Intestinal Stromal Tumors Workup

  • Author: Michael A Choti, MD, MBA, FACS; Chief Editor: Jules E Harris, MD   more...
 
Updated: Oct 17, 2011
 

Laboratory Studies

Conduct a complete preoperative workup including blood panel, complete metabolic panel, and coagulation factors.

GISTs are not associated with elevation of any serum tumor markers. Performing tumor marker assays (eg, CA19-9, CEA, CA-125, AFP) for other abdominal neoplasms may be appropriate, however, depending on the location, size, and appearance of the tumor on imaging studies.

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Imaging Studies

The diagnostic evaluation for GISTs is very similar to that pursued for other GI malignancies. Note that the appropriate imaging workup depends on the size and location of the tumor.

Characteristic findings on computed tomography (CT) scan and magnetic resonance imaging (MRI) can be highly suggestive of a GIST versus other GI malignancies.

  • A CT scan of the abdomen and pelvis with oral and IV contrast is the most essential study to assess primary tumor extension and presence of metastasis, especially in the peritoneum or liver. On contrast-enhanced CT scans, the intramural component of GIST is typically evident, though it may be more difficult to visualize large masses with extension into adjacent structures. Most of these tumors show peripheral enhancement with central areas of low attenuation suggesting hemorrhage, necrosis, or a cystic component. Typically, the enhancement is heterogeneous. Cavitary lesions may be present with air fluid levels. Metastatic lymphadenopathy is not a feature of GISTs. Metastatic disease may be evident with CT findings consistent with organ invasion, ascites, omental or peritoneal spread, or liver metastasis.
  • MRI can be an especially helpful adjunct to CT in the evaluation of large tumors that have necrotic and hemorrhagic components. Solid tumor portions show low intensity on T1 images and high intensity on T2 images, with enhancement of the mass when intravenous gadolinium is given. Signal intensity of hemorrhagic components of the tumor can vary from high to low, depending on the age of the hemorrhage.

Barium and Gastrografin studies of the stomach, small intestine, and colon aid in the diagnosis of GISTs. These studies include upper gastrointestinal series, small bowel series, and barium enema studies. Typically, the lesions have the classic features of submucosal masses such as leiomyomas and leiomyosarcomas. They appear as a smooth-lined filling defect in the lumen with well-demarcated borders. Focal areas of ulceration can be seen in 60% of cases.

Ultrasonography may suggest the presence of a malignant GIST, marked by cystic spaces, echogenic foci, and irregular extraluminal borders. Ultrasonography offers no benefit over CT or MRI, however, and so is rarely used if CT or MRI provide sufficient information for a tentative diagnosis.

Fluorodeoxyglucose positron emission tomography (FDG-PET) scanning may be helpful in the staging and evaluation of GISTs. Its value has been reported in studying disease progression or response to therapy in people receiving imatinib for primary or metastatic GISTs.[19]

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Procedures

Procedures performed in the evaluation of GISTs are similar to those used for other GI malignancies. Base the choice of procedure on the location and size of the mass and the need for any further information after pursuing imaging modalities.

For tumors of the upper GI tract, esophagogastroduodenoscopy may aid in the extent of intraluminal involvement and in obtaining definitive tissue diagnosis. Typically, they appear as a submucosal mass. Any endoscopic biopsy, however, needs to be deep enough to obtain tissue below the mucosa. For small-bowel tumors, double-balloon endoscopy has proved effective for detection and biopsy of GISTs.[20]

GISTs typically appear as a smooth protrusion of the bowel wall with preserved mucosal lining and may have components of ulceration and bleeding. Endoscopic ultrasonography may show a hypoechoic mass originating in the muscularis propria of the bowel wall. Similarly, anorectal ultrasonography and colonoscopy can provide findings consistent with GISTs of the colon, rectum, and anus.

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Histologic Findings

On histology, as shown in images below, spindle-shaped cells are most common (70%), followed by epithelioid cells (20%) and a mixed spindle cell-epithelioid pattern. The tumor cells are highly cellular with less eosinophilic cytoplasm than smooth muscle neoplasm’s. They have indistinct cell margins and minimal tumor stroma. Malignancy is associated with histology consistent with nuclear atypia, high cellularity, high mitotic rate (more than 5 per HPF), mucosal invasion, necrosis, and a mixed spindle cell–epithelioid morphology.

