IMAGING OF GIST

GASTROINTESTINAL
STROMAL TUMOURS
 GIST Overview
Most common gastrointestinal (GI) sarcoma
– A tumor of mesenchymal (connective tissue) origin
– 0.2% of all GI tumors, but 80% of GI sarcomas
Highest incidence in the 40-60 year age group
– Similar male/female incidence, although some reports suggest a
slightly higher incidence in men
Recently identified as a distinct clinical and histopathologic entity
– Previously misclassified as leiomyosarcoma/other spindle cell
cancers
GIST have an incidence of 14.5 per million annually (comparable
with
Cancer Facts chronic myeloid leukemia) and a prevalence of 129 per million
& Figures. 2003.
Fletcher et al. Hum Pathol. 2002;33:459.
Miettinen et al. Pol J Pathol. 2003;54:3.
Joensuu et al. Lancet Oncol. 2002;3:655.
Kindblom et al. Ann Oncol. 2002;13:157. Abstract 577O.
Kindblom. At: http://www.asco.org.
 GIST: Historical Classification as
Other Soft-Tissue Sarcomas

28%
GIST
Leiomyoma
7% Leiomyosarcoma
N=600 Leiomyoblastoma
34%
13% Other

18%

A retrospective Swedish study determined that 72% of GI tumors

now identified as GIST had been originally classified as other tumors
ndblom et al. Ann Oncol. 2002;13:157. Abstract 577O.
ndblom. At: www.peerviewpress.com/asco2003c.
 GIST: Clinical Presentation (cont’d)
GIST may occur anywhere along the GI tract or
elsewhere in the abdomen or retroperitoneum

Colon Other (rectum, esophagus,

mesentery, retroperitoneum)
10%
15%

25%
Small
50% intestine
Stomach

Emory et al. Am J Surg Pathol. 1999;23:82.

 GIST: Clinical Presentation
Often asymptomatic, especially when small
– May be symptomatic if large
Symptomatic: signs/symptoms related to
location and size of tumor
– Vague GI pain or discomfort
– GI hemorrhage
– Anemia
– Anorexia, weight loss, nausea, fatigue, and additional
GI complaints
– Acute intraperitoneal bleeding or perforation

Miettinen et al. Hum Pathol. 1999;30:1213.

 PATHOLOGY
GIST share several characteristics with
interstitial cells of Cajal (ICC)
– Mixture of neural and myogenous features by electron
microscopy
– Expression of KIT (CD117) in ~95% of cases
ICC hyperplasia is evident in the GI tract of
patients with familial GIST
GIST and ICC may arise from a common
mesenchymal stem cell associated with the
enteric neural plexus
Sircar et al. Am J Surg Pathol. 1999;23:377.
Wang et al. Arch Pathol Lab Med. 2000;124:1471.
 GIST: Immunophenotype
~95% of reported cases of GIST
are positive for KIT (CD117)
Other markers often positive in
GIST
– CD34 (mesenchymal/hematopoietic
precursor cell marker)
Positive in 60%-70%
– Smooth-muscle actin
Positive in 15%-60%
– S-100
Positive in 10%
GIST rarely express desmin Different KIT staining
patterns in GIST
Courtesy of Dr. C. Corless.
Miettinen and Lasota. Virchows Arch. 2001;438:1.
 Structure of KIT Receptor
Type III receptor tyrosine
kinase
Extracellular domain binds − SCF binding site
− 5 IgG domains
ligand: stem cell factor (SCF)
Downstream effects of SCF
binding to KIT are proliferative
and antiapoptotic Cell membrane
Intracellular domain has
– 2 tyrosine kinase domains
– Multiple autophosphorylation Tyrosine kinase
sites domains

Taylor and Metcalfe. Hematol Oncol Clin North Am. 2000;14:517.

 GIST: Major Morphologic Patterns

Spindle Cell Epithelioid

urtesy of Dr. C. Corless.

 GIST: Methods of Detection
Endoscopic ultrasound (EUS)
CT
MRI
PET scan

Demetri et al. JNCCN. 2004;21(suppl 1):S1.

 Ulcerated Gastric GIST

Ulcerated submucosal Irregular homogenous

mass in gastric body submucosal mass
urtesy of Dr. W. Brugge.
 GIST: Assessing Malignant
Potential
Risk Size Mitotic Rate
High Any size >10/50 HPF
>10 cm Any rate
>5 cm >5/50 HPF
Intermediate 5-10 cm <5/50 HPF
<5 cm 6-10/50 HPF
Low 2-5 cm <5/50 HPF
Very low <2 cm <5/50 HPF

However, even tumors classified as low risk can become

metastatic
HPF = high power fields.
Reprinted from Fletcher et al. Hum Pathol. 2002;33:459 with permission from Elsevier.
CT Features Of Primary Tumour
Variable size- Small to very large mass
May have air if they communicate with
lumen
Solid or necrotic
Usually enhance
Calcifications are unusual
D/D- primary gastric tumour, lymphoma
Intra & Extraluminal gastric
GIST
SB GIST
Surgical specimen
Rectal GIST
Large SB GIST
GIST: CT Imaging of Primary Disease

A solid, exophytic mass arising Massive hyperdense mass

from the stomach surrounding the stomach
Endoscopic biopsy was negative
Notice small tumor vessels ( )

Courtesy of Dr. H. Choi.

