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Sarcoma
A sarcoma (from the Greek 'sarx' meaning "flesh") is a cancer of the connective or
supportive tissue (bone, cartilage, fat, muscle, blood vessels) and soft tissue. his is in
contrast to carcinomas, !hich are of epithelial origin (breast, colon, pancreas, and others).
Classification
"arcomas are given a number of different names, based on the t#pe of tissue from !hich
the# arise. $or example, osteosarcoma arises from bone, chondrosarcoma arises from
cartilage, and leiom#osarcoma arises from smooth muscle. "arcomas strike people in all age
ranges, but the# are ver# rare, accounting for onl# 1% of all cases of cancer.
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"oft tissue
sarcomas, such as leiom#osarcoma, chondrosarcoma, and gastrointestinal stromal tumor
(G("), are more common in adults than in children. G(" is the most common form of
sarcoma, !ith approximatel# )***+),** cases per #ear in the -nited "tates.
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his should be
compared !ith breast cancer, !ith approximatel# .**,*** cases per #ear in /orth America.
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0one sarcomas, such as osteosarcoma and 1!ing's sarcoma, are more common in children
than in adults. hese tumors most commonl# strike adolescents and #oung adults bet!een
the ages of 1. and .,. (n addition to being named based on the tissue of origin, sarcomas are
also assigned a grade, such as lo! grade or high grade. 2o! grade sarcomas are usuall#
treated surgicall#, although sometimes radiation therap# or chemotherap# are used. 3igh
grade sarcomas are more fre4uentl# treated !ith chemotherap#. "ince these tumors are more
likel# to undergo metastasis (spreading to distant sites), these tumors are treated more
aggressivel#. 5hildhood sarcomas are almost al!a#s treated !ith a combination of surger#
and chemotherap#, and radiation is fre4uentl# used as !ell. he recognition that childhood
sarcomas are sensitive to chemotherap# has dramaticall# improved the survival of patients.
$or example, in the era before chemotherap#, long term survival for patients !ith locali6ed
osteosarcoma !as onl# approximatel# .*%, but no! has risen to 7*+8*%.
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Types of sarcoma
((5:+; codes are provided !here available.)
"oft tissue sarcoma, including
o Alveolar soft part sarcoma (<,=1>))
o Angiosarcoma (<1.*>))
o 5#stosarcoma ?h#lloides &1'
o :ermatofibrosarcoma (==).>)+==))>))
o :esmoid umor (==.1>1+==..>1)
o :esmoplastic small round cell tumor (==*7>))
o 1pithelioid "arcoma (==*9>))
o 1xtraskeletal chondrosarcoma (<..*>))
o 1xtraskeletal osteosarcoma (<1=*>))
o $ibrosarcoma (==1*>))
o 3emangioperic#toma (<1,*)
o 3emangiosarcoma (<1.*>))
o @aposi's sarcoma (<19*>))
o 2eiom#osarcoma (==<*>)+==<7>))
o 2iposarcoma (==,*>)+==,=>))
o 2#mphangiosarcoma (<18*+<18,)
o 2#mphosarcoma
.
o Aalignant fibrous histioc#toma (==)*>))
o /eurofibrosarcoma (<,9*>))
o Bhabdom#osarcoma (=<**+=<.*)
o "#novial sarcoma (<*9*>)+<*9)>))
Askin's umor (==*)>))
1!ing's (<.7*>)) + ?/1 (<98)>))
Aalignant 3emangioendothelioma (<1)*>))
Aalignant "ch!annoma (<,7*>)+<,71>))
;steosarcoma (<1=*>)+<1<*>))
5hondrosarcoma (<..*>)+<.9*>))
Soft tissue sarcoma
A soft tissue sarcoma is a malignant (cancerous) tumor that develops in mesench#mal
tissue. Aesench#mal tissues encompass all the muscle, connective tissues, and bones of the
bod#.
"oft tissue sarcomas can invade surrounding tissue and can metastasi6e (spread) to other
organs of the bod#, forming secondar# tumors. he cells of secondar# tumors are similar to
those of the primar# (original) cancer. "econdar# tumors are referred to as "metastatic soft
tissue sarcoma" because the# are part of the same cancer and are not a ne! disease. he most
common site of spread is to the lungs.
"ome tumors of the soft tissue are benign (noncancerous) and are not sarcomas. hese
tumors do not spread and are rarel# life+threatening. 3o!ever, benign tumors can cro!d
nearb# organs and cause s#mptoms or interfere !ith normal bod# functions.
Risk factors
"cientists do not full# understand !h# some people develop sarcomas !hile the vast
maCorit# does not. he vast maCorit# develop in patients !ith no kno!n risk factors or
identifiable etiolog#. 3o!ever, b# identif#ing common characteristics in groups !ith
unusuall# high occurrence rates, researchers have been able to single out some factors that
ma# pla# a role in causing soft tissue sarcomas.
"tudies suggest that !orkers !ho are exposed to ?henox# herbicide in
herbicides and chlorophenols in !ood preservatives ma# have an increased risk of
developing soft tissue sarcomas. An unusual percentage of patients !ith a rare blood
vessel tumor, angiosarcoma of the liver, have been exposed to vin#l chloride in their
!ork. his substance is used in the manufacture of certain plastics, notabl# ?D5.
(n the earl# 1<**s, !hen scientists !ere Cust discovering the potential uses of
radiation to treat disease, little !as kno!n about safe dosage levels and precise
methods of deliver#. At that time, radiation !as used to treat a variet# of noncancerous
medical problems, including enlargement of the tonsils, adenoids, and th#mus gland.
2ater, researchers found that high doses of radiation caused soft tissue sarcomas in
some patients. 0ecause of this risk, radiation treatment for cancer is no! planned to
ensure that the maximum dosage of radiation is delivered to diseased tissue !hile
surrounding health# tissue is protected as much as possible.
