Gastrointestinal stromal tumour

The gastrointestinal stromal tumour, abbreviated GIST, is an uncommon tumour of the gastrointestinal tract.

General

Definition

• Mutation in the Kit gene or PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene.

Epidemiology

• Arise from Interstitial cells of Cajal.

May be familial/syndromic:

• Neurofibromatosis 1 (Recklinghausen).
• Carney triad.
• Others.

Treatment

• Imatinib (Gleevec) - drug was developed for chronic myelogenous leukemia.
  • There are other similar drugs, e.g. nilotinib and dasatinib.

Factors predictive of malignant behaviour

Features suggesting a bad prognosis:

• Large size.
  • Often benign if small size.
• High mitotic rate (for area 5mm^2).
• Site - small intestine GISTs worse than stomach GISTs.

Small intestine bad prognosis:

• >5 mitoses/5 mm^2 or size >10 cm.

Stomach bad prognosis:

• >5 mitoses/5 mm^2 and size >5 cm.

Location

Most common locations in order:

• 60% in stomach.
• 35% in small intestine.
• 5% elsewhere.

Small intestinal GISTs have a worse prognosis than gastric ones.

Microscopic

Features:

• Classically, spindle cell morphology; however, may be epithelioid (round).
• +/-Cytoplasmic inclusions.
• Classically splits the layers of the muscularis propria - as this is where the interstitial cells of Cajal are located.

IHC

• CD34 +ve in 70%.
• CD117 +ve in 95%.
  • Mast cells are the internal positive control.

• Desmin +ve in 5%.

ICH Work-up panel

• S-100 (neural tumours, rarely +ve in GISTs).
• CD34, CD117 (GIST).
• Desmin (muscle tumours).

DDx

• Leiomyosarcoma.
• Leiomyoma - esp. in the esophagus.
• Neural tumours.
  • Neurofibroma.
  • Schwannoma (GFAP +ve).
    • GFAP uniformly neg. in GISTs.

Special tests

• Sequence Kit gene, PDGFRA gene.
  • Kit gene sequencing is being done more frequently as of late-- if a mutation is found it suggest the drug imatinib will be effective.

See also

• Stomach.
• Small bowel.
• Gastrointestinal pathology.