FA is a rare cancer susceptibility syndrome with increased
predisposition to leukemias and squamous cell
carcinomas of the head and neck or female genitalia as
well as liver tumors [
8,
11]. One thousand three hundred cases of FA were evaluated by Alter BP [
12] during the
years between 1927-2001. Nine percent of these cases had
leukemia, 7% had myelodysplastic syndrome, 5 % had
solid tumors and 3 % had liver tumors. It is unclear which
patients are prone to develop such tumors.
Rosenberg et al. [13] have estimated the cumulative
incidence of malignancies among 145 FA patients with 9
developing leukemia and 18 solid tumors developing in
14 patients. The ratio of observed to expected neoplasm
(O/E) patients was 50 for all cancers, 48 for all solid tumors
and 785 for leukemias. These increased risks were
calculated to be statistically significant. The overall excess
also includes nonsignificant increases in osteosarcomas,
soft-tissue sarcomas and brain tumors. The median
age at onset of leukemias was 11.3 years, which showed a
significantly lower age compared to those of the onset for
the median 28.9 years for solid tumors [13].
FA presented with aplastic anemia leads to the development
of solid tumors later in life [12]. Soft tissue sarcomas
were diagnosed very rarely in the patients with FA but
FA-D1 subgroup can be associated with a high incidence
of solid tumors of early childhood [13,14]. Most interestingly,
our case represents an abdominal rhabdomyosarcoma
with metastasis as the first manifestation of FA in a
six-year-old-boy who subsequently developed AML as a
second malignancy.
The recent identification of the breast and ovarian
cancer susceptibility gene BRCA2, as the FANCD1 gene,
implicates the FA/BRCA pathway in homology-directed
DNA repair and suggests that disruption of the pathway
may promote breast and ovarian cancer [11].
The types of leukemia which occur in FA are primarily
non-lymphocytic leukemias although a few lymphoblastic types have also been reported [15,16]. The incidence
of AML in FA patients is more than 15,000 times than
those observed in children in the general population [17].
In these patients, all FAB subtypes occur except promyelocytic
type (M3); the myelomonocytic (M4) and acute
monocytic (M5) types are the most common [18]. Auerbach
et al. [17] suggested that all FA patients may be considered
preleukemic and this disorder represents a model
for study of the etiology of AML. Altay et al. [4] reported
that 5 of the 52 FA patients developed malignancies. Three
had AML and one developed a squamous cell carcinoma
of the gingiva and another a hepatocellular carcinoma.
There was increased risk for AML and for other cancers
among family members of FA patients [4]. In our series,
4 of the 39 FA patients developed AML and one had two
malignancies as reported in the presented case [19].
AML in FA is generally very difficult to treat and
survival has been very poor as observed in the presented
case. The defect in DNA repair leads to increased sensitivity
to chemotherapy and the patients are either vulnerable
to treatment toxicity or may receive inadequate treatment
[15]. Our patient achieved complete remission following
modified Denver treatment protocol and remained in remission
for the following two months, before finally dying
with relapse and massive bleeds.
The clinician should be aware of and alert for other
concomitant leukemias and solid tumors especially when
congenital malformations encountered in FA are present.
On the other hand, the prognosis in the patients with FA
and AML is still poor. The effective treatment modalities
have to be further developed.
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