NcXHF

TINOCO ET AL
TABLE 2. Malignant Cartilaginous Tumors of Bone
Malignant Molecular Features Clinical Features
Central Conventional Chondrosarcoma IDH1 or IDH2 mutation Most common type (approx. 70%); may arise from enchondroma or Ollier’s disease;
arises in pelvis, humerus, femur, or ribs; chemotherapy and radiotherapy resistant
Peripheral Conventional Chondrosarcoma IDH1 or IDH2 mutation Rare (approx. 10%); always arise from osteochondroma; younger individuals; arise
in pelvis or shoulder; chemotherapy and radiotherapy resistant
Periosteal Conventional Chondrosarcoma Not EXT, possibly Hedgehog
pathway activation
Very rare (approx. 1%); younger individuals; distal femur or humerus; prognosis
better than other histologies; chemotherapy and radiotherapy resistant
Mesenchymal Chondrosarcoma HEY1-NCOA2 Very rare (approx. 2%); younger individuals, arise in head/neck, vertebrae, ribs,
pelvis; round cell component is chemotherapy and radiotherapy sensitive
Dedifferentiated Chondrosarcoma IDH1 or IDH2 (50% of cases) Rare (approx. 10%); arise in conventional chondrosarcoma; older individuals; arise
in femur and pelvis; High grade by definition; low response rates to chemotherapy
to affect patients between age 50 and 70, with no particular
gender predilection. Clinically, patients present with pain
(85% of cases), followed by pathologic fracture (31%) and a
soft-tissue mass (29%). 29 The majority of tumors occur centrally
in medullary bone usually affecting the pelvis, femur,
and humerus. 6,30 Dedifferentiated chondrosarcoma is a highgrade
malignant neoplasm usually with the histologic appearance
of an osteosarcoma, an undifferentiated high-grade
pleomorphic sarcoma or fıbrosarcoma that arises in a preexisting
conventional chondrosarcoma. 11,31,32 Unusual histologies,
such as squamous cell carcinoma, have been
reported. 33 The pathogenesis of dedifferentiated chondrosarcoma
remains incompletely understood. It has been postulated
that the high-grade noncartilaginous component arises
in a long-standing low-grade cartilaginous element. 33,34 Dedifferentiated
chondrosarcomas are highly aggressive tumors
with a grim prognosis. In a multicenter review of 337 patients,
71 (21%) had metastases at the time of diagnosis with
only 10% survival at 2 years. 35 Systemic chemotherapy with
poor-prognosis osteosarcoma regimens is often used, but unlike
traditional osteosarcoma, response rates to chemotherapy
are only 20%. 36 Moreover, therapy with high-dose
ifosfamide-containing regimens are slightly superior with
33% survival at 2 years, but only 15% at 5 years. 37
Mesenchymal Chondrosarcoma
Mesenchymal chondrosarcoma is a rare high-grade malignant
cartilaginous tumor that may originate in either bone or
soft tissue (dura). 6 These tumors are characterized by a bimorphic
cellular pattern that is composed of islands of differentiated
cartilage and highly cellular areas that are
composed of undifferentiated small round blue cells. 11 Unlike
other chondrosarcoma subtypes, the median age at presentation
is age 25 and extraosseous tumors are observed. 38
The principal symptoms are pain and swelling. Mesenchymal
chondrosarcoma most commonly arise in the craniofacial
bones, ribs, ilium, and the vertebrae. 11,39 The meninges
are one of the most common sites of extra skeletal involvement.
40 The overall prognosis is poor for conventional
chondrosarcomas. Approximately 20% have metastatic
disease at diagnosis. 39 Reported 10-year survival rates are
10 to 20%. 41 However, approximately 30% of mesenchymal
chondrosarcomas will respond to Ewing sarcomatype
chemotherapy regimens, with evidence of improved
survival as a result. 36,38,39
Clear Cell Chondrosarcoma
Clear cell chondrosarcoma is a rare low-grade subtype of
chondrosarcoma that is characterized histologically by
bland clear cells in addition to hyaline cartilage. 6,11 Less than
2% of chondrosarcomas are classifıed as clear cell histology.
Men are almost three times more likely to develop clear cell
chondrosarcoma than women and most patients are between
age 25 and 50. 42 Approximately two-thirds of lesions occur in
the humeral or femoral head. 42 Although clear cell chondrosarcomas
are low-grade tumors, partial excision or curettage
leads to recurrence in at least 70% of the cases, and it should
be avoided. 43,44 Local excision commonly is curative. The
overall recurrence rate is 16%, and approximately 15% of patients
die of the disease. Metastases to the lung, brain, and
bones have been reported. 11 These tumors do not respond to
chemotherapy or radiation; surgical resection is the only
known therapy.
Myxoid Chondrosarcoma
Primary skeletal myxoid chondrosarcoma is a rare neoplasm.
It remains unclear whether this constitutes a separate clinicopathologic
entity or if it is part of the spectrum of conventional
chondrosarcoma with prominent myxoid stroma. 23
Histologically, myxoid chondrosarcoma of bone has similar
characteristics to the extraskeletal myxoid chondrosarcoma
(EMC), but these are two distinct diagnoses. 45
Extraskeletal myxoid chondrosarcoma is a malignant softtissue
tumor characterized by a multinodular architecture,
abundant myxoid matrix, and malignant chondroblast-like
cells. 11,46,47 Typically, EMC has a characteristic translocation,
t(9;22)(q22;q12.2), fusing EWSR1 to NR4A3 (genes formerly
termed EWS and CHN, TEC, or NOR1, respectively). 48-51 A
small proportion of EMC have a different translocation, t(9;
17)(q22;q11.2), which results in a RBP56-NR4A3 fusion gene
and neuroendocrine differentiation in some cases. 51 Given
that these tumors can arise in the extremities and may
mimic chondrosarcoma, this is an instance in which genetic
testing for the translocation can affect therapy
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