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.