Most patients suffering from GIST are either asymptomatic or report non-specific complaints.

• With regards to the latter, gastrointestinal hemorrhages are most commonly observed. Depending on the location of the neoplasms, patients may show hematemesis, melena or hematochezia: Hematemesis implies a gastric disorder; melena occurs in case of GIST affecting the small intestines. Hematochezia would be expected in patients having large bowel GIST, which is a rare. In rare cases, hemorrhages lead to symptoms of blood loss.
• Hindrance of gastrointestinal passage due to obstruction is also common, and affected individuals may report dysphagia, bloating, early satiety, constipation. If the common bile duct is compressed, jaundice may manifest.
• Acute onset of severe abdominal pain, fever, shock and cardiovascular failure may indicate gastrointestinal perforation or tumor torsion and peritonitis.
• GIST are rarely palpable as abdominal masses.

• Pain

  A male patient, 63 years old, was admitted in the emergency room complaining of stretching and continuous abdominal pain for one day. [hindawi.com]

  Symptoms of GIST tumors include: bloody stools pain or discomfort in the abdomen nausea and vomiting bowel obstruction a mass in the abdomen that you can feel fatigue or feeling very tired feeling very full after eating small amounts pain or difficulty [healthline.com]

  CASE REPORT A 55-year-old male, presented with pain upper abdomen, weight loss and anorexia for 4 month. The pain has increased in intensity for past 4 days, with associated malaise and vomiting. [academic.oup.com]

  We report the case of a 70-year-old man who presented with sudden right lower quadrant abdominal pain and was diagnosed with a spontaneously ruptured hepatic metastasis of a malignant gastric GIST. [ncbi.nlm.nih.gov]

• Pathologist

  Pathologists at DF/BWCC are among the best and most experienced in the world with special expertise in providing an accurate diagnosis for complex cases. [brighamandwomens.org]

  Despite that, there remains a certain aura of mystery about these tumors which fosters confusion among pathologists and clinicians alike. [propath.org]

  Ovarian localizations, as far as rare, can be a clinical finding in case of ileal GIST patients, and both gynecologists, pathologists and medical oncologists should be able to recognize them. [ncbi.nlm.nih.gov]

  A pathologist studies the tumor under a microscope. The pathologist can then tell if the tumor is a GIST. He/she will also be able to test the tumor for Kit (CD 117). Sometimes, the tumor is large or has spread and cannot be removed successfully. [my.clevelandclinic.org]

• Fatigue

  Symptoms such as abdominal pain, nausea, and fatigue overlap with many other conditions and diseases. If you’re experiencing any of these or other abnormal symptoms, you should talk with your doctor. [healthline.com]

  GISTs may also produce symptoms secondary to obstruction or hemorrhage (GI bleeding, malaise, fatigue, and dyspnea). [secure.ssa.gov]

  The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. [ncbi.nlm.nih.gov]

  GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass [orpha.net]

• Anemia

  The article presents the case of a 44-year-old otherwise healthy man with anemia, who was diagnosed lower gastrointestinal bleeding. An abdominal CT scan revealed a clearly demarcated solid tumor in hypogastric region, measuring 65 x 45 mm. [ncbi.nlm.nih.gov]

  GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass [orpha.net]

• Surgical Procedure

  The surgical procedure was performed as follows: first, the second portion of the duodenum was separated from the pancreatic head; second, the duodenum was cut off with the linear stapler after having confirmed preservation of the papilla by intraoperative [ncbi.nlm.nih.gov]

  The oncology surgeons at BWH are well known for having perfected many progressive surgical procedures including: Laparoscopic surgery for small GISTS. [brighamandwomens.org]

• Dyspnea

  GISTs may also produce symptoms secondary to obstruction or hemorrhage (GI bleeding, malaise, fatigue, and dyspnea). [secure.ssa.gov]

  The patient arrived at the emergency room of our hospital due to sudden onset of dyspnea and chest pain. [revistagastroenterologiamexico.org]

  Case A 49-year-old man, a former smoker with no relevant family history, presented in 2002 with rapidly progressive dyspnea, chest pain, and superior vena cava syndrome. [em-consulte.com]

  Clinical manifestations of GISTs are as follows: Vague, nonspecific abdominal pain or discomfort (most common) Early satiety or a sensation of abdominal fullness Palpable abdominal mass (rare) Malaise, fatigue, or exertional dyspnea with significant blood [emedicine.medscape.com]

