137 00:07:27,667 --> 00:07:32,038 NODULES BOUND THE RED CELLS 138 00:07:32,038 --> 00:07:36,042 PROVIDING ORIGIN FOR FOLLICULAR 139 00:07:36,042 --> 00:07:37,911 B LYMPHOCYTES. 140 00:07:37,911 --> 00:07:41,548 THIS WAS PUBLISHED IN THE NEW 141 00:07:41,548 --> 00:07:43,717 ENGLAND JOURNAL AND ULTIMATELY 142 00:07:43,717 --> 00:07:45,752 NAMED A CITATION CLASSIC. 143 00:07:45,752 --> 00:07:47,554 WHEN THERE WAS THE INTRODUCTION 144 00:07:47,554 --> 00:07:49,322 OF ADDITIONAL TECHNIQUES THAT 145 00:07:49,322 --> 00:07:52,759 COULD IDENTIFY T CELLS AND B 146 00:07:52,759 --> 00:07:59,332 CELLS, WE HAD SHEEP ERYTHROCYTE 147 00:07:59,332 --> 00:08:00,867 ROSETTES AND I MENTIONED THIS 148 00:08:00,867 --> 00:08:04,204 THE OTHER DAY AND THEY HAD NO 149 00:08:04,204 --> 00:08:07,274 IDEA WHAT THIS WAS AND I WAS 150 00:08:07,274 --> 00:08:07,540 SURPRISED. 151 00:08:07,540 --> 00:08:12,012 THIS ANTIGEN IS NOW KNOWN AS CD 152 00:08:12,012 --> 00:08:12,379 2. 153 00:08:12,379 --> 00:08:20,787 THERE WAS THE EXPRESSION IMM 154 00:08:20,787 --> 00:08:23,556 IMMUNOGLOBULIN LEADING TO AN 155 00:08:23,556 --> 00:08:32,766 INTERESTING DEVELOP IING. 156 00:08:32,766 --> 00:08:35,302 AND THERE WERE MEETINGS IN ITALY 157 00:08:35,302 --> 00:08:38,571 AND VIRGINIA. 158 00:08:38,571 --> 00:08:43,276 THIS PRESENTED PROBLEMS FOR THE 159 00:08:43,276 --> 00:08:45,612 HEMATOLOGY, IMMUNOLOGY 160 00:08:45,612 --> 00:08:47,714 COMMUNITY, WHICH CLASSIFICATION 161 00:08:47,714 --> 00:08:48,581 SHOULD BE USED. 162 00:08:48,581 --> 00:08:52,619 THE NCI SPONSORED A STUDY OF THE 163 00:08:52,619 --> 00:08:56,289 VARIOUS SIX CLASSIFICATIONS. 164 00:08:56,289 --> 00:09:02,429 THEY HAD NEARLY 1200 CASES OF 165 00:09:02,429 --> 00:09:04,831 NON HODGKIN'S LYMPHOMA AND HAD A 166 00:09:04,831 --> 00:09:06,132 PATHOLOGIST FROM EACH OF THE 167 00:09:06,132 --> 00:09:08,268 CLASSIFICATIONS AND SIX CONTROL 168 00:09:08,268 --> 00:09:10,170 PATHOLOGISTS. 169 00:09:10,170 --> 00:09:11,137 AND THEY REVIEWED THE NEARLY 170 00:09:11,137 --> 00:09:21,348 1200 CASES. 171 00:09:24,317 --> 00:09:25,719 THEY WERE MADE FIRST WITHOUT 172 00:09:25,719 --> 00:09:28,054 CLINICAL DATA AND GOT TO REVIEW 173 00:09:28,054 --> 00:09:31,358 THE SLIDE KNOWING ONLY AGE, SEX 174 00:09:31,358 --> 00:09:39,099 AND ANATOMIC SITE. 175 00:09:39,099 --> 00:09:39,833 KAP 176 00:09:39,833 --> 00:09:40,600 KAPLAN 177 00:09:40,600 --> 00:09:42,235 KAPLAN-MEIER CURVES WERE 178 00:09:42,235 --> 00:09:43,737 GENERATE AND NO CLASSIFICATION 179 00:09:43,737 --> 00:09:46,706 EMERGED AS SUPERIOR. 180 00:09:46,706 --> 00:09:50,343 THIS LED TO THE WORKING 181 00:09:50,343 --> 00:09:53,079 FORMULATION FOR CLINICAL USAGE. 182 00:09:53,079 --> 00:09:58,451 IT WAS SUPPOSED SORT OF AN 183 00:09:58,451 --> 00:10:00,253 ESPERANTO OF LYMPHOMA 184 00:10:00,253 --> 00:10:01,721 CLASSIFICATIONS YOU CAN USE AND 185 00:10:01,721 --> 00:10:04,924 IT WAS ESSENTIALLY THE RAPPAPORT 186 00:10:04,924 --> 00:10:07,093 SYSTEM WITH MINOR CHANGES IN 187 00:10:07,093 --> 00:10:07,394 TERMINOLOGY. 188 00:10:07,394 --> 00:10:12,165 IT WAS NEVER INTEND BE TO BE A 189 00:10:12,165 --> 00:10:22,675 FREE-STANDING CLASSIFICATION. 190 00:10:27,046 --> 00:10:35,321 THE DIFFUSE MIX WAS HANDY AND IT 191 00:10:35,321 --> 00:10:37,657 WAS ACCEPTED IN THE U.S. BUT 192 00:10:37,657 --> 00:10:41,060 RESISTED IN EUROPE AND ASIA 193 00:10:41,060 --> 00:10:42,829 WHERE THE KEEL SYSTEM PROPOSED 194 00:10:42,829 --> 00:10:44,130 BY CARL LEONARD AND COLLEAGUES 195 00:10:44,130 --> 00:10:47,233 WAS POPULAR. 196 00:10:47,233 --> 00:10:53,706 MEANWHILE RAPID PROGRESS WAS 197 00:10:53,706 --> 00:10:57,644 BEING MADE IN NEOPLASMS. 198 00:10:57,644 --> 00:11:00,814 THERE WAS DEVELOPED 199 00:11:00,814 --> 00:11:03,783 IMMUNOHISTOCHEMISTRY FOR USE ON 200 00:11:03,783 --> 00:11:05,785 ROUTINE PARAFFIN SECTIONS AND 201 00:11:05,785 --> 00:11:09,255 HAD THE EXPLOSION OF MONOCLONAL 202 00:11:09,255 --> 00:11:12,525 ANTIBODIES AND IN 1982 DAVID 203 00:11:12,525 --> 00:11:17,530 MASON USED MONOCLONAL ANTIBODIES 204 00:11:17,530 --> 00:11:19,999 FOR HUMO HISTOCHEMISTRY IN 205 00:11:19,999 --> 00:11:21,501 PARAFFIN SECTIONS. 206 00:11:21,501 --> 00:11:31,611 AND IMMUNOGLOBULIN GENE 207 00:11:31,611 --> 00:11:37,350 ARRANGEMENTS WERE IDENTIFIED AND 208 00:11:37,350 --> 00:11:45,258 THEN BCL2 GENE ARRANGEMENTS WERE 209 00:11:45,258 --> 00:11:46,426 IDENTIFIED. 210 00:11:46,426 --> 00:11:47,594 IMMUNOPATHOLOGISTS WERE STARTING 211 00:11:47,594 --> 00:11:57,637 TO SEE A WAY FORWARD. 212 00:11:57,637 --> 00:11:57,804 . 213 00:11:57,804 --> 00:11:59,906 A GROUP WILL LOOKED TO SEE IF 214 00:11:59,906 --> 00:12:02,375 THEY CAN ARRIVE AT A BETTER 215 00:12:02,375 --> 00:12:03,610 UNDERSTANDING OF THE 216 00:12:03,610 --> 00:12:07,614 CLASSIFICATION OF LYMPHOMAS. 217 00:12:07,614 --> 00:12:09,849 19 INDIVIDUALS WERE INVITED TO 218 00:12:09,849 --> 00:12:12,218 ATTEND THE MEETING IN LONDON AND 219 00:12:12,218 --> 00:12:16,189 THE AGENDA INCLUDED THREE 220 00:12:16,189 --> 00:12:16,422 TOPICS. 221 00:12:16,422 --> 00:12:22,562 ONE DISCUSSION OF LYMPHOMA THAT 222 00:12:22,562 --> 00:12:29,869 WAS CALLED INTERMEDIATE 223 00:12:29,869 --> 00:12:35,909 LYMPHOCIDIC AND THE TOPIC OF 224 00:12:35,909 --> 00:12:39,212 GASTROINTESTINAL LYMPHOMAS AS A 225 00:12:39,212 --> 00:12:41,581 UNIQUE BIOLOGICAL ENTITY AND 226 00:12:41,581 --> 00:12:43,750 FINALLY A DISCUSSION OF THE 227 00:12:43,750 --> 00:12:47,487 INTERRELATIONSHIP OF HODGKIN'S 228 00:12:47,487 --> 00:12:51,224 AND NON-HODGKINS LYMPHOMA. 229 00:12:51,224 --> 00:12:53,726 CONSENSUS WAS EMERGING AND THE 230 00:12:53,726 --> 00:12:54,694 PATHOLOGISTS REALIZED WE WERE 231 00:12:54,694 --> 00:12:58,431 ALL TALKING THE SAME LANGUAGE. 232 00:12:58,431 --> 00:13:01,401 HERE'S SOME OF THE FOLKS AT THAT 233 00:13:01,401 --> 00:13:02,969 MEETING. 234 00:13:02,969 --> 00:13:12,946 NANCY HARRIS, HERALD STEIN, S 235 00:13:12,946 --> 00:13:19,852 STEFANO PALARI AND OTHERS AND 236 00:13:19,852 --> 00:13:20,053 ME. 237 00:13:20,053 --> 00:13:24,057 THERE WAS THE DISCUSSION OF 238 00:13:24,057 --> 00:13:26,993 INTERMED 239 00:13:26,993 --> 00:13:37,437 INTERMEDIATE CENTROCYTIC 240 00:13:39,739 --> 00:13:44,143 LYMPHOMA AND PROPOSED THE THIS 241 00:13:44,143 --> 00:13:48,982 MIGHT BE DERIVED FROM THE LY 242 00:13:48,982 --> 00:13:51,351 LYMPHOSITE OBSERVED IN 243 00:13:51,351 --> 00:13:52,652 HISTOLOGIC SECTIONS. 244 00:13:52,652 --> 00:13:54,020 AN IMPORTANT PIECE OF 245 00:13:54,020 --> 00:13:54,554 INFORMATION WAS THE 246 00:13:54,554 --> 00:13:57,123 IDENTIFICATION OF REARRANGEMENTS 247 00:13:57,123 --> 00:14:01,527 INVOLVING THE BREAK POINT REGION 248 00:14:01,527 --> 00:14:03,096 BCL1 BY SOUTHERN BLOT AND 249 00:14:03,096 --> 00:14:07,266 SEVERAL GROUPS DEMONSTRATED THIS 250 00:14:07,266 --> 00:14:11,371 REARRANGEMENT INVOLVING THE 1114 251 00:14:11,371 --> 00:14:16,042 TRANS LOCATION WAS SEEN IN 252 00:14:16,042 --> 00:14:16,909 CENTROCYTIC LYMPHOMA AND 253 00:14:16,909 --> 00:14:18,478 INTERMEDIATE LYMPHOMA SUGGESTING 254 00:14:18,478 --> 00:14:22,749 THE SAME DISEASE ENTITY. 255 00:14:22,749 --> 00:14:27,320 AT THIS TIME WE AUTHORED AN 256 00:14:27,320 --> 00:14:29,689 EDITORIAL IN BLOOD PROPOSING 257 00:14:29,689 --> 00:14:33,760 THIS DISEASE SHOULD BE 258 00:14:33,760 --> 00:14:35,094 DESIGNATED AS MANTLE CELL 259 00:14:35,094 --> 00:14:38,731 LYMPHOMA AND THIS WAS A CONCEPT 260 00:14:38,731 --> 00:14:39,966 EMBRACED BY THE INTERNATIONAL 261 00:14:39,966 --> 00:14:42,368 LYMPHOMA STUDY GROUP IN A SECOND 262 00:14:42,368 --> 00:14:49,409 ARTICLE. 263 00:14:49,409 --> 00:14:54,080 SUBSEQUENTLY, CYCLIN D1 WAS 264 00:14:54,080 --> 00:14:57,050 IDENTIFIED IMPORTANT IN THE 265 00:14:57,050 --> 00:14:59,819 LOCUS AND THE ANTIBODIES SHOWED 266 00:14:59,819 --> 00:15:02,722 OVER EXPRESSION BY 267 00:15:02,722 --> 00:15:03,189 IMMUNOHISTOCHEMISTRY. 268 00:15:03,189 --> 00:15:04,857 HERE SHOWING THE CHARACTERISTIC 269 00:15:04,857 --> 00:15:11,197 MANTLE ZONE PATTERN. 