Understanding pediatric GIST may provide important clues
Gastrointestinal Stromal Tumors (GIST) in young people is known as pediatric GIST.
It is thought to be very rare. But is it as rare as we think? Are the 27 young members
of The Life Raft Group a significant portion of the pediatric GIST patients in the
world? As we try to answer that question, let's also take a closer look at some
of the different types of pediatric GIST.
Like adult GIST, pediatric GIST can be further divided into subgroups. The most
familiar and perhaps the most common type does not seem to have a distinct name
so let's just call it "Pediatric GIST." It most commonly affects girls between the
ages of about 6 to 18 and almost always starts in the stomach. Dr. Carney
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. It is important that patients less than 35 years of age
who have any one of the three tumors be examined periodically in search of the others
according to Dr. Carney. By 1983, 24 cases had been reported and, by 1999, 79 cases
had been reported. Carney's triad affects mostly younger females but there is one
report of an 84 year old man who was found to have Carney's triad during an autopsy.
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 like there may be one more
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.
A search of the internet found seven scientific papers that report more than one
pediatric GIST patient from a single institution. These papers provide important
insights into the mysteries of pediatric GIST. The Life Raft Group pediatric GIST
database forms an eighth source of this type of data and is the second largest series.
Dr. Sonam Prakash, Dr. Christina Antonescu and others of Memorial Sloan-Kettering
Cancer Center (MSKCC) in New York reported on 15 cases of young people with GIST.
Of the 350 GIST patients in the MSKCC database there were 5 patients less than 18
years old (1.4% of all of their GIST patients) and 10 patients between 18 and 30
years old. Dr. Antonescu is the principal pediatric GIST researcher for The Life
Raft Group research project.
The MSKCC team wanted to look at the differences between the younger patients (below
18) and the older patients (18 to 30 years old). They found that the younger patients
tended to fit the "classical" pattern of pediatric GIST. The older group had characteristics
of both adult GIST (such as a high rate of KIT mutations) and pediatric GIST. The
tumors of patients in the older group tended to express genes in patterns that were
similar to the younger pediatric GIST patients rather that the adult GISTs. Two
of the patients in the older group had characteristics that strongly resembled those
of the younger group, and the MSKCC doctors noted that at least one of these cases
may have developed in childhood and not detected until adulthood.
Some of the things the MSKCC team and others have noted to be typical of pediatric
• Affects mostly females. Almost always occurs in the stomach, often as multiple
• Tumors do not usually have the KIT or PDGFRA mutations that occur in the
vast majority of adult GISTs.
• Metastases to the lymph nodes appear to be more common than adult GIST.
• The tumor cells tend to be shaped differently. Pediatric GISTs tend to resemble
"epithelioid" cells (more rounded and more similar to typical non-sarcoma type cancers),
while adult GISTs tend to have a "spindle" shape.
Dr. Victoria Price, Dr. Alberto Pappo and others from the Hospital for Sick Children
in Toronto, Canada reported on six young GIST patients. They reviewed hospital records
that covered an 11 year span. They had treated five of the patients at their hospital
and had acted as a consultant for the pathology of the sixth patient. Four of the
patients were girls and two were boys. One of the boys and one of the girls had
additional tumor(s) that were typical of "Carney's Triad." Another boy (age 13)
did not fit the usual pattern of pediatric GIST because of his gender (male) and
the fact that he had a mutation in the c-kit gene (which is more typical of adults
Dr. Monica Cypriano, Dr. Najat Daw and others from St. Jude Children's Research
Hospital in Memphis, Tennessee reported on seven young GIST patients. This series
was somewhat unusual in that only two of the seven patients had tumors that started
in the stomach. The patients in this study were diagnosed over a 40 year time span
between 1962 and 2002.
There are reports of two cases from Ireland and three cases from Atlanta, Georgia
in the United States. All five of these cases started in the stomach.
A 1999 report by Dr. Jody Z. Kerr and others reported four cases of Gastrointestinal
autonomic nerve tumors (GANTs). GANTs are tumors that are very similar to GISTs.
The authors noted many features that were similar to pediatric GISTS. Given the
incomplete understanding of GISTs in 1999, the question that arises is whether these
tumors would have been classified as GISTs if they were examined using today's standards.
The largest case series comes from the Armed Forces Institute of Pathology (AFIP).
This study looked at 44 cases of pediatric GISTs that were submitted to the AFIP
from the United States and Canada between 1970 and 1996. Patients in this study
ranged from 5 to 21 years old at the time of diagnosis. Only GISTs with a primary
tumor in the stomach were included in this study. These 44 cases represented 2.5
percent of the stomach GISTs submitted to the AFIP in this time frame (44 of 1782
The AFIP series is particularly striking in its gender distribution according to
age. They report 24 females between the age of 6 and 15 and no males. Between the
ages of 16 and 21, however, the gender distribution is completely different with
11 males and 8 females. They did report one 5 year old male.
When you combine all of the reports some patterns begin to emerge (subject to the
considerable limitations of this review). Patients seem to form several groups according
to age and primary tumor location:
• Newborns-primary tumors tend to be located in
• 1 to 3 years old- We were unable to find any reports
of patients diagnosed between the ages of one to three.
• 4 to 5 years old- Three of four were located in
the intestines, only one in the stomach.
• Summary-Newborns to 6 years old-Seems to affect
both females and males with a tendency towards intestinal primary (includes small
intestine, cecum and colon). Probably needs more expert GIST pathology review to
verify that these are true GISTs and not leiomyosarcomas.
• 6 to 15 years old- The vast majority are females
and the vast majority have a stomach primary. This group appears to be the largest
and probably comes closest to being representative of "Pediatric GIST." It is interesting
to note that 8 of the 9 males in this group had primary tumors in the stomach, just
like the girls.
• 16 years and up- Although still dominated by females
and a primary tumor location in the stomach, we start to see a transition towards
adult GIST with both more males and more non-stomach primary tumors.
Some observations and questions
It is interesting to note that there are more cases of Carney's triad reported in
the literature than pediatric GIST; but in the eight reported series of patients
(including The Life Raft Group series) Carney's triad seemed to be a distinct minority.
This raises the question of the ratio of pediatric GIST to Carney's triad. Are there
a lot more pediatric GIST patients than the 79 reported Carney's triad patients?
1. Are the newborn GISTs really GISTs?
2. Is the intestinal location of GISTs in patients below six years old an important
clue or a red herring?
There are some differences between these series of patients. The AFIP series looked
only at GISTs with a stomach primary. The pathology expertise almost certainly varies
considerably; some of these cases may have incorrectly been classified as GIST.
Some series used different age cutoff points (29 for The Life Raft Group, 21 for
the AFIP and 18 and 30 for the MSKCC series).
There are also some limitations to this newsletter article on pediatric GIST. It
is based on a cursory review of the literature. Many articles were only reviewed
in abstract form. It is very possible that some patients have been counted more
than once (such as in a series and in an individual article).
Six years ago GIST was very poorly understood. The basic research that found a molecular
target (KIT) and an excellent targeted drug (Gleevec) has sparked tremendous advances
in the understanding of GIST. Today adult GIST can be divided into many different
groups. Although in its beginning stages, therapy is beginning to be optimized for
these different groups. The Life Raft Group research team includes many of the top
GIST researchers in the world. This group has led the way, doing research that has
revolutionized the treatment of GIST and they are working to understand and develop
more effective therapies for pediatric GIST. Understanding pediatric GIST may provide
important clues to help them understand adult GIST as well.