>> GOOD AFTERNOON AND WELCOME TO
TODAY'S CLINICAL CENTER GRAND
ROUND THE CODE IS 970 -- 57909.
FOR THOSE APPLYING FOR CME
YOU'LL RECEIVE A SURVEY LINK VIA
E-MAIL AND WILL IMPORTANT
FEEDBACK ABOUT THE PRESENTATION
AND SUBMIT SUGGESTION FOR FUTURE
GRAND ROUNDS TOPICS.
WHILE UNDER PRESENTATION,
QUESTIONS FOR THE SPEAKERS WILL
BE TAKEN FROM THE MICROPHONES IN
THE AISLES.
ADDITIONALLY, YOU CAN CLICK ON
THE LIVE FEEDBACK BUTTON LOCATED
ON THE VIDEOCAST WEBSITE.
THEY'LL BE ANSWERED AS TIME
PERMITS AT THE CONCLUSION OF THE
PRESENTATION.
TODAY'S PRESENTATION IS A 22nd
ANNUAL, JOHN LAWS DECKER LECTURE
AS PART OF THE GREAT TEACHER
SERIES.
WE HONOR THE LEGACY OF DR. JOHN
DECKER.
ADVANCES INCLUDED TOMOGRAPHY
PROGRAM AND INITIATION OF THE
CLINICAL USE OF MAGNETIC USE
IMAGES AND SUPPORT OF RESEARCH.
I'M HONORED AND PLEASED TO
WELCOME THE DECKER FAMILY TO
INCLUDE THE SON OF DR. DECKER
AND GRANDCHILDREN.
NOW, I'D LIKE TO TURN THE PODIUM
OVER TO CHIEF OF TRANSLATIONAL
SCIENCE OFFICER FOR THE NATIONAL
INSTITUTES OF HEALTH FOR REMARKS
ON BEHALF OF THE NIH.
>> THANK YOU.
GOOD AFTERNOON AND WELCOME.
I'M JOE MENNISKI AND I WORK FOR
THE NATIONAL INSTITUTES OF
HEALTH AND CO-SPONSOR OF THE
CLINICAL GRAND ROUNDS AND WE
WELCOME TO TO THE 22nd JOHN LAWS
DECKER LECTURE FEATURING
DR. MARK MIETTINEN.
WE ARE PROUD TO BE A PARTNER IN
THIS SERIES WHEN WE STARTED
RECOGNIZING DR. DECKER IN THE
GRAND ROUNDS SERIES.
DR. DECKER WAS AN OUTSTANDING
TEACHER WHO STRIVED TO CONNECT
SCIENTIFIC COMMUNITY AND THIS IS
A WAY OF EXTENDING THAT LEGACY.
I TOO WOULD LIKE TO INCOME --
TO THANK THE DECKER FAMILY AND
THANK YOU FOR YOUR GENEROSITY
AND I GOT TO MEET IAN AND
THOMAS.
THE NIH IS PROUD AND HAPPY OF
OUR LONG STANDING COLLABORATION
WITH YOU AND THE CLINICAL CENTER
TO RECOGNIZE INNOVATION IN
CLINICAL RESEARCH AND THE IMPACT
OF TRAINING ON THE NEXT
GENERATION OF SCIENTISTS.
AS AN ASIDE, FNIH DESIGNS AROUND
MANY SCIENTIFIC RESEARCH AND IF
YOU'RE INTERESTED CONTACT ME OR
EXPLORE THE PROGRAMS.
THAT'S MY LITTLE COMMENT.
I WILL TURN IT BACK TO DR. BURK
TO INTRODUCE THE NIH CLINICAL
FELLOWS COMMITTEE AND THANK YOU
FOR JOINING US IN THIS EVENT AND
PLEASE ENJOY THE 22nd JOHN LAWS
DECKER MEMORIAL LECTURE.
>> THANK YOU, AND FMIH FOR YOUR
KIND REMARKS AND DECKER FAMILY
FOR YOUR CONTINUING SUPPORT.
EACH YEAR THE CLINICAL FELLOWS
RECEIVED THE DISTINGUISHED
CLINICAL TEACHER AWARD.
DR. DECKER WAS AN INSPIRING
LEADER AND MENTOR SO IT'S
CRUCIAL THEY DELIVER THE ANNUAL
DECKER MEMORIAL.
BEFORE INTRODUCING TODAY'S
SPEAKER AND AWARDEE I'D LIKE IT
TURN THE PODIUM TO THE CO-CHAIR
OF THE CLINICAL COMMITTEE TO
ANNOUNCE THE AWARD.