• Exertional Dyspnea

  Clinical manifestations of GISTs are as follows: Vague, nonspecific abdominal pain or discomfort (most common) Early satiety or a sensation of abdominal fullness Palpable abdominal mass (rare) Malaise, fatigue, or exertional dyspnea with significant blood [emedicine.medscape.com]

• Abdominal Pain

  We report the case of a 70-year-old man who presented with sudden right lower quadrant abdominal pain and was diagnosed with a spontaneously ruptured hepatic metastasis of a malignant gastric GIST. [ncbi.nlm.nih.gov]

  A male patient, 63 years old, was admitted in the emergency room complaining of stretching and continuous abdominal pain for one day. [hindawi.com]

• Vomiting

  A 95-year-old Japanese woman presented to our hospital with intermittent vomiting and several episodes of melena. Abdominal computed tomography revealed intussusception of the gastric tumor into the duodenum. [ncbi.nlm.nih.gov]

  GIST is often diagnosed when blood is detected in the stool or vomit. Should the tumor grow large enough, it can block the passage of food to the stomach or intestine, resulting in severe abdominal pain and vomiting. [pharma.bayer.com]

  These may include: Abdominal discomfort or pain Vomiting Blood in stools or vomit Fatigue due to anemia (low blood counts) Feeling full after eating only a small amount (early satiety) Loss of appetite These symptoms may be the result of GIST or of other [stanfordhealthcare.org]

  Tell your healthcare provider if you have any signs of bleeding while taking STIVARGA, including: vomiting blood or if your vomit looks like coffee grounds, pink or brown urine, red or black (looks like tar) stools, coughing up blood or blood clots, menstrual [stivarga-us.com]

• Nausea

  Symptoms such as abdominal pain, nausea, and fatigue overlap with many other conditions and diseases. If you’re experiencing any of these or other abnormal symptoms, you should talk with your doctor. [healthline.com]

  A 42-year-old hypothyroid shepherd presented with a progressive abdominal lump accompanied by nausea and abdominal fullness. In addition, he had worsening hypothyroidism, despite supranormal doses of thyroxine. [ncbi.nlm.nih.gov]

  Treatments: Current and Future Perspectives Managing the Side Effects of Immunotherapy Understanding the Role of Immunotherapy in Treating Cancer Taking Your Pills on Schedule: Why It Is So Important in Managing Cancer Preventing Chemotherapy Induced Nausea [cancercare.org]

  GISTs can be asymptomatic or present with various non-specific signs, depending on the location and size of tumor, such as loss of appetite, anemia, weight loss, fatigue, abdominal discomfort or fullness, nausea, vomiting, as well as an abdominal mass [orpha.net]

• Abdominal Mass

  The clinical examination demonstrated a large abdominal mass and an abdominal computed tomography scan revealed a voluminous intraperitoneal mass measuring 30 cm in its greatest diameter. [ncbi.nlm.nih.gov]

  Acute onset of severe abdominal pain, fever, shock and cardiovascular failure may indicate gastrointestinal perforation or tumor torsion and peritonitis. GIST are rarely palpable as abdominal masses. [symptoma.com]

• Dysphagia

  All but one patient presented with dysphagia. The average duration of the dysphagia was 6.7 months, but five patients had dysphagia for 3 or fewer months. Frontal chest radiographs revealed a mediastinal mass in five patients. [doi.org]

  The obstructive symptoms can be site-specific (e.g., dysphagia with an esophageal GIST, constipation with a colorectal GIST, obstructive jaundice with a duodenal tumor, etc.) [secure.ssa.gov]

  • Symptoms are site specific and include: dysphagia for tumors of the esophagus, nausea and vomiting caused by gastric outlet obstruction for gastric tumors, obstructive jaundice for periampullary tumors, and bowel obstruction usually caused by intussusceptions [sages.org]

  Most are clinically detected as intraluminal distal oesophageal masses causing dysphagia, but externally extending oesophageal GISTs can manifest as mediastinal tumours. [codes.iarc.fr]

• Heart Failure

  […] or symptoms of heart failure during therapy with GLEEVEC. [gleevec.com]

  failure, cerebrovascular accident including transient ischemic attack or pulmonary embolism. 6. [clinicaltrialsregister.eu]

  Imatinib is a rare of cardiotoxicity such as congestive heart failure, arrhythmias or acute coronary syndromes, occurring in less than 1% of treated patients. [bccancer.bc.ca]

  Radiotherapy continued until the patient passed away by heart failure in 2018. The main features of the patient are presented in Table 1. Table 1. [ircmj.com]

