This document discusses the diagnosis and management of gastrointestinal stromal tumors (GISTs). GISTs originate from interstitial cells in the gastrointestinal tract and were previously misclassified. Diagnosis involves imaging such as CT or EUS to identify tumors. Pathology examines tumor size, mitotic rate, and KIT expression. Complete surgical resection is the primary treatment for localized GISTs. For advanced or metastatic GISTs, the tyrosine kinase inhibitor imatinib is effective therapy and can help make unresectable tumors operable. Adjuvant imatinib after surgery or neoadjuvant imatinib before surgery may improve outcomes for high-risk GISTs. Prognosis depends on tumor

1. Diagnosis and Management of
Gastrointestinal Stromal tumour
(GIST)
Dr Shahbaz Habib Faridi
MS, DNB
Assistant Professor, Department of Surgery
JN Medical College, Aligarh Muslim University, Aligarh

2. Contents
 Introduction of GIST
 Etiopathogenesis of GIST
 Clinical presentation of patients with GIST
 Investigations
 Management

3. Introduction
 The term GIST was coined by Mazur in 1983.
 In the past all mesenchymal tumours of the
digestive tract were considered to be of smooth
muscle or perineural origin.
 They were previously classified as leiomyomas,
leiomyoblastomas, leiomyo-sarcomas or
schwannomas.

4.  After the discovery of mutations in the c-KIT proto-
oncogene these tumors were distinguished from
other subtypes of mesenchymal tumours.
 Originate from the interstitial cell of Cajal, an
intestinal pacemaker cell and also named as
gastrointestinal pacemaker cell tumour.
 GISTs can develop anywhere along the GI tract from
the esophagus to the rectum; however, stomach
(60%) and small intestine (30%) are the most
common locations.

5.  Only 10% of GISTs are found in the esophagus,
mesentery, omentum, colon or rectum.
 Although rare, GIST are the most common
mesenchymal tumours of the gastrointestinal tract.
 GIST are of clinical relevance because in at least
10–30% of cases they are malignant.
 The metastatic pattern is predominantly
hematogenous and intra-abdominal, with spread
throughout the peritoneal cavity and to the liver.

6.  Lymph nodal invasion is uncommon.
 GISTs with indolent (low-risk) behavior are
typically found as small submucosal lesions.

8. Location of GIST

9. Epidemiology
 They form 0.1%-3.0% of gastrointestinal
malignant tumors
 The median age at diagnosis is 60 years.
 There is usually no predilection for either gender.

10. Molecular pathogenesis
 KIT, which is a growth factor transmembrane
receptor, is the product of the proto-oncogene c-kit
(chromosome 4).
 KIT is expressed by haematopoietic progenitor
cells, mast cells, germ cells and interstitial cells of
Cajal.

11.  Thus mutations in KIT seem to play a gate-
keeper role in transformation of the interstitial
cells of Cajal into a GIST (in 90% of the cases).
 Factors causing the transformation of benign to
malignant GIST have still to be identified.

13. Differentiation of GIST from smooth
muscle tumour
KIT CD34 Desmin
GIST + 60-70% rare
Smooth
muscle
tumour
_ 10-15% +

14. Clinical presentation
 Only 70% of the patients with GIST are
symptomatic.
 20% are asymptomatic and the tumors are
detected incidentally.
 10% of the lesions are detected only at autopsy.

15.  Symptoms and signs are not disease specific, they
are related more to the site of the tumor.
 Most common presentation of the patients present
with abdominal discomfort, nausea, vomiting,
weight loss or early satiety (60-70%).
 GI Bleeding which may be either chronic, with
anaemia, or acute, necessitating emergency
treatment (approximately 30-40% of the cases
present with haemorrhage)

16.  Bleeding occurring into the peritoneal cavity due to
a ruptured GIST can lead to acute abdominal pain
presenting as a surgical emergency.
 Intestinal obstruction is not a usual feature because
of tendency of outward growth of the tumour but
may occur, perforation is extremely rare.
 Patients can also present with dysphagia in the
esophagus, biliary obstruction around the ampulla
of Vater or even intussusception of the small bowel.

17.  Lymph node metastases are uncommon in GIST.
 Distant metastases most commonly occur in
GISTs of the peritoneum, omentum, mesentery
and the liver.

