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• Out Line

– Introduction
– Incidence
– Epidemiology
– Molecular Pathogenesis
– Initial Assessment
– Treatment of Extremity and Trunk Wall Sarcoma
– Special Clinical Situations
– Gastrointestinal Stromal Tumors
– Desmoids
– Dermatofibrosarcoma
– Protuberans
– Pediatric Sarcomas
Soft tissue tumours
• Introduction
– The term 'soft tissue' refers to the extraskeletal connective tissue
that accounts for more than 50 per cent of body weight.
– It includes muscle, tendon, fat, fascia, and synovium.
– These all arise embryologically from the mesenchyme.
– Although soft tissue tumors are all thought to arise from primitive
mesodermal tissue, they vary widely in their histologic appearance
and in the mature tissue type that they resemble.
– By convention, tumors arising in the peripheral nerves are also
grouped with soft tissue tumors, as their presentation and
treatment are similar.
• Benign soft tissue tumors such as lipoma or benign fatty
tumor closely resemble specific normal adult tissues.
• They exhibit little tendency to local invasion, rarely recur after
local excision, and do not metastasize.
• Malignant soft tissue tumors are termed sarcomas (from the
Greek 'sarkoma', meaning fleshy growth), while malignant
tumors arising from epithelial tissues are termed
carcinomas.
• Exceptions to this generalization are tumors arising from
the endothelium of blood or lymphatic vessels, or the
mesothelial lining of body cavities, which are grouped with
soft tissue tumors.
• A classification has been developed by Enzinger using the principle
of similarity of histologic appearance to normal tissues (Table 1).
• Unlike most other human neoplasms, the soft tissue tumors are not
grouped simply into benign or malignant.
• Occupying a middle ground between sarcomas and benign
neoplasms is a group of locally aggressive tumors such as
desmoid tumors, aggressive fibromatoses, atypical lipomas, and
aggressive neurofibromas.
• These do not metastasize and are not called sarcomas, but
require more comprehensive treatment than do other benign soft
tissue tumors because their characteristics locally resemble
malignant behavior.
• Incidence
– Benign tumors of soft tissue are far more common than sarcomas,
outnumbering them by about 100:1 in biopsy series.
– As many lipomas and hemangiomas are never submitted for biopsy
examination, the actual ratio is probably considerably higher.
– Lipomas are the most common human neoplasm.
– Sarcomas are rare when the volume of tissue from which they may arise
is considered, with an annual age-adjusted incidence of about 2:100 000.
– Just over 5000 soft tissue sarcomas are diagnosed annually in the United
States, for example, accounting for 0.7 per cent of newly diagnosed
invasive cancers (excluding squamous and basal cell carcinoma of the
skin).
– In children under 15 years of age they account for over 6 per cent of all
cancers.
• Epidemiology
• Molecular epidemiology
– The pathogenesis of most soft tissue tumors is poorly understood.
– Genetic factors are associated with certain benign tumors:
• about 5 per cent of lipomas and angiolipomas are multiple and familial.
– Soft tissue sarcomas have no established genetic predisposition, but
occur with increased frequency in patients with genetically transmitted
conditions such as intestinal polyposis, Gardner's syndrome, and
basal cell nevus syndrome.
– Patients with von Recklinghausen's disease have a 15 per cent
chance of developing a soft tissue sarcoma.
– This is associated with NF1 gene expression.
• As the germ cell mutations associated with these conditions are defined, the
association with sarcomas of soft tissue is being studied and appears to
reflect the loss of tumor suppressor activity of certain genes.
• The mutations of RB genes responsible for retinoblastoma are also
associated with an increased risk of later sarcoma.
• Mutations of the RB genes are seen in sporadic sarcomas as well.
• p53, another tumor suppressor gene, is found to exhibit germline mutations
in the Li-Fraumeni families who are at increased risk for sarcoma.
• This gene is also found to be mutated in sporadic sarcomas.
• This is a very active field of investigation.
• It is hoped that certain genetic markers will be predictive of response to
certain therapies, for instance sensitivity to radiation or to certain cytotoxic
agents, and allow therapy to be specifically tailored to a given tumor.
• Some experimental models suggest the feasibility of this approach.
• p53 nuclear overexpression and loss of pRB expression are both associated with
increased tumor grade, but such work remains at an investigational level without
clinical integration.
• The investigation into the molecular mechanism of the development of Kaposi's
sarcoma in association with AIDS has been a model for future research in this field.
• Kaposi's sarcoma has been found to be linked to the presence of human herpes
virus 8 (HHV-8).
• It is found in all types of Kaposi's sarcoma, not only those that are AIDS associated.
• The role of HHV-8 has proved quite complex with the initial tumor arising as an
angiohyperplastic–inflammatory lesion mediated by inflammatory cytokines and
angiogenic factors triggered by the infection.
• Over time this reactive lesion evolves into a sarcoma, demonstrated by monoclonal
growth in the later nodular lesions.
• Chemical carcinogenesis
– Chemical carcinogens have been implicated in anecdotal reports but no
link has been established.
– Exposure to dioxin, phenoxyacetic acid, or to agent orange (containing
dioxin) has not been shown convincingly to have an association with
development of sarcomas in case–control studies, yet conflicting results
have been published.
• Trauma or foreign bodies
– Although trauma is often incidental to the discovery of a soft tissue
tumor by a patient, no evidence exists of any link between the two.
– Anecdotal reports of sarcoma occurring in association with foreign bodies
such as bullets and shrapnel pieces exist, but prospective studies of large
numbers of patients with metallic or Silastic implants have not shown any
associated tumor development.
• Chronic lymphedema
• There is an increased incidence of lymphangiosarcoma in lymphedematous extremities, first
described in women's arms following radical mastectomy (Steward–Treves' syndrome).
• It has also been seen in lymphedema resulting from filariasis confirming the association with
the lymphedema rather than breast cancer or chest wall irradiation.

• Radiation
• Radiation exposure is associated with a later incidence of sarcoma estimated at between 2
and 4/1000 patients after 10 years.
• Although any type of soft tissue sarcoma can arise,
– malignant fibrous histiocytoma,
– angiosarcoma,
– lymphangiosarcoma, or
– extraskeletal osteosarcoma are most common.
• Most soft tissue tumors arise in individuals in whom no predisposing factor can be identified.
• Benign tumors of soft tissue
• Non-aggressive benign tumors
• Lipomas are among the most common benign tumors.
• They are usually subcutaneous, not tethered or fixed to the underlying fascia,
multilobulated, and vary greatly in size.
• Angiolipomas contain many small vessels and are usually tender or painful.
– Their major significance is their confusion with liposarcomas.
– A biopsy should be taken or they should be removed when evidently growing, when
larger than 5 cm, or if symptomatic.
• Biopsies should be taken of
– large lipomas, or
– those tethered to fascia or
– deep to the fascia, as recommended for liposarcomas.
• Neurofibromas and neurilemmomas both arise from
Schwann cells.
– Simple excision is curative, but when they arise in nerves of clinical
significance, every effort should be made to preserve the affected
nerve.
– Multiple neurofibromas are seen in patients with von
Recklinghausen's disease and are too numerous to be removed: 10
to 15 per cent of these patients will develop neurogenic sarcomas.
– Neurofibromas should be removed when they undergo rapid
enlargement or if they become painful, as well as for cosmetic
reasons.
• Dermatofibromas, also called sclerosing hemangiomas,
occur in the skin and have a very characteristic
appearance.
• They are usually about 1 cm in diameter and do not tend to
grow.
• Excision is curative when desired.
• Myxomas and mesenchymomas present as soft tissue
tumors; the diagnosis is made histologically.
– They are almost always cured by simple excision.
– Mesotheliomas arise in the pleura, pericardium, or peritoneum.
– They project but do not infiltrate and are usually cured by excision.
• Hemangiomas are vascular neoplasms that are usually
present at birth in the head and neck area, but they can be
anywhere.
• Most congenital hemangiomas regress spontaneously by
the age of 5 years, even if they grow rapidly during the first
months of life.
• It is extremely rare for such lesions to compromise vital
structures, but low-dose radiation to a very focused field may
be used to treat this situation.
• Hemangiomas of extremities may not regress, and can result
in limb enlargement.
• Such patients are often best treated by angiographic
embolization, or sometimes by surgical dearterialization.
• The hemangioma may involve bone, and surgery too near the
tumor may be accompanied by severe or even fatal
hemorrhage.
• Lymphangiomas are similar tumors which can be surgically
excised.
• Conservative management of both of these tumor types
allows preservation of function and achieves a favorable
cosmetic result.
• Ongoing definition of mediators of growth of these lesions is
leading to anecdotal reports of dramatic response to therapy
with targeted biologic modulators and specific cytokines.
• This is a rapidly evolving clinical aspect of research in
angiogenesis.
• Ganglions are fibrous walled cysts, most commonly
seen on the dorsal surface of the wrist.
• They result from an excrescence of synovial tissue and
are filled with synovial fluid.
• Simple excision is usually curative.
• They are easily confused with giant cell tumors of the
tendon sheath, which are also most commonly seen in the
wrist or hand and are also treated by simple excision.
• Leiomyomas most commonly arise from the smooth muscle
of the uterus and gastrointestinal tract. Leiomyoblastomas are
similar to leiomyomas, but tend to grow large and to develop
areas of hemorrhage and cystic degeneration. Both are
treated by simple excision.
• Nodular fasciitis has often been mistaken for a fibrosarcoma.
• These tumors usually occur in the superficial or deep fascia
and grow rapidly when they first appear.
• In weeks to months they reach 3 to 5 cm and then usually
stop growing.
• They are generally eliminated by simple excision.
• Aggre s s ive be nign tumors
• De s mo id tumo rs or ag g re s s ive fibro mato s is ca n a ris e from a ny fa s cia l
tis s ue .
– The s e le s ions a re re ma rka ble for the ir infiltrative nature and fall into two
g ro ups .
1.Abdo minal de s mo id tumo rs a ris e from the mus cula r wa ll of the a bdome n,
– ofte n in a s s ocia tion with a bdomina l incis ions , a nd
– a re e s pe cia lly common in pos tpa rtum wome n, in whom the y ma y be re la te d to
hormona l cha nge s a nd s urgica l tra uma .
– If re s e cte d to cle a r ma rgins the y s e ldom re cur.
2.Extra-abdo minal de s mo id tumo rs be ha ve more a ggre s s ive ly.
– The y a re common a bout the s houlde r or within a n e xtre mity, whe re the y infiltra te
diffus e ly.
– Although the s e tumors do not me ta s ta s ize , the y ca us e loca l de s truction of
function.
– S urgica l re s e ction s hort of a mputa tion is ofte n impos s ible , but wide re s e ction is
the pre fe rre d tre a tme nt whe n it ca n be a ccomplis he d with minima l morbidity.
– Re s e ction to clos e ma rgins or to pos itive ma rgins is ge ne ra lly followe d by
re curre nce .
• The hormona l milie u ma y a ffe ct de s moid tumors , a nd
tre a tme nt with pro g e s te ro ne , tamo xife n, indo me thac in,
and as c o rbic ac id ha ve a ll be e n re porte d to induce
re mis s ions .
• The s e the ra pie s a re a s s ocia te d with minima l toxicity a nd
de s e rve furthe r s tudy, but the y us ua lly fa il to produce a
re s pons e .

• Atypic al lipo mas and atypic al fibro us his tio c yto mas
– a re ge ne ra lly loca te d de e p in the s oft tis s ue or mus cle ;
– the y a ppe a r a typica l his tologica lly a nd a lthough the y do not
me ta s ta s ize the y te nd to re cur loca lly a fte r re s e ction, pa rticula rly if
wide ma rgins a re not a chie ve d.
• De rmato fibro s arc o ma pro tube rans
– a ris e s ins idious ly in the s kin or s ubcuta ne ous tis s ue .
– The s e tumors do not me ta s ta s ize , e ve n whe n multiply re curre nt, but the y
be ha ve loca lly a s though ma ligna nt.
– It is importa nt to a chie ve control a t the time of firs t re s e ction, with
ge ne rous (at le as t 2 c m) ma rgins to minimize the ris k of furthe r
re curre nce .
– Ha lf of a ll pa tie nts tre a te d with s imple e xcis ion a nd more limite d ma rgins
will s uffe r re curre nce ; a mputa tion ma y be re quire d a nd de a th ma y re s ult.
– Ra dia tion the ra py a s a s upple me nt to cons e rva tive re s e ction a ppe a rs
be ne ficia l but ha s not be e n s ubje ct to controlle d tria l.
– Ra dia tion ha s be e n us e d in pla ce of ve ry ra dica l re s e ction in s ome
pa tie nts with a fa vora ble re s ult.
So ft Tis s ue Sarco mas
• S a rcoma s a re a he te ro g e ne o us g ro up o f ne o plas ms tha t a ris e pre domina ntly
from ce lls of the e mbryo nic me s o de rm.
• While the majority of s a rcoma s a re s o ft tis s ue s arc o mas , othe r type s of s a rcoma
include
– bo ne s arc o mas (o s te o s arc o ma, c ho ndro s arc o ma, and
– rare bo ne tumo rs like c ho rdo ma, ang io s arc o ma, and le io myo s arc o ma o f bo ne ) and
– Ewing ’s s arc o ma/ pe riphe ral primitive ne uro e c to de rmal tumo r, which ca n occur
e ithe r in the bone or in the s oft tis s ue s .
• Mos t primary s o ft tis s ue s arc o mas origina te in
– an e xtre mity (50%–60%);
– the ne xt mo s t c o mmo n s ite s are the trunk (19%),
– re tro pe rito ne um (15%), and
– he ad and ne c k (9%).
• The a na tomic s ite of a prima ry s a rcoma influe nce s tre a tme nt a nd outcome .
• Soft tis s ue s a rcoma s include more tha n 50 his tologic s ubtype s
• His torica lly, the mos t common s ubtype s in a dults (e xcluding Ka pos i’s
s a rcoma ) we re
– malig nant fibro us his tio c yto ma (28%),
– lipo s arc o ma (15%),
– le io myo s arc o ma (12%),
– s yno vial s arc o ma (10%), and
– malig nant pe riphe ral ne rve s he ath tumo r (6%).
• Toda y, ma ligna nt fibrous his tiocytoma is cla s s ifie d a s e ithe r
le io myo s arc o ma, ple o mo rphic undiffe re ntiate d s arc o ma,
myxo fibro s arc o ma, o r de diffe re ntiate d lipo s arc o ma ba s e d on ce llula r
diffe re ntia tion a nd ge ne tics .
• Embryo nal/alve o lar rhabdo myo s arc o mas a re the mos t common s oft
tis s ue s a rcoma s of childhood, whe re a s ple o mo rphic rhabdo myo s arc o ma
occurs pre domina ntly in a dults , a nd a lthough it s ha re s pa rt of the na me , it
ha s a diffe re nt biology a nd s hould no t be tre ate d as a pe diatric s arc o ma.
• Soft tis s ue s a rcoma (STS ) is a colle ctive te rm for a n unus ua l a nd
dive rs e group of ma ligna ncie s tha t a ris e from ce lls of the e mbryonic
me s ode rm.
• Although tis s ue s de rive d from the me s ode rm conta in a pproxima te ly
75% o f the c e lls in the human bo dy, s a rcoma s re pre s e nt only 1%
o f adult tumo rs and 15% o f pe diatric tumo rs .
• Sa rcoma s ma y occur a nywhe re in the body a nd compris e more tha n
50 dis tinct his tologic s ubtype s .(from ACS)
– Appro ximate ly 43% o f STSs o c c ur in the e xtre mitie s
– 15% in the re tro pe rito ne um
– 10% in the trunk
– 19% in the vis c e ra, and
– 13% in o the r lo c atio ns .
• S oft tis s ue s a rcoma s a ccount for a pproxima te ly 1% of a ll ne w
ca nce r dia gnos e s .
• Almos t ha lf of a ll pa tie nts dia gnos e d with the dis e a s e
e ve ntua lly die a s a re s ult of the ca nce r.
• S oft tis s ue s a rcoma s ca n occur a nywhe re in the body, but
mos t origina te in(from curre nt)
– an e xtre mity (59%),
– the trunk (19%),
– the re tro pe rito ne um (15%), o r
– the he ad and ne c k (9%).
• Ove ra ll, s a rcoma s a ffe ct 5 to 6 individua ls pe r 100,000
inha bita nts pe r ye a r,a ccounting for le s s tha n 1% o f all
malig nanc ie s in a dults a nd 15% o f malig nanc ie s in
c hildre n.
