Gastrointestinal Stromal Tumor
Background
• Gastrointestinal stromal tumor (GIST) is the
most common (80%) mesenchymal tumor of
the alimentary cannel.
– less than 1% of all gastrointestinal tumors and
about 5% all sarcomas
Lancet Oncol 2002;3:655-64.
J Surg Oncol 2008;97:350-9.
Stout and colleagues in 1940
Stromal tumors arising from the GI tract were initially classified
as smooth muscle tumor
1970
Electron microscope found little evidence of
the smooth muscle origin
1980
Antigens related to neural crest cells with the
advent of immunohistochemistry during the
1989
A distinctive subset of these stromal tumors revealing
autonomic neural features was recognized and named
“plexosarcoma” and subsequently as gastrointestinal
autonomic nerve tumor (GANT)
J Gastrointest Oncol. 2012 Sep; 3(3): 189–208.
1994
Immunopositive for CD34
1998
Hirota and colleagues discovered
a specific mutation in the c-KIT protooncogene
as well as a nearuniversal expression of KIT
protein in GISTs by immunohistochemistry.
2002
Approval of imatinib for treatment of GIST by
the US Food and Drug Administration
CD117 expression  The
remarkable therapeutic
efficacy of imatinib
2003
Heinrich and colleagues
Hirota and colleagues
Platelet-derived growth factor receptor alpha
(PDGFRA) gene mutations as an alternative
pathogenesis in GISTs without KIT gene
mutation.
2006
Approval of Sunitinib for the
management of patients
who are refractory or intolerant
to imatinib
J Gastrointest Oncol. 2012 Sep; 3(3): 189–208.
Epidemiology
• GISTs are the most common mesenchymal
neoplasms involving the gastrointestinal tract.
– 1 percent of primary gastrointestinal cancers
• a Surveillance, Epidemiology, and End Results
(SEER)
– 6142 cases diagnosed between 2001 and 2011,
with an incidence of 0.68 per 100,000 after the
implementation of GIST-specific histology
– Annual age-adjusted incidence of GISTs was
0.78/100,000 in 2011
Virchows Arch. 2001;438(1):1.
Cancer Epidemiol Biomarkers Prev. 2015;24(1):298. Epub 2014 Oct 2.
• Mean age at diagnosis was 64 years.
• Familial GIST  5% of patients
– Primary familial GIST syndrome
– Neurofibromatosis type 1 (NF1)
• Pediatric GIST
– Carney-Stratakis syndrome
– Carney triads in  GIST, paraganglioma, and
pulmonary chondromas
• loss of function of a succinate dehydrogenase (SDH) family
enzyme
• Cellular origin of GISTs — The interstitial cells
of Cajal (ICCs)
– Gastrointestinal pacemaker cells  regulate
peristalsis
• Stomach
• Small intestine
• Anorectum
70%
20-25%
7%
– More likely to be high grade
• Colon
• Esophagus
• Extra-gastrointestinal GISTs
– mesentery, omentum and retroperitoneum
Clinical Manifestation
• Overt or occult GI bleeding – 28 percent (small
intestine) and 50 percent (gastric)
• Incidental finding (asymptomatic)
• Acute abdomen
• Asymptomatic abdominal mass
– Paraneoplastic syndrome  RARE
Clinical Manifestation
•
•
•
•
•
Gut obstruction or volvulus
Peritonitis  perforation
Dysphagia  esophageal GIST
Constipation  colorectal GIST
Obstructive jaundice  duodenal GIST
Investigation
• No laboratory test can specifically confirm or
rule out the presence of a gastrointestinal
stromal tumor (GIST).
• GISTs are not associated with elevation of any
serum tumor markers.
Imaging Study
• Radiography
– Plain abdominal radiography
– Barium study
•
•
•
•
Ultrasound
CT scan
MRI
18-FDG PET scanning
CT Scan
• CT scanning with intravenous and oral
contrast material
• Diagnosis and staging
4 cm hyperenhancing
mass arising from the
submucosa of the body of
the stomach
Exophytic GIST arising
from the second portion
of the duodenum, with
area of ulceration along
the descending
duodenum into the mass
Torricelli-Bernoulli phenomena
large exophytic mass arising from posterior wall of stomach (black
arrow).
Mass contains large tubular ulceration (white arrow).
Linear low-attenuation line of air bubbles can be seen arising from ulcer
mouth (arrowhead) with fluid accumulating at ulcer floor (wavy arrow).
AJR1999;173:199-200 0361-803X199/1731-199
• Ghanem and colleagues
– Small (< 5 cm): Sharply demarcated, homogeneous
masses, mainly exhibiting intraluminal growth
patterns
– Intermediate (5-10 cm): Irregular shape,
heterogeneous density, an intraluminal and
extraluminal growth pattern, and signs of biological
aggression, sometimes including adjacent organ
infiltration
– Large (>10 cm): Irregular margins, heterogeneous
densities, locally aggressive behavior, and distant and
peritoneal metastases
MRI
• MRI can be an especially helpful adjunct to CT
in the evaluation of large tumors that have
necrotic and hemorrhagic components.
• T1
– low signal intensity solid component
– enhancement is usually present, and
predominantly peripheral in larger lesions
• T2
– high signal intensity solid component
Endoscopy
• Firm, smooth,
yellowish submucosal
mass displacing the
overlying mucosa.
• Some tumors may be
associated with
ulceration or bleeding
of the overlying
mucosa from pressure
necrosis.
https://www.uptodate.com/contents/image?imageKey=GAS
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Endoscopic Ultrasound
• Valuable tool in the diagnosis and
preoperative assessment of gastric GISTs
• Preferred modality to facilitate biopsy of the
lesion, when biopsy is indicated.
• Typically hypoechoic, homogeneous lesions
with well-defined margins, although they can
rarely have irregular margins and ulcerations
• In general, ultrasonic features of a mass
suspicious for malignancy are as follows:
• Large size
• Irregular extraluminal borders
• Presence of cystic spaces and echogenic foci
World J Gastrointest Endosc. Aug 16, 2010; 2(8): 271-277
• Preoperative biopsy is not generally
recommended for a resectable lesion in which
there is a high suspicion for GIST and the patient
is otherwise operable.
• However, a biopsy is preferred to confirm the
diagnosis if metastatic disease is suspected or if
preoperative imatinib is considered prior to
attempted resection in a patient who has a large
locally advanced lesion thought to represent a
GIST.
Irregular border
Cystic spaces
Ulceration
Echogenic foci
Heterogeneity
Histology
• Highly cellular and composed of spindleshaped cells that resemble smooth-muscle
tissue
• Three main histological subtypes
– Spindle cell type (most common, 70%)
– Epithelioid type (20-25%)
– Mixed spindle cell and epithelioid type
J Gastrointest Oncol 2012;3(3):189-208
J Gastrointest Oncol 2012;3(3):189-208
MANAGEMENT
NCCN Guideline – Soft Tissue Sarcoma
NCCN Guideline – Soft Tissue Sarcoma
CT or MRI every 8-12 weeks
KIT exon 11 mutation  90% response
KIT exon 9 mutation  50% response
PGFRA mutation
NCCN Guideline – Soft Tissue Sarcoma
CT or MRI every 8-12 weeks
KIT exon 11 mutation  90% response
KIT exon 9 mutation  50% response
PGFRA mutation
NCCN Guideline – Soft Tissue Sarcoma
NCCN Guideline – Soft Tissue Sarcoma
NCCN Guideline – Soft Tissue Sarcoma