>> I AM ONE OF THE CO-CHAIRS OF
THE CLINICAL FELLOWS COMMITTEE.
ON BEHALF OF OUR COMMITTEE, I
WOULD LIKE TO EXTEND OUR THANKS
FOR THE SUPPORT OF THE NIH
CLINICAL FELLOWS AND UNWAVERING
DEDICATION TO THE VALUES AND
MENTORSHIP AT THE NIH.
EACH YEAR THE DISTINGUISHED
CLINICAL TEACHER AWARD IS
SELECTED BY A VOTE OF THE
CLINICAL FELLOWS AND PRESENTED
TO AN INDIVIDUAL WHO EMBODIES
MENTORSHIP, CLINICAL TEACHING
AND LEADERSHIP.
IT'S MY HONOR TO INTRODUCE THE
RECIPIENT OF THE 2026
DISTINGUISHED CLINICAL TEACHER
AWARD.
BEFORE THAT WE WOULD LIKE TO
SHARE A FEW WORDS FROM HER
FELLOWS.
ONE FELLOW FOR A SECOND YEAR SHE
EXPECTS US TO HAVE READ
DIAGNOSES AND ENRICHES OUR
UNDERSTANDING WITH HER CLINICAL
WISDOM AND EXPERIENCE.
IF THE LITERATURE IS LACKING SHE
WILL BREAK DOWN THE DIAGNOSIS
HERSELF SO WE CAN FULLY GRASP
WHAT IS HAPPENING.
OFTEN SHE'S ONE OF THE WORLD'S
LEADING EXPERTS ON THE
CONDITIONS WE'RE SEEING.
ANOTHER FELLOW SHARED SHE HAS
PROVIDED TWO DECADES OF
DEDICATED CARE TO PATIENTS WITH
HYPER-IG SYNDROME AND START THE
LARGEST PROSPECTIVE COHORT FOR
THE SYNDROME AND DEFICIENCY.
HER WORK HAS ASSESSED MANAGEMENT
FOR THESE DISEASES.
SHE'S ALSO AN EXCEPTIONALLY
COLLABORATIVE INVESTIGATOR
WORKING WITH COLLEAGUES ACROSS
DISCIPLINES TO DEEPEN OUR
UNDERSTANDING OF DISEASE
MECHANISMS AND OPEN UP NEW
AVENUES FOR TREATMENT.
SO PLEASE JOIN ME IN
CONGRATULATING THE 2026
DISTINGUISHED TEACHER AWARD
WINNER DR. FREEMAN AT THE
LABORATORY OF CLINICAL
IMMUNOLOGY AND MICROBIOLOGY.
I'D LIKE TO TURN THE MIC BACK TO
INTRODUCE DR. MARKKU MIETTINEN
THE 2025 AWARDEE.
I'M HONORED TO INTRODUCE DR
DR. MARKKU MIETTINEN AND THE
HEAD OF SURGICAL PATHOLOGY AND
DIRECTOR OF THE
IMMUNOHISTOLABORATORY AT THE
NATIONAL CANCER INSTITUTE.
HE EARNED HIS MEDICAL DEGREE AT
HELSINKI MEDICAL SCHOOL IN
PATHOLOGY AND GRADUATE WORK ON
THE STUDY OF EPITHELIAL CE
CELLOIDOPATHY.
HE BECAME PROFESSOR OF
PATHOLOGY.
IN 1996 HE BECAME CHAIRMAN AND
REGISTRAR AT THE ARMED FORCES
INSTITUTE OF PATHOLOGY IN
WASHINGTON, D.C. WHERE HE SERVED
BEFORE JOINING THE NATIONAL
CANCER INSTITUTE IN 2011.
AND AN INTERNATIONALLY
RECOGNIZED SCIENTIST AND
PROLIFIC SCHOLAR AND MENTOR HE'S
BEEN THE AUTHOR OR CO-AUTHOR OF
ARTICLES AND HIS RESEARCH
CONSIDERED INCLUDES THE
PATHOLOGY OF SOFT TISSUE AND
TUMORS AND HIS GROUPS HAVE
DELINEATED A PROGNOSTIC SYSTEM
FOR DIGESTIVE TUMORS AND THEIR
PATHOLOGICAL PROFILES.
HIS RESEARCH INCLUDES FOCUS ON
PROGNOSTIC MOLECULAR OF GENOMIC
GIFTs AND THE EVALUATION OF
MARKERS FOR SOFT TISSUE SARCOMAS
AND TUMORS.
HE SERVED ON NUMEROUS BOARDS OF
PATHOLOGY.