Gastric stromal tumor. Photomicrograph of gastroinGastric stromal tumor. Photomicrograph of gastrointestinal stromal tumor (GIST) stained with hematoxylin and eosin (H&E) and magnified 40 times. Note the solid sheet of spindle cells. Image courtesy of Michael Choti, MD. Photomicrograph of a gastric stromal tumor stainedPhotomicrograph of a gastric stromal tumor stained with hematoxylin and eosin (H&E) and magnified 400 times. This stromal tumor demonstrates spindle cells with epithelioid features. Image courtesy of Michael Choti, MD.

GISTs are distinguished from leiomyomas and leiomyosarcomas by immunohistochemistry and electron microscopy. Unlike the latter two tumor types, GISTs are usually positive for CD34 (60-70%). They may be positive for smooth muscle actin, but unlike smooth muscle tumors, GISTs are rarely positive for desmin. The hallmark of GISTs is their positivity for CD117 (KIT) receptor, as shown in the image below. CD117 is the product of c-kit proto-oncogene.[21] Gain of functional mutations of the KIT protein, a tyrosine kinase receptor, is believed to play a critical role in the oncogenesis of GISTs. Although other tumors can be positive for CD117, most of these tumors do not occur in the GI tract. Although other tumors can be positive for CD117, most of these tumors do not occur in the GI tract. Additional mutually exclusive mutations from c-kit have also been identified in PDGFRA (10%) and BRAF (7%) genes, respectively, opening a role in tumorigenesis forothertyrosinekinases.[22]

Gastric stromal tumor: Photomicrograph of gastroinGastric stromal tumor: Photomicrograph of gastrointestinal stromal tumor (GIST) with immunohistochemical staining for CD117. Note the strong positive staining of tumor cells with negative staining of the adjacent vessel. Positive stain for CD117 is diagnostic of GIST. Image courtesy of Michael Choti, MD.

Assigning the risk of malignancy to GISTs tumors can be difficult. Many have observed the risk of recurrence varies by the anatomic location of the primary GIST. Miettinen et al proposed a risk assessment strategy.[23]

Table 2. Risk Classification for Primary GIST by Mitotic Index, Size, and Tumor Site. Adapted from AJCC. (Open Table in a new window)

Tumor Parameters Risk of Progressive Disease*
Mitotic



Index



SizeStomachDuodenumJejunum



or ileum



Rectum
≤5 per 50 HPF≤2cmNoneNoneNoneNone
>2 to ≤5 cmVery low (1.9%)Low (8.3%)Low (4.3%)Low (8.5%)
>5 to ≤10 cmLow (3.6%)Insufficient dataModerate (24%)Insufficient data
>10 cmModerate (10%)High (34%)High (52%)High (57%)
>5 per 50 HPF ≤2 cmNone*Insufficient dataHigh † High (54%)
>2 to ≤5 cmModerate (16%)High (50%)High (73%)High (52%)
>5 to ≤10 cmHigh (55%)Insufficient dataHigh (85%)Insufficient data
>10 cmHigh (86%)High (86%)High (90%)High (71%)
*Defined as metastasis or tumor-related death.



† Denotes small number of cases.



Data based on long-term follow up of 1055 gastric, 629 small intestinal, 144 duodenal, and 111 rectal GISTs.
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Staging

The American Joint Committee on Cancer (AJCC) has introduced new staging criteria for GISTs in its 7th edition manual.[24] There has never been AJCC staging for GISTs in the past, but this new scheme is to be used for all GISTs. The authors of this staging system adopted the accepted risk assessment for all GISTs and applied this to the tumor, node, metastasis (TNM) system.[23] In addition, a "grade" category is assigned based on mitotic rate: "low grade" for 5 or fewer mitoses in 50 HPF and "high grade" for 6 or more mitoses in 50 HPF. Staging is different for gastric and omental versus other GISTs, indicating a greater risk of recurrence for nongastric GISTs.

The new criteria for risk stratification of primary GISTs been incorporated into the AJCC staging seen below. The stratification is by mitotic index (5 or less or more than 5 per 50 HPF) and then further divided by tumor size, nodal disease, and tumor metastasis. Gastric GISTs larger than 10 cm but 5 or less per 50 HPF mitotic index have only a 10% risk of progressive disease despite 34-57% risk of progressive disease in the other tumor locations. Gastric GISTs greater than 10 cm and a high mitotic index (>5 per 50 HPF), however, have an equally high risk of progressive disease (86%) as the other tumor locations. Many studies have shown that tumor diameter greater than 5 cm is associated with increased risk for malignancy. However, the relationship of size to malignant potential may be gradual, with no clear cut-off point.

