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>> GOOD AFTERNOON AND
WELCOME TO

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TODAY'S CLINICAL CENTER GRAND 

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ROUND THE CODE IS 970 -- 57909.

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FOR THOSE APPLYING FOR CME 

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YOU'LL RECEIVE A SURVEY LINK VIA

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E-MAIL AND WILL IMPORTANT 

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FEEDBACK ABOUT THE PRESENTATION 

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AND SUBMIT SUGGESTION FOR FUTURE

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GRAND ROUNDS TOPICS.

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WHILE UNDER PRESENTATION, 

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QUESTIONS FOR THE SPEAKERS WILL 

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BE TAKEN FROM THE MICROPHONES IN

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THE AISLES.

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ADDITIONALLY, YOU CAN CLICK ON 

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THE LIVE FEEDBACK BUTTON LOCATED

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ON THE VIDEOCAST WEBSITE.

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THEY'LL BE ANSWERED AS TIME 

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PERMITS AT THE CONCLUSION OF THE

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PRESENTATION.

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TODAY'S PRESENTATION IS A 22nd 

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ANNUAL, JOHN LAWS DECKER LECTURE

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AS PART OF THE GREAT TEACHER 

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SERIES.

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WE HONOR THE LEGACY OF DR. JOHN 

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DECKER.

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ADVANCES INCLUDED TOMOGRAPHY 

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PROGRAM AND INITIATION OF THE 

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CLINICAL USE OF MAGNETIC USE 

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IMAGES AND SUPPORT OF RESEARCH.

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I'M HONORED AND PLEASED TO 

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WELCOME THE DECKER FAMILY TO 

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INCLUDE THE SON OF DR. DECKER 

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AND GRANDCHILDREN.

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NOW, I'D LIKE TO TURN THE PODIUM

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00:01:52,981 --> 00:02:01,156
OVER TO CHIEF OF TRANSLATIONAL 

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SCIENCE OFFICER FOR THE NATIONAL

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INSTITUTES OF HEALTH FOR REMARKS

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ON BEHALF OF THE NIH.

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>> THANK YOU.

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GOOD AFTERNOON AND WELCOME.

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I'M JOE MENNISKI AND I WORK FOR 

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THE NATIONAL INSTITUTES OF 

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HEALTH AND CO-SPONSOR OF THE 

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CLINICAL GRAND ROUNDS AND WE 

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WELCOME TO TO THE 22nd JOHN LAWS

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DECKER LECTURE FEATURING 

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DR. MARK MIETTINEN.

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WE ARE PROUD TO BE A PARTNER IN 

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THIS SERIES WHEN WE STARTED 

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RECOGNIZING DR. DECKER IN THE 

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GRAND ROUNDS SERIES.

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DR. DECKER WAS AN OUTSTANDING 

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TEACHER WHO STRIVED TO CONNECT 

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SCIENTIFIC COMMUNITY AND THIS IS

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A WAY OF EXTENDING THAT LEGACY.

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I TOO WOULD LIKE TO INCOME  -- 

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TO THANK THE DECKER FAMILY AND 

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THANK YOU FOR YOUR GENEROSITY 

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AND I GOT TO MEET IAN AND 

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THOMAS.

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THE NIH IS PROUD AND HAPPY OF 

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OUR LONG STANDING COLLABORATION 

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00:03:17,499 --> 00:03:20,802
WITH YOU AND THE CLINICAL CENTER

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TO RECOGNIZE INNOVATION IN 

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CLINICAL RESEARCH AND THE IMPACT

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OF TRAINING ON THE NEXT 

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GENERATION OF SCIENTISTS.

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AS AN ASIDE, FNIH DESIGNS AROUND

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MANY SCIENTIFIC RESEARCH AND IF 

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YOU'RE INTERESTED CONTACT ME OR 

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EXPLORE THE PROGRAMS.

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THAT'S MY LITTLE COMMENT.

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I WILL TURN IT BACK TO DR. BURK 

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TO INTRODUCE THE NIH CLINICAL 

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FELLOWS COMMITTEE AND THANK YOU 

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00:03:52,801 --> 00:03:56,438
FOR JOINING US IN THIS EVENT AND

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PLEASE ENJOY THE 22nd JOHN LAWS 

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DECKER MEMORIAL LECTURE.

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>> THANK YOU, AND FMIH FOR
YOUR 

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KIND REMARKS AND DECKER FAMILY 

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FOR YOUR CONTINUING SUPPORT.

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00:04:18,927 --> 00:04:21,830
EACH YEAR THE CLINICAL FELLOWS 

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00:04:21,830 --> 00:04:23,031
RECEIVED THE DISTINGUISHED 

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CLINICAL TEACHER AWARD.

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DR. DECKER WAS AN INSPIRING 

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LEADER AND MENTOR SO IT'S 

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CRUCIAL THEY DELIVER THE ANNUAL 

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DECKER MEMORIAL.

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BEFORE INTRODUCING TODAY'S 

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00:04:37,512 --> 00:04:41,016
SPEAKER AND AWARDEE I'D LIKE IT 

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TURN THE PODIUM TO THE CO-CHAIR 

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OF THE CLINICAL COMMITTEE TO 

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ANNOUNCE THE AWARD.

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>> I AM ONE OF THE
CO-CHAIRS OF 

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THE CLINICAL FELLOWS COMMITTEE.

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ON BEHALF OF OUR COMMITTEE, I 

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WOULD LIKE TO EXTEND OUR THANKS 

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FOR THE SUPPORT OF THE NIH 

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CLINICAL FELLOWS AND UNWAVERING 

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DEDICATION TO THE VALUES AND 

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MENTORSHIP AT THE NIH.

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EACH YEAR THE DISTINGUISHED 

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CLINICAL TEACHER AWARD IS 

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SELECTED BY A VOTE OF THE 

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CLINICAL FELLOWS AND PRESENTED 

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TO AN INDIVIDUAL WHO EMBODIES 

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MENTORSHIP, CLINICAL TEACHING 

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AND LEADERSHIP.

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IT'S MY HONOR TO INTRODUCE THE 

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RECIPIENT OF THE 2026 

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DISTINGUISHED CLINICAL TEACHER 

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AWARD.

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BEFORE THAT WE WOULD LIKE TO 

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SHARE A FEW WORDS FROM HER 

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FELLOWS.

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ONE FELLOW FOR A SECOND YEAR SHE

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EXPECTS US TO HAVE READ 

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DIAGNOSES AND ENRICHES OUR 

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UNDERSTANDING WITH HER CLINICAL 

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WISDOM AND EXPERIENCE.

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IF THE LITERATURE IS LACKING SHE

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WILL BREAK DOWN THE DIAGNOSIS 

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HERSELF SO WE CAN FULLY GRASP 

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WHAT IS HAPPENING.

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OFTEN SHE'S ONE OF THE WORLD'S 

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LEADING EXPERTS ON THE 

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CONDITIONS WE'RE SEEING.

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ANOTHER FELLOW SHARED SHE HAS 

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PROVIDED TWO DECADES OF 

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DEDICATED CARE TO PATIENTS WITH 

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HYPER-IG SYNDROME AND START THE 

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LARGEST PROSPECTIVE COHORT FOR 

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THE SYNDROME AND DEFICIENCY.

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HER WORK HAS ASSESSED MANAGEMENT

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FOR THESE DISEASES.

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SHE'S ALSO AN EXCEPTIONALLY 

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COLLABORATIVE INVESTIGATOR 

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WORKING WITH COLLEAGUES ACROSS 

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DISCIPLINES TO DEEPEN OUR 

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UNDERSTANDING OF DISEASE 

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MECHANISMS AND OPEN UP NEW 

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AVENUES FOR TREATMENT.

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SO PLEASE JOIN ME IN 

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CONGRATULATING THE 2026 

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DISTINGUISHED TEACHER AWARD 

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WINNER DR. FREEMAN AT THE 

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LABORATORY OF CLINICAL 

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IMMUNOLOGY AND MICROBIOLOGY.

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I'D LIKE TO TURN THE MIC BACK TO

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INTRODUCE DR. MARKKU MIETTINEN 

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THE 2025 AWARDEE.

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I'M HONORED TO INTRODUCE DR

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DR. MARKKU MIETTINEN AND THE 

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HEAD OF SURGICAL PATHOLOGY AND 

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DIRECTOR OF THE 

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IMMUNOHISTOLABORATORY AT THE 

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NATIONAL CANCER INSTITUTE.

