S E M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20

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Cartilage-forming tumors
Shadi A. Qasem, MDn, Barry R. DeYoung, MD
Department of Pathology, Wake Forest School of Medicine, Medical Center Blvd, Winston Salem, North Carolina
27157

article info abstract

Keywords: Cartilage-forming tumors as a group are the most common primary bone tumors; this is
Chondroma largely due to the common occurrence of asymptomatic benign lesions such as osteochon-
Osteochondroma droma and enchondroma. The common feature of these tumors is the presence of
Chondroblastoma chondrocytic cells and the formation of cartilaginous tumor matrix. Some of these tumors
Chondromyxoid fibroma are true neoplasms while others are hamartomas or developmental abnormalities. The
Chest wall hamartoma morphologic heterogeneity of these tumors may be explained by a common multipotent
Chondrosarcoma mesenchymal cell differentiating along the lines of fetal–adult cartilage maturation.
Recently mutations in IDH1 and IDH2 have been detected in a variety of benign and
malignant cartilaginous tumors.1–4
& 2014 Elsevier Inc. All rights reserved.

Osteochondroma
It is a benign outgrowth of bone and cartilage and is one of
the most common bone tumors. Often referred to as exo-
stosis, there is debate whether they constitute a true neo-
plasm or bony outgrowths of the metaphyseal plate. They
may develop following surgery or fracture, and they are the
most common radiation-induced benign tumors. Loss of
genetic material from the long arm of chromosome 8 has
been detected in some of these tumors as well as mutation in
exostosin genes. Exostosin genes (EXT) are involved in the
biosynthesis of heparan sulfate chains, which are ubiquitous
and important in the morphogenesis of cartilage.1,5–9
The tumors can be sporadic or multiple and they affect all age
groups; however, patients usually present in their first or second
decades of life. They are often asymptomatic, but they can cause
pain due to pressure on adjacent structures, and sometimes they
present as a palpable mass. The most common sites include the
long bones (femur, tibia, and humerus), pelvis, and spine.
Radiographically, they manifest as pedunculated or sessile
masses on the surface of the bone, adjacent to the metaphyseal
plate and pointing away from the joint. The cortex and medulla
show continuity with the underlying bone. The cartilaginous cap
may not be visible on plain radiograph and is better assessed
using CT or MRI (Fig. 1A). Grossly, the lesions take the form of a
semicircle or a mushroom-like mass composed of a core of
trabecular bone covered by a fairly smooth cartilaginous cap
that can vary in thickness. Unfortunately, the specimen is often
received fragmented in the surgical pathology laboratory.1,6
Microscopically the cartilage cap is composed of mature
hyaline cartilage with clusters of chondrocytes in lacunae
surrounded by abundant chondroid matrix. The underlying
bone shows normal bone trabeculae with intervening bone
marrow elements and/or adipose tissue. The transition zone
may have blue/purple cartilage and linear arrangement of
chondrocytes similar to the growth plate (Fig. 1B).
The differential diagnosis includes other forms of exostoses
such as subungual exostosis, osteophytes, and bizarre paro-
steal osteocartilaginous proliferation (BPOP or Nora's lesion).
The majority of these differentials involve the small bones
(rare for osteochondroma), are usually small, and do not
show continuity with the underlying bone.

n
Corresponding author.
E-mail address: sqasem@wakehealth.edu. (S.A. Qasem)

http://dx.doi.org/10.1053/j.semdp.2014.01.006
0740-2570 & 2014 Elsevier Inc. All rights reserved.
 SE M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20 11

Fig. 1 – (A) An X-ray of leg showing osteochondroma involving the proximal tibial metaphysis and pointing away from the
knee joint. (B) Histology of osteochondroma showing thin cartilaginous cap and fatty replaced bone marrow (H&E, 2  ). (C) MRI
of osteochondroma with secondary chondrosarcoma in the ilium. Notice the thick lobulated cartilaginous cap. (D) A patient
with multiple osteochondromas of the tibia (there is a vascular bypass graft in the background).

