Pediatric-Like GIST

Background/incidence

Although the exact incidence is still somewhat unclear, it is now estimated that, in the United States, between 3,000 and 5,000 people each year develop GISTs. GISTs occuring in young patients (under age 18) is much rarer, occurring in perhaps 1% to 2% of all GIST patients.^{1, 2} In the past, age has defined pediatric GIST. With increased understanding over the last 5 years, the basic cause of pediatric GIST has became much clearer. With this new understanding, we now recognize that this form of GIST can be diagnosed after age 18 as well. This has resulted in a name change from pediatric GIST to pediatric-like GIST. An alternate name is SDH-deficient GIST (as explained below).

Biology

Pictured at the first international pediatric GIST meeting clockwise from lower right are part of the group: Jaap Verweij (back to camera), Tricia McAleer, Cristina Antonescu, David Josephy, Karen Albritton, George Demetri, Alberto Papo, Dick Singleton and Daniel Stepan.

Pediatric GIST can be divided into subgroups. These include Carney’s Triad, Carney Stratakis Syndrome (this also has several other names), and Pediatric GIST. The common thread that links all of these subtypes seems to be that they all have some type of defect in the succinate dehydrogenase (SDH) protein. Several new names have been proposed that cover all of these types. These include pediatric-like GIST and SDH-deficient GIST.

See Wildtype GIST & SDH: What to know by Jennifer Wright

The most familiar and perhaps the most common type of Pediatric-like GIST is when the patient only has GIST and no other tumor types. Pediatric-like GIST is much more common in girls than in boys. It often occurs between the ages of about 6 and 18, but a few cases of GISTs have occurred in younger patients (neonatal GIST, see Understanding Pediatric GIST. Pediatric-lke GIST can also be diagnosed in patients up to about age 35, and more rarely, after age 35. Pediatric GIST typically starts in the stomach (adult GIST can occur throughout the digestive tract).

The second well-known type of GIST affecting young people is called Carney’s Triad. It is named after Dr. P. Aidan Carney who first described it in 1977. Patients with Carney’s triad may have several different types of tumors including GIST, pulmonary chondroma, and/or functioning extra-adrenal paraganglioma. If any two of these tumors are present, a diagnosis of the “triad” can be made, particularly if age and sex factors are supportive. Some experts speculate that pediatric-like GIST’s are simply an incomplete form of Carney’s Triad and that some day these patients may develop chondromas and/or paragangliomas. This seems to be supported by the discovery that the underlying cause of all forms of pediatric-like GIST appears to be SDH deficiencies.

Click to expand image
Patient and disease characteristics by age group at diagnosis

In 2002, Dr. Carney and Dr. Constantine Stratakis reported on a new syndrome that was similar to, yet distinct, from Carney’s triad. They had found 12 patients in 5 families with two parts of the “triad,” paraganglioma and GIST. Since this condition appeared to be inheritable and the “true Carney’s triad” did not, Carney and Stratakis concluded that this syndrome was different than Carney’s triad and called it “Familial Paraganglioma and Gastric Stromal Sarcoma”(GIST is sometimes called “Gastric Stromal Sarcoma”). The patients varied in age from 9 to 46 years old at diagnosis with 9 of the 14 patients under the age of 23.

When looking at multiple medical reports, it appears that there may one other type of Pediatric GIST. The youngest GIST patients of all may be born with GIST and need surgery soon after birth. This type of GIST, called “Neonatal or Congenital GIST”, appears to affect both boys and girls (although girls are more common) and seems to start in the intestines instead of the stomach. We found 6 cases described as GIST in newborns, however there seems to be some doubt about whether or not these are really leiomyosarcomas or GISTs.

Show more pediatric-like GIST stories

The table below describes the differences typically seen between adult GIST and pediatric-like GIST.

 Diagnosis and Monitoring

The most common symptoms of pediatric GIST are:

• Anemia and other symptoms related to bleeding (such as blood in the stool). In one series of 6 patients, all presented with iron-deficient anemia³.
• Abdominal pain or abdominal mass⁴

As in adult GIST, prior to about 2000, pediatric-like GIST patients may have previously been diagnosed with leiomyosarcoma, leiomyoma, leiomyoblastoma, or GANT. As understanding of the biology of GIST increased, it was recognized that many tumors in these other categories were actually GISTs.

Risk Assessment

Pediatric GISTs behave differently than adult GISTs. Pediatric GIST may present with one or multiple tumors in the stomach (multi-focal). A tumor that is removed surgically may recur, either near the original site (a local recurrence) or at a distant site such as the liver. Local recurrences in the stomach may be a single tumor or multiple stomach tumors. When a tumor recurs at a distant site it is called a metastasis.

The risk of recurrence in adults with GIST has been fairly well defined. Two factors, size of the primary tumor and rate of growth, (measured by the mitotic rate) are the primary factors that affect the risk of recurrence in adults. In pediatric GIST however, work done at the U.S. Armed Forces Institute of Pathology (AFIP), suggests that these factors probably do not accurately predict the risk of recurrence in pediatric GIST. The table below is probably one of the most complete risk comparisions between adult GIST and pediatric GIST.

Treatment

It is important to find doctors experienced in GIST. This experience comes in two basic types: experts in pediatric cancers and experts in adult GIST cancer. Both have unique perspectives and experiences. The best approach might be when doctors from both fields collaborate with each other. See Consolidating Resources.

Surgical removal of the tumor(s) has historically been the primary treatment for pediatric GIST. The types of operations have historically varied from a simple local excision to a total gastrectomy. In some cases, surgery provides long-term relief. In other cases, tumors return, either locally (near the original site, such as another stomach tumor(s)), or distant from the original site (metastases).

Recently, dramatic success has occurred in the treatment of adults with metastatic or inoperable GISTs (in cases where surgery is not possible). The genetic defects that cause adult GIST (KIT and PDGFRA mutations) can now be targeted with a drug called Gleevec (also known as imatinib and Glivec). While this drug (and a second generation inhibitor, Sutent) is very effective in adult GIST, the vast majority of pediatric GISTs do not have the same types of mutations. Response data is limited, but the early ancedotal indications are that Gleevec is not as effective in pediatric GIST as it is in adult GIST. Some very preliminary data (3 patients reported at the 2006 American Society of Clinical Oncologists (ASCO) meeting) show some activity for Sutent.

Dr. Lee J. Helman’s Presentation

View The NIH Pediatric & Wildtype GIST Clinic Presentation

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