270 00:15:11,197 --> 00:15:17,537 I WE DESCRIBED A BLASTOID 271 00:15:17,537 --> 00:15:20,073 VARIANT FROM THE DISEASE AND 272 00:15:20,073 --> 00:15:23,009 THIS BLASTOID VARIANT HAD A MORE 273 00:15:23,009 --> 00:15:27,447 AGGRESSIVE CLINICAL COURSE. 274 00:15:27,447 --> 00:15:29,549 IN SUBSEQUENT STUDIES USING GENE 275 00:15:29,549 --> 00:15:31,951 EXPRESSION PROFILING TO SHOW 276 00:15:31,951 --> 00:15:34,520 THAT THE PROLIFERATION SIGNATURE 277 00:15:34,520 --> 00:15:38,424 WAS KEY IN THE PROGNOSIS OF 278 00:15:38,424 --> 00:15:42,762 MANTLE CELL LYMPHOMA AND NOT 279 00:15:42,762 --> 00:15:44,130 SURPRISINGLY THE BLASTOID 280 00:15:44,130 --> 00:15:47,066 VARIANT HAD THE HIGHEST 281 00:15:47,066 --> 00:15:50,837 PROLIFERATION SIGNATURE. 282 00:15:50,837 --> 00:15:53,706 THE MOLECULAR PATHOGENESIS OF 283 00:15:53,706 --> 00:15:58,878 MANTLE CELL LYMPHOMA WAS 284 00:15:58,878 --> 00:16:00,980 INTERESTING IN DEMONSTRATING THE 285 00:16:00,980 --> 00:16:06,552 DISEASE AND MANY STUDIES 286 00:16:06,552 --> 00:16:09,589 DEMONSTRATED MANTLE CELL 287 00:16:09,589 --> 00:16:15,194 VARIANTS INCLUDING THE BLASTOID 288 00:16:15,194 --> 00:16:18,097 MANTLE CELL NON-NODAL CELL AND 289 00:16:18,097 --> 00:16:24,704 EVEN SOME CASES WITH 290 00:16:24,704 --> 00:16:27,507 PLASMACYTOID DIFFERENTIATION. 291 00:16:27,507 --> 00:16:31,611 AND A SECOND RECOMMENDED A 292 00:16:31,611 --> 00:16:34,747 FORMAL WILL DESCRIPTION OF THE 293 00:16:34,747 --> 00:16:37,316 LYMPHOMA FROM CLASSIC HODGKIN'S 294 00:16:37,316 --> 00:16:39,051 LYMPHOMA SAYING IT WAS BIO 295 00:16:39,051 --> 00:16:42,121 LOGICALLY AND CLINICALLY A 296 00:16:42,121 --> 00:16:44,157 TOTALLY SEPARATE DISEASE. 297 00:16:44,157 --> 00:16:47,126 SOMETHING BORN TRUE IN 298 00:16:47,126 --> 00:16:47,527 SUBSEQUENT YEARS. 299 00:16:47,527 --> 00:16:49,929 SO, AS THE DISCUSSIONS AMONG THE 300 00:16:49,929 --> 00:16:53,132 PATHOLOGISTS WENT ON, WE 301 00:16:53,132 --> 00:16:56,169 REALIZED THAT THE MOST PRACTICAL 302 00:16:56,169 --> 00:16:57,637 APPROACH TO LYMPHOMA 303 00:16:57,637 --> 00:16:59,071 CLASSIFICATION AT THIS TIME IS 304 00:16:59,071 --> 00:17:02,942 TO SIMPLY DEFINE DISEASES THAT 305 00:17:02,942 --> 00:17:06,879 WE THINK WE CAN RECOGNIZE WITH 306 00:17:06,879 --> 00:17:09,148 CURRENTLY AVAILABLE MORPHOLOGIC 307 00:17:09,148 --> 00:17:10,249 PHENOTYPIC AND GENETIC 308 00:17:10,249 --> 00:17:10,550 TECHNIQUES. 309 00:17:10,550 --> 00:17:13,553 THUS WAS BORN THE REVISED 310 00:17:13,553 --> 00:17:16,856 EUROPEAN LYMPHOMA CLASSIFICATION 311 00:17:16,856 --> 00:17:19,625 ALSO CALLED IT THE REAL 312 00:17:19,625 --> 00:17:20,259 CLASSIFICATION SOMEWHAT TONGUE 313 00:17:20,259 --> 00:17:22,495 AND CHEEK. 314 00:17:22,495 --> 00:17:33,039 AS THESE WERE THE REAL ENTITIES. 315 00:17:33,472 --> 00:17:34,740 IT REPRESENTED A NEW 316 00:17:34,740 --> 00:17:35,208 CLASSIFICATION. 317 00:17:35,208 --> 00:17:38,511 INDIVIDUALS DISEASES WERE 318 00:17:38,511 --> 00:17:39,912 DEFINED BASED ON A CONSTELLATION 319 00:17:39,912 --> 00:17:41,547 OF CLINICAL AND LABORATORY 320 00:17:41,547 --> 00:17:42,248 FEATURES. 321 00:17:42,248 --> 00:17:45,451 IMPORTANTLY THE CLINICAL 322 00:17:45,451 --> 00:17:47,820 PRESENTATION AND COURSE WAS A 323 00:17:47,820 --> 00:17:48,921 MAJOR FACTOR. 324 00:17:48,921 --> 00:17:50,489 THE SITE OF INVOLVEMENT WAS 325 00:17:50,489 --> 00:17:54,493 OBSERVED AS OFTEN A SIGN POST 326 00:17:54,493 --> 00:17:57,563 FOR UNDERLYING BIOLOGICAL 327 00:17:57,563 --> 00:17:59,899 DISTINCTIONS AS IN MALT LYMPHOMA 328 00:17:59,899 --> 00:18:02,201 AND IMPORTANTLY BASED ON THE 329 00:18:02,201 --> 00:18:05,504 BUILDING OF CONSENSUS THROUGH 330 00:18:05,504 --> 00:18:09,308 INPUT FROM 19 EXPERT HEM 331 00:18:09,308 --> 00:18:13,346 HEMATOPATHOLOGISTS AND AN ENTITY 332 00:18:13,346 --> 00:18:15,948 COULD NOT BE INCLUDED IN THE 333 00:18:15,948 --> 00:18:17,416 CLASSIFICATION UNLESS THERE WERE 334 00:18:17,416 --> 00:18:22,054 AT LEAST TWO PUBLICATIONS ON IT 335 00:18:22,054 --> 00:18:24,290 IN THE PEER REVIEWED LITERATURE. 336 00:18:24,290 --> 00:18:25,558 SO IN ADVANCE OF THE PUBLICATION 337 00:18:25,558 --> 00:18:29,962 WHICH WAS COMING OUT SHORTLY IN 338 00:18:29,962 --> 00:18:35,835 BLOOD, VINCE LAVIDA CONVENED 339 00:18:35,835 --> 00:18:36,335 REPRESENTATIVES FROM 42 340 00:18:36,335 --> 00:18:37,904 INTERNATIONAL LYMPHOMA STUDY 341 00:18:37,904 --> 00:18:40,072 GROUP TO MEET WITH THE CLINICAL 342 00:18:40,072 --> 00:18:42,375 ONCOLOGY COMMUNITY TO PRESENT 343 00:18:42,375 --> 00:18:43,476 THE CLASSIFICATION AND OUR 344 00:18:43,476 --> 00:18:53,753 PROPOSED IDEAS. 345 00:19:00,026 --> 00:19:01,327 MOST QUESTIONING THE VALUE OF 346 00:19:01,327 --> 00:19:02,962 THE APPROACH. 347 00:19:02,962 --> 00:19:05,298 WHEN THE REAL CLASSIFICATION WAS 348 00:19:05,298 --> 00:19:08,267 SUBSEQUENTLY PUBLISHED IN BLOOD 349 00:19:08,267 --> 00:19:11,570 IN SEPTEMBER OF 1994 SAUL 350 00:19:11,570 --> 00:19:15,341 ROSENBERG LEADING ONCOLOGIST AT 351 00:19:15,341 --> 00:19:16,142 STANFORD UNIVERSITY PUBLISHED 352 00:19:16,142 --> 00:19:17,443 THE FOLLOWING EDITORIAL AND 353 00:19:17,443 --> 00:19:20,446 STATED DESPITE THE HOPE OF MANY, 354 00:19:20,446 --> 00:19:22,748 SEPARATION OF LYMPHOID TUMORS 355 00:19:22,748 --> 00:19:25,618 INTO B OR T-CELL ORIGIN AS MAJOR 356 00:19:25,618 --> 00:19:29,422 SUB TYPES, IS NOT HELPFUL TO THE 357 00:19:29,422 --> 00:19:29,689 CLINICIAN. 358 00:19:29,689 --> 00:19:31,490 I SO I WANT TO SEE A SHOW OF 359 00:19:31,490 --> 00:19:33,092 HAND FROM THE CLINICIANS IN THE 360 00:19:33,092 --> 00:19:37,930 AUDIENCE, HOW MANY AGREE WITH 361 00:19:37,930 --> 00:19:38,331 THAT? 362 00:19:38,331 --> 00:19:38,531 OKAY. 363 00:19:38,531 --> 00:19:41,233 HE ALSO OBJECTED TO THE FACT THE 364 00:19:41,233 --> 00:19:42,768 CLASSIFICATION DID NOT CLEARLY 365 00:19:42,768 --> 00:19:46,105 IDENTIFY PROGNOSTIC GROUPS. 366 00:19:46,105 --> 00:19:47,573 CLINICIANS LIKED THE WORKING 367 00:19:47,573 --> 00:19:52,979 FORMULATION BECAUSE THEY HAD 368 00:19:52,979 --> 00:19:53,980 LOW, INTERMEDIATE AND HIGH AND 369 00:19:53,980 --> 00:19:56,282 ONLY HAD THREE BOXES TO PUT THE 370 00:19:56,282 --> 00:19:57,083 TUMORS. 371 00:19:57,083 --> 00:19:59,352 WE FELT YOU COULDN'T RANK 372 00:19:59,352 --> 00:20:01,821 LYMPHOMAS BASED ON PROGNOSIS. 373 00:20:01,821 --> 00:20:03,389 AND FOR MANY DISEASE ENTITIES 374 00:20:03,389 --> 00:20:05,858 THERE WAS A SPECTRUM OF CLINICAL 375 00:20:05,858 --> 00:20:10,730 BEHAVIOR AS WE SEE IN FOLLICULAR 376 00:20:10,730 --> 00:20:15,768 LYMPHOMA OR ADULT T CELL 377 00:20:15,768 --> 00:20:16,168 LEUKEMIA LYMPHOMA. 378 00:20:16,168 --> 00:20:18,838 AND WENT ON WITH TOOLS AND 379 00:20:18,838 --> 00:20:21,607 METHODS TO DISSECT THE CELL OF 380 00:20:21,607 --> 00:20:23,376 ORIGIN AND LEVEL OF 381 00:20:23,376 --> 00:20:25,778 DIFFERENTIATION, EVERY PATIENT'S 382 00:20:25,778 --> 00:20:27,513 LYMPHOMA MIGHT BE DIFFERENT AND 383 00:20:27,513 --> 00:20:28,881 IT'S DOUBTFUL SUCH COMPLETE 384 00:20:28,881 --> 00:20:31,183 KNOWLEDGE WOULD BE HELPFUL. 385 00:20:31,183 --> 00:20:33,819 WELL, I THINK THAT'S ALSO SOME 386 00:20:33,819 --> 00:20:44,263 OF US WOULD DISPUTE TODAY. 387 00:20:46,065 --> 00:20:50,302 HE WENT ON TO SAY IT HAD TO BE 388 00:20:50,302 --> 00:20:53,372 CAPABLE OF USED BY THE WELL 389 00:20:53,372 --> 00:20:55,608 TRAINED PATHOLOGIST USING EASILY 390 00:20:55,608 --> 00:20:57,977 USABLE TECHNIQUES. 391 00:20:57,977 --> 00:21:03,082 THUS WAS BORN ANOTHER STUDY TO 392 00:21:03,082 --> 00:21:04,750 EVALUATE THE CLASSIFICATION. 393 00:21:04,750 --> 00:21:06,185 THE MAIN CLINICIAN AT THE 394 00:21:06,185 --> 00:21:08,587 MEETING THAT EMBRACED OUR 395 00:21:08,587 --> 00:21:12,158 APPROACH AND THE STUDY HE 396 00:21:12,158 --> 00:21:15,795 CONDUCTED VALIDATED THE CLINICAL 397 00:21:15,795 --> 00:21:16,962 CLASSIFICATION FOR CLINICAL 398 00:21:16,962 --> 00:21:19,331 USAGE AND TRIALS. 399 00:21:19,331 --> 00:21:23,035 IT WAS INDEED USEFUL AND 400 00:21:23,035 --> 00:21:23,369 REPRODUCIBLE. 