Besearchers believe that a retrovirus pla#s an indirect role in the development of
@aposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and
mucus membranes. @aposi's sarcoma often occurs in patients !ith A(:" (ac4uired
)
immune deficienc# s#ndrome). A(:"+related @aposi's sarcoma, ho!ever, has different
characteristics and is treated differentl# than t#pical soft tissue sarcomas.
"tudies have focused on genetic alterations that ma# lead to the development of
soft tissue sarcomas. "cientists have also found a small number of families in !hich
more than one member in the same generation has developed sarcoma. here have
also been reports of a fe! families in !hich relatives of children !ith sarcoma have
developed other forms of cancer at an unusuall# high rate. "arcomas in these famil#
clusters, !hich represent a ver# small fraction of all cases, ma# be related to a rare
inherited genetic alteration of the p,) gene and is kno!n as 2i+$raumeni s#ndrome.
5ertain other inherited diseases are associated !ith an increased risk of
developing soft tissue sarcomas. $or example, people !ith neurofibromatosis t#pe (
(also called von Becklinghausen's disease associated !ith alterations in the /$1 gene)
are at an increased risk of developing soft tissue sarcomas kno!n as malignant
peripheral nerve sheath tumors. ?atients !ith inherited retinoblastoma have alterations
in the B01 gene, a tumor suppressor gene, and are likel# to develop soft tissue
sarcomas as the# mature into adulthood.
Frequency
"oft tissue sarcomas are relativel# uncommon cancers. he# account for less than 1 % of
all ne! cancer cases each #ear. he main reason is that soft tissue cells aren't constantl# fast
dividing cells, but rather the opposite. $or instance, gro!th of muscles is made b#
h#pertroph# of muscles cells rather than h#perplasia.
(n .**7, about <,,** ne! cases !ere diagnosed in the -nited "tates.
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"oft tissue
sarcomas are more commonl# found in older patients (E,* #ears old) although in children
and adolescents under age .*, certain histologies are common (rhabdom#osarcoma).
Symptoms
(n their earl# stages, soft tissue sarcomas usuall# do not cause s#mptoms. 0ecause soft
tissue is relativel# elastic, tumors can gro! rather large, pushing aside normal tissue, before
the# are felt or cause an# problems. he first noticeable s#mptom is usuall# a painless lump
or s!elling. As the tumor gro!s, it ma# cause other s#mptoms, such as pain or soreness, as it
presses against nearb# nerves and muscles. (f in the abdomen it can cause abdominal pains
commonl# mistaken for menstrual cramps, indigestion, or cause constipation.
Diagnosis
he onl# reliable !a# to determine !hether a soft tissue tumor is benign or malignant is
through a biops#. herefore, all soft tissue lumps that persist or gro! should be biopsied. A
biops# can be obtained via needle biops# or !ith surgical biops#. :uring this procedure, a
doctor makes an incision or uses a special needle to remove a sample of tumor tissue. A
pathologist examines the tissue under a microscope. (f cancer is present, the pathologist can
usuall# determine the t#pe of cancer and its grade. he grade of the tumor is determined b#
ho! abnormal the cancer cells appear !hen examined under a microscope. he grade
predicts the probable gro!th rate of the tumor and its tendenc# to spread. 2o!+grade
sarcomas, although cancerous, are unlikel# to metastasi6e. 3igh+grade sarcomas are more
likel# to spread to other parts of the bod#.
Treatment
(n general, treatment for soft tissue sarcomas depends on the stage of the cancer. he
stage of the sarcoma is based on the si6e and grade of the tumor, and !hether the cancer has
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spread to the l#mph nodes or other parts of the bod# (metastasi6ed). reatment options for
soft tissue sarcomas include surger#, radiation therap#, and chemotherap#.
"urger# is the most common treatment for soft tissue sarcomas. (f possible, the
doctor !ill remove the cancer and a safe margin of the health# tissue around it.
:epending on the si6e and location of the sarcoma, it ma# occasionall# be necessar#
to remove all or part of an arm or leg (amputation). 3o!ever, the need for amputation
rarel# arisesF no more than 1* % to 1, % of individuals !ith sarcoma undergo
amputation. (n most cases, limb+sparing surger# is an option to avoid amputating the
arm or leg. (t is important to obtain a margin free of tumor to decrease the likelihood
of local recurrence and give the best chance for eradication of the tumor.
Badiation therap# (treatment !ith x+ra#s or radioactive implants) ma# be used
either before surger# to shrink tumors or after surger# to kill an# cancer cells that ma#
have been left behind. (n some cases, it can be used to treat tumours that cannot be
surgicall# removed. (n multiple studies, radiation therap# has been found to improve
the rate of local control, but has not had an# influence on overall survival.
5hemotherap# (treatment !ith anticancer drugs) ma# be used !ith radiation
therap# either before or after surger# to tr# to shrink the tumor or kill an# remaining
cancer cells. (n general, chemotherap# effects for soft tissue sarcoma have had little
impact as opposed to other cancers. (f the cancer has spread to other areas of the bod#,
chemotherap# ma# be used to shrink tumors and reduce the pain and discomfort the#
cause, but is unlikel# to eradicate the disease. he use of chemotherap# to prevent the
spread of soft tissue sarcomas has not been proven to be effective. ?atients !ith soft
tissue sarcomas usuall# receive chemotherap# intravenousl# (inCected into a blood
vessel).
:octors are conducting clinical trials in the hope of finding ne!, more effective
treatments for soft tissue sarcomas, and better !a#s to use current treatments. 5linical trials
are in progress at hospitals and cancer centers around the countr#. 5linical trials are an
important part of the development of ne! methods of treatment. 0efore a ne! treatment can
be recommended for general use, doctors conduct clinical trials to find out !hether the
treatment is safe for patients and effective against the disease.