  If the fluid retention appears in people suffering heart failures or accumulate around the lungs (lung effusion) or the heart (pericardial effusion) it might be dangerous. [grupogeis.org]

• Tachycardia

  Sometimes anemia may cause the patient’s heart to race (tachycardia). The patient may notice weight loss. Very rarely a GIST may rupture, making its presence known with a medical emergency. [gistsupport.org]

  Bleeding may be slow, resulting in anemia, or sudden, causing tachycardia, fainting, stomach pain, melena, or hematemesis. [ascopubs.org]

• Palpitations

  Case presentation A 47 year old African American male presented to the emergency department with intermittent, severe chest pain associated with palpitations and one episode of vomiting.. [bmcresnotes.biomedcentral.com]

• Jaundice

  CASE PRESENTATION: A 66-year-old lady with neurofibromatosis type 1 presented with painless progressive jaundice for six months. Laboratory investigations revealed iron deficiency anemia and conjugated hyperbilirubinemia. Tumor markers were normal. [ncbi.nlm.nih.gov]

  • Symptoms are site specific and include: dysphagia for tumors of the esophagus, nausea and vomiting caused by gastric outlet obstruction for gastric tumors, obstructive jaundice for periampullary tumors, and bowel obstruction usually caused by intussusceptions [sages.org]

  The obstructive symptoms can be site-specific (e.g., dysphagia with an esophageal GIST, constipation with a colorectal GIST, obstructive jaundice with a duodenal tumor, etc.) [secure.ssa.gov]

  If the common bile duct is compressed, jaundice may manifest. Acute onset of severe abdominal pain, fever, shock and cardiovascular failure may indicate gastrointestinal perforation or tumor torsion and peritonitis. [symptoma.com]

• Seizure

  Call your healthcare provider right away if you get severe headaches, seizure, confusion, change in vision, or problems thinking wound healing problems. [stivarga-us.com]

Diagnosis of gastrointestinal tumors is initially based on imaging, while the confirmation of GIST requires further analysis of tissue samples.

Gastrointestinal symptoms as described above may prompt endoscopic examinations, and fine-needle aspirations or biopsies should be carried out if submucosal masses are detected. Sonographic guidance is highly recommended to this end. Pathognomonic findings are not to be expected before histopathological analyses are realized. In general, the most striking finding to this end is a strong positivity for c-Kit upon immunohistochemical staining.

In order to ascertain the extension of the tumor, further imaging is necessary - and depending on the clinical presentation, those techniques described hereinafter may even precede endoscopy. In case of large tumors, plain radiography may be a sufficiently sensitive approach to support the tentative diagnosis of an abdominal mass. However, considerable shares of GIST measure very few centimeters in diameter at the time of symptom onset and here, contrast-enhanced computed tomography is better suited for diagnosis [10]. Additionally, the latter technique allows for a precise assessment of mesenterial or omentum infiltration. Magnetic resonance imaging has been recommended to diagnose rectal GIST; positron-emission tomography has proven valuable to detect metastases and to evaluate the patient's response to therapy.

Of note, most GIST are solitary neoplasms, but multiple tumors have also been described [11]. The latter are often associated with familial GIST that manifest in childhood. Sporadic GIST most frequently affect the stomach, but patients suffering from neurofibromatosis type 1 are more prone to develop small intestinal tumors.

• Hemoglobin Decreased

  Some common side effects that you may experience include: Fluid retention (holding water) Muscle cramps, pain, or bone pain Abdominal pain Anorexia (loss of appetite) Vomiting Diarrhea Decreased hemoglobin (decrease in blood cells which carry oxygen) [gleevec.com]

• Gastric Lesion

  Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. [ncbi.nlm.nih.gov]

  Three months later, CT showed dramatic regression of the gastric lesion ( Figure 1 ), but progression of the lung tumor ( Figure 1 ). [em-consulte.com]

  After 10 months of treatment a new CT scan showed the most relevant liver lesion with a size of 8.5 x 5 cm, and the gastric lesion with a size of 4 x 3.5 cm ( Fig. 2 ). [scielo.isciii.es]

Surgical resection and chemotherapeutic treatment are the mainstays of GIST therapy, but they may be applied differently depending on the results of tumor staging, possible infiltration of adjacent tissues by the primary tumor or its metastases, and the overall condition of the patient.

