2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Desmoid-Type Fibromatosis in Children:
A Step Forward in the Cooperative
Group Setting
By Natalie Pounds, MD, and Stephen X. Skapek, MD
Overview: Desmoid-type (aggressive) fibromatosis (desmoid
tumor) is a soft tissue neoplasm that can occur in both
children and adults. Although it is formally classified as an
intermediate-grade neoplasm because of its propensity for
locally invasive growth, it can lead to severe and lifethreatening
problems. Because metastases do not arise from
desmoid tumor, therapeutic interventions have historically
focused on surgery or radiation to achieve local tumor control.
These approaches may be ineffective or impractical for some
children. In those cases, systemic therapy with cytotoxic or
noncytotoxic therapy has been used. Because of the relative
DESMOID TUMOR, also known as aggressive or
desmoid-type fibromatosis, represents a relatively rare
neoplasm that affects both children and adults. The overall
incidence of desmoid tumor is estimated to be two to four
new diagnoses per 1 million people per year. 1 Desmoid
tumor incidence peaks in individuals from 6 to 15 years of
age and again between puberty and 40 years of age in
women. There seems to be a female predominance during
adolescence. 2,3 Mortality from desmoid tumor is rare but has
been reported in children. Nonetheless, the disease poses
substantial problems related to diseases progression and
consequences from therapy.
The most common sites of origin of desmoid tumor are in
the abdominal wall, intra-abdominal or mesenteric sites, but
extra-abdominal sites include extremities, shoulder girdle,
chest wall, and inguinal region. 1,4 Children tend to develop
desmoid tumors in similar extra-abdominal locations, but
both infants and young children have a higher propensity for
tumors in the head and neck region, 2 a rare disease site for
adults. Patients with intra-abdominal desmoid tumors typically
are asymptomatic or have symptoms associated with
an enlarging mass, including weight loss, cachexia, malaise,
renal failure, and small bowel compression or perforation.
Invasion of adjacent muscle, nerve, or vessels can cause
pain, limitation in joint movement, or contractures and
deformities. Desmoid tumor may be multifocal, but bona-fide
metastasis does not occur. 1,4
Desmoid tumor poses a substantial clinical problem because
it carries a propensity to recur after seemingly complete
surgical resection. The reason for the high recurrence
rate is apparent from histologic studies. Desmoid tumor has
a benign histologic appearance, lacking nuclear and cytoplasmic
features of a malignant tumor. 1 Unlike most sarcomas,
which are usually separated from adjacent structures
by a pseudocapsule, desmoid tumor often displays an irregular,
infiltrating border. Several histologic differences have
been noted between desmoid tumors in children and adults.
First, higher mitotic rates are seen in childhood tumors.
Second, lesions tend to be more cellular. 5 Whether rare
mitotic activity contributes to their relative resistance to
cytotoxic therapy is not clear.
Desmoid tumor is typically a sporadic disease with no
identified cause. However, it is clear that there may be an
underlying genetic component in disease pathogenesis. This
rarity of this neoplasm in children, knowledge on the use of
chemotherapy is based largely on anecdotal reports or retrospective
series. Limited conclusions can be drawn, though,
from these types of reports. In the last 10 years, two prospective
phase II clinical trials of chemotherapy for children with
desmoid tumor have been conducted in cooperative clinical
trials centered in North America. We review the results of
those clinical trials and suggest future directions for systematically
approaching this disease to better define the role of
chemotherapy for children with desmoid tumor.
genetic component is most evident in Gardner syndrome, a
well-described variant of familial adenomatous polyposis
(FAP), an autosomal-dominant disease characterized by the
presence of innumerable adenomatous polyps in the colon
(OMIM #175100). Patients with Gardner syndrome have a
number of extracolonic manifestations, including osteoma
and desmoid tumor. Both FAP and Gardner syndrome are
associated with germline mutation in the adenomatous
polyposis coli (APC) gene. 6 The APC protein acts, in part, to
promote degradation of �-catenin, an intracellular protein
that aids in the transduction of cell proliferation signals to
the nucleus. A number of studies during the past decade
have identified somatic mutations in APC and CTNNB1, the
gene encoding �-catenin, in sporadic desmoid tumor cases 7 ;
both mutations ultimately enhance �-catenin activity. Despite
an association with Gardner syndome, heritable predisposition
is clearly the less common form of desmoid tumor.
Other causative factors include trauma and estrogens.
The former is typically surgical in nature, and it may be
most relevant to FAP patients. The high frequency of abdominal
disease in this population seems to correlate with
mesenteric fibromatosis, a putative precursor lesion the
presence of which correlates with increased numbers of
abdominal operations. 8 The role of estrogen signaling was
originally suggested by the increased incidence during pregnancy
and enhanced tumor growth rate in pregnant women
when compared with that in men or premenopausal or
postmenopausal women. 4 This association is supported by
evidence of strong estrogen receptor expression in more than
80% of desmoid tumors. 9
Surgery and Radiation as the Historical Standard
of Care
Although we make a case that optimal therapy for desmoid
tumor in a child begins with a multidisciplinary
From the University of Texas Southwestern Medical Center and Center for Cancer and
Blood Disorders, Children’s Medical Center, Dallas, TX.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Stephen X. Skapek, MD, University of Texas Southwestern
Medical Center, 5323 Harry Hines Blvd, Mail Code 9063, Dallas, TX-9063; email: Stephen.
Skapek@utsouthwestern.edu.
© 2012 by American Society of Clinical Oncology.
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