Table 1: Major Types of Soft Tissue Sarcomas in Aults
Tissue of !rigin Type of Cancer "sual #ocation in
t$e %oy
Fibrous tissue $ibrosarcoma Arms, legs, trunk
Aalignant fibrous
h#stioc#toma
2egs
:ermatofibrosarcoma runk
Fat 2iposarcoma Arms, legs, trunk
Muscle
"triated muscle
"mooth muscle
Bhabdom#osarcoma
2eiom#osarcoma
Arms, legs
-terus, digestive
tract
%loo &essels 3emangiosarcoma Arms, legs, trunk
,
@aposi's sarcoma 2egs, trunk
#ymp$ &essels 2#mphangiosarcoma Arms
Syno&ial tissue
(linings of Coint cavities,
tendon sheaths)
"#novial sarcoma 2egs
'erip$eral ner&es Aalignant peripheral nerve sheath
tumour>/eurofibrosarcoma
Arms, legs, trunk
Cartilage an bone(
forming tissue
1xtraskeletal chondrosarcoma 2egs
1xtraskeletal osteosarcoma 2egs, trunk (not
involving the bone)
Table ): Major Types of Soft Tissue Sarcomas in C$ilren
Tissue of !rigin Type of Cancer
"sual #ocation
in t$e %oy
Most
common
ages
Muscle
"triated
muscle
Bhabdom#osarcoma
1mbr#onal 3ead and neck,
genitourinar#
tract
(nfantG9
Alveolar soft part sarcoma Arms, legs, head,
and neck
(nfantG1<
"mooth
muscle
2eiom#osarcoma runk 1,G1<
Fibrous tissue $ibrosarcoma Arms and legs 1,G1<
Aalignant fibrous
histioc#toma
2egs 1,G1<
:ermatofibrosarcoma runk 1,G1<
Fat 2iposarcoma Arms and 2egs 1,G1<
%loo &essels (nfantile hemangio+
peric#toma
Arms, legs,
trunk, head, and
(nfantG9
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neck
Syno&ial tissue
(linings of Coint
cavities, tendon
sheaths)
"#novial sarcoma 2egs, arms, and
trunk
1,G1<
'erip$eral ner&es Aalignant peripheral nerve sheath
tumors (also called
neurofibrosarcomas, malignant
sch!annomas, and neurogenic
sarcomas)
Arms, legs, and
trunk
1,G1<
Muscular ner&es Alveolar soft part sarcoma Arms and legs (nfantG1<
Cartilage an
bone(forming
tissue
1xtraskeletal m#xoid chondrosarcoma 2egs 1*G19
1xtraskeletal mesench#mal 2egs 1*G19
Desmoi tumor
A esmoi tumor (sometimes referred to as aggressive fibromatosis) is a rare () per
million population) tumor that ma# or ma# not be part of a genetic s#ndrome such as familial
adenomatous pol#posis ($A?).
3istologicall# the# resemble lo!+grade fibrosarcomas, but the# are ver# infiltrative and
tend to recur even after complete resection (s#stemic metastasis is rare).
:esmoid tumors ma# be classified as extra+abdominal, abdominal !all, or intra+
abdominal (the last is more common in patients !ith $A?). (t is thought that the lesions ma#
develop in relation to estrogen levels or trauma>operations.
reatment ma# consist of !atching and !aiting, complete surgical removal, radiation
therap#, antiestrogens and /"A(:s, or chemotherap#.
Fibrosarcoma
Fibrosarcoma (fibroblastic sarcoma) is a malignant tumor derived from fibrous
connective tissue and characteri6ed b# immature proliferating fibroblasts or undifferentiated
anaplastic spindle cells.
'at$ology
he tumor ma# present different degrees of differentiationH lo! grade (differentiated),
intermediate malignanc# and high malignanc# (anaplastic). :epending on this
differentiation, tumor cells ma# resemble mature fibroblasts (spindle+shaped), secreting
collagen, !ith rare mitoses. hese cells are arranged in short fascicles !hich split and merge,
giving the appearance of "fish bone". ?oorl# differentiated tumors consist in more at#pical
cells, pleomorphic, giant cells, multinucleated, numerous at#pical mitoses and reduced
collagen production. ?resence of immature blood vessels (sarcomatous vessels lacking
endothelial cells) favors the bloodstream metastasi6ing.
#eiomyosarcoma
#eiomyosarcoma is a t#pe of sarcoma !hich is a neoplasm of smooth muscle. (Ihen
benign, it is called a leiom#oma.)
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"mooth muscle cells make up the involuntar# muscles, !hich are found in most parts of
the bod#H in uterus, stomach and intestines, !alls of all blood vessels, and skin.
(t is most commonl# found in the stomach, small intestine and retroperitoneum.
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2eiom#osarcoma is a ver# rare cancer. (t makes up 8% of soft tissue sarcomas.
?resentl# there is no cure, onl# remission if it can be attained, and this rare cancer can
reappear an#!here and at an# time. 0ecause of its rarit#, fe! doctors kno! ho! to treat it
and it attracts ver# little research.
#iposarcoma
#iposarcoma is a malignant tumor that arises in fat cells in deep soft tissue, such as that
inside the thigh or in the retroperitoneum.
he# are t#picall# large bulk# tumors !hich tend to have multiple smaller satellites
extending be#ond the main confines of the tumor.
0ecause of their rarit#, liposarcomas are best treated b# a sarcoma center.
Symptoms
?atients usuall# note a deep seated mass in their soft tissue. ;nl# !hen the tumor is ver#
large do s#mptoms of pain or functional disturbances occur.
Betroperitoneal tumors ma# present themselves !ith signs of !eight loss and emaciation
and abdominal pain. hese tumors ma# also compress the kidne# or ureter leading to kidne#
failure.
*ncience+'re&alence
Aost fre4uent in middle+aged and older adults (age 9* and above), liposarcomas are the
most common of all soft+tissue sarcomas. Annuall# .., cases occur per million population.