Ideally, complete surgical resection of a primary tumor that didn't metastasize is carried out. If this is feasible, patients should subsequently be prescribed imatinib, a tyrosine kinase inhibitor that is effective irrespective of whether KIT or PDGFRA mutations gave rise to the neoplasm. In general, drug treatment shows very good results. However, determined mutations may render the tumor little susceptible to the compound and thereby cause relapses.

Complete remission is not to be expected if the tumor cannot be removed surgically. If the respective intervention cannot be carried out, patients may benefit from partial removal of the primary tumor or its metastases. Imatinib should be prescribed, and in some cases, patients with previously unresectable neoplasms may turn into candidates for surgery after neoadjuvant use of imatinib. This drug should not be withdrawn before surgery can be conducted or before the tumor turns resistant to increased doses of the compound, i.e., administration of imatinib may be required for several years. It is given per os.

In case of resistance to imatinib and tumor progression, sunitinib - another tyrosine kinase inhibitor - may be applicated. Sunitinib seems to be particularly effective in patients whose tumors neither present KIT nor PDGFRA mutations. Eventually, use of regorafenib constitutes another treatment option. This compound has been shown to inhibit a variety of kinases, among them KIT and PDGFRA. Due to rather high risks of adverse events, regorafenib should be reserved as a third-line treatment [12].

Of note, radiation therapy has not been proven effective to treat GIST patients.

About two-thirds of GIST are benign, whereas the remaining part is classified as malignant. GIST may metastasize and interestingly, such behavior seems to be more common in non-gastric tumors [8]. While the precise mutation triggering degeneration does not seem to affect the outcome, secondary gene defects do. In fact, those mutations occurring during later stages of the disease may render the tumor resistant to drug therapy. The patient's prognosis further depends on tumor size upon diagnosis, infiltration of adjacent tissues and mitotic index. In sum, GIST usually respond well to treatment and 5-year survival rates of about 75% have been reported after correction of data for mortality not related to the gastrointestinal neoplasm [7].

Degeneration of interstitial cells of Cajal accounts for the development of GIST, but a precise trigger for such events has not yet been identified. Patients predisposed for tumor development due to systemic disorders like neurofibromatosis type 1 are diagnosed with GIST more often than the general population.

The majority of GIST patients presents mutations of the KIT gene, an oncogene encoding for a receptor tyrosine kinase. Its gene product is often referred to as c-Kit. Because c-Kit plays an important role in cell growth, division and differentiation, gain-of-function mutations that lead to constitutive activity of the enzyme may result in cancer. In fact, KIT mutations have been reported for a variety of neoplasms, especially for hematopoietic malignancies [2]. Distinct types of cancer as well as different mutations of the same gene render the tumor more or less resistant to tyrosine kinase inhibitors. Fortunately, GIST pertain to the rather susceptible group of such tumors.

Another gene frequently associated with GIST is the PDGFRA gene [1], similarly classified as an oncogene. PDGFRA encodes for platelet-derived growth factor receptor α, which is likewise a receptor tyrosine kinase. Distinct mutations have been described, and they are likely to activate downstream signaling cascades that favor cell growth and division over apoptosis [3].

Usually, gene defects leading to GIST are acquired, somatic mutations. Familial GIST are very rare [4].

Of note, a minor share of patients does present neither of the aforementioned mutations. Presumably, as of yet poorly described gene defects account for uncontrolled cell division in these cases.

Although GIST are the most common mesenchymal neoplasms of the gastrointestinal tract, they are still considered rare tumors: Annual incidence rates of less than 5 per 1,000,000 inhabitants have been reported in distinct countries [5] [6], but somewhat higher values can also be found in the literature [7]. They have been estimated to account for less than 3% of malignant tumors of the digestive system [8].

People of all races and both genders may develop GIST, and predilections found in some studies have been refuted by others. However, there is a consensus regarding an age peak among the elderly. In the aforecited studies, for instance, highest incidence rates were calculated for patients aged older than 50 and 70 years, respectively. This is in agreement with a mean age upon diagnosis of 66 years. GIST have rarely been described in pediatric patients [1].

As has been indicated above, GIST originate from the so-called interstitial cells of Cajal. These cells function as pacemakers, trigger smooth muscle contractions and thus contribute to peristalsis. Accordingly, they can be encountered along large parts of the gastrointestinal tract, starting from the esophagus, to stomach, small and large intestines and finally the rectum. And in fact, GIST have been encountered in all these organs, but they show a clear preference for stomach and small intestines: About half of all GIST affect the stomach, one-fourth is detected in jejunum or ileum.