Surgical excision is indicated for symptomatic lesions or risk estimated to affect 1% of patients with solitary lesions
those showing atypical features (e.g., rapid growth and thick and 3–5% of those with multiple ones. A soft tissue mass,
cap). Recurrence may occur if incompletely excised. Malig- thick cartilaginous cap (42 cm), and/or irregular contours are
nant transformation to chondrosarcoma is a small potential suggestive features (Fig. 1C). Microscopically, there is
12 SE M I N A R S I N D I A G N O S T I C
transition from benign mature cartilage to one with increased
cellularity, atypia, necrosis, and myxoid degeneration.6,10–12
Hereditary multiple exostosis
Also known as osteochondromatosis and diaphyseal aclasis,
hereditary multiple exostosis is an autosomal dominant
condition in which patients present with a variable number
of osteochondromas (Fig. 1D). It is the most common heredi-
tary musculoskeletal condition. It is estimated that 15% of
patients with osteochondromas are believed to harbor this
condition. Genetic linkage analysis maps this syndrome to
loci on chromosomes 8, 11, and 19, which are believed to
harbor tumor suppressor genes (EXT1, 2, and 3). Patients
present early with skeletal deformities. Complications are
also more common than the solitary form of disease and
include fracture, vascular compromise, neurologic sequelae,
bursae formation, and malignant transformation.1,6,8,9
Chondroma (enchondroma)
A benign tumor of cartilage involving the medullary cavity
(enchondroma) or the surface (periosteal chondroma) of
bone. It is thought to arise from displaced embryonic growth
plate cartilage. Recently, mutations in isocitrate dehydrogen-
ase (IDH1 and 2) have been reported in this condition. It is a
relatively common tumor, often discovered incidentally. A
wide range of the population is affected, especially young to
middle-aged adults. Patients are usually asymptomatic. The
small bones of the hands are most commonly affected,
followed by long bones. Enchondromas of small bone may
cause pain and pathologic fracture.1,3
Radiologically, enchondromas of small bones appear as
well-demarcated radiolucent areas in the diaphysis or meta-
physis of bone with variable amount of calcifications. Long-
bone enchondromas are often ill-defined, on the other hand,
with no sclerotic borders. The cortex overlying the lesion is
intact (Fig. 2A). MRI shows a classic lobulated hyperintense
mass on T2, consistent with hyaline cartilage. Enchondromas
of small bones can show scalloping and thinning of the cortex
but no extension into soft tissue. Periosteal chondromas, on
the other hand, appear as saucer-shaped depressions in the
cortex of bone and separate from the medullary cavity
(Fig. 2B). They rarely exceed 3 cm in size.1,13
Grossly, the majority of these tumors undergo curettage
and the samples are often fragmented. They are composed of
blue hyaline cartilage admixed with bone tissue. Histologi-
cally, the lesion is composed of lobules of hyaline cartilage
with low cellularity and atypia. The lobules are usually
rimmed by bone; however, there should be no entrapment
of bone within the cartilage (Fig. 2C and D). Small nodules of
cartilage may be seen separate from the main mass. In small
bones and periosteal lesions, chondromas tend be more
cellular and show atypia and binucleation; nevertheless,
