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| MeshID = D046152 | | | MeshID = D046152 | |
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| {{SI}} | | {{Gastrointestinal stromal tumor}} |
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| {{CMG}} | | {{CMG}} |
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| {{EH}}
| | ==[[Gastrointestinal stromal tumor overview|Overview]]== |
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| [[Image:gist.jpg|thumb|left|Gastrointestinal stromal tumor of stomach. Courtesy of Ed Uthman, MD.]] | | ==[[Gastrointestinal stromal tumor historical perspective|Historical Perspective]]== |
| In [[medicine|medical]] [[oncology]], '''gastrointestinal stromal tumors''' ('''GIST''') are a [[rare disease|rare]] [[tumor]] of the [[gastrointestinal tract]] (1-3% of all gastrointestinal malignancies).
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| GIST is a form of [[connective tissue]] cancer, or [[sarcoma]]. GISTs are therefore non-[[epithelium|epithelial]] [[tumor]]s, separate from more common forms of [[bowel cancer]]. 70% occur in the [[stomach]], 20% in the [[small intestine]] and less than 10% in the [[esophagus]]. Small tumors are generally benign, especially when [[mitosis|cell division]] rate is slow, but large tumors disseminate to the [[liver]], [[omentum]] and [[peritoneal cavity]]. They rarely occur in other abdominal organs.
| | ==[[Gastrointestinal stromal tumor pathophysiology|Pathophysiology]]== |
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| ==Signs and symptoms== | | ==[[Gastrointestinal stromal tumor epidemiology and demographics|Epidemiology & Demographics]]== |
| Patients present with [[dysphagia|trouble swallowing]], [[gastrointestinal hemorrhage]] or [[metastasis|metastases]] (mainly in the liver). Intestinal obstruction is rare, due to the tumor's outward pattern of growth. Often, there is a history of vague [[abdominal pain]] or discomfort, and the tumor has become rather large by time the diagnosis is made.
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| Generally, the definitive diagnosis is made with a [[biopsy]], which can be obtained [[endoscope|endoscopically]], percutaneously with CT or ultrasound guidance or at the time of surgery.
| | ==[[Gastrointestinal stromal tumor risk factors|Risk Factors]]== |
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| ==Diagnosis== | | ==[[Gastrointestinal stromal tumor screening|Screening]]== |
| [[Image:GIST 2.jpg|left|thumb|200px|[[Endoscopy|Endoscopic]] image of GIST in fundus of [[stomach]], seen on retroflexion.]]
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| [[Image:GIST 3.jpg|left|thumb|200px|Same GIST seen on forward view of the endoscope showing overlying clot.]] As part of the analysis, [[blood test]]s and [[Computed axial tomography|CT scanning]] are often undertaken (see the ''[[#radiology|radiology]]'' section).
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| A [[biopsy]] sample will be investigated under the [[light microscopy|microscope]]. The [[histopathology|histopathologist]] identifies the characteristics of GISTs (spindle cells in 70-80%, epitheloid aspect in 20-30%). Smaller tumors can usually be found to the muscularis propria layer of the intestinal wall. Large ones grow, mainly outward, from the bowel wall until the point where they outstrip their blood supply and necrose (die) on the inside, forming a cavity that may eventually come to communicate with the bowel lumen.
| | ==[[Gastrointestinal stromal tumor causes|Causes of Gastrointestinal stromal tumor]]== |
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| When GIST is suspected—as opposed to other causes for similar tumors—the histopathologist can use [[immunohistochemistry]] (specific [[antibody|antibodies]] that stain the molecule [[CD117]] (also known as ''c-kit'') —see below). 95% of all GISTs are CD117-positive (other possible markers include CD34, desmin, vimentin and others). Other cells that show CD117 positivity are [[mast cell]]s.
| | ==[[Gastrointestinal stromal tumor differential diagnosis|Differentiating Gastrointestinal stromal tumor from other Diseases]]== |
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| Some tumors of the stomach and small bowel referred to as [[leiomyosarcoma]]s (malignant tumor of [[smooth muscle]]) would most likely be reclassified as GISTs today on the basis of immunohistochemical staining.
