Radiologic-Pathologic CorrelationClinicopathologic study of 275 cases of gastrointestinal stromal tumors: the experience at 3 large medical centers in Mexico
Introduction
Gastrointestinal (GI) stromal tumors (GISTs) are uncommon mesenchymal tumors that arise in the wall of the GI tract. They account for approximately 0.1% to 3% of all GI neoplasms, with about 150 new cases per year diagnosed in the United States [1].
For many years, these tumors were called leiomyomas, epithelioid leiomyomas, leiomyoblastomas, and leiomyosarcomas, depending upon the histologic findings. In recent years, however, it has become clear that GISTs show remarkable cellular variability and histologic appearances, and that the tumor cells in these tumors may be able to differentiate toward a variety of cell types or may be undifferentiated [2], [3]. Recent work has indicated that the interstitial cells of Cajal (ICCs), a complex cellular network thought to act as pacemaker cells that exhibit both myoid and neural features, could be the candidates for this tumor's histogenesis. Expression of the c-kit protooncogene is essential for the slow-wave activity of ICCs and for the development of the ICC system. Although not limited to this cell type, c-kit expression is widely recognized as a molecular marker of ICCs [4], [5]. In one study, GISTs were reported to express the c-kit receptor, as did ICCs. Furthermore, gain of mutations has been reported in several GISTs. Mutations in the KIT gene lead to overexpression of the tyrosine kinase KIT protein. Heightened tyrosine kinase activity appears to drive the neoplastic growth of these tumors [6], [7], [8]. A new adjuvant therapeutic agent, ST1-571 (imatinib [Gleevec], Novartis Pharmaceuticals, Basel, Switzerland) reduces c-kit tyrosine kinase activity and seems to be a very promising treatment of metastatic GIST [9].
Because separating GISTs from other types of mesenchymal tumors can sometimes be difficult because of considerable phenotypic and immunohistochemical overlapping among them [10], [11], the first goal of this study was to aid pathologists in a busy community practice to arrive at a diagnosis or differential diagnosis of GISTs and tumors mimicking GISTs in day-to-day practice; on the other hand, because, to date [12], [13], only a few reports of large clinicopathologic series analyze if there are some differences in the immunohistochemical features between GISTs located in specific parts of the GI tract, the second goal of this series was to evaluate the possible differences of immunoexpression among tumors in different areas of the GI tract and their morphological patterns.
Section snippets
Materials and methods
Archival material accessioned in 3 large diagnostic medical centers in Mexico City (UMAE Oncología DF, UMAE Guadalajara, and UMAE Monterrey) between 1995 and 2004 were reviewed. One thousand six hundred GI or intra-abdominal mesenchymal tumors coded as sarcoma, leiomyoma, leiomyosarcoma, neurogenic sarcoma, or fibromatosis were retrieved for evaluation. All available slides were reviewed. The number of sections per tumor ranged from 6 to 38 (mean, 11). The diagnosis of GIST was made in those
Results
Of the 1600 cases studied, 23 with the previous diagnosis of GIST were reclassified as leiomyomas (9), poorly differentiated carcinomas (3), neuroendocrine carcinomas (malignant carcinoids) (2), inflammatory myofibroblastic tumors (2), pleomorphic sarcomas (2), mesenteric fibromatosis (2), malignant schwannomas/malignant peripheral nerve sheath tumor (2), and paraganglioma (1).
Among the remaining 1577 patients, 275 (17%) tumors were histologically classified as GISTs. Of these, 270 were primary
Discussion
Gastrointestinal stromal tumors are a rare but important group of tumors arising within the gastrointestinal tract [1]. For many years, these tumors were called leiomyoma, leiomyoblastoma, epithelioid leiomyoblastoma, and leiomyosarcoma, depending upon the histologic findings [2], [3]. The use of electron microscopy in the study of human tumors in the late 1960s and early 1970s showed that relatively few of these neoplasms displayed convincing ultrastructural evidence of smooth muscle
References (27)
- et al.
Gastrointestinal stromal tumors: recent advances in understanding of their biology
Hum Pathol
(1999) - et al.
C-Kit immunoreactive interstitial cells in the human gastrointestinal tract
J Auton Nerv Syst
(1999) - et al.
Kit extracellular and kinase domain mutations in gastrointestinal stromal tumors
Am J Pathol
(2000) OncoloGIST, BioloGIST, RadioloGIST: the big impact on the field of oncology of a molecularly-targeted therapy designed to treat a rare disease
Eur J Cancer
(2003)- et al.
Diagnosis of gastrointestinal stromal tumors: a consensus approach
Hum Pathol
(2002) - et al.
Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review
Hum Pathol
(2002) - et al.
Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis
Virchows Arch
(2001) - et al.
Gastrointestinal stromal tumors: new progress, new questions
Curr Opin Gastroenterol
(2004) - et al.
Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal
Am J Pathol
(1998) - et al.
Gain of function mutations of c-kit in human gastrointestinal stromal tumors
Science
(1998)
CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34
Mod Pathol
Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival
Ann Surg
Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management
Ann Surg Oncol
Cited by (36)
Gastrointestinal stromal tumor of the ampulla of Vater with osteoclastic giant cells, osteoid-like matrix deposition, and aneurysmal bone cyst-like features
2013, Annals of Diagnostic PathologyCitation Excerpt :Gastrointestinal stromal tumors are a heterogeneous group with a broad spectrum of histologic features, typically including spindle or epithelioid cells growing in fascicular, storiform, palisading, syncytial, myxoid pattern and focal to extensive hyalinization [1]. Alvarado-Cabrero et al [16] studied a series of 275 patients with GIST from 3 institutions in Mexico, including our own. They analyzed the histologic features of each tumor and found that the cell type included pure spindle (68%), pure epithelioid (16%), and mixed epithelioid/spindle cells (14%).
Perivascular epithelioid cell tumor of the sigmoid colon with transcription factor E3 expression
2012, Annals of Diagnostic PathologyCitation Excerpt :Although most GISTs (about 70%) show spindle cell histology, with only approximately 10% to 20% of cells being epithelioid, most intestinal PEComas contain epithelioid tumor cells only. In addition, a paraganglioma-like pattern is rarer in GISTs than in PEComas [22]. Immunohistochemistry detecting c-kit receptor tyrosine kinase (CD117), CD34, and HMB45 is of value in diagnosis because, unlike GISTs, PEComas express HMB-45, rarely express CD117, and are negative for CD34 [2].
Endoscopic Ultrasonography-Guided Diagnosis of Subepithelial Tumors
2012, Gastrointestinal Endoscopy Clinics of North AmericaCitation Excerpt :Around 90% of cases are diagnosed in patients older than 40 years, with a median age of 63 years.9,13 Most patients are symptomatic at presentation (70%–90%).9,22 Presentations include abdominal pain, gastrointestinal bleeding, nausea/vomiting, weight loss, early satiety, and gastrointestinal obstruction.22