Skip to content

GIST

Gastrointestinal Stromal Tumors (GIST)

  • Most common mesenchymal tumors of the GI tract.
  • Equal incidence in males and females.
  • Typically affects individuals > 50 years.
  • 5-year survival rate: 45%.

Incidence by Location

  1. Stomach: 50-60%
  2. Small intestine: 20-25%
  3. Rectum: 5%
  4. Esophagus: 2%.

MCQ 35: GIST Has Been Reported in All Except

Question:

GIST has been reported in all the following sites except:

  1. Liver
  2. Pancreas
  3. Genitourinary system
  4. Omentum
  5. Spleen

Answer:

5) Spleen

Explanation:

  • GIST has been reported in unusual locations such as the liver, pancreas, genitourinary system, and omentum, but not the spleen.

Interstitial Cells of Cajal (ICC) – Cell of Origin

  • GIST arises from the Interstitial Cells of Cajal (ICC), located between the nerve and smooth muscle.
  • These cells are responsible for intrinsic slow wave activity in the GI tract.
  • ICC are also found in the omentum, pancreas, portal vein, and genitourinary system.

MCQ 36: GIST – All Are True Except

Question:

Which of the following is false about GIST?

  1. Named as GIST by Mazur and Clark in 1983
  2. CD117 mutation is nearly universal
  3. New nomenclature for leiomyoma
  4. Arise from ICC

Answer:

3) New nomenclature for leiomyoma

Explanation:

  • GIST is not a new nomenclature for leiomyoma. While leiomyomas arise from smooth muscle, GISTs arise from the Interstitial Cells of Cajal (ICC). The other statements are true.

Molecular Markers for GIST

  1. CD117 (C-KIT):
    • A tyrosine kinase receptor for SCF-KIT.
    • Present in 95% of GISTs and highly specific.
  2. CD34:
    • A myeloid progenitor cell antigen, found in 60-70% of cases.
  3. PDGFRA:
    • Found in 15% of cases, especially if KIT-negative.
  4. DOG1 (Discovered On GIST):
    • 95% sensitive, useful if C-KIT and PDGFRA are negative.

Histopathology (HPE) of GIST

  • Spindle cell type (70%).
  • Epithelioid cell type.
  • Mixed cell type.

Molecular Mechanism for Carcinogenesis in GIST

  • CD117 (C-KIT): Gain of function mutation.
  • PDGFRA: Gain of function mutation.
  • BRAF/STK: Gain of function mutation.

KIT Wild-Type GIST (5-15%)

  • Negative for C-KIT mutations but positive for PDGFRA mutations.
  • These mutations are mutually exclusive.
  • Wild-Type GIST:
    • Negative for both C-KIT and PDGFRA mutations.
    • Rely on histology for diagnosis.

Pediatric GIST

  • Exceptionally rare in children.
  • Female predominance.
  • Most common presenting symptom is severe anemia.
  • The most common tumor site is the stomach.
  • Nearly all pediatric GISTs express CD117, but fewer than 15% harbor a C-KIT or PDGFRA mutation.
  • Imatinib is less responsive in pediatric cases due to the absence of these mutations.

MCQ 37: Familial GIST Not Found in

Question:

Familial GIST is not found in the following:

  1. Carney triad
  2. Neurofibromatosis 2
  3. Carney-Stratakis syndrome
  4. Familial GIST syndrome

Answer:

2) Neurofibromatosis 2

Explanation:

  • Neurofibromatosis 2 is not associated with familial GIST. Familial GIST is seen in syndromes like Carney triad, Carney-Stratakis syndrome, and Familial GIST syndrome.

Carney Triad vs Carney-Stratakis Syndrome

  • Carney Triad:
    • Consists of GIST, paraganglioma, and pulmonary chondromas.
    • Seen predominantly in females under the age of 30.
    • Lacks C-KIT or PDGFRA mutations.
  • Carney-Stratakis Syndrome:
    • Consists of GIST and paraganglioma.
    • Also predominantly in females.
    • Lacks C-KIT or PDGFRA mutations.