'rognosis
he prognosis varies depending on the site of origin, the t#pe of cancer cell, the tumor
si6e, the depth, and proximit# to l#mph nodes. Aetastases are common. he , #ear survival
rate for a high+grade liposarcoma is less than ,*%.
R$abomyosarcoma
A r$abomyosarcoma is a t#pe of cancer, specificall# a sarcoma (cancer of connective
tissues), in !hich the cancer cells are thought to arise from skeletal muscle progenitors. (t
can also be found attached to muscle tissue, !rapped around intestines, or an#!here, to
include the neck area. (t is most common in children ages one to five, and teens aged 1, to
1<, although 4uite rare in the latter.
Bhabdom#osarcoma is a relativel# rare form of cancer. (ts t!o most common forms are
embr#onal rhabdom#osarcoma and alveolar rhabdom#osarcoma. (n the former, !hich is
more common in #ounger children, the cancer cells resemble those of a t#pical 7+to+=+!eek
embr#o. (n the latter, !hich is more common in older children and teenagers, the# resemble
those of a t#pical 1*+to+1.+!eek embr#o.
Diagnosis
Ihen rhabdom#osarcoma is suspected, tests !ill be run for blood, muscle, and
marro!.:iagnosis of rhabdom#osarcoma depends on recognition of differentiation to!ard
skeletal muscle cells. he protein myo D1 is a protein normall# found in developing skeletal
muscle cells !hich disappears after the muscle matures and becomes innervated b# a nerve.
hus, m#o :1 is not found in normal skeletal muscle and serves as a useful
immunohistochemical marker of rhabdom#osarcoma.
Treatment
=
reatment for rhabdom#osarcoma consists of chemotherap#, radiation therap# and
sometimes surger#. "urger# to remove the tumor is often difficult or impossible because the
tumor is usuall# embedded deep !ithin the tissue, leaving it difficult to reach. (f a tumor
presents itself in the extremities, amputation is often necessar# to improve chances of
survival.
(f there is no evidence of metastasis, surger# combined !ith chemotherap# and radiation
offer the best prognosis. ?atients !hose tumors have metastasi6ed usuall# have a poor
chance for long+term survival. (n patients !ho began treatment before metastasis, the
prognosis is better, although the disease is generall# incurable because the tumors that cannot
be surgicall# removed tend to spread.
Syno&ial sarcoma
A syno&ial sarcoma is a rare form of cancer !hich usuall# occurs near to the Coints of
the arm or leg. (t is one of the soft tissue sarcomas.he cells of a syno&ial sarcoma have a
microscopic appearance similar to that of the s#novium, giving the disease its name, but the
actual cells from !hich the tumour develops are unkno!n and not necessaril# s#novial.
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?rimar# s#novial sarcomas are most common in the soft tissue near the large Coints of the
arm and leg but have been documented in most human tissues and organs, including the
brain, prostate and heart."#novial sarcoma occurs most commonl# in the #oung, representing
about =% of all soft tissue sarcomas
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but about 1,+.*% of cases in adolescents and #oung
adults.
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he peak of incidence is before the )*th birthda# and males are affected more often
than females (ratio around 1..H1).
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,istopat$ology
!o cell t#pes can be seen microscopicall# in s#novial sarcoma. ;ne fibrous t#pe,
kno!n as a spindle or sarcomatous cell, is relativel# small and uniform and found in sheets.
he other is epithelial in appearance. 5lassical s#novial sarcoma has a biphasic appearance
!ith both t#pes present. "#novial sarcoma can also appear to be poorl# differentiated or to be
monophasic fibrous, consisting onl# of sheets of spindle cells. "ome authorities
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state that,
extremel# rarel#, there can be a monophasic epithelial form !hich causes difficult# in
differential diagnosis.
2ike other soft tissue sarcomas, there is no universal grading s#stem for reporting
histopatholog# results.
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(n 1urope, the roCani or $rench s#stem is gaining in popularit#
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!hile the /5( grading s#stem is more common in the -nited "tates. he roCani s#stem
scores the sample, depending on tumour differentiation, mitotic index, and tumour necrosis,
bet!een * and 7 and then converts this into a grade of bet!een 1 and ), !ith 1 representing a
less aggressive tumour.
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he /5( s#stem is also a three grade one but takes account of a
number of other factors.
Molecular biology
Aost, and perhaps all, cases of s#novial sarcoma are associated !ith a reciprocal
translocation t(xF1=)(p11..F411..). here is some debate about !hether the molecular
observation itself is definitional of s#novial sarcoma.
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he diagnosis of s#novial sarcoma is
t#picall# made based on histolog# and is confirmed b# the presence of t(JF1=).
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his
translocation event bet!een the "K gene on chromosome 1= and one of ) ""J genes
(""J1, ""J. and ""J9) on chromosome J causes the presence of a "K+""J fusion gene.
he resulting fusion protein brings together the transcriptional activating domain of "K and
the transcriptional repressor domains of ""J. "K+""J is thought to underlie s#novial
<
sarcoma pathogenesis through d#sregulation of gene expression.
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here is some association
bet!een the "K+""J1 or "K+""J. fusion t#pe and both tumour morpholog# and five+
#ear survival.
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Symptoms
"#novial sarcoma usuall# presents !ith an other!ise as#mptomatic s!elling or mass,
although general s#mptoms related to maligancies can be reported such as fatigue.
Treatment
reatment usuall# involvesH
"urger#, to remove the tumor and a safet# margin of health# tissue. his is the
mainsta# of s#novial sarcoma treatment and is curative in approximatel# .*+8*% of
patients, depending on the particular stud# being 4uoted.
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5onventional chemotherap#, (for example, :oxorubicin h#drochloride and
(fosfamide), to reduce the number of remaining microscopic cancer cells. he benefit
of chemotherap# in s#novial sarcoma to overall survival remains unclear, although a
recent stud# has sho!n that survival of patients !ith advanced, poorl# differentiated
disease marginall# improves !ith doxorubicin>ifosfamide treatment.
