Elsevier

Human Pathology

Volume 33, Issue 5, May 2002, Pages 478-483
Human Pathology

GIST Symposium
Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: A review*,**,*

https://doi.org/10.1053/hupa.2002.124123Get rights and content

Abstract

This paper reviews data on the prognosis of gastrointestinal stromal tumors (GISTs). These tumors are specific KIT-expressing and KIT-signaling–driven mesenchymal tumors, many of which have KIT-activating mutations. GISTs occur in the entire gastrointestinal (GI) tract and may also arise from the omentum, mesenteries, and retroperitoneum. They range from small benign tumors to sarcomas at all sites of occurrence. A KIT tyrosine kinase inhibitor, STI-571 (imatinib [Gleevec]; Novartis, Basel, Switzerland), has recently shown promise in the treatment of metastatic GISTs. Understanding the natural history of GIST before introduction of STI-571 will help assess the impact and position of this new treatment. The frequency of benign versus malignant GISTs varies between sites. Benign GISTs outnumber malignant GISTs in the stomach, whereas malignant GISTs are more common in the intestines. Tumors that have metastasized at presentation have a very poor prognosis. Traditionally, the 3 key prognostic factors have been mitotic rate, tumor size, and site. Tumors that are small (≤2 cm) and show mitotic activity not exceeding 5 mitoses per 50 high-power fields (HPFs) have an excellent prognosis, probably independent of site, although this has not been shown specifically for all sites. In the stomach, most epithelioid GISTs are benign, provided that mitotic counts do not exceed 5/50 HPFs. However, a small proportion of tumors apparently lacking mitotic activity do metastasize. Tumors with a mitotic rate >5/50 HPFs usually have a malignant behavior. The Ki67 index may help identify tumors with malignant potential, but large site-specific series are not yet available. Genetic markers, including DNA-copy number changes, telomerase activity, and KIT mutation status, may be useful in more accurately identifying tumors with malignant potential. HUM PATHOL 33:478-483. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Tumor stage at presentation

The presence of peritoneal or liver metastases at presentation is an adverse prognostic sign conferring a shorter survival, according to large clinicopathologic studies.10, 11 Conversely, small serosal tumors incidentally detected during unrelated surgery have a uniformly benign course.12

Tumor site

Site-specific series indicate that GISTs range from small, benign, usually incidentally detected nodules to larger overt sarcomas at most sites of occurrence.3, 13 However, small GISTs are more often detected

Losses and gains of genetic material

The earliest data on gains and losses of genetic material were based on DNA cytometry and ploidy analyses, which detect the overall net losses or gains of DNA. Today, these analyses are being replaced by more sophisticated topographically correlated analyses, including comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) studies.

Numerous studies have addressed nuclear DNA content in smooth-muscle tumors (i.e., leiomyomas, leiomyoblastomas, and leiomyosarcomas) of the GI

Conclusion

In most cases, the clinical behavior of a GIST can be predicted with relative accuracy based on the combination of tumor size and mitotic activity, although some small tumors (<5 cm) with low mitotic activity (<5 mitoses per 50 HPFs) do metastasize. Changes in DNA copy numbers are new genetic parameters that may aid prognostic evaluation, whereas the independent value of Ki67 analogs has not been uniformly agreed on. Evaluation of KIT mutation may have both prognostic and therapeutic

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    *

    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.

    **

    Supported by the American Registry of Pathology.

    *

    Address correspondence and reprint requests to Markku Miettinen, MD, Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, 14th Street and Alaska Avenue, N.W. Washington, DC 20306-6000.

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