401 00:21:23,369 --> 00:21:24,870 SO WHAT ARE THE ADVANTAGES OF A 402 00:21:24,870 --> 00:21:28,307 DISEASE ORIENTED APPROACH TO 403 00:21:28,307 --> 00:21:28,674 CLASSIFICATION? 404 00:21:28,674 --> 00:21:31,610 IT HAS TO BE REQUIRED FOR THE 405 00:21:31,610 --> 00:21:33,879 DEVELOPMENT OF NEW THERAPIES. 406 00:21:33,879 --> 00:21:37,650 SHOWN HERE ARE THREE LYMPHOID 407 00:21:37,650 --> 00:21:40,986 MALIGNANCIES DERIVED FROM SMALL 408 00:21:40,986 --> 00:21:41,387 B CELLS. 409 00:21:41,387 --> 00:21:42,922 CLEARLY THEY'RE DIFFERENT BIO 410 00:21:42,922 --> 00:21:44,056 LOGICALLY AND TREATED IN 411 00:21:44,056 --> 00:21:47,293 DIFFERENT WAYS. 412 00:21:47,293 --> 00:21:48,494 IT'S ALSO REQUIRED FOR THE 413 00:21:48,494 --> 00:21:50,496 INVESTIGATION INTO THE 414 00:21:50,496 --> 00:21:53,132 PATHOGENESIS OF SPECIFIC 415 00:21:53,132 --> 00:21:56,902 ENTITIES SUCH AS ADULT T CELL 416 00:21:56,902 --> 00:22:07,413 LEUKEMIA, BURKITT LYMPHOMA OR 417 00:22:09,148 --> 00:22:12,551 ANAPLASTIC LARGE CELL LYMPHOMA. 418 00:22:12,551 --> 00:22:16,188 AND THE W.H.O. INVITE THE MAJOR 419 00:22:16,188 --> 00:22:17,056 SOCIETIES TO DEVELOP A 420 00:22:17,056 --> 00:22:20,059 CLASSIFICATION FOR THE UPCOMING 421 00:22:20,059 --> 00:22:21,961 THIRD EDITION OF THE W.H.O. BLUE 422 00:22:21,961 --> 00:22:31,070 BOOK. 423 00:22:31,070 --> 00:22:36,575 THE FIRST EDITION WAS IN 1976. 424 00:22:36,575 --> 00:22:39,211 THERE WAS NEVER A THIRD 425 00:22:39,211 --> 00:22:39,478 ADDITION. 426 00:22:39,478 --> 00:22:45,718 IN 1994 ABOUT THIS TIME THE 427 00:22:45,718 --> 00:22:49,021 DIRECTOR TRANSFORMED THE BLUE 428 00:22:49,021 --> 00:22:50,556 BOOK SERIES TO ITS CURRENT 429 00:22:50,556 --> 00:22:52,057 FORMAT. 430 00:22:52,057 --> 00:22:55,661 THE PRIOR BLUE BOOKS WERE SIMPLE 431 00:22:55,661 --> 00:23:00,266 HANDBOOKS WITH A SERIES OF PHOTO 432 00:23:00,266 --> 00:23:01,800 MICROGRAPHS AND FIGURE LEGENDS 433 00:23:01,800 --> 00:23:04,036 WITHOUT DISCUSSION OF THE 434 00:23:04,036 --> 00:23:06,972 DISEASE ENTITIES. 435 00:23:06,972 --> 00:23:08,874 IN THE NEW BLUE BOOK FORMAT HE 436 00:23:08,874 --> 00:23:11,610 SAWS THE IMPORTANCE OF 437 00:23:11,610 --> 00:23:12,878 INTEGRATING PATHOLOGY, GENETICS 438 00:23:12,878 --> 00:23:16,048 AND CLINICAL FINDINGS AS 439 00:23:16,048 --> 00:23:18,517 PROPOSED IN THE REAL 440 00:23:18,517 --> 00:23:20,619 CLASSIFICATION AND THUS THE 441 00:23:20,619 --> 00:23:21,253 W.H.O. 2001 CLASSIFICATION WAS 442 00:23:21,253 --> 00:23:24,757 BORN. 443 00:23:24,757 --> 00:23:26,825 HOWEVER PRIOR TO PUBLICATION OF 444 00:23:26,825 --> 00:23:29,128 THE CLASSIFICATION, WE REALIZED 445 00:23:29,128 --> 00:23:32,031 THAT AT THIS POINT IT WAS 446 00:23:32,031 --> 00:23:34,833 IMPORTANT TO INVOLVE CLINICIANS. 447 00:23:34,833 --> 00:23:38,437 SO IN PREPARATION FOR THIS WE 448 00:23:38,437 --> 00:23:40,472 ORGANIZED A CLINICAL ADVISORY 449 00:23:40,472 --> 00:23:41,540 COMMITTEE MEETING. 450 00:23:41,540 --> 00:23:43,809 THE MEETING WAS ORGANIZED AROUND 451 00:23:43,809 --> 00:23:46,378 A SERIES OF QUESTIONS. 452 00:23:46,378 --> 00:23:48,714 THE PATHOLOGISTS PRESENTED THEIR 453 00:23:48,714 --> 00:23:51,116 PROPOSED CLASSIFICATIONS. 454 00:23:51,116 --> 00:23:53,652 CLINICIANS PRESENTED DATA 455 00:23:53,652 --> 00:23:54,720 RELEVANT TO THE FACT. 456 00:23:54,720 --> 00:23:56,689 A DISCUSSION WAS HELD AND VOTING 457 00:23:56,689 --> 00:23:59,892 WAS HELD IF NECESSARY. 458 00:23:59,892 --> 00:24:01,460 MEETING REPORTS WERE PUBLISHED 459 00:24:01,460 --> 00:24:03,729 IN BOTH CLINICAL AND PATHOLOGY 460 00:24:03,729 --> 00:24:07,233 JOURNALS IN ADVANCE OF THE BLUE 461 00:24:07,233 --> 00:24:09,668 BOOK AND THE MEETING WAS A GREAT 462 00:24:09,668 --> 00:24:11,704 SUCCESS WITH PARTICIPATION OF 463 00:24:11,704 --> 00:24:16,041 MORE THAN 200 INDIVIDUALS FROM 464 00:24:16,041 --> 00:24:17,309 24 DIFFERENT COUNTRIES. 465 00:24:17,309 --> 00:24:20,980 THIS IS THE GROUP THAT GATHERED 466 00:24:20,980 --> 00:24:24,817 IN VIRGINIA AND AS YOU CAN SEE 467 00:24:24,817 --> 00:24:26,418 PEACE AND TRANQUILITY PREVAILED 468 00:24:26,418 --> 00:24:34,760 IN THE VIRGINIA COUNTRY SIDE. 469 00:24:34,760 --> 00:24:39,465 AT A CONFERENCE IN 1975 WHICH 470 00:24:39,465 --> 00:24:41,734 FAILED, WHILE THIS THIS WAS ONE 471 00:24:41,734 --> 00:24:42,368 HIGHLY SUCCESSFUL. 472 00:24:42,368 --> 00:24:45,237 SO WHAT WERE THE DIFFERENCES? 473 00:24:45,237 --> 00:24:48,173 WELL, IN 1975 THE CLASS 474 00:24:48,173 --> 00:24:51,944 CLASSIFICATIONS WERE THE WORK OF 475 00:24:51,944 --> 00:24:54,513 INDIVIDUAL EXPERTS BROUGHT TO 476 00:24:54,513 --> 00:24:56,081 ARLIE UNDER DURESS. 477 00:24:56,081 --> 00:24:58,851 AT THIS TIME THE KNOWLEDGE OF 478 00:24:58,851 --> 00:25:01,253 THE IMMUNE SYSTEM WAS AT INFANCY 479 00:25:01,253 --> 00:25:04,056 AND PHENOTYPING WAS NOT 480 00:25:04,056 --> 00:25:04,323 AVAILABLE. 481 00:25:04,323 --> 00:25:07,693 MOLECULAR ONCOLOGY WAS STILL 482 00:25:07,693 --> 00:25:08,727 UNDISCOVERED AND THERE WAS NO 483 00:25:08,727 --> 00:25:14,133 WAY TO TEST THE PROPOSALS 484 00:25:14,133 --> 00:25:14,533 EMPIRICALLY. 485 00:25:14,533 --> 00:25:17,269 IN 1997 THE WORK WAS THE RESULT 486 00:25:17,269 --> 00:25:19,204 OF MULTIPLE EXPERTS AND THE 487 00:25:19,204 --> 00:25:20,105 PATHOLOGISTS AND CLINICIANS 488 00:25:20,105 --> 00:25:22,808 WORKED SIDE BY SIDE TO FORMULATE 489 00:25:22,808 --> 00:25:23,876 THE CLASSIFICATION. 490 00:25:23,876 --> 00:25:27,546 AT THIS POINT WE HAD A BETTER 491 00:25:27,546 --> 00:25:29,581 UNDERSTANDING OF THE IMMUNE 492 00:25:29,581 --> 00:25:30,149 SYSTEM. 493 00:25:30,149 --> 00:25:32,718 PRAYER FIN HISTOCHEMISTRY COULD 494 00:25:32,718 --> 00:25:37,756 DETECT MOST ANTIGENS IN ROUTINE 495 00:25:37,756 --> 00:25:40,859 BIOPSIES AND MOLECULAR STUDIES 496 00:25:40,859 --> 00:25:43,362 WERE BEING AVAILABLE TO 497 00:25:43,362 --> 00:25:44,063 DELINEATE DISEASE. 498 00:25:44,063 --> 00:25:50,402 THIS WAS NOT ONLY USED IN 1997 499 00:25:50,402 --> 00:25:52,638 BUT IN SUBSEQUENT EDITIONS IN 500 00:25:52,638 --> 00:25:56,041 2008 AND 2017. 501 00:25:56,041 --> 00:26:00,879 SO AT THIS TIME WE FULFILLED THE 502 00:26:00,879 --> 00:26:03,682 HOLY GRAIL OF LYMPHOMA 503 00:26:03,682 --> 00:26:08,053 CLASSIFICATION AND DEVELOPED A 504 00:26:08,053 --> 00:26:12,091 MODERN TAXONOMY AND DISEASE AS 505 00:26:12,091 --> 00:26:13,892 RECOMMENDED IN THE REPORT 506 00:26:13,892 --> 00:26:17,996 BUILDING A NETWORK TO PROMOTE 507 00:26:17,996 --> 00:26:19,998 DISEASE DISCOVERY AND 508 00:26:19,998 --> 00:26:21,233 PATHOGENETIC INSIGHTS PROVIDING 509 00:26:21,233 --> 00:26:24,002 A FRAMEWORK FOR MEDICINE AND 510 00:26:24,002 --> 00:26:26,672 FACILITATING CLINICAL TRIALS AND 511 00:26:26,672 --> 00:26:28,440 HOPEFULLY IMPROVING THE STANDARD 512 00:26:28,440 --> 00:26:29,274 OF DIAGNOSIS AND TREATMENT IN 513 00:26:29,274 --> 00:26:31,877 THE COMMUNITY. 514 00:26:31,877 --> 00:26:34,313 SO I THINK THE MICROSCOPE TODAY 515 00:26:34,313 --> 00:26:36,648 IS STILL A TOOL FOR DISEASE 516 00:26:36,648 --> 00:26:36,915 DISCOVERY. 517 00:26:36,915 --> 00:26:40,052 FOR MOST OF THE DISEASE ENTITIES 518 00:26:40,052 --> 00:26:45,391 THAT HAVE BEEN INCLUDED, THE 519 00:26:45,391 --> 00:26:49,561 DISEASE WAS FIRST DESIGN BY 520 00:26:49,561 --> 00:26:50,896 CLINICAL CRITERIA LEADING TO 521 00:26:50,896 --> 00:26:55,200 IDENTIFICATION OF THE 522 00:26:55,200 --> 00:26:55,534 PATHOGENESIS. 523 00:26:55,534 --> 00:26:59,138 THAT'S TRUE FOR ANPLASTIC LARGE 524 00:26:59,138 --> 00:27:00,639 CELL AND T CELL LEUKEMIA 525 00:27:00,639 --> 00:27:04,042 LYMPHOMA AND ALL THE DISEASES 526 00:27:04,042 --> 00:27:11,383 LISTED HERE. 527 00:27:11,383 --> 00:27:14,019 ONCE YOU UNDERSTAND THE GENESIS 528 00:27:14,019 --> 00:27:15,154 YOU HAVE THE DIAGNOSTIC TOOLS 529 00:27:15,154 --> 00:27:17,856 YOU CAN USE TO STUDY THE DISEASE 530 00:27:17,856 --> 00:27:21,193 AND THIS HELPS DEFINE THE 531 00:27:21,193 --> 00:27:23,162 DISEASE AND IDENTIFY IT'S BORDER 532 00:27:23,162 --> 00:27:23,796 LANDS. 