THE TITLE OF HIS PRESENTATION
TODAY IS SOLVING PROBLEMS IN
SOFT TISSUE PATHOLOGY.
PLEASE JOIN ME IN WELCOMING OUR
SPEAKER AND THE DISTINGUISHED
TEACHER AWARD DR. MARKKU
MIETTINEN.
THANK YOU AND DECKER FAMILY
MEMBERS AND OUR CLINICAL FELLOWS
COMMITTEE AND NIH.
FOR PARTICIPATING AND SPONSORING
THIS.
THIS PRESENTATION IS AN EXAMPLE
OF DIAGNOSTIC PROBLEMS AND SOFT
TISSUE WE HAVE MAYBE 150 OR 200
TUMOR ENTITIES SO IT IS A
CHALLENGE FOR EVERY PATHOLOGIST
AND NOW WITH THE EXAMPLES I WILL
SHOW HOW WE CAN SOLVE THESE
PROBLEMS.
SO WHAT ARE THE DIAGNOSTIC
PROBLEMS?
SO NUMBER ONE, IS OF COURSE IF
YOU DON'T KNOW THAT TUMOR
EXISTING HOW CAN YOU DIAGNOSIS
IT?
SO IT'S SAME IN THE EXCURSION
YOU NEED IT KNOW WHAT IS WHAT TO
RECOGNIZE IT.
THEN THERE ARE MANY VARIANTS IN
TUMORS AND I'LL USE TWO EXAMPLES
CAN BE DIFFICULT.
WE OFTEN GET MANY BIOPSIES,
SMALL CORE BIOPSIES AND HAVE TO
MAKE A DIAGNOSIS WITH THAT
MINIMAL EVIDENCE WHICH CAN BE
VERY CHALLENGING.
SOMETIMES THE SPECIMENS ARE NOT
GOOD.
THEY'RE CRUSHED OR YOU KNOW,
UNREADABLE AND SOMETIMES WE HAVE
TUMORS THAT NOBODY HAS YET
DESCRIBED AND MAYBE WITH OUR
WORK WE CAN LAUNCH A NEW TUMOR
ENTITY.
SO OUR DIAGNOSTIC ARMAMENT HAS
INCREASED AND DIVERSIFIED HUGELY
OVER THE DECADES.
FIRST OF COURSE WE DID ONLY
HISTOLOGY.
THERE WAS NOTHING ELSE AND WE
STILL DO IT EVEN IF WE STARTED
THIS 1900 NOW IT'S AS VALUABLE
AS IT WAS THEN.
BUT WE HAVE SO MANY MORE DEVICES
AND THIS IS AN EXAMPLE OF PAST
AND WE USE MICROSCOPES NIH
DEVELOPED 15 YEARS AGO.
IN THE CHEMISTRY IS BIG.
AS WE KNOW THERE ARE 100,000
PROTEINS AND WE ONLY CHECK 250
OF THEM BY HISTOCHEMISTRY.
THERE WILL BE HUGE POTENTIAL IN
BIOMARK
BIOMARKERS IN THE FUTURE.
AND TECHNIQUES HAVE BEEN
EXPANDING RAPIDLY AND WE HAVE
OVER 30,000 GENES AND YOU SEND
THE CONSULTATION CASE FOR AN
EXPERT AND SOMETIMES GOOGLE WILL
HELP.
NOW, I START EXAMPLES.
HERE THIS IS HARD TO TELL WHAT
IT IS, A LOT OF LYMPHO-FELLS AND
ENDOTHELIA AND YOU CAN SEE
SMOOTH MUSCLE AND VESSELS.
IT TOOK A WHILE FOR ME TO FIGURE
THIS OUT SO I STOPPED AND JUST
GOT IT FOR NEXT MORNING AND
LET'S DO THE STUDY.
AND IT'S VERY POSITIVE BACTERIA.
THIS IS HEME -- HEMOTOSIS AND
THIS WAS MORE ASSOCIATED WITH
THE AIDS EPIDEMIC WITH THE
IMMUNOSUPPRESSOR.
IMMUNOMARKERS ARE THERE YOU CAN
SEE ON THE LEFT AND THEN NOW
TUMORS WITH FUSION WE CAN HUNT
THEM WITH THE FUSION PROTEINS
AND THAT IS VERY SUCCESSFUL
THERE'S LIPO SARCOMA AND MANY
MORE AND MOST OF THESE MARKERS
ARE EXCELLENT AND VERY SPECIFIC.
AND THEY MAY ALMOST COVER OR THE
THING WE WOULD GET FROM RNA
SEQUENCING.
