Gastrointestinal Stromal Tumor (GIST): Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC
April 5, 2026

A gastrointestinal stromal tumor, or GIST, is a type of cancer that starts in the wall of the digestive tract. The most common locations are the stomach and small intestine, but GISTs can occur anywhere from the esophagus to the rectum. GISTs are distinct from other gastrointestinal cancers because they arise from specialized cells called interstitial cells of Cajal (ICCs), which act as pacemakers for the muscles in the digestive tract, coordinating the rhythmic contractions that move food through the gut.

This article will help you understand the findings in your pathology report — what the terms mean, what the numbers indicate, and why each piece of information matters for your care.

What causes a GIST?

GISTs are caused by genetic mutations in interstitial cells of Cajal or their precursor cells. The most common mutations are in the KIT gene (found in approximately 75% of GISTs) and the PDGFRA gene (found in approximately 10%). These mutations keep growth signals permanently switched on, causing the cells to grow and divide uncontrollably.

Most GISTs occur sporadically — meaning the mutations happen by chance and are not inherited. However, a small number arise in the setting of inherited genetic syndromes:

• Neurofibromatosis type 1 (NF1) — People with NF1 (caused by mutations in the NF1 gene) have an increased risk of developing multiple GISTs, typically in the small intestine and without KIT or PDGFRA mutations.
• Carney-Stratakis syndrome — A rare inherited syndrome caused by germline mutations in the SDH subunit genes, associated with GISTs and paragangliomas (tumors of nerve tissue).
• SDH-deficient GIST syndromes — Discussed in detail below.

If a genetic syndrome is suspected — particularly in younger patients or those with multiple tumors — genetic counseling and testing may be recommended, as the findings can have important implications for family members.

What are the symptoms?

Symptoms vary depending on the size and location of the tumor. Small, slow-growing GISTs often cause no symptoms and are discovered incidentally during imaging or endoscopy done for another reason. As the tumor grows, symptoms may include:

• Abdominal pain or discomfort — the most common symptom, ranging from mild to severe.
• A feeling of fullness after eating only small amounts, particularly if the tumor is in the stomach.
• Nausea and vomiting — may occur if the tumor partially blocks the digestive tract.
• Bleeding into the digestive tract — GISTs can bleed internally, producing black or tarry stools, or, less commonly, vomiting blood.
• Fatigue and weakness — from anemia caused by chronic blood loss.

How is the diagnosis made?

The diagnosis of GIST is made after a tissue sample is examined under the microscope by a pathologist. The sample is obtained either by biopsy during an endoscopy or endoscopic ultrasound, or by surgical removal of the tumor. Biopsy before surgery is commonly performed to confirm the diagnosis before starting targeted therapy with a tyrosine kinase inhibitor, or to assess whether neoadjuvant treatment (treatment before surgery) is appropriate for larger tumors.

Under the microscope, GISTs are made up of cells growing in the muscular wall of the digestive tract, outside the inner lining. The pathologist identifies characteristic cell shapes and growth patterns, and then confirms the diagnosis using immunohistochemistry — special staining tests that detect specific proteins in the tumor cells.

Histologic types

Pathologists classify GISTs into three types based on the shape of the tumor cells under the microscope. The cell type does not change the overall treatment approach but can provide additional diagnostic and prognostic information.

• Spindle cell type — The most common type. The tumor cells are long and thin, like a spindle. This pattern is most commonly seen in gastric GISTs.
• Epithelioid type — The tumor cells are round and plump, resembling epithelioid cells. This pattern is more common in PDGFRA-mutant GISTs and SDH-deficient GISTs.
• Mixed type — The tumor contains both spindle and epithelioid cells.

Tumor grade and mitotic count

Pathologists grade GISTs based on the percentage of tumor cells that are actively dividing, as seen under the microscope. Dividing cells are called mitotic figures, and counting them in a defined area of the tumor gives the mitotic count. The mitotic count is one of the three most important factors (along with tumor size and location) in predicting how a GIST will behave.

• Low grade (low mitotic count) — 5 or fewer mitotic figures per 5 mm² of tumor tissue. These GISTs tend to grow more slowly and are less likely to spread.
• High grade (high mitotic count) — More than 5 mitotic figures per 5 mm². These GISTs are more likely to grow aggressively and spread to other organs.

