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Gastrointestinal Stromal Tumors PowerPoint Presentation

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Description : Check out this medical presentation on Familial GIST, which is titled "Gastrointestinal Stromal Tumors", to know about the GIST, the most common MESENCHYMAL tumor of GIT. Gastrointestinal Stromal Tumors (GIST) are Tumors that arise from the PLEURIPOTENT MESENCHYMAL CELLS in the intestinal tract that differentiate to neural, ganglionic or mixed mass.

Tags : Familial GIST, Gastrointestinal Stromal Tumors, common MESENCHYMAL, tumor of GIT, PLEURIPOTENT MESENCHYMAL CELLS, intestinal tract, neural, ganglionic, mixed mass

Published on : May 18, 2021 | Views : 1880 | Downloads : 8

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GASTROINTESTINAL STROMAL TUMORS Dr ananth prabhu Razvi Rasid
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HISTORY Until late 1960s –SMOOTH MUSCLE NEOPLASM OF GI. In 1980-IMMUNOHISTOCHEMISTRY lacked features of smooth muscle differentiation. MAZUR and CLARK - GIST
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WHAT IS GIST ? Most common MESENCHYMAL tumor of GIT. Definition- Tumors that arise from the PLEURIPOTENT MESENCHYMAL CELLS in the intestinal tract that differentiate to neural, ganglionic or mixed mass.
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WHAT IS GIST ? Can be BENIGN or MALIGNANT. Recent research- tumor start in cells found in the wall of GI tract called INTERSTITIAL CELLS OF CAJAL (ICC). Or from a very early (primitive) cell in GI which ICC.
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ICC Ramon Y Cajal Modified smooth muscle cells with incomplete neurogenic and myogenic differentiation Between PNS and GI smooth muscle cell Muscularis propria Pacemaker activity
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ICC IN ACTION
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INCIDENCE Most common benign tumor M:F is 1:1 Peak at 5 th to 7 th decade
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DISTRIBUTION Stomach - 50-60% Small intestine - 20-30% Large intestine - 10% Esophagus - 5% Else where in abdomen - 5%
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RISK FACTORS Presence of NEUROFIBROMATOSIS Familial urticaria pigmentosa Familial GIST Carney’s triad -GIST, extra-adrenal paraganglioma and pulmonary chondroma
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Familial GIST I II III IV II I I II I III IV V III VI II VII VIII III IV
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CLASSIFICATION Differentiation towards smooth muscle cells- SMOOTH MUSCLE TYPE Differentiation towards neural elements- NEURAL TYPE(GANT) Dual differentiation- SMOOTH MUSCLE-NEURAL TYPE Lacking differentiation of either cell type- UNCOMMITTED
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GROSS APPEARANCE Single or Multiple Size- 1 cm to more than 20 cm Lobulated / multilobulated and well circumscribed (lack true capsule)
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GROSS…. Submucosal , Intramuscular or Subserosal mass Originates from muscular layer
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GROSS…. Prone to surface ulcerations and bleeding Shows areas of cystic degeneration,infarction ,h’ge and necrosis
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GROSS…. Cut surface gray to pink in color
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GROSS….
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MICROSCOPIC APPEARANCE 2 main cell types – SPINDLE TYPE EPITHELIOID TYPE
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SPINDLE TYPE
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SPINDLE TYPE Short,uniform,blunt ended,eosinophilic cytoplasm. Paranuclear vacuoles. Arranged in sheets,fascicles whorled,storiform or palisaded pattern. Gastric GISTs( corpus) and some SI and LI GISTs
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SPINDLE TYPE
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EPITHELIOID TYPE
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EPITHELIOID TYPE Abundant cytoplasm,round nuclei. Cytoplasmic vacuoles. Arranged in sheets or nest Variants- Clear cell, Signet ring, Oncocytic and Plasmacytoid Previously – Leiomyoblastoma. Gastric antrum
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EPITHELIOID TYPE
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GANT Epithelioid cell coponent more prominent Lymphocytic infiltration in stroma Greater MALIGNANT potential and risk of METASTASIS
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BENIGN vs MALIGNANT
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BENIGN vs MALIGNANT Features favoring benign lesion Size less than 5 cm Low number of mitosis / HPF NO mucosal invasion Low cellularity Low markers of cell proliferation WITH PROLONGED FOLLOW UP ANY GIST HAS MALIGNANT POTENTIAL