• Nb
– 80%-s o ft tis s ue ,20%-bo ne
• Me s e nc hyme is a type of tis s ue cha ra cte rize d by loos e ly a s s ocia te d
ce lls tha t lac k po larity a nd a re s urrounde d by a la rge e xtra ce llula r
ma trix.
• Me s e nchyma l ce lls a re a ble to de ve lop into the tis s ue s of
the lympha tic a nd circula tory s ys te ms , a s we ll a s conne ctive
tis s ue s throughout the body, s uch a s bone a nd ca rtila ge .
• A s a rcoma is a ma ligna nt ca nce r of me s e nchyma l ce lls .
• Me s e nchyme is cha ra cte rize d morphologica lly by a
promine nt ground s ubs ta nce ma trix conta ining a loos e a ggre ga te
of re ticula r fibrils a nd uns pe cia lize d ce lls .
• Me s e nchyma l ce lls ca n migra te e a s ily, in contra s t to e pithe lial c e lls ,
which lac k mo bility and are o rg anize d into c lo s e ly adhe re nt
s he e ts , a nd a re pola rize d in a n apic al-bas al o rie ntatio n.
• Sa rcoma s a re a ra re a nd he te roge ne ous group of ma ligna nt tumors
of me s e nchyma l origin tha t compris e le s s tha n 1 pe rce nt of a ll a dult
ma ligna ncie s a nd 12 pe rce nt of pe dia tric ca nce rs .
• Approxima te ly 80 pe rce nt of s a rcoma s origina te from s oft tis s ue a nd
the re s t from bone .
• The re a re a bout 11,930 ne w ca s e s of s oft tis s ue s a rcoma dia gnos e d
e a ch ye a r in the Unite d Sta te s , with 4870 de a ths .
• The his topa thologic s pe ctrum of s a rcoma s is broa d, pre s uma bly
be ca us e the e mbryonic me s e nchyma l ce lls from which the y a ris e
ha ve the ca pa city to ma ture into s tria te d s ke le ta l a nd s mooth
mus cle , a dipos e a nd fibrous tis s ue , bone , a nd ca rtila ge .
• Although e ctode rma l in origin, ma ligna nt tumors a ffe cting pe riphe ra l
ne rve s a re include d be ca us e of s imila ritie s in the ir clinica l be ha vior,
ma na ge me nt, a nd outcome .
• 2 Appro ximate ly two thirds o f s o ft tis s ue s arc o mas aris e in the
e xtre mitie s ; the re ma ining o ne third is dis tribute d be twe e n the
re tro pe rito ne um, trunk, a bdome n, he a d, a nd ne ck.
• 3 Multimo dality tre atme nt, inc luding s urg ic al re s e c tio n,
radiatio n the ra py, a nd, in s e le cte d ca s e s , s ys te mic che mothe ra py,
ha s be e n a pplie d to pa tie nts with loca lly a dva nce d, high-gra de ,
e xtre mity s a rcoma s .
• 4 Ove rall 5-ye ar s urvival rate fo r patie nts with all s tag e s o f s o ft
tis s ue s a rcoma is 50% to 60%.
• 5 The s e rare tumo rs ac c o unt fo r le s s than 1% o f c anc e r in
a dults (e s tima te d 10,000 ca s e s pe r ye a r in the Unite d Sta te s ) a nd
re pre s e nt 15% of ca nce rs in childre n.
• 6 The tre atme nt alg o rithm fo r s o ft tis s ue s arc o mas
de pe nds on tumor s tag e , s ite , and his to lo g y.
• 7 Of the patie nts who die o f s arc o ma, mo s t will
s uc c umb to me tas tatic dis e as e in the lung s , which
80% o f the time o c c urs within 2 to 3 ye ars o f the initial
diag no s is .
• 8 Pro g re s s in the unde rs tanding o f s o ft tis s ue
s arc o ma bio lo g y is crucia l for the de ve lopme nt of ne w
tre a tme nts .
• Ana tomic dis tribution
– Soft tiss ue sa rcoma s occur at all ana tomic body site s , and their
freque ncy is no t a s imple func tio n of abundanc e of the
tis s ue type .
– Lipos a rcoma s are not common in the large fatty de posits of the
abdominal wall; while in the thigh, a freque nt site , the y often
arise de e p in the mus c le mas s , rathe r tha n in the
subcuta ne ous fat.
• Howe ve r, s ome his tologic type s of s oft tis s ue s a rcoma ha ve a pre dile ction
for ce rta in a na tomic s ite s .
• As a n e xa mple , o nly 14 pe rc e nt of a ll s oft tis s ue s a rcoma s pre s e nt in the
uppe r e xtre mity.
• In contra s t, 40 to 50 pe rce nt of a ll e pithe lio id s arc o mas a ris e on the
fo re arm and finge r
• Epithe lio id s arc o mas
– A ma ligna nt tumour of unce rta in diffe re ntia tion c o mpo s e d o f no dule s and
g arlands of ro unde d, g las s y e o s ino philic c e lls circums cribing a re a s of ce ntra l
hya liniza tion a nd ne cros is .
– The ce lls conta in cytoke ra tins .
– This tumour cha ra cte ris tica lly occurs in s upe rficia l s oft tis s ue s of the dis tal
po rtio ns o f the e xtre mitie s o f ado le s c e nts and yo ung adults .
• Thig h, butto c k, and g ro in — 46
pe rc e nt
• Uppe r e xtre mity — 13 pe rc e nt
• To rs o — 18 pe rc e nt
• Re tro pe rito ne um — 13 pe rc e nt
• He ad and ne c k — 9 pe rc e nt
Ana tomic distribution and site -s pe cific histologic subtype s of 7563 cons e cutive STS se e n at the University of
Texa s MD
Approxima te relation of age to incide nce of various type s of sa rcoma . Continuous line indica te s
pe a k incide nce of tumor. Dotte d line indica te s re duc e d inc ide nc e o f tumor.
• Exce pt for malig nant pe riphe ral ne rve s he ath tumo rs
in pa tie nts with ne uro fibro mato s is , s a rcoma s do not
s e e m to re s ult from progre s s ion or de diffe re ntia tion of a
be nig n s o ft tis s ue tumo r.
• While mos t s a rcoma s a re of unknown ca us e , a fe w
s a rcoma s ubtype s ha ve be e n obs e rve d in s e tting s
s ug g e s ting e tio lo g y.
• In ne arly all ins tance s , s a rcoma s a re thought to a ris e de
no vo and no t fro m a pre e xis ting be nig n le s ion.
• The re is no cle a rly de fine d e tiology in mos t ca s e s of s oft
tis s ue s a rcoma , but a numbe r of a s s ocia te d or
pre dis pos ing fa ctors ha ve be e n ide ntifie d.
• The s e include
– g e ne tic pre dis po s itio n,
– e xpo s ure to radiatio n o r c he mo the rapy,
– c he mic al c arc ino g e ns ,
– c hro nic irritatio n, and
– lymphe de ma.
GENETIC PREDISP OSITION
• Some pa tie nts , pa rticula rly childre n, ha ve a fa milia l pre dis pos ition to
ca nce r
• Li-Fraume ni s yndro me
– As ma ny a s 7 pe rc e nt of childre n with soft tiss ue sa rcoma s ma y ha ve Li-
Fra ume ni syndrome (LFS)
– The LFS is inhe rite d a s a n auto s o mal do minant trait, a nd is prima rily
cha ra cte rize d by
• s o ft tis s ue and bo ne s arc o mas
• bre as t c anc e r;
• brain tumo r,
• le uke mia, and
• adre no c o rtic al c anc e r o c c urring be fo re the ag e o f 45
– A ge rmline muta tion in the p53 tumo r s uppre s s o r g e ne is fo und in mo s t
affe c te d familie s
• FAP and Gardne r's s yndro me
– The re is a high freque ncy of intra a bdominal de s moid tumors
among pa tients with familial ade no mato us po lypo s is or
Gardner's s yndrome
• Re tinobla s toma
– Sa rcoma s of soft tiss ue and bone , pa rticularly os te os a rcoma ,
de velop late r in life in surviving pa tients with retinoblas toma
(RB), pa rticularly of the familial or bilate ral type , in which
individuals inherit a mutant co py of RB
• Ne urofibroma tos is
– Some of the multiple be nign ne urofibroma s of vo n
Rec kling haus e n's dise a s e (type 1 ne urofibromato s is , NF1)
ca n unde rgo maligna nt cha nge to malig nant peripheral nerve
s he ath tumors
• (MPNS Ts , including ne uro fibro s arc o mas , malig nant s c hwanno mas )
• Radiatio n Expo s ure
– Exte rnal radiation the ra py is a rare but well-es ta blishe d risk
factor for soft tiss ue sa rcoma tha t ma y be as s ociate d with
radiatio ninduc e d mutatio ns of the p53 ge ne
– The incide nce of sa rcoma among pa tients who are often
trea te d with radiation for ca nce r of the breas t, cervix, ovary,
tes te s , or lymphatic s ys te m is 8 to 50 time s the ge neral-
po pulatio n ris k
• In a re vie w of 160 pa tie nts with pos tirra dia tion s a rcoma s ,
the mos t common his tologic type s we re
– os te o g e nic s arco ma,
– malig nant fibrous his tio c yto ma,
– ang io s arco ma, and
– lymphang io s arco ma.
• The ris k of de ve loping a s a rcoma incre a s e d with ra dia tion
dos e , a nd the me dia n time be twe e n ra dia tion the ra py a nd
dia gnos is of s a rcoma wa s 10 ye ars .
• Oc c upatio nal Che mic al Expo s ure
• Expos ure to he rbicide s s uch a s phe noxya ce tic a cids a nd
to wood pre s e rva tive s conta ining chlorophe nols ha s be e n
linke d to a n incre a s e d ris k of s oft tis s ue s a rcoma
• Trauma
• Although pa tie nts with s a rcoma ofte n re port a his tory of
tra uma , no c aus al re latio ns hip has be e n e s tablis he d.
• More ofte n, a minor injury c alls atte ntio n to a pre -
e xis ting tumo r.
• Chro nic Lymphe de ma
– In 1948, Ste wa rt and Treve s first de s cribe d the as s ociation
be twe e n chronic lymphe de ma afte r axillary diss e ction and
subs e que nt lympha ngios a rcoma
– Lympha ngios a rcoma ha s be e n es tima te d to occur in 0.07% of
patie nts who underg o axillary no de dis s e c tio n.
– It als o ha s be e n reporte d to occur afte r filarial infections and in
the lowe r extre mities of pa tients with conge nital lymphe de ma .
– Lymphang io s arco ma is ge ne rally an ag gre s s ive tumor;
averag e s urvival of patie nts with lymphang io s arco ma is 19
mo nths .
• The ge ne tics of s a rcoma s s e gre ga te into two major type s :
– thos e with s pe c ific ge ne tic alteratio ns and us ually simple
karyotype s , including fusion ge ne s due to reciprocal
transloca tions (eg, PAX3-FKHR in alve olar
rha bdomyos a rcoma s ) or spe cific point muta tions (eg, c-kit
muta tions in ga s trointe s tinal stromal tumors [GIST]), and
– thos e with no ns pe c ific ge ne tic alteratio ns and complex,
unbala nce d karyotype s , reflecte d by nume rous ge ne tic los s e s
and gains (eg, os te os a rcoma , MFH, lipos a rcoma s othe r tha n
the myxoid type , angios a rcoma , leiomyos a rcoma ).
• Sa rcoma s ca n be broa dly cla s s ifie d into thre e groups
a ccording to the ge ne tic e ve nts unde rlying the ir
de ve lopme nt:
– s pe c ific trans lo c atio ns or ge ne amplific atio n,
– de fining onc o g e nic mutatio ns , and
– co mple x ge no mic rearrang e me nts .
• In ge ne ra l, s a rcoma s re s ulting from ide ntifia ble mole cula r
e ve nts te nd to occur in yo ung e r patie nts with his to lo g y
s ug g e s ting a c le ar line o f diffe re ntiatio n.
• In contra s t, s a rcoma s witho ut ide ntifiable g e ne tic
cha nge s or e xpre s s ion profile s igna ture s te nd to occur in
olde r pa tie nts a nd e xhibit ple omorphic cytology a nd p53
dys func tio n
• Trans lo catio n-As s o c iate d Sarc o mas
• To da te , tra ns loca tions ha ve be e n ide ntifie d in 14 s ubtype s of
s oft tis s ue s a rcoma , a ccounting for 20% to 30% of a ll
s a rcoma s
• Tra ns loca tions re s ult in in-fra me ge ne fus ion, which in turn
re s ults in fus e d products e ncoding oncoprote ins tha t function
a s tra ns criptiona l a ctiva tors or re pre s s ors .
• The be s t cha ra cte rize d ge ne fus ions a re in Ewing’s s a rcoma
(EWS -FLI1), cle a r ce ll s a rcoma (EWS -ATF1), myxoid/round
ce ll lipos a rcoma (TLS CHOP), a lve ola r rha bdomyos a rcoma
(PAX3-FHKR), de s mopla s tic s ma ll round ce ll tumor (EWS -
WT1), a nd s ynovia l s a rcoma (S S 18-S S X).
• Fus ion ge ne –re la te d s a rcoma s ha ve be e n e s tima te d to
a ccount for 30% o r more of a ll s a rcoma s .
• Dire ct or indire ct inte ra ctions be twe e n fus ion tra ns cripts a nd
ce ll cycle re gula tors ha ve be e n e lucida te d by s e ve ra l
inve s tiga tor a nd ide ntify the s e tra ns cripts a s pote ntia lly
promis ing mole cula r the ra pe utic ta rge ts .
• Howe ve r, fus ion ge ne s in s a rcoma ha ve be e n s ucce s s fully
ta rge te d in only a fe w ca s e s , in which fus ion re s ulte d in
ove re xpre s s ion of a growth fa ctor or growth fa ctor re ce ptor.
• S e ve ra l growth fa ctors a nd the ir re ce ptors (e .g., e pide rma l
growth fa ctor re ce ptor) pre vious ly re porte d to pla y a n
importa nt role in a utocrine or pa ra crine s timula tion of
ca rcinoma growth ha ve be e n a s s ocia te d with high his tologic
gra de a nd poor prognos is in s oft tis s ue s a rcoma s .
• Amplificatio n-As s o ciate d Sarc o mas
– Oncoge ne s a re ge ne s tha t ca n induce ma ligna nt tra ns forma tion a nd
te nd to drive ce ll prolife ra tion.
– S e ve ra l oncoge ne s ha ve be e n a s s ocia te d with s oft tis s ue s a rcoma s ,
including MDM2, N-myc, c-erbB2, and members of the ras family.
– These oncogenes produce s pe cific oncoprote ins tha t e ithe r pla y a role
in nucle a r function a nd ce llula r s igna l tra ns duction or function a s
growth fa ctors or growth fa ctor re ce ptors .
– This typica lly occurs in de diffe re ntia te d lipos a rcoma , whe re the
a mplifica tion of MDM2 drives the neoplastic process.
– Amplification of these ge ne s ha s be e n s hown to corre la te with
a dve rs e outcome in s e ve ra l type s of s oft tis s ue s a rcoma .
• Onc o g e nic Mutatio ns
• GISTs a re the cla s s ic e xa mple of s a rcoma s in which
tumorige ne s is is prima rily drive n by a s ingle a ctiva ting
muta tion, in the ge ne e ncoding KIT re ce ptor tyros ine
kina s e or pla te le t-de rive d growth fa ctor re ce ptor-α
(PDGFRA)
• Co mple x Ge no mic Re arrang e me nts
• The la rge s t group of s a rcoma s is the group with comple x
cytoge ne tic a lte ra tions , which include s high-gra de s pindle
ce ll s a rcoma s a nd ple omorphic s a rcoma s .
• Ma ny s a rcoma s in this group e xhibit ina ctiva tion of tumor
s uppre s s or ge ne s .
• The two ge ne s mos t re le va nt to s oft tis s ue s a rcoma a re
re tinobla s toma (Rb) and p53.
• Muta tions or de le tions in Rb ca n le a d to re tinobla s toma , the
mos t common ma ligna nt ocula r ne opla s m of childhood.
• S urvivors of re tinobla s toma a re a t ris k for de ve loping s oft
tis s ue a nd bone s a rcoma s la te r in life .
• Pa tie nts with ge rmline muta tions in p53 (Li-Fra ume ni
s yndrome ) ha ve a high incide nce of s oft tis s ue s a rcoma s
• Muta nt p53 expression is thought to correlate with poor ove ra ll
s urviva l.
• S tra te gie s to ta rge t p53 mutation a re be ing inve s tiga te d for
tre a tme nt of s ome s a rcoma s .