HERE IS AN EXAMPLE OF A PATIENT
WHO HAS TWO TUMORS AND HAVE
INTESTINAL TUMOR, SMALL ONE ON
THE LEFT AND THEN A BIGGER TUMOR
WHICH LOOKS KIND OF UGLIER BUT
STILL THOUGHT TO BE METASTASIS
OF THE INTERNAL TUMOR AND THIS
ONE WAS ORIGINALLY I THINK IT
CAME TO US AS METASTATIC AND
HIGH GRADE TUMOR AND TUMOR
NECROSIS.
WHAT COULD IT BE IN THE BASIN
AND ACTUAL LY AND THIS IS
EXPECTED AND THE LIVER PART OF
THE TUMOR IS NOT POSITIVE SO
THERE'S SOMETHING ELSE RATHER
THAN -- AND THEN IT'S A TUMOR 3
AND YOU SEE NORMAL CELLS ON THE
POSITIVE TUMOR SO THIS IS
MALIGNANT TUMOR WHICH IS VERY
EXPECTED ACTUALLY IN THIS.
THIS KIND OF LOOKS LIKE SARCOMA
AND UGLY AND LOOKS IN THE
HISTIOCYTES AND IT'S KERATIN
POSITIVE 5 AND 6.
AND IT IS CARCINOMA AND
IMMUNIZED IN THE CHEMIST.
HERE WE HAVE A TUMOR WHICH IN
THE PAST ALMOST CERTAINLY WOULD
HAVE BEEN CALLED FIBROSARCOMA.
NOW WE KNOW FIBROSARCOMA IS A
RARE TUMOR ALMOST INCONSISTENT
AND ALMOST ALWAYS CAN BE
CLASSIFIED SOMETHING ELSE AND SO
IT IS IN THIS CASE AND THIS IS
ACTUALLY IT IS SOMETHING
DIFFICULT TO SAY HISTOLOGICALLY.
YOU CAN DO THE IMMUNOPANEL.
AND THIS MEANS VERY LITTLE NO
SMA, NOT GOING TO BE SMALL CELL
TUMOR BUT 100% POSITIVE AND THIS
IS A SARCOMA WHICH IS A TRICKY
TUMOR AND OVER THE YEARS EVEN
HERE WE SEE IT ALMOST EVERY YEAR
MAYBE ONE OR TWO BUT IT IS A
DIFFICULT TUMOR TO DIAGNOSE
BECAUSE IT IS NOT TYPICALLY
DIFFERENCE FROM THE SARCOMA YOU
WOULD EXPECT POSITIVE.
LET'S SEE WHAT THE METHYLATION
CLASSIFIER SAYS.
SO ACTUALLY, METHYLATION
CLASSIFIER IS EXCELLENT FOR THIS
FOR OUR ANALYSIS AND CLASSIFIER
WHICH IS AN EXPRESSION PROFILING
AND TUMORS ARE IN THE
METHYLATION AND METHYLATION
CLASSIFIER WILL TELL US THE
DIAGNOSIS.
IT FEELS LIKE IT WASN'T POSITIVE
WE DID METHYLATION AND
RANDOMIZED SARCOMA AND MYOGENI
SARCOMA AND THESE ARE FIBER LIKE
AND THE SAME TUMOR BUT STILL
QUITE DIFFERENT.
THIS IS A TUMOR AND EASY TO SEE
WHEN IT'S MYOGENIN POSITIVE AND
HIGH GRADE TUMOR.
THIS SARCOMA THE TUMORS CAN
CHANGE AND THAT'S AN ADDITIONAL
CHALLENGE FOR US.
OF COURSE UNDIFFERENTIATED
TUMORS IS ALWAYS A PROBLEM.
HERE IS A TUMOR WHICH WAS
THOUGHT TO BE LYMPHOMA IN 1986,
ACTUALLY.
THIS IS AN OLD CASE IN OUR
LIBRARY AND IN OUR STUDY WE
TOTALLY CHANGED THE DIAGNOSIS.
YOU SEE THE POSITIVE NOW RAISES
THE ABILITY OF THE LYMPHOMA.
BUT WE STUDIED THE LIBRARIES FOR
THE NEW ENDOTHELIAL MARKER AND
SURPRISIN
SURPRISINGLY IT WAS POSITIVE AND
CAN IT BE THAT?
THEN WE DO MORE ENDOTHELIAL
MARKERS.
CD 31 POSITIVE, 34 NOT POSITIVE.
THAT'S OKAY.
AND AND THE GROWTH FACTOR
POSITIVE.
SO, IT'S ANGIOSARCOMA.
DIDN'T LOOK LIKE THAT BUT THAT'S
WHAT WE NOW THINK BECAUSE WE
HAVE SO MANY MARKERS POSITIVE
FOR THAT.