| | ==[[Gastrointestinal stromal tumor natural history|Natural History, Complications & Prognosis]]== |
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| ==Radiology== | | ==Diagnosis== |
| Barium fluoroscopic examinations ([[upper GI series]] and [[small bowel series]] (small bowel follow-through)) and [[computed tomography|CT]] are commonly used to evaluate the patient with upper [[abdominal pain]]. Both are adequate to make the diagnosis of GIST, although small tumors may be missed, especially in cases of a suboptimal examination.
| | [[Gastrointestinal stromal tumor history and symptoms|History & Symptoms]] | [[Gastrointestinal stromal tumor physical examination|Physical Examination]] | [[Gastrointestinal stromal tumor laboratory tests|Lab Tests]] | [[Gastrointestinal stromal tumor electrocardiogram|Electrocardiogram]] | [[Gastrointestinal stromal tumor chest x ray|Chest X Ray]] | [[Gastrointestinal stromal tumor CT|CT]] | [[Gastrointestinal stromal tumor MRI|MRI]] | [[Gastrointestinal stromal tumor echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Gastrointestinal stromal tumor other imaging findings|Other Imaging Findings]] | [[Gastrointestinal stromal tumor other diagnostic studies|Other Diagnostic Studies]] |
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| Small GISTs appear as intramural masses. When large (> 5 cm), they most commonly grow outward from the bowel. Internal [[calcification]]s may be present. As the tumor outstrips its blood supply, it can [[necrosis|necrose]] internally, creating a central fluid-filled cavity that can eventually [[ulcer]]ate into the lumen of the bowel or stomach.
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| The tumor can directly invade adjacent structures in the abdomen. The most common site of spread is to the [[liver]]. Spread to the [[peritoneum]] may be seen. In distinction to [[gastric adenocarcinoma]] or gastric/small bowel [[lymphoma]], malignant [[adenopathy]] (swollen lymph nodes) is uncommon (<10%).
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| == Pathophysiology ==
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| GISTs are thought to arise from [[interstitial cells of Cajal]] (ICC),<ref name=miettinen>{{cite journal |author=Miettinen M, Lasota J |title=Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis |journal=Arch Pathol Lab Med |volume=130 |issue=10 |pages=1466-78 |year=2006 |id=PMID 17090188}}</ref> that are normally part of the [[autonomic nervous system]] of the intestine. They serve a pacemaker function in controlling [[motility]].
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| Most (50-80%) GISTs arise because of a mutation in a [[gene]] called ''[[c-kit]]''. This gene encodes a [[transmembrane receptor]] for a growth factor termed ''scf'' (stem cell factor). The ''c-kit''/CD117 receptor is expressed on ICCs and a large number of other cells, mainly [[bone marrow]] cells, [[mast cell]]s, [[melanocyte]]s and several others. In the gut, however, a mass staining positive for [[CD117]] is likely to be a GIST, arising from ICC cells.
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| The ''c-kit'' [[molecule]] comprises a long [[Membrane protein|extracellular domain]], a [[Membrane protein|transmembrane segment]], and an intracellular part. Mutations generally occur in the [[deoxyribonucleic acid|DNA]] encoding the intracellular part (exon 11), which acts as a [[tyrosine kinase]] to activate other [[enzyme]]s. Mutations make ''c-kit'' function independent of activation by ''scf'', leading to a high cell division rate and possibly genomic instability. It is likely that additional mutations are "required" for a cell with a ''c-kit'' mutation to develop into a GIST, but the ''c-kit'' mutation is probably the first step of this process.
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| The [[tyrosine kinase]] function of ''c-kit'' is vital in the therapy for GISTs, please see below.
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| ==Genetics==
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| Although some families with [[genetic disorder|hereditary]] GISTs have been described, most cases are sporadic.
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| In GIST cells, the ''c-kit'' gene is mutated approximately 85% to 90% of the time. 35% of the GIST cells that do not have a mutated ''c-kit'' ("wild-type") do have a mutation in another gene, PDGFR-α (platelet derived growth factor receptor alpha), which is a related tyrosine kinase. Mutations in the [[exon]]s 11, 9 and rarely 13 and 17 of the ''c-kit'' gene are known to occur in GIST. D816V [[point mutation]]s in ''c-kit'' exon 17 are responsible for resistance to targeted therapy drugs like [[imatinib mesylate]]. Mutations in ''c-kit'' and ''PDGFrA'' are mutually exclusive[http://www.liferaftgroup.org/gist_genetics.html][http://www.liferaftgroup.org/LondnPPT/Fletcher/Fletcher_files/frame.htm].