• Ne urofibroma tos is type 1 (von Re cklingha us e n’s dis e a s e )
occurs in a pproxima te ly 1 of e ve ry 3000 pe ople a nd is due to
va rious muta tions in the NF-1 tumo r s uppre s s o r g e ne ,
loca te d on chromos ome
• Pa tie nts with ne uro fibro mato s is type 1 have an e s timate d
3% to 15% additio nal ris k of ma ligna nt dis e a s e compa re d
with the ge ne ra l popula tion life time ris k, including ma ligna nt
pe riphe ra l ne rve s he a th tumors (MPNS T) a nd GIST.
• In turn, 25% to 50% of pa tie nts with MPNS T ha ve a muta tion
in NF-1.
• INITIAL ASS ES SMENT
• The clinica l be ha vior of mos t s oft tis s ue s a rcoma s is de te rmine d by
a na tomic loca tion (de pth in re latio n to the inve s ting fas c ia), his tologic
s ubtype a nd gra de of a ggre s s ive ne s s , a nd s ize .
• The domina nt pa tte rn of me ta s ta s is is he ma toge nous , primarily to the
lung s .
• Lymph node me ta s ta s is is ra re (affe c ting <5% o f patie nts ) e xce pt in a
fe w his tologic s ubtype s , including
– e pithe lio id s arco ma,
– pe diatric rhabdo myo s arc o ma,
– cle ar ce ll s arco ma,
– ang io s arco ma, and,
– mo re rare ly, s yno vial s arco ma and myxo fibro s arc o ma
Nb
• Dis ta nt s ite s of me ta s ta s e s va ry in a ccorda nce with the tumor
his to lo g y and the s ite o f the primary tumo r.
• Extre mity s a rcoma s mos t commonly me ta s ta s ize to the lung,
whe re a s abdo minal and re tro pe rito ne al s a rcoma s more
fre que ntly me ta s ta s ize to the live r, with the lung be ing a
s e conda ry s ite of me ta s ta tic impla nta tion.
• In a ddition, the re a re a fe w s arco mas that te nd to
me tas tas ize to re giona l lymph node s
• The s e diffe ring pa tte rns of me ta s ta tic s pre a d mus t be
ca re fully cons ide re d during the initia l e va lua tion of s a rcoma
pa tie nts .
Incide nce of Nodal Meta s ta s e s for Sele cte d Sa rcoma s

Sarc o ma Type Inc ide nc e o f No dal


Me tas tas e s (%)
Epithe lioid sa rcoma 17-80
Cle a r ce ll sa rcoma 25 -50
Angiosa rcoma 11-40
Rha bdomyos a rcoma 11-36
Synovia l sa rcoma 2-17
• Clinical Pre s e ntatio n
– S oft tis s ue s a rcoma s mos t commonly pre s e nt a s a n as ympto matic
mas s .
– Extre mity s a rcoma s ma y pre s e nt a s a de e p ve no us thro mbo s is ,
pa rticula rly in pa tie nts without s ig nificant ris k facto rs for
thro mbo s is .
– Tumors in the dis ta l e xtre mitie s a re ge ne ra lly s maller, where as
tumors in the pro ximal e xtre mitie s and re tro perito ne um can
gro w quite larg e be fo re be c o ming appare nt.
– Tumors ofte n gro w ce ntrifug ally a nd ca n compre s s s urrounding
norma l s tructure s .
– Infre que ntly, tumor imping e me nt o n bo ne or ne uro vas c ular
bundle s pro duce s pain, e de ma, and s we lling .
• Mos t pa tients with s us pecte d s oft tis s ue ne opla s ms pres e nt with a
pa inle s s ma s s , a lthough pa in is reporte d in one -third of ca s es .
• Dela y in dia gnos is is common; the mos t common mis dia gnos e s
include pos t-tra uma tic or s ponta ne ous he ma toma a nd “lipoma .”
• La te dia gnos is of pa tients with retrope ritone a l s a rcoma s is very
common beca us e of
– the larg e s ize o f the re tro pe rito ne al s pac e ,
– g e ne rally s lo w g ro wth rate , and
– the te nde nc y o f s arc o mas to g radually dis plac e ra the r tha n to inva de
a nd compromise a dja ce nt visce ra .
– Thus, re trope ritone a l sa rcoma s ca n re a ch conside ra ble size be fore
dia gnos is
• Phys ica l e xa mina tion s hould include a s s e s s me nt of tumor
s ize , re la tive mobility, a nd fixa tion.
• Pa tie nts with e xtre mity s oft tis s ue tumors s hould be
e va lua te d for tumor-re la te d ne uropa thy.
• Exa mina tion of re giona l lymph node ba s ins s hould a ls o
be pe rforme d with the unde rs ta nding tha t noda l
me ta s ta s e s a re re la tive ly uncommon, o c c urring in le s s
than 15% o f patie nts with e xtre mity s oft tis s ue s a rcoma s
• Le s s fre que ntly, tumors ca us e o bs truc tive gas tro inte s tinal s ympto ms
o r ne uro lo g ic s ympto ms re la te d to compre s s ion of lumbar o r pe lvic
ne rve s .
• Ofte n a n e xtre mity ma s s is dis c o ve re d afte r a traumatic e ve nt tha t
dra ws a tte ntion to a pre -e xis ting le s ion.
• The diffe re ntia l dia gnos is of a s oft tis s ue ma s s s hould include
cons ide ra tion of
– lipo ma (whic h is 100 time s mo re co mmo n than s arco ma),
– lymphang io ma,
– le io myo ma,
– ne urino ma,
– primary o r me tas tatic carc ino ma,
– me lano ma, and
– lympho ma.
• Supe rficia l s ma ll le s ions (<5 c m) tha t a re ne w or tha t a re
not e nla rging a s indica te d by clinica l his tory ca n be
obs e rve d.
• Enla rging ma s s e s a nd ma s s e s la rge r than 5 c m o r de e p
to the fas c ia s hould be e va lua te d with a his to ry,
imag ing , and bio ps y.
• Dia gnos tic Ima ging
• Dia gnos tic ima ging s hould be pe rforme d be fore a ny inva s ive
proce dure to a void the pos s ibility of s oft tis s ue s we lling or
he morrha ge complica ting the ima ge inte rpre ta tion.
• Pre tre a tme nt dia gnos tic ima ging is he lpful for de fining the
s ize a nd a na tomic loca tion of a tumor a nd its proximity to
a dja ce nt s tructure s ; s ta ging dis e a s e with re s pe ct to re giona l
or me ta s ta tic s pre a d; guiding pe rcuta ne ous biops y; a nd
e s ta blis hing whe the r a tumor is be nign or ma ligna nt a nd low
gra de or high gra de .
• Radio graphs
– provide us e ful informa tion on prima ry bone tumors , but the y a re not us e ful in the
e va lua tion of s oft tis s ue s a rcoma s of the e xtre mitie s unle s s unde rlying bone
involve me nt from a n a dja ce nt s oft tis s ue tumor is s us pe cte d.
– Che s t ra diogra phy s hould be pe rforme d for pa tie nts with prima ry s a rcoma s to
a s s e s s for lung me ta s ta s e s .
• CT s ca n
– For pa tie nts with hig h-g rade le s io ns o r tumo rs >5 cm (T2), compute d
tomogra phy (CT) of the che s t s hould be cons ide re d.
– CT is the pre fe rre d te chnique for e va lua ting re tro pe rito ne al s arco mas , whe re a s
ma gne tic re s ona nce ima ging (MRI) ofte n is favo re d fo r s o ft tis s ue s arco mas
o f the e xtre mitie s .
– Both ultra s onogra phy a nd CT ca n a s s is t in guiding fine -ne e dle a s pira tion, core
biops y for initia l dia gnos is , a nd a t re curre nce .
• Ultras o no graphy
– Ultra s onogra phy ma y ha ve a dia gnos tic role for pa tie nts who ca nnot unde rgo
MRI.
– Ultra s onogra phy a ls o ca n be a us e ful a djunct to MRI whe n findings a re
inde te rmina te a nd for de line a ting a dja ce nt va s cula r s tructure s .
• Co mpute d To mo g raphy
– Contra s t-e nha nce d CT ca n a s s e s s the e xte nt of s oft tis s ue tumor
burde n a nd the proximity of the tumor to vita l s tructure s .
– CT is the pre fe rre d ima ging te chnique for e va lua ting re trope ritone a l
s a rcoma s .
– Curre nt CT te chnique s ca n provide a de ta ile d s urve y of the
a bdome n a nd pe lvis a nd ca n de line a te a dja ce nt orga ns a nd
va s cula r s tructure s .
– For e xtre mity s a rcoma s , CT ma y be us e ful if MRI is not a va ila ble or
ca nnot be us e d.
– CT of the a bdome n a nd pe lvis s hould be done whe n his tologic
a s s e s s me nt of a n e xtre mity s a rcoma re ve a ls a myxo id
lipo s arco ma, be ca us e this s ubtype is known to me tas tas ize to the
abdo me n.
A 27-yea r-old ma n pre s e nte d with symptoms of ba ck pain. Compute d tomogra phy of the abdome n de mons tra ting a
4.1 x 3.3 cm hypode ns e ma s s in the retroca val region involving the inferior vena ca va . Subs e que nt biops y of the
tumor confirme d leiomyos a rcoma
• Ma gne tic Re s ona nce Ima ging
– MRI a ccura te ly de line a te s muscle groups a nd distinguis he s a mong bone ,
va scula r structure s, a nd tumor.
– Sa gitta l a nd corona l vie ws a llow e va lua tion of a na tomic compa rtme nts in
thre e dime nsions .
– Soft tiss ue sa rcoma s of the e xtre mitie s usua lly pre se nt on MRI a s
he te roge ne ous ma ss e s .
– The ir signa l inte nsity te nds to be e qua l to or slightly highe r tha n tha t of
a dja ce nt ske le ta l muscle on T1-we ighte d ima ge s a nd he te ro g e ne o us
and hig h o n T2-we ig hte d imag e s .
– He morrha gic, cystic, or ne crotic cha nge s a lso ma y be obse rve d in the
tumor.
– Spe cia l MRI te chnique s, including ma gne tic re sona nce a ngiogra phy, ma y
be pe rforme d if a dja ce nt va scula r structure s must be de line a te d.
• MRI ha s s uppla nte d CT a s the ima ging te chnique of choice
for e va lua tion of s oft tis s ue s a rcoma s of the e xtre mitie s .
• MRI a ls o is va lua ble for a s s e s s ing tumor re curre nce a fte r
s urge ry.
• A ba s e line ima ge us ua lly is obta ine d 3 months a fte r s urge ry.
• S ome clinicia ns be lie ve tha t routine pos tope ra tive ima ging of
a prima ry e xtre mity tumor s ite is not ne ce s s a ry for
a s ymptoma tic pa tie nts , citing the difficultie s in de te cting e a rly
re curre nce in s ca rre d, irra dia te d tis s ue .
• Othe rs a dvoca te routine ima ging e ve ry 6 months for the firs t 2
ye a rs .
A 55-yea r-old woma n pre s e nte d with right thigh pain and enlarging ma s s . Corona l ima ge de mons tra ting an 18-cm
ma s s within the adductor ma gnus mus culature with evide nce of ne crosis and he morrha ge .
• Biops y Tec hnique s
• Fine -Ne e dle As piration.
• At cente rs whe re cytopa thologis ts ha ve expe rie nce with eva lua tion
of mes e nchyma l tumors , fine -ne e dle as piration is a n a ccepta ble
method of dia gnos ing mos t s oft tis s ue s arc omas , pa rticula rly
whe n the res ults corre la te clos e ly with c linic al and radiolo g ic
finding s .
• Fine -ne e dle as piration of prima ry tumors ha s a lowe r dia gnos tic
a ccura cy ra te (60%–90%) tha n core ne e dle biops y a nd is ofte n not
s ufficient for es ta blis hing a s pec ific his to lo g ic diag no s is and
grade.
• Howe ve r, fine -ne e dle a s pira tion is the proce dure of choice to confirm
or rule out the pres e nc e of a metas tatic foc us or loc al
• Although fine -ne e dle a s pira tion of s uperficia l les ions ca n ofte n be
done in the clinic, fine -ne e dle a s pira tion of dee pe r tumors ma y ne e d
to be done by a n inte rve ntiona l ra diologis t unde r s onogra phic or CT
guida nce .
• Generally, a 21- to 23-g aug e ne e dle is introduce d into the ma s s
a fter a ppropria te clea ns ing of the s kin a nd injection of loca l
a ne s the tic.
• Neg ative pres s ure is applied, a nd the ne e dle is move d ba ck a nd
forth s eve ra l times in va rious directions .
• After the ne ga tive pres s ure is rele a s e d, the ne e dle is withdra wn, a nd
the conte nts of the ne e dle a re us ed to prepa re s mea rs .
• A c yto patho lo g is t the n exa mine s the s lides to dete rmine whe the r
s ufficient dia gnos tic ma teria l is pres e nt.
• Co re Ne e dle Bio ps y.
• Core ne e dle biops y is s a fe , a ccura te ,a nd e conomica l a nd ha s
be come the pre fe rre d te chnique for dia gnos ing s oft tis s ue
le s ions .
• Dupuy a nd colle a gue s found tha t ne e dle biops y ha d a n
a ccura cy of 93% in 221 pa tie nts with mus culos ke le ta l
ne opla s ms .
• S onogra phy/CT guida nce ca n pre ve nt s a mpling of
nondia gnos tic ne crotic or cys tic a re a s of the tumor a nd thus
incre a s e the pos itive yie ld ra te .
• Sonogra phy/CT guida nce a ls o pe rmits biops y of tumors in
othe rwis e ina cce s s ible loca tions a nd tumors loca te d ne a r
vita l s tructure s .
• The tis s ue s a mple obta ine d from core ne e dle biops y is
us ua lly s ufficie nt for s e ve ra l dia gnos tic te s ts , s uch a s
e le ctron micros copy, cytoge ne tic a na lys is , a nd flow
cytome try.
• The re porte d complica tion ra te for core ne e dle biops y is
le s s tha n 1%.
• Incis io nal Bio ps y.
• His torica lly, a n ope n s urgica l biops y wa s the g o ld s tandard
fo r achie ving ade quate tis s ue fo r de finitive a nd s pe cific
his tologic dia gnos is of bone or s oft tis s ue s a rcoma s .
• Conte mpora ry guide line s re comme nd incis iona l biops y whe n
core ne e dle biops y ca nnot produce a de qua te tis s ue for
dia gnos is or whe n findings on core ne e dle biops y a re
nondia gnos tic.
• The dis a dva nta ge s of incis iona l biops y include the ne e d to
s che dule the proce dure , the ne e d for ge ne ra l a ne s the s ia , a nd
high cos ts .
• In a ddition, a n ina ppropria te ly pla ce d incis ions ca n
ne ce s s ita te more e xte ns ive de finitive re s e ction to e ncompa s s
the biops y s ite .
• In a s e rie s of 107 pa tie nts with s oft tis s ue s a rcoma , pla nne d
s urgica l tre a tme nts ha d to be cha nge d be ca us e of poorly
orie nte d biops ie s in 25% of ca s e s .
• Complica tion ra te s up to 17% ha ve be e n re porte d a fte r
incis iona l biops ie s .
• Pote ntia l complica tions include he ma toma , infe ction, wound
de his ce nce , a nd tumor funga tion, a ny of which ca n de la y
de finitive tre a tme nt
• Incis iona l biops ie s s hould be pe rforme d only by s urge ons
e xpe rie nce d in the ma na ge me nt of s oft tis s ue s a rcoma ,
ide a lly in a ce nte r s pe cia lizing in the tre a tme nt of s a rcoma
a nd by the s urge on who will pe rform the de finitive
s urge ry.
• The biops y incis ion s hould be orie nte d longitudina lly
a long the e xtre mity to a llow a s ubs e que nt wide loca l
e xcis ion tha t e ncompa s s e s the biops y s ite , s ca r, a nd
tumor e n bloc.
• A poorly orie nte d biops y incis ion ofte n ne ce s s ita te s a n
e xce s s ive ly la rge s urgica l de fe ct for a wide loca l e xcis ion,
which in turn ca n re s ult in a la rge r pos tope ra tive ra dia tion
the ra py fie ld to e ncompa s s a ll tis s ue s a t ris k.
• Ade qua te he mos ta s is mus t be a chie ve d a t the time of
biops y to pre ve nt dis s e mina tion of tumor ce lls into
a dja ce nt tis s ue pla ne s by he ma toma .
• Exc is io nal Bio ps y.
