!"#$%&'()(*'+(+,"#-'(./&,0,12,"'+)+1((3456375($/"#(8933(

!"#$%%&&'('

)*+,*-./*'0'123/#$.4'5##.#+%/+2%&%4')2./.$$'63-'7.*&/3#8$$'3&'./+%-9%/#:3/4''597;'63-'<*+323&.4''=#23'>/.9%-#.+%+##?$%,>#@A.$#,3#<.+*2%+'

Sykehistorie

B  CD'"-'&*EE%2'$9.//%4'&-*9.7'.'F'E/7;'

B  )2./.#$'G%#$-%9%+'#+3-',%E3--3.7%'$2;'H'#3E'G2%'./#.7%-+;'

B 03I*I'7%G-.#E*+%-.*2'JKL(L('3&'DLHLH'EE'82',.#+3<*+323&.#$'>/7%-#M$%2#%;'

HE

HE

N.*&/3#%63-#2*&'

B  O'L'P#E*22'-3>/7'G2>%'Q%22'+>E3-P'B  D'L'2?E63E'

B  R'L'!"##$!%&'()*+",$&B  J'L'E*2.&/'/%9-3%/73$-./'+>E3-'

B  J'L'&-*/>23#*Q%22%+>E3-'

B  J'L',%E*/&.3<%-.Q?+3E'

B  J'L'*/&.3#*-$3E'

Negativ immunhistokjemisk farging for:

B  S<.+%2.*2'7.T%-%/#.%-./&U'V)'B  W?E63Q?+X-'7.T;U'VN'CK4'VN'H'

B  Y%9-3%/73$-./'7.T;U'Z?/*<+36?#./4'V,-3E3&-*/./4''

'VN'(['

B  0>#$%2'7.T;U'0?3&%/./4'N%#E./''

B  \*#$>2X-'7.T;U'VN'HJ4'VN'HD'

B  ].#83Q?+X-'7.T;U'VN'[R'

CK CD 34

CD 68 Synaptofysin

S 100 Vimentin

CD 99 FLI 1

Immunhistokjemisk undersøkelse av CD 99:

'!3#.89'.'S^./&'#*-$3E'_SZ`'3&'<-.E.89'/%>-3%$+37%-E*2'+>E3-'_!YSa`;'

'!3#.89'.'/3-E*2%'M?Q%22%-'.'<*/Q-%*#4'$3-8$*2%'+,?E3Q?I%-4'#%-+32.Q%22%-'3&'39*-.*2%'&-*/>23#*Q%22%-;''

'b%/%+'0cVC'#3E'$37%-'63-'39%-d*+%'*/8&%/%+'VN'OO'%-'23$*2.#%-+'<"'7%/'<#%>73*>+3#3E*2%'-%&.3/'_!5A`'<"'G%&&%'$3-+%'*-E%-'*9'e'3&'f'Q,-3E3#3E%-'_3g%'-%*--*/&%-+'.'+>E3-%#`;'

Immunhistokjemisk undersøkelse for FLI-1:

'a-*/#$-.<#:3/#6*$+3-4'./9329%-+'.'Q%22>2X-'<-32.6%-*#:3/'3&'/%3<2*#.>+9.$2./&;'

'OKh'*9'*22%'SZi!YSa',*-'%/'#<%#.j$$'+-*/#23$*#:3/4'+_JJ4CC`_kCD4'kJC`4'#3E'6M-%-'82'6>#:3/'*9'SlZ'82'm2.J'3&'39%-<-37>$#:3/'*9'm2.J'<-3+%./%+;'N%I%'<-3+%./'7%+%$+%-%#'E%7'*/8#+3T'E3+'m2.J;''

'nI-?$$%#'3&#"'.'%/73+%2Q%22%-4'2?E63Q?I%-'3&'$*-#9>2#+%-'_*/&.3#*-$3E4',%E*/&.3%/73+,%2.3E4',%E*/&.3E4')*<3#.'#*-$3E`;''

Foreløpig diagnose

'ZE"Q%22%+'E*2.&/'+>E3-'_G.3<#.'6-*'o,%E3--3.7%o`4'E3-6323&.#$'3&'.EE>/6%/3+?<.#$'63-%/2.&'E%7''

'S^./&'#*-$3E;'

Foreløpig diagnose

'ZE"Q%22%+'E*2.&/'+>E3-'_G.3<#.'6-*'o,%E3--3.7%o`4'E3-6323&.#$'3&'.EE>/6%/3+?<.#$'63-%/2.&'E%7''

'S^./&'#*-$3E;'

'0%/4'63-'"'#+MI%'7.*&/3#%/'*9'%+'S^./&'#*-$3E'GM-'E*/'63-#M$%'"'<"9.#%'%/'*9'd%-%'E>2.&%'+-*/#23$*#:3/%-U'+_JJpCC`_kCDpkJC`4'+_CJpCC`_kCCpkJC`'%22%-'+_FpCC`_kCCpkJC`;'

Translokasjonsanalyser: Split/break-off prober analyserer kun én av

translokasjonspartnere!