18.  The diagnosis of GIST may be suggested Per-
operatively by the presence of
1. A well defined extraluminal mass,
2. Polylobulate with a pseudocapsule,
3. Projecting into the abdominal cavity and
displacing other organs.

19. Stomach GIST

20. Jejunal GIST

21. Pathology
 GIST vary greatly in size from a few millimeters
to more than 30 cm, the median size being
between 5 and 8 cm.
 They not infrequently exhibit areas of necrosis,
cystic degeneration or focal haemorrhage.

22.  The tumours are well circumscribed and pseudo-
encapsulated.
 In contrast to leiomyomas and leiomyosarcomas,
GIST are typically immunoreactive for KIT
(CD117).
 While assessing a specimen, a pathology report
should include the location, size and mitotic rate
reported as the number of mitoses in 50 high
power fields

24. Diagnosis
 Due to the vague and protean presentation of GIST,
initial diagnosis can be delayed.
 As for the other intra-abdominal malignancies,
computed tomography scan (CT scan) is the standard
preoperative imaging technique.
 GISTs appear as a large, well-defined soft tissue
mass of varying density and show patchy
enhancement after intravenous contrast.

25.  Varying degrees of necrosis may frequently be
demonstrated within the mass.
 Non-homogeneous tumor, the presence of a
limiting capsule and the lack of the locoregional
adenopathies favour the diagnosis of GIST on CT
Scan.
 CT scan can also detect the presence of secondary
localizations (i.e. hepatic metastases).

27.  Endoscopic ultrasound (EUS) has been used in the
diagnosis of GIST; it assesses the depth of invasion
and is useful in obtaining a tissue sample.
 EUS features of a high grade GIST include irregular
extra-luminal borders, heterogeneous echo patterns,
presence of cystic spaces and echogenic foci
 The efficacy of EUS guided fine needle aspiration
cytology is 80%-85%.

30.  GISTs are positron emission tomography (PET)
avid tumors because the receptor tyrosine kinase
increases the glucose transport protein signaling.
 PET is useful in revealing small metastases
which would otherwise not have been picked up
on CECT.
 It helps differentiate an active tumor from
necrotic or inactive scar tissue. PET also
differentiates malignant from benign tissue.

31. Staging the GIST and classifying the
risk of tumor progression
 The TNM classification along with histological
criteria are more useful then TNM alone.
 Unlike the digestive tract carcinomas, GIST do
not metastasize through a lymphatic way, but
only sanguine and peritoneal ways.

33.  The histological criteria accepted are: mitosis rate,
tumor size and location.
 Additional prognostic factors are the resection
margins status and tumor rupture.
 The tumor rupture represents a negative very
important prognosis factor.
 Intestinal GISTS (30%) have a more aggressive
behavior compared to gastric GISTS (60%).

34. Principles of biopsy and pathological
assessment
 Routine preoperative biopsy is not mandatory but
biopsy is necessary prior to the initiation of
preoperative therapy with TKI.
 EUS-FNAC of the primary site is preferred over
percutaneous biopsy as it reduces the risk of tumor
hemorrhage and intra-abdominal tumor
dissemination.

35.  Percutaneous image guided biopsy can be used
while confirming the presence of metastatic
disease.
 Demonstration of KIT positive cells may assist in
diagnosing GIST on needle biopsy.
 The specimen is subjected to IHC for KIT

37. Management of Small GIST
Tumors which are less than 2 cm in the widest
dimension are defined as small GIST. They are
usually discovered incidentally on endoscopy.
Small asymptomatic gastric GISTs with no high-
risk EUS features can be managed conservatively
with endoscopic surveillance 3 to 6 months
interval.
If these lesions are symptomatic, complete surgical
resection is recommended.

38.  For rectal GISTS standard approach is the tumor
excision/biopsy after echo-endoscopic
evaluation, no matter the tumor size, due to the
high risk and the important surgical
implications.

39. Management of Larger GIST
 The standardized approach to the nodules
suspected to be GIST, ≥ 2 centimeters is the
tumor biopsy/excision, because if they are GIST,
they have a higher risk of progression.
 If the structure is not accessible to endoscopic
evaluation, the excision – by laparoscopy or
laparotomy - in order to obtain a specimen for
diagnosis, is the standard approach.

