Differentiation and Risk Assessment of Gastrointestinal Stromal Tumors

Franquemont, Douglas W.

doi:10.1093/ajcp/103.1.41

Cited by 296 publications

(220 citation statements)

References 69 publications

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“…They postulated that these lesions display various lines of differentiation reflecting the various elements of the gut wall (e.g., muscle, autonomic nerve) and proposed the term (gastrointestinal) stromal tumor (GIST). Over the past few years, it has become increasingly apparent that these tumors need to be studied on a sitespecific basis because of differences in behavior (2,9) and that malignancy is best described in terms of risk factors (10). Although numerous studies have addressed these issues in GIST (11)(12)(13)(14)(15)(16)(17)(18)(19)(20), there has been no study of those rare stromal tumors that develop outside the gastrointestinal tract in the soft tissues of the abdomen with respect to histologic features that predict outcome.…”

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confidence: 99%

Extragastrointestinal (Soft Tissue) Stromal Tumors: An Analysis of 48 Cases with Emphasis on Histologic Predictors of Outcome

et al. 2000

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The clinicopathologic features of 48 tumors that were histologically similar to gastrointestinal stromal tumors but occurred in the soft tissues of the abdomen were analyzed to determine their overall similarity to their gastrointestinal counterpart, their biologic behavior, and the parameters that predict risk for adverse outcome. Classic leiomyomas and leiomyosarcomas were specifically excluded. The tumors occurred in 32 women and 16 men, who ranged in age from 31 to 82 years (mean, 58 years). Forty tumors arose from the soft tissue of the abdominal cavity, and the remainder arose from the retroperitoneum. They ranged in size from 2.1 to 32.0 cm and varied from tumors composed purely of rounded epithelioid cells to those composed of short fusiform cells set in a fine fibrillary collagenous background with some cases showing a mixed pattern. Tumors displayed variable amounts of stromal hyalinization, myxoid change, and cyst formation. The tumors expressed CD117 (c-kit receptor) (100%), CD34 (50%), neuron-specific enolase (44%), smooth muscle actin (26%), desmin (4%), and S-100 protein (4%). Tumors were evaluated with respect to several parameters: size (<10 cm or >10 cm), cellularity (low or high), mitoses (0 to 2 per 50 high-power fields, >2 per 50 high-power fields), nuclear atypia (1 to 3؉), cell type (epithelioid, spindled, or mixed), and necrosis (absent or present). These parameters were then evaluated in univariate and multivariate analysis with respect to adverse or nonadverse outcome, the former defined as metastasis or death from tumor. Follow-up information was obtained for 31 patients (range, 4 to 84 months; median, 24 months). One patient presented with an adverse event and, therefore, was excluded from subsequent analysis. Twelve patients (39%) developed metastases or died of tumor. In univariate analyses, cellularity, mitotic activity (>2 per 50 high-power fields), and necrosis were associated with statistically significant increases in the risk for adverse outcome. Despite the relatively small sample size, in a multivariable analysis mitotic activity (relative risk, 7.46; P ‫؍‬ .09) and necrosis (relative risk, 3.75; P ‫؍‬ .07) displayed trends toward independent predictive value. Mesenchymal tumors that arise from the wall of the gastrointestinal tract have attracted a great deal of attention over the years. It is generally accepted that those that arise from the esophagus and rectum recapitulate the appearance of mature smooth muscle (1-3), whereas the vast majority of tumors that arise from the remainder of the gastrointestinal

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confidence: 99%

Extragastrointestinal (Soft Tissue) Stromal Tumors: An Analysis of 48 Cases with Emphasis on Histologic Predictors of Outcome

et al. 2000

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“…It suggests that the origin of GISTs is from smooth muscles of blood vessels rather than muscularis mucosae or propria. IHe studies demonstrate no correlation of the tumor grade with the immunoreactivity [7,16].…”

Section: Discussionmentioning

confidence: 91%

“…The importance of mitotic figures have been accepted uniformly by various authors to separate benign from malignant lesions, but with variable number. However most workers considered unfavourable outcome of the case if the number of mitotic figures were more than 5 in 50 high power fields [2][3][4][5][6][7]16]. Poor prognosis was also predicted, if in addition to the criteria of the tumor size it showed high cellularity, absence of predominant organoid growth pattern and absence of skeinoid fibres on microscopic examination.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Stromal Tumours