FURTHERMORE WE FOUND CD 30 IN
THE SARCOMAS AND WHEN THEY ARE
TOTALLY UNDIFFERENTIATE D AND TP
FOR THE LYMPHOMA POSITIVE.
IT'S A BIG DIAGNOSTIC PITFALL
AND THAT'S WHAT WE FACE EVERY
DAY IN DIAGNOSTIC PATHOLOGY.
FUSION TUMORS ARE A BIG GROUP OF
SARCOMAS AND NOW THERE ARE
PROBABLY A FEW HUNDRED OF
DIFFERENT TUMOR TYPES WITH
FUSIONS SO THAT'S A CHALLENGE.
BUT OUR RNA SEQUENCING WE CATCH
THEM AND AS WE SAW BEFORE,
IMMUNOHISTOCHEMISTRY CAN CATCH
QUITE A LOT OF THEM TOO.
EWING SARCOMA USED TO BE A
DIFFICULT DIAGNOSIS BECAUSE
THERE WAS NO GOOD IMMUNOMARKER
BUT JUST THIS YEAR WE ARE
FINDING THAT THIS IS AN ACCIDENT
MARKER FOR EWING SARCOMA.
THERE IS A SMALL NUMBER OF OTHER
TUMORS THAT CAN BE POSITIVE.
USUALLY LESS CLEARLY POSITIVE AS
YOU CAN SEE IN EWING SARCOMA
CASE.
THIS WAS DONE IN EARLIER TIMES
BUT NOW WE HAVE SWITCHED TO
IMMUNOHISTOCHEMISTRY AND RNA
COMBINATION.
THEN HERE IS A LITTLE EWING
SARCOMA LIKE TUMOR BUT DOESN'T
QUITE LOOK ACTUALLY THIS IS
NEGATIVE THE MARKER.
IS ONE IMMUNO WOULD SOLVE THIS
AND THIS IS A NICE TOOL.
HERE IS AN INTESTINAL TUMOR AND
THREE DAYS OF THIS AND AFTER
THAT WE NEVER SAW IT.
AND WE DID RNA SEQUENCING AND
FOUND A FUSION.
AND IT IS NOT A FUSION TUMOR AND
HERE YOU SEE NOT POSITIVE ALSO
BY IMMUNOHISTOCHEMISTRY TO
DIAGNOSE THIS IN MANY WAYS.
NOT M FUSION SARCOMA.
HERE IS EWING SARCOMA, CD 99 AND
POSITIVE BUT WE HAVE LEARNED
THIS IS NOT SPECIFIC AND
RELIABLE OR SOMETHING ELSE HAS
TO BE THIS MAY BE IN EWING CD 34
BUT LOW IN THIS THIS WAS A
RESULT OF THE IMMUNOSTAIN TUMOR
6 POSITIVE AND ALSO RNA
SEQUENCING SO THIS IS A VARIANT
OF FIBROTUMOR REPORTED YEARS AGO
BY A JAPANESE GROUP.
THIS LOOKS LIKE A
[INDISCERNIBLE] TUMOR DOESN'T
IT?
FULL OF FAT CELLS AND VERY
LITTLE OF THE SOLID TUMOR CELLS
IN THE LEFT HERE YOU CAN SEE AN
AREA WITH MORE SOLID ROUND CELLS
AND WHAT IT LOOKS LIKE BUT
IMMUNOSTAINS START POSITIVE WE
PUT IT IN METHYLATION BUT IT
DIDN'T CATCH IT BECAUSE IT DID
NOT HAVE SO MUCH OF THE RIGHT
TUMOR CELLS AND HAD A LOT OF
FAT.
SO SOLITARY FIBROS TUMORS AND IT
WAS POSITIVE YOU WOULD THINK AHA
HERE IS A SOLITARY FIBROTUMOR IN
A 6-YEAR-OLD BOY.
AND WE HAVE THE RNA SEQUENCING
AND WE SEE THE FUSION TOOL.
AND IT'S AN EASIER WAY TO DO IT.
THE IMPORTANCE OF THIS IS THERE
IS A SPECIFIC TARGETED TREATMENT
AGAINST AGAINST NTRK PROTEIN
WHICH IS DRIVING THE TUMOR.
I THINK THIS BOY GOT YOU CAN GET
A PHONE CALL FROM PATHOLOGIST
AND THE MOTHER AND IN A CERTAIN
SENSE IT MIGHT BE BUT IT'S NOT
SAYING AS THE TUMOR IT IS
SOMEWHAT LOW GRADE TUMOR.
