الفهرس 
Pathology of Gastrointestinal Stromal TumorsOnly 14 pages are availabe for public view
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Abstract
Gastrointestinal stromal tumors (GISTs) are a subset of gastrointestinal mesenchymal tumors of varying differentiation. Previously, these tumors were classified as gastrointestinal leiomyomas, leiomyosarcomas, leiomyoblastomas, or schwannomas, on the basis of histologic findings and the fact that these tumors apparently originate in the muscularis propria layer of the intestinal wall. With the advent of immunohistochemical staining techniques and ultrastructural evaluation, GISTs now are recognized as a distinct group of mesenchymal tumors. In the present classification, GISTs account for approximately 80% of gastrointestinal mesenchymal tumors.
Gastrointestinal stromal tumors (GISTs) arise from the embryological mesoderm of the gastrointestinal tract, they can affect any part of the gastrointestinal tract most frequently the stomach, and can occur in extra intestinal sites such as mesentry and pancreas.
The non-specific collective term gastrointestinal stromal tumors was used initially to describe all gastrointestinal mesenchymal tumors. However, it was clear that this group has variable histological features and in 1998, Hirota & co-workers, reported the association between gastrointestinal stromal tumors and mutations of a receptor tyrosine kinase known as KIT. Tyrosine kinase receptor (KIT) is expressed in a number of cell types, but KIT mutations occurring in interstitial cells of Cajal (ICC) which are part of the autonomic nervous system controlling peristalsis within the gut ”pacemakers of the GI tract”, have been shown to lead to GISTs formation. There are interstitial Cajal-like cells (ICLC) in extra-intestinal sites, and these are the presumed cell of origin for extra-intestinal GISTs.
Grossly, gastrointestinal stromal tumors are well-demarcated spherical masses that appear to arise from the muscularis propria layer of the GI wall. Microscopically, most GISTs are composed of a fairly uniform population of spindle-shaped cells (70% of cases). However, some GISTs are dominated by epithelioid cells (10% of cases) or contain a mixture of spindle and epithelioid morphologies (20%).
GISTs pathogenesis relies on mutations in KIT or PDGFRA receptor tyrosine kinase proteins, mutations cause functional changes in KIT and PDGFRA proteins, usually leading to ligand-independent dimerization and constitutional activation, leading to formation of the tumor.
The most important marker for GISTs which is the key feature is positivity for the KIT (CD117) receptor tyrosine kinase, observed in more than 95% of GISTs. Other markers include CD34 and nestin. GISTs also show variable positivity for many smooth muscle and neural markers. DOG1, a new gene so named being “discovered on GIST” and encoding for a protein of unknown function, seems to be expressed in GIST independent of mutation type and is absent in non-GISTs.
Histological differential diagnosis includes smooth muscle tumors, nerve sheath tumors, desmoids, inflammatory myofibroblastic tumors, inflammatory fibroid polyps, and undifferentiated sarcomas.
GISTs may be asymptomatic, or may be presented clinically by abdominal discomfort, pain, bleeding into the intestinal tract and abdominal mass. It may be presented as an emergency by intestinal obstruction or acute abdomen due to tumor rupture. Approximately 20% to 25% of gastric and 40% to 50% of small intestinal GISTs are clinically malignant and may be presented with metastases.
Investigations for GISTs include endoscopy, capsule endoscopy, pelvi-abdominal ultrasound, endoscopic ultrasound, barium studies, pelvi-abdominal CT, MRI and PET scan.
Total surgical resection still constitutes the standard treatment for non-metastatic GISTs . The complete R0 resection represents one of the most important determinant factors in the treatment outcome. The goals of surgery are the total resection of the tumor, en bloc resection of the involved organs and avoidance of tumor rupture. Lymph node metastasis is an infrequent occurrence and so lymphadenectomy is not routine except if gross examination suggests lymph node involvement.
The goals of pharmacotherapy (including Imatinib mesylate and Sunitinib malate) are to induce remission, reduce morbidity, and prevent complications. It’s used in unresectable tumors, resectable tumors with gross residual disease or after complete resection in high risk tumors (size > 5 cm, positive margins, mitosis >1/10 HPF, tumor necrosis, rupture or hemorrhage).
Prognosis factors influencing survival and tumor recurrence depend on patient characteristics (age and sex), tumor gross (size, location, and resection margin), and microscopic features (mitotic index, cellular markers, presence of necrosis or ulceration).