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HE EARNED HIS MEDICAL DEGREE AT 

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HELSINKI MEDICAL SCHOOL IN 

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PATHOLOGY AND GRADUATE WORK ON 

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THE STUDY OF EPITHELIAL CE

163
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CELLOIDOPATHY.

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HE BECAME PROFESSOR OF 

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PATHOLOGY.

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IN 1996 HE BECAME CHAIRMAN AND 

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REGISTRAR AT THE ARMED FORCES 

168
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INSTITUTE OF PATHOLOGY IN 

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WASHINGTON, D.C. WHERE HE SERVED

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BEFORE JOINING THE NATIONAL 

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CANCER INSTITUTE IN 2011.

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AND AN INTERNATIONALLY 

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RECOGNIZED SCIENTIST AND 

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PROLIFIC SCHOLAR AND MENTOR HE'S

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BEEN THE AUTHOR OR CO-AUTHOR OF 

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ARTICLES AND HIS RESEARCH 

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CONSIDERED INCLUDES THE 

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PATHOLOGY OF SOFT TISSUE AND 

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TUMORS AND HIS GROUPS HAVE 

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DELINEATED A PROGNOSTIC SYSTEM 

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FOR DIGESTIVE TUMORS AND THEIR 

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PATHOLOGICAL PROFILES.

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HIS RESEARCH INCLUDES FOCUS ON 

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PROGNOSTIC MOLECULAR OF GENOMIC 

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GIFTs AND THE EVALUATION OF 

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MARKERS FOR SOFT TISSUE SARCOMAS

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AND TUMORS.

188
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HE SERVED ON NUMEROUS BOARDS OF 

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PATHOLOGY.

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THE TITLE OF HIS PRESENTATION 

191
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TODAY IS SOLVING PROBLEMS IN 

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SOFT TISSUE PATHOLOGY.

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PLEASE JOIN ME IN WELCOMING OUR 

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SPEAKER AND THE DISTINGUISHED 

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TEACHER AWARD DR. MARKKU 

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MIETTINEN.

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THANK YOU AND DECKER FAMILY 

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00:10:07,309 --> 00:10:14,582
MEMBERS AND OUR CLINICAL FELLOWS

199
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COMMITTEE AND NIH.

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FOR PARTICIPATING AND SPONSORING

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00:10:35,270 --> 00:10:35,470
THIS.

202
00:10:35,470 --> 00:10:37,505
THIS PRESENTATION IS AN EXAMPLE 

203
00:10:37,505 --> 00:10:40,675
OF DIAGNOSTIC PROBLEMS AND SOFT 

204
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TISSUE WE HAVE MAYBE 150 OR 200 

205
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TUMOR ENTITIES SO IT IS A 

206
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CHALLENGE FOR EVERY PATHOLOGIST 

207
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AND NOW WITH THE EXAMPLES I WILL

208
00:10:53,154 --> 00:10:53,755
SHOW HOW WE CAN SOLVE THESE 

209
00:10:53,755 --> 00:10:59,260
PROBLEMS.

210
00:10:59,260 --> 00:11:00,962
SO WHAT ARE THE DIAGNOSTIC 

211
00:11:00,962 --> 00:11:01,229
PROBLEMS?

212
00:11:01,229 --> 00:11:04,799
SO NUMBER ONE, IS OF COURSE IF 

213
00:11:04,799 --> 00:11:07,569
YOU DON'T KNOW THAT TUMOR 

214
00:11:07,569 --> 00:11:11,039
EXISTING HOW CAN YOU DIAGNOSIS 

215
00:11:11,039 --> 00:11:11,740
IT?

216
00:11:11,740 --> 00:11:17,145
SO IT'S SAME IN THE EXCURSION 

217
00:11:17,145 --> 00:11:21,149
YOU NEED IT KNOW WHAT IS WHAT TO

218
00:11:21,149 --> 00:11:26,988
RECOGNIZE IT.

219
00:11:26,988 --> 00:11:30,325
THEN THERE ARE MANY VARIANTS IN 

220
00:11:30,325 --> 00:11:33,328
TUMORS AND I'LL USE TWO EXAMPLES

221
00:11:33,328 --> 00:11:35,130
CAN BE DIFFICULT.

222
00:11:35,130 --> 00:11:41,136
WE OFTEN GET MANY BIOPSIES, 

223
00:11:41,136 --> 00:11:44,339
SMALL CORE BIOPSIES AND HAVE TO 

224
00:11:44,339 --> 00:11:47,242
MAKE A DIAGNOSIS WITH THAT 

225
00:11:47,242 --> 00:11:49,511
MINIMAL EVIDENCE WHICH CAN BE 

226
00:11:49,511 --> 00:11:50,578
VERY CHALLENGING.

227
00:11:50,578 --> 00:11:53,148
SOMETIMES THE SPECIMENS ARE NOT 

228
00:11:53,148 --> 00:11:53,348
GOOD.

229
00:11:53,348 --> 00:11:57,118
THEY'RE CRUSHED OR YOU KNOW, 

230
00:11:57,118 --> 00:12:04,092
UNREADABLE AND SOMETIMES WE HAVE

231
00:12:04,092 --> 00:12:10,098
TUMORS THAT NOBODY HAS YET 

232
00:12:10,098 --> 00:12:11,099
DESCRIBED AND MAYBE WITH OUR 

233
00:12:11,099 --> 00:12:12,567
WORK WE CAN LAUNCH A NEW TUMOR 

234
00:12:12,567 --> 00:12:20,909
ENTITY.

235
00:12:20,909 --> 00:12:25,146
SO OUR DIAGNOSTIC ARMAMENT HAS 

236
00:12:25,146 --> 00:12:28,850
INCREASED AND DIVERSIFIED HUGELY

237
00:12:28,850 --> 00:12:30,952
OVER THE DECADES.

238
00:12:30,952 --> 00:12:33,254
FIRST OF COURSE WE DID ONLY 

239
00:12:33,254 --> 00:12:33,521
HISTOLOGY.

240
00:12:33,521 --> 00:12:36,424
THERE WAS NOTHING ELSE AND WE 

241
00:12:36,424 --> 00:12:39,828
STILL DO IT EVEN IF WE STARTED 

242
00:12:39,828 --> 00:12:45,166
THIS 1900 NOW IT'S AS VALUABLE 

243
00:12:45,166 --> 00:12:46,034
AS IT WAS THEN.

244
00:12:46,034 --> 00:12:54,843
BUT WE HAVE SO MANY MORE DEVICES

245
00:12:54,843 --> 00:13:03,518
AND THIS IS AN EXAMPLE OF PAST 

246
00:13:03,518 --> 00:13:07,922
AND WE USE MICROSCOPES NIH 

247
00:13:07,922 --> 00:13:11,793
DEVELOPED 15 YEARS AGO.

248
00:13:11,793 --> 00:13:15,196
IN THE CHEMISTRY IS BIG.

249
00:13:15,196 --> 00:13:19,234
AS WE KNOW THERE ARE 100,000 

250
00:13:19,234 --> 00:13:23,638
PROTEINS AND WE ONLY CHECK 250 

251
00:13:23,638 --> 00:13:25,740
OF THEM BY HISTOCHEMISTRY.

252
00:13:25,740 --> 00:13:29,010
THERE WILL BE HUGE POTENTIAL IN 

253
00:13:29,010 --> 00:13:29,711
BIOMARK

254
00:13:29,711 --> 00:13:40,155
BIOMARKERS IN THE FUTURE.

255
00:13:41,222 --> 00:13:46,027
AND TECHNIQUES HAVE BEEN 

256
00:13:46,027 --> 00:13:50,498
EXPANDING RAPIDLY AND WE HAVE 

257
00:13:50,498 --> 00:14:01,042
OVER 30,000 GENES AND YOU SEND 

258
00:14:20,495 --> 00:14:23,398
THE CONSULTATION CASE FOR AN 

259
00:14:23,398 --> 00:14:29,337
EXPERT AND SOMETIMES GOOGLE WILL

260
00:14:29,337 --> 00:14:30,905
HELP.

261
00:14:30,905 --> 00:14:41,149
NOW, I START EXAMPLES.

262
00:14:41,149 --> 00:14:51,459
HERE THIS IS HARD TO TELL WHAT 

263
00:14:51,459 --> 00:14:53,795
IT IS, A LOT OF LYMPHO-FELLS AND

264
00:14:53,795 --> 00:14:58,967
ENDOTHELIA AND YOU CAN SEE 

265
00:14:58,967 --> 00:15:01,903
SMOOTH MUSCLE AND VESSELS.

