Clin Colon Rectal Surg 2006; 19(2): 069-077
DOI: 10.1055/s-2006-942347
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Colorectal Gastrointestinal Stromal Tumors: A Brief Review

Rishindra M. Reddy1 , James W. Fleshman2
  • 1Department of Surgery, Washington University School of Medicine, St. Louis, Missouri
  • 2Section of Colon and Rectal Surgery; Washington University School of Medicine, St. Louis, Missouri
Further Information

Publication History

Publication Date:
23 May 2006 (online)

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are rare lesions that constitute the majority of mesenchymal tumors in the gastrointestinal tract. Within the colon and rectum, they represent 0.1% of all cancers. They can present with a variety of symptoms but are often asymptomatic. Although many lesions may be benign, up to half of patients develop recurrent disease within a few years. Almost all GISTs contain a mutation in the c-kit tyrosine kinase that leads to its constitutive activation and results in cell proliferation. This discovery has led to the immunostaining of the c-kit antigen (CD117) to distinguish GISTs from other malignancies. Radiologic examinations can be helpful in initial diagnosis and staging. Surgery is the best treatment for cure, but recent advances have led to the use of imatinib mesylate, a tyrosine kinase inhibitor, to treat metastatic or unresectable disease, or both. There are currently many clinical trials available to help treat GISTs.

