patient care perspectives

Differential Diagnosis of Gastrointestinal Stromal Tumors

by Jonathan C. Trent, MD, PhD

Overview

The diagnosis of gastrointestinal stromal tumors (GIST) is based on an evaluation that identifies a mass and leads to biopsy. Symptoms at presentation are generally determined by the anatomic location of the GIST.

Expert Commentary

Jonathan C. Trent, MD, PhD

Professor of Medicine
Associate Director for Clinical Research
Sylvester Comprehensive Cancer Center
University of Miami Miller School of Medicine
Miami, FL

When a patient has gastric GIST, it is more likely to come to medical attention due to bleeding and anemia than due to obstructive symptoms.”

Jonathan C. Trent, MD, PhD

The symptoms of GIST can be somewhat vague and nonspecific, and there may be no symptoms early on because of submucosal localization and noninvasive behavior. Patients with GIST might initially be thought to have irritable bowel syndrome, anemia, gastric ulcers, gallbladder disease, or any number of possible diagnoses. Most of the time, a patient with GIST presents with some type of symptom, and that symptom is generally determined by the anatomic location of the GIST. There may be gastrointestinal bleeding and subsequent anemia, or the patient may present with danger signs such as obstruction, dysphasia, or odynophagia. However, when a patient has gastric GIST, it is more likely to come to medical attention due to bleeding and anemia than due to obstructive symptoms. Although these are submucosal tumors, they can, at times, erode through the mucosa and cause hemorrhage into the stomach. There may be a more rapid hemorrhage, but, more commonly in the stomach, it is chronic bleeding that leads to anemia.

For a patient who presents in the primary care setting with only anemia, the standard workup involves an esophagogastroduodenoscopy (EGD) and a colonoscopy. This approach will generally detect things such as colon carcinoma, gastric ulcers, or gastritis. However, if the patient has submucosal gastric GIST or small intestinal GIST, there is a high likelihood that it could be missed by standard EGD. In this instance, a patient with an unexplained iron deficiency anemia and a positive fecal occult blood test could undergo a colonoscopy and EGD, and those investigations would not reveal the GIST. The patient could return for the same tests in 6 months, and still nothing would be found. Eventually, a computed tomography (CT) scan of the abdomen and pelvis is typically be obtained, in which case a mass is generally identified, leading to biopsy. From my perspective, I would favor ordering the CT immediately after a negative EGD and colonoscopy in this scenario; however, this does not seem to be the standard practice in many settings. Nonetheless, once a CT scan of the abdomen and pelvis is performed, generally, we can detect that mass and perform the biopsy that leads to the diagnosis. Importantly, in cases of suspected GIST, we prefer the biopsies to be transmucosal rather than percutaneous to reduce the risk of rupturing the tumor.

Light microscopy can be diagnostic if the pathologist is experienced with diagnosing GIST. Immunohistochemistry is generally supportive but not really diagnostic for GIST. Not all GIST express KIT and PDGFRA, and there are other types of tumors that can express KIT and PDGFRA. The antibody against DOG1 is much more sensitive for GIST than the KIT antibodies, and this includes several unusual GIST subtypes.

References

Arshad J, Ahmed J, Subhawong T, Trent JC. Progress in determining response to treatment in gastrointestinal stromal tumor. Expert Rev Anticancer Ther. 2020;20(4):279-288. doi:10.1080/14737140.2020.1745068

Boonstra PA, Ter Elst A, Tibbesma M, et al. A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors. Oncotarget. 2018;9(17):13870-13883. doi:10.18632/oncotarget.24493

Liegl B, Hornick JL, Corless CL, Fletcher CDM. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol. 2009;33(3):437-446. doi:10.1097/PAS.0b013e318186b158

Nannini M, Biasco G, Astolfi A, Pantaleo MA. An overview on molecular biology of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumours (GIST). J Med Genet. 2013;50(10):653-661. doi:10.1136/jmedgenet-2013-101695

Rossi S, Gasparotto D, Miceli R, et al. KIT, PDGFRA, and BRAF mutational spectrum impacts on the natural history of imatinib-naive localized GIST: a population-based study. Am J Surg Pathol. 2015;39(7):922-930. doi:10.1097/PAS.0000000000000418

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