Badiotherap# to reduce the chance of local recurrence. he benefit of
radiotherap# in this disease is less clear than for chemotherap#.
Sarcoma t$at originates in t$e bone L primar# bone malignant
tumour L is rare. he condition affects more children than adults. ;steosarcoma and
1!ing's sarcoma occur most often in children, adolescents and #oung adults, ages 1* to .,.
5hondrosarcoma is more common in adults. Aore often, cancer cells spread (metastasi6e) to
the bones from other areas of cancer in the patient s bod#. he most common forms of
primar# bone sarcomas areH
!steosarcoma, !hich occurs primaril# in gro!ing bone tissue
C$onrosarcoma, !hich occurs in cartilage
-.ing/s sarcoma, !hich arises primaril# in immature tissue in bone marro!
"igns and s#mptoms
?ain is the most common s#mptom of bone malignant tumour. Although bone cancer can
arise in an# of patientMs bod#'s .*7 bones, it most fre4uentl# occurs in the long bones of #our
arms and legs. ;ther possible signs and s#mptoms of bone cancer includeH
Ieakened bones, sometimes leading to fractures
Noint s!elling and tenderness (for tumors in or near Coints)
$atigue
$ever
Ieight loss
Anemia
5auses
Aost of the time, rather than starting in bones, cancer cells spread (metastasi6e) to the
bones from other areas of cancer in the bod#. his is called secondar# or metastatic bone
cancer. his means that the cancer originated in a different place but has no! migrated to the
bones. $or example, lung cancer commonl# spreads from the lungs to the bones.
(n general, no one kno!s for certain !hat causes most primar# bone cancer. Adults !ith
?aget's disease of bone, !hich involves abnormal development of ne! bone cells, ma# be at
increased risk of osteosarcoma.
1*
(n a fe! cases, bone cancers ma# have a hereditar# component, such as inH
#i(Fraumeni synrome0 his condition is characteri6ed b# an increased risk of
man# different cancers, including osteosarcoma, leukemia, breast cancer, ovarian
cancer and others.
Rot$mun(T$omson synrome0 his condition causes short stature, skeletal
problems and rashes, and increases risk of bone cancer.
,ereitary retinoblastoma0 5hildren !ith this rare cancer of the e#e have an
increased risk of osteosarcoma.
Multiple e1ostoses0 5hildren !ith this inherited condition that causes cartilage
bumps to form on #our bones have an increased risk of chondrosarcoma.
Badiation is occasionall# associated !ith bone cancer. 1xposure to radiation from an J+
ra# !on't harm the patient. 0ut heav# doses of radiation, such as radiation therap# given for
other cancers, can increase the risk of developing bone cancer, especiall# if the patient has
received the therap# at a #oung age. "till, radiation therap# is becoming more and more
sophisticated, !hich ma# lead to fe!er of such side effects. $or example, doctors toda# are
better able to regulate doses of radiation and more precisel# target the tumor being treated.
"creening and diagnosis
(f the doctor suspects on a bone tumor, he takes a medical histor# and performs a
ph#sical exam. (maging tests, such as J+ra#s, computeri6ed tomograph# (5) scans,
ultrasound and magnetic resonance imaging (AB(), enable the doctor to see and evaluate the
area of concern. he doctor ma# also re4uest a bone scan, a procedure in !hich the patient is
inCected !ith a tin# amount of radioactive material, called a tracer, !hich can be detected b#
a special camera used to create images of the bones. :etermining !hether a tumor is
malignant re4uires removal of a sample of tissue (biops#) from the tumor for examination.
echni4ues for removing a sample of a suspected bone tumor includeH
2eele biopsy0 he doctor uses a thin needle to remove small pieces of tissue
from the tumor. here are t!o t#pes of needle biops# L fine+needle aspiration and
core biops#. A core biops# involves using a slightl# larger needle to remove a small,
solid core of tissue.
Surgical biopsy0 he doctor makes an incision through the skin and removes
either the entire tumor (excisional biops#) or a portion of the tumor (incisional
biops#). (n some cases the patient ma# need onl# local anesthesia. $or a larger or
deep+seated tumor, the patient'll likel# re4uire general anesthesia for the procedure. (t's
important that a doctor experienced in the treatment of sarcomas perform the
excisional biops#.
Grading and staging
0esides determining !hether the tissue is cancerous, examining tissue can determine ho!
aggressive the cancer is (its grade). $urther testing, such as scans and blood tests, !ill
determine if the cancer has spread and ho! far (its stage).5hildhood bone cancers, such as
osteosarcoma and 1!ing's sarcoma, are generall# grouped into t!o stages, depending on
!hether the cancer is contained in one part of the bod# (locali6ed) or has spread to other
parts (metastasi6ed).
"urvival is based on a number of factors, including the t#pe of cancer, at !hat stage the
cancer !as discovered and !here the tumor is located. (f the tumor is ver# small and
locali6ed, the five+#ear survival rate is close to <* percent. (f the cancer has begun to spread,
ho!ever, survival becomes more difficult.
11
5omplications
he complications of bone cancer ma# include !eakened bones and bone fractures. (f the
cancer spreads to other organs, complications include d#sfunction of the affected organ, such
as shortness of breath if it spreads to the lungs.
reatment
As !ith other cancers, treatment for bone malignancies depends on the si6e, t#pe,
location and stage of the tumour, including !hether it has spread to the lungs or other parts
of the patient s bod#, and his overall health. "urger# is the most common treatment for bone
tumour. "urger# for cancer that hasn't spread involves removing the cancer and a rim of
health# tissue surrounding it. (n the past, amputation !as common for bone cancer in an arm
or leg. oda#, advances in surgical techni4ues and chemotherap# before surger#
(neoadCuvant chemotherap#) or after surger# (adCuvant chemotherap#) and radiation therap#
make limb+sparing surger# possible in man# cases. Iith osteosarcoma, limb+sparing surger#
involves replacing the cancerous bone !ith an artificial device (prosthesis) or bone from
another part of the bod# or from another person (transplant).(f osteosarcoma spreads, it often
goes to the lungs. reatment ma# involve surgical removal of both the bone tumor and the
cancer in the lung.