533 00:27:23,796 --> 00:27:27,933 SO IN MY REMAINING TIME TODAY, 534 00:27:27,933 --> 00:27:31,103 I'D LIKE TO ILLUSTRATE THREE 535 00:27:31,103 --> 00:27:34,640 VIGNETTES THAT ILLUSTRATE THE 536 00:27:34,640 --> 00:27:37,276 IMPORTANCE OF THIS APPROACH. 537 00:27:37,276 --> 00:27:41,046 WE'LL REVIEW INCIPIENT NEOPLASIA 538 00:27:41,046 --> 00:27:46,552 AND CLONAL EVOLUTION, LINEAGE 539 00:27:46,552 --> 00:27:52,958 PLASTICITY OF LYMPHOID NEOPLASMS 540 00:27:52,958 --> 00:27:55,994 AND THE INTERFACE OF HODGKIN'S 541 00:27:55,994 --> 00:28:01,767 AND NON-HODGE KINGS LYMPHOMA. 542 00:28:01,767 --> 00:28:05,704 SOME ARE LINKED TO THE BCL II 543 00:28:05,704 --> 00:28:09,241 REARRANGEMENT AND IN ADDITION 544 00:28:09,241 --> 00:28:10,676 THERE'S CHARACTERISTIC AND 545 00:28:10,676 --> 00:28:14,112 RECURRENT MUTATIONS LISTED HERE. 546 00:28:14,112 --> 00:28:18,484 THIS IS A DISEASE ESSENTIALLY 547 00:28:18,484 --> 00:28:24,323 CONFINED TO ADULTS AND MOSTLY 548 00:28:24,323 --> 00:28:26,091 INCURABLE AND MOST PATIENTS 549 00:28:26,091 --> 00:28:28,093 PRESENTING WITH ADVANCED STAGE 550 00:28:28,093 --> 00:28:28,360 DISEASE. 551 00:28:28,360 --> 00:28:32,130 AN IMPORTANT STEP AFTER THE 552 00:28:32,130 --> 00:28:32,865 IDENTIFICATION OF THE TRANS 553 00:28:32,865 --> 00:28:34,333 LOCATION WAS OF WAS THE 554 00:28:34,333 --> 00:28:36,168 DEVELOPMENT OF MONOCLONAL 555 00:28:36,168 --> 00:28:39,471 ANTIBODIES TO BCL2 BY DAVID 556 00:28:39,471 --> 00:28:42,441 MASON SHOWING THE CELLS OF 557 00:28:42,441 --> 00:28:43,542 FOLLICULAR LYMPHOMA SHOWED OVER 558 00:28:43,542 --> 00:28:48,080 EXPRESSION OF BCL2 AND NORMAL 559 00:28:48,080 --> 00:28:57,155 GERMINAL CENTERS WERE NEGATIVE. 560 00:28:57,155 --> 00:28:59,291 WE RECEIVED A CASE AND 561 00:28:59,291 --> 00:29:00,425 PRESENTATION FROM A 23-YEAR-OLD 562 00:29:00,425 --> 00:29:02,961 FEMALE WHO PRESENTED WITH AN 563 00:29:02,961 --> 00:29:10,302 ISOLATED AND LARGE FEMORAL LYMPH 564 00:29:10,302 --> 00:29:14,873 NODE AND THE CLINICIAN SENT IT 565 00:29:14,873 --> 00:29:17,142 FOR CYTOGENETICS. 566 00:29:17,142 --> 00:29:19,077 WHILE THE LYMPH NODE SHOWED 567 00:29:19,077 --> 00:29:21,780 REACTIVE IT SHOWED A LOW NUMBER 568 00:29:21,780 --> 00:29:26,618 OF CELLS WITH THE 1418 TRANS 569 00:29:26,618 --> 00:29:29,755 LOCATION BY ROUTINE TYPE AND 570 00:29:29,755 --> 00:29:31,823 SEPT THE CASE WITH US IN 571 00:29:31,823 --> 00:29:33,992 CONSULTATION. 572 00:29:33,992 --> 00:29:37,596 FORTUNATELY, I JUST HAD GOTTEN A 573 00:29:37,596 --> 00:29:38,830 BCL2 BEYOND AND WERE STARTING TO 574 00:29:38,830 --> 00:29:42,568 USE IT IN THE LAB TO SEE ITS 575 00:29:42,568 --> 00:29:46,505 UTILITY AND WHEN I STAINED THIS 576 00:29:46,505 --> 00:29:52,077 LYMPH NODE I SAW SELECTIVE 577 00:29:52,077 --> 00:29:57,516 GERMINAL CENTERS POSITIVE OF 578 00:29:57,516 --> 00:29:59,251 CELLS EXPRESSING THE PROTEIN. 579 00:29:59,251 --> 00:30:01,186 INTERESTINGLY, WE CONTINUED AT 580 00:30:01,186 --> 00:30:02,721 FOLLOW-UP OF THE INDIVIDUAL 581 00:30:02,721 --> 00:30:05,424 PATIENT FOR MORE THAN 15 YEARS 582 00:30:05,424 --> 00:30:07,726 SHOWED SHE NEVER DEVELOPED 583 00:30:07,726 --> 00:30:10,762 FOLLICULAR LYMPHOMA. 584 00:30:10,762 --> 00:30:12,564 WE WENT ON TO STUDY ADDITIONAL 585 00:30:12,564 --> 00:30:15,434 CASES AND IDENTIFIED WHAT WE 586 00:30:15,434 --> 00:30:20,939 TERMED FOLLICULAR LYMPHOMA IN 587 00:30:20,939 --> 00:30:27,779 SI 588 00:30:27,779 --> 00:30:27,980 SITU. 589 00:30:27,980 --> 00:30:29,181 THE LYMPH NODE LOOKS REACTIVE 590 00:30:29,181 --> 00:30:31,316 AND SEE WELL FORMED GERMINAL 591 00:30:31,316 --> 00:30:32,784 CENTERS BUT WHEN YOU STAIN FOR 592 00:30:32,784 --> 00:30:35,187 THE BCL2 YOU SEE SEVERAL OF THE 593 00:30:35,187 --> 00:30:37,889 CENTERS HAVE CELLS THAT STRONGLY 594 00:30:37,889 --> 00:30:41,760 EXPRESS THE BCL2 PROTEIN. 595 00:30:41,760 --> 00:30:44,997 IN FURTHER STUDIES WE SHOWED THE 596 00:30:44,997 --> 00:30:48,467 BCL2 POSITIVE CELLS WERE CLONAL 597 00:30:48,467 --> 00:30:50,435 BY GENE REARRANGEMENT AND 598 00:30:50,435 --> 00:30:55,273 CONTAINED THE REARRANGEMENT AS 599 00:30:55,273 --> 00:30:55,574 WELL. 600 00:30:55,574 --> 00:30:56,875 IN SUBSEQUENT STUDIES WE STUDY 601 00:30:56,875 --> 00:30:59,878 THE CLINICAL OUTCOME OF THESE 602 00:30:59,878 --> 00:31:03,482 CASES WITH FOLLICULAR LYMPHOMA 603 00:31:03,482 --> 00:31:06,485 IN SITU AND OBSERVED THE 604 00:31:06,485 --> 00:31:14,660 PATIENTS AT LOW RISK TO DEVELOP 605 00:31:14,660 --> 00:31:15,794 SUBSEQUENT FOLLICULAR LYMPHOMA 606 00:31:15,794 --> 00:31:18,230 FIT WASN'T DETECTED AT INITIAL 607 00:31:18,230 --> 00:31:21,533 STAINING AND WERE INCIDENTAL 608 00:31:21,533 --> 00:31:23,502 FINDINGS SEEN IN OTHER B CELL 609 00:31:23,502 --> 00:31:26,505 LYMPHOMAS SEEN ABOUT 15% OF THE 610 00:31:26,505 --> 00:31:28,874 IN SITU CASES. 611 00:31:28,874 --> 00:31:33,278 BUT MOST THE PATIENTS HAD NO 612 00:31:33,278 --> 00:31:36,081 EVIDENCE OF DISEASE ON LONG-TERM 613 00:31:36,081 --> 00:31:38,016 FOLLOW-UP. 614 00:31:38,016 --> 00:31:39,184 IT'S SUBSEQUENTLY BEEN 615 00:31:39,184 --> 00:31:41,119 RECOGNIZED BCL2 TRANS LOCATION 616 00:31:41,119 --> 00:31:44,523 IS NOT RARE IN HEALTHY 617 00:31:44,523 --> 00:31:44,856 INDIVIDUALS. 618 00:31:44,856 --> 00:31:47,025 IT'S FOUND IN THE PERIPHERAL 619 00:31:47,025 --> 00:31:49,528 BLOOD UP TO 70% OF NORMAL ADULTS 620 00:31:49,528 --> 00:31:52,297 OVER THE AGE OF 50. 621 00:31:52,297 --> 00:31:56,001 THE NUMBERS INCREASE WITH AGE 622 00:31:56,001 --> 00:31:57,869 AND INCREASE WITH PESTICIDE USE 623 00:31:57,869 --> 00:32:05,877 IN FARMERS AS SHOWN WE THE WORK 624 00:32:05,877 --> 00:32:06,078 DONE. 625 00:32:06,078 --> 00:32:11,149 THE BCL2 ARE MEMORY B CELLS THAT 626 00:32:11,149 --> 00:32:16,088 HAVE UNDER GONE CLASS SWITCHING. 627 00:32:16,088 --> 00:32:23,028 THEY AND PRONE TO INTENSE 628 00:32:23,028 --> 00:32:24,629 TRAFFICKING AMONG GERMINAL 629 00:32:24,629 --> 00:32:25,964 CENTERS LEADING TO THEIR READY 630 00:32:25,964 --> 00:32:30,769 IDENTIFICATION BY IMMUNOHISTORIC 631 00:32:30,769 --> 00:32:31,036 CHEMISTRY. 632 00:32:31,036 --> 00:32:36,775 AND FOLLICULAR LYMPHOMA IN SITU 633 00:32:36,775 --> 00:32:40,712 AND B CELLS CO-EXIST IN THE SAME 634 00:32:40,712 --> 00:32:41,313 PATIENT. 635 00:32:41,313 --> 00:32:47,052 IT'S USUALLY A LARGE LYMPH NODE 636 00:32:47,052 --> 00:32:57,596 FOR DIAGNOSIS AND THEY FOUND IN 637 00:32:59,064 --> 00:33:00,065 IT BIOPSIES REMOVED FOR A 638 00:33:00,065 --> 00:33:02,868 VARIETY OF CAUSES. 639 00:33:02,868 --> 00:33:05,837 IT'S LIKELY AN IMMUNE STIMULUS 640 00:33:05,837 --> 00:33:06,571 LEADS TO THE INCREASED 641 00:33:06,571 --> 00:33:10,609 TRAFFICKING OF THE B CELLS IN 642 00:33:10,609 --> 00:33:12,310 GERMINAL CENTERS. 643 00:33:12,310 --> 00:33:16,648 THESE LYMPH NODES ALWAYS SHOW 644 00:33:16,648 --> 00:33:18,016 FOLLICULAR HYPERPLASIA THE B 645 00:33:18,016 --> 00:33:19,451 CELLS ARE ALWAYS FOUND WITHIN 646 00:33:19,451 --> 00:33:22,888 THE GERMINAL CENTER AND NOT 647 00:33:22,888 --> 00:33:25,957 RANDOMLY IN THE LYMPH NODE. 648 00:33:25,957 --> 00:33:27,959 THIS IS THE MODEL OF GENESIS 649 00:33:27,959 --> 00:33:29,094 THAT EMERGED. 650 00:33:29,094 --> 00:33:34,966 IT OCCURS BY A MISTAKE IN VDJ 651 00:33:34,966 --> 00:33:37,269 REARRANGE 652 00:33:37,269 --> 00:33:37,602 REARRANGEMENT. 653 00:33:37,602 --> 00:33:39,304 THE CELLS LEAVE THE BONE MARROW 654 00:33:39,304 --> 00:33:41,840 TO ENCOUNTER ANTIGEN IN THE 655 00:33:41,840 --> 00:33:44,376 GERMINAL CENTER AND EXPAND OVER 656 00:33:44,376 --> 00:33:47,579 TIME AND SECONDARY GENOMIC 657 00:33:47,579 --> 00:33:51,316 CHANGES ULTIMATELY LEAD TO 658 00:33:51,316 --> 00:33:54,452 FOLLICULAR LYMPHOMA. 659 00:33:54,452 --> 00:34:02,761 SOMEWHAT RELATED DISEASE IS A 660 00:34:02,761 --> 00:34:06,264 SIMILAR IT FOLLICULAR LYMPHOMA 661 00:34:06,264 --> 00:34:10,635 BUT POSITIVE FOR IGA AND 662 00:34:10,635 --> 00:34:12,070 COMMONLY PRESENTS IN THE 663 00:34:12,070 --> 00:34:18,510 DUODENUM AND OTHER SITES IN THE 664 00:34:18,510 --> 00:34:24,082 BOWEL AND INTERESTINGLY THE 665 00:34:24,082 --> 00:34:28,086 CELLS HAVE A HOMING CENTER AND 666 00:34:28,086 --> 00:34:30,856 HAVE LOCAL REOCCURRENCES BUT 667 00:34:30,856 --> 00:34:32,090 GENERALLY DO NOT DEVELOP 668 00:34:32,090 --> 00:34:33,859 DISSEMINATED DISEASE AND USUALLY 669 00:34:33,859 --> 00:34:36,261 HAVE A BENIGN CLINICAL COURSE. 