there should be no bone permeation or destruction and no
extension into soft tissue.1,10
Enchondromas should be differentiated from low-grade chon-
drosarcoma. Clinically, patients present with pain. In addition,
radiologic studies may show a newly developed lucency,
P A T H O L O G Y 31 (2014) 10–20
periosteal reaction, and/or soft tissue mass. Histologically, bone
permeation, increased cellularity, atypia, binucleation, and
myxoid change are helpful features for malignancy.10,14,15
Chondromas are benign lesions; they do not require ther-
apy unless they are symptomatic and/or they have worri-
some features radiologically.14
Multiple chondromas (enchondromatosis)
These encompass a group of disorders characterized by multi-
ple chondromas. Patients present early in life with skeletal
abnormalities or pathologic fractures. The lesions can involve
any part of the skeleton and often involve the small bones too.
Prototypical examples of this entity are Ollier's disease and
Maffucci's syndrome. Both are characterized by multiple
chondromas; in addition, soft tissue hemangiomas are present
in Maffucci's. Both enchondromas and periosteal chondromas
are common in these disorders.16,17
The radiologic features are similar to those of solitary
chondromas, albeit more extensive; in the long bones, they
are often centered towards the ends of bones. In advanced
stages, the hemangiomas can be seen on plain radiographs
due to thrombosis and calcification. Grossly the bones appear
expanded and nodular in appearance. Histologically, the
lesions show increased cellularity and atypia making it
difficult to distinguish them from chondrosarcoma. Marked
myxoid change and bone permeation/destruction are helpful
features. The hemangiomas in Maffucci's are reported to be
of the spindle cell type.10,16,17
Surgery may be required for skeletal deformities and
fractures. Risk of malignant transformation to conventional
chondrosarcoma, dedifferentiated chondrosarcoma or osteo-
sarcoma is reported in as much as 15–60% of patients and
appears higher in Maffucci's syndrome than Ollier's disease.
Any change in the size of the lesions or patient symptoms
should warrant workup for malignancy.10
Chondroblastoma
It is a benign tumor of bone involving mainly the epiphysis. It
is relatively rare, accounting for approximately 1% of bone
tumors. It can affect a wide age range but is most common in
the second decade, males more often than females. The long
bones are most commonly affected followed by foot (calca-
neus and talus). Localized pain and/or swelling are often the
presenting symptoms.1,18
Radiologically, these tumors manifest as a round or oval
radiolucent area in the epiphysis. Extension into the meta-
physis is not uncommon in young patients with an open
metaphyseal plate. Tumors often have a sclerotic rim on
plain radiograph, and occasionally there may be a periosteal
reaction. A lobulated contour and peritumoral edema are
characteristic on MRI1,18 (Fig. 3A).
Grossly the tumor does not have the typical appearance of
cartilage but rather pink–gray tissue. The tumor is composed
predominantly of mononuclear cells with variable numbers
of giant cells. The mononuclear cells are round or polygonal
with a characteristic “coffee-been” shape, an oval nucleus
with a central grove. Chondroid matrix is invariably present
 SE M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20 13