The number of mitotic figures is the most accepted index for grade classification, although other histologic parameters, such as cellularity, atypia, and necrosis, are also taken into consideration. A high mitotic index of more than 5 mitoses per 10 HPF usually signifies highly malignant disease. However, a low mitotic index is not always associated with a benign course. As many as 25% of tumors with mitotic index of less than 5 mitoses per 10 HPF may manifest aggressive biological behavior.

Tumor (T) is as follows:

  • TX - Primary tumor cannot be assessed
  • T0 - No evidence of primary tumor
  • T1 - Tumor smaller than 2 cm, localized
  • T2 - Tumor more than 2 cm but not more than 5 cm
  • T3 - Tumor more than 5 cm but not more than 10 cm
  • T4 - Tumor rupture more than 10 cm in greatest dimension

Regional lymph node (N) is as follows:

  • N0 - No regional lymph node metastasis
  • N1 - Regional lymph node metastasis

Metastasis (M) is as follows:

  • M0 - No distant metastasis
  • M1 - Distant metastases

Table 3. Proposed Staging System for Malignant Gastrointestinal Stromal Tumors[24] (Open Table in a new window)

GroupTNMMitosis
Stage IT1 or T2N0M0Low
Stage IIT3N0M0Low
Stage IIIAT1N0M0High
T4N0M0Low
Stage IIIBT2N0M0High
T3N0M0High
T4N0M0High
Stage IVAny TN1M0Any Rate
Any TAny NM1Any Rate
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Contributor Information and Disclosures
Author

Michael A Choti, MD, MBA, FACS  Jacob C Handelsman Professor of Surgery, Professor of Oncology, Radiology, Engineering, Johns Hopkins University School of Medicine

Michael A Choti, MD, MBA, FACS is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Surgeons, American Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology, American Surgical Association, Association for Academic Surgery, International Hepato-Pancreato-Biliary Association, Society for Surgery of the Alimentary Tract, Society of Surgical Oncology, and Society of University Surgeons

Disclosure: Nothing to disclose.

Coauthor(s)

Fabian M Johnston, MD  Fellow, Department of Surgery, Division of Surgical Oncology, Johns Hopkins University School of Medicine

Fabian M Johnston, MD is a member of the following medical societies: American Medical Association, National Medical Association, Society of Black Academic Surgeons, and Society of Surgical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert C Shepard, MD, FACP  Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Alex J Mechaber, MD, FACP  Senior Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine

Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

References

  1. Mazur MT, Clark HB. Gastric stromal tumors. Reappraisal of histogenesis. Am J Surg Pathol. Sep 1983;7(6):507-19. [Medline].

  2. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. Jan 23 1998;279(5350):577-80. [Medline].

  3. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney Triad): natural history, adrenocortical component, and possible familial occurrence. Mayo Clin Proc. Jun 1999;74(6):543-52. [Medline].

  4. Ishida T, Wada I, Horiuchi H, Oka T, Machinami R. Multiple small intestinal stromal tumors with skeinoid fibers in association with neurofibromatosis 1 (von Recklinghausen's disease). Pathol Int. Sep 1996;46(9):689-95. [Medline].

  5. Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. Nov 15 2001;61(22):8118-21. [Medline].

  6. Corless CL, McGreevey L, Haley A, Town A, Heinrich MC. KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol. May 2002;160(5):1567-72. [Medline].

  7. Chompret A, Kannengiesser C, Barrois M, Terrier P, Dahan P, Tursz T, et al. PDGFRA germline mutation in a family with multiple cases of gastrointestinal stromal tumor. Gastroenterology. Jan 2004;126(1):318-21. [Medline].

  8. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. Jan 31 2003;299(5607):708-10. [Medline].

  9. Agaimy A, Terracciano LM, Dirnhofer S, Tornillo L, Foerster A, Hartmann A, et al. V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol. Jul 2009;62(7):613-6. [Medline].

  10. Fukasawa T, Chong JM, Sakurai S, Koshiishi N, Ikeno R, Tanaka A. Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor. Jpn J Cancer Res. Dec 2000;91(12):1241-9. [Medline].

  11. Miettinen M, El-Rifai W, H L Sobin L, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. May 2002;33(5):478-83. [Medline].

  12. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. Jan 2000;231(1):51-8. [Medline].

  13. Ng EH, Pollock RE, Munsell MF, Atkinson EN, Romsdahl MM. Prognostic factors influencing survival in gastrointestinal leiomyosarcomas. Implications for surgical management and staging. Ann Surg. Jan 1992;215(1):68-77. [Medline].