– Excis iona l biops y ca n be pe rforme d for e a s ily a cce s s ible
(s upe rficia l) e xtre mity or trunca l le s ions s maller than 3 cm.
– Howe ve r, e xcis iona l biops y ra re ly provide s be ne fits ove r othe r
biops y te chnique s .
– Excis iona l biops ie s s ho uld no t be performe d for le s io ns
invo lving the hands and fe e t be ca us e s uch biops ie s ma y
complica te de finitive re -e xcis ion.
– For s a rcoma s with initia l dia gnos is confirme d with e xcis iona l biops y,
micros copic re s idua l dis e a s e ha s be e n re porte d in up to 69% of re -
e xcis ion s pe cime ns ; without re -e xcis ion, the re porte d ra te of loca l
re curre nce is 30% to 40% whe n ma rgins a re pos itive or unce rta in.
• Wide en bloc exc is io n is s eldom performe d a s a dia gnos tic
proce dure .
• Whe n en bloc exc is io n is done for dia gnos is , the ma rgin s ta tus is
ofte n not a dequa te ly eva lua te d during pa thologic a s s es s me nt of the
s pecime n.
• Unle s s deta ile d des criptions of the s urgica l proce dure a nd the
pa thology s pecime n a re provide d, the ma rgins s hould be cla s s ified
a s unce rta in or unknown, a cla s s ifica tion a s s ocia te d with the s a me
prognos is a s res e ction ma rgins tha t a re pos itive for tumor cells .
• In pa tients with unce rta in or unknown ma rgins , re-e xcis ion s hould be
performe d if pos s ible to ens ure ne ga tive ma rgins .
• The biops y s ite or tra ct (if a pplica ble) s hould be include d en bloc
with the re-re s e cte d s pecime n.
• Patho lo g ic As s es s me nt and Clas s ific ation
• Sa rcoma is gene ra lly dia gnos e d by morphologic a s s es s me nt ba s ed
on micros copic exa mina tion of his tologic s ections by a n expe rie nce d
s a rcoma pa thologis t.
• Howe ve r, eve n expe rt s a rcoma pa thologis ts dis a gree on the s pecific
his tologic dia gnos is a nd the tumor gra de in 25% to 40% of ca s es .
• Morphologic a s s es s me nt ca n be s upporte d by a ncilla ry technique s ,
including
– c o nve ntio nal c yto g e ne tic s ;
– immuno his to c he mis try; and
– mo le c ular g e ne tic te s ting , which is use ful for cla ss ifying soft tiss ue
sa rcoma subtype s with multiple ge ne tic a be rra tions.
• Othe r mole cula r dia gnos tic te chnique s include
cytoge ne tic a na lys is , fluore s ce nce in s itu hybridiza tion,
a nd polyme ra s e cha in re a ction–ba s e d me thods .
• Howe ve r, mole cula r ge ne tic te chnique s a re a s s ocia te d
with s ignifica nt te chnica l limita tions a nd s hould be
inte rpre te d in the conte xt of the s a rcoma ’s morphologic
fe a ture s .
• S ome e xpe rts ha ve s ugge s te d tha t pa thologic cla s s ifica tion of
s oft tis s ue s a rcoma s ha s more prognos tic s ignifica nce tha n
doe s tumor gra de whe n othe r pre tre a tme nt va ria ble s a re
ta ke n into a ccount.
• Tumors with limite d me ta s ta tic pote ntia l include de s moid,
a typica l lipoma tous tumor (a ls o ca lle d we lldiffe re ntia te d
lipos a rcoma ), de rma tofibros a rcoma protube ra ns , a nd s olita ry
fibrous tumor.
• Tumors with a n inte rme dia te ris k of me ta s ta tic s pre a d us ua lly
ha ve a la rge myxoid compone nt a nd include myxoid
lipos a rcoma , myxofibros a rcoma , a nd e xtra s ke le ta l myxoid
• Among the highly a ggre s s ive tumors with s ubs ta ntia l me ta s ta tic pote ntia l
a re
– ang io s arco ma,
– cle ar ce ll s arco ma,
– ple o mo rphic and de diffe re ntiate d lipo s arco ma,
– le io myo s arco ma,
– MPNST,
– rhabdo myo s arc o ma, and
– s yno vial s arco ma.
• It ha s re ce ntly be e n note d tha t ma ligna nt fibrous his tiocytoma is not
a s s ocia te d with a dis tinct ge ne clus te r, s ugge s ting tha t ma ligna nt fibrous
his tiocytoma is not a s e pa ra te tumor e ntity but ra the r a common
morphologic a ppe a ra nce of va rious s a rcoma s ubtype s .
• For exa mple , mos t tumors initia lly dia gnos e d a s ma ligna nt fibrous
his tiocytoma in the retrope ritone um ha ve bee n recla s s ified us ing
genomic profiling a s dediffere ntia te d lipos a rcoma s ,whe re a s thos e in
the extre mitie s ha ve bee n recla s s ified a s leiomyos a rcoma ,
myxofibros a rcoma , or pleomorphic undiffere ntia te d s a rcoma .
• Guide line s for the pa thologic reporting of s a rcoma ha ve bee n
es ta blis he d.
• Include d in the report s hould be the prima ry dia gnos is , a na tomic
s ite, depth, s ize, a nd his tologic gra de, pres e nce or a bs ence of
ne cros is , s ta tus of excis ion ma rgins a nd lymph node s , TNM s ta ge,
a nd a dditiona l fea ture s of the tumor (i.e., mitotic ra te a nd pres e nce
or a bs ence of va s cula r inva s ion).
Gra ding And Sta ging Soft Tis s ue Sa rcoma s
• Gra ding a s s e s s e s the de gre e of ma ligna ncy of a s a rcoma
a nd is ba s e d on a n e va lua tion of s e ve ra l his tologic
pa ra me te rs
• Limitatio ns o f Grading
• De s pite the wide s pre a d us e of s ome form of gra ding
s ys te m in the dia gnos is a nd ma na ge me nt of s a rcoma s ,
the re is a gre e me nt a mong e xpe rts tha t no gra ding s ys te m
pe rforms we ll on e ve ry type of s a rcoma .
• Des pite the limita tions note d previous ly, gra ding rema ins one of the
mos t powe rful a nd ine xpe ns ive wa ys of a s s es s ing the prognos is in a
s a rcoma a nd is currently rega rde d a s a major inde pe nde nt predictor
of meta s ta s is in the major his tologic types of a dult s oft tis s ue
s a rcoma s .
• Cons e que ntly, a gra de s hould be provide d by the pa thologis t,
whe ne ve r pos s ible .
• It s hould not be cons ide re d a s ubs titute for a n a ccura te his tologic
dia gnos is , howe ve r.
• Gra ding, like dia gnos ing s oft tis s ue s a rcoma s , require s
repre s e nta tive , well-fixe d, well-s ta ine d his tologic ma teria l tha t s hould
be obta ine d before ne oa djuva nt the ra py beca us e this proce s s a lters
ma ny of the fea ture s ne ce s s a ry for a ccura te gra ding.
• Thick or he a vily s ta ine d s e ctions a re mis le a ding be ca us e the y
ma y s ugge s t le s s ce llula r diffe re ntia tion tha n is a ctua lly
pre s e nt.
• S e le ction of the tis s ue s a mple a nd the le ngth of fixa tion ma y
a ls o influe nce the de gre e of ne cros is a nd the mitotic inde x.
• Ne cros is ma y be promine nt in tumors of which a biops y ha s
be e n pre vious ly pe rforme d or tha t ha ve be e n irra dia te d or
e mbolize d a nd, the re fore , ca nnot be a ccura te ly a s s e s s e d in
the s e s itua tions .
• Gra ding is us ua lly ba s e d on the le a s t diffe re ntia te d a re a of a
tumor, unle s s it compris e s a ve ry minor compone nt of the
ove ra ll tumor
Definitions of Gra ding Pa ra me te rs for the FNCLCC Syste m
• Sta ging Sys te ms
• Se ve ra l s ta ging s ys tems ha ve bee n deve lope d for s oft tis s ue
s a rcoma s in a n a ttempt to predict a prognos is a nd to eva lua te
the ra py by s tra tifying s imila r tumors a ccording to prognos tic fa ctors
s uch a s
– the his to lo g ic g rade ,
– tumo r s ize ,
– c o mpartme ntalizatio n o f the tumo r, and
– the pre s e nc e o r abs e nc e o f me tas tas is .
• The two major s ta ging s ys tems us ed a t pres e nt for a dult s oft tis s ue
s a rcoma s were deve lope d by The America n Joint Committe e on
Ca nce r (AJCC) a nd the Mus culos ke le ta l Tumor Socie ty
• AJCC Sta ging Sys te m
– This sys te m is ba s e d on the TNM sta ging sys te m us e d for
sta ging ca rcinoma s , with the addition of histologic gra de as a
prognos tic variable .
– Tumor de pth was subs e que ntly incorpora te d into this sta ging
sys te m.
– In a thre e -tiere d gra ding sys te m, gra de 1 is conside re d low
gra de and gra de s 2 and 3 are high gra de .
– In 2010, the AJCC publishe d the se ve nth edition of its sta ging
ma nual, upda ting the sta ging sys te m for soft tiss ue sa rcoma
• Mus culos ke le ta l Tumor Socie ty Sta ging Sys te m
• The Enne king s ys tem, des igne d for s a rcoma s of s oft tis s ue a nd bone ,
dis tinguis he s two a na tomic s ettings :
– T1, intrac o mpartme ntal tumo rs confine d within the bounda rie s of we ll-
de fine d a na tomic structure s, such a s a func tio nal mus c le g ro up, jo int,
and s ubc utis ; a nd
– T2, e xtrac o mpartme ntal ne o plas ms tha t a rise within or involve
se conda rily e xtra fa scia l spa ce s or pla ne s tha t ha ve no na tura l a na tomic
ba rrie rs to e xte nsion.
• The re a re two gra des (G1 a nd G2) a nd thre e s ta ges .
• In this s ys tem, two gra des a re fa vore d beca us e the y ca n be bette r
rela te d to the two s urgica l proce dure s (wide and radic al exc is io ns )
a nd beca us e of the reporte d la ck of a ny differe nce in the meta s ta tic
ra te betwe e n inte rme dia te - a nd high-gra de tumors .
Nb
• Enne king Stag ing Sys te m
– Surgic al rathe r tha n histological
– Empha sis on co mpartme ntalizatio n in the extremitie s
• Adva nta ge s a nd Dis a dva nta ge s of S ta ging S ys te ms
• The s e two principa l s ta ging s ys te ms s e rve a s a va lua ble
guide to the ra py a nd provide us e ful prognos tic informa tion.
• Although the AJCC s ys te m is a pplica ble to s oft tis s ue
s a rcoma s a t a ny s ite , the de ve lopme nt of this s ys te m wa s
ba s e d on s tudie s tha t include d le s ions from a va rie ty of
a na tomic loca tions , including the e xtre mitie s , re trope ritone um,
a nd he a d a nd ne ck.
• It is difficult to compa re da ta from pa tie nts with tumors a t
the s e s ite s , give n the diffe re nce s in the a bility to e ra dica te
tumors s urgica lly in the s e a na tomic loca tions .
• The AJCC s ys te m a ls o us e s 5 cm a s a n importa nt dime ns ion
for de te rmining a prognos is , a lthough the de s igna tion is
s ome wha t a rbitra ry be ca us e s ize is a continuous va ria ble .
• The Mus culos ke le ta l Tumor S ocie ty s ys te m, with its e mpha s is
on compa rtme nta liza tion, is mos t popula r with s urge ons a nd
is be s t ta ilore d for le s ions in the e xtre mitie s .
• It doe s not include the type , s ize , or de pth of the tumor a s
s e pa ra te pa ra me te rs ; a nd its two-tie re d gra ding s ys te m ma y
be too na rrow for the wide biologic ra nge of s oft tis s ue
s a rcoma s .
• Be ca us e of the ne e d for a de qua te ly de fining
compa rtme nta liza tion, the s ys te m doe s not le nd its e lf to
re tros pe ctive s ta ging.
From Sc hwartz(s tag ing grading )
• Soft tis s ue s a rcoma is mos t commonly s ta ge d us ing e ithe r the Ame ric an
Jo int Co mmitte e o n Canc e r (AJCC) s ys te m (ge ne ra lly us e d in the
Unite d Sta te s ) or the World He a lth Orga niza tion s ys te m.
• A unique a s pe ct of s a rcoma s ta ging is the inclus ion of tumo r grade ,
which is one of the mos t importa nt prognos tic fa ctors .
• The s e ve nth e dition of the AJCC s ta ging s ys te m for s oft tis s ue s a rcoma s
is ba s e d on his tologic gra de of a ggre s s ive ne s s , tumor s ize a nd de pth, a nd
the pre s e nce of noda l or dis ta nt me ta s ta s e s .
• This s ys te m doe s not a pply to
– GIST,
– fibro mato s is (de s mo id tumo r),
– Kapo s i’s s arco ma, o r
– infantile fibro s arco ma.
• His to lo g ic Grade o f Ag g re s s ive ne s s .
– His tologic gra de is the mos t importa nt prognos tic fa ctor for pa tie nts
with s oft tis s ue s a rcoma .
– For a ccura te de te rmina tion of gra de , a n a de qua te tis s ue s a mple
mus t be a ppropria te ly fixe d, s ta ine d, a nd re vie we d by a n
e xpe rie nce d s a rcoma pa thologis t.
– The fe a ture s tha t de fine gra de a re
• ce llularity,
• diffe re ntiatio n (g o o d, mo de rate , o r po o r/ anaplas tic ),
• ple o mo rphis m,
• ne cro s is (abs e nt, <50%, o r ≥50%), and
• numbe r o f mito s e s pe r hig h-po we r fie ld (<10, 10–19, o r ≥20).
• Tumor gra de ha s be e n s hown to pre dict me tas tas is a nd
ove ra ll s urviva l.
• Me ta s ta s is ha s be e n e s tima te d to occur in
– 5% to 10% o f lo w-grade le s io ns ,
– 25% to 30% o f interme diate -grade le s io ns , and
– 50% to 60% o f hig h-grade le s io ns .
• The numbe r of gra de s va rie s a ccording to the cla s s ifica tion
s ys te m us e d.
• The mos t common cla s s ifica tion s ys te ms , thos e of the
Na tiona l Ca nce r Ins titute a nd the Fre nch Fe de ra tion of
Ca nce r Ce nte rs , us e thre e -tie r tumo r g rade s .
• The Na tiona l Ca nce r Ins titute s ys tem is ba s ed prima rily on
– his to lo g ic s ubtype ,
– lo c atio n, and
– amo unt o f ne c ro s is .
• The French Fede ra tion of Ca nce r Cente rs s ys tem is ba s ed on
– tumo r diffe re ntiatio n (g o o d, mo de rate , o r po o r/anaplas tic ),
– numbe r o f mito s e s pe r hig h-po we r fie ld (<10, 10–19, o r ≥20), and
– amo unt o f tumo r ne c ro s is (abs e nt, <50%, o r ≥50%).
• A compa ra tive a na lys is of the two s ys tems s ugges te d tha t the
French Fede ra tion of Ca nce r Cente rs s ys tem ha s bette r prognos tic
ca pa bility, predicting 5-ye a r s urviva l rates of 90%, 70%, and 40%
for grade 1, 2, a nd 3 tumors , res pe ctively.
• Following the recomme nda tion of the College of America n Pa thologists , the committe e tha t
developed the 2008 AJCC sta ging sys te m cha nge d the sys tem from a four-gra de to a thre e -
gra de sys tem in which the gra de s a re
– we ll differe ntiate d (grade 1),
– mo derate ly diffe rentiate d (grade 2), and
– po o rly differe ntiate d (grade 3).
• Gra de 1 is cons ide re d low gra de , a nd g rade s 2 and 3 are co ns ide re d hig h g rade .
• Tumo r S ize and Lo catio n.
• Tumor size is a n importa nt prognos tic va ria ble in soft tiss ue sa rcoma s .
• Sa rcoma s ha ve cla ss ica lly be e n stra tifie d into two s ize g ro ups ;
– T1 les io ns are 5 cm or s maller, and
– T2 les io ns are larg er than 5 cm.
• Some a uthors ha ve a dding a third group for tumors larg er than 15 cm, be c aus e s uc h
tumo rs are as s o c iate d with a wo rs e pro g no s is than tumo rs meas uring be twee n 5 and
15 cm.
• Ana tomic tumor loca tion wa s incorpora te d into the AJCC
s ta ging s ys te m in 1998.
