[tri-med] FYI - Hepatoblastoma and Wilm's Tumours

This is a repost of an a mail that I sent to the list some time ago
regarding Wilm's. The letter from John is probably old now, but the
information contained in it is still valuable.


I am including two previous posts on the subject - one a letter (with
references) from Dr Carey that was published in the Soft Times and another
post that I made some time ago

PROFESSIONAL VIEWPOINT by Dr. John C. Carey

In this article I will summarize the known information on the
association of Wilms tumor in the trisomy 18 syndrome. Wilms tumor is a
complex malignancy (cancer) arising from the kidney and develops almost
exclusively in children. It occurs in about 1 in 10,000 chlordane under
the age of 15 and is one of the most common solid tumors of the
pediatric population.


The idea that Wilms tumor occurs with increased frequency in individuals
with trisomy 18 was originally raised in 2 case reports in the medical
literature that appeared in 1969 and 1981. Then about 10 years ago 2
children, both that I knew through my connections with SOFT, developed a
Wilms tumor. The observation of these two children led my colleagues and
I to present these individuals at a number of scientific meetings in the
early 1990's.

After that time three other children with trisomy 18 who had a Wilms
tumor came to my attention during the mid-1990's. These cases led us to
feel that Wilms tumor does occur with increased frequency in older
children with trisomy 18 as part of the syndrome.

Let me briefly review the reasoning process that supports the idea that
the occurrence of the Wilms tumor is a feature of trisomy 18, rather
than a coincidence. The evidence proceeds like this:
1) WE re now aware of a total of 11 children with trisomy 18 who have
developed a Wilms tumor. Nine of the children are from the USA
(including 2 recently recognized children currently under treatment) and
2 from Europe. Based on the frequency of trisomy 18, the possibility of
survival after 12 months, and the occurrence of Wilms tumor, in general
we would expect the occurrence of only 1 case in the last 50 years in
the USA. Since we are aware of 9 cases in about 30 years, we feel there
is an association.
2) The Wilms tumor in children with trisomy 18 is different than that
seen in the general population: The age of onset is later, rather than
the average age being near 2 years of age, the age at diagnosis in
trisomy 18 is around 7 years. Also, the Wilms tumor in trisomy 18 is
frequently associated with premalignant kidney findings that are called
"nephrogenic rests". Moreover, we are aware of 7 additional children
with trisomy 18 that have developed a different, but somewhat related,
malignancy of the liver called hepatoblastoma. (Wilms tumor and
hepatoblastoma are both known to occur with increased frequency in other
birth defect syndromes, supporting that there is some connection between
the two).
In summary, these points indicate to us that children with trisomy 18
are at increased risk for Wilms tumor, and probably the related tumor
called hepatoblastoma.

The actual risk for a child with trisomy 18 to develop either one of
these tumors is probably low and certainly less than 1%. We would
recommend periodic ultrasound to include examination of the kidney and
liver starting at 6 months of age. Most likely the risk for
hepatoblastoma is eliminated after three years of age. From that point
the exam would focus on both kidneys. The exact time to stop the
abdominal examinations is not known, but most certainly should proceed
into adolescent years. The oldest child that we are aware of with
trisomy 18 and a Wilms tumor was almost 14 years of age at diagnosis.
The timing regarding how frequently to do the ultrasounds is not clearly
known, but based on the recommendations for similar conditions we
suggest examinations every 6 months.

I have included two key recent references for anyone interested in
obtaining all of the written information on this topic:

Beckwith B. AMERICAN JOURNAL OF MEDICAL GENETICS 79:268-273,1998

Olson JM et al. MEDICAL AND PEDIATRIC ONCOLOGY 24:305-309, 1995

John C. Carey, M.D.M.P.H.
Professor of Pediatrics
Division on Medical Genetics
University Hospital
Health Science Center
50 North Medical Dr. MREB 4213
Salt Lake City, UT 84132
(801)581-8943
(801)585-7252 Fax

from the September/October 1999 edition of the SOFT TIMES.

Here is a post I made a while back with some journal references at the end
The history behind the Wilm's Tumour alert started about 10 or more years
ago.
Children with mosaicism and hemihypertrophy have always been known to have
an increased risk of tumours, particularly Wilm's. One of the mums, Joan
Harper (Kyle T-18 mosaic) was aware of this and doing the regular screening.
As she spoke to other mums she started to see more and more T-18 children
developing Wilm's tumour so she raised this with Dr Carey.

There were a couple of cases only reported in the literature but indeed they
felt (10 years ago) that the 6 known cases of Wilm's Tumour (and that
includes heptablastoma's - a similar type of tumour in the liver) in
surviving T-18ers within the US was significant. As a result it was
suggested that children with T-18 have regular screenings for Wilm's Tumour.

Since then there have been even more correlations in the literature between
chromosome 18 and Wilm's Tumour. (I will tack some references on the end of
this mail). Currently the recommendations for screening from Dr Carey are
every 3 to 6 months from 12 months to 15 years of age or so. These are the
same guidelines as for Beckwith-Wiedemann Syndrome where again there is a
correlation between Trisomy 11p and Wilm's Tumour.

I know of two more cases this year alone of children with T-18 being
diagnosed with Wilm's which includes our very own Dylan from the list.
Although there is a link between T-18 and Wilm's we really shouldn't be
alarmist about it - its still rare, but being on the rare side of statistics
once I for one am not taking the chance again. Besides ultrasounds are
fairly harmless and not invasive (Alex actually goes to sleep during his) My
biggest problem is remembering to get the scans done!! But now that Alex is
in school I think I have a system as we have a 4 term school year so I will
get the scans done each set of school holidays. Alex's pediatrician actually
wants a CT scan of Alex's kidneys every few years (because of the
limitations of ultrasounds) but we have agreed that we will not do them
until Alex can co-operate for the scan without sedation.

If you have a fax I can send the information from SOFT that Joan sent me
which includes a letter of explanation from Dr Carey as to why.

Here are a number of references from med-line
Kaneko Y, et al; Further chromosome studies on Wilms' tumor cells of
patients without aniridia. (Cancer Genet Cytogenet, 1983 Oct,)

2   Olson JM, et al; Non-11p constitutional chromosome abnormalities in
Wilms' tumor patients. (Med Pediatr Oncol, 1995 May,)

3   Karayalcin G, et al; Wilms' tumor in a 13-year old girl with trisomy 18.
(Am J Dis Child, 1981 Jul)

4   Sheng WW, et al; Chromosome analysis of 31 Wilms' tumors. (Cancer Res,
1990 May,)

5   Bove KE, et al; Hepatoblastoma in a child with trisomy 18: cytogenetics,
liver anomalies, and literature review. (Pediatr Pathol Lab Med, 1996 Mar,)

6   Kondo K, et al; Chromosome abnormalities in tumor cells from patients
with sporadic Wilms' tumor. (Cancer Res, 1984 Nov,)

7   Betts DR, et al; Routine karyotyping in Wilms tumor. (Cancer Genet
Cytogenet, 1997 Jul,)

8   Kullendorff CM, et al; Chromosomal aberrations in Wilms' tumour. (Eur J
Pediatr Surg, 1997 Oct,)

9   Solis V, et al; Cytogenetic changes in Wilms' tumors. (Cancer Genet
Cytogenet, 1988 Sep,)

10   Mertens F, et al; Cytogenetic analysis in the examination of solid
tumors in children. (Pediatr Hematol Oncol, 1994 Jul, )

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