  14. McGrath PC, Neifeld JP, Lawrence W Jr, Kay S, Horsley JS 3rd, Parker GA. Gastrointestinal sarcomas. Analysis of prognostic factors. Ann Surg. Dec 1987;206(6):706-10. [Medline].

  15. Shiu MH, Farr GH, Papachristou DN, Hajdu SI. Myosarcomas of the stomach: natural history, prognostic factors and management. Cancer. Jan 1 1982;49(1):177-87. [Medline].

  16. Akwari OE, Dozois RR, Weiland LH, Beahrs OH. Leiomyosarcoma of the small and large bowel. Cancer. Sep 1978;42(3):1375-84. [Medline].

  17. Singer S, Rubin BP, Lux ML, Chen CJ, Demetri GD, Fletcher CD, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. J Clin Oncol. Sep 15 2002;20(18):3898-905. [Medline].

  18. Dougherty MJ, Compton C, Talbert M, Wood WC. Sarcomas of the gastrointestinal tract. Separation into favorable and unfavorable prognostic groups by mitotic count. Ann Surg. Nov 1991;214(5):569-74. [Medline].

  19. van den Abbeele A, Badawi R, Cliche J-P, et al. 18F-FDG PET predicts response to imatinib mesylate (Gleevec) in patients with advanced gastrointestinal stromal tumors (GIST). Proc Am Soc Clin Oncol. 2002;abstr1610.

  20. Mitsui K, Tanaka S, Yamamoto H, Kobayashi T, Ehara A, Yano T, et al. Role of double-balloon endoscopy in the diagnosis of small-bowel tumors: the first Japanese multicenter study. Gastrointest Endosc. Sep 2009;70(3):498-504. [Medline].

  21. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol. May 2002;33(5):459-65. [Medline].

  22. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. Aug 15 2002;347(7):472-80. [Medline].

  23. Eisenberg BL, Harris J, Blanke CD, Demetri GD, Heinrich MC, Watson JC, et al. Phase II trial of neoadjuvant/adjuvant imatinib mesylate (IM) for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumor (GIST): early results of RTOG 0132/ACRIN 6665. J Surg Oncol. Jan 1 2009;99(1):42-7. [Medline].

  24. Edge SE, Byrd DR, Carducci MA, Compton CC. AJCC Cancer Staging Manual. 7th ed. Springer; 2010.

  25. Fiore M, Palassini E, Fumagalli E, Pilotti S, Tamborini E, Stacchiotti S, et al. Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal stromal tumors (GIST). Eur J Surg Oncol. Jul 2009;35(7):739-45. [Medline].

  26. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol. Feb 1 2008;26(4):626-32. [Medline].

  27. Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology. Sep 2008;53(3):245-66. [Medline].

  28. Renouf D, Blay JY, Blanke C. Accomplishments in 2008 in the management of gastrointestinal stromal tumors. Gastrointest Cancer Res. Sep 2009;3(5 Supplement 2):S67-72. [Medline].

  29. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. Jan 2009;45(2):228-47. [Medline].

  30. Le Cesne A, Van Glabbeke M, Verweij J, Casali PG, Findlay M, Reichardt P, et al. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol. Aug 20 2009;27(24):3969-74. [Medline].

  31. Pisters PW, Patel SR. Gastrointestinal stromal tumors: Current management. J Surg Oncol. Jan 8 2010;[Medline].

  32. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. Oct 14 2006;368(9544):1329-38. [Medline].

  33. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. Jun 1 2005;11(11):4182-90. [Medline].

  34. Antonescu CR, Viale A, Sarran L, Tschernyavsky SJ, Gonen M, Segal NH, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res. May 15 2004;10(10):3282-90. [Medline].

  35. Bedikian AY, Khankhanian N, Valdivieso M, Heilbrun LK, Benjamin RS, Yap BS, et al. Sarcoma of the stomach: clinicopathologic study of 43 cases. J Surg Oncol. 1980;13(2):121-7. [Medline].

  36. Blair SC, Zalupski MM, Baker LH. Ifosfamide and etoposide in the treatment of advanced soft tissue sarcomas. Am J Clin Oncol. Dec 1994;17(6):480-4. [Medline].

  37. Carroll M, Ohno-Jones S, Tamura S, Buchdunger E, Zimmermann J, Lydon NB, et al. CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. Dec 15 1997;90(12):4947-52. [Medline].

