mesenchymal tumor of stomach,gastro intestinal stomal tumor ,pathology,cd117spindle and epitheloid tyme,grading and staging

1. •GASTROINTESTINAL
STROMAL TUMOR (GIST)

3. INTERSTITIAL CELLS
OF CAJAL
• Mesenchymal cells-origin of gist
• Present in the muscularis Propria layer of GI
tract
• Intercalated cells between autonomic nerves
and smooth muscle cells
• Control peristaltic activity in GI tract
• They are +ve for KIT gene that encode
transmembrane tyrosine kinase receptor
(CD117)

5. • 2% are malignant gastric tumours
• Gain of function of KIT gene mutation 95%
• Some show mutation in PGDFRA gene
• Stomach >> small intestine >colon rectum>
oesophagus
• Rarely appendix
• Extra intestinal GIST – mesentry omentum
retroperitoneum
GIST

6. • GIST associated syndromes:
1. familial GIST
2.carney triad (GIST, paraganglioma , pulomonary chondroma)
3.carney-stratkias syndrome( GIST , paraganglioma , SDH
germline mutations)
4. neurofibromatosis-1

8. PATHOGENESIS
85% to 90% have gain of function mutation
of KIT gene
Produce intracellular signals
promote tumor cell proliferation and
inhibit tumor supressor genes (CDKN2A)

9. • Some show mutations in PDGFRA gene
• Some show mutation in NF1 BRAF HRAS and
NRAS
• Mutation of succinate dehydrogenase (carney triad
and carney stratkias triad)

10. CLINICAL
FEATURES
• Mass per abdomen
• Anaemia (blood loss due to mucosal
ulceration)
• Mostly it is found as incidental finding in
endoscopy or any abdominal surgeries.

11. GROSS
FEATURES:
• Single or multiple ,with clearly defined
margins.
• In stomach -Sub mucosa (60%) grow towards
lumen, smooth projection into lumen
• Sometimes subseroasl extension may occur
and peritoneal cavity involved
• C/S : flat, whorled ,firm ,foci of necrosis or
haemorrhage

12. • Gastric GIST with mucosal ulceration

14. • In intestine: involves all layers
• Grow extramurally and may extend intraluminally
to cause mucosal ulceration
• Circumscribed , solitary , round or ovoid masses,
pendunculated mass.
• C/S: not whorled or no bulging
pinkish white appearance often with areas of
haemorrhage, necrosis , myxoid change.
Both benign and malignant gist have same gross
features
30% - 40% are malignant.

16. MICROSCOPIC
APPEARANCE
• 2 types
1. spindle cell type
2. epithelioid type
some times admixture of both can be seen.
• most gastric GIST are spindle cell type
• SDH deficient GIST usually show epitheliod
morphology.

17. SPINDLE CELL
TYPE
Low risk type
•Bland spindle cells
•arranged in packets or whorls
•Normochromatic nuclei
•Per nuclear vacuoles
High risk type
•atypical spindle cells
•Arranged in fascicles
•Easily identifiable mitotic
figures
•Little mitotic activity •Necrosis
•Mucosal invasion.

18. • Sub types in spindle type morphology:
sclerosing type ,palisaded vacuolated sub type
are most common
• some show skeinoid fibers, small globular,
curvilinear, eosinophilic aggregates of
filamentous material sacttered among tumor
cells. PAS +ve
• Most common in corpus and antrum of
stomach

19. LOW POWER VIEW OF LOW RISK GIST
OF STOMACH

20. HIGH POWER VIEW OF LOW RISK GIST
OF STOMACH

21. EPITHELIOID TYPE OF
STOMACH GIST
• Epitheloid cells with abundant eosinophilic or
clear cytoplasm( signet ring forms)
• Multinucleation
• Rare mitotic figures
• Abundant stroma
• No necrosis or mucosal invasion
• They are previously termed as leiomyoblastomas
• Occasionally they resemble plasmacytoid
appearence .

24. D/D for gastric GIST:
• solitary fibrous tumor
• fibromatosis
• inflammatory fibroid polyp
• glomus tumor
• schwannoma
• leiomyoma/ leiomyosarcoma
• malignant lymphoma
• carcinoma

25. IHC
• Positive for CD117 (KIT)- cytoplasmic , membrane associated
or sometimes perinuclear dot like

26. • Some PDGFRA gene mutated GIST show negativity to
CD117( KIT negative GIST)
• DOG1 is most sensitive and specific marker for GIST
• DOG1 and CD117 are expressed in interstitial cells of
cajal.
• Some GIST also show +ve to vimentin , protein kinase
c, nestin , bcl2 ,caldesmon, s100
• Spindle type GIST positivity to CD34

27. • DOG 1 show diffuse cytoplasmic and/or
membranous staining.

29. METASTASIS
Mc sites for metastases of malignant GIST are
liver, peritoneum and lungs
• Occasionally to ovary
• Mets occur after 30 yrs of removal of primary
tumour
treatment:
• Imatinib
• Complete surgical resection

30. Risk stratification in GIST
• Tumour characteristics of size of tumour and mitotic
rate helps in stratification of risk.
• Invasion into lamina propria in stomach is highly
suggestive of malignancy
• Epitheliod type in intestinal GIST is high malignant
• According to WHO anatomical site is also an indicator

33. WHO TUMOUR STAGING OF
GIST:
• Anatomical sites and sub sites
• Regional lymph nodes
• TNM classification
• pTNM pathological classification
• G histopathological grading
• Stage

35. Histopathological grading
low mitotic rate : 5 or fewer/hpf
High mitotic rate : >5 /hpf
pTNM classification
pM : distant metastasis
pM1 : distant metastasis microscopically
confirmed

37. THANK YOU