– Soft tiss ue sa rcoma s above the s uperfic ial inve s ting fas c ia of
the extre mity or trunk are de signa te d “a” les io ns within the T
ca te gory,
– whe re a s tumors inva ding or de e p to the fas cia and all
retrope ritone al, me dias tinal, and visce ral tumors are de signa te d
“b” les io ns .
• No dal Metas tas is .
• Overa ll, lymph node meta sta s e s a rising from soft tissue sa rcoma s a re ra re, but the incide nce
of noda l involveme nt is highe r for
– epithe lio id s arco ma,
– pe diatric rhabdo myo s arco ma,
– cle ar ce ll s arco ma,
– s yno vial s arco ma,
– myxo fibro s arco ma, and
– ang io s arco ma.
• In the seve nth edition of the AJCC sta ging sys te m, sa rcoma a ss ocia te d with noda l
meta s ta s e s wa s recla ss ifie d as s tag e III rathe r than s tag e IV be c aus e s e ve ral s tudie s
repo rte d be tter s urvival fo r patients with is o late d reg io nal lymph no de metas tas e s
trea te d with ra dica l lympha de ne ctomy tha n for pa tients with dis ta nt meta s ta s e s .
• Pa tie nts with clinica lly or ra diologica lly suspicious regiona l node s should ha ve meta sta s e s
confirme d or ruled out by fine -ne e dle a spira tion be fore ra dica l lympha de ne ctomy.
• Dis tant Me tas tas is .
• Dis ta nt me ta s ta s e s occur mos t ofte n in the lungs .
• Se le cte d pa tie nts with pulmo nary me tas tas e s ma y
s urvive for lo ng pe rio ds afte r s urg ic al re s e c tio n and
c he mo the rapy.
• Othe r pote ntia l s ite s of me ta s ta s is include bo ne , brain,
and live r.
• Vis ce ra l a ndre trope ritone a l s a rcoma s ha ve a highe r
incide nce of live r a nd pe ritone a l me ta s ta s e s .
• Prog no s tic Fac tors .
– Prognos tic va ria ble s in soft tiss ue sa rcoma include
• primary tumo r s ize ,
• g rade , and
• de pth, all o f whic h are inc o rpo rate d into the s tag ing s ys te m,
• as well as his to lo g y,
• tumo r s ite, and
• pres e ntatio n (lo cal rec urre nc e o r initial diag no s is ).
– Pa tie nt fa ctors such a s olde r a ge a nd ge nde r ha ve a lso be e n a ss ocia te d
with re curre nce a nd morta lity in se ve ra l studie s .
– A positive mic ro s c o pic marg in and e arly re c urre nc e afte r re s e c tio n o f
an e xtre mity s arc o ma have be e n s ho wn to be as s o c iate d with
de c re as e d s urvival.
• Se ve ra l groups ha ve re porte d tha t Ki-67, a pro life ratio n
marke r, is corre la te d with a poor clinica l outcome in high-
gra de e xtre mity s a rcoma s .
• E-c adhe rin and c ate nins , prote ins e s s e ntia l for
inte rce llula r junctions , ha ve be e n a s s ocia te d with poor
outcome in pa tie nts with s oft tis s ue s a rcoma .
• Simila rly, hig he r CD100 e xpre s s ion ha s be e n s hown to
corre la te with highe r prolife ra tive pote ntia l a nd poore r
outcome .
• Pro g no s tic No mo g rams .
– Prognos tic nomogra ms for soft tiss ue sa rcoma ha ve be e n
introduce d for us e in pa tient couns eling, sele cting appropriate
surveillance stra te gies , and s e le c ting patie nts for clinic al
trials .
– One such nomogra m, de velope d by Katta n and collea gue s at
Memorial Sloa n-Kette ring Ca nce r Ce nte r, conside rs age ,
histology, gra de , loca tion, de pth, and size to de te rmine the
likelihood of 12-ye a r sa rcoma -s pe cific survival.
– Two valida tion studies using the nomogra m de mons tra te d good
pre dictive value .
• More re ce ntly, the s a me group of inve s tiga tors de ve lope d
his tology s ubtype -s pe cific nomogra ms for pa tie nts with
lipos a rcoma , s ynovia l s a rcoma , a nd
• GIST72 a nd de mons tra te d tha t the y we re a ccura te in
pre dicting dis e a s e -s pe cific s urviva l.
• Othe r inve s tiga tors ha ve jus t de ve lope d a s ite -s pe cific
nomogra m for pa tie nts with re trope ritone a l s a rcoma ,
de mons tra ting a n a ccura te pre diction of s urviva l a nd
dis e a s e re curre nce
• TREATMENT OF EXTREMITY AND TRUNK WALL
SARCOMA
– The goa ls of tre a tme nt of s oft tis s ue s a rcoma a re to ma ximize the
like lihood of lo ng -term re curre nce -fre e s urvival while minimizing
morbidity a nd ma ximizing function.
– In the pa s t two de ca de s , a multimoda lity tre a tme nt a pproa ch with
optima l s e que ncing of tre a tme nts for individua l pa tie nts ha s be e n
s hown to improve s urviva l.
– Furthe rmore , pa tie nts with s oft tis s ue s a rcoma tre a te d a t high-
volume ce nte rs ha ve be e n s hown to ha ve improve d s urviva l a nd
functiona l outcome s .
– Ca re a t s uch ce nte rs is pa rticula rly importa nt for pa tie nts with high-
ris k a nd a dva nce d dis e a s e .
• The ove ra ll 5-ye a r s urviva l ra te for pa tie nts with a ll s ta ge s
of s oft tis s ue s a rcoma is 50% to 60%.
• For pa tie nts with e xtre mity s a rcoma s , a multidis ciplina ry
tre a tme nt a pproa ch ha s re s ulte d in loca l control ra te s
e xce e ding 90% a nd 5-ye a r s urviva l ra te s e xce e ding 70%.
• Mos t pa tie nts who die of s oft tis s ue s a rcoma die of
me ta s ta tic dis e a s e , which be come s e vide nt within 2 to 3
ye a rs of initia l diag no s is in 80% o f c as e s .
Trea tme nt algorithm of extre mity soft tiss ue sa rcoma . CT = compute d tomogra phy; CXR = che s t x-ray;
MRI = ma gne tic res ona nce ima ging; US = ultras ound.
Pre tre a tme nt evalua tion and sta gin algorithm for as s e s s me nt of the pa tient
pre s e nting with an extre mity soft tiss ue ma s s . AJCC, Ame rica n Joint Committee on
Pre tre a tme nt evalua tion, sta ging, and trea tme nt algorithm for as s e s s me nt of the
pa tient pre s e nting with a retrope ritone al (nonvisce ral) ma s s .
• Surg e ry
• Prima ry tumors with no e vide nce of dis ta nt me ta s ta s is a re
ma na ge d with s urg e ry alo ne o r, whe n wide patho lo g ic
marg ins canno t be achie ve d be ca us e of a na tomic
cons tra ints a nd/or the gra de is high, s urg e ry plus radiatio n
the rapy.
• The type of s urgica l re s e ction is de te rmine d by s e ve ra l
fa ctors , including tumor loca tion, tumor s ize , de pth of
inva s ion, involve me nt of ne a rby s tructure s , ne e d for s kin
gra fting or a utoge nous tis s ue re cons truction, a nd the pa tie nt’s
pe rforma nce s ta tus .
• Ma rgin s ta tus a fter s urgica l res e ction ha s bee n s hown to be a n
inde pe nde nt prognos tic fa ctor.
• The goa l of s urgica l res e ction is to a chie ve a comple te res e ction
beca us e micros copica lly pos itive or gros s ly pos itive res e ction
ma rgins a re a s s ocia te d with incre a s e d ris k of loca l recurre nce a nd
dea th.
• If a n une xpe cte d pos itive ma rgin is found on pa thologic exa mina tion
of the res e ction s pecime n, re -e xcis ion s hould be performe d.
• In pa tients with a pos itive ma rgin, pa rticula rly in pa tients with
ma cros copic res idua l dis ea s e , loca l control is unlike ly eve n with the
a ddition of pos tope ra tive ra dia tion the ra py.
• Wide Lo cal Exc is io n.
• The pre fe rre d tre a tme nt for e xtre mity s a rcoma s is wide loca l e xcis ion tha t include s
re s e ction of the biops y s ite .
• The goa l of wide loca l e xcis ion is to re move the tumor with appro ximate ly 1 to 2
cm of s urrounding norma l s oft tis s ue ,but na rrowe r ma rgins ma y be ne ce s s a ry to
pre s e rve uninvolve d critica l ne urova s cula r s tructure s a nd ma y be a de qua te for
pa tie nts unde rgoing ra dia tion the ra py.
• Dis s e ction s hould proce e d through gros s ly norma l tis s ue pla ne s not a butting the
tumor.
• Soft tis s ue s a rcoma s a re ge ne ra lly s urro unde d by a zo ne o f co mpre s s e d
re active tis s ue tha t forms a ps e udoca ps ule , but this ps e udoca ps ule s hould not be
us e d to guide re s e ction (e nucle atio n).
• If the tumor is a dja ce nt to or dis pla cing major ne urova s cula r s tructure s , the s e do not
ne e d to be re s e cte d, but the adve ntitia o r pe rine urium s hould be re move d.
• For s ome ma s s ive tumors of the e xtre mitie s , wide loca l e xcis ion e nta ils a ra dica l or
co mple te anato mic co mpartme nt re s e ctio n.
• Surgica l clips s hould be pla ced to deline a te the exte nt of the
res e ction bed for pa tients likely to require pos tope ra tive ra dia tion
the ra py.
• Re ce nt reports demons tra te encoura ging res ults following ra dica l en
bloc res e ction with va s cula r recons truction in the lowe r extre mitie s .
• While en bloc res e ction with va s cula r recons truction ha s bee n
a s s ocia te d with incre a s e d ra tes of pos tope ra tive complica tions ,
reporte d loca l recurre nce a nd 5-ye a r s urviva l ra tes a re s imila r to
thos e for pa tients not requiring ves s e l res e ction.
• Simila rly, s tudies ha ve s hown a ccepta ble functiona l outcome s with
res e ction of the s c iatic , tibial, and pero ne al nerve s with
appropriate rec o ns truc tion and rehabilitation.
• Bone inva s ion from e xtre mity s oft tis s ue s a rcoma , which ca n ge ne ra lly be ide ntifie d
us ing hig h-quality cro s s -s e c tio nal imag ing s uch as MRI, ha s be e n e s tima te d to
occur in a bout 5% of pa tie nts a nd is a s s ocia te d with re duce d ove ra ll s urvival.
• In ca s e s of bone inva s ion, bone re s e ction is re quire d to obta in a n a de qua te s urgica l
ma rgin a nd to a chie ve loca l control.
• Although tumor re s e ction a nd re pa ir of s kele tal de fe cts a re pos s ible , the likelihood
of pos tope ra tive complica tions ma y be incre a s e d, a nd functiona l outcome s ma y be
le s s fa vora ble .
• Lin a nd colle a gue s 88 re ce ntly a na lyze d 55 pa tie nts with s oft tis s ue s a rcoma s
a butting bone a nd re porte d tha t in the a bs e nce of fra nk cortica l bone pe ne tra tion,
pe rios te um wa s a n a de qua te s urgica l ma rgin in pa tie nts tre a te d with wide loca l
e xcis ion a nd ra dia tion.
• Soft tis s ue s a rcoma s a ris ing in the dis tal e xtre mitie s , pa rticula rly the ha nds a nd fe e t,
pre s e nt unique te chnica l cha lle nge s .
• While dis tal-e xtre mity tumo rs a re ofte n de te cte d a t a
s ma lle r s ize (<5 cm) tha n proxima l-e xtre mity tumors ,
re s e ction a nd re cons truction te chnique s a re ofte n more
comple x for dis ta l e xtre mity tumors , a nd pre ope ra tive
pla nning is critica l to obta in fa vora ble functiona l outcome s .
• Ide ntifying the proximity of the tumor to unde rlying critica l
s tructure s (e .g., bone , te ndon, or ne urova s cula r s tructure s )
us ing MRI is e s s e ntia l for s urgica l pla nning.
• In a re porte d s e rie s of pa tie nts with s a rcoma s of the ha nds or
fe e t tre a te d with limite d s urge ry only, 32% of pa tie nts ha d
loca l re curre nce s .
• Pre s e rvatio n o f functio n and acc e ptable re curre nc e ra te s
with limite d s urge ry a nd a djuva nt ra dia tion the ra py for s oft
tis s ue s a rcoma s of the dis ta l e xtre mitie s ha ve be e n re porte d.
• Fo r lo cally advance d tumo rs , re pa ir of bone de fe cts ,
va s cula r re cons truction, te ndon tra ns fe rs , a nd s oft tis s ue
re cons truction us ing re giona l or fre e fla ps ha ve re s ulte d in
good functiona l outcome s .
• Amputatio n re mains a re as o nable o ptio n fo r patie nts with
s oft tis s ue s a rcoma s of the dis ta l e xtre mitie s whe n a cce pta ble
oncologic or functiona l outcome s ca nnot be a chie ve d us ing
a va ila ble limb s a lva ge te chnique s .
• In a n inte re s ting s tudy conducte d in Onta rio a nd Quebe c,
• inve s tiga tors found pa tients expe cting a difficult recove ry a nd
• pa tients with unce rta in expe cta tions ha d wors e functiona l outcome s
• tha n pa tients a nticipa ting a n ea s y recove ry, indica ting
• tha t preo perative educ atio n including cons ulta tion with
reha bilita tion
• s ervice s ma y optimize outcome s .92 Furthe rmore , a ll
• pa tients unde rgoing res e ction of extre mity s a rcoma s s hould
• unde rgo phys ica l the ra py beginning immedia te ly a fter s urgery
• a nd continuing until ma ximum function is a chie ve d.1
• Lo c o re g io nal Lymphade ne c to my.
– Se ve ral studies ha ve reporte d improve d survival for pa tients
with isolate d reg io nal lymph no de me tas tas e s trea te d with
radical lympha de ne ctomy.
– Pa tients with clinically or radiologically sus picious regional
node s should ha ve me ta s ta s e s confirme d before radical
lympha de ne ctomy.
– At our ins titution, we pe rform ultras ound-guide d fine -ne e dle
as piration of lymph node s in sele cte d pa tients with sus picious
clinical or radiologic findings .
• The utility of s e ntine l lymph node biops y ha s re ma ine d
c o ntro ve rs ial de s pite the re cognition tha t s e ve ra l
his tologic s ubtype s of high-gra de s a rcoma a re known to
ha ve a pro pe ns ity fo r lymph no de me tas tas is .
• Howe ve r, the re ha ve be e n no pros pe ctive s tudie s of the
s e ns itivity and s pe c ific ity of s e ntine l lymph node biops y
for s uch tumors .
• Amputa tion.
– Amputa tion is the tre a tme nt of cho ic e for the 5% o f patie nts with
primary or re curre nt e xtre mity tumors whos e tumors ca nnot be
gros s ly re s e cte d with limb-s paring pro ce dure s and pre s ervatio n
o f functio n.
– His torica lly, loca l e xcis ion of la rge , high-gra de s oft tis s ue s a rcoma s
re s ulte d in lo cal failure rate s o f 50% to 70%, e ve n whe n a
marg in o f normal tis s ue aro und the tumor was e xcis e d;
cons e que ntly, ra dica l re s e ction or a mputa tion wa s re comme nde d.
– Toda y, howe ve r, the additio n o f radiatio n therapy to le s s ra dica l
s urgica l re s e ction ha s ma de limb s a lva ge pos s ible in mos t ca s e s .
• A compa ris on of amputation vers us limb-s paring s urg ery
follo we d by adjuvant radiation the ra py performe d by the Na tiona l
Ca nce r Ins titute betwe e n 1975 a nd 1981 demons tra te d no s ignifica nt
differe nce betwe e n the two groups in loc al rec urrenc e or overall
s urvival rate.
• Potte r a nd colle a gue s la ter revie we d the entire Na tiona l Ca nce r
Ins titute expe rie nce with 123 pa tients trea te d with cons e rva tive
s urgery plus ra dia tion the ra py a nd 83 trea te d with a mputa tion.
– The loca l re curre nce ra te wa s significa ntly highe r in the surge ry a nd
a djuva nt ra dia tion the ra py group: 8% ve rs us 0% in the amputatio n
g ro up.
– Howe ve r, s urvival rate s did no t diffe r be twe e n the g ro ups .
• Se ve ra l la rge s ingle -ins titution s tudies ha ve s ince a ls o reporte d
fa vora ble loca l control ra tes with cons e rva tive res e ction plus
ra dia tion the ra py.
