Gastrointestinal mesenchymal tumors – immunophenotypic classification and survival analysis

Abstract

The current definition of gastrointestinal tumors (GIST) as CD117-positive mesenchymal tumors of uncertain malignant potential fails to include a number of cases with similar histology. In an attempt to improve the classification of these neoplasms, we conducted an immunohistochemical analysis of 244 mesenchymal tumors with histological features of GIST. According to their immunophenotype, the tumors were classified as GISTs, which are characterized by CD117 (c-kit) expression; gastrointestinal CD117-negative CD34 positive stromal tumors (GINST); alpha-smooth muscle actin and/or desmin positive gastrointestinal leiomyogenic tumors (GILT); S-100 and glial fibrillary acidic protein positive gastrointestinal glial/schwannian tumors (GIGT); gastrointestinal neuronal/glial tumors (GINT), which are positive for S-100/glial fibrillary acidic protein plus neuronal/glial markers; and gastrointestinal fibrous tumors (GIFT), which are only vimentin positive. The most common type of tumors were GIST, followed in order of frequency by GINST, GILT, GIGT, GIFT, and GINT. GISTs did not show any preferential location, whereas GINSTs occurred almost exclusively in the stomach and duodenum, and GILTs preferentially in the large intestine. Over a median follow-up period of 71 months, malignant behavior, i.e., metastatic spread, was observed in all tumor types except GINTs. Malignancy was associated with distal gut location, high mitotic activity, large tumor size, and nuclear pleomorphism, though none of these criteria alone discriminated between benign and malignant. Kaplan-Meier analysis of disease-specific survival showed significant differences in the long-term outcome of the newly defined subgroups. We conclude that, despite strong morphological similarities, gastrointestinal mesenchymal tumors are heterogeneous in their immunophenotype and biology.

Cellular hamartoma resembling gastrointestinal stromal tumor: a solid tumor of the pancreas expressing c-kit (CD117)

“…[12][13][14][15][16] Gain-offunction mutations of the c-kit gene lead to stem cell factor-independent activation of intracytoplasmic signal transduction and finally tumor growth and differentiation. c-kit mutations have been found in mast cell tumors 17 and gastrointestinal stromal tumors (GISTs), 18 which are classified on the basis of About two-thirds of GISTs coexpress CD34 19,20 and/or bcl-2. 9,10,21-23 Expression of c-kit, CD34 and bcl-2 in the stromal elements suggests a GIST, which may also occur outside the gut.…”

Mesenchymal Tumors of Gastrointestinal Tract- The Role of Immunohistochemistry in Characterizing Specific Tumors

“…Study by Rudoph. P et al on 244 cases of mesenchymal tumors of GIT state that GISTs were diagnosed when the tumors showed CD-117 positivity (13) . SMA and / or Desmin positive tumors were diagnosed as leiomyogenic, S-100 positive tumors as schwannian and vimentin only positive tumors as Gastrointestinal fibrous tumors.…”

Primary gastrointestinal stromal tumors: Current advances in diagnostic biomarkers, prognostic factors and management of its duodenal location

“…It can also be seen in the omentum, mesentery, and retroperitoneum (1)(2)(3). GIST was historically classified as smooth muscle, nerve sheath or autonomic nerve tumors (4)(5)(6)(7)(8)(9)(10)(11); actually GIST were first described by Golden and Stout (12) as a set of mesenchymal tumors arising in the bowel wall in 1941, however, until 1983 when Mazur and Clark (13) first introduced the term "stromal tumors" for these mesenchymal tumors, the terminology and understanding of GIST were still in chaos. The second milestone for GIST took place in 1998, when Japanese researchers Hirota and his colleagues (14) presented that most GIST possessed CD117 (c-kit) mutations that resulted in full-length KIT proteins with ligandindependent activation, and also discovered that most GIST were positive for CD117.…”