266
00:15:01,903 --> 00:15:05,907
IT TOOK A WHILE FOR ME TO FIGURE

267
00:15:05,907 --> 00:15:16,451
THIS OUT SO I STOPPED AND JUST 

268
00:15:17,852 --> 00:15:19,954
GOT IT FOR NEXT MORNING AND 

269
00:15:19,954 --> 00:15:23,791
LET'S DO THE STUDY.

270
00:15:23,791 --> 00:15:28,196
AND IT'S VERY POSITIVE BACTERIA.

271
00:15:28,196 --> 00:15:38,706
THIS IS HEME -- HEMOTOSIS AND 

272
00:15:44,646 --> 00:15:49,150
THIS WAS MORE ASSOCIATED WITH 

273
00:15:49,150 --> 00:15:53,154
THE AIDS EPIDEMIC WITH THE 

274
00:15:53,154 --> 00:15:59,661
IMMUNOSUPPRESSOR.

275
00:15:59,661 --> 00:16:03,865
IMMUNOMARKERS ARE  THERE YOU CAN

276
00:16:03,865 --> 00:16:07,902
SEE ON THE LEFT AND THEN NOW 

277
00:16:07,902 --> 00:16:10,705
TUMORS WITH FUSION WE CAN HUNT 

278
00:16:10,705 --> 00:16:13,808
THEM WITH THE FUSION PROTEINS 

279
00:16:13,808 --> 00:16:17,145
AND THAT IS VERY SUCCESSFUL 

280
00:16:17,145 --> 00:16:23,184
THERE'S LIPO SARCOMA AND MANY 

281
00:16:23,184 --> 00:16:27,188
MORE AND MOST OF THESE MARKERS 

282
00:16:27,188 --> 00:16:31,793
ARE EXCELLENT AND VERY SPECIFIC.

283
00:16:31,793 --> 00:16:35,863
AND THEY MAY ALMOST COVER OR THE

284
00:16:35,863 --> 00:16:37,131
THING WE WOULD GET FROM RNA 

285
00:16:37,131 --> 00:16:47,342
SEQUENCING.

286
00:16:50,411 --> 00:16:51,446
HERE IS AN EXAMPLE OF A PATIENT 

287
00:16:51,446 --> 00:16:55,283
WHO HAS TWO TUMORS AND HAVE 

288
00:16:55,283 --> 00:16:58,920
INTESTINAL TUMOR, SMALL ONE ON 

289
00:16:58,920 --> 00:17:05,026
THE LEFT AND THEN A BIGGER TUMOR

290
00:17:05,026 --> 00:17:09,630
WHICH LOOKS KIND OF UGLIER BUT 

291
00:17:09,630 --> 00:17:14,202
STILL THOUGHT TO BE METASTASIS 

292
00:17:14,202 --> 00:17:17,338
OF THE INTERNAL TUMOR AND THIS 

293
00:17:17,338 --> 00:17:21,142
ONE WAS ORIGINALLY I THINK IT 

294
00:17:21,142 --> 00:17:30,985
CAME TO US AS METASTATIC AND 

295
00:17:30,985 --> 00:17:35,823
HIGH GRADE TUMOR AND TUMOR 

296
00:17:35,823 --> 00:17:36,090
NECROSIS.

297
00:17:36,090 --> 00:17:39,260
WHAT COULD IT BE IN THE BASIN 

298
00:17:39,260 --> 00:17:49,804
AND ACTUAL LY AND THIS IS 

299
00:17:49,804 --> 00:17:50,671
EXPECTED AND THE LIVER PART OF 

300
00:17:50,671 --> 00:17:55,977
THE TUMOR IS NOT POSITIVE SO 

301
00:17:55,977 --> 00:17:58,146
THERE'S SOMETHING ELSE RATHER 

302
00:17:58,146 --> 00:18:08,689
THAN -- AND THEN IT'S A TUMOR 3 

303
00:18:13,961 --> 00:18:15,229
AND YOU SEE NORMAL CELLS ON THE 

304
00:18:15,229 --> 00:18:18,132
POSITIVE TUMOR SO THIS IS 

305
00:18:18,132 --> 00:18:22,570
MALIGNANT TUMOR WHICH IS VERY 

306
00:18:22,570 --> 00:18:33,014
EXPECTED ACTUALLY IN THIS.

307
00:18:37,185 --> 00:18:41,155
THIS KIND OF LOOKS LIKE SARCOMA 

308
00:18:41,155 --> 00:18:51,599
AND UGLY AND LOOKS IN THE 

309
00:18:52,533 --> 00:18:57,138
HISTIOCYTES AND IT'S KERATIN 

310
00:18:57,138 --> 00:19:07,448
POSITIVE 5 AND 6.

311
00:19:15,990 --> 00:19:17,725
AND IT IS CARCINOMA AND 

312
00:19:17,725 --> 00:19:21,128
IMMUNIZED IN THE CHEMIST.

313
00:19:21,128 --> 00:19:21,195
 

314
00:19:23,898 --> 00:19:26,667
HERE WE HAVE A TUMOR WHICH IN 

315
00:19:26,667 --> 00:19:28,669
THE PAST ALMOST CERTAINLY WOULD 

316
00:19:28,669 --> 00:19:32,874
HAVE BEEN CALLED FIBROSARCOMA.

317
00:19:32,874 --> 00:19:37,144
NOW WE KNOW FIBROSARCOMA IS A 

318
00:19:37,144 --> 00:19:43,618
RARE TUMOR ALMOST INCONSISTENT 

319
00:19:43,618 --> 00:19:47,922
AND ALMOST ALWAYS CAN BE 

320
00:19:47,922 --> 00:19:49,891
CLASSIFIED SOMETHING ELSE AND SO

321
00:19:49,891 --> 00:19:53,928
IT IS IN THIS CASE AND THIS IS 

322
00:19:53,928 --> 00:19:59,033
ACTUALLY IT IS SOMETHING 

323
00:19:59,033 --> 00:20:01,002
DIFFICULT TO SAY HISTOLOGICALLY.

324
00:20:01,002 --> 00:20:06,040
YOU CAN DO THE IMMUNOPANEL.

325
00:20:06,040 --> 00:20:11,178
AND THIS MEANS VERY LITTLE NO 

326
00:20:11,178 --> 00:20:14,715
SMA, NOT GOING TO BE SMALL CELL 

327
00:20:14,715 --> 00:20:20,388
TUMOR BUT 100% POSITIVE AND THIS

328
00:20:20,388 --> 00:20:23,925
IS A SARCOMA WHICH IS A TRICKY 

329
00:20:23,925 --> 00:20:27,161
TUMOR AND OVER THE YEARS EVEN 

330
00:20:27,161 --> 00:20:29,130
HERE WE SEE IT ALMOST EVERY YEAR

331
00:20:29,130 --> 00:20:33,134
MAYBE ONE OR TWO BUT IT IS A 

332
00:20:33,134 --> 00:20:35,937
DIFFICULT TUMOR TO DIAGNOSE 

333
00:20:35,937 --> 00:20:39,840
BECAUSE IT IS NOT TYPICALLY 

334
00:20:39,840 --> 00:20:45,179
DIFFERENCE FROM THE SARCOMA YOU 

335
00:20:45,179 --> 00:20:50,084
WOULD EXPECT POSITIVE.

336
00:20:50,084 --> 00:20:51,852
LET'S SEE WHAT THE METHYLATION 

337
00:20:51,852 --> 00:20:53,921
CLASSIFIER SAYS.

338
00:20:53,921 --> 00:20:57,992
SO ACTUALLY, METHYLATION 

339
00:20:57,992 --> 00:21:08,536
CLASSIFIER IS EXCELLENT FOR THIS

340
00:21:12,239 --> 00:21:14,542
FOR OUR ANALYSIS AND CLASSIFIER 

341
00:21:14,542 --> 00:21:17,979
WHICH IS AN EXPRESSION PROFILING

342
00:21:17,979 --> 00:21:28,356
AND TUMORS ARE IN THE 

343
00:21:30,257 --> 00:21:31,792
METHYLATION AND METHYLATION 

344
00:21:31,792 --> 00:21:35,930
CLASSIFIER WILL TELL US THE 

345
00:21:35,930 --> 00:21:36,330
DIAGNOSIS.