1!ing's sarcoma has a tendenc# to metastasi6e rapidl#. reatment ma# involve
chemotherap# !ith multiple drugs as !ell as radiation therap# and surger# to remove the
primar# tumor.
!steosarcoma
!steosarcoma is the most common t#pe of malignant bone cancer, accounting for ),%
of primar# bone malignancies. here is a preference for the metaph#seal region of tubular
long bones. ,*% of cases occur around the knee. (t is a malignant connective (soft) tissue
tumor !hose neoplastic cells present osteoblastic differentiation and form tumoral bone.
;steogenic "arcoma is the 7th leading cancer in children under age 1,. ;steogenic
"arcoma affects 9** children under age .* and ,** adults (most bet!een the ages of 1,+)*)
ever# #ear in the -"A. Approximatel# 1>) of the <** !ill die each #ear, or about )** a #ear.
A second peak in incidence occurs in the elderl#, usuall# associated !ith an underl#ing bone
patholog# such as ?aget's disease, medullar# infarct, or prior irradiation. Although about
<*% of patients are able to have limb+salvage surger#, complications, such as infection,
prosthetic loosening and non+union, or local tumor recurrence ma# cause the need for further
surger# or amputation.
'at$ology
he tumor ma# be locali6ed at the end of the long bones. Aost often it affects the upper
end of tibia or humerus, or lo!er end of femur. he tumor is solid, hard, irregular ("fir+tree"
or "sun+burst" appearance on J+ra# examination) due to the tumor spicules of calcified bone
radiating in right angles. hese right angles form !hat is kno!n as 5odman's triangle.
"urrounding tissues are infiltrated.
Aicroscopicall#H he characteric feature of osteosarcoma is presence of osteoid (bone
formation) !ithin the tumour. umor cells are ver# pleomorphic (anaplastic), some are giant,
numerous at#pical mitoses. hese cells produce osteoid describing irregular trabeculae
(amorphous, eosinophilic>pink) !ith or !ithout central calcification
(hematox#linophilic>blue, granular) + tumor bone. umor cells are included in the osteoid
1.
matrix. :epending on the features of the tumour cells present (!hether the# resemble bone
cells, cartilage cells or fibroblast cells), the tumour can be subclassified.
Causes
he causes of osteosarcoma are not kno!n. Ouestions remain about !hether radium, or
fluoride, in drinking !ater can act as "environmental triggers" for increasing the incidence of
the disease. A lo! selenium or Ditamin :) level or a high level of inflammation, as
measured b# interleukin+7, interleukin+=, or /f+k0, umor /ecrosis $actor Alpha ma# have
a significant role as tumor suppressors and tumor initiators respectivel#. Becent studies sho!
that an increased level of c+$os can lead to osteosarcoma. he stud# that sho!ed this result
!as done on transgenic mice in !hich the $luid "heer "tress ($"") !as increased to increase
the number of osteoblast. "ince c+$os is ubi4uitous in its over expression it can not onl#
increase the osteoblast resulting in the s#mptoms osteosarcoma. herefore it is recentl#
believed that a biological effect that ma# cause osteosarcoma is an error in the molecular
path!a# that controls c+$os, causing an overexpression !ith no other counter stimuli to stop
over production.
Symptoms an clinical presentation
Aan# patients first complain of pain that ma# be !orse at night, and ma# have been
occurring for some time. (f the tumor is large, it can appear as a s!elling. he affected bone
is not as strong as normal bones and ma# fracture !ith minor trauma (a pathological
fracture).he most commonl# affected bones are the proximal humerus, the distal radius, the
distal femur, and the tibia,
&7'
follo!ing the basic premise "far from the elbo!, close to the
knee". ;ther sites include the ribs, the mandible, the spine, and the pelvis. Barel#,
osteosarcoma ma# arise from soft+tissues (extraskeletal osteosarcoma). Aetastasis of tumors
involving the limb bones is ver# common, usuall# to the lungs. he tumor causes a great deal
of pain, and can even lead to fracture of the affected bone.
Diagnosis
$amil# ph#sicians and orthopedists rarel# see a malignant bone tumor (most bone tumors
are benign). hus, man# patients are initiall# misdiagnosed !ith c#sts or muscle problems,
and some are sent straight to ph#sical therap# !ithout an x+ra#.
he route to osteosarcoma diagnosis usuall# begins !ith an x+ra#, continues !ith a
combination of scans (5 scan, ?1 scan, bone scan, AB() and ends !ith a surgical biops#.
Auch can be seen on films, but the biops# is the onl# definitive proof that a bone tumor is
indeed malignant or benign.
he biops# of suspected osteosarcoma should be performed b# a 4ualified orthopedic
oncologist. he American 5ancer "ociet# statesH "?robabl# in no other cancer is it as
important to perform this procedure properl#. An improperl# performed biops# ma# make it
difficult to save the affected limb from amputation."
Treatment
?atients !ith osteosarcoma are best managed b# a medical oncologist !hen possible (or
amputation in some cases) and an orthopedic oncologist experienced in managing sarcomas.
5urrent standard treatment is to use neoadCuvant chemotherap# (chemotherap# given before
surger#) follo!ed b# surgical resection. he percentage of tumor cell necrosis (cell death)
seen in the tumor after surger# gives an idea of the prognosis and also lets the oncologist
kno! if the chemotherap# regime should be altered after surger#.
