Gastrointestinal stromal tumor

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

A gastrointestinal stromal tumor (GIST) is a type of tumor that occurs in the gastrointestinal tract, most commonly in the stomach or small intestine. This type of tumor is thought to grow from specialized cells found in the gastrointestinal tract called interstitial cells of Cajal (ICCs) or precursors to these cells. Affected individuals can develop one or more tumors. GISTs are usually found in adults between ages 40 and 70; rarely, children and young adults develop this type of tumor.

Small tumors may cause no signs or symptoms. However, some people with GISTs may experience pain or swelling in the belly area (abdomen), nausea, vomiting, loss of appetite, or weight loss. Sometimes, tumors cause bleeding into the gastrointestinal tract, which may lead to low red blood cell counts (anemia) and, consequently, weakness and tiredness. Bleeding into the intestines may cause black and tarry stools, and bleeding into the throat or stomach may cause vomiting of blood.

Affected individuals with no family history of GIST typically have only one tumor (called a sporadic GIST). People with a family history of GISTs (called familial GISTs) often have multiple tumors and additional signs or symptoms, including noncancerous overgrowth (hyperplasia) of other cells in the gastrointestinal tract and patches of dark skin on various areas of the body. Some affected individuals have a skin condition called urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis), which is characterized by raised patches of brownish skin that sting or itch when touched.

A rare form of GIST, called succinate dehydrogenase (SDH)-deficient GIST, tends to occur in childhood or young adulthood and affects females more commonly than males. In this form, tumors are almost always in the stomach. Individuals with an SDH-deficient GIST have a high risk of developing other types of tumors, particularly noncancerous tumors in the nervous system called paragangliomas and noncancerous lung tumors called pulmonary chondromas. When GISTs occur in combination with paragangliomas, the condition is known as Carney-Stratakis syndrome; the combination of GISTs, paragangliomas, and pulmonary chondromas is known as Carney triad; and the combination of GISTs and pulmonary chondroma is known as incomplete Carney triad.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Genetic changes in one of several genes are involved in the formation of GISTs. About 80 percent of cases are associated with a mutation in the KIT gene, and about 10 percent of cases are associated with a mutation in the PDGFRA gene. Mutations in the KIT and PDGFRA genes are associated with both familial and sporadic GISTs. Less than 10 percent of cases are SDH-deficient GISTs, which are associated with mutations or other changes in the SDHA, SDHB, SDHC, or SDHD gene. SDH-deficient GIST can be familial or sporadic. A small number of people with a GIST have mutations in other genes.

The KIT and PDGFRA genes provide instructions for making receptor proteins that are found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When a ligand attaches (binds), the KIT or PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and survival.

Mutations in the KIT and PDGFRA genes lead to proteins that no longer require ligand binding to be activated. As a result, the proteins and the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells and leads to the formation of tumors.

The SDHA, SDHB, SDHC, and SDHD genes provide instructions for making proteins that come together to form the succinate dehydrogenase (SDH) enzyme. The SDH enzyme is involved in cellular pathways that are critical for converting the energy from food into a form that cells can use. Specifically, the SDH enzyme converts a compound called succinate to another compound called fumarate. Succinate acts as an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia).

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Most cases of GIST are sporadic and are not inherited. These cases are associated with a somatic mutation, which is a genetic change that occurs only in the tumor cells and occurs during a person's lifetime.

In some cases of familial GIST, including those associated with mutations in the KIT and PDGFRA genes, the condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing tumors. A second, somatic mutation is needed for tumor formation.

When familial GIST is associated with mutations in other genes, it can have an autosomal recessive pattern of inheritance, which means alterations in both copies of the gene in each cell increase a person's chance of developing tumors.

SDH-deficient GIST follows an autosomal dominant inheritance pattern; a mutation in one copy of the SDHA, SDHB, SDHC, or SDHD gene is sufficient to increase a person's chance of developing tumors, and a somatic mutation altering the other copy of the gene is needed for tumor formation. A particular alteration in the SDHC gene is not inherited. This genetic change is typically associated with Carney triad.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Approximately 5,000 new cases of GIST are diagnosed in the United States each year. SDH-deficient GIST accounts for about 5 to 7 percent of cases. However, GISTs may be more common than the estimate because small tumors may remain undiagnosed.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Neoplasm of the stomach · Very frequent (99-80%)

A tumor (abnormal growth of tissue) of the stomach.

Sarcoma · Very frequent (99-80%)

A connective tissue neoplasm formed by proliferation of mesodermal cells. Bone and soft tissue sarcomas are the main types of sarcoma. Sarcoma is usually highly malignant.

Gastrointestinal stroma tumor · Very frequent (99-80%)

Constipation · Frequent (79-30%)

Infrequent or difficult evacuation of feces.

Dysphagia · Frequent (79-30%)

Difficulty in swallowing.

Fatigue · Frequent (79-30%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Gastrointestinal hemorrhage · Frequent (79-30%)

Hemorrhage affecting the gastrointestinal tract.

Intestinal obstruction · Frequent (79-30%)

Blockage or impairment of the normal flow of the contents of the intestine towards the anal canal.

Other findings in the same source

From: Orphanet

Additional reported features include Nausea and vomiting (Frequent (79-30%)); Abnormality of the liver (Occasional (29-5%)); Anemia (Occasional (29-5%)); Esophageal neoplasm (Occasional (29-5%)); Neoplasm of the gastrointestinal tract (Occasional (29-5%)); Neoplasm of the small intestine (Occasional (29-5%)); Skin rash (Occasional (29-5%)); Irregular hyperpigmentation (Occasional (29-5%)); Neoplasm of the colon (Occasional (29-5%)); Neoplasm of the rectum (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Gastrointestinal stromal tumor is Oncology, with a oncologist and relevant organ specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics; Relevant organ specialist / Surgical Oncology as indicated.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Has the exact tumour type been confirmed, and is staging relevant?
• What is the goal of each proposed treatment option?
• How will side effects, daily function and supportive care be addressed?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Gastrointestinal stromal tumor. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.