C h a p t e r 7
Neoplasia
153
Childhood Cancers and Late
Effects on Cancer Survivors
Despite progressively improved 5-year survival rates,
from 56% in 1974 to 75% in 2000, cancer remains the
leading cause of disease-related deaths among children
between 1 to 14 years in the United States.
68
Leukemia
(discussed in Chapter 11) accounts for one-third of
cases of cancer in children ages 1 to 14 years.
1
Cancer
of the brain and other parts of the nervous system are
the second most common, followed by tissue sarcoma,
neuroblastoma, renal cancer (Wilms tumor, discussed
in Chapter 26), and non-Hodgkin and Hodgkin lym-
phoma (discussed in Chapter 11).
1
Two young girls with acute lymphocytic leukemia are
receiving chemotherapy (From National Cancer Institute
Visuals. No. AV-8503-3437.)
Incidence andTypes
of Childhood Cancers
The spectrum of cancers that affect children differs
markedly from those that affect adults. Although most
adult cancers are of epithelial cell origin (e.g., lung can-
cer, breast cancer, colorectal cancers), childhood cancers
usually involve the hematopoietic system (leukemia),
brain and other parts of the nervous system, soft tissues,
kidneys (Wilms tumor), and bone.
1,68
The incidence of childhood cancers is greatest during
the first years of life, decreases during middle childhood,
and then increases during puberty and adolescence.
68
During the first 2 years of life, embryonal tumors such
as neuroblastoma, retinoblastoma, and Wilms tumor
are among the most common types of tumors. Acute
lymphocytic leukemia has a peak incidence in children
2 to 5 years of age. As children age, especially after they
pass puberty, bone malignancies, lymphoma, gonadal
germ cell tumors (testicular and ovarian carcinomas),
and various carcinomas such as thyroid cancer and
malignant melanoma increase in incidence.
A number of the tumors of infancy and early child-
hood are embryonal in origin, meaning that they exhibit
features of organogenesis similar to that of embryonic
development. Because of this characteristic, these tumors
are frequently designated with the suffix “
-blastoma
”
(e.g., nephroblastoma [Wilms tumor], retinoblastoma,
neuroblastoma).
2
Wilms tumor (discussed in Chapter 25)
and neuroblastoma are particularly illustrative of this
type of childhood tumor.
Biology of Childhood Cancers
As with adult cancers, there probably is no one cause
of childhood cancer. Although a number of genetic
conditions are associated with childhood cancer, such
conditions are relatively rare, suggesting an interac-
tion between genetic susceptibility and environmental
exposures. The most notable heritable conditions that
impart susceptibility to childhood cancer include Down
syndrome (20- to 30-fold increased risk of acute lym-
phoblastic leukemia),
1
neurofibromatosis (NF) type 1
(neurofibromas, optic gliomas, brain tumors), NF type 2
(acoustic neuroma, meningiomas), xeroderma pigmen-
tosum (skin cancer), ataxia-telangiectasia (lymphoma,
leukemia), and the Beckman-Wiedemann syndrome
(Wilms tumor).
2,69
While constituting only a small percentage of
childhood cancers, the biology of a number of these
tumors illustrates several important biologic aspects
of neoplasms, such as the two-hit theory of recessive
tumor-suppressor genes (e.g., RB gene mutation in
retinoblastoma); defects in DNA repair; and the histo-
logic similarities between embryonic organogenesis and
oncogenesis. Syndromes associated with defects in DNA
repair include xeroderma pigmentosa, in which there is
increased risk of skin cancers due to defects in repair
of DNA damaged by ultraviolet light. The development
of childhood cancers has also been linked to genetic
imprinting, which is characterized by selective inacti-
vation of one of the two alleles of a certain gene (dis-
cussed in Chapter 5).
69
The inactivation is determined
by whether the gene is inherited from the mother or
father. For example, normally the maternal allele for the
insulin-like growth factor-2 (IGF-2) gene is inactivated
(imprinted). The Beckwith-Wiedemann syndrome is an
overgrowth syndrome characterized by organomegaly,
macroglossia (enlargement of the tongue), hemihyper-
trophy (muscular or osseous hypertrophy of one side
of the body or face), renal abnormalities, and enlarged
adrenal cells.
2
The syndrome, which reflects changes
in the imprinting of IGF-2 genes located on chromo-
some 11, is also associated with increased risk of Wilms
tumor, hepatoblastoma, rhabdomyosarcoma, and adre-
nal cortical carcinoma.
Diagnosis andTreatment
Because many childhood cancers are curable, early
detection is imperative. In addition, there are several
types of cancers for which less therapy is indicated than
for more advanced disease. Therefore, early detection
often minimizes the amount and duration of treatment
required for cure.