"tandard therap# is a combination of limb+salvage orthopedic surger# !hen possible (or
amputation in some cases) and a combination of high dose methotrexate !ith leucovorin
1)
rescue, intra+arterial cisplatin, adriam#cin, ifosfamide !ith mesna, 05:, etoposide, muram#l
tri+peptite (A?).
(fosfamide can be used as an adCuvant treatment if the necrosis rate is lo!. )+#ear event
free survival ranges from ,*% to 8,%. And ,+#ear survival ranges from 7*% to =,P% in
some studies. ;verall, 7*+7,% treated ,+#ears ago !ill be alive toda#. hese survival rates
are overall averages and var# greatl# depending on the individual necrosis rate.
;steosarcoma has one of the lo!est survival rates for pediatric cancer despite
chemotherap#'s success in osteosarcoma of 7 chemotherapies, interferon+alpha, interleukin+
., and being the protot#pe of solid tumors in cancer.
$luids are given for h#dration.:rugs like @#tril and Qofran help !ith nausea and
vomiting.
/eupogen, epogen, /eulasta help !ith !hite blood cell counts and neutrophil counts.
0lood helps !ith anemia.
%est treatment protocols
op , treatment protocols are ranked here b# osteosarcoma support
1. <8% ,+#ear survival "ept. .**, :r. Boss Iilkins, et al, :enver 5linic for
1xtremities at Bisk, :enver, 5olorado
.. <1 ,+#ear survival 1<<< :r. suchi#a @ana6a!a, Napan
). <* ,+#ear survival 1<<< :r. suchi#a @ana6a!a Napan
9. 8= ,+#ear survival arm 9 Aarch .**, ?;G ?ediatric ;ncolog# Group
,. 87 ,+#ear survival Nan. 1<<. 1*+?rotocol A"@55 :r. Ae#ers, :r. 3eale#,
:r. 3uvos, :r. Bosen
'rognosis
?rognosis is separated into three groups.
Stage * osteosarcoma is rare and includes parosteal osteosarcoma or lo!+grade
central osteosarcoma. (t has an excellent prognosis (E<*%) !ith !ide resection.
Stage **b prognosis depends on the site of the tumor (proximal tibia, femur,
pelvis, etc.) si6e of the tumor mass (in cm.), and the degree of necrosis from
neoadCuvant chemotherap# (chemotherap# prior to surger#). ;ther pathological factors
such as the degree of p+gl#coprotein, !hether the tumor is cxcr9+positive
&1'
, or 3er.+
positive are also important, as these are associated !ith distant metastases to the lung.
he prognosis for patients !ith metastatic osteosarcoma improves !ith longer times to
metastases, (more than 1. months+.9 months), a smaller number of metastases (and
their resectabilit#). (t is better to have fe!er metastases than longer time to metastases.
hose !ith a longer length of time(E.9months) and fe! nodules (. or fe!er) have the
best prognosis !ith a .+#ear survival after the metastases of ,*% ,+#ear of 9*% and
1* #ear .*%. (f metastases are both local and regional, the prognosis is !orse.
(nitial ?resentation of stage *** osteosarcoma !ith lung metastates depends on
the resectabilit# of the primar# tumor and lung nodules, degree of necrosis of the
primar# tumor, and ma#be the number of metastases. ;verall prognosis is )*% or
greater depending.
C$onrosarcoma
A c$onrosarcoma is a t#pe of cancer of the bone. 5hondrosarcoma is a cartilage+based
tumor and is in a categor# of cancers called sarcomas. About .,% of primar# bone cancers
(meaning those !hich start in the bone) are chondrosarcomas. his disease can affect people
19
or animals of an# age, although it is more common among older people than among children.
&1'
Classification
he aggressiveness of chondrosarcoma is graded based on ho! fast it gro!s and its
likelihood to metastasi6e or spread to other parts of the bod#. Grade 1 is a lo! grade (slo!
gro!ing) cancer, and grades . and ) are higher grades (fast gro!ing) cancers. :epending on
the grading s#stem used b# #our medical facilit#, it's also possible to have grade 9 !hich
!ould be even more aggressive than lo!er grade tumors.he most common bones for
chondrosarcoma to gro! are the pelvic and shoulder bones along !ith the superior regions of
the arms and legs. &.' 0ut the# can also be found in an# bones of the bod#, even in the base
of the skull.
Diagnosis
/earl# all chondrosarcoma patients appear to be in good health. "ince it is not like other
cancers, it doesn't affect the !hole s#stem. Aan# patients are not a!are that there is a tumor
gro!ing inside them until there is a noticeable lump or pain. "ometimes a patient has no
s#mptoms and no a!areness of an# lump and perhaps, b# having a test for something else
gets diagnosed accidentall#. "ometimes an unexpected fracture !ill be the first indication of
a bone tumor.&)'
Causes
he cause is unkno!n. ?atients ma# have a histor# of enc$onroma or
osteoc$onroma.
Treatment
reatment depends on the location of the disease and the aggressiveness of the tumors
&9'. 0ecause chondrosarcomas are rare, the# are treated at specialist hospitals !ith "arcoma
5enters.
"urger# is the main form of treatment for chondrosarcoma. Ausculoskeletal tumor
specialists or orthopedic oncologists are usuall# chosen to treat chondrosarcoma, unless it is
located in the skull, spine, or chest cavit#, in !hich case, a neurosurgeon or thoracic surgeon
experienced !ith sarcomas is chosen. ;ften, a limb+sparing operation can be performed &,',
ho!ever in some cases amputation is unavoidable. Amputation of the arm, leg, Ca!, or half
of the pelvis (called a hemipelvectom#) ma# be necessar# in some cases.
5hemotherap# or traditional radiotherap# are not ver# effective for most
chondrosarcomas, although proton therap# is sho!ing promise !ith local tumor control at
over =*% &7'.
5omplete surgical ablation is the most effective treatment, but sometimes this is difficult.
