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7/29/2019 Gist Clinical Diagnosis
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GASTROINTESTINALSTROMAL TUMOR(CLINICAL DIAGNOSIS)
PROF. IGN. RIWANTO SP.B.KBD
Seminar GIST, Semarang 14 September 2013
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Biarawati 54 tahun, 4bulan yang laluoperasi pseudokistapankreas yang
sangat besar (lihatCT Scan) dilakukangastro -sistostomidan biopsi dindingkista
Dalam perawatantumor mengecil.
Saat ini datangdengan tumormembesar lagi.
KASUS
CT-SCAN ABDOMEN
BULAN PEBRUARI 2004
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ABDOMEN & PA
Bekas insisi median atas
Abdomen bagian atas cembung,
teraba masa tumor sebesar kepala,agak fixed bergerak sedikit pada
pernafasan.
PA : leiomyoma yang bisa berasaldari lambung
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CT-SCAN
BULAN JUNI
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LAPARATOMI
Tumor capsulated mudah dibebaskan
dari pankreas, lien dinding belakang
abdomen tetapi melekat dengandinding belakang korpus lambung
sekitar 7 cm. Diputuskan dilakukan
eksisi sekitar 2 cm dari batas
perlekatan tumor.
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PA :
Gambaran spindel cell, curiga
Leiomyosarcoma lambung
IHS: CD 117+
GIST
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DEFINITION
Gastrointestinal stromal tumors (GISTs) are the mostcommon mesenchymal tumors of the gastrointestinaltract, resulting from activating mutations in one of thereceptor protein tyrosine kinases, KIT (CD117) orplatelet-derived growth factor receptor alpha
(PDGFRA).
KIT-positive : 80% ,
Mutations in the PDGFRA gene 5% to 10%
no detectable KITorPDGFRA mutations (wild-type
GIST).: 10-15%
Soft Tissue Sarcoma, Version 2. 2012 Featured Updates to the NCCN Guidelines J Natl Compr Canc Netw. 2012;10:951-960
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GIST ? MALIGNANT SCHWANOMA?
LEIOMYOSARCOMA?
GIST : FROM ICC
(Interstitial Cells of Cajal)
LEIOMYOSARCOMA
From smooth muscle
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KIT AND PDGFRA MUTATIONS:
OVERALL MUTATION FREQUENCY 86%
Exon 11 (67%)
Exon 9 (9%)
Exon 13 (1%)
Exon 17 (1%)
KIT (~70%)
Exon 14 (rare)
PDGFRA (~6.5% total)
Exon 12 (2%)
Exon 18 (5.5%)
(~30% of KIT-WT)
Abbreviation: PDGFRA, platelet-derived growth factor receptor.
Corless Cl, et al.Annu Rev Pathol. 2008;3:557-586.10
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HISTOLOGIC FEATURES OF GISTS
spindle cell pattern : 60 70%,
epithelioid cytology : 20 - 30%
pleomorphic pattern :
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MICROSCOPIC
APPEARANCE
OF GASTRIC
GIST
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MICROSCOPIC
APPEARANCE
OF INTESTINAL
GIST
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IMMUNOHISTOC
HEMICAL
STAINING
KIT POSITIF
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HISTORY OF GIST
Early years- smooth muscle tumor(leiomyoma, leiomyosarcoma)
1970-1980s (electron microscope &immunohistochemistry):
-Partial smooth muscle differentiation, neural,mixed or null phenotypes-GANT (gastrointestinal associated neural
tumor) 1980s- term GIST widespread used
Hornick JL: Mesenchymal tumor of the GI tract: an update, 2011
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HISTORY OF GIST
1998 : KIT activating mutations
1998: KIT immunoreactivity
2002: Imatinib mesylate (gleevec) RCT
2003: PDGFRA activating mutation 2006: sunitinib malate (sutent) RCT
2009: adjuvant imatinib after resection of
localized GIST RCT 2011: genotyping to guide TKI therapy
Hornick JL: Mesenchymal tumor of the GI tract: an update, 2011
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EPIDEMIOLOGY OF GIST
United States: about 5000 new cases annually, providing1520 cases per million per year, and the black race is arisk factor
