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GIST Pathology Questions and Terminology

 

Questions Patients Often Ask

 

1. Some of my pathology samples were shipped to another lab for analysis: does this mean my hospital pathologist is unfamiliar with GIST?

Many labs routinely send away samples needing tests not regularly performed on-site.  These might include immunohistochemistry and mutational testing.

 

2. My pathology report shows a mitotic count per 10 high-power fields (not 50 fields) or does not actually give any count but says "scant mitoses": Is this reliable?  Could it be re-counted if necessary?

It is important to get an actual count of mitoses per 50 HPF because too small a sample may give unrepresentative results.  Your surgeon or your oncologist can request the pathologist to provide a more complete analysis if the information would change the way your case will be managed.  This is generally the case for a large sample (i.e., surgical resection specimen).  In a small biopsy sample (core needle biopsy or endoscopic mucosal biopsy), there is usually not enough tissue for a mitotic count in 50 high power fields, but in certain cases the mitotic count in a smaller number of fields can help guide subsequent clinical management.

 

3. If my GIST pathology report seems to be missing some information compared to the descriptions in this discussion, should I ask for my sample to be sent to an expert sarcoma pathologist?

You should feel comfortable asking your doctor about your pathology report.  Your doctor may discuss the diagnosis with your pathologist, who should be able to provide additional details if needed for risk assessment.  In rare cases with unusual histologic patterns or unusual findings by immunohistochemistry (for example, KIT-negative GISTs), your pathologist may decide to send your slides to a pathologist with special expertise in GIST diagnosis to help confirm the diagnosis.

 

4. My pathology report calls my tumor "benign" - what does this mean?  Was it cancer?  Do I need follow-up?  Or does it mean the pathologist is not very familiar with GIST?

If a GIST is said to be benign, that means that at the time of resection it had not metastasized, and the chance of future metastasis is deemed to be very, very small.  Expert pathologists prefer not to use the word "benign" for GIST, as there is a chance of recurrence for all GISTs 2 centimeters in size or larger, and surgical removal is recommended for all such GISTs.  Only GISTs smaller than 2 centimeters may be considered benign by some, since the risk of aggressive behavior approaches 0%.  Some of these small tumors may be destined to acquire the characteristics that enable them to grow, but most "tumorlets" less than 2 cm do not grow larger and are commonly found in stomachs resected for other reasons and in autopsies.

 

5. Why doesn't my pathology report give a "grade" or a "stage" for my GIST?

The AJCC "TNM" staging was not available for GIST prior to 2010; therefore, older reports will not include a stage.  Staging schemes for other sarcomas do not apply to GIST.  Pre-2010 reports on primary tumors should compare to the risk-of-recurrence criteria available at the time of the report.  The NIH consensus criteria became available in 2002, and the AFIP criteria were recommended by the NCCN in 2007.   However, if older reports include the required information, it is possible to assign a stage using the 2010 AJCC staging scheme later.  Since the AJCC staging and the NCCN guidelines are essentially equivalent, either scheme is appropriate.

 

6. Why doesn't my GIST pathology report include information about lymph nodes?

GIST very seldom spreads to lymph nodes (unlike many cancers), with the exception of very rare GISTs in children.  If the surgeon had noticed any lymph nodes that looked enlarged, they would have been removed.  The pathologist will describe any nodes included in your surgical specimen.


7. Do I need a second opinion about my GIST diagnosis or risk of recurrence since GIST is rare and many pathologists will seldom see GIST cases?

Most pathologists are very aware of GIST and able to apply the criteria discussed above.  Only in a small subset of unusual cases are additional expert opinion needed and this is usually requested by the initial pathologist who first examined the case. 


8. Why doesn't my pathology report include mutation testing of the genes for KIT and PDGFRA?

Some cancer centers do mutation testing automatically, but most do not.  Rarely, mutational testing might be needed for diagnosis, if other test results are not definitive (such as KIT-negative GISTs and/or unusual immunohistochemical or morphologic features).  Even if mutation testing is done, it may be reported separately from your surgical pathology report.  Not all experts agree that mutational testing of every GIST is necessary prior to initial treatment.

 

9. Do I need mutation testing on my GIST?

Mutation testing should be considered in these situations:

  • for intermediate-risk and high-risk non-gastric tumors, because they could have the exon 9 KIT mutation, for which a higher drug dose would be appropriate if the tumor recurs
  • for KIT-expression-negative tumors or others suspected of having PDGFRA mutations for which a drug other than imatinib might be appropriate if the tumor recurs
  • for young patients whose tumors are more likely to be wild-type (lacking mutations in KIT or PDGFRA genes)

 

10.  If I need mutation testing done now or later, how would I get that done?

Your surgeon or oncologist can order this.  Your pathologist might perform the analysis locally or else send samples away to a reference laboratory.

 

11.  Are there additional tests that may refine the risk of recurrence for GIST (either local recurrence of distant metastasis)? 

Pathologists and their colleagues have not reached consensus about additional testing that might help predict how likely it is that a surgically resected primary GIST might recur, but this is a focus of attention.  Patients at high risk of recurrence might choose to take imatinib (Gleevec) on a preventive basis (called adjuvant therapy); therefore, improved risk assessment is a clinically useful goal. 


12.  How long will my tumor samples be kept in case I need more testing later?

  • Formalin-fixed paraffin embedded (FFPE) blocks are retained for at least 10 years by most institutions; many retain this material indefinitely.  All current tests for GIST can be performed using FFPE tissue; it is likely that any new testing will also be adapted to this type of tissue preservation as it is the most common type of sample available.
  • Frozen samples may be stored and can be used for most tests, but offers few advantages at this point since all testing has been optimized for FFPE use.