670 00:34:36,261 --> 00:34:39,898 HERE'S AN EXAMPLE OF DUO DENIAL 671 00:34:39,898 --> 00:34:43,168 TYPE FOLLICULAR LYMPHOMA 672 00:34:43,168 --> 00:34:46,571 PRESENTING AS A SMALL POLYP AS A 673 00:34:46,571 --> 00:34:48,473 PATIENT UNDERGOING ENDOSCOPY FOR 674 00:34:48,473 --> 00:34:50,041 AN UNRELATED CAUSE. 675 00:34:50,041 --> 00:34:53,411 WE WANTED TO FURTHER INVESTIGATE 676 00:34:53,411 --> 00:34:57,015 THE GENOMIC PROFILE OF THE 677 00:34:57,015 --> 00:34:58,216 LESIONS. 678 00:34:58,216 --> 00:35:02,020 A FELLOW IN THE HEMOPATH SECTION 679 00:35:02,020 --> 00:35:04,856 PERFORMED LASER CAPTURE 680 00:35:04,856 --> 00:35:07,025 DISSECTION OF THE BCL2 POSITIVE 681 00:35:07,025 --> 00:35:09,594 CELLS. 682 00:35:09,594 --> 00:35:13,265 WE STUDIED A SERIES OF CASES 683 00:35:13,265 --> 00:35:18,470 INCLUDING FOLLICULAR LYMPHOMA IN 684 00:35:18,470 --> 00:35:22,107 SITU AND WERE SOMEWHAT BEYOND 685 00:35:22,107 --> 00:35:26,811 WHAT WE CALLED IN SITU DUO 686 00:35:26,811 --> 00:35:35,453 DENIAL TYPE FOLLICULAR LYMPHOMA. 687 00:35:35,453 --> 00:35:38,123 WE PERFORMED A RAY CGH IN THE 688 00:35:38,123 --> 00:35:44,129 CASES AND WHAT WE SAW WAS DUE 689 00:35:44,129 --> 00:35:47,799 AND FOUND A LOW NUMBER OF 690 00:35:47,799 --> 00:35:52,070 ALTERATIONS OR GENOMIC CHANGES 691 00:35:52,070 --> 00:35:57,042 IN DUODENAL TYPE LYMPHOMA AND 692 00:35:57,042 --> 00:35:58,977 THOSE WE CALLED PARTIALLY 693 00:35:58,977 --> 00:35:59,377 INVOLVED. 694 00:35:59,377 --> 00:36:03,815 THEY SEEM RELATIVELY CLOSE TO IN 695 00:36:03,815 --> 00:36:13,024 SITU BUT CLEARLY AND OTHERS IN 696 00:36:13,024 --> 00:36:16,561 FULL BLOWN FOLLICULAR LYMPHOMA 697 00:36:16,561 --> 00:36:18,663 AND BEING GREATER THAN GRADE 2. 698 00:36:18,663 --> 00:36:21,933 NOTABLY WE DID NOT DETECT 699 00:36:21,933 --> 00:36:24,903 ABERRATIONS IN CASES OF 700 00:36:24,903 --> 00:36:26,638 FOLLICULAR HYPERPLASIA NOR IN 701 00:36:26,638 --> 00:36:28,306 THE BACKGROUND TISSUE AWAY FROM 702 00:36:28,306 --> 00:36:31,943 THE INVOLVED FOLLICLES. 703 00:36:31,943 --> 00:36:35,313 SO, THIS SUMMARIZES THE 704 00:36:35,313 --> 00:36:38,717 EVOLUTION OF FOLLICULAR LYMPHOMA 705 00:36:38,717 --> 00:36:41,386 AS THE EPIGENOMIC LEVEL. 706 00:36:41,386 --> 00:36:43,621 IT BEGINS IN THE BONE MARROW 707 00:36:43,621 --> 00:36:48,626 WITH THE 418 TRANS LOCATION. 708 00:36:48,626 --> 00:36:52,197 FL LIKE B CELLS IN HEALTHY 709 00:36:52,197 --> 00:36:58,303 INDIVIDUALS HAVE AN ALMOST 710 00:36:58,303 --> 00:37:08,780 INFINITE RISK WHERE THE RISK IN 711 00:37:08,780 --> 00:37:11,916 IN SITU FOLLICULAR IS 2-3%. 712 00:37:11,916 --> 00:37:20,291 IN ADDITION TO THE BCL2 REA 713 00:37:20,291 --> 00:37:21,760 MAN 714 00:37:21,760 --> 00:37:23,294 RANGEMENT WE SEE SOME INCLUDING 715 00:37:23,294 --> 00:37:31,936 KREB EP AND TNFRSF14 AND 716 00:37:31,936 --> 00:37:34,806 MUTATIONS APPEAR TO BE A LATE 717 00:37:34,806 --> 00:37:39,110 EVENT AND GENERALLY ABSENT. 718 00:37:39,110 --> 00:37:41,746 SO THIS SUMMARIZES THE 719 00:37:41,746 --> 00:37:45,116 CONCEPTUAL MODEL OF FOLLICULAR 720 00:37:45,116 --> 00:37:46,918 LYMPHOMA FROM PRECURSOR B CELLS 721 00:37:46,918 --> 00:37:50,155 AND ACQUIRE THE 14-18. 722 00:37:50,155 --> 00:37:51,823 MOST PATIENT WITH THESE CELLS IN 723 00:37:51,823 --> 00:37:53,725 THE BLOOD WILL NEVER PROGRESS. 724 00:37:53,725 --> 00:37:55,994 FOLLOWING ANTIGEN STIMULATION 725 00:37:55,994 --> 00:37:59,664 THE CLONAL PROGENITORS UNDER GO 726 00:37:59,664 --> 00:38:02,133 CYCLES OF GERMINAL CENTER 727 00:38:02,133 --> 00:38:03,735 RE-ENTRY WITH CLONAL EXPANSION 728 00:38:03,735 --> 00:38:05,270 AND GENOMIC INSTABILITY AND 729 00:38:05,270 --> 00:38:09,040 ULTIMATELY DISSEMINATION. 730 00:38:09,040 --> 00:38:16,081 AND KMT2D IS RELATED TO RISK BE 731 00:38:16,081 --> 00:38:17,682 WITH DEVELOPMENT OF CLINICALLY 732 00:38:17,682 --> 00:38:18,483 SIGNIFICANT DISEASE. 733 00:38:18,483 --> 00:38:21,653 THE RELAPSES DEVELOP BY LINEAR 734 00:38:21,653 --> 00:38:25,390 EVOLUTION AND DIVERGENT 735 00:38:25,390 --> 00:38:29,961 EVOLUTION AND THAT MAY LEAD TO 736 00:38:29,961 --> 00:38:32,363 TRANSFORMATION WHICH CAN ACQUIRE 737 00:38:32,363 --> 00:38:34,065 DIVERSION PHENOTYPES AND EVEN 738 00:38:34,065 --> 00:38:34,632 LINEAR SWITCH AS WE'LL SEE 739 00:38:34,632 --> 00:38:38,236 LATER. 740 00:38:38,236 --> 00:38:41,539 SO, A COMMON ASSOCIATION WITH 741 00:38:41,539 --> 00:38:43,241 PROGRESSION OF FOLLICULAR 742 00:38:43,241 --> 00:38:47,812 LYMPHOMA IS THE DEVELOPMENT OF 743 00:38:47,812 --> 00:38:50,315 LARGE B CELL LYMPHOMA AND OFTEN 744 00:38:50,315 --> 00:38:51,950 ASSOCIATED WITH B53 MUTATION. 745 00:38:51,950 --> 00:38:58,289 IN A SERIES OF STUDIES LED BY A 746 00:38:58,289 --> 00:39:00,792 GROUP THEY STUDIED SECONDARY 747 00:39:00,792 --> 00:39:03,495 GENETIC EVENTS ASSOCIATED WITH 748 00:39:03,495 --> 00:39:05,663 FOLLICULAR LYMPHOMA PROGRESSION. 749 00:39:05,663 --> 00:39:09,868 P53 MUTATION IS A COMMON EVENT 750 00:39:09,868 --> 00:39:13,238 AND ASSOCIATED WITH 751 00:39:13,238 --> 00:39:16,474 TRANSFORMATION DIFFUSE LARGE B 752 00:39:16,474 --> 00:39:20,578 CELL LYMPHOMA AND SUPPRESSER 753 00:39:20,578 --> 00:39:21,946 GENES ARE ASSOCIATED WITH 754 00:39:21,946 --> 00:39:25,283 PROGRESSION AND SIGNIFICANTLY 755 00:39:25,283 --> 00:39:32,590 MICK REARRANGEMENT HIT NO DOUBLE 756 00:39:32,590 --> 00:39:35,560 HIT LYMPHOMAS HAVING AN 757 00:39:35,560 --> 00:39:41,699 AGGRESSIVE CLINICAL COURSE. 758 00:39:41,699 --> 00:39:48,072 SO, THESE ARE THE VARIOUS FORMS 759 00:39:48,072 --> 00:39:50,408 DIFFUSED B CELL AND DOUBLE HIT 760 00:39:50,408 --> 00:39:52,043 AND INTERESTINGLY SOME OF THESE 761 00:39:52,043 --> 00:39:56,514 DOUBLE HIT LYMPHOMAS EXPRESS TDT 762 00:39:56,514 --> 00:40:01,119 AND CAN MIMIC LYMPHOBLASTIC 763 00:40:01,119 --> 00:40:05,023 LYMPHOMA AND ONE CAN SEE 764 00:40:05,023 --> 00:40:06,724 DEVELOPMENT OF HODGKIN'S 765 00:40:06,724 --> 00:40:11,529 LYMPHOMA AND WERE SURPRISED TO 766 00:40:11,529 --> 00:40:14,265 ENCOUNTER CASES THAT RESEMBLE 767 00:40:14,265 --> 00:40:18,036 SARCOMA OR DENDRITIC CELLS. 768 00:40:18,036 --> 00:40:19,704 THIS IS CASE 2. 769 00:40:19,704 --> 00:40:22,006 A 60-YEAR-OLD MAN WITH A 770 00:40:22,006 --> 00:40:24,776 DIAGNOSIS OF FOLLICULAR 771 00:40:24,776 --> 00:40:25,243 LYMPHOMA. 772 00:40:25,243 --> 00:40:27,078 THREE YEARS AFTER DIAGNOSIS HE 773 00:40:27,078 --> 00:40:30,048 HAD A SECOND LYMPH NODE BIOPSY 774 00:40:30,048 --> 00:40:31,916 SHOWING A PLEOMORPHIC AND 775 00:40:31,916 --> 00:40:36,054 PLASTIC LOOKING TUMOR THAT 776 00:40:36,054 --> 00:40:39,824 EXPRESSED MARKERS OF HISTIOCYTES 777 00:40:39,824 --> 00:40:43,094 AND NEGATIVE FOR CU20 AND FOR 778 00:40:43,094 --> 00:40:47,932 PAX 5 BUT POSITIVE FOR CD 68 AND 779 00:40:47,932 --> 00:40:49,901 S100 AMONG OTHERS. 780 00:40:49,901 --> 00:40:52,003 IN A SUBSEQUENT STUDY CONDUCTED 781 00:40:52,003 --> 00:40:59,244 BY ANDY FELDMAN A FELLOW IN THE 782 00:40:59,244 --> 00:41:00,878 LABORATORY, WE STUDIED THE 783 00:41:00,878 --> 00:41:06,084 FOLLICULAR LYMPHOMAS WITH 784 00:41:06,084 --> 00:41:08,052 SARCOMA AND PROVIDED EVIDENCE 785 00:41:08,052 --> 00:41:10,455 FOR TRANS DIFFERENTIATION FROM 786 00:41:10,455 --> 00:41:12,790 THE FOLLICULAR LYMPHOMA CLONE. 787 00:41:12,790 --> 00:41:14,892 ALL EIGHT CASES SHARED CLONAL 788 00:41:14,892 --> 00:41:18,229 IDENTITY WITH THE PRIOR 789 00:41:18,229 --> 00:41:20,531 FOLLICULAR LYMPHOMA BASED ON 790 00:41:20,531 --> 00:41:24,068 IMMUNOGLOBULIN SEQUENCING AND 791 00:41:24,068 --> 00:41:27,171 IDENTICAL BCL2 REARRANGEMENT. 792 00:41:27,171 --> 00:41:28,940 THERE WAS A CHANGE IN THE 793 00:41:28,940 --> 00:41:30,575 TRANSCRIPTION FACTORS WITH LOSS 794 00:41:30,575 --> 00:41:34,312 OF PAX 5, LOSS OF OTHER MARKERS 795 00:41:34,312 --> 00:41:37,949 OF B CELL LINEAGE BUT EXPRESSION 796 00:41:37,949 --> 00:41:42,654 OF WILL PU 1 AND THE BETA 797 00:41:42,654 --> 00:41:44,122 ASSOCIATE WILL WITH THE 798 00:41:44,122 --> 00:41:45,857 DIFFERENT IS SAYING THATS. 