346
00:21:36,330 --> 00:21:46,874
IT FEELS LIKE IT WASN'T POSITIVE

347
00:22:26,480 --> 00:22:31,085
WE DID METHYLATION AND 

348
00:22:31,085 --> 00:22:41,629
RANDOMIZED SARCOMA AND MYOGENI 

349
00:22:45,399 --> 00:22:47,001
SARCOMA AND THESE ARE FIBER LIKE

350
00:22:47,001 --> 00:22:54,642
AND THE SAME TUMOR BUT STILL 

351
00:22:54,642 --> 00:23:04,919
QUITE DIFFERENT.

352
00:23:05,186 --> 00:23:09,123
THIS IS A TUMOR AND EASY TO SEE 

353
00:23:09,123 --> 00:23:17,164
WHEN IT'S MYOGENIN POSITIVE AND 

354
00:23:17,164 --> 00:23:27,475
HIGH GRADE TUMOR.

355
00:23:44,925 --> 00:23:46,327
THIS SARCOMA THE TUMORS CAN 

356
00:23:46,327 --> 00:23:46,961
CHANGE AND THAT'S AN ADDITIONAL 

357
00:23:46,961 --> 00:23:52,767
CHALLENGE FOR US.

358
00:23:52,767 --> 00:23:54,268
OF COURSE UNDIFFERENTIATED 

359
00:23:54,268 --> 00:24:04,745
TUMORS IS ALWAYS A PROBLEM.

360
00:24:05,646 --> 00:24:07,448
HERE IS A TUMOR WHICH WAS 

361
00:24:07,448 --> 00:24:09,049
THOUGHT TO BE LYMPHOMA IN 1986, 

362
00:24:09,049 --> 00:24:17,224
ACTUALLY.

363
00:24:17,224 --> 00:24:19,026
THIS IS AN OLD CASE IN OUR 

364
00:24:19,026 --> 00:24:23,931
LIBRARY AND IN OUR STUDY WE 

365
00:24:23,931 --> 00:24:30,337
TOTALLY CHANGED THE DIAGNOSIS.

366
00:24:30,337 --> 00:24:33,841
YOU SEE THE POSITIVE NOW RAISES 

367
00:24:33,841 --> 00:24:38,813
THE ABILITY OF THE LYMPHOMA.

368
00:24:38,813 --> 00:24:42,383
BUT WE STUDIED THE LIBRARIES FOR

369
00:24:42,383 --> 00:24:45,986
THE NEW ENDOTHELIAL MARKER AND 

370
00:24:45,986 --> 00:24:47,588
SURPRISIN

371
00:24:47,588 --> 00:24:51,292
SURPRISINGLY IT WAS POSITIVE AND

372
00:24:51,292 --> 00:24:53,127
CAN IT BE THAT?

373
00:24:53,127 --> 00:24:57,131
THEN WE DO MORE ENDOTHELIAL 

374
00:24:57,131 --> 00:24:57,364
MARKERS.

375
00:24:57,364 --> 00:25:02,136
CD 31 POSITIVE, 34 NOT POSITIVE.

376
00:25:02,136 --> 00:25:05,139
THAT'S OKAY.

377
00:25:05,139 --> 00:25:13,214
AND AND THE GROWTH FACTOR 

378
00:25:13,214 --> 00:25:16,217
POSITIVE.

379
00:25:16,217 --> 00:25:17,985
SO, IT'S ANGIOSARCOMA.

380
00:25:17,985 --> 00:25:23,924
DIDN'T LOOK LIKE THAT BUT THAT'S

381
00:25:23,924 --> 00:25:27,194
WHAT WE NOW THINK BECAUSE WE 

382
00:25:27,194 --> 00:25:29,296
HAVE SO MANY MARKERS POSITIVE 

383
00:25:29,296 --> 00:25:39,473
FOR THAT.

384
00:25:40,474 --> 00:25:41,942
FURTHERMORE WE FOUND CD 30 IN 

385
00:25:41,942 --> 00:25:47,181
THE SARCOMAS AND WHEN THEY ARE 

386
00:25:47,181 --> 00:25:51,852
TOTALLY UNDIFFERENTIATE D AND TP

387
00:25:51,852 --> 00:25:55,956
FOR THE LYMPHOMA POSITIVE.

388
00:25:55,956 --> 00:25:58,893
IT'S A BIG DIAGNOSTIC PITFALL 

389
00:25:58,893 --> 00:26:02,663
AND THAT'S WHAT WE FACE EVERY 

390
00:26:02,663 --> 00:26:11,972
DAY IN DIAGNOSTIC PATHOLOGY.

391
00:26:11,972 --> 00:26:15,576
FUSION TUMORS ARE A BIG GROUP OF

392
00:26:15,576 --> 00:26:17,311
SARCOMAS AND NOW THERE ARE 

393
00:26:17,311 --> 00:26:21,115
PROBABLY A FEW HUNDRED OF 

394
00:26:21,115 --> 00:26:23,083
DIFFERENT TUMOR TYPES WITH 

395
00:26:23,083 --> 00:26:26,620
FUSIONS SO THAT'S A CHALLENGE.

396
00:26:26,620 --> 00:26:29,957
BUT OUR RNA SEQUENCING WE CATCH 

397
00:26:29,957 --> 00:26:35,229
THEM AND AS WE SAW BEFORE, 

398
00:26:35,229 --> 00:26:36,163
IMMUNOHISTOCHEMISTRY CAN CATCH 

399
00:26:36,163 --> 00:26:41,068
QUITE A LOT OF THEM TOO.

400
00:26:41,068 --> 00:26:41,969
EWING SARCOMA USED TO BE A 

401
00:26:41,969 --> 00:26:44,638
DIFFICULT DIAGNOSIS BECAUSE 

402
00:26:44,638 --> 00:26:48,943
THERE WAS NO GOOD IMMUNOMARKER 

403
00:26:48,943 --> 00:26:52,713
BUT JUST THIS YEAR WE ARE 

404
00:26:52,713 --> 00:26:58,852
FINDING THAT THIS IS AN ACCIDENT

405
00:26:58,852 --> 00:27:03,857
MARKER FOR EWING SARCOMA.

406
00:27:03,857 --> 00:27:05,960
THERE IS A SMALL NUMBER OF OTHER

407
00:27:05,960 --> 00:27:10,631
TUMORS THAT CAN BE POSITIVE.

408
00:27:10,631 --> 00:27:14,268
USUALLY LESS CLEARLY POSITIVE AS

409
00:27:14,268 --> 00:27:17,304
YOU CAN SEE IN EWING SARCOMA 

410
00:27:17,304 --> 00:27:27,414
CASE.

411
00:27:34,655 --> 00:27:36,190
THIS WAS DONE IN EARLIER TIMES 

412
00:27:36,190 --> 00:27:41,128
BUT NOW WE HAVE SWITCHED TO 

413
00:27:41,128 --> 00:27:45,132
IMMUNOHISTOCHEMISTRY AND RNA 

414
00:27:45,132 --> 00:27:49,136
COMBINATION.

415
00:27:49,136 --> 00:27:53,140
THEN HERE IS A LITTLE EWING 

416
00:27:53,140 --> 00:27:55,609
SARCOMA LIKE TUMOR BUT DOESN'T 

417
00:27:55,609 --> 00:27:59,179
QUITE LOOK ACTUALLY THIS IS 

418
00:27:59,179 --> 00:28:06,153
NEGATIVE THE MARKER.

419
00:28:06,153 --> 00:28:14,962
IS ONE IMMUNO WOULD SOLVE THIS 

420
00:28:14,962 --> 00:28:23,137
AND THIS IS A NICE TOOL.

421
00:28:23,137 --> 00:28:26,073
HERE IS AN INTESTINAL TUMOR AND 

422
00:28:26,073 --> 00:28:26,807
THREE DAYS OF THIS AND AFTER 

423
00:28:26,807 --> 00:28:31,645
THAT WE NEVER SAW IT.

424
00:28:31,645 --> 00:28:37,951
AND WE DID RNA SEQUENCING AND 

425
00:28:37,951 --> 00:28:41,121
FOUND A FUSION.

426
00:28:41,121 --> 00:28:45,025
AND IT IS NOT A FUSION TUMOR AND

427
00:28:45,025 --> 00:28:48,062
HERE YOU SEE NOT POSITIVE ALSO 

428
00:28:48,062 --> 00:28:53,167
BY IMMUNOHISTOCHEMISTRY TO 

429
00:28:53,167 --> 00:29:00,507
DIAGNOSE THIS IN MANY WAYS.