?roton therap# Badiation can be useful in a!k!ard locations to make surger# more effective.
'rognosis
?rognosis depends on ho! earl# the cancer is discovered and treated. $or the least
aggressive grade, about <*% of patients survive more than five #ears after diagnosis.&8' $or
the most aggressive grade, more than a 4uarter of patients live more than five #ears.
umors ma# recur in the future. $ollo! up scans are extremel# important for
chondrosarcoma to make sure there has been no recurrence or metastasis, !hich usuall#
occurs in the lungs.
-piemiology
1,
5hondrosarcomas are more common in people over the age of 9*. 5hondrosarcoma is
considered to be a rare form of bone cancer. 1ven more rare are chondrosarcoma located in
the skull base, spine, rib cage, or lar#nx.
-.ing/s sarcoma
-.ing/s sarcoma is the common name for primitive neuroectodermal tumor. (t is a rare
disease in !hich cancer cells are found in the bone or in soft tissue. he most common areas
in !hich it occurs are the pelvis, the femur, the humerus, and the ribs. Names 1!ing (1=77+
1<9)) first described the tumor, establishing that the disease !as separate from l#mphoma
and other t#pes of cancer kno!n at that time. 1!ing's sarcoma occurs most fre4uentl# in
male teenagers. 1!ing's sarcoma is the result of a translocation bet!een chromosomes 11
and .., !hich fuses the 1I" gene of chromosome .. to the $2(1 gene of chromosome 11.
Clinical finings
1!ing's sarcoma is more common in males and usuall# presents in childhood or earl#
adulthood, !ith a peak bet!een 1* and .* #ears of age. (t can occur an#!here in the bod#,
but most commonl# in the pelvis and proximal long tubular bones. he diaph#ses of the
femur are the most common sites, follo!ed b# the tibia and the humerus. hirt# percent are
overtl# metastatic at presentation.
*maging finings
;n conventional radiographs, the most common osseous presentation is a permeative
l#tic lesion !ith periosteal reaction. he classic description of lamellated or "onion skin"
t#pe periosteal reaction is often associated !ith this lesion. ?lain films add valuable
information in the initial evaluation or screening. he !ide 6one of transition (e.g.
permeative) is the most useful plain film characteristic in differention of benign versus
aggressive or malignant l#tic lesions.
AB( should be routinel# used in the !ork+up of malignant tumors. AB( !ill sho! the
full bon# and soft tissue extent and relate the tumor to other nearb# anatomic structures (e.g.
vessels). Gadolinium contrast is not necessar# as it does not give additional information over
noncontrast studies, though some current researchers argue that d#namic, contrast enhanced
AB( ma# help determine the amount of necrosis !ithin the tumor, thus help in determining
response to treatment prior to surger#.
5 can also be used to define the extraosseous extent of the tumor, especiall# in the
skull, spine, ribs and pelvis. 0oth 5 and AB( can be used to follo! response to radiation
and>or chemotherap#.
0one scintigraph# can also be used to follo! tumor response to therap#.
Differential iagnosis
;ther entities that ma# have a similar clinical presentation include osteom#elitis,
osteosarcoma (especiall# telangiectatic osteosarcoma) and eosinophilic granuloma. "oft
tissue neoplasms such as malignant fibrous histioc#toma that erode into adCacent bone ma#
also have a similar appearance.
1!ing's sarcoma can be differentiated from acute osteom#elitis b#H
+Jra#H in 1!ing's sarcoma, onion+peel appearance + in osteom#elitis, first .!eeks +ve ..
after .!eeks periosteal ne! bone formation .. after )!eeks se4uestrum and cloaca and
invoclum
+site of painH osteom#elitis, epiph#sis + 1!ing's sarcoma, diaph#sis or metaph#sis
+5achexia in 1!ing's sarcoma
17
-piemiology
he fre4uenc# in the -nited "tates depends on the patient's age, !ith a rate of *.) cases
per 1,***,*** children in those #ounger than ) #ears of age to as high as 9.7 cases per
1,***,*** in adolescents aged 1,+1< #ears. (nternationall# the annual incidence rate averages
less than . cases per 1,***,*** children.
&1'
(n the -nited @ingdom an average of six children
per #ear are diagnosed, mainl# males in earl# stages of pubert#. :ue to the prevalence of
diagnosis during teenage #ears, there ma# possibl# be a link bet!een the onset of pubert#
and the earl# stages of this disease, although no research is currentl# being conducted to
confirm this theor#.
Treatment
0ecause almost all patients !ith apparentl# locali6ed disease at diagnosis have occult
metastatic disease, multidrug chemotherap# as !ell as local disease control !ith surger#
and>or radiation is indicated in the treatment of all patients (.). reatment often consists of
neo+adCuvant chemotherap# generall# follo!ed b# !ide or radical excision, and ma# also
include radiotherap#. 5omplete excision at the time of biops# ma# be performed if
malignanc# is confirmed at that time. reatment lengths var# depending on location and
stage of the disease at diagnosis. Badical chemotherap# ma# be as short as 7 treatments at )
!eek c#cles, ho!ever most patients !ill undergo chemotherap# for 7+1. months and
radiation therap# for ,+= !eeks.
'rognosis
"taging attempts to distinguish patients !ith locali6ed from those !ith metastatic
disease. Aost commonl#, metastases occur in the chest, bone and>or bone marro!. 2ess
common sites include the central nervous s#stem and l#mph nodes."urvival for locali6ed
disease is 7,+8*% !hen treated !ith chemotherap#. 2ong term survival for metastatic
disease can be less than 1*% but some sources state it is .,+)*%.
References
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18
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<. S
a

b

c
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1*. S
a

b

&"httpH>>!!!.lidd#shriversarcomainitiative.org>/e!sletters>D*./*7>"#novial>s#novia
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1=
J+Ba# of a child !ith
1!ing's sarcoma of the
tibia