Gastrointestinal stromal tumors: Pathology and prognosis at different sites
Section snippets
Esophageal GISTs
In the esophagus, GISTs are rare, and true leiomyomas are the most common mesenchymal tumors by a 3:1 margin. The relative frequency of esophageal GISTs is low, not exceeding 1% to 2% of all GISTs.8, 9 These tumors typically occur in the lower third of esophagus in older adults and vary from small incidental tumors to large masses. The larger tumors often cause dysphagia, but some form mediastinal masses with no apparent esophagus-related symptoms.
Histologically, esophageal GISTs vary from
Gastric GISTs
Gastric GISTs form a large, clinicopathologically complex group comprising a majority of all GISTs. Their relative frequency among all GISTs in three studies, including two population-based ones, varied in a narrow range of 59% to 61%.10, 11, 12 Median or mean ages of patients have varied in a range of 63 to 70 years, and several series have found a mild male predominance of 52% to 55%.13, 14, 15 Less than 1% of gastric GISTs occur in children, and <10% are diagnosed in patients under the age
Duodenal GISTs
Approximately 4% to 5% of all GISTs with specified location originate in the duodenum. They can occur in any part of the duodenum, but are most common in its second part.18, 19 Those tumors that arise in the second part can involve pancreas and clinically simulate a pancreatic tumor. One reported pancreatic GIST that also had duodenal wall involvement20 apparently represents a duodenal GIST with pancreatic extension. Clinicopathologic series have shown 35% to 50% tumor-related mortality.
Small intestinal GISTs
Small intestinal GISTs involving jejunum or ileum comprise approximately 30% of all GISTs with specified location. As a group, these GISTs are more often malignant than gastric GISTs with 40% to 50% tumor-related mortality with mortality being higher with tumors >5 cm or with mitotic rate >5 per 50 HPFs. Location in the jejunum is more common than in the ileum by a factor of 1.6:1, and in 2 studies, ileal tumors were found to be more commonly clinically malignant,12, 21 although in the latter,
Pathology of GIST of colon and appendix
GISTs of colon (excluding rectum) are rare comprising no more than 1% to 2% of all GISTs. They occur throughout the colon but seem to be more common on the left than the right side. Like other GISTs, they usually occur in older adults (median age of two series: 60 years).
A study on 20 colonic GISTs segregated them into 2 groups: those that metastasized, and those that did not. This study did not evaluate KIT expression. The two best predictive adverse prognostic factors were found to be high
Pathology of GISTs of rectum
GISTs of rectum comprise approximately 4% of all GISTs of defined localized origin, based on the AFIP series.28 They vary from incidental minimal tumors to sarcomas.28, 29, 30, 31, 32 Small tumors can be found during prostate or pelvic examination and have been incidentally detected in stapled hemorrhoidopexy specimens.33 Larger tumors are often symptomatic by rectal obstruction, bleeding, or both. Especially those rectal GISTs that involve the anterior rectal wall can extend to posterior
Extragastrointestinal GISTs
GISTs have been reported outside of the tubular GI tract as apparent primary tumors, sometimes designated as “extragastrointestinal GISTs” (EGISTs).34, 35, 36 However, a great majority of GISTs outside the GI tract are metastases from GI primaries. It is important to recognize GIST in this setting, and KIT immunostaining should therefore be performed on unclassified epithelioid and mesenchymal neoplasms in the abdomen, and also on suspected GIST metastases in peripheral tissues.
The frequency of
GISTs in children
Less than 1% of GISTs occur in children in the second decade at or under the age of 16 years, and these tumors have a strong (90%) predilection to stomach and female patients and are more common in antrum.47, 48 The majority of these GISTs (75%) have epithelioid morphology, and few are associated with Carney Triad in combination with pulmonary chondroma, paraganglioma, or both. However, Carney triad is not exclusive to pediatric age.49 Prognosis of pediatric GISTs varies and seems to be
GISTs in neurofibromatosis type 1 (NF1) patients
NF1 patients have a significant predisposition to GISTs.50, 51, 52, 53 In our experience, 5% to 7% of duodenal jejunoileal GISTs occur in the setting of NF1, and GISTs are the most common GI mesenchymal tumors in these patients markedly outnumbering nerve sheath tumors. One study on 100 consecutive GIST patients found the frequency of NF1 to be 5%, a 150-fold enrichment from the overall incidence of NF1, which is 1:3000.51 The NF1-associated GISTs typically occur in small intestine and only
Immunohistochemical features of GIST
The key feature of GIST is positivity for the KIT (CD117), as observed in >95% of cases. Although KIT-positivity is a major defining feature for GIST, it is no longer considered an absolute requirement. Other, commonly expressed but less GIST-specific antigens are CD34, nestin, and protein kinase C theta. GISTs are variably positive for smooth muscle markers but are generally negative for desmin. Positivity for S100 protein is rare, and GFAP is absent. Keratins and neurofilaments are
Evaluation of biologic potential of GISTs
GISTs have a wide spectrum of biologic potential at all sites of their occurrence, ranging from minute nearly uniformly indolent tumors to sarcomas. Older studies on GI smooth muscle tumors (largely reflecting GISTs in modern terminology) often reported separately on benign and malignant tumors creating an illusion of a distinct separation between benign and malignant GISTs. Because criteria of separation were not precisely stated, it is impossible to determine predictive parameters based on
References (91)
- et al.
