Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2019; 25(30): 4261-4277
Published online Aug 14, 2019. doi: 10.3748/wjg.v25.i30.4261
Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia
Johanna Waidhauser, Anne Bornemann, Martin Trepel, Bruno Märkl
Johanna Waidhauser, Anne Bornemann, Bruno Märkl, Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, Augsburg 86156, Germany
Johanna Waidhauser, Martin Trepel, Department of Hematology and Clinical Oncology, University Medical Center Augsburg, Augsburg 86156, Germany
Author contributions: Waidhauser J performed literature research, collected and analyzed the data, performed statistical analysis and drafted the manuscript. Bornemann A performed literature research. Trepel M provided analytical oversight and revised the manuscript. Märkl B designed the review, was involved in literature research and statistical analysis and revised the manuscript.
Conflict-of-interest statement: All authors declare that no conflicting interests (including but not limited to commercial, personal, political, intellectual or religious interests) exist.
Data sharing statement: Statistical code, and dataset available from the corresponding author at Dryad repository, who will provide a permanent, citable and open-access home for the dataset.
PRISMA 2009 Checklist statement: The guidelines of the Prisma 2009 Statement have been adopted.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Bruno Märkl, MD, Professor, Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, Stenglinstrasse 2, Augsburg 86156, Germany. bruno.maerkl@outlook.de
Telephone: +49-821-4002150 Fax: +49-821-400173199
Received: April 19, 2019
Peer-review started: April 19, 2019
First decision: June 16, 2019
Revised: June 22, 2019
Accepted: July 5, 2019
Article in press: July 5, 2019
Published online: August 14, 2019
ARTICLE HIGHLIGHTS
Research background

In recent years, numerous case reports, mostly retrospective studies and a few reviews on the topic of second neoplasias associated with gastrointestinal stromal tumors (GIST) have been published. To our knowledge, however, this is the first systematic review of the existing data.

Research motivation

The aim of this review was to prepare a compilation, as complete as possible, of all reported second tumor entities that have been described in association with GIST, and to systematically analyze the published studies with regard to frequency, localization, and types of GIST-associated neoplasms.

Research objectives

The main focus of this review was on frequency, localization, dependence of gender, age and risk classification of GIST associated neoplasias. Summarizing the data of a large number of patients could especially help in the daily clinical work with GIST patients.

Research methods

The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary, synchronous, coincident/tumor, neoplasm, and relevant publications were selected by two independent authors. All case reports were summarized according to the reported tumor entity and included clinical studies were analyzed with regard to the previously mentioned topics.

Research results

Of the initially found 3042 publications, 130 papers were selected; 22 of these were original studies, and 108 were case reports. In the 22 selected studies, comprising a total number of 12050 patients, an overall rate of GIST-associated neoplasias of 20% could be calculated. Most second neoplasias were found in the gastrointestinal tract (32%) and in the male and female urogenital tract (30%). The male-to-female ratio revealed a predominance of male gender in cases with associated neoplasia. The specific risk scores of GISTs associated with other tumors were significantly lower than those of GIST without associated neoplasias. The question if there are specific genetic mutations that occur with a higher frequency in GIST patients with second tumors could not be answered and would be an interesting topic for future research.

Research conclusions

GISTs are associated with other neoplasias with a rate of 20% and occur most frequently in the gastrointestinal and urogenital tract. This confirms previous findings on a larger number of patients. GIST associated neoplasias occur with a higher likelihood in older, male patients with low grade GIST. 50% of GIST associated neoplasias are detected synchronously. Our findings should be a reason to consider frequent controls or extended staging for early detection of second neoplasias, especially in the gastrointestinal and urogenital tract.

Research perspectives

If there is a causal relation between GIST and second tumors remains unclear. As data on genetic mutations of the GIST were reported very heterogeneously focusing on this topic could be an interesting point for future research.