• Is o late d Re g io nal Pe rfus io n.
– Isolate d regional pe rfusion is a limb-s paring tec hnique in
which a soft tiss ue sa rcoma is pe rfus e d with high
conce ntra tions of tumor ne cro s is fac tor-α and me lphalan
under hyperthermic co nditio ns .
– The technique is ge ne rally us e d for locally adva nce d,
multifocal, or locally recurre nt dise a s e ; it ha s als o se rve d as a
palliative trea tme nt to achieve loc al co ntrol for patie nts with
dis tant me tas tas e s .
– Limb perfus io n requires isolating the main arte ry and vein of
the pe rfus e d limb from the sys te mic circulation.
• The anato mic appro ac h is de te rmine d by tumor s ite :
e xte rna l ilia c ve s s e ls a re us e d for thig h tumo rs , fe mora l
or poplite a l ve s s e ls for ca lf tumors , a nd a xilla ry ve s s e ls
for uppe r e xtre mity tumors .
• The ve s s e ls a re dis s e c te d, and all c o llate ral ve s s e ls
are lig ate d.
• The ma in a rte ry a nd ve in a re the n ca nnula te d a nd
conne cte d to a pump o xyg e nato r s imila r to tha t us e d in
ca rdiopulmona ry bypa s s .
• Eithe r a tournique t or a n Es ma rch ba nd is a pplie d to the
limb to a chie ve comple te va s cula r is ola tion.
• Che mo the rape utic ag e nts a re the n a dde d to the
pe rfus ion circuit a nd circula te d for 90 minute s .
• Sys te mic le a ka ge from the pe rfus e d limb is monitore d
continuous ly with 99Tc -radio labe le d human s e rum
albumin inje c te d into the pe rfus ate , and radio ac tivity
a bove the pre cordia l a re a is re corde d with a Ge ig e r
c o unte r.
• During the entire proc e dure, hype rthe rmia of the perfus e d limb is
ma inta ine d by exte rna l he a ting a nd by wa rming the perfus ate to
40°C.
• At the end of the proce dure , the limb is was he d out, the c annulas
are extrac ted, and the bloo d ve s s e ls are repaired.
• Des pite the 40-ye a r his tory of us ing is ola te d limb perfus ion to trea t
extre mity s a rcoma s , ma ny ques tions a bout this technique rema in to
be a ns we re d.
• The optimal c he mo therape utic ag ent in the perfus ion circuit, the
bene fits of hyperthermia, a nd the effe c tive ne s s of hyperthermic
perfus io n a s ne oa djuva nt or a djuva nt trea tme nt rema in to be
elucida te d.
• Studie s publis he d to da te ha ve involve d he te roge ne ous
pa tie nt groups a nd va rious che mothe ra pe utic a ge nts .
• De s pite the s e limita tions , re s pons e ra te s from 18% to 80%
a nd ove ra ll 5-ye a r s urviva l ra te s from 50% to 70% ha ve
be e n re porte d.
• Howe ve r, s urviva l outcome s following is ola te d limb
pe rfus ion ha ve not ye t be e n dire ctly compa re d with
s urviva l outcome s a fte r more conve ntiona l tre a tme nt
a pproa che s .
• Radiation Therapy
– Ra dia tion the ra py is pa rt of the sta nda rd tre a tme nt for hig h g rade
e xtre mity and trunk wall s o ft tis s ue s arc o mas e ithe r in the pre - or
postope ra tive se tting.
– Pa tie nts with lo w-g rade tumo rs o r s mall, s upe rfic ial hig h-g rade
tumo rs tha t ha ve be e n re se cte d with a de qua te ma rgins ma y sa fe ly avo id
radiatio n the rapy.
– The e vide nce supporting a djuva nt ra dia tion the ra py for pa tie nts e ligible for
conse rva tive surgica l re se ction come s from two ra ndomize d tria ls a nd
thre e la rge single -ins titution re ports.
– In a ra ndomize d tria l by the Na tiona l Ca nce r Institute , 91 pa tie nts with
high-gra de e xtre mity tumors we re tre a te d with limb-spa ring surge ry
followe d by c he mo the rapy alo ne o r radiatio n the rapy plus
c he mo the rapy.
• The 10-ye a r loca l control ra te wa s 98% for pa tie nts re ce iving
ra dia tion the ra py compa re d with 70% for thos e not re ce iving
ra dia tion the ra py (P = .0001).
• S imila rly, in a ra ndomize d tria l from Me moria l S loa n-Ke tte ring
Ca nce r Ce nte r, 164 pa tie nts unde rwe nt cons e rva tive s urge ry
followe d by obs e rva tion or bra chythe ra py.
• For pa tie nts with high-gra de tumors , the 5-ye a r loca l control
ra te wa s 66% in the obs e rva tion group a nd 89% in the
bra chythe ra py group (P = .003).
• For pa tie nts with low-gra de tumors , no s ignifica nt diffe re nce
wa s obs e rve d be twe e n tre a tme nt groups .
• Until re ce ntly, the s ta nda rd tre a tme nt guide line s re quire d ra dia tion the ra py
a fte r s urge ry for a ll pa tie nts with inte rme diate -o r hig h-g rade tumo rs o f
any s ize .
• Howe ve r, s mall tumo rs (≤5 c m) have no t ge ne rally be e n a s s ocia te d
with loca l re curre nce , a nd ra dia tion the ra py for s uch tumors ma y not be
ne ce s s a ry.
• In a s e rie s of 174 pa tie nts re porte d by Ge e r a nd colle a gue s , pos tope ra tive
ra dia tion the ra py did not improve 5-ye a r loca l re curre nce or ove ra ll
s urviva l ra te s for pa tie nts with s ma ll s oft tis s ue s a rcoma s .
• Ka ra kous is a nd colle a gue s re porte d a 5-ye a r loca l re curre nce rate o f 6%
fo r 80 patie nts with e xtre mity s arc o mas tre a te d with wide loca l e xcis ion
a nd obs e rva tion, a ra te s imila r to tha t for the 64 pa tie nts who unde rwe nt
re s e ction with narro we r s urg ic al margins and po s to pe rative radiatio n
the rapy.
• The optima l mode of ra dia tion the ra py (e xte rnal-be am
radiatio n the rapy, brac hythe rapy, o r inte ns ity-
mo dulate d radiatio n the rapy [IMRT]) a nd timing of
ra dia tion the ra py (pre ope ra tive , intra ope ra tive , or
pos tope ra tive ) have ye t to be de fine d.
• Exte rnal-be am radiatio n the rapy ca n be de live re d us ing
photons or pa rticle be a ms (e le c tro ns , pro to ns , pio ns , o r
ne utro ns ).
• Conve ntiona l fra ctiona tion is us ua lly 1.8 to 2 Gy pe r day.
• CT is a n inte gra l pa rt of ra dia tion the ra py, us e d to de fine the
g ro s s tumo r vo lume and to e s timate the marg in o f tis s ue
at ris k fo r micro s c o pic tumo r invo lve me nt.
• The optima l radiatio n marg in is no t we ll de fine d: a marg in
o f 5 to 7 cm is s tandard, but s ome ce nte rs a dvoca te wide r
ma rgins for tumors la rge r than 15 cm.
• At mos t ins titutions , the typica l pre o pe rative dos e is 50 Gy
g ive n in 25 fractio ns , a nd re s e ction is pe rforme d 4 to 8
we e ks a fte r comple tion of ra dia tion the rapy to allo w acute
radiatio n chang e s to s ubs ide .
• Pos tope ra tive ra dia tion the ra py pla nning is ba s e d on tumo r
s ite , tumo r g rade , s urg ical marg ins , and ins titutio nal
pre fe re nce s .
• The e ntire s urg ical s car and drain s ite s s hould be include d
in the fie ld s o tha t a ne a r-full dos e ca n be a dminis te re d to the
s upe rficia l s kin.
• Me tallic clips place d in the tumo r be d during s urg e ry ca n
he lp de fine the limits of the re s e ction a nd a id in ra dia tion
the ra py pla nning.
• Dos e s of 60 to 70 Gy a re us ua lly ne ce s s a ry for pos tope ra tive
tre a tme nt.
• No co ns e ns us e xis ts o n the o ptimal s e que nce of ra dia tion
the ra py a nd s urge ry.
• The a va ila ble da ta come la rge ly from s ingle -ins titution,
nonra ndomize d s tudie s .
• Propone nts of pre o pe rative radiatio n the rapy note tha t
multidis ciplina ry pla nning with ra dia tion oncologis ts , me dica l
oncologis ts , a nd s urge ons is e as ie r e arly in the co urs e o f
the rapy.
• In a ddition, for s ome radio s e ns itive his to lo g ic s ubtype s ,
s uch a s myxo id lipo s arco ma, pre ope ra tive ra dia tion the ra py
ma y s hrink the tumor, fa cilita ting re s e ction with ne g ative
marg ins .
• Furthe rmore , a tis s ue be d undis turbe d by re s e ction ha s
be tte r tis s ue oxyge na tion a nd ca n be s ucce s s fully tre a te d
with lowe r dos e s of ra dia tion.
• In a ddition, Nie ls e n a nd colle a gue s 111 de mons tra te d tha t
pre ope ra tive radiatio n fie lds are s malle r than
po s to pe rative radiatio n fie lds a nd tha t the a ve ra ge numbe r
of joints include d in the fie ld is lowe r with pre ope ra tive tha n
pos tope ra tive ra dia tion the ra py, which ma y re s ult in improve d
functiona l outcome .
• Critics of pre ope ra tive ra dia tion the ra py cite the difficulty of
pa thologica s s e s s me nt of ma rgins a nd the incre a s e d ra te of
pos tope ra tive wound complica tions .
• Howe ve r, re cons tructive s urgica l te chnique s with a dva nce d tis s ue tra ns fe r
proce dure s a re be ing us e d more ofte n in the s e high-ris k wounds a nd
re porte dly re s ult in be tte r outcome s .
• The highe r dos e s ge ne ra lly re quire d for pos tope ra tive ra dia tion the ra py
ha ve a ls o be e n s hown to be a s s ocia te d with gre a te r long-te rm functiona l
impa irme nt.
• The only ra ndomize d compa ris on of pre ope ra tive a nd pos tope ra tive
ra dia tion the ra py to da te wa s pe rforme d by the Na tiona l Ca nce r Ins titute
of Ca na da Clinica l Tria ls –Ca na dia n Sa rcoma Group.
• This tria l wa s de s igne d to e xa mine complica tions a nd functiona l outcome .
• The 190 pa tie nts e nrolle d from Octobe r 1994 to De ce mbe r 1997 we re
ra ndomize d to pre ope ra tive ra dia tion the ra py (50 Gy) or pos tope ra tive
ra dia tion the ra py (66 Gy).
• With a media n follow-up time of 3.3 yea rs , the recurre nce a nd
progre s s ion-fre e s urviva l ra tes were s imila r in the two groups .
• Howe ve r, the incide nce of wound complica tions wa s
• s ignifica ntly lowe r with preope ra tive ra dia tion the ra py (3% vs .
• 17%), a nd the incide nce of wound complica tions wa s s ignifica ntly
• highe r for tumors of the lowe r extre mity (43%) tha n for
• thos e of the upper extre mity (5%).113 La te ra dia tion toxic effe cts
• (e.g., fibros is , joint s tiffne s s , a nd ede ma ) were more common
• with pos tope ra tive tha n preope ra tive ra dia tion the ra py (48% vs .
• 32%) beca us e of highe r pos tope ra tive ra dia tion dos e s a nd la rger
• trea tme nt field s izes .114
• Bra chythe ra py involve s the plac eme nt of multiple radioac tive
• s ee ds throug h c athe ters ins erte d in the tumor res e c tio n bed.
• The prima ry bene fit of bra chythe ra py is the s horte r ove ra ll trea tme nt
• time of 4 to 6 days , compa re d to the 4 to 6 wee ks gene ra lly
require d for preope ra tive or pos tope ra tive ra dia tion the ra py
regime ns .
• A cos t-a na lys is compa ris on of a djuva nt bra chythe ra py
• vers us a djuva nt exte rna l-be a m irra dia tion for s oft tis s ue
• s a rcoma s s howe d tha t cos ts were lowe r with bra chythe ra py.115
• Bra chythe ra py ca n a ls o be us ed for recurre nt dis ea s e previous ly
• trea te d with exte rna l-be a m ra dia tion.
• Guide line s es ta blis he d a t
• Memoria l Sloa n-Kette ring Ca nce r Cente r recomme nd s pa cing
• the a fterloa ding ca the te rs in 1-cm incre me nts while lea ving a
• 2-cm ma rgin a round the s urgica l bed.104 After a dequa te wound
• he a ling is confirme d, us ua lly a fter the fifth pos tope ra tive da y,
• the ca the te rs a re loa de d with s ee ds conta ining iridium-192
• tha t delive r 42 to 45 Gy of radiation to the tumor bed over
• 4 to 6 days . The prima ry dis a dva nta ge of bra chythe ra py is tha t it
• require s s ignifica nt expe rtis e , exte nde d inpa tie nt hos pita l s ta ys ,
• a nd bed res t.
• IMRT delive rs ra dia tion more pre cis e ly to the tumor tha n
• e xte rna l-be a m irra dia tion while minimizing the volume of s urrounding
• tis s ue s e xpos e d to high ra dia tion dos e s . The propos e d
• be ne fits of pre ope ra tive IMRT include re duce d ris k of pos tope ra tive
• wound infe ctions be ca us e of minimiza tion of the dos e
• to the s kin116 a nd prote ction of unde rlying bone (e .g., fe mur)
• a s a re s ult of conca ve dos e dis tributions .117 The re ha ve be e n
• no pros pe ctive ra ndomize d trials compa ring the long-te rm outcome s
• following IMRT ve rs us othe r type s of ra dia tion the ra py.
• In a re tros pe ctive a na lys is of IMRT, pa tie nts with ne ga tive a nd
• pos itive /clos e (within 1 mm) ma rgins we re found to ha ve 5-ye a r
• loca l control ra te s of 94%.
• 118 In a ddition, the ra te s of pos ttre a tme nt
• e de ma a nd joint s tiffne s s with IMRT we re lowe r tha n the
• e xpe cte d ra te s with conve ntiona l ra dia tion the ra py.
• Loca l toxic e ffe cts of ra dia tion the ra py va ry a ccording to
• ra dia tion dos e , fie ld s ize , a nd timing (pre ope ra tive or
pos tope ra tive ).
• With pre ope ra tive ra dia tion the ra py, the mos t fre que nt
• wound complica tions a re wound de his ce nce , wound
ne cros is ,
• pers is te nt dra ina ge , infe ction, s eroma forma tion, ulcera tion,
• a nd cellulitis .113 Pos tope ra tive irra dia tion of free fla ps is ofte n
• a s s ocia te d with wound complica tions , a nd pa tients s hould
• be a dvis ed tha t s econda ry s urgica l repa ir ma y be ne ce s s a ry.
• Wound complica tion ra tes of 13% to 37% ha ve bee n reporte d
• for preope ra tive ra dia tion the ra py, compa re d to 5% to 20% for
• pos tope ra tive ra dia tion the ra py.119 If ca the te rs a re loa de d a fter
• the fifth pos tope ra tive da y, ra tes of wound complica tions a fter
• bra chythe ra py a re s imila r to thos e a fter pos tope ra tive ra dia tion
• the ra py.
• Long-te rm (chronic) e ffe cts of ra dia tion the ra py (thos e
occurring >1 ye a r a fte r comple tion of the ra py) a re ge ne ra lly
re la te d to fibros is /contra cture s , lymphe de ma , ne urologic
injury, os te itis , a nd fra cture s , a ll of which ca n ca us e
s ubs ta ntia l functiona l impa irme nt.
• Va ria ble s a s s ocia te d with poore r functiona l outcome a fte r
ra dia tion the ra py include la rge r tumors , highe r dos e s of
ra dia tion (>63 Gy), lo ng e r radiatio n fie lds (>35 cm), po o r
radiatio n te chnique , ne ural s acrific e , po s to pe rative
fracture s , and wo und co mplic atio ns .
• Additiona lly, complica tions of a ny kind a re les s likely a fter trea tme nt
for upper extre mity s a rcoma tha n a fter trea tme nt for lowe r extre mity
s a rcoma
• Definitive ra dia tion the ra py tha t delive rs ma xima l-tis s uetole ra nce
dos e s of ra dia tion ma y be a ppropria te for s ele cte d pa tients with
unre s e cta ble s oft tis s ue s a rcoma s .
• In a s tudy of 112 pa tients with unre s e cta ble s oft tis s ue s a rcoma s ,
tumor s ize a nd ra dia tion dos e were found to influe nce loca l control
a nd s urviva l.