CT & MRI
 Pattern Of Metastasis
Liver
Peritoneal
Lung & Bony-Only in advanced cases
Nodal-very rare
Recurrence & progression
 GIST: Triphasic Imaging in CT

Early arterial Late arterial Portavenous

Hypervascular lesions in the liver may escape detection during
portal-venous phase imaging
Triphasic imaging improves detection, but timing of imaging is
critical
Noncontrast study can be an alternative approach when triphasic
imaging is not feasible

Courtesy of Dr. H. Choi.

 GIST: CT Imaging of Advanced
Disease

Hepatic metastasis: Hepatic metastasis and Peritoneal implants and

Hyperdense or rim peritoneal implants: a subcutaneous mass:
enhancing lesions Hyperdense masses filled Multiple hyperdense
with enhancing tumor enhancing masses
nodules or nodules at the
periphery
Notice small tumor vessels
Courtesy of Dr. H. Choi. ( )
 Positron Emission Tomography
Diagnosis
18 FDG-PET is highly sensitive, but not specific,
for metabolically active GIST
Staging workup
Local and metastatic disease
Follow up:
To assess response/ relapse

Demetri et al. JNCCN. 2004;21(suppl 1):S1.

 GIST: CT and 18FDG-PET
Comparison
CT 18
FDG-PET
Anatomic information Metabolic information
Information
Tumor viability Tumor viability
Diagnosis
Initial workup Staging
Staging
Response evaluation
Response evaluation (earlier than CT)
Follow-up
Surveillance Surveillance
Problem solving
Wide availability Limited availability
Cost/Availability
Reasonable cost Expensive

CT and 18FDG-PET should not be approached with an “either/or”

perspective; each provides critical information for diagnosis
GIST Treatment Options
 GIST: Surgical Considerations
Complete gross resection with the intact
pseudocapsule is the goal of resection
– Careful tumor handling is critical
– Rupturing of the pseudocapsule can cause tumor
bleeding and/or dissemination
Unlike adenocarcinomas, GIST tend to displace,
not invade, surrounding organs
Negative microscopic margins are desirable
Lymphadenectomy is unnecessary, as GIST
rarely metastasize to the regional lymph nodes
Demetri et al. JNCCN. 2004;21(suppl 1):S1.
 GIST: Primary Tumor

Tumor
Gastric mucosa

Gross pathology of primary GIST

urtesy of Dr. C. Corless.
 Operation: Partial Gastrectomy,
Pancreatectomy, and Splenectomy

Courtesy of Dr. M.J. Heslin.

 Presurgical CT Scan

Courtesy of Dr. M.J. Heslin.

 Postoperative CT Scans

16 months 22 months
Courtesy of Dr. M.J. Heslin.
 GIST: Chemotherapy and
Radiation Therapy
Standard sarcoma chemotherapy is ineffective
– Limited response rate ~5%
– Median time to progression 3-4 months
– No impact on survival
Comorbidity due to tumor localization limits
effectiveness of radiation therapy
– Possible role in treatment of rectal tumors
Surgery remains the principal treatment for
resectable primary GIST

Rossi et al. Int J Cancer. 2003;107:171.

DeMatteo et al. Hum Pathol. 2002;33:466.
 Clinical Efficacy: Summary
Imatinib mesylate has proven clinical efficacy in
unresectable or metastatic GIST
– Imatinib mesylate is the only approved therapy
effective in treating metastatic, unresectable GIST
– Imatinib mesylate in effect at 400 and 800 mg/d
– 800-mg/d dose was associated with PFS in one
ongoing phase III trial
Efficacy of imatinib mesylate is under
investigation in the adjuvant and neoadjuvant
settings
– Phase II/III trials are ongoing
Response Evaluation
Pre & Post Imatanib
 Adjuvant Imatinib Mesylate: CT
Scans

Courtesy of Dr. R. DeMatteo.

 Imatinib Mesylate in GIST:
Rapid Response in Liver Metastasis

CT

18
FDG-PET

Pre-imatinib mesylate 4 weeks of imatinib mesylate

Courtesy of Dr. G.D. Demetri and Dr. A.D. Van den Abbeele.
Progression on imatinib
13 days Post Imatinib
 GIST: Patient Flow
Multidisciplinary teams GI PCP Surgeon
needed to optimize care
Pathologist and radiologist
involvement ensures correct
diagnosis and response Pathologist
evaluation
Patient education about
malignant potential key for Radiologist
adequate follow-up

PCP = primary care physician.

Medical oncologist
GI = gastroenterologist.
Demetri et al. JNCCN. 2004;21(suppl 1):S1.
 Conclusions
GIST is a rare tumor but is the most
common sarcoma of the GI tract.
The incidence of GIST is much higher than
previously estimated
– 14.5 per 1 million individuals annually
All GIST have malignant potential
The majority of GIST express high levels
of the tyrosine kinase KIT
 Conclusions (cont’d)
Surgical resection is the primary treatment.
Imatinib mesylate is effective in treating
metastatic, unresectable GIST
Imatinib mesylate is currently being investigated
in phase II/III trials to evaluate its efficacy in
treating GIST in the adjuvant and neoadjuvant
settings
New treatment options are under investigation
– SU11248
– RAD001