Your pathology report will state the mitotic count as a specific number per area, which helps determine your risk assessment score (see below).

Tumor size

The tumor size is measured at its widest point and is one of the three main factors used in risk assessment. Larger tumors carry a higher risk of recurrence or spread after treatment. Tumor size can only be accurately determined after the tumor has been completely removed by surgery. If your report is from a biopsy before surgery, the final tumor size will be reported after the surgical specimen is examined.

Necrosis

Necrosis means areas of dead tissue within the tumor. In GISTs, necrosis typically occurs when parts of the tumor outgrow their blood supply. The presence of significant necrosis is generally associated with more aggressive tumor behavior and a higher risk of recurrence.

Tumor rupture

Tumor rupture means the tumor broke open before or during surgery, releasing tumor cells into the abdominal cavity. Rupture can occur spontaneously or as a result of a surgical complication. It is an important finding because it is associated with a substantially higher risk of tumor spread within the abdomen (peritoneal metastasis) and changes the overall risk category to high risk regardless of tumor size or mitotic count. Your pathology report will state whether rupture was identified.

Surgical margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margin surfaces to determine whether tumor cells are present at the cut edge.

• Negative margin — No tumor cells at the cut edge. This suggests the tumor was completely removed, which is the goal of surgery.
• Positive margin — Tumor cells are present at the cut edge, suggesting some tumor may remain. This increases the risk of local recurrence and may influence decisions about additional treatment.

Unlike carcinomas, GISTs do not typically spread along tissue planes or through lymphatics, so the margin distance is particularly important for assessing local control.

Lymph nodes

In most types of cancer, spread to lymph nodes is a common and early event. GISTs are unusual in that lymph node spread is extremely rare in conventional KIT- or PDGFRA-mutant GISTs. For this reason, lymph nodes are not routinely removed during GIST surgery unless they appear enlarged on imaging.

However, SDH-deficient GISTs (see below) are an important exception — lymph node spread does occur in this subtype and may be mentioned in the pathology report. Your report will state whether any lymph nodes were examined and, if so, whether tumor cells were present.

Immunohistochemistry

Immunohistochemistry is a laboratory test that uses antibodies to detect specific proteins inside tumor cells. It is essential for confirming the diagnosis of GIST and distinguishing it from other tumors that can look similar under the microscope. The following proteins are typically tested:

• CD117 (KIT) — The KIT protein is present on the surface of normal interstitial cells of Cajal and is abnormally overproduced in most GISTs. A positive CD117 result is the most important marker supporting a GIST diagnosis. Approximately 95% of GISTs are CD117-positive.
• DOG1 — DOG1 is a protein that helps regulate ion flow in interstitial cells of Cajal. It is expressed in most GISTs, including some that are CD117-negative (such as certain PDGFRA-mutant GISTs). DOG1 positivity is highly specific for GIST and is used in conjunction with CD117 to confirm the diagnosis.
• CD34 — A marker of certain connective tissue and blood vessel cells that is positive in approximately 70% of GISTs. It is used as a supporting marker alongside CD117 and DOG1.
• Smooth muscle actin (SMA) — Sometimes weakly positive in GISTs; helps the pathologist distinguish GIST from true smooth muscle tumors.
• S100 — Typically negative in GISTs; helps distinguish GIST from nerve sheath tumors, which are usually S100-positive.
• Desmin — Typically negative in GISTs; helps distinguish GIST from smooth muscle and skeletal muscle tumors.
• SDHB — An immunohistochemistry marker used to screen for SDH-deficient GISTs (see below). Loss of SDHB staining in the tumor cells indicates SDH deficiency and prompts further evaluation.

Biomarker and molecular testing

Molecular testing is one of the most important parts of a GIST workup. The specific gene mutation present in the tumor determines which targeted treatments are most likely to work, and can also provide important prognostic information. Testing is recommended for all patients with GIST who may receive or are receiving targeted therapy.