799 00:41:45,857 --> 00:41:53,364 THIS WAS A SURPRISE TO US AND 800 00:41:53,364 --> 00:41:56,567 THIS PROVIDED THE DIFFERENCE AND 801 00:41:56,567 --> 00:41:59,837 IN EARLIER WORK DONE BY GRAPH 802 00:41:59,837 --> 00:42:03,408 AND COLLEAGUES, THEY SHOWED 803 00:42:03,408 --> 00:42:09,447 MATURE B CELLS COULD BE 804 00:42:09,447 --> 00:42:12,784 REPROGRAMMED FUNCTIONALLY INTO 805 00:42:12,784 --> 00:42:14,485 MACROPHAGES WITH BLOCKAGE OF PAX 806 00:42:14,485 --> 00:42:16,788 5 AND OVER EXPRESSION OF PU 1 AS 807 00:42:16,788 --> 00:42:23,194 WE SAW IN OUR CLINICAL CASES. 808 00:42:23,194 --> 00:42:33,771 IN SUBSEQUENT WORK DONE AND WE 809 00:42:33,771 --> 00:42:37,108 HAVE A HISTORY OF SARCOMA 810 00:42:37,108 --> 00:42:39,177 ASSOCIATED WITH LYMPHOID 811 00:42:39,177 --> 00:42:39,477 MALIGNANCY. 812 00:42:39,477 --> 00:42:50,021 IN THIS SETTING THE HISTIOCYTIC 813 00:42:55,126 --> 00:42:59,030 TUMORS ARE SEEN IN MALIGNANCIES 814 00:42:59,030 --> 00:43:09,540 SEEN WITH FOLLICULAR LYMPHOMA. 815 00:43:12,443 --> 00:43:14,979 HERE'S ONE OF THE CASES STUDIED. 816 00:43:14,979 --> 00:43:16,147 HERE'S A NUMBER OF MUTATIONS 817 00:43:16,147 --> 00:43:19,784 THAT WERE SHARED BY BOTH THE 818 00:43:19,784 --> 00:43:23,955 FOLLICULAR LYMPHOMA AND 819 00:43:23,955 --> 00:43:27,492 HISTORYIOCYTIC LYMPHOMA AND SOME 820 00:43:27,492 --> 00:43:30,795 MUTATIONS UNIQUE TO THE 821 00:43:30,795 --> 00:43:31,429 FOLLICULAR LYMPHOMA AND OTHERS 822 00:43:31,429 --> 00:43:36,000 TO THE KEV DEF 823 00:43:44,242 --> 00:43:46,177 HISTIOCYTIC LYMPHOMA AND SOME 824 00:43:46,177 --> 00:43:54,018 ARE ASSOCIATED WITH THE GENE 825 00:43:54,018 --> 00:43:59,424 ARRANGEMENT AND CONVENTIONAL 826 00:43:59,424 --> 00:44:09,967 FOLLICULAR LYMPHOMA AND THAT'S 827 00:44:13,070 --> 00:44:16,808 NOT THE CASE FOR ALL. 828 00:44:16,808 --> 00:44:23,314 CASE 3 WAS A LYMPH NODE THAT 829 00:44:23,314 --> 00:44:30,521 SHOWED SCLERROSING HODGKIN'S AND 830 00:44:30,521 --> 00:44:31,255 ONE MONTH FOLLOWING COMPLETION 831 00:44:31,255 --> 00:44:35,893 OF THERAPY HE PRESENTED WITH A 832 00:44:35,893 --> 00:44:43,501 NEW MEDIASTINAL MASK. 833 00:44:43,501 --> 00:44:44,769 WE DIDN'T SEE EVIDENCE OF 834 00:44:44,769 --> 00:44:48,906 HODGKIN'S BUT SAW A TUMOR THAT 835 00:44:48,906 --> 00:44:53,177 RESEMBLED LARGE B CELL LYMPHOMA. 836 00:44:53,177 --> 00:45:00,618 THE QUESTION WAS IS THIS ONE OR 837 00:45:00,618 --> 00:45:01,018 TWO TUMOR. 838 00:45:01,018 --> 00:45:06,257 ON THE RIGHT YOU SEE THE PRIMARY 839 00:45:06,257 --> 00:45:09,694 MEDIASTINNAL LARGE B CELL 840 00:45:09,694 --> 00:45:14,298 LYMPHOMA AND THE AND ON THE LEFT 841 00:45:14,298 --> 00:45:15,766 HODGKINS EXPRESSING CD 30 AND 15 842 00:45:15,766 --> 00:45:25,009 AND ON THE RIGHT A B CELL 843 00:45:25,009 --> 00:45:27,512 EXPRESSING OCT 2 AND SINGLE CELL 844 00:45:27,512 --> 00:45:28,646 MICROEXPRESSION OF BOTH DON'TS 845 00:45:28,646 --> 00:45:29,180 SHOWED THEY WERE CLONALLY 846 00:45:29,180 --> 00:45:31,349 RELATED. 847 00:45:31,349 --> 00:45:33,017 SO IT HAD BEEN RECOGNIZED FOR 848 00:45:33,017 --> 00:45:35,319 SOME TIME THERE WERE COMMON 849 00:45:35,319 --> 00:45:39,390 FEATURES OF PRIMARY MEDIA STINAL 850 00:45:39,390 --> 00:45:44,595 OR THYMIC LARGE B CELL LYMPHOMA 851 00:45:44,595 --> 00:45:46,497 AND HODGKIN'S. 852 00:45:46,497 --> 00:45:48,332 BOTH ARE MORE COMMON IN FEMALES 853 00:45:48,332 --> 00:45:55,673 AND PRESENT IN ADOLESCENCE AND 854 00:45:55,673 --> 00:45:56,674 YOUNG ADULTS AN SHARE 855 00:45:56,674 --> 00:45:59,210 ALTERATIONS AND HAVE A SIMILAR 856 00:45:59,210 --> 00:46:02,313 GENE EXPRESSION PROFILE WITH 857 00:46:02,313 --> 00:46:07,418 ACTIVATION OF THE NF CAPA B 858 00:46:07,418 --> 00:46:10,321 PATHWAY SHOWN IN LABS. 859 00:46:10,321 --> 00:46:16,060 AND BOTH ARE THOUGHT ARISE FROM 860 00:46:16,060 --> 00:46:20,398 A THYMIC B CELL. 861 00:46:20,398 --> 00:46:24,869 WE PROPOSED A B CELL SARCOMA 862 00:46:24,869 --> 00:46:26,270 PRESENTING A MISSING LINK FROM A 863 00:46:26,270 --> 00:46:33,444 TYPE OF HODGKIN'S AND PMBL. 864 00:46:33,444 --> 00:46:36,180 THEY CAN'T BE READILY CLASSIFIED 865 00:46:36,180 --> 00:46:40,751 AS PMBL OR CLASSIC HODGKIN'S AND 866 00:46:40,751 --> 00:46:45,289 THERE'S ASYNCHRONY IN THE 867 00:46:45,289 --> 00:46:45,823 PHENOTYPE. 868 00:46:45,823 --> 00:46:47,658 THEY'RE SIMILAR TO THE ENTITIES 869 00:46:47,658 --> 00:46:49,160 EXCEPT FOR UNKNOWN REASONS 870 00:46:49,160 --> 00:46:52,063 THEY'RE MORE COMMON IN MALES 871 00:46:52,063 --> 00:46:56,000 THAN FEMALES AND COMPOSITE AND 872 00:46:56,000 --> 00:46:58,836 SEQUENTIAL LYMPHOMAS ARE A 873 00:46:58,836 --> 00:47:01,606 RELATED PHENOMENON. 874 00:47:01,606 --> 00:47:05,910 HERE'S ONE EXAMPLE OF MEDIA 875 00:47:05,910 --> 00:47:09,413 STINAL GRAY ZONE LYMPHOMA WITH 876 00:47:09,413 --> 00:47:16,253 AN ARRANGEMENT OF CELLS THAT 877 00:47:16,253 --> 00:47:17,321 SHOW STRONG EXPRESSION OF THE B 878 00:47:17,321 --> 00:47:19,357 CELL LOCATION PROGRAM AND 879 00:47:19,357 --> 00:47:22,093 ANOTHER TYPE OF GRAY ZONE 880 00:47:22,093 --> 00:47:26,097 LYMPHOMA IN WHICH HISTOLOGICALLY 881 00:47:26,097 --> 00:47:29,533 IT LOOKS LIKE B CELL LYMPHOMA 882 00:47:29,533 --> 00:47:34,705 BUT EXPRESS THE IMMUNOTYPIC 883 00:47:34,705 --> 00:47:38,042 MARKERS OF CLASSIC HODGKIN'S 884 00:47:38,042 --> 00:47:39,644 LYMPHOMA. 885 00:47:39,644 --> 00:47:42,413 MEDIASTINAL GRADE CELL LYMPHOMA 886 00:47:42,413 --> 00:47:44,715 IS THIS INTERMEDIATE FORM AND 887 00:47:44,715 --> 00:47:46,651 INTERESTINGLY THIS IS A 888 00:47:46,651 --> 00:47:49,286 TWO-DIRECTIONAL HIGHWAY. 889 00:47:49,286 --> 00:47:51,989 YOU CAN SEE NS HODGKIN'S RELAPSE 890 00:47:51,989 --> 00:48:01,932 AS PMBL OR PMBL RELAPSING AS NS 891 00:48:01,932 --> 00:48:02,600 HODGE KINDS AND IT'S THE MISSING 892 00:48:02,600 --> 00:48:05,069 LINK WE DESCRIBED. 893 00:48:05,069 --> 00:48:06,570 THERE WERE A NUMBER OF 894 00:48:06,570 --> 00:48:07,038 CONTINUING QUESTIONS. 895 00:48:07,038 --> 00:48:10,775 CAN BIOLOGICAL STUDIES PROVIDE 896 00:48:10,775 --> 00:48:14,378 INSIGHTS INTO THE BIOLOGY OF 897 00:48:14,378 --> 00:48:16,881 MEDIASTINAL GRAY CELL IS IT 898 00:48:16,881 --> 00:48:21,085 CLOSER TO HODGKIN'S OR PMBL. 899 00:48:21,085 --> 00:48:24,088 IN INITIAL WORK DONE IN THE LAB 900 00:48:24,088 --> 00:48:28,059 THEY PERFORMED A METHYLATION 901 00:48:28,059 --> 00:48:28,325 PROFILING. 902 00:48:28,325 --> 00:48:30,428 SHE DID MICRODISSECTION OF TUMOR 903 00:48:30,428 --> 00:48:32,096 CELLS FROM GRAY CELL,ING 904 00:48:32,096 --> 00:48:35,266 HODGKIN'S AND PMBL AND SHOWED 905 00:48:35,266 --> 00:48:37,201 THE EPIGENETIC PROFILE OF THE 906 00:48:37,201 --> 00:48:47,745 GRAY ZONE PHOMAS HAD A SHOWING 907 00:49:02,393 --> 00:49:10,134 AND GRAY ZONE LYMPHOMA AND PMB 908 00:49:10,134 --> 00:49:10,568 4L 909 00:49:10,568 --> 00:49:13,537 AND THE GRAY CELL SHOWED CLOSER 910 00:49:13,537 --> 00:49:19,877 TO CLASSIC HODGKIN'S THAN PMBL. 911 00:49:19,877 --> 00:49:22,980 IN WORK THEY LOOKED AT A VARIETY 912 00:49:22,980 --> 00:49:27,151 OF KEY SIGNATURES AGAIN SHOWING 913 00:49:27,151 --> 00:49:29,286 MEDIASTINAL GRAY ZONE LYMPHOMA 914 00:49:29,286 --> 00:49:32,857 IN GENERAL ABUTTED THE GENE 915 00:49:32,857 --> 00:49:35,059 EXPRESSION PROFILE OF HODGKIN'S 916 00:49:35,059 --> 00:49:38,662 MORE THAN THAT OF PMBL. 917 00:49:38,662 --> 00:49:40,431 NEVERTHELESS THE DIFFERENTIAL 918 00:49:40,431 --> 00:49:43,601 DIAGNOSIS OF CLASSIC HODGKIN'S 919 00:49:43,601 --> 00:49:44,902 IS STILL IMPORTANT AS THERE'S 920 00:49:44,902 --> 00:49:46,971 MAJOR TREATMENT DIFFERENCES. 