Gastrointestinal Stromal Tumors: A Review of Case Reports, Diagnosis, Treatment, and Future Directions

Abstract

Gastrointestinal stromal tumor (GIST) is a nonepithelial, mesenchymal tumor first described by Mazur and Clark in 1983. Since then, its molecular biology has been studied in great detail. Special interest in the role of tyrosine kinase in its regulation has been the target by different drug research. Mutation in c-kit exons 9, 11, 13, 17 and PDGFRA mutation in exons 12, 14, 18 are responsible for activation of gene signaling system resulting in uncontrolled phosphorylation and tissue growth. However, 5 to 15% of GISTs does not harbor these mutations, which raises additional questions in another alternate signaling pathway mutation yet to be discovered. Diagnosis of GISTs relies heavily on KIT/CD117 immunohistochemical staining, which can detect most GISTs except for a few 3% to 5% that harbors PDGFRA mutation. Newer staining against PKC theta and DOG-1 genes showed promising results but are not readily available. Clinical manifestation of GISTs is broad and highly dependent on tumor size. Surgery still remains the first-line treatment for GISTs. The advancement of molecular biology has revolutionized the availability of newer drugs, Imatinib and Sunitinib. Together with its advancement is the occurrence of Imatinib/Sunitinib drug resistance. With this, newer monoclonal antibody drugs are being developed and are undergoing clinical trials to hopefully improve survival in patients with GISTs.

Laparoscopy-assisted resection of CD117 and CD34 negative gastrointestinal tumor of stomach following tyrosine kinase inhibitor therapy

“…2 c-kit, a transmembrane tyrosine kinase receptor for steel factor/stem cell factor, which is responsible for proliferation and decreased apotosis, is mutated in most GISTs (85-95%). 2,3 Mutations are most common in exons 11 (70%), 9 (30%), 13 (10%), and 17 (<1%). Gastric GISTs have most commonly exon 11 mutation -either in-frame codon deletion or missense point mutation.…”

“…5-15% of GISTs do not have either of the above two mutations and are labeled as wild GISTs. [1][2][3] They are known to be less responsive or unresponsive to Imatinib therapy.…”

“…Depending on the location and adjacent organ being compressed/invaded, other manifestations, such as, satiety, anorexia, nausea/vomiting, dysphagia, jaundice, and obstruction, are also well known. 2,4 Metastases are mostly intra-abdominal and occur in peritoneum, omentum, mesentery, liver, and pancreas. Lymph node metastasis is exceptional.…”

“…1 Endoscopy has poor yield for biopsy, as seen in our case, tumor being beneath the mucosa. 2 Endoscopic ultrasonography-guided biopsy may prove better. We opted for trucut biopsy, as we had a bowel-free window, and had a need to downstage tumor in view of its large size, loss adjacent organ interface, and poor performance status.…”

“…3 The crucial diagnostic test for GISTs is immunohistochemistry (IHC). [1][2][3] In addition to the important CD117 (95%), which is the epitope on the extracellular domain of kit, GIST stains positive for less specific CD34 (60-70%), vimentin/ smooth muscle actin (15%), caldesmon, calponin, and embryonic smooth muscle myosin. Discovered on GIST-1 (DOG-1) and Protein Kinase C Theta (PKC u) are novel markers, which are seen in 97% of GISTs, including those which are wild type; hence, it may prove of benefit in identifying them.…”