42.  Surgery is the primary treatment of choice in
localized or potentially resectable GIST.
 It is imperative to avoid tumor rupture. The tumors
are fragile and should be handled with care, with
an aim to achieve complete gross resection of the
tumor with an intact pseudocapsule.
 Multivisceral and radical surgery should be
avoided where possible. Segmental or wedge
resection with an aim to obtain histologically
negative margins is sufficient.

44.  Resection should be accomplished with minimal
morbidity. Re-resection is not indicated for
patients with an R1 resection.
 Lymphadenectomy is not required as GISTs
have a low incidence of nodal metastases.
 In the case of metastatic clear determinations,
the biopsy of the metastasis is usually sufficient
and the patient does not require diagnostic
laparotomy.

45. Role of Laparoscopy
 Although prospective trials are lacking, small
series and retrospective analyses have shown
low recurrence rates, shorter hospital stay and
low morbidity with a laparoscopic approach.
 It has been recommended for selected GISTs
present in favorable anatomic locations like the
anterior wall of the stomach, jejunum and ileum.

46.  The same surgical principles as open surgery are
applicable in laparoscopic surgery for GIST.
 The specimen is removed from the abdomen in a
plastic bag to avoid spillage or seeding of port
sites.
 Endoscopic resection of small GISTs is more
controversial due to the risks of positive margins,
tumor spillage and intact specimen retrieval

48. Localized GIST
Tumour Diameter
<2cm >2cm
EUS with 3 month
Follow-up
Core needle biopsy Surgical resection
IHC for KIT
Stable
disease
Size increase/
Symptoms
Follow-up
Surgical
resection
Biopsy
IHC for KIT

49. Metastatic GIST
Metastasis biopsy Diagnostic Laparotomy
IHC for KIT

50. Imatinib Mesylate
 Imatinib mesylate is a tyrosine kinase inhibitor with
activity against ABL, BCR-ABL, KIT.
 Its structure mimics adenosine triphosphate (ATP)
and it binds competitively to the ATP binding site of
the target kinases.
 This prevents substrate phosphorylation and
signaling, thereby inhibiting proliferation and
survival.

51.  Patients with advanced GIST started on Imatinib
have shown a 35%-49% 9 year survival.
 The initial dose of Imatinib is 400 mg/d and it is
increased depending on response and adverse
effects.

52. Neoadjuvant therapy
 If tumour is very large, then neoadjuvant Imatinib
should be considered.
 Imatinib is effective in reducing the size of the tumor
prior to resection, increasing the likelihood of
negative margins without significant morbidity.

53. Adjuvant Therapy
 Although surgery is the therapeutic modality of
choice, it does not routinely cure GIST.
 Complete resection is possible in approximately
85% of patients and 50% patients will develop
recurrence or metastasis following complete
resection.
 The 5-year survival rate is approximately 50%,
while the median time to recurrence after resection
of primary high-risk GIST is 2 years.

54.  Adjuvant imatinib has been shown to improve
Progression free survival (PFS) and overall
survival (OS) in postsurgical patients.
 Imatinib should be continued for 36 month,
especially in patients with an intermediate or
high risk of recurrence.

55. Outcome after complete resection
 5yr survival (overall) : 48-65%
 Poor outcome is associated with
Big tumour size (>5cm)
High mitotic figure (>5/50HPF)

56. Unresectable, metastatic or recurrent disease
 Imatinib has a very high likelihood of clinical
benefit and a positive response in patients with
documented unresectable GIST.
 Imatinib is indicated when primary resection would
carry the risk of severe postoperative functional
deficit.
 It is also indicated in those who have a widespread
metastatic disease or a recurrence after resection.

57.  The lesion is assessed within 3 months of
initiating therapy to determine if it has become
resectable.
 In cases where the tumor remains unresectable,
imatinib is continued indefinitely

58. Take home message
 GISTs are the most common mesenchymal tumors
of the GI system.
 Diagnosis is late in majority of the patients because
of vague presentation.
 Most common site of GIST is stomach (60% and
low risk) followed by small intestine (30% and
more aggressive)

59.  CECT and EUS(FNAC) are the investigations of
choice.
 TNM classification along with histological criteria
(mitosis rate and location) is used for staging.
 Surgery and imatinib form the first-line therapy in
resectable case and Imatinib alone in metastatic or
unresectable GIST.
 The tumour is fragile and it is important to avoid
tumour rupture.

60. Thank you