430
00:29:00,507 --> 00:29:10,884
NOT M FUSION SARCOMA.

431
00:29:15,923 --> 00:29:20,094
HERE IS EWING SARCOMA, CD 99 AND

432
00:29:20,094 --> 00:29:22,396
POSITIVE BUT WE HAVE LEARNED 

433
00:29:22,396 --> 00:29:25,766
THIS IS NOT SPECIFIC AND 

434
00:29:25,766 --> 00:29:29,970
RELIABLE OR SOMETHING ELSE HAS 

435
00:29:29,970 --> 00:29:39,346
TO BE THIS MAY BE IN EWING CD 34

436
00:29:39,346 --> 00:29:49,823
BUT LOW IN THIS THIS WAS A 

437
00:29:51,692 --> 00:29:56,530
RESULT OF THE IMMUNOSTAIN TUMOR 

438
00:29:56,530 --> 00:30:05,973
6 POSITIVE AND ALSO RNA 

439
00:30:05,973 --> 00:30:16,517
SEQUENCING SO THIS IS A VARIANT 

440
00:30:16,717 --> 00:30:20,320
OF FIBROTUMOR REPORTED YEARS AGO

441
00:30:20,320 --> 00:30:28,929
BY A JAPANESE GROUP.

442
00:30:28,929 --> 00:30:29,997
THIS LOOKS LIKE A 

443
00:30:29,997 --> 00:30:31,765
[INDISCERNIBLE] TUMOR DOESN'T 

444
00:30:31,765 --> 00:30:32,299
IT?

445
00:30:32,299 --> 00:30:34,034
FULL OF FAT CELLS AND VERY 

446
00:30:34,034 --> 00:30:36,003
LITTLE OF THE SOLID TUMOR CELLS 

447
00:30:36,003 --> 00:30:39,873
IN THE LEFT HERE YOU CAN SEE AN 

448
00:30:39,873 --> 00:30:45,145
AREA WITH MORE SOLID ROUND CELLS

449
00:30:45,145 --> 00:30:53,453
AND WHAT IT LOOKS LIKE BUT 

450
00:30:53,453 --> 00:31:03,997
IMMUNOSTAINS START POSITIVE WE 

451
00:31:05,866 --> 00:31:09,002
PUT IT IN METHYLATION BUT IT 

452
00:31:09,002 --> 00:31:12,573
DIDN'T CATCH IT BECAUSE IT DID 

453
00:31:12,573 --> 00:31:15,576
NOT HAVE SO MUCH OF THE RIGHT 

454
00:31:15,576 --> 00:31:16,176
TUMOR CELLS AND HAD A LOT OF 

455
00:31:16,176 --> 00:31:23,050
FAT.

456
00:31:23,050 --> 00:31:33,594
SO SOLITARY FIBROS TUMORS AND IT

457
00:31:35,762 --> 00:31:38,498
WAS POSITIVE YOU WOULD THINK AHA

458
00:31:38,498 --> 00:31:42,236
HERE IS A SOLITARY FIBROTUMOR IN

459
00:31:42,236 --> 00:31:52,546
A 6-YEAR-OLD BOY.

460
00:31:56,350 --> 00:32:00,120
AND WE HAVE THE RNA SEQUENCING 

461
00:32:00,120 --> 00:32:05,492
AND WE SEE THE FUSION TOOL.

462
00:32:05,492 --> 00:32:16,036
AND IT'S AN EASIER WAY TO DO IT.

463
00:32:18,639 --> 00:32:20,641
THE IMPORTANCE OF THIS IS THERE 

464
00:32:20,641 --> 00:32:25,145
IS A SPECIFIC TARGETED TREATMENT

465
00:32:25,145 --> 00:32:35,289
AGAINST AGAINST NTRK PROTEIN 

466
00:32:35,289 --> 00:32:39,359
WHICH IS DRIVING THE TUMOR.

467
00:32:39,359 --> 00:32:49,903
I THINK THIS BOY GOT YOU CAN GET

468
00:32:53,206 --> 00:32:58,111
A PHONE CALL FROM PATHOLOGIST 

469
00:32:58,111 --> 00:33:08,655
AND THE MOTHER AND IN A CERTAIN 

470
00:33:13,660 --> 00:33:19,533
SENSE IT MIGHT BE BUT IT'S NOT 

471
00:33:19,533 --> 00:33:23,470
SAYING AS THE TUMOR IT IS 

472
00:33:23,470 --> 00:33:26,773
SOMEWHAT LOW GRADE TUMOR.

473
00:33:26,773 --> 00:33:37,284
AND SHOULD BE GOOD PROGNOSIS.

474
00:33:41,188 --> 00:33:48,095
AND THIS WOULD RAISE THE  CHANCE

475
00:33:48,095 --> 00:33:51,131
OF A TUMOR AND WE DID RNA 

476
00:33:51,131 --> 00:33:52,866
SEQUENCING AND METHYLATION.

477
00:33:52,866 --> 00:33:56,203
AND RNA SEQUENCING AND FUSION 

478
00:33:56,203 --> 00:34:03,243
WHICH MEANS THE FIBROUS SARCOMA 

479
00:34:03,243 --> 00:34:09,616
AND METHYLATION SO DOUBLE 

480
00:34:09,616 --> 00:34:12,219
CONFIRMATION WHICH IS FAIRLY 

481
00:34:12,219 --> 00:34:19,426
GOOD.

482
00:34:19,426 --> 00:34:29,936
THIS IS AN ELITE POSITIVE MIX.

483
00:34:31,071 --> 00:34:34,007
AND IT'S NOT A SOLITARY FIBROUS 

484
00:34:34,007 --> 00:34:35,208
TUMOR VARIANT.

485
00:34:35,208 --> 00:34:41,114
SO ONE TUMOR CAN GET SO MUCH 

486
00:34:41,114 --> 00:34:41,648
PROBLEMS.

487
00:34:41,648 --> 00:34:44,918
BUT THEN WE LEARN FROM THAT AND 

488
00:34:44,918 --> 00:34:54,094
CAN START THE IMMUNOSTAIN WHEN 

489
00:34:54,094 --> 00:34:55,929
WE START THE DIAGNOSIS.

490
00:34:55,929 --> 00:35:04,671
HERE THE TUMOR IS CRUSHED.

491
00:35:04,671 --> 00:35:05,505
DEFINITEL

492
00:35:05,505 --> 00:35:12,245
DEFINITELY MENINGIOMA BUT MANY 

493
00:35:12,245 --> 00:35:22,622
MARKERS WERE NEGATIVE.

494
00:35:24,858 --> 00:35:29,129
IT'S EXTRA AXIAL INTERCRANIAL 

495
00:35:29,129 --> 00:35:38,438
TUMOR.

496
00:35:38,438 --> 00:35:41,541
AND THEN WE DO THE MARKER NOT 

497
00:35:41,541 --> 00:35:42,442
CLEAR POSITIVITY CONFIRMS THE 

498
00:35:42,442 --> 00:35:52,619
DIAGNOSIS.

499
00:35:53,787 --> 00:35:57,123
SOMETIMES THIS TUMOR IS A 

500
00:35:57,123 --> 00:35:57,357
PROBLEM.

501
00:35:57,357 --> 00:36:06,199
IT'S SMA POSITIVE AND IT DOESN'T

502
00:36:06,199 --> 00:36:07,868
RING A BELL.

503
00:36:07,868 --> 00:36:12,172
WE'RE GOING TO PUT IT IN FURTHER

504
00:36:12,172 --> 00:36:12,405
STUDIES.

505
00:36:12,405 --> 00:36:16,510
METHYLATION NOT ONLY SEI AND 

506
00:36:16,510 --> 00:36:22,582
THEN WE DO USB6 THE DIFFUSION 

507
00:36:22,582 --> 00:36:32,826
AND POSITIVE.

508
00:36:42,769 --> 00:36:47,908
THESE ARE VARIANTS BUT NEGATIVE 

509
00:36:47,908 --> 00:36:52,145
FOR PDGFB FISH AND THERE IS A 

510
00:36:52,145 --> 00:37:02,656
FUSION USUALLY IN THE CONTROL.

511
00:37:05,191 --> 00:37:10,263
WE STUDIED FURTHER AND THERE'S 

512
00:37:10,263 --> 00:37:16,336
AN ALTERNATE SO IT IS A GENE

513
00:37:16,336 --> 00:37:17,437
GENETICGENE

514
00:37:17,437 --> 00:37:21,141
GENETICALLY ODD VARIANT OF THE 

515
00:37:21,141 --> 00:37:31,284
SARCOMA.

