The Morphology Illusion Lymphoma Cases Presentation Dr Hebah Ali - PowerPoint PPT Presentation

AP  17 Oc to b e r 2018  De a d Se a , Jo rda n XXXI I Co ng re ss o f the I The Morphology Illusion Lymphoma Cases Presentation Dr Hebah Ali  Consultant Haematopathologist  Haematological Malignancy Diagnostic Service  Leeds, UK “T he S un S e ts S ail” Painting by Ro b Go nsalve s

hyroid ma ss. 20- ye a r- old fe ma le . T Ca se 5

Morpholog y

Morpholog y

Hodg kin L ymphoma s in T hyroid Wa ng e t a l Ho dg kin's lympho ma o f the thyro id: a c linic o pa tho lo g ic study o f five c a se s a nd re vie w o f the lite ra ture . Mo d Pa tho l. 2005

Immunohistoc he mistry CD30 CD30 IRF IRF 4 4 CD15 CD15 Pa x5 Pa x5 L L MP1 MP1 CD20,79,138- CD20,79,138- AL AL K1 - K1 - CD3,2,8,7 - CD3,2,8,7 - CD5 CD5 CD4 CD4 GRANZ GRANZ

Diffe re ntia l Dia g nosis Site Pa x5- AL K -1 - L MP1- CD15 + T CA+ HRS Mo rpho lo g y Cyto to xic + CD15 + T - c e ll Ag e L ine a g e Cla ssic a l Hodg kin Ana pla stic L a rg e Ce ll

T CA a nd Cytotoxic Mole c ule s in c HL Ve nka ta ra ma n e t a l Ab e rra nt T -c e ll a ntig e n e xpre ssio n in c la ssic a l Ho dg kin lympho ma is a sso c ia te d with de c re a se d e ve nt-fre e surviva l a nd o ve ra ll surviva l. Blo o d. 2013 Asa no e t a l , Cyto to xic mo le c ule -po sitive c HL : a c linic o pa tho lo g ic a l c o mpa riso n with c yto to xic mo le c ule -po sitive PT CL NOS type . Ha e ma to lo g ic a . 2011

DUSP22/ IRF4 E xtra Copie s 4 (re d/ g re e n) DUSP22/ IRF

No Clona l T Ce ll Popula tion T CR g a mma multiple x PCR a na lysis sug g e sts pa uc ity of T c e ll ta rg e ts

Clona l B Ce ll Popula tion Clona l re a rra ng e me nts we re ide ntifie d

Clona l B Ce ll Popula tion Clona l re a rra ng e me nts we re ide ntifie d

F ina l Dia g no sis Ce llula r c la ssic a l Hodg kin lymphoma with a be rra nt CD4 a nd c ytotoxic e xpre ssion Ra dio lo g y: T hyro id no dule a nd ipsila te ra l lymph no de s

E xtra - noda l Hodg kin L ymphoma in HMDS T o nsil 7 Pa ro tid 4 T hyro id 1 Me dia stinum 17 L ung / ple ura 9 Skin 3 Bo ne 3 Musc le 1 L ive r 16 Sple e n 5 I nte stine 2 T issue b io psie s in L e e ds HMDS [2014-2018]

Biolog y of Hodg kin L ymphoma ‘ I n summa ry, c la ssic a l HD is a B-c e ll ne o pla sm in ne arly all insta nc e s.’ Ma ra fio ti e t a l Ho dg kin a nd re e d-ste rnb e rg c e lls re pre se nt a n e xpa nsio n o f a sing le c lo ne o rig ina ting fro m a g e rmina l c e nte r B-c e ll with func tio na l immuno g lo b ulin g e ne re a rra ng e me nts b ut de fe c tive immuno g lo b ulin tra nsc riptio n. Blo o d. 2000

How reliable is microscopy?

24- ye a r- old fe ma le . Ne c k lympha de nopa thy. Ca se 6

Morpholog y

Immunohistoc he mistry CD68 CD68 CD3 CD3 CD21 CD21

CD20

CD20 CD20 BCL BCL 6 6 IRF IRF 4 4 CD79a + CD79a + CD10- CD10- Ki- 67 in c yc le Ki- 67 in c yc le

-c e ll/ histio c yte ric h B-c e ll lympho ma T

C - MYC / IG H Re a rra ng e me nt C- MYC/ IGH (re d/ g re e n) Bre a k- a pa rt C - MYC F ISH

BC L 6 Re a rra ng e me nt Bre a k- a pa rt F ISH

Hig h G ra de B- c e ll L ymphoma s Se sq ue s P, Jo hnso n NA. Appro a c h to the dia g no sis a nd tre a tme nt o f hig h-g ra de B-c e ll lympho ma s with MYC a nd BCL 2 a nd/ o r BCL 6 re a rra ng e me nts. Blo o d. 2017. Swe rdlo w SH e t a l. WHO c la ssific a tio n o f tumo urs o f ha e ma to po ie tic a nd lympho id tissue s. L yo n, F ra nc e : I ARC Pre ss, 2017

Clinic a l F ollow Up Pa tie nt e nte re d into a c linic a l tria l Re c e ive d c o mb ina tio n o f c o mb ina tio n o f a c a la b rutinib with rituxima b , c yc lo pho spha mide , do xo rub ic in, vinc ristine a nd pre dniso lo ne (R-CHOP)

C - MYC in Hig h G ra de B- c e ll L ymphoma s Shi M e t a l. F ive impo rta nt a dva nc e s in he ma to pa tho lo g y. Arc h Pa tho l L a b Me d. 2014. Re vie w.

Alg orithm of C - MYC T e sting in HMDS HE morphological screening by senior BMS Auto request extended-B IHC panel (1d TAT) Auto request extended-B IHC panel (1d TAT) Includes: CD10 BCL6 BCL2 ● Does NOT include C-MYC Includes: CD10 BCL6 BCL2 ● Does NOT include C-MYC Reporting by pathologist Auto request of FISH (3d TAT) Auto request of FISH (3d TAT) High grade B-cell lymphoma bcl-2 negative , further tests awaiting High grade B-cell lymphoma bcl-2 negative , further tests awaiting DLBCL and variants DLBCL and variants High grade B-cell lymphoma, further tests awaiting High grade B-cell lymphoma, further tests awaiting C-MYC , BCL2 & BCL6 C-MYC , BCL2 & BCL6 C-MYC C-MYC All three -ve All three -ve Any combination +ve Any combination +ve C-MYC -ve C-MYC -ve C-MYC +ve C-MYC +ve 11q testing 11q testing BCL2 & BCL6 testing BCL2 & BCL6 testing Immuno-profile, COO, FISH results Immuno-profile, COO, FISH results Updating by clinical scientist Auto e-mail notification & MDT listing Auto e-mail notification & MDT listing

Can we spot the difference?

Double a nd T riple Hit L ymphoma s in HMDS 75% originally reported as DLBCL and variants 82 cases 25% originally reported as High grade B-cell lymphoma, further testing pending F o r c a se s re c e ive d 2017 o nwa rds

Painting by Ro b Go nsalve s