Secondary Chondrosarcoma

is required for secondary chondrosarcomas
to arise within the benign
cartilaginous origin. This process is
sometimes accompanied by chromosomal
instability and aneuploidy, the
severity of which may depend on the
particular genes that are mutated.
These have not been well characterized.
Most secondary chondrosarcomas
arise in osteochondromas; thus, it
seems as though the model of tumorigenesis
starting with mutation of
EXT genes would apply to most of
the tumors. However, this may not
account for all secondary chondrosarcomas,
and the genetic pathway
may well be distinct in chondrosarcomas
that arise in enchondromas.
Ollier disease and Maffucci syndrome
are characterized by multiple
enchondromas dispersed through the
skeleton. Maffucci syndrome is distinguished
from Ollier disease by the
presence of multiple soft-tissue hemangiomas,
and it is less common
than Ollier disease. Both diseases are
known to give rise to secondary
chondrosarcoma, but because of the
rarity of the conditions, the rate at
which malignant transformation occurs
is not well-documented. Estimates
range from 10% to 40% in
patients with Ollier disease at longterm
follow-up. 9,11,35 Some authors
believe that patients with Maffucci
syndrome may be at greater risk of
developing malignancy; in one series,
4 of 7 patients with Maffucci syndrome
developed chondrosarcoma. 35
However, reviews of published case
reports have indicated estimates approximately
15% to 20%. 12,36
The genetics of Ollier disease and
Maffucci syndrome differ from those
of HME. Both diseases seem to arise
sporadically without an obvious genetic
inheritance pattern. It is believed
that a combination of multiple
genes may be involved, but those
have not been identified. One report
identified two cases of a mutation
(one somatic, one germline) in the
gene encoding the PTH/PTHrP type I
receptor. 37 It was hypothesized that
the mutation could delay the differentiation
of proliferating chondrocytes
by constitutively activating
hedgehog signaling. However, this
mutation was not found consistently
in other tumors upon further study. 38
Prevention, Treatment,
and Outcome
The risk of malignant transformation
of benign cartilage tumors has not been
well established, and estimates vary
widely. For solitary osteochondromas,
the risk is most likely 5-year
follow-up. 5,7,13 Patients with solitary
osteochondromas tend to have a better
overall prognosis, with a 5-year
mortality rate of 6.5%, compared
with 19.6% for patients with HME. 7
Metastasis may be more apt to occur
in the rare high-grade secondary
chondrosarcoma. 7
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