Extragastrointestinal (soft tissue) stromal tumorsAn analysis of 48 cases with emphasis on histological predictors of outcome
Mod Pathol
(2000) - et al.
Uterine gastrointestinal stromal tumor
Gynecol Oncol
(2005) - et al.
Malignant stromal tumor, so called “gastrointestinal stromal tumor”, with rhabdomyomatous differentiation occurring in the gallbladder
Pathol Res Pract
(2005) Gastric stromal sarcoma, pulmonary chondroma, and extra-adrenal paraganglioma (Carney triad): natural history, adrenocortical component, and possible familial occurrence
Mayo Clin Proc
(1999)- et al.
A great majority of GISTs with PDGFRA mutations represent gastric tumors with low or no malignant potential
Lab Invest
(2004) - et al.
The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status
Am J Pathol
(2004) - et al.
Blockade of kit signaling induces transdifferentiation of interstitial cells of Cajal to a smooth muscle phenotype
Gastroenterology
(1999) - et al.
Embryonic form of smooth muscle myosin heavy chain (SMEmb/MHC-B) is gastrointestinal stromal tumor and interstitial cell of Cajal
Am J Pathol
(1999) - et al.
Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal
Am J Pathol
(2001) - et al.
Diagnosis of gastrointestinal stromal tumors: a consensus approach
Hum Pathol
(2002)
Prognostic significance of expressions of cell-cycle regulatory proteins in gastrointestinal stromal tumor and the relevance of the risk grade
Hum Pathol
Immunophenotype, proliferation
DNA ploidy, and biological behavior of gastrointestinal stromal tumors: a multivariate clinicopathologic study
Molecular analysis of the 9p21 locus and p53 genes in Ewing family tumors
Lab Invest
Loss of heterozygosity of chromosome 9p and loss of p16 INK4A expression are associated with malignant gastrointestinal stromal tumors
Mod Pathol
Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors markers with potential prognostic implications
Hum Pathol
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors
Science
Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal
Am J Pathol
Gastrointestinal stromal tumors (GISTs): -Definition, occurrence, pathology, differential diagnosis and molecular genetic features
Pol J Pathol
Gastrointestinal autonomic nerve tumor: immunohistochemical and molecular identity with gastrointestinal stromal tumor
Am J Surg Pathol
Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site
Clin Cancer Res
Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles
Oncogene
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors
N Engl J Med
Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas
Am J Surg Pathol
Gastrointestinal stromal tumors in Koreans: its incidence and the clinical, pathologic and immunohistochemical findings
J Korean Med Sci
Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era: a population-based study in western Sweden
Cancer
Gastrointestinal stromal tumors in Iceland, 1990-2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study
Int J Cancer
Gastrointestinal stromal tumors (GISTs) of the jejunum and ileum: a clinicopathologic, immunohistochemical and molecular genetic study of 906 cases prior to imatinib with long-term follow-up
Am J Surg Pathol
Gastric stromal tumorsA clinicopathologic study of 77 cases with correlation of features with non-aggressive and aggressive behaviors
Am J Surg Pathol
Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach
Histopathology
Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic studies of 1765 cases with long-term follow-up
Am J Surg Pathol
“Seedling” mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common in the esophagogastric region
Mod Pathol
Gastric epithelioid leiomyoma and leiomyosarcoma (leiomyoblastoma)
Cancer
Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas of the duodenum: a clinicopathologic, immunohisto-chemical, and molecular genetic study of 167 cases
Am J Surg Pathol
Stromal tumors of the duodenumA histologic and immunohistochemical study of 20 cases
Am J Surg Pathol
Gastrointestinal stromal tumors of the pancreas: case report with documentation of KIT gene mutation
Virchows Arch
Stromal tumors of the jeujunum and ileum
Mod Pathol
Small intestinal stromal tumors with skeinoid fibersClinicopathological, immunohistochemical, and ultrastructural investigations
Am J Surg Pathol
Stromal tumors of the jejunum and ileum: a clinicopathologic study of 39 cases
Am J Surg Pathol
Gastrointestinal stromal tumors: an ultrastructural study
Int J Surg Pathol
Stromal tumors of the abdominal colonA clinicopathologic study of 20 cases
Am J Surg Pathol
Gastrointestinal stromal tumors and leiomyosarcomas in the colonA clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases
Am J Surg Pathol
Gastrointestinal stromal tumors in the appendixA clinicopathologic and immunohistochemical study of four cases
Am J Surg Pathol
Appendiceal gastrointestinal stromal tumorLetter to the editor
Am J Surg Pathol
Stromal tumors of the anorectumA clinicopathologic study of 22 cases
Am J Surg Pathol
Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anusA clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases
Am J Surg Pathol
Cited by (1569)
Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence
2024, Computational and Structural Biotechnology JournalHarnessing the supremacy of MEG3 LncRNA to defeat gastrointestinal malignancies
2024, Pathology Research and PracticeA nomogram for predicting liver metastasis in patients with gastric gastrointestinal stromal tumor
2024, Journal of Gastrointestinal SurgeryNonmesothelial Spindle Cell Tumors of Pleura and Pericardium
2024, Surgical Pathology Clinics
The opinions and assertions contained herein are the expressed views of the authors and are not to be construed as official or reflecting the views of the Departments of the Army or Defense.