Specialespecifikt kursus i gastropatologi 2016 Mesenkymale tumorer Louise Klarskov
Mesenkym Fibroblaster Histiocytter Fedtvæv Glat muskulatur - leiomyomer Skeletmuskulatur Kar Perifere nerver - schwanomer Mesotel
MV
MV
MV
ASMA MV
DES MV
CD117 MV
Gastrointestinale stromale tumorer Hyppigste gastrointestinale mesenkymale tumor Udgør 95% af de mesenkymale tumorer i ventriklen Incidens 10-15/mill/år ~ 70/år i DK Median alder 55-65 år; M~F Hyppigt maligne Kan være familiære /syndrome MV
GIST fordeling Colon/rectum 6% Andet (esphagus, mesenteriet, retroperitoneum, pancreas, galdeveje ) 6% Tyndtarm 32% Ventrikel 56% Søreide et al Cancer Epidemiology 2016
Gastrointestinale stromale tumorer Cajal celler Pacemaker celler i tarmen Associeret med enterale neurale plexus Indskudt mellem intramurale neuroner og glatte muskelceller Genererer elektriske slow waves CD117 1998 Kindblom et al. (AJP) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal MV
Gastrointestinale stromale tumorer MV
Gastrointestinale stromale tumorer Tumor Gastrisk mucosa MV
Gastrointestinale stromale tumorer MV
Gastrointestinale stromale tumorer MV
Gastrointestinale stromale tumorer Spindle cell ~70 % Epitheloid - Mixed MV
Gastrointestinale stromale tumorer Storiform (~ Mal fibrøst histiocytom) Pallisaderende (~ schwannom) Organoid (~ NET) MV
Virchows Arch (2001) 438:1 12 Markku Miettinen Jerzy Lasota
Gastrointestinale stromale tumorer Tidligere fejl -klassificeret som: Epiteloidt/bizart leiomyom Leiomyoblastom Leiomyosarkom Schwannom Fibromatose Udifferentieret sarkom Lymfom Malignt melanom NET Karcinomer MV
Gastrointestinale stromale tumorer 70% af tumorerne var CD34+ Ingen var CD31+ Leiomyom og schwannom er CD34- Kaposis sarkom er CD34+ og CD31+ Fibroblastære og endotheliale tumorer er dog også CD34+ CD34 1995 Miettinen et al. (AJSP): Gastrointestinal stromal tumors value of CD34 in their identification and separation from true leiomyomas and schwannomas. MV
Gastrointestinale stromale tumorer CD117 er et tyrosin kinase receptor protein 85% af GIST tumorer var CD117+ - både epiteloide og spindlecelle varianter Også CD117+ i CD34- tumorer 1998 Sarlomo-Rikala et al. (Mod.Pathol.): CD117: a sensitive marker for gastrointestinal stromal tumors more specific than CD34 MV
Gastrointestinale stromale tumorer CD117-farvningsmønstre MV
CD117 mutationer i GIST Science 279:577-580, 1998 Positiv KIT (CD117) reaktion i 46/49 GIST (94%) 5/6 GIST havde mutationer i KIT-genet Mutant former af KIT er konstitutivt aktive øget proliferation og nedsat apoptose
Gastrointestinale stromale tumorer CD34: 50 70 % CD117: 95 % ASMA: 50 % DES: 5 %? MV
Gastrointestinale stromale tumorer S-100 protein: 10 20 % (MV)
DOG1: Discovered On GIST 1 2009 Miettinen et al. Am J Surg Pathol: DOG1 antibody in the differential diagnosis of GIST
GIST CD117+ ca. 95% DOG1+ ca. 95% CD117+/DOG1+ ca. 92% 2-3 % af GIST er neg for begge
CD117 negative GIST CD117 negative GIST har mutationer i PDGFRA i stedet for KIT Særligt en undertype af GIST med myxoid epitheloid morfologi 2004 Sakurai et al (Hum pathol) : Myxoid Epitheloid GIST with mast cell infiltrations: A subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene. (MV)
GIST, paragangliom GIST, ekstra adrenal paragangliom, pulmonalt chondrom
GIST malignitetskriterier Absolutte peritonealt udsæd infiltration i andre organer Fjernmetastaser (lever, oment, lunger, knogle, retroperitoneum) Relative mitoser tumorstørrelse? mucosainfiltration? skenoide fibre; epiteloid vækst? nekrose; pleomorfi? neural differentiering? mib1 positivitet > 10%; low p27 Demaetto, Hum. Pathol. 2002 MV
GIST malignitetskriterier Recurrence-free survival is predicted by tumor size and mitotic index 1.0 1.0 3 mitoses/30 HPF Recurrence-free survival 0.75 0.50 0.25 0 <5 cm 5-10 cm >10 cm P=0.03 0 20 40 60 80 Months Recurrence-free survival 0.75 0.50 0.25 0 0 P=0.0001 >3 to 15 mitoses/30 HPF >15 mitoses/30 HPF 20 40 60 80 Months Singer et al. J Clin Oncol. 2002;20:3898. MV
Imatinib hæmning i GIST 344, 14:1052, 2001 MV
Imatinib hæmning i GIST T = 0 1 mo. 8 mo. MV
Imatinib hæmning i GIST T = 0 3 weeks Ki67 MV
Metastaserende GIST overall survival 100% 80% 60% Imatinib 40% 20% Chemotherapy (historical data) 0% 0 1 2 3 4 5 Years After Registration År efter registrering MV
IMATINIB C-kit og PDGFRA wt er Imatinib resistente Mutationer i exon 17 og exon 18 er Imatinib resistente
GIST mimics 75-årig kvinde med ventrikel-tumor
CD117 Schwannom S100 Actin
CASE 12 60-årig kvinde med subileus tilfælde. Ved ultralyd findes tumor i tyndtarmskrøset. Hvad er diagnosen? Er der behov for yderligere farvninger?
CASE 12 Mesenteriel fibromatose 4 (2) Desmoid tumor 3 GIST 3 (5) Mesenkymal tumor 3 Leiomyosarkom (1) Fibrose 1 CD34, CD117, DOG1, S100, SMA, desmin, BCL2?, B-cat, basis panel (Vim, CK, S100)
Mesenteriel CASE fibromatose 12
CD117 S100 Actin CD34
Tidligere strålet for cervix cancer
Angiosarkom CD31
Immuner Tumor CD117 DOG1 CKA S100 CD34 CD31 Act Des Andet GIST +++ +++ + + ++ - + + MF +/- - - +/- +/- - +Bcat Leiomyom - -/+ (+) -/+ +++ + Schwannom - - +++ + - - Karcinom (+) (+) +++ MM + +++ +MelanA, Sox Angiosarkom + ++ ++ -/+ - +ERG
Supplerende læsning SAGE-Hindawi Access to Research Pathology Research International Volume 2011, Article ID 952569, 10 pages doi:10.4061/2011/952569 Review Article GastrointestinalMesenchymal Neoplasms other than Gastrointestinal Stromal Tumors: Focusing on Their Molecular Aspects Thomas P. Plesec
Take Home Identifikation af GIST er vigtig for korrekt behandling Mistænk enhver abdominal mesenkymal tumor for GIST Glem ikke at der er andre diagnostiske muligheder Brug altid immunhistokemi En CD117-positiv tumor er ikke nødvendigvis en GIST En CD117-negativ tumor kan være en GIST Tak til Mogens Vyberg for udlån af materiale