  38. Caterino S, Lorenzon L, Petrucciani N, Iannicelli E, Pilozzi E, Romiti A, et al. Gastrointestinal stromal tumors: correlation between symptoms at presentation, tumor location and prognostic factors in 47 consecutive patients. World J Surg Oncol. Feb 1 2011;9:13. [Medline]. [Full Text].

  39. Chen H, Pruitt A, Nicol TL, Gorgulu S, Choti MA. Complete hepatic resection of metastases from leiomyosarcoma prolongs survival. J Gastrointest Surg. Mar-Apr 1998;2(2):151-5. [Medline].

  40. Chen LL, Trent JC, Wu EF, Fuller GN, Ramdas L, Zhang W, et al. A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res. Sep 1 2004;64(17):5913-9. [Medline].

  41. Conlon KC, Casper ES, Brennan MF. Primary gastrointestinal sarcomas: analysis of prognostic variables. Ann Surg Oncol. Jan 1995;2(1):26-31. [Medline].

  42. Crosby JA, Catton CN, Davis A, Couture J, O'Sullivan B, Kandel R, et al. Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database. Ann Surg Oncol. Jan-Feb 2001;8(1):50-9. [Medline].

  43. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. Mar 28 2009;373(9669):1097-104. [Medline].

  44. Dematteo RP, Heinrich MC, El-Rifai WM, Demetri G. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol. May 2002;33(5):466-77. [Medline].

  45. Dematteo RP, Maki RG, Antonescu C, Brennan MF. Targeted molecular therapy for cancer: the application of STI571 to gastrointestinal stromal tumor. Curr Probl Surg. Mar 2003;40(3):144-93. [Medline].

  46. Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H. NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw. Jul 2007;5 Suppl 2:S1-29; quiz S30. [Medline].

  47. Down-Kelly E, Rubin BP. Gastrointestinal Stromal Tumors: molecular mechanisms and targeted therapies. Path Res Int. Apr 2011;1-7. [Medline]. [Full Text].

  48. Edmonson JH, Marks RS, Buckner JC, Mahoney MR. Contrast of response to dacarbazine, mitomycin, doxorubicin, and cisplatin (DMAP) plus GM-CSF between patients with advanced malignant gastrointestinal stromal tumors and patients with other advanced leiomyosarcomas. Cancer Invest. 2002;20(5-6):605-12. [Medline].

  49. Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. Jan 1999;23(1):82-7. [Medline].

  50. Evans HL. Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years. Cancer. Nov 1 1985;56(9):2242-50. [Medline].

  51. Fujimoto Y, Nakanishi Y, Yoshimura K, Shimoda T. Clinicopathologic study of primary malignant gastrointestinal stromal tumor of the stomach, with special reference to prognostic factors: analysis of results in 140 surgically resected patients. Gastric Cancer. 2003;6(1):39-48. [Medline].

  52. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. Aug 3 2001;293(5531):876-80. [Medline].

  53. Graadt van Roggen JF, van Velthuysen ML, Hogendoorn PC. The histopathological differential diagnosis of gastrointestinal stromal tumours. J Clin Pathol. Feb 2001;54(2):96-102. [Medline].

  54. Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol. May 2002;33(5):484-95. [Medline].

  55. Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. Apr 5 2001;344(14):1052-6. [Medline].

  56. Karakousis CP, Blumenson LE, Canavese G, Rao U. Surgery for disseminated abdominal sarcoma. Am J Surg. Jun 1992;163(6):560-4. [Medline].

  57. Lev D, Kariv Y, Issakov J, Merhav H, Berger E, Merimsky O, et al. Gastrointestinal stromal sarcomas. Br J Surg. Apr 1999;86(4):545-9. [Medline].

  58. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol. May 2006;23(2):70-83. [Medline].

  59. Nishida T, Hirota S. Biological and clinical review of stromal tumors in the gastrointestinal tract. Histol Histopathol. Oct 2000;15(4):1293-301. [Medline].

  60. Pidhorecky I, Cheney RT, Kraybill WG, Gibbs JF. Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann Surg Oncol. Oct 2000;7(9):705-12. [Medline].

  61. Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. May 20 2006;24(15):2325-31. [Medline].

  62. Rudolph P, Gloeckner K, Parwaresch R, Harms D, Schmidt D. Immunophenotype, proliferation, DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study. Hum Pathol. Aug 1998;29(8):791-800. [Medline].

  63. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol. Aug 1998;11(8):728-34. [Medline].

