GISTs are rare connective tissue tumours that show similar differentiation patterns to the interstitial cells of Cajal and approximately 60e70% arise in the stomach.
Activating mutations of the KIT or PDGFRA protooncogenes are thought to be the causal molecular events.
Approximately 95% of tumours are therefore positive for CD117 (c-KIT) by immunohistochemistry.
The degree of local and metastatic spread of gastric GISTs should be evaluated by CT scan and endoscopic ultrasound.
If the tumour is localised to the stomach it should be surgically resected.
If the tumour is unresectable or if metastases are present at diagnosis or during follow-up, treatment with the tyrosine kinase inhibitor, imatinib, should be considered and treatment should usually be continued until progression, intolerance or patient refusal occurs.
‘Consensus meeting for the management of gastrointestinal stromal tumors’.
The most common mesenchymal neoplasms affecting the gastrointestinal (GI) tract are collectively referred to as gastrointestinal stromal tumors (GISTs).
ReplyDeleteGISTs that arise in adults are characterized by the near-universal expression of the CD117 antigen, in contrast to other spindle-cell tumors of the GI tract (ie, leiomyomas, leiomyosarcomas), which are typically CD117-negative. The CD117 antigen is part of the KIT transmembrane receptor tyrosine kinase that is the product of the KIT (also denoted c-kit) protooncogene. In more than 80 percent of GIST cases, a mutation in the KIT gene leads to an abnormally activated KIT protein and enables oncogenic signaling in the cell. A subset of GISTs lacking KIT mutations have activating mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA).
A subset of GIST that are wild-type for both KIT and PDGFRA have mutations in a subunit of the enzyme succinate dehydrogenase (SDH).
GISTs occur predominantly in middle-aged and older individuals, and rarely in those under the age of 40. Although the majority of GISTs are sporadic, several kindreds with heritable mutations in the KIT gene have been identified. These families have a predisposition to multiple gastric and small bowel GISTs, and in some cases, skin hyperpigmentation, dysphagia, or GI autonomic nerve tumors such as paragangliomas.
GISTs are rare in children and often arise as a component of a defined syndrome (Carney-Stratakis syndrome, Carney triad, Neurofibromatosis type 1). In contrast to adults, 85 percent of GISTs arising in children are wild-type for KIT and PDGFRA.
The clinical behavior of GISTs is highly variable; the main prognostic determinants are tumor size, mitotic rate, and tumor location.
Some GISTs are asymptomatic and discovered incidentally. More often, they are associated with nonspecific symptoms (ie, early satiety, bloating) unless they ulcerate, bleed, or grow large enough to cause pain or obstruction. While GISTs are most often located in the stomach and proximal small intestine, they can occur in any portion of the alimentary tract including occasionally in the omentum, mesentery, and peritoneum.
Contrast-enhanced CT is a preferred initial imaging study for screening and staging, except perhaps in a patient who cannot receive IV contrast. MRI may be preferred for GISTs at specific sites, such as rectum or liver, where it provides better anatomic definition, especially in evaluating for surgery.
Preoperative biopsy is not generally recommended for a resectable lesion in which there is a high suspicion for GIST and the patient is otherwise operable. However, a biopsy is preferred to confirm the diagnosis if metastatic disease is suspected or if preoperative imatinib is considered prior to attempted resection in a patient who has a large locally advanced lesion thought to represent a GIST.
The combined use of cytologic analysis, immunohistochemistry, and reverse transcriptase polymerase chain reaction (RT-PCR) for KIT mutations may permit the preoperative diagnosis of some GISTs by endoscopic ultrasound-guided fine-needle aspiration (FNA). Tissue rather than cytologic study may be required for a definitive diagnosis.
PET scanning using fluorodeoxyglucose (FDG-PET) is highly sensitive for detecting tumors with a high glucose metabolism, including GIST, but is not specific for making a diagnosis. While a baseline PET may be indicated for patients in whom PET will be used to monitor the response to therapy with a tyrosine kinase inhibitor, nearly all the data obtained by PET scan imaging can be found in a good quality traditional IV contrasted CT scan, with superior anatomic definition.
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