Malignant Potential

1. Assessing Malignant Potential of Gastric Gastrointestinal Stromal Tumors (GISTs) [ Sabi box 49.5]

1. Benign (No Tumor-Related Mortality)

  • Size: No larger than 2 cm
  • Mitotic Count: No more than 5 mitoses/50 HPF

2. Probably Benign (<3% With Progressive Disease)

  • Size: >2 cm but ≤5 cm
  • Mitotic Count: No more than 5 mitoses/50 HPF

3. Uncertain or Low Malignant Potential

  • Size: No larger than 2 cm
  • Mitotic Count: >5 mitoses/50 HPF

4. Low to Moderate Malignant Potential (12%–15% Tumor-Related Mortality)

  • Size: >2 cm but ≤5 cm
  • Mitotic Count: >5 mitoses/50 HPF

5. High Malignant Potential (49%-86% Tumor-Related Mortality)

  • Size: >5 cm but ≤10 cm
  • Mitotic Count: >5 mitoses/50 HPF
  • For the really big ones, >10 cm with >5 mitoses/50 HPF, watch out!

This table is a handy guide to gauge how GISTs might behave based on size and how busy those cells are under the microscope. Remember, the smaller and less busy, the better! Keep it simple, keep it small! 😄 If you need more info or a deeper dive into anything, just give me a shout!

2. Fletcher Criteria for Gastrointestinal Stromal Tumor (GIST) Risk Assessment

The Fletcher criteria are used to assess the risk of GIST based on primary tumor size and mitotic count per 50 high-power fields (HPF).

Risk Categories:

  1. Very Low Risk:
    • Primary Tumor Size: < 2 cm
    • Mitotic Count: < 5 per 50 HPF
  2. Low Risk:
    • Primary Tumor Size: 2–5 cm
    • Mitotic Count: < 5 per 50 HPF
  3. Intermediate Risk:
    • Primary Tumor Size: 5–10 cm
    • Mitotic Count: 6–10 per 50 HPF
    • OR: Tumor size < 5 cm with mitotic count 6–10
  4. High Risk:
    • Primary Tumor Size: > 5 cm with mitotic count > 5
    • Any size tumor with mitotic count > 10
    • Any size tumor with any mitotic rate

3. Joensuu Modification of NIH Consensus Classification for GIST Adjuvant Therapy

The Joensuu modification is used to classify the risk of GIST and guide decisions on adjuvant therapy, incorporating additional factors such as tumor rupture and tumor location (gastric vs non-gastric).

Risk Categories:

  1. Very Low Risk:
    • Tumor Size: < 2.0 cm
    • Mitotic Count: ≤ 5 per 50 HPFs
    • Tumor Site: Any
  2. Low Risk:
    • Tumor Size: 2.1–5.0 cm
    • Mitotic Count: ≤ 5 per 50 HPFs
    • Tumor Site: Gastric
  3. Intermediate Risk:
    • Tumor Size: 2.1–5.0 cm, Mitotic Count 6–10 per 50 HPFs (Any site)
    • Tumor Size: 5.1–10.0 cm, Mitotic Count ≤ 5 per 50 HPFs (Gastric)
  4. High Risk:
    • Tumor Rupture: Any size, any mitotic rate, any location.
    • Tumor Size: > 10 cm, any mitotic rate, any location.
    • Tumor Size: > 5 cm, mitotic rate > 5, any location.
    • Non-gastric tumors: Tumors > 2 cm with mitotic count > 5 per 50 HPFs.

MCQ 38: Malignant Potential of GIST Determined by All Except

Question:

The malignant potential of GIST is determined by all of the following except:

  1. Size
  2. Nodal status
  3. Location
  4. Tumor rupture

Answer:

2) Nodal status

Explanation:

  • Unlike other malignancies, nodal status does not typically influence the malignant potential of GIST. Malignant potential is determined by factors such as size, location, and tumor rupture.

Diagnosis of GIST

  • Imaging of Choice (IOC):
    • CT scan is the primary diagnostic tool for GIST.
  • PET-CT:
    • Ideal for follow-up after neoadjuvant therapy.
  • OGD:
    • Can show smooth surface, submucosal tumors.
  • Preoperative pathological diagnosis is not always required, except in palliative or neoadjuvant settings.

Tissue Diagnosis

  • Endoluminal sampling (e.g., EUS-FNAC) is preferred over transcutaneous sampling.
  • EUS-FNAC:
    • 82% sensitive and 100% specific.
    • Indicated in small GISTs planned for follow-up.