Probene

•  hybridiserer til områder på hver side av EWS-genet

•  splittes ved translokasjon

Ewing sarkom

EWS

FLI1

PNET/Ewing sarkom Analyse av cytologisk prøve med EWS/22q12 split/

break-off probe

Normale lymfocytter PNET/EWS

cen22q12 tel22q12

cen22q12 tel22q12

Påskeegg 5: Analyse av parafinsnitt med EWS split probe

PNET/Ewing sarkom kan ha flere varianter av translokasjoner

som alle involverer EWS genet

&:33;88<:=8>;=38< ( (?@A3 ( (BCD(&:83;88<:=88;=38< ( (EFG ( (39D(&:4;88<:=88;=38< ( (EHI63( (JCD(&:34;88<:=38;=38< ( (E3K? ( (JCD(&:8;88<:=LL;=38< ( (?EI (

(JCD( ( ( ( ( ( (( ( ( ( (!"#"$"% && & & & &'$&()*&%(+(

PCR analyse

B  !VA'*/*2?#%'<"'<*-*j/G23$$U']9%-$%/'SlZAJ@mWcJ4'SlZAJ@SAb'%22%-'

ZZJR@ZZeJiCiD'+-*/#23$*#:3/'%-'<"9.#+;'

B  Y?'!VA'*/*2?#%'<"'6%-#$+'E*+%-.*2U'

SlZAJ@mWcJ'&%/6>#:3/'%-'<"9.#+;'

Translokasjoner av 22q12 (EWS) forekommer også ved andre tumores

'SlZ'%-'G2;*;'./9329%-+'.'+-*/#23$*#:3/%-'9%7'D'*/7-%'+>E3-%#U''!'N%#E3<2*#8#$'->/7Q%22%+'+>E3-'_NAVa`'

'+_JJpCC`_<JHpkJC` ' 'SlZ@laJ ' 'O(h'

!'S$#+-*#$%2%+*2+'E?$#3.7'Q,3/7-3#*-$3E''+_OpCC`_kCCpkJC` ' 'SlZ@V]Y ' 'F(h'

!'0?$#3.7'2.<3#*-$3E''+_JCpCC`_kJHpkJC` ' 'SlZ@NNcaH '' '(h'

!')2*-Q%22%+'#*-$3E'_E*2;'E%2*/3E*'36'#3g'8##>%`''+_JCpCC`_kJHpkJC` ' 'SlZ@5amJ ' 'q'

NB! Rearrangering av EWS på 22q12 er kun diagnostisk for EWS/PNET

hvis også morfologi og immunfenotype støtter diagnosen!

Diagnose

'ZE"Q%22%+'E*2.&/'+>E3-'_G.3<#.'6-*'o,%E3--3.7%o`4'

'E3-6323&.#$4'.EE>/6%/3+?<.#$'3&'Q?+3iE32%$?2X-&%/%8#$'9%2'63-%/2.&'E%7'

'S^./&'#*-$3E;'

Radiologisk undersøkelse''

B  Va@*G73E%/iG%$$%/U'a>E3-'.'3&'>+%/63-'*/>#'E%7'39%-9%$+'9%;'#.7%;''

B 0A@G%$$%/U'a>E3-'.'3&'>+%/63-'*/>#'E%7'39%-9%$+'9%;'#.7%'E%7'*T%$#:3/'*9'%$#+%-/%'#<,./$+%-'3&'/%7-%'7%2'*9'*/*2$*/*2%/;'

B  c/&%/'E%+*#+*#%-'<"9.#+;'

Klinisk forløp

B  )%.#%-#/.I'.'>$%'HD'r'D;'B  V%22%&.gG%,*/72./&'%I%-'<-3+3$322'cZbiZZb@ccc'E%7'9./Q-.#8/4'73L3->G.Q./4'Q?Q2363#6*E.7'3&'E%#/*'3&'./+%-<3/%-+'#+-"2%G%,*/72./&;'m.$$'#.#+%'$>-'7%/'JF;KR;JK;''

B  !*#.%/+%/',*-'-*7.323&.#$'$3E<2%I'-%E.#:3/;'

B  =<<6M2&./&'E%7'<32.$2./.#$%'$3/+-322%-;'''

Ekstraskeletalt Ewing sarkom

B  'E%//'s'$9.//%'B  '>/&%'93$#/%'_7%'d%#+%'%-'>/7%-'HK'"-`'B  ',?<<.&#+'23$*2.#%-+'.'<*-*9%-+%G-*2'-%&.3/%/'B  ',%E*+3&%/'E%+*#+*#%-./&'_E%#+'.'2>/&%`'

B  '(@"-#'39%-2%9%2#%'(K@[(h'_%I%-'$:%E3+%-*<.`'

B  '7"-2.&'<-3&/3#%'%I%-'-%#.7.9'