Fig. 2 – (A) An enchondroma of middle phalanx showing central lucency with bone expansion and a rim of sclerosis. (B) An
excision specimen of periosteal chondroma. Notice the smooth contour and the overlying periosteum. (C) Low-power view of
enchondroma showing well-circumscribed border (H&E, 4  ). (D) High-power view showing clustered chondrocytes with
bland-appearing nuclei (H&E, 40  ).

and sometimes characteristic fine granular calcification is
noted, often described as “chicken-wire calcification” (Fig. 3B).
Other less common features include aneurysmal bone cyst
change, vesicular or bizarre nuclei, brown pigment, and
hemangiopericytoma-like pattern.10,18,19
These tumors should be mainly differentiated from giant cell
tumors of bone. Chondroblastomas tend to affect younger
individuals and have sclerotic borders, nuclear groves, chon-
droid matrix, and characteristic calcifications. When atypia is
prominent, they can be confused with osteosarcoma and clear
cell chondrosarcoma; however, correlation with radiologic stud-
ies and attention to other microscopic features (groves, calcifi-
cations, and giant cells) should help establish the diagnosis.18,19
Surgical curettage is preferred over wide resection to avoid
growth impairment. Cryosurgery is recommended to reduce
recurrence. Benign pulmonary metastases have been
reported, albeit extremely rarely. In a recent study, driver
mutations in H3F3A and H3F3B gene have been identified.
Interestingly giant cell tumors of bone show similar muta-
tions.18–24
Chondromyxoid fibroma
Is a very rare benign chondromyxoid neoplasm often mis-
diagnosed as chondrosarcoma. It affects patients of all ages
14 SE M I N A R S I N D I A G N O S T I C
Fig. 3 – (A) MRI of chondroblastoma of the proximal tibial epiphysis. Notice the surrounding edema. (B) Histology of
enchondroma showing central hypocellular area surrounded by chicken-wire calcifications (H&E, 10  ).
with a peak incidence in second and third decades. Pain is the
most common presenting symptom. The long bones are
commonly affected followed by the iliac wings, ribs, and feet
(metatarsal bones).1,18,25
The typical radiologic appearance is that of an eccentric,
elongated, radiolucent defect in the metaphysic or diaphysis
of long bones. The margins are scalloped and well-
demarcated and can be sclerotic. The cortex can be thin or
absent, and mineralization is uncommon. If resected intact,
the tumor is well-circumscribed and lobulated with semi-
translucent blue–gray appearance. Microscopically, the tumor
is composed of ill-defined lobules with a central hypocellular
areas composed of stellate cells with scant eosinophilic
cytoplasm suspended in a gray–blue chondromyxoid matrix.
The periphery of the lobules is more cellular and the cells are
round/polygonal in shape. Scattered atypia, giant cells, and
calcifications may be seen1,10,18 (Fig. 4).
The differential diagnosis includes aneurysmal bone cyst
(ABC), giant cell tumor of bone, chondroblastoma, and chon-
drosarcoma. Chondroblastomas are typically epiphyseal, the
cells are round and have nuclear grooves, giant cells are more
prominent, and they often have the characteristic chicken-
wire calcifications. Differentiating chondromyxoid fibroma
from chondrosarcoma can be challenging especially in small
biopsies. The most important thing is to keep this entity in
mind when evaluating chondromyxoid lesions of bone,
especially in young people. The radiologic impression for
chondromyxoid fibroma is usually benign, despite thinning
of the cortex. Histologically, the lobulation with enhanced
cellularity at the periphery is a clue. In the skull base,
chondromyxoid fibroma should be differentiated from a
chordoma.26
If recognized properly, the treatment is curettage. There is a
small risk of local recurrence; however, malignant trans-
formation is not expected. Recurrent abnormalities of chro-
mosome 6 have been reported in this tumor.1,5,18,25,27,28
P A T H O L O G Y 31 (2014) 10–20
Chest wall hamartoma (chondro-mesenchymal
hamartoma)
This is not a true neoplasm but rather a congenital malfor-
mation. It is often included in the differential and can be
mistaken for other cartilaginous tumors. This condition
typically affects infants and presents as a large chest wall
mass, which can cause breathing problems and chest wall
deformity.29–31
Radiologically, there is a large expansile mass that destroys
and deforms the adjacent ribs; however, it is well-demarcated
and does not involve the lung parenchyma. Grossly, the mass
is well-circumscribed and composed of nodules of cartilage
with intervening cystic/hemorrhagic spaces. Microscopically,
the lesion is a combination of a chondroma and an aneur-
ysmal bone cyst (ABC). The cartilage is benign in appearance
and shows maturation into normal bone. Other areas show
bland spindle cells and giant cells surrounding cystic spaces
with hemorrhage reminiscent of an ABC31,32 (Fig. 5).
Although the clinical presentation is alarming for malig-
nancy, the location, age and well-circumscription of the mass,
in addition to the typical histology, should be diagnostic.
These lesions often regress spontaneously; surgery should be
conservative and only used for symptomatic patients because
there is a higher risk of deformity after surgery.33,34
Chondrosarcoma
Conventional chondrosarcoma is a malignant neoplasm
composed of hyaline cartilage. It is the second most common
malignant primary bone tumor. The tumor may arise de novo
(primary) or secondary to other tumors. The following dis-
cussion refers to conventional chondrosarcoma; other special
types of chondrosarcoma will be discussed separately.35
 SE M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20 15