• The loca l control ra te wa s 51% for tumors s ma ller tha n 5 cm a nd 9%
for tumors la rger tha n 10 cm, a nd pa tients who rece ive d a t lea s t 64
Gy ha d bette r loca l control a nd s urviva l.
• Sys te mic The rapy
– Des pite improve me nts in local control rate s , me tas tas is and
de ath remain s ig nific ant proble ms for pa tients with high-risk
soft tiss ue sa rcoma s .
– Pa tients conside re d at high risk of de a th from sa rcoma include
thos e pre s e nting with me ta s ta tic dise a s e , localize d sa rcoma s at
none xtre mity site s , or sa rcoma s of inte rme diate -or high-gra de
histology large r tha n 5 cm.
• Standard Che mo the rapy.
• For mo s t patie nts with s arco ma, re s ults of conve ntiona l che mo the rapy re gime ns
have be e n po o r.
• The che mos e ns itivity of s oft tis s ue s a rcoma va rie s by his tologic s ubtype .
• Syno vial s arco ma, myxo id/ro und ce ll lipo s arco ma, and ute rine
le io myo s arc o ma a re s e ns itive to che mo the rapy
• Whe re a s ple o mo rphic lipo s arco ma, myxo fibro s arc o ma, e pithe lio id s arco ma,
le io myo s arc o ma, MPNSTs , angio s arc o ma, and de s mo plas tic ro und ce ll
tumo rs ha ve inte rme diate s e ns itivity to che mo the rapy.
• Re la tively che more s is ta nt his tologic s ubtype s include cle ar ce ll s arco ma,
e ndo me trial s tro mal s arco ma, alve o lar s o ft part s arco ma, and e xtras ke le tal
myxo id cho ndro s arc o ma.
• Cons ide ring the va ria bility of re s pons e s by his tologic s ubtype , it is not s urpris ing tha t
clinica l trials of s ta nda rd che mothe ra py, which ofte n include he te roge ne ous
popula tions with re s pe ct to tumor gra de a nd his tology, ha ve de mons tra te d no ove ra ll
s urvival be ne fit.
• Do xo rubic in and ifo s famide a re the two mos t a ctive a ge nts
a ga ins t s oft tis s ue s a rcoma , with cons is te ntly re porte d
re s pons e ra te s of 20% o r g re ate r and po s itive do s e -
re s po ns e curve s .
• The Europe a n guide line s re comme nd doxorubicin 75 mg /m2
e ve ry 3 we e ks as firs t-line tre atme nt for a dva nce d dis e a s e .
• Tre a tme nt dura tion is ba s e d on re s pons e , but a maximum o f
s ix cyc le s is g e ne rally re comme nde d be ca us e of the ris k of
cumula tive ca rdiotoxicity.
• Ifos fa mide is the re comme nde d s e cond-line tre a tme nt a nd is
re comme nde d for firs t-line tre atme nt in patie nts with
cardiac mo rbidity.
• The s ta nda rd dos e of ifos fa mide is 9 to 10 g/m2; howe ve r,
s ingle -ins titution s e rie s us ing highe r-dos e re gime ns (>10
g/m2) or s ta nda rd-dos e ifos fa mide combine d with doxorubicin
ha ve s hown re s pons e ra te s of 20% to 60%.
• Syno vial s arco mas ha ve be e n s hown to be pa rticula rly
s e ns itive to ifo s famide .
• Ifos fa mide -a s s ocia te d toxic e ffe cts include he morrha gic
cys titis , ne urotoxicity, a nd re na l tubula r a cidos is .
• His torica lly, co mbinatio n the rapy with do xo rubic in plus
ifo s famide , dacarbazine , o r bo th ha s re s ulte d in incre a s e d
re s pons e ra te s but no improve me nt in ove ra ll s urviva l.
• Dac arbazine a s a s ingle a ge nt ha s a ls o de mons tra te d a ctivity in clinica l
tria ls .
• Ove r the pa s t de ca de , s e ve ra l a dditiona l che mothe ra pe utic a ge nts ,
including ge mcita bine , ta xa ne s , a nd tra be cte din, ha ve be e n note d to be
a ctive a ga ins t s oft tis s ue s a rcoma s .
• Ge mcita bine a s a s ingle a ge nt wa s re porte d to produce re s pons e s in 18%
of pa tie nts with a dva nce d s a rcoma .
• Ge mcita bine combine d with doce ta xe l ha s be e n re porte d to produce
re s pons e ra te s a s high a s 53% in pa tie nts with ute rine le io myo s arc o ma.
• Ge mcita bine combine d with vinore lbine ha s a ls o be e n a s s ocia te d with
clinica l be ne fit in pa tie nts with a dva nce d s a rcoma s .
• The taxane s (do c e taxe l and pac litaxe l) ha ve be e n found to be a ctive
a ga ins t angio s arc o mas , pa rticula rly of the fa ce a nd s ca lp, like ly be ca us e
of the ir pote nt antiangio g e nic e ffe c ts .
• Nove l Che mo therape utic Ag ents .
– Tra becte din, a ma rinede rive d a lka loid tha t binds DNA, a ffecting
tra nscription a nd inducing the forma tion of DNA double -s tra nd brea ks , ha s
shown bene fit in the trea tme nt of a dva nced soft tiss ue sa rcoma s ,
pa rticula rly leiomyos a rcoma , myxoid liposa rcoma , a nd other tra nsloca tion-
rela te d sa rcoma s .
– Tra becte din is gene ra lly well tolera te d but ca n be a ss ocia te d with
prolonge d a nd se ve re neutrope nia , thrombocytopenia , a nd hepa tic toxic
effe cts .
– Pa lifos fa mide is a sta bilize d formula tion of the a ctive meta bolite of
ifosfa mide tha t ha s bee n reporte d to be better tolera te d tha n ifosfa mide .
– Ea rly tria ls ha ve sugge s te d a ntitumor a ctivity compa ra ble or supe rior to
tha t of ifosfa mide without nephrotoxicity.
• Targ ete d Therapie s .
– Se ve ra l ta rgete d a gents a re being inves tiga te d for the trea tme nt of soft
tiss ue sa rcoma s .
– Among thes e a re tyro s ine kinas e inhibito rs (e.g., ima tinib, sunitinib,
sora fe nib, a nd da sa tinib) tha t ha ve bee n deve lope d a nd a pproved for
trea tme nt of GIST.
– Clinica l da ta a ccumula te d in pha se II tria ls a lso support the us e of tyrosine
kina se inhibitors (e.g., ima tinib, sora fe nib, a nd sunitinib) in the
ma na geme nt of other a dva nced sa rcoma s .
– Anti–vas c ular endo thelial g ro wth fac to r antibo dies such a s
beva cizuma b ha ve demons tra ted a ctivity in pa tients with meta s ta tic or
unre s e cta ble a ngiosa rcoma , solita ry fibrous tumor, a nd epithe lioid
hema ngioe ndothe lioma .
• Pa zopa nib is a n ora l a ngioge ne s is inhibitor tha t ta rge ts va s cula r e ndothe lial growth
fa ctor re ce ptors , pla tele t-de rive d growth fa ctor re ce ptor (PDGFR), a nd c-kit.
• In a re ce nt pha s e III s tudy, pa zopa nib s howe d e ffica cy a ga ins t pla ce bo in s e cond or
furthe r line of the ra py in pa tie nts with a dva nce d s oft tis s ue s a rcoma .
• Inhibitors of the ma mma lia n ta rge t of ra pa mycin pa thwa y, including te ms irolimus ,
e ve rolimus , a nd rida forolimus , ha ve als o s hown a ctivity a ga ins t s ome s oft tis s ue
s a rcoma s (i.e ., PEComa s ).135
• Be ne fits o f Sys te mic The rapy.
– The use of a djuva nt a nd ne oa djuva nt che mothe ra py for soft tiss ue sa rcoma s rema ins
controvers ia l.
– More tha n a doze n individua l ra ndomize d trials of a djuva nt che mothe ra py ha ve fa iled to
demons tra te improveme nt in dis e a s e -fre e or overa ll surviva l for pa tients with soft tiss ue
sa rcoma .
• Ne o adjuvant (Pre o pe rative ) Che mo the rapy.
– The us e of ne oa djuva nt (pre ope ra tive) che mothe ra py for soft
tiss ue sa rcoma s is ba s e d on the be lie f that only 30% to 50%
of patie nts res pond to sta nda rd adjuva nt (pos tope ra tive)
che mothe ra py.
– The rationale for us ing ne o adjuvant che mo therapy is tha t it
ena bles oncologists to ide ntify pa tients whos e dise a s e is
se nsitive to a pa rticular che mothe ra py regime n by as s e s sing
res pons e while the prima ry tumor is in situ.
• Pa tie nts whos e tumors do no t re s po nd to s ho rt
c o urs e s o f ne o adjuvant c he mo the rapy ca n thus be
s pa re d the toxic e ffe cts of prolonge d a djuva nt
che mothe ra py.
• Anothe r a dva nta ge of ne o adjuvant c he mo the rapy is
tha t it ma y s hrink tumors , e na bling le s s morbid
ope ra tions .
• The the o re tic al dis advantag e s o f ne o adjuvant
c he mo the rapy a re re la te d to mye los uppre s s ion a nd
pote ntia l pos tope ra tive wound he a ling complica tions .
• A re ce nt ra ndomize d s tudy compa ring thre e pre ope ra tive
cycle s of full-dos e a nthra cycline -ifos fa mide –ba s e d
che mothe ra py with thre e pre ope ra tive plus two
pos tope ra tive cycle s of the s a me re gime n in high-ris k
e xtre mity a nd trunk wa ll s oft tis s ue s a rcoma s s howe d
e quiva le nce be twe e n the two a pproa che s , s ugge s ting the
pos s ibility of limiting che mothe ra py a dminis tra tion to the
thre e pre ope ra tive cours e s , improving the ra tio be twe e n
toxicity a nd e xpe cte d be ne fit.
• The a ddition of ifos fa mide to
• othe r a ge nts (doxorubicin a lone or doxorubicin a nd cis pla tin)
• incre a s e d the ra te of pa thologic ne cros is to 48% compa re d to
• 13% with othe r combina tions . The 5- a nd 10-ye a r loca l
re curre nce
• ra te s we re s ignifica ntly lowe r for pa tie nts with 95% or
• gre a te r pa thologic ne cros is (6% a nd 11%, re s pe ctive ly) tha n
for
• pa tie nts with le s s tha n 95% pa thologic ne cros is (17% a nd
23%,
• re s pe ctive ly).
• Co ncurre nt Che mo radiatio n The rapy
– Tre atme nt appro ache s that co mbine s ys te mic che mo therapy
with ra dios e ns itize rs a nd concurre nt e xte rna l-be a m ra dia tion the ra py
ma y improve dis e a s e -fre e s urviva l by tre a ting micros copic dis e a s e
a nd e nha ncing the tre a tme nt of ma cros copic dis e a s e .
– Co ncurre nt che moradiatio n the ra py with do xorubic inbas e d
re g ime ns re porte dly produce s fa vora ble loca l control ra te s for
pa tie nts with s a rcoma .
– S ince thos e findings we re publis he d, s e ve ra l groups ha ve e va lua te d
route s of a dminis tra tion, a lte rna tive che mothe ra pe utic a ge nts , a nd
the toxicity of combine d the ra pie s .
• The o re tic al advantag e s no twiths tanding , concurre nt
che mora dia tion the ra py de cre a s e s the tota l tre a tme nt
time for pa tie nts with high-ris k s a rcoma .
• This de c re as e re pre s e nts a s ubs tantial advantag e ove r
curre nt s e que ntia l combine d-moda lity tre a tme nt
a pproa che s , for which the tota l dura tion of ra dia tion
the ra py, che mothe ra py, s urge ry, a nd re habilitatio n
fre que ntly e xc e e ds 6 to 9 mo nths .
• Curre ntly, pos ttre a tme nt s urve illa nce is re comme nde d for a ll pa tie nts with
s oft tis s ue s a rcoma s ba s e d on a fe w re ports involving s ma ll numbe rs of
pa tie nts indica ting tha t loca l re curre nce ca n be s ucce s s fully tre a te d with
ra dica l re -e xcis ion with or without ra dia tion the ra py.
• Simila rly, s e ve ra l groups ha ve re porte d tha t s urviva l ca n be prolonge d by
re s e ction of pulmona ry me ta s ta s e s .
• The Na tiona l Compre he ns ive Ca nce r Ne twork (NCCN) re comme nds a
his tory a nd phys ica l a nd che s t CT or ra diogra phy e ve ry 3 to 6 months for
2 to 3 ye a rs a fte r comple tion of tre a tme nt.
• Be ca us e mos t ca s e s of dis ta nt me ta s ta s is occur within 2 to 3 ye a rs of
initia l dia gnos is , the NCCN guide line s indica te tha t follow-up inte rva ls ca n
be le ngthe ne d to e ve ry 6 months a nd ima ging ca n be done a nnua lly
during ye a rs 2 through
• Cons ide ra tion s hould a ls o be given to ima ging the prima ry
• tumor s ite; mos t expe rts recomme nd tha t the tumor s ite be
eva lua te d
• eve ry 6 months with MRI for extre mity tumors or CT
• for intra -a bdomina l or retrope ritone a l tumors . Guide line s ha ve
• bee n es ta blis he d for us ing MRI to dis tinguis h recurre nce s from
• typica l pos ts urgica l cha nge s : a dis crete nodule with low s igna l
• inte ns ity on T1-weighte d ima ges a nd highe r s igna l inte ns ity on
• T2-we ighte d ima ges tha t enha nce s a fter a dminis tra tion of
intra ve nous
• contra s t ma teria l is s trongly s ugges tive of recurre nce
• a nd s hould be biops ie d.
• Ultra s onogra phy ma y be a n a lte rna tive
• to MRI or CT for a s s e s s ing for re curre nce in the e xtre mitie s .
• Re curre nce is common a fte r s urge ry for a bdomina l s oft tis s ue
• s a rcoma s . CT is us e ful for de te cting re curre nce s a t prima ry
• a nd dis ta nt a na tomic s ite s in the a bdome n a nd pe lvis . Afte r s urge ry,
• CT e ve ry 3 to 6 months during the firs t 2 ye a rs a nd e ve ry
• 6 months for 3 ye a rs the re a fte r ha s be e n re comme nde d. Howe ve r,
• toda y ma ny e xpe rie nce d s urge ons a re a dvoca ting le s s
• a ggre s s ive ima ging for a s ymptoma tic pa tie nts , pa rticula rlya fte r a s e cond
re curre nce of re trope ritone a l s a rcoma , a rguing
• tha t the re is ins ufficie nt e vide nce to s ugge s t tha t s urviva l is
• improve d by e a rlie r de te ction
• Manag e me nt o f Re curre nt Sarc o ma
– Up to 20% o f patie nts with e xtre mity s arco ma de ve lop loca lly
re curre nt dis e a s e , which is ofte n a ccompa nie d by dis ta nt
me ta s ta s e s ; thus , a ll pa tie nts with re curre nt e xtre mity s a rcoma
s hould unde rgo a full s ta ging a s s e s s me nt.
– Pa tie nts with micros copica lly pos itive s urgica l ma rgins a re a t
incre a s e d ris k of loca l re curre nce .
– Inde pe nde nt prognos tic fa ctors for dis e a s e -s pe cific s urviva l a fte r
loca l re curre nce include d tumor grade , lo cal re curre nce s ize , and
lo cal re curre nce - fre e interval.
– The s e da ta indica te tha t a n is ola te d loca l re curre nce s hould be
tre a te d ag gre s s ive ly with re s e ctio n with ne g ative marg ins .
• For pa tients with extremity sa rcoma s, a chie ving ne ga tive ma rgins on res e ction of recurre nt
dis ea s e freque ntly require s a mputa tion.
• Howeve r, in some pa tients with recurre nt extremity sa rcoma , function-pre s e rving res e ction
combine d with a dditiona l ra dia tion the ra py, with or without che mothe ra py, ca n produce
a cce pta ble ra tes of loca l control.
• No ri and co lle ag ue s repo rte d a lo cal co ntro l rate o f 69% amo ng 40 patients with
rec urre nt tumo rs trea te d with re-e xcis ion a nd bra chythe ra py to a media n dos e of 45 Gy.
• In a simila r se rie s , Midis a nd collea gues reported tha t limb-spa ring surgery wa s poss ible in
66% of pa tients , a nd the 5-ye a r loca l recurre nce -fre e surviva l ra te wa s 72% in thos e pa tients .
