Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract.
GIST is typically characterized by immunohistochemical expression of c-kit. The interstitial cell of Cajal also expresses c-kit and CD34. Therefore, GIST is considered to show differentiation along the lines of interstitial cell of Cajal.
In the earlier literature, GIST was classified as a smooth muscle tumor variously termed leiomyoma, epithelioid leiomyoma, leiomyoblastoma, leiomyosarcoma, epithelioid leiomyosarcoma, or malignant leiomyoblastoma.
GIST of the digestive tract is now considered to be the distinctive entity, distinguished from leiomyoma, leiomyosarcoma, schwannoma, and other mesenchymal tumors.
MicroGISTs
Although Gastrointestinal stromal tumors (GISTs) affect about 0.0014% of the population, GISTs smaller than 1 cm (microGISTs) are detectable in about 20% to 30% of elderly individuals. This suggests that microGISTs likely represent premalignant precursors that evolve only in a minute fraction of cases toward overt GISTs. (20861712)
Small GISTs share with overt GIST KIT/PDGFRA mutation. Nevertheless, microGISTs display an overall lower frequency of mutations, particularly canonical KIT mutations, and also carry rare and novel mutations. (20861712)
These molecular features, together with the peculiar pathologic characteristics, suggest that the proliferation of these lesions is likely sustained by weakly pathogenic molecular events, supporting the epidemiologic evidence that microGISTs are self-limiting lesions. (20861712)
Etiology
sporadic GISTs
- gain-of-function mutations of c-kit receptor tyrosine kinase (KIT) gene
- gain-of-function mutations of PDGFR-alpha gene coding for platelet-derived growth factor receptor (PDGFRA) alpha (12949711)
NF-associated GISTs
Variants
KIT+ gastrointestinal stromal tumor
KIT- gastrointestinal stromal tumor
pediatric gastrointestinal stromal tumor (pediatric GIST)
NF1-associated gastrointestinal stromal tumor
Predisposition
neurofibromatosis type 1 (NF1) (16096406)
Carney triad (15712189)
Differential diagnosis (11215292)
digestive sarcomas
- digestive leiomyosarcoma
- digestive fibrosarcoma
Prognosis
local recurrence
metastasis
- ovary (15958857)
Cytogenetics
ploidy anomalies
- hypo- to near-diploid
- near-triploid
- hypotetraploid
loss of chromosome 14
loss of 22q: 22q13, (15580284)
loss of both chromosomes 14 and 22
loss of 9p21 (54%) (p16INK4a and p14ARF gene loss) (15929122)
loss of 1p
loss of 15
loss of 3p
loss of 13q
loss of 10q
loss of 19
CGH (14730211, 9406576, 16982739, 17330260)
CGH losses
CGH gains
allelic losses (loss of heterozygosity)
- 9p21 LOH (15181453)
- 14q LOH (47%-65%) (11123422, 10942800)
- 22q LOH (50%-75%) (15580284, 11123422, 10942800)
gene overpexpression and amplification (15864317)
Molecular biology
KIT overexpression (95%)
rare KIT amplification (15869870)
Videos
Gleevec
See also
STI-571 (imatinib mesylate, Gleevec)
anti-tyrosine kinase drug
References
Molecular and clinicopathologic characterization of gastrointestinal stromal tumors (GISTs) of small size. Rossi S, Gasparotto D, Toffolatti L, Pastrello C, Gallina G, Marzotto A, Sartor C, Barbareschi M, Cantaloni C, Messerini L, Bearzi I, Arrigoni G, Mazzoleni G, Fletcher JA, Casali PG, Talamini R, Maestra R, Dei Tos AP. Am J Surg Pathol. 2010 Oct;34(10):1480-91. PMID: 20861712
Liu H, Li W, Zhu S. Clinical images. Extragastrointestinal stromal tumor of lesser omentum mimicking a liver tumor. Am J Surg. 2009 Jan;197(1):e7-8. Epub 2008 Aug 29.
Assamaki R, Sarlomo-Rikala M, Lopez-Guerrero JA, Lasota J, Andersson LC, Llombart-Bosch A, Miettinen M, Knuutila S. Array comparative genomic hybridization analysis of chromosomal imbalances and their target genes in gastrointestinal stromal tumors. Genes Chromosomes Cancer. 2007 Jun;46(6):564-76. PMID: 17330260
Badalamenti G, Rodolico V, Fulfaro F, et al. Gastrointestinal stromal tumors (GISTs): focus on histopathological diagnosis and biomolecular features. Ann Oncol 2007;6:136–40.
Hirota M, Shimada S, Yamamoto K, et al. Pancreatectomy using the no-touch isolation technique followed by extensive intraoperative peritoneal lavage to prevent cancer cell dissemination: a pilot study. JOP 2005; 6:143–51.
Verweij J., van Oosterom A., Blay J.Y., Judson I., Rodenhuis S., van der Graaf W. , et al. Imatinib mesylate (STI-571 Glivec®, Gleevec®) is an active agent for gastrointestinal stromal tumors, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study Eur. J. Cancer 2003 ; 39 : 2006-2011.
Demetri G.D., von Mehren M., Blanke C.D., van den Abbeele A.D., Eisenberg B., Roberts P.J. , et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors N. Engl. J. Med. 2002 ; 347 : 472-480
Reith JD, Goldblum JR, Lyles RH, Weiss SW. Extragastrointestinal (Soft Tissue) stromal tumors: an analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 2000;13:577–85.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-offunction mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-80.
Yamamoto H, Oda Y, Kawaguchi K, Nakamura N, Takahira T, Tamiya S, Saito T, Oshiro Y, Ohta M, Yao T, Tsuneyoshi M. c-kit and PDGFRA mutations in extragastrointestinal stromal tumor (gastrointestinal stromal tumor of the soft tissue). Am J Surg Pathol 2004; 28:479-488.
Kim JH, Boo YJ, Jung CW, Park SS, KimSJ, Mok YJ, et al. Multiple malignant extragastrointestinal stromal tumors of the greater omentum and results of immunohistochemistry and mutation analysis: A case report. World J Gastroenterol 2007;13:3392-5.
Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006;23:70–83.
Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 1999; 30: 1213-20. Ann Chir Gynecol 1998;87:278–81.
Miettinen M, Majidi M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur J Cancer 2002; 38:39–51.
Miettinen M, Monihan JM, Sariomo RM, Kovavitch AJ, Carr NJ, Emory TS, et al. Gastrointestinal Stromal Tumors/Smooth muscle Tumors (GISTs) Primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol 1999; 23:1109–18.
Tervahartiala P., Halavaara J. Radiology of GIST Ann. Chir. Gynaecol. 1998 ; 87 : 291-292
Mazur MT, Clark HB. Gastric stromal tumours: Reappraisal of histogenesis. Am J Surg Pathol 1983; 7:507-19
