Gist Clinical Diagnosis

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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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


Abdominal mass

Some find during emergency surgery for perforated

viscus


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SYMPTOM COLORECTAL GIST Hematoscezia

Diarrhea

Constipation


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



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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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Gist Clinical Diagnosis

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