AND SHOULD BE GOOD PROGNOSIS.
AND THIS WOULD RAISE THE CHANCE
OF A TUMOR AND WE DID RNA
SEQUENCING AND METHYLATION.
AND RNA SEQUENCING AND FUSION
WHICH MEANS THE FIBROUS SARCOMA
AND METHYLATION SO DOUBLE
CONFIRMATION WHICH IS FAIRLY
GOOD.
THIS IS AN ELITE POSITIVE MIX.
AND IT'S NOT A SOLITARY FIBROUS
TUMOR VARIANT.
SO ONE TUMOR CAN GET SO MUCH
PROBLEMS.
BUT THEN WE LEARN FROM THAT AND
CAN START THE IMMUNOSTAIN WHEN
WE START THE DIAGNOSIS.
HERE THE TUMOR IS CRUSHED.
DEFINITEL
DEFINITELY MENINGIOMA BUT MANY
MARKERS WERE NEGATIVE.
IT'S EXTRA AXIAL INTERCRANIAL
TUMOR.
AND THEN WE DO THE MARKER NOT
CLEAR POSITIVITY CONFIRMS THE
DIAGNOSIS.
SOMETIMES THIS TUMOR IS A
PROBLEM.
IT'S SMA POSITIVE AND IT DOESN'T
RING A BELL.
WE'RE GOING TO PUT IT IN FURTHER
STUDIES.
METHYLATION NOT ONLY SEI AND
THEN WE DO USB6 THE DIFFUSION
AND POSITIVE.
THESE ARE VARIANTS BUT NEGATIVE
FOR PDGFB FISH AND THERE IS A
FUSION USUALLY IN THE CONTROL.
WE STUDIED FURTHER AND THERE'S
AN ALTERNATE SO IT IS A GENE
GENETICGENE
GENETICALLY ODD VARIANT OF THE
SARCOMA.
IT LOOKS PRETTY MUCH BENIGN AND
THE ONLY THING IS IT'S 29
CENTIMETER.
WHICH IS LIKE A HUGE TUMOR.
CAN BE LIKE THAT IN ALMOST LIKE
A WHOLE LEG IB THAT SARCOMA CAN
BE ABDOMINAL AND WE SEE A
METHYLATION CLASSIFIER AND SEE
THE LIPO SARCOMA HERE AND WE NOT
ONLY LOOK AT THAT AND THEN WE
LOOK AT THE CHANGE EXPECTED IN
THE LIPO SARCOMA.
AND THAT IS ACTUALLY HERE.
AND THE AMPLIFICATION WHICH
FURTHER WHICH IS GOOD FOR
LIPOSARCOMA.
WE SOMEWHERE CD 34 POSITIVE AND
IF WE WANT TO CONFIRM THIS IS A
TUMOR WITH PLASTOMA AND LET'S
SEE WHAT THE METHYLATION DNA ARE
HERE.
SINGLE CELL LIPOMA.
UNDIFFERENTIATED TUMORS ARE A
BIG PROBLEM OF COURSE BUT ACTUAL
LY MANY ARE UNDIFFERENTIATED
SARCOMAS AND MARKERS ARE NOTHING
HERE AND WE DO NOT PUT IT IN
METHYLATION CLASSIFIER AND DNA
ANALYSIS LOTS OF OTHER CHANGES
SO IT'S A DIFFERENTIATED
LIPOSARCOMA WHICH HISTOLOGICALLY
MIMICS UNDIFFERENTIATED SARCOMA
BUT DRIVEN BY AMPLIFICATION.
THIS LOOKS LIKE RHABDOMYOSARCOMA
AND WE HAVE THE PRESIDENT WHO IS
THE PIONEER OF RHABDOMYOSARCOMA
WHO FOUNDED FUSION ABOUT 30
YEARS AGO.
ONE OF THE FIRST TUMOR SARCOMA
FUSIONS EVER DETECTED.
AND USUALLY THIS IS FOX 3 OR FOX
7 WITH FOX 01 BUT FOX 01 FISH
WAS NEGATIVE IN THIS ONE STILL
WOULD BE GOOD FOR OTHER
RHABDOMYOSARCOMA MEANING 100%
POSITIVE.
THIS IS TYPICAL OF THE
RHABDOMYOSARCOMA.
SO WE'RE GOING TO PUT THIS IN
METHYLATION CLASSIFIER AND RNA
SEQUENCING AND WHAT DO WE FIND?
WE FOUND FOX 03 FUSION WHICH IS
ALTERNATIVE FUSION IN THE
SARCOMA AND WE CONFIRMED THE
DIAGNOSIS.