Fig. 4 – (A) Chest CT scan showing destruction and expansion of the seventh rib with residual bone at the periphery. (B) Gross
picture of the lesion in (A). Notice the fusiform expansion of the rib and the shiny parietal pleura on the surface. (C)
Chondromyxoid fibroma showing central chondroid matrix with enhanced cellularity at the periphery (H&E, 10  ). (D) Cellular
area of chondromyxoid fibroma showing bland-appearing stellate cells and myxoid matrix (H&E, 20  ).

In contrast to osteosarcoma, chondrosarcoma is a disease
of middle-aged to old adults, although individuals of any age
can be affected. Pain is the presenting symptom and some
patients present with pathologic fracture. The tumor most
commonly affects the pelvis and shoulder, and it rarely
affects the small bones of the hands and feet.35,39,40
These tumors may not be easy to appreciate on plain
radiograph albeit their large size. They are typically meta-
physeal or diaphyseal and show an ill-defined expansile
lucency with scalloping, thickening, or destruction of the
cortex. Mineralization may or may not be present. CT and
MRI are helpful in delineating the extent of tumor and any
soft tissue component (Fig. 6A). Grossly the bone is often
expanded by the tumor and, on cross section, appears as a
white–blue translucent mass involving the medullary cavity
and permeating bone. The cartilage may show significant
liquefaction and mucoid change. Calcifications can be seen as
chalky-white deposits.10,35
Microscopically, the tumor is composed of blue hyaline
cartilage. The lobules of cartilage are not well defined and the
cellularity and atypia are increased depending on the grade of
the tumor. Well-differentiated (low grade) tumors are difficult
to differentiate from malignant ones without the help of
radiologic studies, whereas high-grade tumors are frankly
malignant with marked atypia and diffuse cellularity. The
lobules may be surrounded by reactive bone, but the tumor
16 SE M I N A R S I N D I A G N O S T I C
Fig. 5 – (A) CT scan showing large expansile mass destroying the rib and impinging on lung mediastinal structures. (B)
Histology of the lesion in (A) showing a chest wall hamartoma composed of large cartilaginous nodules, dense fibrous tissue,
and central ABC-like cystic area (H&E, 2  ).
itself does not make osteoid or bone. Helpful features in
determining malignancy include atypia, binucleation, myxoid
change in the stroma, necrosis, and permeation of bone10,14,36
(Fig. 6B).
Grading can be subjective and the criteria are not well
defined. Grade 1 tumors are not easy to differentiate from
enchondroma; the atypica is often subtle and the diagnosis
depends largely on radiologic features. Grade 2 tumors show
more diffuse cellularity and atypical features, often with
areas of myxoid change and necrosis. Grade 3 tumors are
pleomorphic; however, in contrast with dedifferentiated
tumors, they retain chondroid matrix10,35 (Fig. 6C and D).
Chondrosarcoma should be differentiated form enchondro-
mas and chondroblastic osteosarcomas. It is important to
incorporate both histologic and radiologic findings when
trying to make the distinction from enchondroma. Destruc-
tion of cortex (radiologically) and bone permeation (histolog-
ically) are the most helpful features. It is important to note
that enchondromas of small bone can show some atypical
features including scalloping of bone, mild cytologic atypia,
and increased cellularity; therefore, soft tissue extension is
important to confirm malignancy in these locations. Like-
wise, the differentiation of periosteal enchondroma from a
periosteal chondrosarcoma can be difficult; large size, ill-
defined borders, and soft tissue infiltration are malignant
features. A younger patient age and the presence of a
malignant osteoid should warrant the diagnosis of chondro-
blastic osteosarcoma in a cartilaginous neoplasm. Recently,
the presence of IDH mutation has been used to confirm the
diagnosis of chondrosarcoma.3,37
Low-grade tumors tend to be locally recurrent, whereas high-
grade tumors metastasize more frequently to the lungs. Meta-
stases are often late; it is uncommon for patients to present with
metastasis. Surgical management is the mainstay of treatment
since these tumors are not sensitive to chemo- or radiation
therapy. Intralesional curettage with or without cryosurgery has
P A T H O L O G Y 31 (2014) 10–20
been shown to be effective for low-grade chondrosarcoma. On
the other hand, wide surgical excision offers best local control.
Chondrosarcomas of small bones carry an excellent prognosis.
Survival for pelvic and spinal tumors is lower due to their ability
to grow to a large size and/or incomplete resection. Abnormal-
ities in 12q1 and in chromosome 7 and 17 have been reported in
chondrosarcoma, and complex karyotypic abnormalities are
often noted in high-grade ones.5,35–40
Dedifferentiated chondrosarcoma
This is a biphasic neoplasm composed of a well-differentiated
cartilaginous tumor and a high-grade non-cartilaginous sar-
coma. The term “dedifferentiated,” which is a misnomer, refers
to the belief that the high-grade tumor arises from a long-
standing well-differentiated tumor. The presence of shared
cytogenetic abnormalities supports a common origin. It is
estimated to occur in 10% of chondrosarcoma cases. The age
of presentation is a decade older than conventional chondro-
sarcoma. Patients often present with pain and swelling with or
without fracture. Similar to conventional chondrosarcoma, the
pelvis and shoulder are the common sites.10,41–43
The radiologic diagnosis is suggested by a large lytic lesion
with aggressive features (bone destruction and soft tissue
extension) being associated with a low-grade calcified lesion.
Grossly, the medullary portion of the tumors shows blue–gray
translucent tissue (cartilage) that is adjoined by a fleshy
white heterogenous tumor extending into the soft tissue.
Microscopically, the tumor is composed of a low-grade
cartilaginous tumor (enchondroma or low-grade chondrosar-
coma) with abrupt transition to a malignant spindle cell
neoplasm. Typically, the spindle cell component resembles
undifferentiated sarcoma; however, fibrosarcomatous and
osteosarcomatous differentiation can also be seen42,43 (Fig. 7).
This entity needs to be differentiated from chondroblastic
osteosarcoma, where the malignant cartilage shows
 SE M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20 17