KIT and PDGFRA mutation testing

The most common method is next-generation sequencing (NGS), which analyzes the DNA of the tumor cells to identify the specific location (exon) and type of mutation. This matters clinically because different mutations predict different responses to targeted therapy:

• KIT exon 11 mutations — The most common mutation, found in approximately 65% of GISTs. These tumors respond very well to imatinib (Gleevec), the standard first-line targeted therapy for GIST.
• KIT exon 9 mutations — Found in approximately 10% of GISTs, more often in small intestinal tumors. These tumors are less sensitive to standard-dose imatinib and may benefit from a higher dose (800 mg daily instead of 400 mg).
• PDGFRA exon 18 D842V mutation — Found in approximately 6% of GISTs, almost exclusively in gastric tumors. This mutation makes the tumor resistant to imatinib. However, a different targeted drug called avapritinib (Ayvakit) is specifically approved and highly effective for PDGFRA D842V-mutant GIST.
• Other PDGFRA exon 18 mutations (non-D842V) — Generally sensitive to imatinib.
• PDGFRA exon 12 mutations — Uncommon; generally have a favorable prognosis.
• Wild-type GIST (no KIT or PDGFRA mutation) — Approximately 15% of GISTs have no KIT or PDGFRA mutation. These tumors require further testing (including BRAF and SDH subunit gene evaluation) to identify the underlying driver. Wild-type GISTs often do not respond well to imatinib.

Your pathology report will describe the mutation result using the gene name and specific exon (e.g., “KIT exon 11 deletion” or “PDGFRA exon 18 D842V substitution”). Your oncologist will use this to select the most appropriate targeted therapy.

SDH-deficient GISTs

A distinct subset of GISTs — accounting for approximately 5–10% of all cases — lacks mutations in KIT, PDGFRA, or BRAF. Instead, they have abnormalities in the succinate dehydrogenase (SDH) complex, a group of proteins involved in cellular energy production. These are called SDH-deficient GISTs, and they have several important differences from conventional GISTs:

• Who they affect — SDH-deficient GISTs tend to occur in younger patients, including children and young adults. Nearly all GISTs in children are SDH-deficient.
• Location — Almost all arise in the stomach.
• Microscopic appearance — Most have an epithelioid cell shape and often form multiple nodules with a distinctive growth pattern throughout the stomach wall.
• Lymph node spread — Unlike conventional GISTs, SDH-deficient GISTs commonly spread to regional lymph nodes. This is why lymph node involvement may be mentioned in the report for this subtype.
• Treatment response — SDH-deficient GISTs do not respond well to imatinib or other standard KIT/PDGFRA-targeted therapies. Management typically involves surgery for localized disease and clinical trial participation for advanced disease.
• Prognosis — SDH-deficient GISTs can behave in a very unpredictable way. Some patients with liver spread from SDH-deficient GIST can live for many years or even decades with relatively stable disease. The standard GIST risk stratification system does not apply to this subtype.

SDH deficiency is caused either by an inherited (germline) mutation in one of the SDH subunit genes (SDHA, SDHB, SDHC, or SDHD) or by chemical silencing of the SDHC gene (SDHC promoter methylation), an epigenetic change. When a germline SDH mutation is identified, genetic counseling is strongly recommended because family members may be at risk for the same syndrome (Carney-Stratakis syndrome) or related tumors.

For more information about biomarker testing in gastrointestinal cancers, visit our Biomarkers and Molecular Testing section.

Risk assessment

For conventional (KIT/PDGFRA-mutant) GISTs, risk assessment is a structured method for estimating the likelihood that the tumor will recur or spread after surgery. It is based on three factors from the pathology report:

1. Tumor size
2. Mitotic count (≤5 or >5 per 5 mm²)
3. Tumor location (gastric GISTs generally carry a lower risk than small intestinal, duodenal, or rectal GISTs of comparable size and mitotic count)

Tumor rupture automatically places a GIST in the highest-risk category, regardless of size or mitotic count.

Based on these factors, GISTs are classified into one of four risk categories:

• No risk of progressive disease
• Low risk of progressive disease
• Moderate risk of progressive disease
• High risk of progressive disease

This risk category is used directly to determine whether adjuvant targeted therapy (imatinib given after surgery) is recommended. Patients with high-risk GISTs are typically offered three years of adjuvant imatinib, which has been shown to reduce the risk of recurrence significantly. Patients with no or low risk generally do not require adjuvant therapy. Note that this risk system does not apply to SDH-deficient GISTs or GISTs arising in the setting of NF1.

