Radiologic-Pathologic Correlation
Clinicopathologic study of 275 cases of gastrointestinal stromal tumors: the experience at 3 large medical centers in Mexico

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Abstract

It is important to distinguish gastrointestinal (GI) stromal tumors (GISTs) from other GI mesenchymal tumors (GIMTs) because of the availability of molecular-targeted therapy for GISTs. The aim of the study was to reclassify GIMTs and to determine the clinicopathologic features of GISTs in Mexico. Cases of GIMT identified from the database of 3 large diagnostic centers in Mexico between 1995 and 2004 were reclassified according to current criteria. Hematoxylin and eosin–stained sections and clinical histories were reviewed, and immunohistochemistry was performed using anti-CD117, CD34, smooth muscle actin, and S-100 protein. A total of 275 GISTs were identified. The tumors were located in the stomach (40%), small intestine (35%), colorectum (12%), abdominal cavity (11%), and esophagus (2%). There were equal numbers of men and women with a mean age at diagnosis of 61 years. The tumors ranged in size from 3.5 to 34 cm (mean, 9.1 cm); 95 tumors (34%) were larger than 10 cm. Colorectal and omental tumors were the largest. The cell types included pure spindle (68%), pure epithelioid (16%), and mixed epithelioid/spindle (14%). Whereas 17.8% of tumors were regarded as low risk, 43% of tumors were in the high-risk category. CD117 positivity was detected in most of the tumors (96%). In addition to CD117, 255 cases (92%) were positive for CD34, 82 cases (32%) were positive for smooth muscle actin, and 13 cases (4.7%) were positive for desmin. Gastrointestinal stromal tumors in Mexico have the same clinicopathologic and immunohistochemical features as those reported in other countries. It is not always easy to distinguish GISTs from other soft tissue lesions. The diagnosis can be difficult even for experienced pathologists.

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

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