  64. Strickland L, Letson GD, Muro-Cacho CA. Gastrointestinal stromal tumors. Cancer Control. May-Jun 2001;8(3):252-61. [Medline].

  65. Subramanian S, West RB, Corless CL, Ou W, Rubin BP, Chu KM, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. Oct 14 2004;23(47):7780-90. [Medline].

  66. van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. Oct 27 2001;358(9291):1421-3. [Medline].

  67. van Oosterom AT, Judson IR, Verweij J, Stroobants S, Dumez H, Donato di Paola E, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. Sep 2002;38 Suppl 5:S83-7. [Medline].

  68. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. Sep 25-Oct 1 2004;364(9440):1127-34. [Medline].

  69. Wardelmann E, Thomas N, Merkelbach-Bruse S, Pauls K, Speidel N, Buttner R, et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol. Apr 2005;6(4):249-51. [Medline].

  70. Zalupski M, Metch B, Balcerzak S, Fletcher WS, Chapman R, Bonnet JD, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. Jul 3 1991;83(13):926-32. [Medline].

 
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Gastric stromal tumor: Gross specimen following partial gastrectomy. Note the submucosal tumor mass with the classic features of central umbilication and ulceration. Image courtesy of Michael Choti, MD.
CT scan of the abdomen with oral contrast in a 60-year-old woman with gastric stromal tumor. A huge mass with central necrosis is observed originating from the gastric wall and narrowing its lumen. An ulcer crater can be identified within the mass (arrow). Image courtesy of Michael Choti, MD.
Gastric stromal tumor. Photomicrograph of gastrointestinal stromal tumor (GIST) stained with hematoxylin and eosin (H&E) and magnified 40 times. Note the solid sheet of spindle cells. Image courtesy of Michael Choti, MD.
Photomicrograph of a gastric stromal tumor stained with hematoxylin and eosin (H&E) and magnified 400 times. This stromal tumor demonstrates spindle cells with epithelioid features. Image courtesy of Michael Choti, MD.
Gastric stromal tumor: Photomicrograph of gastrointestinal stromal tumor (GIST) with immunohistochemical staining for CD117. Note the strong positive staining of tumor cells with negative staining of the adjacent vessel. Positive stain for CD117 is diagnostic of GIST. Image courtesy of Michael Choti, MD.
Liver resection specimen demonstrating 2 hepatic metastases from a gastrointestinal stromal tumor. Image courtesy of Michael Choti, MD.
Table 1. Survival in Patients Undergoing Resection of GISTs[12, 13, 14, 15, 16, 17]
ReferencePeriodPatients, No.Complete Resections, No.5-y Survival Rate After Complete Resection, %
Caterino et al1999-2009474665
DeMatteo et al1982-19982008054
Ng et al1957-19971919948
McGrath et al1951-1984513063
Shiu et al1949-1973382065
Akwari et al1950-19741085250
Table 2. Risk Classification for Primary GIST by Mitotic Index, Size, and Tumor Site. Adapted from AJCC.
Tumor Parameters Risk of Progressive Disease*
Mitotic



Index



SizeStomachDuodenumJejunum



or ileum



Rectum
≤5 per 50 HPF≤2cmNoneNoneNoneNone
>2 to ≤5 cmVery low (1.9%)Low (8.3%)Low (4.3%)Low (8.5%)
>5 to ≤10 cmLow (3.6%)Insufficient dataModerate (24%)Insufficient data
>10 cmModerate (10%)High (34%)High (52%)High (57%)
>5 per 50 HPF ≤2 cmNone*Insufficient dataHigh † High (54%)
>2 to ≤5 cmModerate (16%)High (50%)High (73%)High (52%)
>5 to ≤10 cmHigh (55%)Insufficient dataHigh (85%)Insufficient data
>10 cmHigh (86%)High (86%)High (90%)High (71%)
*Defined as metastasis or tumor-related death.



† Denotes small number of cases.



Data based on long-term follow up of 1055 gastric, 629 small intestinal, 144 duodenal, and 111 rectal GISTs.
Table 3. Proposed Staging System for Malignant Gastrointestinal Stromal Tumors[24]
GroupTNMMitosis
Stage IT1 or T2N0M0Low
Stage IIT3N0M0Low
Stage IIIAT1N0M0High
T4N0M0Low
Stage IIIBT2N0M0High
T3N0M0High
T4N0M0High
Stage IVAny TN1M0Any Rate
Any TAny NM1Any Rate
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