921 00:49:46,971 --> 00:49:50,107 TO ANSWER HOW THESE PATIENTS 922 00:49:50,107 --> 00:49:52,843 SHOULD BE TREATED, LINDA WILSON 923 00:49:52,843 --> 00:49:57,114 LED A STUDY OF MEDIASTINAL GRAY 924 00:49:57,114 --> 00:50:03,554 CELL LYMPHOMA WITH EPOCR AND 925 00:50:03,554 --> 00:50:07,491 SUCCESSFUL IN CURING PMBL AND 926 00:50:07,491 --> 00:50:10,795 WAS EFFICACIOUS IN THE GRAY ZONE 927 00:50:10,795 --> 00:50:14,098 LYMPHOMAS BUT STILL WITH 928 00:50:14,098 --> 00:50:19,503 INFERIOR OUTCOME THOSE PATIENTS 929 00:50:19,503 --> 00:50:20,638 WITH THE RELAPSE DISEASE COULD 930 00:50:20,638 --> 00:50:23,040 BE RESCUED WITH RADIATION 931 00:50:23,040 --> 00:50:23,641 THERAPY OR OTHER THERAPEUTIC 932 00:50:23,641 --> 00:50:32,483 APPROACHES. 933 00:50:32,483 --> 00:50:37,221 IN ADDITION THE BLOCKADE HAS 934 00:50:37,221 --> 00:50:39,590 EMERGED AS A TOOL IN THE 935 00:50:39,590 --> 00:50:43,427 TREATMENT OF NON HODGKIN'S 936 00:50:43,427 --> 00:50:50,701 LYMPHOMA HAS EXPRESSION OF PHO 937 00:50:50,701 --> 00:50:55,606 XSTAT 3 AND SHOWN TO BE 938 00:50:55,606 --> 00:50:57,174 EFFECTIVE IN CLASSIC HODGKIN'S 939 00:50:57,174 --> 00:50:58,909 LYMPHOMA AND ANOW USED IN 940 00:50:58,909 --> 00:50:59,844 UNTREATED PATIENTS. 941 00:50:59,844 --> 00:51:04,281 IN A PILOT CLINICAL STUDY, CHRIS 942 00:51:04,281 --> 00:51:06,717 MELANI SHOWED THE APPROACH IS 943 00:51:06,717 --> 00:51:11,455 ALSO EFFECTIVE IN MEDIA STINAL 944 00:51:11,455 --> 00:51:14,325 GRAY CELL LYMPHOMA WITH PATIENTS 945 00:51:14,325 --> 00:51:18,162 ACHIEVING COMPLETE REMISSION 946 00:51:18,162 --> 00:51:22,633 AFTER RELAPSE WITH JAK POINT 947 00:51:22,633 --> 00:51:23,300 INHIBITOR THERAPY. 948 00:51:23,300 --> 00:51:26,937 IN CONCLUSION THE TIME LINE 949 00:51:26,937 --> 00:51:29,874 ILLUSTRATES THE CHANGES IN 950 00:51:29,874 --> 00:51:32,476 LYMPHOMA CLASSIFICATION AND THE 951 00:51:32,476 --> 00:51:38,916 IMPACT IN CLINICAL AND TECHNICAL 952 00:51:38,916 --> 00:51:39,216 ADVANCES. 953 00:51:39,216 --> 00:51:46,790 AND WE HAVE SEEN THE IMPACT OF 954 00:51:46,790 --> 00:51:48,058 IMMUNOLOGIC CHARACTERIZATION, 955 00:51:48,058 --> 00:51:49,226 MOLECULAR CHARACTERIZATION WITH 956 00:51:49,226 --> 00:51:53,931 NGS EMERGING AS AN IMPORTANT NEW 957 00:51:53,931 --> 00:51:56,066 TOOL FOR DIAGNOSIS AND 958 00:51:56,066 --> 00:52:02,106 CLASSIFICATION. 959 00:52:02,106 --> 00:52:06,577 SO SOME CLOSING THOUGHTS, THESE 960 00:52:06,577 --> 00:52:09,780 ARE CARICATURES OF THE SYSTEM 961 00:52:09,780 --> 00:52:15,252 AND INFORM OUR THINK OF CLASSIC 962 00:52:15,252 --> 00:52:18,188 AND NEOPLASTIC CELLS AND SPREAD 963 00:52:18,188 --> 00:52:20,457 AS PART OF THEIR FUNCTION. 964 00:52:20,457 --> 00:52:22,493 BENIGN CLONAL EXPANSIONS OF 965 00:52:22,493 --> 00:52:25,663 LYMPHOCYTES DO NOT REMAIN 966 00:52:25,663 --> 00:52:28,065 LOCALIZED BY DISSEMINATE ON 967 00:52:28,065 --> 00:52:31,635 HOMING AND THUS WITH LYMPHOID 968 00:52:31,635 --> 00:52:32,469 NEOPLASMS THE DISTINCTION 969 00:52:32,469 --> 00:52:43,013 BETWEEN BENIGN AND MALIGNANT AND 970 00:52:49,820 --> 00:52:51,322 MIGHT BE LOOKED AT AND ONE OF 971 00:52:51,322 --> 00:52:53,791 THE LYMPHOMA OF THE LYMPHOID 972 00:52:53,791 --> 00:52:54,992 SYSTEM AND OBSERVATIONS THAT WE 973 00:52:54,992 --> 00:52:59,530 MAKE AT THE MICROSCOPE AND IN 974 00:52:59,530 --> 00:53:03,033 THE CLINIC ARE STILL A STARTING 975 00:53:03,033 --> 00:53:06,203 POINT FOR DISEASE DISCOVERY. 976 00:53:06,203 --> 00:53:09,640 SO I'D LIKE TO ACKNOWLEDGE 977 00:53:09,640 --> 00:53:19,984 MEMBERS OF THE TEAM AT THE NCI 978 00:53:19,984 --> 00:53:24,054 AND OF COURSE FROM THE LYMPHOMA 979 00:53:24,054 --> 00:53:30,961 BRANCH, . 980 00:53:30,961 --> 00:53:34,365 I'VE HAD WONDERFUL LONG-TERM 981 00:53:34,365 --> 00:53:35,132 INTERNATIONAL COLLABORATORS. 982 00:53:35,132 --> 00:53:37,434 INTERESTINGLY, BOTH DID 983 00:53:37,434 --> 00:53:41,271 FELLOWSHIPS HERE AT THE NCI AND 984 00:53:41,271 --> 00:53:44,141 WENT ON TO HAVE STELLAR CAREERS 985 00:53:44,141 --> 00:53:46,076 IN LYMPHOMA RESEARCH. 986 00:53:46,076 --> 00:53:50,881 OTHER COLLABORATORS IN 987 00:53:50,881 --> 00:53:53,150 MARSEILLE, FRANCE AND THE ANSWER 988 00:53:53,150 --> 00:53:55,419 AGENCY AND MEMBERS OF THIS LLMPP 989 00:53:55,419 --> 00:54:00,691 AND OTHER MEMBERS OF THE NCI, 990 00:54:00,691 --> 00:54:03,260 CCR TEAM SHOWN HERE. 991 00:54:03,260 --> 00:54:05,896 I THINK NONE OF THIS WOULD HAVE 992 00:54:05,896 --> 00:54:09,633 HAPPENED WITHOUT THE WORK OF SO 993 00:54:09,633 --> 00:54:11,969 MANY -- I'M GOING TO TEAR UP. 994 00:54:11,969 --> 00:54:13,237 SO MANY FELLOWS OVER THE YEAR. 995 00:54:13,237 --> 00:54:16,874 IT'S BEEN AN HONOR AND PRIVILEGE 996 00:54:16,874 --> 00:54:18,909 TO TRAIN THESE WONDERFUL PEOPLE. 997 00:54:18,909 --> 00:54:21,478 SINCE 1974 WE'VE TRAINED MORE 998 00:54:21,478 --> 00:54:24,014 THAN 80 CLINICAL FELLOWS, MORE 999 00:54:24,014 --> 00:54:27,117 THAN 25 VISITING FELLOWS. 1000 00:54:27,117 --> 00:54:30,421 THESE ARE LEADERS IN THEHEMATO 1001 00:54:30,421 --> 00:54:32,423 PATHOLOGY COMMUNITY IN THE 1002 00:54:32,423 --> 00:54:39,463 U.S. AND AROUND THE WORLD A -- 1003 00:54:39,463 --> 00:54:41,498 AND AN IMPORTANT MISSION I HOPE 1004 00:54:41,498 --> 00:54:42,466 WILL BE FULFILLED IN THE FUTURE 1005 00:54:42,466 --> 00:54:44,101 AT THE NCI. 1006 00:54:44,101 --> 00:54:45,803 THANK YOU. 1007 00:54:45,803 --> 00:54:49,273 >> YOU CAN STAY THERE. 1008 00:54:49,273 --> 00:54:52,042 SO PLEASE USE THE MICS FOR 1009 00:54:52,042 --> 00:54:52,309 QUESTIONS. 1010 00:54:52,309 --> 00:55:02,719 NO QUESTIONS ONLINE YET. 1011 00:55:08,792 --> 00:55:10,861 DR. STOUT, YOU WANT TO LEAD OFF? 1012 00:55:10,861 --> 00:55:14,131 >> WONDERFUL, ELAINE. 1013 00:55:14,131 --> 00:55:19,236 I HAVE ENJOYED YOU ON PART OF 1014 00:55:19,236 --> 00:55:19,736 THAT RIDE. 1015 00:55:19,736 --> 00:55:23,640 I WANTED YOU TO WAX A LITTLE 1016 00:55:23,640 --> 00:55:23,974 PHILOSOPHICAL. 1017 00:55:23,974 --> 00:55:25,576 I THINK YOU NICELY CATEGORIZED 1018 00:55:25,576 --> 00:55:28,045 THE MISSION OF THE PATHOLOGISTS 1019 00:55:28,045 --> 00:55:30,614 AS ONE THAT DEFINES BIOLOGICAL 1020 00:55:30,614 --> 00:55:36,920 DISEASE ENTITIES. 1021 00:55:36,920 --> 00:55:38,021 AND IT STARTS WITH THE 1022 00:55:38,021 --> 00:55:40,691 MICROSCOPE BUT THE SCOPE OF IT 1023 00:55:40,691 --> 00:55:44,761 ENCOMPASSES THE MOLECULAR 1024 00:55:44,761 --> 00:55:47,831 ABNORMALITIES AS WELL. 1025 00:55:47,831 --> 00:55:49,800 THE QUESTION IS HOW DOES ONE 1026 00:55:49,800 --> 00:55:50,234 DIAGNOSE DISEASE? 1027 00:55:50,234 --> 00:55:53,003 THAT'S ONE POINT OF VIEW BUT THE 1028 00:55:53,003 --> 00:55:55,205 OTHER POINT OF VIEW SO 1029 00:55:55,205 --> 00:55:56,840 ELOQUENTLY PUT BY HENRY KAPLAN 1030 00:55:56,840 --> 00:55:59,843 IS I DON'T CARE ABOUT IT UNTIL 1031 00:55:59,843 --> 00:56:00,978 IT'S GOING TO CHANGE HOW I TREAT 1032 00:56:00,978 --> 00:56:04,848 THE PATIENT. 1033 00:56:04,848 --> 00:56:08,418 THOSE CAN BE SEEN AS IN CONFLICT 1034 00:56:08,418 --> 00:56:11,989 BUT I DON'T SEE THEM AS IN 1035 00:56:11,989 --> 00:56:12,256 CONFLICT. 1036 00:56:12,256 --> 00:56:16,026 I WANTED TO SEE HOW WE SHOULD 1037 00:56:16,026 --> 00:56:20,063 ARRIVE AT A REAL CLASSIFICATION 1038 00:56:20,063 --> 00:56:25,068 OF CANCERS AND WHEN TO 1039 00:56:25,068 --> 00:56:26,470 INCORPORATE MOLECULAR 1040 00:56:26,470 --> 00:56:27,171 UNDERSTANDING IN THAT. 1041 00:56:27,171 --> 00:56:29,773 >> I MEAN, I THINK THE MOLECULAR 1042 00:56:29,773 --> 00:56:34,111 TECHNIQUES ARE BECOMING PART OF 1043 00:56:34,111 --> 00:56:35,679 OUR DAILY ARMAMENTARIUM AND I 1044 00:56:35,679 --> 00:56:38,982 TALKED ABOUT THE CLASSIC FORM OF 1045 00:56:38,982 --> 00:56:40,284 FOLLICULAR LYMPHOMA BUT WE HAVE 1046 00:56:40,284 --> 00:56:43,754 OTHER TUMORS WE CALL, QUOTE, 1047 00:56:43,754 --> 00:56:44,588 FOLLICULAR LYMPHOMA DIFFERENT AT 1048 00:56:44,588 --> 00:56:45,689 THE MOLECULAR LEVEL AND 1049 00:56:45,689 --> 00:56:46,924 UNDERSTAND THOSE HAVE TO BE 1050 00:56:46,924 --> 00:56:47,758 TREATED IN DIFFERENT WAYS. 1051 00:56:47,758 --> 00:56:52,062 AS AN EXAMPLE, WE HAVE QUOTE, 1052 00:56:52,062 --> 00:56:55,599 PEDIATRIC TYPE FOLLICULAR 1053 00:56:55,599 --> 00:56:58,035 LYMPHOMA WHICH IS A BENIGN 1054 00:56:58,035 --> 00:56:58,535 DISEASE. 