REFERENCES

  • 1 Pidhorecky I, Cheney R T, Kraybill W F, Gibbs J F. Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management.  Ann Surg Oncol. 2000;  7 705-712
  • 2 Miettinen M, Majidi M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review.  Eur J Cancer. 2002;  38(suppl 5) S39-S51
  • 3 Stout A P. Bizarre smooth muscle tumors of the stomach.  Cancer. 1962;  15 400-409
  • 4 Appelman H D. Smooth muscle tumors of the gastrointestinal tract. What we know now that Stout didn't know.  Am J Surg Pathol. 1986;  10(suppl 1) 83-99
  • 5 Mazur M T, Clark H B. Gastric stromal tumors: reappraisal of histogenesis.  Am J Surg Pathol. 1983;  7 507-519
  • 6 Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology.  Hum Pathol. 1999;  30 1213-1220
  • 7 Nilsson B, Bumming P, Meis-Kindblom J M et al.. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era.  Cancer. 2005;  103 821-829
  • 8 Robinson T L, Sircar K, Hewlett B R, Chorneyko K, Riddel R H, Huizinga J D. Gastrointestinal stromal tumors may originate from a subset of CD34-positive interstitial cells of Cajal.  Am J Pathol. 2000;  156 1157-1163
  • 9 Sircar K, Hewlett B R, Huizinga J D, Chorneyko K, Berezin I, Riddell R H. Interstitial cells of Cajal as precursors for gastrointestinal stromal tumors.  Am J Surg Pathol. 1999;  23 377-389
  • 10 Kindblom L G, Remotti H E, Aldenborg F, Meis-Kindblom J M. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.  Am J Pathol. 1998;  152 1259-1269
  • 11 Berman J, O'Leary T J. Gastrointestinal Stromal Tumor Workshop.  Hum Pathol. 2001;  32 578-582
  • 12 Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin L H, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases.  Am J Surg Pathol. 2001;  25 1121-1133
  • 13 Hirota S, Isozaki K, Moriyama Y et al.. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.  Science. 1998;  279 577-580
  • 14 http://www.glivec.com/images/
  • 15 Tuveson D A, Willis N A, Jacks T et al.. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.  Oncogene. 2001;  20 5054-5058
  • 16 Hirota S, Nishida T, Isozaki K et al.. Gain-of-function mutation at the extracellular domain of KIT in gastrointestinal stromal tumours.  J Pathol. 2001;  193 505-510
  • 17 van der Zwan S M, DeMatteo R P. Gastrointestinal stromal tumor: 5 years later.  Cancer. 2005;  104 1781-1788
  • 18 Tran T, Davila J A, El-Serag H B. The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992 to 2000.  Am J Gastroenterol. 2005;  100 162-168
  • 19 Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S. Gastrointestinal stromal tumors: consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade.  Hum Pathol. 2002;  33 669-676
  • 20 Miettinen M, Sarlomo-Rikala M, Sobin L H, Lasota J. Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases.  Am J Surg Pathol. 2000;  24 1339-1352
  • 21 Conlon K C, Casper E S, Brennan M F. Primary gastrointestinal sarcomas: analysis of prognostic variables.  Ann Surg Oncol. 1995;  2 26-31
  • 22 DeMatteo R P, Lewis J J, Leung D, Mudan S S, Woodruff J M, Brennan M F. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.  Ann Surg. 2000;  231 51-58
  • 23 Burkill G JC, Badran M, Al-Muderis O et al.. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread.  Radiology. 2003;  226 527-532
  • 24 Orosz Z, Tornoczky T, Sapi Z. Gastrointestinal stromal tumors: a clinicopathologic and immunohistochemical study of 136 cases.  Pathol Oncol Res. 2005;  11 11-21
  • 25 Greenson J K. Gastrointestinal stromal tumors and other mesenchymal lesions of the gut.  Mod Pathol. 2003;  16 366-375
  • 26 Horton K M, Juluru K, Montogomery E, Fishman E K. Computed tomography imaging of gastrointestinal stromal tumors with pathology correlation.  J Comput Assist Tomogr. 2004;  28 811-817
  • 27 Emory T S, Sobin L H, Lukes L, Lee D H, O'Leary T J. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site.  Am J Surg Pathol. 1999;  23 82-87
  • 28 Tateishi U, Hasegawa T, Satake M, Moriyama N. Gastrointestinal stromal tumor; correlation of computed tomography findings with tumor grade and mortality.  J Comput Assist Tomogr. 2003;  27 792-798
  • 29 Kurokawa Y, Nishisho I, Kawahara K, Mishima H, Hirota S, Kikkawa N. Gastrointestinal stromal tumor of the rectum with activating mutation of c-kit: report of a case.  Dis Colon Rectum. 2000;  43 1316-1318
  • 30 Shibata Y, Ueda T, Seki H, Yagihashi N. Gastrointestinal stromal tumour of the rectum.  Eur J Gastroenterol Hepatol. 2001;  13 283-286
  • 31 Michalopoulos A, Papadopoulos V N, Basdanis G et al.. Colorectal gastrointestinal mesenchymal tumours. Report of a stromal case of the rectum (GIST) and leiomyosarcoma of the transverse colon.  Tech Coloproctol. 2004;  8(suppl 1) s155-s157
  • 32 Lo S S, Papachristou G I, Finkelstein S D, Conroy W P, Schraut W H, Ramanathan R K. Neoadjuvant imatinib in gastrointestinal stromal tumor of the rectum: report of a case.  Dis Colon Rectum. 2005;  48 1316-1319
  • 33 Gupta S, Punia R S, Kaushik R. Gastrointestinal stromal tumour of the colon presenting with intestinal obstruction.  Indian J Cancer. 2004;  41 175-177
  • 34 Neuhaus S J, Clark M A, Hayes A J, Thomas J M, Judson I. Surgery for gastrointestinal tumour in the post-imatinib era.  ANZ J Surg. 2005;  75 165-172
  • 35 Levy A D, Remotti H E, Thompson W M, Sobin L H, Miettinen M. Anorectal gastrointestinal stromal tumors: CT and MR imaging features with clinical and pathologic correlation.  AJR Am J Roentgenol. 2003;  180 1607-1612