Chand

Chatterjee

2000

Medical Journal Armed Forces India

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The histogenesis of 10 spindle cell tumors of gastrointestinal tract (GIT) of last three years of our institution was studied, on the basis of immunohistochemical (rnC) staining. The tumours were categorized into benign, borderline malignant and malignant, mainly based on the histologic parameters (HP) such as predominant cell type, cellularity, type of growth pattern, mitotic figures etc. The study included 7 males and 3 females in the age group from 21 to 56 years. 4 tumors were located in stomach and 6 in the small intestine. The initial symptoms included pain abdomen, palpable mass and general weakness. There were 7 benign, 1 borderline and 2 malignant leiomyomatous tumors according to the histologic parameters we followed. Vimentin, desmin, S-100, and non-specific enolase (NSE) were the immunological markers used to identify the cellular lineage. Smooth muscle differentiation was demonstrated by nine (6 benign and 3 malignant) tumours. One male patient (Case 1), originally reported as leiomyoma based on HP, was positive for S-100 and NSE. Another case, a female, categorised as leiomyosarcoma, showed dual differentiation toward myogenic and neural elements on IHC staining (Case 2). IHC study played important role in the identification of cellular differentiation of these tumors as the same was not possible on light microscopic findings alone. MJAFI 2000; 56 : 40-44

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“…However, the differentiation between benign and malignant myogenic tumors can be endosonographically difficult. Several criteria have been suggested to indicate malignancy including size (> 3 cm), irregular border and the presence of internal cystic spaces [25,29,30]. Surgical resection has classically been recommended for those lesions with suspicious features.…”

Section: Gastrointestinal Stromal Tumors (Gist)mentioning

confidence: 99%

“…This receptor, the product of the proto-oncogene c-kit (located on chromosome 4q11-q12), can be detected by immunohistochemical staining for CD117. All GISTs are immunohistochemically positive for KIT (CD117) [27,28,25]. Although many other tumor types could be CD117 positive, most of them do not occur in the gastrointestinal tract.…”

Section: Gastrointestinal Stromal Tumors (Gist)mentioning

confidence: 99%

Molecules and markers for endosonographers: What do we need to know and measure?

Al‐Haddad

Wallace²

2006

Endoscopy

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IntroductionEndoscopic ultrasound (EUS) has become an indispensable tool for the diagnosis and staging for gastrointestinal and thoracic malignancies. Thanks to the safety and reliability of fine needle aspiration (FNA), this has become the method of choice for tissue acquisition from lymph nodes and tumors in various locations within the thoracic and abdominal cavities.In the recent years, EUS-FNA has offered a better understanding of the pathophysiology of cancer. Similar to the adenoma-carcinoma sequence, other cancers including pancreas, lung, and esophagus may follow a comparable multi-step process of carcinogenesis. A necessary component of these is the ability to go ªbeyond cytologyº to use fine needle aspirates to characterize the genomic and proteomic profiles of cancer and precancerous tissue. Molecular characterization of FNA samples: The basic conceptsAlthough DNA is relatively stable in excised tissue, proteins and particularly RNA are unstable and must be handled in special ways to preserve them for characterization. The first role of the endoscopist is to obtain and preserve tissue suitable for further molecular characterization. In the first part of this review, we will focus on these initial steps. The methods for genomic and proteomic analyses are beyond the scope of this article and interested readers are referred to recent reviews [1,2].RNA destroying-enzymes (RNAase enzymes) are very ubiquitous in the environment. Therefore, it is imperative to prevent rapid degradation of RNA in order to preserve fine needle aspirates for genomic studies. The simplest method to do this is through the use of RNAase inhibitor solutions such as RNA-later (Quagen Inc. Valencia Ca, USA) or RNA Stat 60 (RNA STAT-60 ; TEL-TEST, Friendswood, TX, USA). The needle aspirate can be quickly mixed with these reagents. In our laboratory, we immediately place the FNA sample into an eppendorf tube in a wet ice bath, centrifuge in a small desktop device in the EUS room (1000 RPM at 4 deg. C, 1 minute), remove the supernatant, and resuspend the cell pellet in RNA stat 60. If RNA stabilization is not available on-site, the aspirate can also be snap frozen in liquid nitrogen and stored (preferably at ±70 to ±80C) for later RNA stabilization. Every effort should be made to handle the specimen in an RNAase-free environment including clean gloves and a surface that has been cleaned with an RNAase inhibitor solution.In the remainder part of this review, we will focus on organspecific applications of the biological markers. This will include lesions of the pancreas and gastrointestinal stromal tumors (GIST). The use of biomarkers in staging non-small call lung cancer will be discussed in a separate review. Pancreatic lesionsDiagnosis of early pancreatic cancer remains a challenge mainly due to the lack of a standard screening test. Therefore, improving long-term survival relies primarily on detecting and treating early pancreatic cancer and thus reducing the incidence of pancreatic cancer.EUS is increasingly considered a valuable to...

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Differentiation and Risk Assessment of Gastrointestinal Stromal Tumors

Cited by 296 publications

References 69 publications

Extragastrointestinal (Soft Tissue) Stromal Tumors: An Analysis of 48 Cases with Emphasis on Histologic Predictors of Outcome

Extragastrointestinal (Soft Tissue) Stromal Tumors: An Analysis of 48 Cases with Emphasis on Histologic Predictors of Outcome

Gastrointestinal Stromal Tumours

Molecules and markers for endosonographers: What do we need to know and measure?

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