1055 00:56:58,535 --> 00:57:00,871 YOU TAKE OUT THE LYMPH NODE AND 1056 00:57:00,871 --> 00:57:03,373 THE CANCER IS CURED AND YOU HAVE 1057 00:57:03,373 --> 00:57:04,975 OTHER LYMPHOMA THAT MAY HAVE 1058 00:57:04,975 --> 00:57:08,045 MORE EXTENSIVE DISEASE BUT ARE 1059 00:57:08,045 --> 00:57:17,154 STILL BIO LOGICALLY AND 1060 00:57:17,154 --> 00:57:18,889 CLINICALLY DIFFERENT AND THEY 1061 00:57:18,889 --> 00:57:20,724 EXPRESS CD 23 AND MUTATIONS. 1062 00:57:20,724 --> 00:57:24,061 WE DON'T KNOW HOW MUCH THERAPY 1063 00:57:24,061 --> 00:57:24,861 THOSE PATIENTS NEED. 1064 00:57:24,861 --> 00:57:27,297 THAT'S SOMETHING WE NEED TO WORK 1065 00:57:27,297 --> 00:57:29,466 WITH CLINICIANS TO ANSWER. 1066 00:57:29,466 --> 00:57:31,335 WHAT NEEDS SYSTEMIC THERAPY? 1067 00:57:31,335 --> 00:57:35,372 WHAT CAN WE WAIT AND WATCH? 1068 00:57:35,372 --> 00:57:39,576 WE HAVE TO WORK HAND IN HAND TO 1069 00:57:39,576 --> 00:57:43,013 ANSWER THESE QUESTIONS. 1070 00:57:43,013 --> 00:57:46,817 I DIDN'T TOUCH ON B CELL 1071 00:57:46,817 --> 00:57:47,484 LYMPHOMA BECAUSE THAT'S YOU'RE 1072 00:57:47,484 --> 00:57:50,420 DISEASE AND NEED YOU THERE. 1073 00:57:50,420 --> 00:57:54,157 WHEN IT COMES TO THE 1074 00:57:54,157 --> 00:58:00,063 MICROSCOPE -- WHEN IT COMES TO 1075 00:58:00,063 --> 00:58:02,266 DIFFUSE B CELL LYMPHOMA WE'RE 1076 00:58:02,266 --> 00:58:04,167 NOT AS HELPFUL AS WE NEED TO BE 1077 00:58:04,167 --> 00:58:06,603 BUT YOU'RE SHOWING UP THE WAY IN 1078 00:58:06,603 --> 00:58:08,939 TERMS OF UNDERSTANDING DIFFUSE B 1079 00:58:08,939 --> 00:58:12,709 CELL LYMPHOMA AND HOPEFULLY IT 1080 00:58:12,709 --> 00:58:15,612 WILL HAVE RELATIVENESS FOR THE 1081 00:58:15,612 --> 00:58:15,879 TREATMENT. 1082 00:58:15,879 --> 00:58:17,114 WE STILL DON'T KNOW HOW THE 1083 00:58:17,114 --> 00:58:18,649 INFORMATION SHOULD BE USED IN 1084 00:58:18,649 --> 00:58:19,483 THE CLINICAL SETTING AND THAT'S 1085 00:58:19,483 --> 00:58:20,083 WE NEED TO WORK TOGETHER TO 1086 00:58:20,083 --> 00:58:25,422 ANSWER. 1087 00:58:25,422 --> 00:58:26,056 >> THANK YOU. 1088 00:58:26,056 --> 00:58:27,724 WHAT A WONDERFUL TALK. 1089 00:58:27,724 --> 00:58:30,961 I ALWAYS LOVE THINKING ABOUT THE 1090 00:58:30,961 --> 00:58:31,361 HISTORY. 1091 00:58:31,361 --> 00:58:33,764 MY MIND WENT IN A SIMILAR 1092 00:58:33,764 --> 00:58:38,068 DIRECTION AS LOU'S. 1093 00:58:38,068 --> 00:58:39,936 AS A CLINICIAN WE'RE REALLY 1094 00:58:39,936 --> 00:58:43,307 FORTUNATE TO HAVE YOU AND STEFAN 1095 00:58:43,307 --> 00:58:45,409 AND RELY ON THAT AND SOME OF THE 1096 00:58:45,409 --> 00:58:46,910 PROBLEMS WE SEE ACROSS THE FULL 1097 00:58:46,910 --> 00:58:51,048 FIELD OF LYMPHOMA IS WE CHANGE 1098 00:58:51,048 --> 00:58:54,418 DIAGNOSIS AND THEN ALSO SEE THAT 1099 00:58:54,418 --> 00:58:57,721 MEANING NOT EVERYONE IS AS 1100 00:58:57,721 --> 00:59:00,057 ACCURATE IN MAKING THESE 1101 00:59:00,057 --> 00:59:10,567 DECISION -- DIAGNOSES AND MY 1102 00:59:11,201 --> 00:59:14,037 QUESTION IS DO YOU THINK THERE 1103 00:59:14,037 --> 00:59:16,039 ARE OPPORTUNITIES PERHAPS WITH 1104 00:59:16,039 --> 00:59:16,807 ARTIFICIAL INTELLIGENCE OR OTHER 1105 00:59:16,807 --> 00:59:20,177 THINGS TO CLOSE THESE GAPS TO 1106 00:59:20,177 --> 00:59:25,782 MAYBE SYNCHRONIZE THE INPUTS 1107 00:59:25,782 --> 00:59:28,518 WHERE THERE'S UNMET NEEDS OR 1108 00:59:28,518 --> 00:59:30,554 LACK OF EXPERTISE OR SYNTHESIS 1109 00:59:30,554 --> 00:59:36,293 OF ACCURATE SYNTHESIS OF 1110 00:59:36,293 --> 00:59:36,827 INFORMATION. 1111 00:59:36,827 --> 00:59:37,461 >> ARTIFICIAL INTELLIGENCE MAY 1112 00:59:37,461 --> 00:59:38,028 PLAY A ROLE IN THE FUTURE. 1113 00:59:38,028 --> 00:59:43,967 WE'RE NOT THERE YET. 1114 00:59:43,967 --> 00:59:46,103 IN FRANCE THEY'RE ACTIVELY 1115 00:59:46,103 --> 00:59:48,038 WORKING ON THIS AND TRYING TO 1116 00:59:48,038 --> 00:59:48,805 DEVELOP MODELS. 1117 00:59:48,805 --> 00:59:51,074 WE'VE DABBLED IN IT A LITTLE BIT 1118 00:59:51,074 --> 00:59:52,075 HERE AT NIH. 1119 00:59:52,075 --> 01:00:00,217 I THINK IT HAS POTENTIAL. 1120 01:00:00,217 --> 01:00:02,719 SOMETHING THEY DO IN FRANCE 1121 01:00:02,719 --> 01:00:05,288 SUCCESSFULLY IS DEVELOPED 1122 01:00:05,288 --> 01:00:08,859 CENTERS OF DIAGNOSTIC EXCELLENCE 1123 01:00:08,859 --> 01:00:11,995 ACROSS THE COUNTRY AND ALMOST 1124 01:00:11,995 --> 01:00:14,398 EVERY NEWLY DIAGNOSED PATIENT 1125 01:00:14,398 --> 01:00:19,436 HAS A BIOPSY THAT GETS SENT TO A 1126 01:00:19,436 --> 01:00:19,736 PATHOLOGIST. 1127 01:00:19,736 --> 01:00:20,670 THAT DOESN'T EXIST IN THE 1128 01:00:20,670 --> 01:00:22,672 U.S. AND THERE'S A HUGE 1129 01:00:22,672 --> 01:00:24,207 VARIATION INABILITY AMONG 1130 01:00:24,207 --> 01:00:27,110 DIFFERENT PATHOLOGISTS AND 1131 01:00:27,110 --> 01:00:28,445 EXPERIENCE 37 1132 01:00:31,948 --> 01:00:33,150 ANOTHER UNFORTUNATE SITUATION IS 1133 01:00:33,150 --> 01:00:37,954 MORE AND MORE WE SEE THESE TINY 1134 01:00:37,954 --> 01:00:42,392 NEEDLE CORE BIOPSIES THAT ARE 1135 01:00:42,392 --> 01:00:42,692 INADEQUATE. 1136 01:00:42,692 --> 01:00:43,727 IT HURTS THE FIELD CLINICALLY 1137 01:00:43,727 --> 01:00:46,096 BECAUSE IT'S HARD TO MAKE A 1138 01:00:46,096 --> 01:00:48,665 DIAGNOSIS AND IT HURTS IN TERMS 1139 01:00:48,665 --> 01:00:50,667 OF RESEARCH BECAUSE YOU DON'T 1140 01:00:50,667 --> 01:00:52,803 HAVE THE MATERIALS YOU NEED TO 1141 01:00:52,803 --> 01:00:57,941 REALLY STUDY THE DISEASES. 1142 01:00:57,941 --> 01:01:01,178 >> ELAINE, THANK YOU SO MUCH. 1143 01:01:01,178 --> 01:01:03,513 YOU'VE CLEARLY HAD A FANTASTIC 1144 01:01:03,513 --> 01:01:03,747 CAREER. 1145 01:01:03,747 --> 01:01:06,183 I WAS JUST WONDERING IF YOU 1146 01:01:06,183 --> 01:01:08,985 WOULD JUST IN THE LAST QUESTION 1147 01:01:08,985 --> 01:01:10,020 HERE, JUST WHAT ADVICE WOULD YOU 1148 01:01:10,020 --> 01:01:16,860 HAVE FOR THE TRAINEES NOW HERE? 1149 01:01:16,860 --> 01:01:19,429 YOU'VE DONE PHENOMENALLY WELL. 1150 01:01:19,429 --> 01:01:20,964 IS THERE ANYTHING YOU CAN TELL 1151 01:01:20,964 --> 01:01:25,402 THEM TO TAKE A GRAIN OF WHAT 1152 01:01:25,402 --> 01:01:26,436 YOU'VE ACCOMPLISHED AND WHY 1153 01:01:26,436 --> 01:01:27,103 YOU'VE ACCOMPLISHED THAT AND USE 1154 01:01:27,103 --> 01:01:30,707 THAT IN THEIR CAREER? 1155 01:01:30,707 --> 01:01:33,910 >> MY APPROACH TO MY RESEARCH IS 1156 01:01:33,910 --> 01:01:36,046 OFTEN TO FOCUS ON THE CASES THAT 1157 01:01:36,046 --> 01:01:38,048 I DON'T UNDERSTAND RATHER THAN 1158 01:01:38,048 --> 01:01:39,749 THE ONES I DO UNDERSTAND. 1159 01:01:39,749 --> 01:01:43,487 I USED TO HAVE A GOODY FILE. 1160 01:01:43,487 --> 01:01:46,690 A LITTLE BLACK BOX OF 3X5 CARDS 1161 01:01:46,690 --> 01:01:48,391 AND SAW A CASE AND DIDN'T KNOW 1162 01:01:48,391 --> 01:01:50,794 WHAT IT WAS OR PRESENTED A 1163 01:01:50,794 --> 01:01:52,162 QUESTION I'D MAKE A NOTE ON THIS 1164 01:01:52,162 --> 01:01:53,797 CARD AND PUT IT IN THE BOX AND 1165 01:01:53,797 --> 01:01:56,032 IF I SAW ANOTHER ONE I'D GO TO 1166 01:01:56,032 --> 01:01:58,702 THE BOX AND GO I REMEMBER THAT 1167 01:01:58,702 --> 01:01:59,736 CASE. 1168 01:01:59,736 --> 01:02:01,338 ACTUALLY THAT'S HOW I CAME UP 1169 01:02:01,338 --> 01:02:03,907 WITH THE EIGHT CASES OF 1170 01:02:03,907 --> 01:02:06,576 HISTIOCYTIC SARCOMA. 1171 01:02:06,576 --> 01:02:08,245 THEY WERE ALL IN MY LITTLE BLACK 1172 01:02:08,245 --> 01:02:08,612 BOX. 1173 01:02:08,612 --> 01:02:11,248 WE HAVE TO MAINTAIN A 1174 01:02:11,248 --> 01:02:12,449 QUESTIONING MIND SET AND 1175 01:02:12,449 --> 01:02:13,583 CONTINUE TO ASK THE NEXT 1176 01:02:13,583 --> 01:02:19,256 QUESTION AND NOT SIT BACK ON OUR 1177 01:02:19,256 --> 01:02:20,056 LAURELS. 1178 01:02:20,056 --> 01:02:21,658 THANK YOU. 1179 01:02:21,658 --> 01:02:23,693 >> JOIN ME IN SAYING THANK YOU 1180 01:02:23,693 --> 01:02:25,662 TO ELAINE AND I WANT TO ALSO 1181 01:02:25,662 --> 01:02:29,032 INVITE ALL OF YOU TO THE 1182 01:02:29,032 --> 01:02:29,933 RECEPTION OUT FRONT IMMEDIATELY 1183 01:02:29,933 --> 01:02:30,300 FOLLOWING THIS. 1184 01:02:30,300 --> 01:02:30,700 THANK YOU SO MUCH. 1185 01:02:30,700 --> 01:02:30,767