WE NEED THE IMMUNOSTAINS MORE
THAN WE ALLOWED PEOPLE TO NOW
ORDER BECAUSE ONLY 8 OR 7
IMMUNOSTAINS WE HAD TO DO MANY
EVEN FACTOR 1 FOR OTHER
CARCINOMA I WAS TRYING BUT I GOT
NOTHING HERE.
EVERYTHING WAS NEGATIVE.
SO NOW WHAT DO WE DO?
WE PUT IT IN BOTH METHYLATION
CLASSIFIER AND SEQUENCING.
AND IN THIS CASE WE DID DNA
SEQUENCING.
SO NOTHING WAS POSITIVE.
NOT CARCINOMA, NOT MELANOMA OR
ANY SPECIFIC SARCOMA AND
SOMETHING WAS WRONG ON THIS.
SO WHAT IS IT?
IT'S UNDIFFERENTIATED MELANOMA
AND THIS TUMOR SHEDS ALL THE
MARKERS, NOTHING POSITIVE AND
INDEED METHYLATION GAVE A LOW
SCORE FOR MELANOMA BUT ALSO VERY
IMPORTANTLY TUMOR CONTAINS Q61
WHICH IS TYPICAL OF MELANOMA AND
ACTUALLY MOST COMMON DRIVER IN
UNDIFFERENTIATED MELANOMA IN OUR
EXPERIENCE.
HERE IS ANOTHER ONE
UNDIFFERENTIATED TUMOR.
THIS MEANS POSITIVE A LITTLE BIT
POSITIVITY AND WHAT IT IS, IT
HAS ROUGHLY 600 AND GRAY
METHYLATION CAUSED MELANOMA.
SOMETIMES IT'S BETTER THAN THE
SOFT TISSUE METHYLATION AND
ANOTHER EXAMPLE OF IN DURCHB
SH --
DIFFERENTIATED MELANOMA.
AND THIS IS MY LAST EXAMPLE.
THIS IS ABOUT VERY HIGH VIEWS.
SO IT LOOKS LIKE A PRIMITIVE
UNDIFFERENTIATED TUMOR HAS
DIFFERENTIATION.
SO COULD MELANOMA LIKE RELATED
SOMETHING BUT ACTUALLY LITTLE
CHILDREN DON'T HAVE THAT TYPE OF
MELANOMA BUT CAN HAVE TUMORS OR
LIKE TUMORS AND WHAT IS THIS IN
INFANT SCROTUM IS NOT OBVIOUS
BUT THIS IS WHAT IT EXACTLY WAS.
HERE IS THE GOOGLE MY QUESTION
OF THIS ANSWER COULD BE
CONGENITAL [INDISCERNIBLE] AND
THAT WAS THE DIAGNOSIS.
I THANK YOU SO MUCH FOR YOUR
ATTENTION.
AND I HOPE THAT YOU HAVE A GOOD
DAY.
THANK YOU, ALL.
>> THANK YOU, DR. MIETTINEN.
FIRST OF ALL, I'M HAPPY TO KNOW
I'M NOT THE ONLY PERSON TO USE
GOOGLE FOR DIAGNOSES.
THANK YOU FOR SHOWING THE
IMMUNOHISTOCHEMISTRY.
THE QUESTION COMES TO MIND IS
WHAT IS THE NEXT STEP?
YOU GAVE US AT THE BEGINNING A
TIME LINE GOING FROM SIMPLE
STAINS TO IMMUNOHISTOCHEMISTRY.
WHAT IS THE NEXT STEP IN
DIAGNOSTIC FOR SOFT TISSUE
TUMORS AND I KNOW THIS QUESTION
GETS RAISED A LOT DOES A.I. PLAY
A ROLE IN THAT?
>> AND TO PREDICT THE FUTURE IS
VERY DIFFICULT ACTUALLY.
SO ALMOST IMPOSSIBLE TO ANSWER.
EXCELLENT QUESTION IN ITSELF BUT
THE NEWEST ONE AND WHAT WE HAVE
AND IS TILL EXPERIMENTAL IS THE
SARCOMA CLASSIFIER WHICH IS
HIGHLIGHTED IN SOME OF THE
PICTURES HERE AND THAT WILL GROW
IN THE FUTURE.
THE SECOND VERSION IS IN MAKING
AND WE HERE AT NIH, NCI, ARE
PART OF THE SECOND VERSION
MAKING OR SO WITH OUR 1,500
CASES.
>> AND HOW COMMON -- BECAUSE
OBVIOUSLY NCI HAS THE MOST
CAPABILITY BUT HOW COMMON ARE
THESE AND ARE THERE REFERENCE
LABORATORIES?