516
00:37:42,929 --> 00:37:46,733
IT LOOKS PRETTY MUCH BENIGN AND 

517
00:37:46,733 --> 00:37:48,768
THE ONLY THING IS IT'S 29 

518
00:37:48,768 --> 00:37:49,069
CENTIMETER.

519
00:37:49,069 --> 00:37:51,438
WHICH IS LIKE A HUGE TUMOR.

520
00:37:51,438 --> 00:37:56,476
CAN BE LIKE THAT IN ALMOST LIKE 

521
00:37:56,476 --> 00:38:00,313
A WHOLE LEG IB THAT SARCOMA CAN 

522
00:38:00,313 --> 00:38:10,657
BE  ABDOMINAL AND WE SEE A 

523
00:38:10,657 --> 00:38:12,325
METHYLATION CLASSIFIER AND SEE 

524
00:38:12,325 --> 00:38:18,031
THE LIPO SARCOMA HERE AND WE NOT

525
00:38:18,031 --> 00:38:20,967
ONLY LOOK AT THAT AND THEN WE 

526
00:38:20,967 --> 00:38:24,638
LOOK AT THE CHANGE EXPECTED IN 

527
00:38:24,638 --> 00:38:29,109
THE LIPO SARCOMA.

528
00:38:29,109 --> 00:38:39,552
AND THAT IS ACTUALLY HERE.

529
00:38:40,854 --> 00:38:45,158
AND THE AMPLIFICATION WHICH 

530
00:38:45,158 --> 00:38:47,827
FURTHER WHICH IS GOOD FOR 

531
00:38:47,827 --> 00:38:58,038
LIPOSARCOMA.

532
00:39:02,409 --> 00:39:04,244
WE SOMEWHERE CD 34 POSITIVE AND 

533
00:39:04,244 --> 00:39:12,318
IF WE WANT TO CONFIRM THIS IS A 

534
00:39:12,318 --> 00:39:18,324
TUMOR WITH PLASTOMA AND LET'S 

535
00:39:18,324 --> 00:39:24,497
SEE WHAT THE METHYLATION DNA ARE

536
00:39:24,497 --> 00:39:34,607
HERE.

537
00:39:35,275 --> 00:39:38,712
SINGLE CELL LIPOMA.

538
00:39:38,712 --> 00:39:41,114
UNDIFFERENTIATED TUMORS ARE A 

539
00:39:41,114 --> 00:39:45,151
BIG PROBLEM OF COURSE BUT ACTUAL

540
00:39:45,151 --> 00:39:51,991
LY MANY ARE UNDIFFERENTIATED 

541
00:39:51,991 --> 00:39:55,829
SARCOMAS AND MARKERS ARE NOTHING

542
00:39:55,829 --> 00:40:00,300
HERE AND WE DO NOT PUT IT IN 

543
00:40:00,300 --> 00:40:05,138
METHYLATION CLASSIFIER AND DNA 

544
00:40:05,138 --> 00:40:15,281
ANALYSIS LOTS OF OTHER CHANGES 

545
00:40:15,281 --> 00:40:19,486
SO IT'S A DIFFERENTIATED 

546
00:40:19,486 --> 00:40:23,056
LIPOSARCOMA WHICH HISTOLOGICALLY

547
00:40:23,056 --> 00:40:29,129
MIMICS UNDIFFERENTIATED SARCOMA 

548
00:40:29,129 --> 00:40:39,606
BUT DRIVEN BY AMPLIFICATION.

549
00:40:50,984 --> 00:40:52,318
THIS LOOKS LIKE RHABDOMYOSARCOMA

550
00:40:52,318 --> 00:40:55,088
AND WE HAVE THE PRESIDENT WHO IS

551
00:40:55,088 --> 00:40:58,525
THE PIONEER OF RHABDOMYOSARCOMA 

552
00:40:58,525 --> 00:41:00,593
WHO FOUNDED FUSION ABOUT 30 

553
00:41:00,593 --> 00:41:03,163
YEARS AGO.

554
00:41:03,163 --> 00:41:06,699
ONE OF THE FIRST TUMOR SARCOMA 

555
00:41:06,699 --> 00:41:09,903
FUSIONS EVER DETECTED.

556
00:41:09,903 --> 00:41:17,110
AND USUALLY THIS IS FOX 3 OR FOX

557
00:41:17,110 --> 00:41:21,014
7 WITH FOX 01 BUT FOX 01 FISH 

558
00:41:21,014 --> 00:41:25,852
WAS NEGATIVE IN THIS ONE STILL 

559
00:41:25,852 --> 00:41:28,688
WOULD BE GOOD FOR OTHER 

560
00:41:28,688 --> 00:41:32,625
RHABDOMYOSARCOMA MEANING 100% 

561
00:41:32,625 --> 00:41:34,527
POSITIVE.

562
00:41:34,527 --> 00:41:36,429
THIS IS TYPICAL OF THE 

563
00:41:36,429 --> 00:41:37,130
RHABDOMYOSARCOMA.

564
00:41:37,130 --> 00:41:41,134
SO WE'RE GOING TO PUT THIS IN 

565
00:41:41,134 --> 00:41:44,070
METHYLATION CLASSIFIER AND RNA 

566
00:41:44,070 --> 00:41:48,041
SEQUENCING AND WHAT DO WE FIND?

567
00:41:48,041 --> 00:41:55,882
WE FOUND FOX 03 FUSION WHICH IS 

568
00:41:55,882 --> 00:42:00,153
ALTERNATIVE FUSION IN THE 

569
00:42:00,153 --> 00:42:10,430
SARCOMA AND WE CONFIRMED THE 

570
00:42:10,430 --> 00:42:20,607
DIAGNOSIS.

571
00:42:25,612 --> 00:42:27,247
WE NEED THE IMMUNOSTAINS MORE 

572
00:42:27,247 --> 00:42:31,251
THAN WE ALLOWED PEOPLE TO NOW 

573
00:42:31,251 --> 00:42:35,121
ORDER BECAUSE ONLY 8 OR 7 

574
00:42:35,121 --> 00:42:40,593
IMMUNOSTAINS WE HAD TO DO MANY 

575
00:42:40,593 --> 00:42:43,396
EVEN FACTOR 1 FOR OTHER 

576
00:42:43,396 --> 00:42:45,732
CARCINOMA I WAS TRYING BUT I GOT

577
00:42:45,732 --> 00:42:46,065
NOTHING HERE.

578
00:42:46,065 --> 00:42:50,136
EVERYTHING WAS NEGATIVE.

579
00:42:50,136 --> 00:42:52,305
SO NOW WHAT DO WE DO?

580
00:42:52,305 --> 00:42:55,541
WE PUT IT IN BOTH METHYLATION 

581
00:42:55,541 --> 00:42:58,778
CLASSIFIER AND SEQUENCING.

582
00:42:58,778 --> 00:43:01,114
AND IN THIS CASE WE DID DNA 

583
00:43:01,114 --> 00:43:02,715
SEQUENCING.

584
00:43:02,715 --> 00:43:05,084
SO NOTHING WAS POSITIVE.

585
00:43:05,084 --> 00:43:11,291
NOT CARCINOMA, NOT MELANOMA OR 

586
00:43:11,291 --> 00:43:12,859
ANY SPECIFIC SARCOMA AND 

587
00:43:12,859 --> 00:43:17,897
SOMETHING WAS WRONG ON THIS.

588
00:43:17,897 --> 00:43:20,466
SO WHAT IS IT?

589
00:43:20,466 --> 00:43:22,936
IT'S UNDIFFERENTIATED MELANOMA 

590
00:43:22,936 --> 00:43:26,306
AND THIS TUMOR SHEDS ALL THE 

591
00:43:26,306 --> 00:43:30,410
MARKERS, NOTHING POSITIVE AND 

592
00:43:30,410 --> 00:43:35,915
INDEED METHYLATION GAVE A LOW 

593
00:43:35,915 --> 00:43:41,020
SCORE FOR MELANOMA BUT ALSO VERY

594
00:43:41,020 --> 00:43:46,559
IMPORTANTLY TUMOR CONTAINS Q61 

595
00:43:46,559 --> 00:43:51,898
WHICH IS TYPICAL OF MELANOMA AND

596
00:43:51,898 --> 00:43:56,269
ACTUALLY MOST COMMON DRIVER IN 

597
00:43:56,269 --> 00:43:57,136
UNDIFFERENTIATED MELANOMA IN OUR

598
00:43:57,136 --> 00:44:01,107
EXPERIENCE.