Data obtained from 14 different countries from all overthe world participating in the EORTC study the incidence
rate was calculated as approximately 45 cases permillion per year
Similar in men and women
The mean age at the diagnosis is 5563 years , rare
before 40 and very rare in children Metastatic disease is more common in younger patients
POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
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* EGIST: Extra Gastro Intestinal Stromal Tumor
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FREQUENCY OF GIST
Less 1% of Gastrointestinal tumor
LOCATION PERCENTAGE
STOMACH 60%
SMALL INTESTINE 30%
DUODENUM 5%
COLORECTAL < 5%
ESOPHAGUS & APPENDIX
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MUTATION SUBTYPES ACCORDING
TO THE PRIMARY LOCATION
GenotypeStomach
(n = 738)Small Bowel
(n = 261)
KIT mutation
Exon 9
Exon 11
Exon 13
Exon 17
65.2%
1.8%
61.4%
1.2%
0.8%
79.7%
23%
54%
2.3%
0.4%
PDGFRA mutation
Exon 12Exon 14
Exon 18
22.9%
3.1%0.5%
19.3%
1.2%
0%0.4%
0.8%
Wild type 11.9% 19.1%
Abbreviation: PDGFRA, platelet-derived growth factor receptor.Data from Wardelmann E, et al. Pathologe. 2010;31(3):195-198. 20
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STAGING OF GISTAMERICAN JOINT COMMITTEE ON CANCER
(AJCC)
T: The size of the primary tumor, and whether it
has spread to nearby organ
N: The extent of which the cancer has spread tonearby lymph nodes
M: Whether the cancer has spread, or
metastasized, to distant parts of the body
Mitotic rate: The measure of how fast the cancer
cells are growing and dividing
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CLASSIFICATION OF GIST
In the SSGXVIII/AIO trial, risk stratification was basedon:tumor size, site, mitotic count, and rupture;
patients with high-risk of recurrence:- mitotic count > 5 mitoses/50 HPF;
- size > 5 cm;
- nongastric location; and
- tumour ruptureJoensuu H, JAMA 2012;307:1265-7
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POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
HUMAN PATHOLOGY Volume33, No. 5 (May 2002)
NIH CLASSIFICATION
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NIH CLASSIFICATION
FOR RISK OF
RECURRENCEVery Low Risk Low Risk Intermediate Risk High Risk
NIHconsensuscriteria1
Tumor size < 2cmMitotic index < 5
Tumor size 2-5 cmMitotic index < 5
Tumor size 5-10 cmMitotic index < 5
ORTumor size < 5 cmMitotic index 6-10
Tumor size > 5 cmMitotic index > 5
ORTumor size > 10 cmMitotic index, any
ORTumor size, any
Mitotic index > 10Modified NIHconsensusclassification2
Any location:Tumor size < 2cmMitotic index 5
Any location:Tumor size 2.1-5 cmMitotic index 5
Any location:Tumor size < 5 cmMitotic index 6-10
Gastric:Tumor size 2.1-5 cmMitotic index > 5
ORTumor size 5.1-10 cmMitotic index 5
Any location:Tumor rupture
ORTumor size > 10 cm
ORMitotic index > 10
OR
Tumor size > 5 cmMitotic index > 5
Nongastric:Tumor size 2.1-5 cmMitotic index > 5
ORTumor size 5.1-10 cmMitotic index 5
Abbreviations: Mitotic index, number of mitoses per 50 high-power fields; NIH, National Institutes of health.1. Fletcher CD, et al. Hum Pathol. 2002;33(5):459-465; 2. Joensuu H. Hum Pathol. 2008;39(10):1411-1419. 24
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SPECIFIC KIT MUTATIONS HAVE
PROGNOSTIC IMPORTANCE
RFS in 127 pts with completely resected localized GIST based on mutation type
Propo
rtion
Recurrence-Free
Time After Resection, y
1.0
0.8
0.6
0.4
0.2
0.0
0 1 2 3 4 5 6 7 8 9 10
P < .001
KITexon 9 mutation (n = 4)
No mutation (n = 29)
KITexon 11 PM/INS (n = 32)
Abbreviation: RFS, recurrence-free survival.Adapted from DeMatteo RP, et al. Cancer. 2008;112(3):608-615. 25
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SYMPTOMS OF GIST
GIST is often asymptomatic until it reaches a
certain location, grows to a certain size or
bleeds.