>> YEAH.
IT REALLY IS CHALLENGING FOR A
SMALL HOSPITAL.
THEY DON'T HAVE 250 IMMUNOSTAINS
AND THEY PROBABLY DON'T HAVE RNA
OR DNA SEQUENCING SO THEY OFTEN
SEND CASES IN CONSULTATION.
THAT'S THE MOST PRACTICAL THING
TO DO FOR SMALL PLACES.
TO LET THE CONSULTANT DO IT AND
THEN OF COURSE THERE ARE
LABORATORIES FOR SEQUENCING.
>> ARE THERE ANY QUESTIONS?
>> WONDERFUL TALK, MARKKU.
YOU SHOWED NICE CASES MUCH
MIMICS WHERE HISTOLOGY AND THE
IHC MIGHT SUGGEST ONE THING BUT
THEN YOU DO ADVANCED MOLECULAR
TECHNIQUES AND IT SHOWS
SOMETHING ELSE.
AND I THINK YOU VERY NICELY
SHOWED THAT'S BECOME THE NEW
PARADIGM.
DO YOU FIND THERE'S UNIVERSAL
ACCEPTANCE IN THE FIELD TO THESE
NEW TECHNIQUES WHEN YOUR
DIAGNOSIS MIGHT DRAMATICALLY
CHANGE FROM THE MOLECULAR
TECHNIQUES?
YOU KNOW, IN CONTRAST TO WHAT
MIGHT HAVE BEEN EXPECT FROM THE
TRADITIONAL H AND E AND IHC DO
YOU FIND IN THE COMMUNITY YOU
CONSULT WITH THERE'S UNIVERSAL
ACCEPTANCE OR CHALLENGE THERE?
WHAT'S YOUR EXPERIENCE THERE?
>> I THINK THE COMMUNITY IS ALSO
THIRSTY FOR NEW WAYS OF
DIAGNOSIS AND NEW WAYS OF
PERSISTENT DIAGNOSIS AND I THINK
SEQUENCING AND METHYLATION WHICH
IS LED BY THE BRAIN METH LAYING
AND SARCOMA METHYLATION FOR ALL
OF US AND FOR THE WHOLE AMERICAN
COMMUNITY BECAUSE THE CONFERENCE
WHICH IS PROBABLY HUNDREDS OF
PEOPLE ATTENDING.
I THINK THE METHYLATION CLASS
CLASSIFIER REALLY IS SOMETHING
WHICH IS GROWING AND WILL BECOME
IMPORTANT.
I THINK IT'S ALSO COST EFFICIENT
TO SOME DEGREE AND MAYBE LESS
EXPENSIVE THAN TRADITIONAL FULL
SEQUENCING.
BUT AGAIN HARD TO SAY WHAT
HAPPENS.
MAYBE SOMETHING TOTALLY NEW WILL
COME.
>> A COUPLE QUESTIONS FROM OUR
VIRTUAL AUDIENCE.
ONE, HOW DOES TUMOR METHYLATION
CLASSIFIER LEAD TO PROGNOSIS AND
TREATMENT?
I THINK DIAGNOSIS LINKS WITH
TREATMENT.
METHYLATION LEADS TO DIAGNOSIS
AND THERE ARE OTHER ASPECTS LIKE
METHYLATION CLASSIFIER GIVES
ESPECIALLY BRAIN TUMORS THIS IS
IMPORTANT.
MG, NT METHYLATION STATUS AND IF
FG, NT IS METHYLATE D AND
CHEMOTHERAPY CAN BE USED.
THE METHYL TRANSFERASES.
>> ONE OTHER QUESTION SAYS IS
YOUR LAB LINKED TO GROUPS AT
NCI?
SO THE DEFINITIVE DIAGNOSIS CAN
BE LINKED TO KNOWLEDGE FOR THE
PATIENT?
>> YES, IT IS.
ALL OUR DIAGNOSIS CAPABILITIES
ARE FOR USE FOR CLINICAL CENTER
AND WE DO THESE STUDIES FOR
PATIENTS AS NEEDED.
>> DR. MIETTINEN THANK YOU FOR
YOUR PRESENTATION AND
CONGRATULATIONS AGAIN.
THAT CONCLUDES TODAY'S GRAND
ROUNDS.
FOR THOSE INVITED THERE'S A
RECEPTION FOR DR. MIETTINEN AND
THE DECKER FAMILY AND WE LOOK
FORWARD TO THE PRESENTATION NEXT
YEAR.
HAVE A GOOD AFTERNOON THANK YOU
EVERYBODY.