599
00:44:01,107 --> 00:44:03,943
HERE IS ANOTHER ONE 

600
00:44:03,943 --> 00:44:06,312
UNDIFFERENTIATED TUMOR.

601
00:44:06,312 --> 00:44:10,249
THIS MEANS POSITIVE A LITTLE BIT

602
00:44:10,249 --> 00:44:17,123
POSITIVITY AND WHAT IT IS, IT 

603
00:44:17,123 --> 00:44:21,828
HAS ROUGHLY 600 AND GRAY 

604
00:44:21,828 --> 00:44:23,062
METHYLATION CAUSED MELANOMA.

605
00:44:23,062 --> 00:44:25,999
SOMETIMES IT'S BETTER THAN THE 

606
00:44:25,999 --> 00:44:28,601
SOFT TISSUE METHYLATION AND 

607
00:44:28,601 --> 00:44:34,474
ANOTHER EXAMPLE OF IN DURCHB 

608
00:44:34,474 --> 00:44:38,411
SH --

609
00:44:38,411 --> 00:44:41,114
DIFFERENTIATED MELANOMA.

610
00:44:41,114 --> 00:44:46,185
AND THIS IS MY LAST EXAMPLE.

611
00:44:46,185 --> 00:44:50,656
THIS IS ABOUT VERY HIGH VIEWS.

612
00:44:50,656 --> 00:44:55,161
SO IT LOOKS LIKE A PRIMITIVE 

613
00:44:55,161 --> 00:44:58,998
UNDIFFERENTIATED TUMOR HAS 

614
00:44:58,998 --> 00:44:59,365
DIFFERENTIATION.

615
00:44:59,365 --> 00:45:03,469
SO COULD MELANOMA LIKE RELATED 

616
00:45:03,469 --> 00:45:05,138
SOMETHING BUT ACTUALLY LITTLE 

617
00:45:05,138 --> 00:45:07,874
CHILDREN DON'T HAVE THAT TYPE OF

618
00:45:07,874 --> 00:45:14,080
MELANOMA BUT CAN HAVE TUMORS OR 

619
00:45:14,080 --> 00:45:20,787
LIKE TUMORS AND WHAT IS THIS IN 

620
00:45:20,787 --> 00:45:29,128
INFANT SCROTUM IS NOT OBVIOUS 

621
00:45:29,128 --> 00:45:39,505
BUT THIS IS WHAT IT EXACTLY WAS.

622
00:45:39,505 --> 00:45:41,140
HERE IS THE GOOGLE MY QUESTION 

623
00:45:41,140 --> 00:45:46,279
OF THIS ANSWER COULD BE 

624
00:45:46,279 --> 00:45:46,913
CONGENITAL [INDISCERNIBLE] AND 

625
00:45:46,913 --> 00:45:48,347
THAT WAS THE DIAGNOSIS.

626
00:45:48,347 --> 00:45:52,618
I THANK YOU SO MUCH FOR YOUR 

627
00:45:52,618 --> 00:45:53,119
ATTENTION.

628
00:45:53,119 --> 00:46:00,526
AND I HOPE THAT YOU HAVE A GOOD 

629
00:46:00,526 --> 00:46:00,693
DAY.

630
00:46:00,693 --> 00:46:04,831
THANK YOU, ALL.

631
00:46:04,831 --> 00:46:07,400
>> THANK YOU, DR.
MIETTINEN.

632
00:46:07,400 --> 00:46:09,469
FIRST OF ALL, I'M HAPPY TO KNOW 

633
00:46:09,469 --> 00:46:12,038
I'M NOT THE ONLY PERSON TO USE 

634
00:46:12,038 --> 00:46:14,807
GOOGLE FOR DIAGNOSES.

635
00:46:14,807 --> 00:46:18,010
THANK YOU FOR SHOWING THE 

636
00:46:18,010 --> 00:46:18,811
IMMUNOHISTOCHEMISTRY.

637
00:46:18,811 --> 00:46:19,912
THE QUESTION COMES TO MIND IS 

638
00:46:19,912 --> 00:46:21,147
WHAT IS THE NEXT STEP?

639
00:46:21,147 --> 00:46:22,849
YOU GAVE US AT THE BEGINNING A 

640
00:46:22,849 --> 00:46:26,586
TIME LINE GOING FROM SIMPLE 

641
00:46:26,586 --> 00:46:29,122
STAINS TO IMMUNOHISTOCHEMISTRY.

642
00:46:29,122 --> 00:46:31,991
WHAT IS THE NEXT STEP IN 

643
00:46:31,991 --> 00:46:33,292
DIAGNOSTIC FOR SOFT TISSUE 

644
00:46:33,292 --> 00:46:36,529
TUMORS AND I KNOW THIS QUESTION 

645
00:46:36,529 --> 00:46:39,866
GETS RAISED A LOT DOES A.I. PLAY

646
00:46:39,866 --> 00:46:42,535
A ROLE IN THAT?

647
00:46:42,535 --> 00:46:49,108
>> AND TO PREDICT THE
FUTURE IS 

648
00:46:49,108 --> 00:46:53,412
VERY DIFFICULT ACTUALLY.

649
00:46:53,412 --> 00:46:55,948
SO ALMOST IMPOSSIBLE TO ANSWER.

650
00:46:55,948 --> 00:46:57,116
EXCELLENT QUESTION IN ITSELF BUT

651
00:46:57,116 --> 00:47:00,553
THE NEWEST ONE AND WHAT WE HAVE 

652
00:47:00,553 --> 00:47:04,657
AND IS TILL EXPERIMENTAL IS THE 

653
00:47:04,657 --> 00:47:06,792
SARCOMA CLASSIFIER WHICH IS 

654
00:47:06,792 --> 00:47:08,227
HIGHLIGHTED IN SOME OF THE 

655
00:47:08,227 --> 00:47:09,729
PICTURES HERE AND THAT WILL GROW

656
00:47:09,729 --> 00:47:11,764
IN THE FUTURE.

657
00:47:11,764 --> 00:47:15,935
THE SECOND VERSION IS IN MAKING 

658
00:47:15,935 --> 00:47:20,506
AND WE HERE AT NIH, NCI, ARE 

659
00:47:20,506 --> 00:47:23,876
PART OF THE SECOND VERSION 

660
00:47:23,876 --> 00:47:29,115
MAKING OR SO WITH OUR 1,500 

661
00:47:29,115 --> 00:47:32,185
CASES.

662
00:47:32,185 --> 00:47:35,254
>> AND HOW COMMON --
BECAUSE 

663
00:47:35,254 --> 00:47:39,192
OBVIOUSLY NCI HAS THE MOST 

664
00:47:39,192 --> 00:47:42,295
CAPABILITY BUT HOW COMMON ARE 

665
00:47:42,295 --> 00:47:45,531
THESE AND ARE THERE REFERENCE 

666
00:47:45,531 --> 00:47:45,865
LABORATORIES?

667
00:47:45,865 --> 00:47:47,099
>> YEAH.

668
00:47:47,099 --> 00:47:49,135
IT REALLY IS CHALLENGING FOR A 

669
00:47:49,135 --> 00:47:50,937
SMALL HOSPITAL.

670
00:47:50,937 --> 00:47:54,540
THEY DON'T HAVE 250 IMMUNOSTAINS

671
00:47:54,540 --> 00:47:58,144
AND THEY PROBABLY DON'T HAVE RNA

672
00:47:58,144 --> 00:48:00,546
OR DNA SEQUENCING SO THEY OFTEN 

673
00:48:00,546 --> 00:48:06,485
SEND CASES IN CONSULTATION.

674
00:48:06,485 --> 00:48:09,388
THAT'S THE MOST PRACTICAL THING 

675
00:48:09,388 --> 00:48:13,693
TO DO FOR SMALL PLACES.

676
00:48:13,693 --> 00:48:16,696
TO LET THE CONSULTANT DO IT AND 

677
00:48:16,696 --> 00:48:19,632
THEN OF COURSE THERE ARE 

678
00:48:19,632 --> 00:48:24,904
LABORATORIES FOR SEQUENCING.

679
00:48:24,904 --> 00:48:30,409
>> ARE THERE ANY
QUESTIONS?

