[MIM 606 764]

Acronym for Gastro Intestinal Stromal Tumors

Rare: incidence of 10 to 15 cases per year per million; accounts for about 1 % of all the tumors of the digestive tract.  The gastrointestinal stromal tumors are usually sporadic, located in the stomach or the small bowell and made of connective tissue. They originate from the interstitial cells of Cajal  (responsible for the peristalsis) or one of their precursors. They express the   CD117 / KIT (95 % of cases) and DOG-1 (95 % of cases) cytokine receptors on their surface. About 60 % of GISTS's develop in the stomach, 30 % in the small bowell, and about 5 % in the colon or rectum.

Different forms are identified::

So-called adult forms:

       frequency peak around 50-60 years of age; an usually somatic mutation of the KIT (small bowell or colon) or  the platelet derived growth factor receptor alpha (PDGFRA) (stomach) (4q12), coding for tyrosine kinase receptors, is found in about 85 % of cases. These mutations induce the activation of the KIT or CEOFRA proteins.

So-called pediatric forms:

       occur in children or young adults (< 30 years of age), most often in female. They are often multiple and gastric. Their evolution is generally slow, with the possibility of lymph node metastases. They do not have a KIT/PDGFRA mutation, but a loss of somatic SDH-B expression in immunohistochemistry. GIST with loss of SDH-B expression can cause metastases in the drainage lymph nodes.

Syndromic forms:

  1.        neurofibromatosis type 1: mutation of the NF1 gene, without any somatic mutation of the KIT and PDGFRA genes, multiple GIST, mainly in the small bowell

  2.        Carney triad (very rare): no constitutional mutation but deficit of the expression of SDH-B (sub-unit B of succinate dehydrogenase)(SDHB gene on 1p36.13); mainly in young woman, presents as 3 synchronous or metachronic entities: multiple gastric GIST, pulmonary chondroma and extra-adrenal paraganglioma

  3.        Carney-Stratakis syndrome (or dyad) : caused by a constitutional mutation or epigenetic alteration of the subunits A, B, C or D of SDH: multiple gastric GIST, extra-adrenal paraganglioma (but no pulmonary chondroma)

Familial forms: autosomal dominant transmission with variable penetrance of

1.        a constitutional mutation of the KIT gene (4q12) (exceptional): young patient, family history of GIST, intestinal motility disorder (dysphagia, constipation), cutaneous pigmented spots, Cajal cell hyperplasia,

2.        a constitutional mutation of the PDGFRA gene (4q12)[MIM 175 510]: it causes GIST syndrome plus (formerly called intestinal neurofibromatosis): combination of GIST, inflammatory polyps (stomach and small intestine) and fibroid tumors with a coarse traits, broad hands and feet, early tooth loss

3.        a mutation of the SDHB (1p36.13) or SDHC (1q23.3) gene: epithelioid cells, young patient, family history of GIST.

GIST are often indolent, and can manifest as digestive hemorrhage, pain, anemia, dysphagia, occlusion or an abdominal mass. The risk of recurrence is assessed by different classifications based on retrospective series.

For example, Joensuu's table:

Treatment: complete surgical resection. There is a significant risk of peritoneal sarcomatosis in case of tumor rupture. In case of metastases or high risk of recurrence: treatment with imatrinib (Glyvec®), a tyrosine-kinase inhibitor, especially in case of mutation of the KIT gene. In case of failure or resistance to imatrinib: sunitinib.

Anesthetic implications:

check the hemoglobin level; depending on location; oncology-type surgery; imatrinib drug interactions.

References :

-        Landi B, Blay JY, Bonvalot S, Brasseur M, Coindre JM et al.
Thésaurus National de Cancérologie Digestive (TNCD).
Dig Liver Dis. 2019 ; 51:1223-31. doi:10.1016/j.dld.2019.07.006.

Updated: July 2020