Gastrointestinal stromal tumor

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A duodenal GIST in a dog, showing an exophytic tumor bulging outward from tunica muscularis, with overlying intact mucosa[1]

Gastrointestinal stromal tumor (GISTs) are a non-epithelial mesenchymal neoplasms of the canine cecum, large intestine and stomach.

These tumors are less common than gastric carcinoma but have been reported in the dog[2]. They are thought to arise from interstitial cells of Cajal or their stem cell precursors which are normally part of the autonomic nervous system of the intestine[3], serving as a pacemaker in controlling gastric motility.

GISTs usually arise in the stomach, small intestine and to a lesser extent the esophagus, colon, and rectum[4][5][6].

Gastrointestinal stromal tumors can also develop outside the intestinal tract, within the abdominopelvic cavity such as the omentum, mesentery, uterus, and the retroperitoneum; they are called extragastrointestinal stromal tumors (eGIST) and usually behave aggressively.

Clinical symptoms are those similar to gastric carcinomas and include dysphagia, vomiting, anorexia and weight loss.

Barium meal may reveal irregularities of the gastric mucosa, and endoscopy may reveal gastric mucosal thickening and reddening (ulcerations are rare) and stenosis or narrowing at the pyloric antrum.

Ultrasonography may show varying degrees of gastric wall thickening and loss of layering, with a visible sessile masses and regional lymphadenopathy[7].

Diagnosis usually requires histopathological analysis of biopsied material obtained during endoscopy or gastrotomy. Highly differentiated cell with a high mitotic index infers a poorer prognosis in most cases[8].

Definitive diagnosis requires the demonstration of the expression of KIT (CD117), a type III tyrosine kinase receptor encoded by the proto-oncogene c-KIT[9], although a small proportion of GISTs do not exhibit CD117 immunoreactivity[10].

A differential diagnosis includes lymphoma, leiomyoma, leiomyosarcoma, gastric carcinoma and malignant mesenchymoma[11].

The mainstay of treatment for GIST was surgical resection and adjuvant chemotherapy[12], but up to 50% of patients develop tumor recurrence, with a median survival time of 12 months[13].

Fortunately, with the recent advancement of proto-oncogene testing and immunohistochemical staining, treatment for GIST has improved with gene therapy directed against specific kit/PDGFRA proto-oncogene, showing promising results.

The use of small-molecule protein kinase inhibitors such as imatinib and sunitinib which target the underlying pathogenic mutant kinase and have revolutionized the treatment of GIST[5].

References

  1. Frost, D et al (2003) Gastrointestinal Stromal Tumors and Leiomyomas in the Dog: A Histopathologic, Immunohistochemical, and Molecular Genetic Study of 50 Cases. Vet Path 40:42-54
  2. Hanazono K et al (2012) Predicting metastatic potential of gastrointestinal stromal tumors in dog by ultrasonography. J Vet Med Sci 74(11):1477-1482
  3. Laurini JA & Carter JE (2010) Gastrointestinal stromal tumors: a review of the literature. Arch Path Lab Med 134(1):134–141
  4. Miettinen M & Lasota J (2006) Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Path Lab Med 130(10):1466–1478
  5. 5.0 5.1 Patil DT & Rubin BP (2011) Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Path Lab Med 135(10):1298–1310
  6. Demetri GD et al (2010) NCCN task force report: Update on the management of patients with gastrointestinal stromal tumors. JNCCN Journal of the National Comprehensive Cancer Network 8(2):S1–S44
  7. Lamb CR & Grierson J (1999) Ultrasonographic appearance of primary gastric neoplasia in 21 dogs. J Small Anim Pract 40(5):211-215
  8. Gillespie V et al (2011) Canine gastrointestinal stromal tumors: immunohistochemical expression of CD34 and examination of prognostic indicators including proliferation markers Ki67 and AgNOR. Vet Pathol 48(1):283-291
  9. Frost D et al (2003) Gastrointestinal Stromal Tumors and Leiomyomas in the Dog: A Histopathologic, Immunohistochemical, and Molecular Genetic Study of 50 Cases. Vet Pathol 40:42–54
  10. Debiec-Rychter M et al (2004) Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity. J Pathol 202(4):430–438
  11. Maas CP et al (2007) Reclassification of small intestinal and cecal smooth muscle tumors in 72 dogs: clinical, histologic, and immunohistochemical evaluation. Vet Surg 36(4):302-313
  12. De Martin I & Gagnon AM (2006) Surgical resection of a gastrointestinal stromal cell tumor by double enterectomy and partial pancreatectomy on a 13-year-old mixed breed dog. Can Vet J 47(4):370-373
  13. Russell KN et al (2007) Clinical and immunohistochemical differentiation of gastrointestinal stromal tumors from leiomyosarcomas in dogs: 42 cases (1990-2003). J Am Vet Med Assoc 230(9):1329-1333