MCQ 39: Risk of Recurrence After Surgery

Question:

The risk of recurrence after GIST surgery is increased by all of the following except:

  1. Stomach location
  2. Tumor rupture
  3. Ring enhancement in PET-CT before surgery
  4. Tumor size above 10 cm

Answer:

1) Stomach location

Explanation:

  • Stomach location is associated with a lower risk of recurrence compared to other locations (e.g., small intestine). Factors like tumor rupture, ring enhancement on PET-CT, and large tumor size (>10 cm) increase the risk of recurrence.

Treatment of GIST

  • R0 resection is recommended for all tumors greater than 2 cm.
  • Lymphadenectomy is not required in GIST.
  • If R1 is found on pathological examination, repeat surgery is not required.

Management of GIST < 2 cm

  • Mini GIST: 1–2 cm.
  • Micro GIST: < 1 cm.
  • Surveillance:
    • For mini GIST (1–2 cm), use EUS (+/- CT).
    • For micro GIST (<1 cm), use EUS.
  • High-risk features on EUS include:
    • Ulceration.
    • Irregular borders.
    • Cystic areas or heterogeneity.
    • If high-risk features are present, surgery is recommended.
    • If high-risk features are absent, repeat OGD and EUS every 6–12 months.

Recurrence of GIST

  • Recurrence rate: 40%.
  • Distant metastasis is the most common mode of recurrence.
  • Only 1/3 of recurrences are isolated local recurrences.

Adjuvant Treatment

  • Imatinib is used for tumors with:
    • Size > 3 cm.
    • Mitotic count > 3/HPF.
  • Imatinib dosage: 400 mg daily for 12 months, now extended to 36 months.
    • Tumors with Exon 11 mutations in C-KIT show a good response to Imatinib.

Neoadjuvant Treatment

  • Indications:
    • Tumors > 10 cm.
    • Local organ invasion.
  • PET-CT is useful for assessing the response.
  • Response assessment:
    • 70–80% show some response.
    • 2% have a complete response.
    • 10% have no response.
    • For patients with complete or no response, surgery is not required.
    • All other cases should undergo surgery.
    • < 5% develop hemorrhage or perforation during neoadjuvant therapy.

Metastatic GIST

  • Imatinib is administered indefinitely in metastatic GIST.

MCQ 40: C-KIT Mutations – False Statement

Question:

Which of the following is false regarding C-KIT mutations?

  1. Exon 11 mutations have a good response to Imatinib.
  2. Exon 9 mutations have a good response to Imatinib.
  3. Exon 11 deletion has a high recurrence rate.
  4. Absence of C-KIT mutations means poor response to Imatinib.

Answer:

2) Exon 9 mutations have a good response to Imatinib

Explanation:

  • Exon 9 mutations have a poor response to Imatinib compared to Exon 11 mutations. Patients with Exon 9 mutations may require higher doses of Imatinib for efficacy.

Laparoscopic Resections (Privette Classification)

  • Type I:
    • Fundus and greater curvature – Laparoscopic partial gastrectomy.
  • Type II:
    • Prepyloric and antrum – Laparoscopic distal gastrectomy.
  • Type III:
    • Lesser curvature and near GEJ – Laparoscopic transgastric resection.

image.png

Side Effects of Imatinib

  • Most common side effects:
    • Diarrhea and fatigue.
    • Periorbital edema.
    • Peripheral edema.
  • Bleeding is uncommon.
  • Only 1% of patients experience serious grade 3/4 side effects.

MCQ 41: Most Common Side Effect of Imatinib

Question:

What is the most common side effect of Imatinib?

  1. Diarrhea and fatigue
  2. Giddiness
  3. Periorbital edema
  4. Renal failure

Answer:

1) Diarrhea and fatigue

Explanation:

  • The most common side effects of Imatinib include diarrhea, fatigue, and edema. Severe side effects like renal failure are rare.

Second-Line Adjuvant Therapy for GIST

  • Sunitinib: A promiscuous tyrosine kinase inhibitor (targets CD117, PDGFR, VEGF).
    • Indications:
      • Resistance to Imatinib.
      • Imatinib discontinued due to side effects.