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PATHOPHYSIOLOGY c-KIT(85%) and PDGFRA(35%) mutation c-KIT – receptor for stem cell factor PDGFRA – receptor for PDGF Both have cytoplasmic TYROSINE KINASE that activates similar intracellular pathway KIT identified by looking for CD 117 antigen
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PATHOPHYSIOLOGY MUTATION Activation of TYROSINE KINASE pathway PROMOTING CELL PROLIFERATION and INHIBITION OF APOPTOSIS
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MUTATION Human pathology, Vol 33, May 2002
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CLINICAL FEATURE Depends upon – Tumor size and Location Many ASYMPTOMATIC – discovered incidentally during laparotomy or autopsy. Small lesion - INCIDENTALOMAS
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SIGNS AND SYMPTOMS ABDOMINAL PAIN BLEEDING OBSTRUCTION DYSPHAGIA ALTERED BOWEL HABITS PALPABLE ABDOMINAL MASS ENLARGED LIVER
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STAGING Stage 1 - Localised or locally advanced disease Stage 2 - Patients who present with perforated tumor at diagnosis Stage 3 – Patients with multiple primary lesion or distant metastases at diagnosis.
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GRADING
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INVESTIGATIONS RADIOLOGICAL ENDOSCOPY IMMUNOHISTOCHEMISTRY
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BARIUM X - RAY Used in past Barium swallow Barium enema RADIOLOGICAL
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RADIOLOGICAL… ENDOSCOPIC US Used to identify the precise location of the tumor and to determine size Also extend of spread
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RADIOLOGICAL… COMPUTED TOMOGRAPHY Location and size Speard into abdomen or liver.
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RADIOLOGICAL… MRI Useful in looking for RECURRENCE or METASTASES.
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RADIOLOGICAL… PET Most useful for spotting GIST Radioactive GLUCOSE given I.V Used to see if drug therapy is working
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ENDOSCOPY
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ENDOSCOPY…
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IMMUNOHISTOCHEMISTRY To confirm the tumor after getting tissue sample. Antibodies attach to KIT protein (CD 117) Color changes on cell surface if KIT present Specific for GIST
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DIFFERENTIAL DIAGNOSIS GASTRIC CARCINOMA LYMPHOMA LEIOMYOSARCOMA
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SURGICAL AIMS – Remove all gross tumor Wide margin not generally necessary Systemic lymphadenectomy unnecessary LAPAROTOMY LAPAROSCOPY
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SURGICAL… COMPLETE SURGICAL RESECTION WITHOUT RUPTURE Smaller lesion (<4 cm) – WEDGE RESECTION Large lesion can’t be distinguished from malignant counterpart- GASTRECTOMY with minimal proximal margin of 4 cm
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LAPAROSCOPIC SURGERY INDICATIONS Small (3 cm) Localised Typically characterised as being BENIGN or LOW GRADE MALIGNANT COMPLICATIONS Perforation Tumor rupture
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LAPAROSCOPIC SURGERY
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MEDICAL TARGETED THERAPY COMBINED THERAPY TARGETED THERAPY Imatinib mesylate Selective tyrosine kinase inhibitor Given orally Dose- 400-600mg/day
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ATP = imanitib contact point Proliferation Survival Adhesion Invasion Metastasis Angiogenesis Imatinib MEDICAL…
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INDICATIONS FOR IMATINIB High risk tumor Tumor rupture Multifocal tumor Positive margin Metastasis
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EFFECT OF IMATINIB ON GIST
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RESISTANCE TO IMATINIB
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MEDICAL… COMBINED THERAPY GIST –vascular tumor so VEGF Bevacizumab + imatinib RAD 001 +imatinib PKC412 + imatinib
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RECURRENT OR METASTATIC GIST Before IMATINIB era = POOR Median survival- 6 – 18 mth Cause- TUMOR RUPTURE Site – PERITONEUM and LIVER Treatment -SURGICAL RESECTION -IMATINIB -CHEMOEMBOLIZATION OF LIVER METS
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HEPATIC ARTERY EMBOLISATION
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FOLLOW UP EVERY 3 MONTHS FOR 2 YEARS THEN EVERY 6 MONTHS FOR 3 YEARS
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SUMMARY GIST is now well characterized. All have malignant potential. Complete surgical resection important. Metastatic disease respond to IMATINIB.
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THANK YOU