Not infrequently, GIST is discovered incidentallyduring radiologic imaging for an unrelated
condition or as a secondary finding in a surgical
resection, which is the removal of all or part of
an organ. At diagnosis, approximately half of malignant
GIST are metastatic.
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SYMPTOMS OF GIST (conts)
Smaller GISTs, may have no symptoms or vague, nonspecific
abdominal pain or discomfort.
Large, aggressive GISTs may cause some of the following
symptoms:
Pain or discomfort in the abdomen, the area of the body
that contains the stomach, intestines, and other organs
Nausea and vomiting
Blood in the stool or vomiting blood
Fatigue due to low red blood cell counts (anemia)
Diarrhea
Intestinal obstruction
Weight loss
Abdominal mass
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RELATIONSHIP BETWEEN TUMOR
SIZE AND TIME OF DETECTION
TIME OF TUMOR DETECTION MEAN DIAMETER
(CM)
Based on symptom 8.9
Incidental finding 2,7
During autopsy 3.4
Behazin. Gastrointestinal Stromal Tumor. Medscape 2013
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Small GISTno symptomfound
incidentally Moderate
size GIST:dysphagia
Large GIST:obstruction
SYMPTOMS OF
ESOPHAGEAL GIST
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SYMPTOMS OF GASTRIC GIST
Upper GI Bleeding (due to ulcer forming) :40-65%
Epigastric pain
Anorexia
Nausea
Vomiting
Weight loss
Epigastric fullness
Early satiety Epigastric mass
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SYMPTOMS OF DUODENAL
GIST
Symptom as in gastric GIST may present
Obstructive jaundice
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SYMPTOMS OF SMALL BOWEL
GIST
Diarrhea
Bleeding
Intestinal obstruction
Abdominal mass
Some find during emergency surgery for perforated
viscus
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SYMPTOM COLORECTAL GIST Hematoscezia
Diarrhea
Constipation
Intestinal obstruction
Some find during emergency surgery for perforated
viscus
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DIAGNOSTIC MODALITY
Contras gastrointestinal imaging
Endoscopy & biopsy
Imaging (CT with iv contras)
Endoscopic ultrasonography
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SPACE
OCCUPAYING
LESSION
SMOOTH
ROUND NODULE
WITH NICE
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SMOOTH ROUNDNODULE WITH
NICHE
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IMMUNOHITOCHEMISTRY
STAINING
cKIT (+)
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Useful diagnostic method in the identification of
malignant tumors
Features associated with malignant GIST areindependently:
- size more than 40 mm,
- an irregular outer margin,
- the presence of cysts and
- non-homogenous echo pattern
ENDOSCOPIC ULTRASONOGRAPHY
POLSKIE ARCHIWUM MEDYCYNY WEWNTRZNEJ 2008; 118 (4)
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CONCLUSION
GIST IS ICC MALIGNANCY AND DIFFER FROM
LYOMYOSARCOMA
MUTATION OF KIT (70%) OR PDGFRA (20%)
NO SYMPTOM IN SMALL GIST OR JUST VAGUE
ABDOMINAL PAIN AND FOUND INCIDENTALLY
DURING GASTROINTESTINAL SERIES OR
ENDOSCOPY
LARGE GIST GIVE SYMPTOM ACCORDING TO
LOCATION: BLEEDING OR OBSTRUCTION OR JUST
MASS
INCREASE AWARRNESS FOR SUBMUCOSALINTESTINAL TUMOR IHC FOR KIT
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