680
00:48:30,409 --> 00:48:32,845
>> WONDERFUL TALK, MARKKU.

681
00:48:32,845 --> 00:48:34,580
YOU SHOWED NICE CASES MUCH 

682
00:48:34,580 --> 00:48:38,317
MIMICS WHERE HISTOLOGY AND THE 

683
00:48:38,317 --> 00:48:39,986
IHC MIGHT SUGGEST ONE THING BUT 

684
00:48:39,986 --> 00:48:42,555
THEN YOU DO ADVANCED MOLECULAR 

685
00:48:42,555 --> 00:48:43,089
TECHNIQUES AND IT SHOWS 

686
00:48:43,089 --> 00:48:45,024
SOMETHING ELSE.

687
00:48:45,024 --> 00:48:46,459
AND I THINK YOU VERY NICELY 

688
00:48:46,459 --> 00:48:48,861
SHOWED THAT'S BECOME THE NEW 

689
00:48:48,861 --> 00:48:49,128
PARADIGM.

690
00:48:49,128 --> 00:48:52,932
DO YOU FIND THERE'S UNIVERSAL 

691
00:48:52,932 --> 00:48:54,533
ACCEPTANCE IN THE FIELD TO THESE

692
00:48:54,533 --> 00:48:57,103
NEW TECHNIQUES WHEN YOUR 

693
00:48:57,103 --> 00:48:58,871
DIAGNOSIS MIGHT DRAMATICALLY 

694
00:48:58,871 --> 00:49:00,906
CHANGE FROM THE MOLECULAR 

695
00:49:00,906 --> 00:49:01,207
TECHNIQUES?

696
00:49:01,207 --> 00:49:04,577
YOU KNOW, IN CONTRAST TO WHAT 

697
00:49:04,577 --> 00:49:05,745
MIGHT HAVE BEEN EXPECT FROM THE 

698
00:49:05,745 --> 00:49:09,515
TRADITIONAL H AND E AND IHC DO 

699
00:49:09,515 --> 00:49:13,119
YOU FIND IN THE COMMUNITY YOU 

700
00:49:13,119 --> 00:49:15,821
CONSULT WITH THERE'S UNIVERSAL 

701
00:49:15,821 --> 00:49:16,989
ACCEPTANCE OR CHALLENGE THERE?

702
00:49:16,989 --> 00:49:18,124
WHAT'S YOUR EXPERIENCE THERE?

703
00:49:18,124 --> 00:49:22,395
>> I THINK THE COMMUNITY
IS ALSO

704
00:49:22,395 --> 00:49:24,697
THIRSTY FOR NEW WAYS OF 

705
00:49:24,697 --> 00:49:28,367
DIAGNOSIS AND NEW WAYS OF 

706
00:49:28,367 --> 00:49:35,174
PERSISTENT DIAGNOSIS AND I THINK

707
00:49:35,174 --> 00:49:41,113
SEQUENCING AND METHYLATION WHICH

708
00:49:41,113 --> 00:49:44,917
IS LED BY THE BRAIN METH LAYING 

709
00:49:44,917 --> 00:49:47,386
AND SARCOMA METHYLATION FOR ALL 

710
00:49:47,386 --> 00:49:52,291
OF US AND FOR THE WHOLE AMERICAN

711
00:49:52,291 --> 00:49:58,431
COMMUNITY BECAUSE THE CONFERENCE

712
00:49:58,431 --> 00:49:59,865
WHICH IS PROBABLY HUNDREDS OF 

713
00:49:59,865 --> 00:50:00,433
PEOPLE ATTENDING.

714
00:50:00,433 --> 00:50:03,836
I THINK THE METHYLATION CLASS 

715
00:50:03,836 --> 00:50:05,971
CLASSIFIER REALLY IS SOMETHING 

716
00:50:05,971 --> 00:50:09,842
WHICH IS GROWING AND WILL BECOME

717
00:50:09,842 --> 00:50:10,109
IMPORTANT.

718
00:50:10,109 --> 00:50:14,313
I THINK IT'S ALSO COST EFFICIENT

719
00:50:14,313 --> 00:50:19,919
TO SOME DEGREE AND MAYBE LESS 

720
00:50:19,919 --> 00:50:20,820
EXPENSIVE THAN TRADITIONAL FULL 

721
00:50:20,820 --> 00:50:25,925
SEQUENCING.

722
00:50:25,925 --> 00:50:28,527
BUT AGAIN HARD TO SAY WHAT 

723
00:50:28,527 --> 00:50:29,095
HAPPENS.

724
00:50:29,095 --> 00:50:29,929
MAYBE SOMETHING TOTALLY NEW WILL

725
00:50:29,929 --> 00:50:37,403
COME.

726
00:50:37,403 --> 00:50:39,638
>> A COUPLE QUESTIONS FROM
OUR 

727
00:50:39,638 --> 00:50:40,806
VIRTUAL AUDIENCE.

728
00:50:40,806 --> 00:50:44,110
ONE, HOW DOES TUMOR METHYLATION 

729
00:50:44,110 --> 00:50:44,744
CLASSIFIER LEAD TO PROGNOSIS AND

730
00:50:44,744 --> 00:50:54,553
TREATMENT?

731
00:50:54,553 --> 00:51:00,659
I THINK DIAGNOSIS LINKS WITH 

732
00:51:00,659 --> 00:51:05,798
TREATMENT.

733
00:51:05,798 --> 00:51:06,599
METHYLATION LEADS TO DIAGNOSIS 

734
00:51:06,599 --> 00:51:10,603
AND THERE ARE OTHER ASPECTS LIKE

735
00:51:10,603 --> 00:51:11,437
METHYLATION CLASSIFIER GIVES 

736
00:51:11,437 --> 00:51:16,609
ESPECIALLY BRAIN TUMORS THIS IS 

737
00:51:16,609 --> 00:51:17,109
IMPORTANT.

738
00:51:17,109 --> 00:51:25,050
MG, NT METHYLATION STATUS AND IF

739
00:51:25,050 --> 00:51:33,125
FG, NT IS METHYLATE D AND 

740
00:51:33,125 --> 00:51:36,829
CHEMOTHERAPY CAN BE USED.

741
00:51:36,829 --> 00:51:41,000
THE METHYL TRANSFERASES.

742
00:51:41,000 --> 00:51:43,302
>> ONE OTHER QUESTION SAYS
IS 

743
00:51:43,302 --> 00:51:46,939
YOUR LAB LINKED TO GROUPS AT 

744
00:51:46,939 --> 00:51:47,606
NCI?

745
00:51:47,606 --> 00:51:49,608
SO THE DEFINITIVE DIAGNOSIS CAN 

746
00:51:49,608 --> 00:51:52,778
BE LINKED TO KNOWLEDGE FOR THE 

747
00:51:52,778 --> 00:51:53,012
PATIENT?

748
00:51:53,012 --> 00:51:57,616
>> YES, IT IS.

749
00:51:57,616 --> 00:52:00,419
ALL OUR DIAGNOSIS CAPABILITIES 

750
00:52:00,419 --> 00:52:04,857
ARE FOR USE FOR CLINICAL CENTER 

751
00:52:04,857 --> 00:52:12,698
AND WE DO THESE STUDIES FOR 

752
00:52:12,698 --> 00:52:15,601
PATIENTS AS NEEDED.

753
00:52:15,601 --> 00:52:17,136
>> DR. MIETTINEN THANK YOU
FOR 

754
00:52:17,136 --> 00:52:18,237
YOUR PRESENTATION AND 

755
00:52:18,237 --> 00:52:20,606
CONGRATULATIONS AGAIN.

756
00:52:20,606 --> 00:52:21,674
THAT CONCLUDES TODAY'S GRAND 

757
00:52:21,674 --> 00:52:22,041
ROUNDS.

758
00:52:22,041 --> 00:52:26,145
FOR THOSE INVITED THERE'S A 

759
00:52:26,145 --> 00:52:32,384
RECEPTION FOR DR. MIETTINEN AND 

760
00:52:32,384 --> 00:52:34,820
THE DECKER FAMILY AND WE LOOK 

761
00:52:34,820 --> 00:52:36,922
FORWARD TO THE PRESENTATION NEXT

762
00:52:36,922 --> 00:52:38,357
YEAR.

763
00:52:38,357 --> 00:52:39,024
HAVE A GOOD AFTERNOON THANK YOU 

764
00:52:39,024 --> 00:52:39,291
EVERYBODY.

765
00:52:39,291 --> 00:52:41,060