Treatment effect

Some patients with large or locally advanced GISTs receive imatinib before surgery (called neoadjuvant therapy) to shrink the tumor and make surgical removal safer and more complete. After surgery, the pathologist assesses the amount of viable tumor tissue remaining in the specimen. A significant tumor response — seen as extensive areas of scarring, cystic change, or myxoid degeneration with very few surviving tumor cells — is associated with a better outcome. Your report will describe the extent of viable tumor and any treatment-related changes in the tissue if neoadjuvant therapy was given.

Pathologic stage (pTNM)

The pathologic stage for GISTs uses the TNM staging system developed by the American Joint Committee on Cancer (AJCC). Note that this staging system applies to conventional adult GISTs without a known genetic syndrome. Tumor stage (pT) is based solely on tumor size.

Tumor stage (pT)

• pT1 — Tumor is 2 cm or smaller.
• pT2 — Tumor is more than 2 cm but no more than 5 cm.
• pT3 — Tumor is more than 5 cm but no more than 10 cm.
• pT4 — Tumor is more than 10 cm.

Nodal stage (pN)

• pN0 — No tumor cells found in any lymph nodes examined.
• pN1 — Tumor cells found in one or more lymph nodes.
• pNX — No lymph nodes were available for examination.

Because lymph node spread is so rare in conventional GIST, the overall stage and prognosis are driven primarily by the risk assessment score rather than by the TNM stage alone.

What is the prognosis for GIST?

The prognosis for GIST varies enormously depending on the risk category, mutation type, and subtype.

For conventional KIT/PDGFRA-mutant GISTs, the risk assessment score is the primary predictor of outcome. No-risk and low-risk GISTs are associated with an excellent prognosis — most patients are cured by surgery alone and do not experience recurrence. Intermediate-risk GISTs have a moderate chance of recurrence and are monitored closely. High-risk GISTs have a substantially higher chance of recurrence, particularly within the first several years after surgery, and adjuvant imatinib therapy is recommended to reduce this risk.

The specific gene mutation also affects both prognosis and treatment response:

• KIT exon 11 mutations respond best to imatinib and are associated with a relatively favorable prognosis among high-risk GISTs.
• KIT exon 9 mutations tend to be more aggressive and require higher-dose imatinib for optimal response.
• PDGFRA D842V mutations are resistant to imatinib but respond well to avapritinib, with good outcomes in most patients.
• Wild-type GISTs (including NF1-associated tumors) often do not respond to imatinib; management depends on the specific underlying driver.

For SDH-deficient GISTs, the standard risk assessment system does not apply, and prognosis is harder to predict. Some patients with metastatic SDH-deficient GIST follow an indolent course and survive for many years, while others experience more rapid progression. Clinical trial participation is recommended for advanced SDH-deficient GIST.

Overall, the development of targeted therapies — particularly imatinib and its successors — has transformed GIST from a cancer with very limited treatment options into one with among the best outcomes of any solid tumor in the metastatic setting. Your treatment team will use all of the information in your pathology report to develop a management plan tailored to your individual situation.

Questions to ask your doctor

Your pathology report contains important information that will guide your care. The following questions may help you prepare for your next appointment.

• Where exactly did my GIST start — stomach, small intestine, or another location?
• What is the tumor size, and what was the mitotic count?
• What risk category was my GIST assigned — no risk, low, moderate, or high?
• Did the tumor rupture during surgery, and does that affect my risk category?
• Were the surgical margins negative? Was the tumor completely removed?
• What was the result of molecular testing — was a KIT or PDGFRA mutation found, and in which exon?
• Is my tumor PDGFRA D842V-mutant, and does that affect which drug I should receive?
• Was my tumor tested for SDH deficiency — is it a conventional or SDH-deficient GIST?
• If SDH deficiency was found, should I be referred for genetic counseling?
• Do I need adjuvant imatinib after surgery, and for how long?
• If I received imatinib before surgery, how well did the tumor respond?
• Are there clinical trials available for my mutation type?
• What follow-up imaging and appointments will I need, and how often?