Age -5th and 6th decades (rarely in young patients)
Sex – Slight male predominance
Exception is in carney triad (gastric GISTS, pulmonary chondromas and extraadrenal parangangliomas) generally affects women under the age of 20years and they are multifocal.
Familial GIST – in patients with germ line activating KIT or platelet derived growth factor-α (PDGFRA) mutations
Other conditions associated with GISTS are
Neurofibromatosis type 1
Tuberous sclerosis
Following radiation therapy
Cell of origin:
Arise from CD117 positive interstitial cells of Cajal present in and around the myentric plexus.
These cells show both myogenic and neural differentiation.
Molecular genetic features:
85% of cases have activating KIT mutations. KIT gene encodes a trans membrane tyrosine kinase receptor for stem cell factor (SCF). SCF receptor binding causes receptor dimerization and phosphorylation inducing proliferation and inhibiting apoptosis.
4 to 18% of GISTS harbour PDGFRA activating mutations. The gene lies adjacent to KIT locus.
Some tumors do not have KIT and PDGFRA gene mutations indicating some other aetiology of this tumor.
Clinical features:
Usually-asymptomatic
If large produces symptoms like dysphagia, abdominal pain, GI bleeding or obstruction
Gross features:
Commonly arise in stomach (60 to 70%) followed by small intestine (20to 30%), colo rectum(5%) esophagus(<5%)
GIST centre around the submucosa or muscularis propria
Well circumscribed with thin pseudo capsule of compressed normal tissues
Tumor has both endocentric and exocentric growth pattern having a dumbell shape.
Overlying mucosa can be intact or ulcerated.
Cut section pink, granular with patchy areas of haemorrhages necrosis or cystic degeneration (No whorling or bulging pattern as seen in leiomyomas)
Size – 0.5 to 45cms.
Histologic features:
GIST can be divided into
Spindle cell variant
Epithelioid variant
Mixed
Pleomorphic lesions
Spindle cell GIST
70% are spindle cells with cells exhibiting storiform, palisading or herringbone pattern
Nuclei have blunt ends and are bullet or cigar shaped.
Areas of hyalinization and skenoid fibers are noted.
Epitheloid tumors-
Composed of closely packed polygonal cells.
Some tumors contain nests of cells with an alveolar pattern.
Focal pleomorphism can be present
High mitotic rate measuring 10 mitosis/ 10hpf can be present
Another variant is with signet ring cells .These tumors affect women and the tumors have prominent myxoid matrix.
Other Varaints:
Sclerosing spindle cell GIST:
Pausi cellular tumor with extensive extracellular collagen
No nuclear atypia low mitotic activity and common calcification
Palisading and vacuolated spindle cell GISTS:
Plump spindle cells with nuclear palisading and perinucelear vacuolization
Mitotic activity –exceedes 10/ 50hpf.
Hypercellular spindle cell GIST
Uniform densely packed spindle cells
Mitotic activity exceeds 15/50mph
Sarcomatous spindle cell GIST
Diffuse atypia and with myxoid stroma
Mitotic activity >20/50pf
Sclerosing epithelioid GIST
Syncytial pattern and cohesive uniform polygonal cells with indistinct cell borders.
Epithelioid GIST with discohesive patterns
Large polygonal cells, discohesive growth pattern, scant interstitial matrix, multinucleated, possible focal atypia and low mitotic rate
Hypercelluar epithelioid GIST:
High nuclear cytoplasmia ratio than epithelioid GIST with discohesive pattern
Mitotic activity >10 / 50hpf.
Sarcomatous epithelioid GIST
High nuclear cytoplasmic ration
Mitotic activity > 20 mitosis/ 50hpf.
Other variants of GIST are
Mesothelioma like GIST variant
With Rhabdoid phenotype
Oncocytic variant
Small cell variants
Cytotoxic T-lymphocyte with GIST
Immunohistochemically –
CD117 positive ,CD34 positive
CD34 positive is the epithelioid GIST in the absence of CD117
Vimentin, S-100 and actin variable staining
Esophageal tumors sensivity – CD34 positive and C-kit positive