Fig. 6 – (A) MRI showing chondrosarcoma of the proximal humerus with extension into soft tissue. (B) Grade 1
chondrosarcoma with bland-appearing nuclei. Notice the myxoid change on the left side of the picture (H&E, 10  ). (C) Cellular
atypical cartilaginous tissue (grade 2 chondrosarcoma) with entrapment of bone trabeculae (H&E, 10  ). (D) Grade 3
chondrosarcoma with marked pleomorphism and frequent mitosis (H&E, 20  ).

significant atypia and blends with the spindle cell component
with no sharp transition. Mesenchymal chondrosarcoma is
also a biphasic tumor; however, the non-cartilaginous com-
ponent is composed of small round cells and often shows
hemangiopericytoma-like vasculature.10
The treatment is surgery, and the prognosis is poor with a
median survival of less than 1 year. Metastases often affect
the lungs, lymph nodes, and visceral organs.41–43
Mesenchymal chondrosarcoma
This biphasic tumor of cartilage is very rare. It is composed
of hyaline cartilage and a small round cell component.
It often presents in young adults with pain and swelling.
Sinonasal tumors may present with nasal obstruction and/
or epistaxis. The craniofacial bones are commonly affected;
other sites of involvement include the spine, ilium, and
ribs. Extraskeletal sites including the brain and the spinal
cord have also been reported. Radiographically, this tumor
presents with an ill-defined, often mineralized, mass
with features of malignancy (bone expansion and cortical
destruction).44–46
Grossly, the tumor is well-demarcated and gray to pink
with calcifications. Histologically, the tumor is composed of
nodules of atypical cartilage surrounded by a small round cell
proliferation. The small cells are arranged in sheets, which
are often separated by a characteristic hemangiopericytoma-
like vasculature. The small cell component may be spindly
18 SE M I N A R S I N D I A G N O S T I C P A T H O L O G Y 31 (2014) 10–20