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| ==Epidemiology==
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| GISTs occur in 10-20 per one million people; one out of 3-4 is malignant. The true incidence might be higher, as novel laboratory methods are much more sensitive in diagosing GISTs. In all, there are approximately 3000-3500 cases of GIST per year in the United States. This makes GIST the most common form of [[sarcoma]], which constitutes more than 70 types of cancer, but in all forms constitutes less than 1% of all cancer.
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| ==Therapy==
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| Most small GISTs (<5 and especially <2 cm) with a low rate of [[mitosis]] (<5 dividing cells per 50 high-power fields) are benign and—after surgery—do not require adjuvant therapy.
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| Larger GISTs (>5 cm), and especially when the cell division rate is high (>6 [[mitosis|mitoses]]/50 HPF), may disseminate and/or recur.
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| Until recently, GISTs were notorious for being resistant to [[chemotherapy]], with a success rate of <5%. Recently, the ''c-kit'' [[tyrosine kinase]] inhibitor [[imatinib]] (Glivec®/Gleevec®), a drug initially marketed for [[chronic myelogenous leukemia]], was found to be useful in treating GISTs, leading to a 40-70% response rate in metastatic or inoperable cases.
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| Patients who become refractory on imatinib may respond to the multiple tyrosine kinase inhibitor [[sunitinib]] (marketed as Sutent).
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| Therapy for GIST is best directed by physicians familiar with the disease. Such doctors, specifically surgeons and medical oncologists, are found at major cancer centers.
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| ==History==
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| Until the 1990s, all non-[[epithelium|epithelial]] [[tumor]]s of the [[gastrointestinal tract]] were called "gastrointestinal stromal tumors" from [[smooth muscle]] origin. [[Histopathology|Histopathologists]] generally did not distinguish between the types, as this did affect neither therapy nor prognosis. Subsequently, [[Cluster of differentiation|CD34]], and later CD117 were identified as markers that could distinguish the various types.
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| ==Sources== | | ==Sources== |
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| ==References== | | ==References== |
| <references/>
| | {{reflist|2}} |
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| ==External links==
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| ====Research Links====
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| * [http://www.asco.org/ac/1,1003,_12-002626-00_18-0034-00_19-0029,00.asp American Society of Clinical Oncology] "Other Gastrointestinal Cancer" Abstracts (2005)
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| ====Patient-Oriented Websites====
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| * [http://www.gistsupport.org/ GIST Support International], An international organization for the support of GIST patients, families, and friends. Includes detailed information from some of the foremost experts on GIST, links to research, treatment options, GIST registry.
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| *[http://www.liferaftgroup.org/ Life Raft Group] International GIST Advocacy Organization. Provides support to patients & families, through information, education, and innovative research.
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| * [http://www.gistinfo.org/ GIST Info] Patient links, includes information on new clinical trials and research
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| *[http://www.cancer.org/docroot/CRI/CRI_2_3x.asp?rnav=cridg&dt=81 American Cancer Society] Patient Guide to GIST tumors.
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| ====Online Support Groups====
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| * [http://acor.org ACOR] [http://listserv.acor.org/archives/sti571-gist.html STI571-GIST] support group, started in Dec 2000 by the Life Raft Group
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| * [http://community.lsoft.com/scripts/WA-LSOFTDONATIONS.exe?SUBED1=GISTSUPPORT&A=1 GIST Support International listserv] support and information, started in March 2003 and [http://gistsupport.medshelf.org/Main_Page associated wiki].
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| *[http://community.lsoft.com/scripts/WA-LSOFTDONATIONS.exe?SUBED1=PEDIATRIC-GIST&A=1 Pediatric and Carney Triad listserv] support and information for all families facing pediatric GIST or Carney Triad, started in Jan 2007.
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| {{SIB}} | |
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| [[Category:Gastroenterology]] | | [[Category:Gastroenterology]] |
| [[Category:Types of cancer]] | | [[Category:Types of cancer]] |
| [[Category:Oncology]] | | [[Category:Oncology]] |
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| </br>
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| [[de:Gastrointestinaler Stromatumor]]
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| [[it:Tumore stromale gastrointestinale]]
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| [[ja:消化管間質腫瘍]]
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| {{WikiDoc Help Menu}} | | {{WikiDoc Help Menu}} |
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