Interstitial cells of Cajal are located in the muscular layer of the intestinal wall. Any tumor arising from these cells may thus grow towards the lumen of the respective hollow organ, or in the opposite direction. Exophytic growth has been reported to be more common in GIST. According to the fact that stomach and small intestines are most frequently affected, many GIST grow in the abdominal cavity. Contrary to endophytically growing tumors that interfere with the gastrointestinal passage during early stages of the disease, exophytic neoplasms may not provoke any symptoms until reaching a considerable size [8]. Upon torsion of pedunculated GIST, however, acute symptom onset may be observed independent of the size of the tumor [9].

No specific measures can be recommended to prevent GIST.

A gastrointestinal stromal tumor (GIST) is a rare type of tumor, yet it is the most common form of mesenchymal gastrointestinal neoplasm. GIST originate from interstitial cells of Cajal, which act as pacemakers and coordinate peristaltic motions along large parts of the digestive system.

In general, GIST are diagnosed in patients aged 50 years and older. However, children have been reported to suffer from GIST as well, and such findings may result from a general disposition for tumor growth, as seen, for instance, in neurofibromatosis patients. Non-specific gastrointestinal symptoms like bloating, early satiety, hemorrhages and obstruction may prompt patients to seek medical attention; in other cases, GIST are incidental findings.

GIST may obstruct the lumen of the affected hollow viscera, but they more commonly invade neighboring tissues like mediastinum, mesenterium and omentum. This fact explains why GIST are often diagnosed only after the tumor has reached a considerable size - case reports of neoplasms measuring more than 30 centimeters in diameter and weighing several kilogram have been published [1].

Workup aims at tumor staging, i.e., assessment of the neoplasm's extension and possible metastazation, and tumor grading. GIST may show features of benign or malignant neoplasms, but histopathological findings don't necessarily correlate with the likelihood of recurrence and formation of metastases. Complete surgical resection and adjuvant administration of tyrosine kinase inhibitors is the therapeutic approach of choice.

In general, intestinal walls consist of an inner mucosal layer, smooth muscle whose contraction permits peristaltic movements, and an outer layer called adventitia. However, there's a wide variety of specific cell types distributed throughout these layers, each of which fulfills important functions. Some are termed interstitial cells of Cajal - these cells function as pacemakers and thus contribute to regular peristaltic motions. If interstitial cells of Cajal grow and divide in an uncontrolled manner, tumors may develop. The affected patient is diagnosed with a gastrointestinal stromal tumor (GIST).

GIST may occur along large parts of the digestive system, starting from the esophagus, to stomach, small and large intestines and finally the rectum. Most commonly, stomach and small bowels are affected. Although they may grow towards the lumen of the respective hollow viscera, they tend to expand within the abdominal cavity. Thus, they may reach a considerable size before being detected. In fact, some GIST are incidental findings encountered while realizing endoscopy or radiography for other reasons.

If GIST patients become symptomatic, they may vomit blood or detect blood in their stools. Non-specific gastrointestinal complaints like difficulties when swallowing, bloating, early satiety and constipation. Such symptoms prompt diagnostic imaging; physicians may also need to obtain a tissue sample, either by fine-needle aspiration or by biopsy. Endoscopy, sonography and computed tomography are most frequently applied to this end. The latter also allows for an evaluation of possible infiltration of adjacent tissues.

In general, complete surgical resection is recommended to treat GIST patients. Adjuvant chemotherapy is often required, particularly in case of metastatic cancer. It significantly reduces the probability of recurrence and renewed metastatic spread. In sum, GIST usually respond well to treatment and 5-year survival rates of about 75% have been reported.

1. Kuroiwa M, Hiwatari M, Hirato J, et al. Advanced-stage gastrointestinal stromal tumor treated with imatinib in a 12-year-old girl with a unique mutation of PDGFRA. J Pediatr Surg. 2005; 40(11):1798-1801.
2. Ashman LK, Griffith R. Therapeutic targeting of c-KIT in cancer. Expert Opin Investig Drugs. 2013; 22(1):103-115.
3. Velghe AI, Van Cauwenberghe S, Polyansky AA, et al. PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations. Oncogene. 2014; 33(20):2568-2576.
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5. Wang ZH, Liang XB, Wang Y, Ma GL, Qu YQ, Tian XW. [Epidemiology survey of gastrointestinal stromal tumor in Shanxi Province in 2011]. Zhonghua Yi Xue Za Zhi. 2013; 93(32):2541-2544.
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