  • 36 Tworek J A, Goldblum J R, Weiss S W, Greenson J K, Appelman H D. Stromal tumors of the anorectum: a clinicopathologic study of 22 cases.  Am J Surg Pathol. 1999;  23 946-954
  • 37 McGrath P C, Neifeld J P, Lawrence Jr W, Kay S, Horsley III J S, Parker G A. Gastrointestinal sarcomas. Analysis of prognostic factors.  Ann Surg. 1987;  206 706-710
  • 38 Hama Y, Okizuka H, Odajima K, Hayakawa M, Kusano S. Gastrointestinal stromal tumor of the rectum.  Eur Radiol. 2001;  11 216-219
  • 39 Van den Berg J C, van Heesewijk J P, van Es H W. Malignant stromal tumour of the rectum: findings at endorectal ultrasound and MRI.  Br J Radiol. 2000;  73 1010-1012
  • 40 Hsieh J S, Huang C J, Wang J Y, Huang T J. Benefits of endorectal ultrasound for management of smooth-muscle tumor of the rectum: report of three cases.  Dis Colon Rectum. 1999;  42 1085-1088
  • 41 Connolly E M, Gaffney E, Reynolds J V. Gastrointestinal stromal tumours.  Br J Surg. 2003;  90 1178-1186
  • 42 Fletcher C D, Berman J J, Corless C et al.. Diagnosis of gastrointestinal stromal tumors: a consensus approach.  Hum Pathol. 2002;  33 459-465
  • 43 Tworek J, Goldblum J R, Weiss S W, Greenson J K, Appelman H D. Stromal tumors of the abdominal colon: a clinicopathologic study of 20 cases.  Am J Surg Pathol. 1999;  23 937-945
  • 44 Miettinen M, Sobin L H, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT).  Mod Pathol. 2000;  13 1134-1142
  • 45 Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics.  Pol J Pathol. 2003;  54 3-24
  • 46 Sarlomo-Rikala M, Kovatich A J, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34.  Mod Pathol. 1998;  11 728-734
  • 47 Yamaguchi U, Hasegawa T, Masuda T et al.. Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis.  Virchows Arch. 2004;  445 142-150
  • 48 Daum O, Hes O, Vanecek T et al.. Vanek's tumor(inflammatory fibroid polyp). Report of 18 cases and comparison with three cases of original Vanek's series.  Ann Diagn Pathol. 2003;  7 337-347
  • 49 Miettinen M, Sarlomo-Rikala M, Sobin L H. Mesenchymal tumors of muscularis mucosae of colon and rectum are benign leiomyomas that should be separated from gastrointestinal stromal tumors-a clinicopathologic and immunohistochemical study of eighty-eight cases.  Mod Pathol. 2001;  14 950-956
  • 50 Dougherty M J, Compton C, Talbert M, Wood W C. Sarcomas of the gastrointestinal tract. Separation into favorable and unfavorable prognostic groups by mitotic count.  Ann Surg. 1991;  214 569-574
  • 51 Lee C H, Jan Y J, Chen J T, Ho W L, Tseng C H, Wang J. Colorectal mesenchymal tumor: a clinicopathologic study of 25 cases.  J Chin Med Assoc. 2005;  68 291-298
  • 52 Haque S, Dean P J. Stromal neoplasms of the rectum and anal canal.  Hum Pathol. 1992;  23 762-767
  • 53 Chak A, Canto M I, Rosch T et al.. Endosonographic differentiation of benign and malignant stromal cell tumors.  Gastrointest Endosc. 1997;  45 468-473
  • 54 Taniguchi M, Nishida T, Hirota S et al.. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors.  Cancer Res. 1999;  59 4297-4300
  • 55 Sturgeon C, Chejfec G, Espat N J. Gastrointestinal stromal tumors: a spectrum of disease.  Surg Oncol. 2003;  12 21-26
  • 56 Plaat B E, Hollema H, Molenaar W M et al.. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins.  J Clin Oncol. 2000;  18 3211-3220
  • 57 Masuoka H, Kawagishi N, Inoue T et al.. Giant hepatic metastasis from gastrointestinal stromal tumor of the rectum 12 years after surgery.  Hepatogastroenterology. 2003;  50 1454-1456
  • 58 Lanteri R, Aliotta I, Racalbuto A, Licata A. Anal GIST in older old patient: a case report.  G Chir. 2005;  26 135-137
  • 59 Van Oosterom A T, Judson I, Verweij J et al.. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumors: a phase I study.  Lancet. 2001;  358 1421-1423
  • 60 Demetri G D, von Mehren M, Blanke C D et al.. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.  N Engl J Med. 2002;  347 472-480
  • 61 Van Glabbeke M, Verweij J, Casali P G et al.. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study.  J Clin Oncol. 2005;  23 5795-5804
  • 62 Dagher R, Cohen M, Williams G et al.. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors.  Clin Cancer Res. 2002;  8 3034-3038
  • 63 Vanel D, Albiter M, Shapeero L et al.. Role of computed tomography in the follow-up of hepatic and peritoneal metastases of GIST under imatinib mesylate treatment: a prospective study of 54 patients.  Eur J Radiol. 2005;  54 118-123
  • 64 Joensuu H, Roberts P J, Sarlomo-Rikala M et al.. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor.  N Engl J Med. 2001;  344 1052-1056
  • 65 Antoch G, Kanja J, Bauer S et al.. Comparison of PE, CT, and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors.  J Nucl Med. 2004;  45 357-365
  • 66 Scaife C L, Hunt K K, Patel S R et al.. Is there a role for surgery in patients with “unresectable” cKIT + gastrointestinal stromal tumors treated with imatinib mesylate?.  Am J Surg. 2003;  186 665-669
  • 67 Koon N, Schneider-Stock R, Sarlomo-Rikala M et al.. Molecular targets for tumour progression in gastrointestinal stromal tumours.  Gut. 2004;  53 235-240
  • 68 http://www.cancer.gov/clinicaltrials/

Rishindra M ReddyM.D. 

Department of Surgery, Washington University School of Medicine, House Staff Office

Campus Box 8109, 1701 West Bldg., 660 S. Euclid Ave., St. Louis, MO 63110

Email: reddyr@wudosis.wustl.edu

    >