 

13.  If I later go to a different cancer center, will pathology testing be repeated?

If you go to a specialized sarcoma clinic, your samples would usually be at least reviewed by an expert GIST pathologist.  Some testing might be repeated if the slides are not provided by your home institution or if the expert pathologist is more comfortable with results from his or her own laboratory.

 

14.   Can I have extra tumor samples of my GIST stored for future use? 

This is a good idea because more is being learned about GIST every year.  If new treatments are offered in the future, you may need a test on your tumor sample to know if the treatment applies to our type of GIST.  You can arrange for extra samples to be saved by asking your surgeon in advance of your surgery.  The surgeon will have to contact the pathology department to make arrangements.  See this link for details.  However, it should be noted that in almost all instances, the FFPE tumor sections taken for routine pathology will be enough for any additional testing.

 

15.   Can I contribute GIST samples to a tumor bank or to GIST researchers?

Yes, and this is a great help to GIST research!  You can give samples to the hospital where your surgery is done (if they are doing GIST research) as well as to other tumor banks or investigators.  You must request this in advance to ensure that extra tissue is saved at the time of your surgery.  See the page GIST Tissue Banks.

 

16.  How does tumor rupture affect prognosis, and does it matter whether the rupture was pre-surgery or during surgery?

When a tumor ruptures, cells are spilled into the peritoneal cavity.  This increases the risk of recurrence since some of these cells could potentially survive and begin growing on the abdominal membranes or elsewhere.  The current risk schemes do not account for this, but some physicians would treat a ruptured GIST similarly to one with positive margins or incomplete resection.  Very careful monitoring is needed, and the physician and patient may consider adjuvant (preventive) drug therapy. With regard to rupture, it is not always clear to the pathologist that this has occurred. In some cases, the surgeon will send part of the tumor separately, or in many separate pieces. However, the pathologist doesn't know if rupture occurred intraoperatively or if the tumor fell apart after removal. The gross examination would include the description if the the tumor was received fragmented, or seemed to have been excised piecemeal. For accurate information regarding rupture, the operative report is needed (not just the pathology report).
 

 

Terminology

My GIST pathology report includes some of these terms.  What do these mean and why do they matter?

Atypia:  abnormal shape and/or size of cells; may be focal (in particular spots) or diffuse (throughout the sample)

Coagulative necrosis:  an area of tissue that has died due to lack of blood supply.  Under the microscope the cells appear "ghostly" because they do not take up stain as living cells do, but their cell structure is preserved.

Cystic degeneration: cyst-like areas of degenerated or necrotic (dead) tissue within the tumor.  While the degree of necrosis is important in other sarcomas for grading, this does not seem to be the case for GIST.

Cytology: examination of cells under the microscope; the study of cells.  Usually this refers to an area of pathology that uses the features of individual cells (rather than the architectural properties of tissues) for diagnosis.

Cytoplasm:  The parts of a cell between the cell membrane and the border of the cell nucleus (the nucleus is excluded)

Dedifferentiation: An abnormal process by which tumor cells lose their characteristic specialized form and become more primitive and less readily recognized as having a specific type of differentiation.

Differentiation: The normal process by which a less specialized cell becomes a more specialized cell type that is structurally and functionally different; recognizable as a more mature phenotype.  The pathologist may form a working diagnosis of tumor type from the differentiation of the tumor cells and how closely they resemble normal cells of some tissue type.

Dysplasia: Excess growth of abnormal-appearing cells, usually a precancerous condition in which cells show extra proliferation causing an accumulation of abnormal tissue that may be the start of a tumor

Eosinophilic cytoplasm: Cell cytoplasm that stains with the pink dye, eosin.

Fascicles: The appearance of bundles of cells within the structure of tumor tissue.

Fusiform: Cells shaped like a spindle, wider in the middle and tapering toward the two ends.

Golgi-pattern staining: perinuclear dot-like staining on KIT immunohistochemistry; this feature has no known significance or association with particular KIT mutations.

Hemorrhage: Bleeding into an organ, body cavity or tumor.

High cellularity, cell density:  Tightly packed cells within the tumor, sometimes indicating faster cell proliferation.

Hyperplasia: Excessive growth of normal-appearing cells in a tissue.

Infiltration or invasion:  growth of tumor cells into the tissue of adjacent anatomical structures.  Usually GISTs grow with non-invasive, pushing borders.  Invasive or infiltrative borders may indicate a more aggressive tumor.

Liquifactive necrosis: An area of tissue that has died and the cell structure is no longer present because the dead cells have been digested, leaving a liquid-like appearance.

Necrosis:  See coagulative necrosis and liquifactive necrosis

Nuclear atypia:  Abnormal cell nuclei; can suggest malignancy in the correct context.

Nuclear palisading:  Alignment of cell nuclei so that their appear to be alternating blue and pink regions.  There is no known significance of this pattern.

Perinuclear vacuolization: The presence of usually one or two large vacuoles (large intracytoplasmic vesicle) near the cell nucleus that can indent the nucleus.  The significance of this is uncertain.
 
Pleomorphic:  Tumors showing marked variation in cell size and shape.

Serosal penetration: GISTs normally grow outward from their origin in the wall of the GI tract, eventually piercing the outer covering (serosal membrane) and growing within the abdominal cavity (peritoneum).

Skeinoid fibers: thread-like structures often seen in the tissue of GISTs from the small intestine.  Their significance is uncertain.

Ulceration:  Describes damage to the inner lining of the GI tract (the mucosa) at the point where a GIST undermines and creates a defect in the inner lining of the bowel through which blood or necrotic material from the GIST may enter the GI tract.

 

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