MCQ 42: Drug of Choice for Recurrent GIST

Question:

What is the drug of choice for recurrent GIST?

  1. Imatinib
  2. Sunitinib
  3. Regorafenib
  4. Nilotinib

Answer:

1) Imatinib

Explanation:

  • Imatinib is the first-line treatment for recurrent GIST. If resistant, second-line agents like Sunitinib can be used.

MCQ 43: Wild-Type GIST – False Statement

Question:

Which of the following is false about wild-type GIST?

a. Negative for KIT mutation

b. Negative for PDGFRA

c. Rare

d. Good response to Imatinib

Answer:

d) Good response to Imatinib

Explanation:

  • Wild-type GIST lacks KIT and PDGFRA mutations and generally shows a poor response to Imatinib, relying more on histological diagnosis.

MCQ 44: Microscopic Margin Positive After GIST Resection – True Statement

Question:

After resection for GIST, if the microscopic margin is positive (R1), which statement is true?

a. Carry worse prognosis

b. Poor overall survival rate

c. Re-resection not needed

d. Recurrence is linked with R1 resection

Answer:

c) Re-resection not needed

Explanation:

  • If the margin is R1 (microscopically positive), re-resection is generally not required, as it doesn't significantly impact overall survival.

MCQ 45: Drug Approved for 3rd-Line Treatment of GIST

Question:

The only drug approved for 3rd-line treatment of GIST is:

  1. Sunitinib
  2. Sorafenib
  3. Regorafenib
  4. Nilotinib

Answer:

3) Regorafenib

Explanation:

  • Regorafenib is the only drug approved for third-line treatment of GIST after failure of Imatinib and Sunitinib.

MCQ 46: GIST of Stomach – Management After Resection

Question:

A 12 x 5 cm GIST of the stomach was resected. Histopathology showed 2 mitoses per HPF and tumor-free margins. The next line of management will be:

  1. CT abdomen and Upper GI scopy every year for five years
  2. Imatinib 400 mg/year for 3 years
  3. Imatinib 400 mg/year for 1 year
  4. Reassurance as the mitotic count is low

Answer:

2) Imatinib 400 mg/year for 3 years

Explanation:

  • Despite the low mitotic count, the tumor size of 12 cm warrants adjuvant therapy with Imatinib 400 mg for 3 years due to the high risk of recurrence.

MCQ 47: GIST with Low Mitotic Count – Next Management

Question:

A 5 cm GIST was resected, and the biopsy showed a low mitotic count. The next line of management is:

a. No further therapy

b. Imatinib 400 mg for 3 years

c. Imatinib 600 mg for 1 year

d. Imatinib 400 mg for 1 year

Answer:

b) Imatinib 400 mg for 3 years

Explanation:

  • Imatinib 400 mg for 3 years is recommended for tumors > 5 cm even with low mitotic activity to prevent recurrence.

MCQ 48: GIST – False Statement

Question:

Which of the following is false about GIST?

a. PDGFRA mutations are present

b. Wild-type has a good prognosis

c. Exon 11 mutation has poor response to Imatinib

d. Multifocal GIST is associated with Carney triad

Answer:

c) Exon 11 mutation has poor response to Imatinib

Explanation:

  • Exon 11 mutations actually have a good response to Imatinib, not a poor response.

MCQ 49: Sunitinib – Inhibits All Except

Question:

Sunitinib inhibits all of the following except:

a. CD117

b. Fibroblast growth factor

c. Platelet-derived growth factor (PDGF)

d. Vascular endothelial growth factor (VEGF)

Answer:

b) Fibroblast growth factor

Explanation:

  • Sunitinib inhibits CD117, PDGF, and VEGF, but does not inhibit fibroblast growth factor.

MCQ 50: Features of GIST – False Statement

Question:

Which of the following is false regarding GIST?

a. The second most common site is the small bowel

b. The most common site of genetic mutation is Exon 11

c. Carney's triad – no mutation in c-KIT/PDGFRA

d. The most common presenting symptom of pediatric GIST is mass abdomen

Answer:

d) The most common presenting symptom of pediatric GIST is mass abdomen

Explanation:

  • The most common presenting symptom of pediatric GIST is severe anemia, not a mass abdomen.