Fig. 7 – (A) Aggressive lesion in the distal femur with central mineralization and cortical destruction. (B) Gross picture of
chondrosarcoma with necrosis, bone permeation, and soft tissue extension. (C) Dedifferentiated chondrosarcoma. Notice the
abrupt transition from mature cartilage to a spindle cell, non-cartilaginous neoplasm (H&E, 4  ). (D) The dedifferentiated
tumor in (C) showing significant bone formation consistent with osteosarcoma (H&E, 10  ).

and there is often calcification in the cartilage. CD99 is
usually positive in the small cells10,46 (Fig. 8A).
This tumor can be mistaken for other small round blue cell
tumors (e.g., Ewing sarcoma) or a hemangiopericytoma on a
small biopsy; however, the presence of cartilage should help rule
out these entities on the resection. Chondroblastic osteosarcoma
is also in the differential, especially given the overlapping age of
presentation for these tumors, but the presence of small round
cells with hemangiopericytoma-like pattern in mesenchymal
chondrosarcoma and the formation of malignant lacy osteoid in
osteosarcoma should be helpful in making the distinction.47
Surgery is the treatment of choice. The role of chemotherapy
and/or radiation therapy is not clear. This is a high-grade
tumor with a variable clinical course. Metastases are often late
and are commonly to the lungs. Recently a recurrent molec-
ular abnormality involving the fusion of HEY1 and NCOA2
genes (both on chromosome 8) has been identified.44–46,48–50
Clear cell chondrosarcoma
This is another rare variant of chondrosarcoma with some
features overlapping with chondroblastoma. The majority of
 SE M I N A R S I N D I A G N O S T I C
Fig. 8 – (A) A round cell area of a mesenchymal chondrosarcoma. Notice the hemangiopericytoma-like vasculature (H&E,
10  ). (B) A clear cell chondrosarcoma. The tumor is composed of sheets of cells with clear cytoplasm, scattered giant cells,
and focal osteoid formation (H&E, 20  ).
cases are in the third to fifth decades of life with a strong
male predilection. Long-standing pain is a common symp-
tom. The epiphyses of bones are commonly affected, espe-
cially the proximal femur. Radiology shows a lytic lesion
extending to the end of the bone with or without cortical
destruction. Some lesions may be well-demarcated with
sclerosis. Calcifications may be present.51–55
Grossly, the tumor is gray with gross nodules of cartilage.
Small cystic spaces are often noted. Microscopically, the
tumor is composed of sheets of cells with abundant clear–
pink cytoplasm and distinct cytoplasmic borders. Short
woven trabeculae and giant cells are usually present. Occa-
sionally, nodules of conventional chondrosarcoma are also
present. The clear cytoplasm is attributable to abundant
glycogen, which can be highlighted with a Periodic acid–
Schiff (PAS) stain10,54–56 (Fig. 8B).
This tumor shares histologic and radiologic features with
several entities including chondroblastoma, giant cell tumor
of bone, osteoblastoma, chordosarcoma, osteosarcoma, and
renal cell carcinoma. Attention to the morphologic and
clinical features including age, location, clear cytoplasm,
giant cells, and distinct cytoplasmic borders should help
differentiate this entity. The lack of bone marrow edema
favors clear cell chondrosarcoma over chondroblastoma.55
As with other forms of chondrosarcoma, surgery is the
mainstay of therapy. En bloc resection is recommended to
prevent recurrence. The prognosis is good and metastases are
often delayed and are usually to the lungs.51,52,54,57
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