• The prima ry de te rmina nt of surviva l in pa tients with soft tiss ue sa rcoma is the de velopme nt of
dis ta nt meta s ta s e s .
• Pa tie nts with extremity sa rcoma s gene ra lly de velop pulmona ry meta sta s e s .
• Les s common site s of meta s ta s is for soft tiss ue sa rcoma s include bone (7%), liver (4%),49 a nd
lymph node s (5%–7%).
• Myxo id lipo s arco ma o f the extre mity is known to meta s ta s ize to the a bdome n a nd pelvis;
the re fore , sta ging CT of the s e regions must be performed be fore de finitive loca l the ra py is
a dminis te re d
• Manage me nt o f Re curre nt and Dis tant Me tas tatic Sarc o ma.
– In selecte d individua ls with dista nt meta sta tic dis e a s e, s urg ical res e c tio n o f a primary
s o ft tis s ue s arc o ma may be appro priate as a palliative pro ce dure .
– The de cis ion should be ba s e d on the pa tient’s symptoms, which often include
• pain; ability to ac hie ve loc al tumo r co ntrol;
• co morbiditie s ; antic ipate d mo rbidity of the s urgic al proc e dure; and
• the exte nt of me tas tas e s .
– The most common initia l site of dista nt meta sta s is of soft tiss ue sa rcoma s is the lung .
– Se lecte d pa tients with
• a limite d numbe r of pulmo nary no dule s (les s than four no dule s ),
• long dis e as e -free inte rvals , and
• no endo bronc hial invas io n ma y be come long-te rm survivors after pulmona ry res e ction;
– 15% to 40% of pa tients with complete res e ction of meta sta tic dis e a s e confine d to the lung
a re long-term survivors.
– In a retrospe ctive multiins titutiona l study of 255 pa tients with lung meta s ta s e s , the 5-ye a r
overa ll surviva l ra te a fter metas tas e c to my was 38%.
• Fa vora ble prognos tic fa ctors in tha t s tudy include d
mic ro s c o pic ally tumo r-fre e marg ins , ag e yo ung e r
than 40 ye ars , and g rade 1 o r 2 tumo r.
• For pa tie nts who a re s urgica l ca ndida te s , pulmona ry
re s e ction a lone ca n be more cos t-e ffe ctive tha n wa tchful
wa iting, che mothe ra py, or che mothe ra py plus s urge ry.
• Che mo the rapy fo r Dis tant Me tas tatic Sarc o ma.
– Doxorubicin, either alone or combine d with othe r a gents, has be e n the primary
treatme nt mo dality fo r patients with advanc e d o r dis tant metas tatic s arc o mas for
se vera l de ca de s .
– Although most pa tients with meta sta tic dis e a s e a re not cura ble, some pa tients with
limited dis ea s e experie nce sta biliza tion of dis e a s e with multidis ciplina ry trea tme nt, which
often include s surge ry a nd ra dia tion the ra py in a ddition to che mothe ra py.
– Se vera l fa ctors predict be tter outcome for pa tients with recurrent meta sta tic sa rcoma
unde rgoing che mothe ra py, including
• go o d pe rformanc e s tatus ,
• previo us res po ns e to che mothe rapy,
• yo ung e r ag e ,
• abs e nc e of he patic me tas tas e s ,
• low-g rade tumor, and
• long dis e as e -free inte rval.
– Isola ted liver meta sta s e s , if s table o ve r s e ve ral mo nths , ma y be a mena ble to res e ction,
ra diofre que ncy a bla tion,or che moe mboliza tion.
• As da ta a ccumula te rega rding the s ens itivity of s a rcoma s ubtypes to
pa rticula r che mothe ra pie s , it is critica l tha t his tologydrive n trea tme nt
a pproa che s be us ed.
• New the ra pie s a re a ls o being identifie d ba s ed on the unique
mole cula r s igna ture s of s a rcoma s .
• Palliative Radiation Therapy.
– Definitive ra dia tion thera py ca n be conside re d when no a ccepta ble
surgica l option is a va ila ble (e.g., in pa tients with significa nt medica l
comorbiditie s ).
– In this se tting, ra dia tion dose s grea te r tha n 63 Gy yielde d supe rior tumor
control, but dose s grea te r tha n 68 Gy res ulte d in increa s e d ra tes of ma jor
complica tions
• SPECIAL CLINICAL SITUATIONS
• Myxo id Lipos arc oma
• Myxoid lipos a rcoma s belong to the group of s oft tis s ue s a rcoma s
with lipomato us differe ntiatio n.
• Howe ve r, myxoid lipos a rcoma s differ from the othe r lipos a rcoma
s ubtypes with res pe ct to morphology (i.e., myxo id s troma and
lipomato us differe ntiatio n) a nd clinica l beha vior.
• Myxoid lipos a rcoma s freque ntly pres e nt a s s low-growing , dee p
tumors in the lower extremity a nd ca n metas tas ize to other s oft
tis s ue loc atio ns , including the retroperito ne um and extremitie s .
• For this rea s on, CT of the c he s t, abdome n, and pelvis is
recomme nde d for a dequa te s tag ing and s urve illanc e of myxo id
lipos arc oma.
• Re tro pe rito ne al Sarc o ma
– Mos t re trope ritone a l tumors a re ma ligna nt, a nd abo ut o ne third are
s o ft tis s ue s arco mas .
– Als o to be cons ide re d in the diffe re ntia l dia gnos is of a
re trope ritone a l tumor a re primary g erm ce ll tumors , lympho ma,
and me tas tatic te s ticular canc e r.
– Approxima te ly 1000 ne w ca s e s of re trope ritone a l s a rcoma a re
dia gnos e d a nnua lly in the Unite d S ta te s , a nd the s e tumors a ccount
for 10% to 15% o f all adult tis s ue s arco mas .
– Approxima te ly two thirds o f re tro perito ne al s arco mas a re hig h
grade (e ithe r gra de 2 or 3), a nd lipo s arco ma and
le io myo s arco ma a re the mos t common his tologie s .
• Re trope ritone a l s a rcoma s ge ne ra lly pre s e nt a s large mas s e s : 70% are large r than
10 cm a t dia gnos is .
• The y typica lly do not produce s ymptoms until the y grow la rge e nough to compre s s
or inva de contiguous s tructure s , although pa in, e a rly s a tie ty, a nd obs tructive
ga s trointe s tina l s ymptoms ma y occur e a rly in the dis e a s e cours e in s ome pa tie nts .
• Eva lua tion of a pa tie nt with a re trope ritone a l ma s s be gins with a n a ccura te his tory
tha t s hould e xclude s igns a nd s ymptoms a s s ocia te d with lymphoma (e .g ., fe ve r
and night s we ats ).
• A comple te phys ica l e xa mina tion, with pa rticula r a tte ntion to all noda l ba s ins a nd
with a te s ticula r e xa mina tion in me n, is critica lly importa nt.
• La bora tory a s s e s s me nt ca n be he lpful; ele va te d la cta te de hydroge na s e le vels ma y
s ugge s t lymphoma , a nd ele va te d β-huma n chorionic go nado tro pin le ve ls o r α-
fe to pro te in le ve ls may indicate a ge rm ce ll tumo r.
• Although the ge ne ra l principle s of e va lua tion a nd
ma na ge me nt for re trope ritone a l s a rcoma s a re s imila r to thos e
for e xtre mity s a rcoma s , the re a re s ome diffe re nce s .
• Co ntras te nhanc e d CT o f the abdo me n and pe lvis is us e d
to de fine the e xte nt of the tumor a nd its re la tions hip to
s urrounding s tructure s , pa rticula rly va s cula r s tructure s , for
s urgica l pla nning; contra s t-e nha nce d CT ca n a ls o ofte n
dis tinguis h be twe e n we lldiffe re ntia te d a nd de diffe re ntia te d
lipos a rcoma .
• CT ima ging is a ls o done to e va lua te the live r for the e vide nce
of me ta s ta s e s , the pe ritone a l ca vity for e vide nce of
dis contiguous dis e a s e , a nd the kidne ys for a s s e s s me nt of
function.
• Angiogra phy or ma gne tic re s ona nce
a rte riogra phy/ve nogra phy ca n a ls o be us e d to de line a te
va s cula r a na tomy whe n involve me nt of critica l va s cula r
s tructure s is s us pe cte d.
• Thora cic CT s hould be pe rforme d to e va lua te for pote ntia l
lung me tas tas e s be caus e 11% o f patie nts with
re tro pe rito ne al s arco ma pre s e nt with s ynchronous
me ta s ta tic dis e a s e .
• CT-guide d core ne e dle biops y is a ppropria te to provide a
tis s ue dia gnos is ; howe ve r, ne ga tive biops y findings s hould
not de la y ope ra tive inte rve ntion.
• Comple te s urgica l re s e ction is the mos t e ffe ctive tre a tme nt for
prima ry or re curre nt re trope ritone a l s a rcoma .
• En blo c re s e c tio n o fte n ne c e s s itate s s ac rific ing
contiguous s tructure s s uch a s the c o lo n, kidne y, s ple e n,
panc re as , ps o as mus c le , s mall bo we l, infe rio r ve na
c ava, and ao rta.
• In a re vie w of 25 pa tie nts who unde rwe nt re s e ction of
re trope ritone a l s a rcoma with major blood ve s s e l
involve me nt in a 16-ye ar time s pan, pos tope ra tive
morbidity a nd morta lity ra te s we re 36% and 4%,
re s pe c tive ly.
• Ve s s e l pa te ncy ra te s we re gre a te r tha n 88% with a
me dia n follow-up time of 19.3 months .
• Loca l control a nd s urviva l ra tes were fa vora ble in pa tients with
tumor-fre e res e ction ma rgins .
• The a uthors conclude d tha t vas c ular res e c tio n is the treatme nt of
c ho ic e in s arc omas that invo lve major bloo d ve s s e ls in the
retrope ritone um.
• Simila r cons ide ra tions were ma de by othe r groups reporting
s pecifica lly on inferior ve na c ava res e c tio n in the conte xt of
multivis cera l res e ction for retrope ritone a l s a rcoma a nd on s urgica l
morbidity a fter exte nde d s urgica l res e ction of retrope ritone a l
s a rcoma .
• Extende d proce dure s , including a ls o ves s e ls , a re fea s ible a nd s a fe if
ca rried out in expe rie nce d cente rs .
• While the goa l of s a rcoma res e ction is wide excis ion, this is unlike ly
to be a chie va ble in mos t pa tients with retrope ritone a l s a rcoma s .
• Surg ery is c ons idere d marg inal in mos t ca s es , eve n whe n
ma cros copica lly comple te , but eve ry a ttempt s hould be ma de to
minimize this ma rgina lity by liberally res e c ting s urroundin org ans
whe n ne e de d.
• The exte ns ion of s urgery s hould the n ta ke into cons ide ra tion a tra de-
off betwe e n expe cte d morbidity a nd bene fit a nd s hould be bes t
ca rried out a t high-volume cente rs , whe re technica l s kills a nd
knowle dge of the na tura l his tory of this very ra re dis ea s e ca n be
found.
• Adjuvant The rapy.
– Mos t studies ha ve failed to show a survival be nefit from
adjuva nt che mothe ra py for retroperito ne al s arco ma.
– Beca us e of the high rate s of local recurre nce , adjuva nt
radiation the ra py ha s be e n propo s e d for treating
micro s c o pic res idual dis e as e follo wing s urgic al res e c tio n.
– Howe ve r, the optimal technique and timing of radiation the ra py
ha ve not be e n es ta blishe d, and the pote ntial be nefits of
radiation the ra py mus t be weighe d agains t the incre as e d ris k
of treatme nt-relate d toxic effe c ts .
• Ra dia tion tre a tme nt of re trope ritone a l s a rcoma s is comple x
be ca us e tumors a re us ua lly la rge , which ne ce s s ita te s la rge
tre a tme nt fie lds clos e to radio s e ns itive s tructure s (e .g .,
bo we l).
• Se ve ra l te chnique s ha ve be e n us e d, including pre ope ra tive
a nd pos tope ra tive e xte rna l-be a m ra dia tion the ra py,
intra ope ra tive ra dia tion the ra py, a nd bra chythe ra py.
• Pre ope ra tive ra dia tion the ra py is fe a s ible a nd we ll tole ra te d.
• Toxic e ffe cts ma y be le s s s e ve re with pre ope ra tive ra dia tion
the ra py give n tha t the tumor borde rs a re de fina ble , the tumor
dis pla ce s ra dios e ns itive vis ce ra a wa y from the tre a tme nt
fie ld, a nd e ffe ctive dos e s of ra dia tion ma y be lowe r
pre ope ra tive ly.
• Curre nt re comme nda tions for ra dia tion the ra py for pa tie nts with re trope ritone a l
s a rcoma a t MD Ande rs on Ca nce r Ce nte r a re bas e d o n dis e as e charac te ris tic s at
pre s e ntatio n.
• For highris k pa tie nts , de fine d a s thos e with la rge , high-gra de tumors or re curre nt
low-gra de tumors , pre ope ra tive ra dia tion the ra py to a tota l dos e of 50 Gy followe d
by s urgica l re s e ction is cons ide re d.
• Pos tope ra tive ra dia tion is dis coura ge d unle s s the re s e cte d tumor be d is cle a rly
a wa y from dos e -limiting s tructure s .
• Tre atme nt o f Re curre nc e .
– Retro perito ne al s arc o mas rec ur more o ften than extremity a nd trunk wall one s .
– Re troperitonea l leiomyos a rcoma s , in a ddition to recurring loca lly in the tumor be d a nd
meta s ta s izing to the lungs , freque ntly s pre ad to the live r.
– Re troperitonea l sa rcoma s ca n also recur diffus e l thro ug ho ut the perito ne al cavity
(s arco mato s is ).
• Re s e ction of re curre nt re trope ritone a l s a rcoma is s imila r to
re s e ction of re curre nt e xtre mity s a rcoma .
• Howe ve r, the like lihood tha t a re curre nt re trope ritone a l
s a rcoma will be re s e cta ble de cline s pre cipitous ly with e a ch
re curre nce .
• In a la rge s e rie s of pa tie nts tre a te d a t Me moria l Sloa n-
Ke tte ring Ca nce r Ce nte r, the a uthors we re a ble to re s e ct
re curre nt tumors in 57% of pa tie nts with a firs t re curre nce but
only 20% of pa tie nts with a s e cond re curre nce a nd 10% of
pa tie nts with a third re curre nce .
• In up to 25% of pa tie nts , we ll-diffe re ntia te d re trope ritone a l
lipos a rcoma re curs in a po o rly diffe re ntiate d fo rm o r
re c urs with are as o f de diffe re ntiatio n.
• De diffe re ntia te d re trope ritone a l lipos a rcoma is more
a ggre s s ive tha n its we ll-diffe re ntia te d pre curs or a nd ha s a
gre a te r prope ns ity for dis ta nt me ta s ta s is .
• Gas tro inte s tinal Sarc o ma
• Pa tie nts with ga s trointe s tina l s a rcoma mos t ofte n pre s e nt with
no ns pe c ific gas tro inte s tinal s ympto ms tha t a re de te rmine d by the s ite
of the prima ry tumor.
• Ea rly s a tie ty a nd dys pe ps ia we re note d in pa tie nts with tumors of the
uppe r ga s trointe s tina l tra ct, whe re a s te ne s mus a nd cha nge s in bowe l
ha bits we re common in pa tie nt with tumors of the lowe r ga s trointe s tina l
tra ct.
• In a s e rie s of 80 pa tie nts with va rious s mooth-mus cle tumors of the
ga s trointe s tina l tra ct, Chou a nd colle a gue ide ntifie d the mos t common
pre s e nting s ymptoms a nd s igns a s
– gas tro inte s tinal ble e ding (44%),
– abdo minal mas s (38%), and
– abdo minal pain (21%).
• Es ta blis hing the dia gnos is of a ga s trointe s tina l s a rcoma pre ope ra tive ly is
ofte n difficult.
• Ra diologic a s s e s s me nt, including CT of the a bdome n or pe lvis , is
s ome time s us e ful to de te rmine the a na tomic loca tion, s ize , a nd e xte nt of
dis e a s e .
• Pa tie nts with loca lize d dis e a s e fre que ntly pre s e nt with a large
intraabdo minal mas s .
• Howe ve r, the re is no radio g raphic e vide nc e o f re gio nal lymph no de
me tas tas e s , which would be typica l of a n a de noca rcinoma of s imila r s ize
a nd a na tomic loca tion.
• In pa tie nts with a dva nce d ga s trointe s tina l s a rcoma , CT ma y de mons tra te
dis s e mina te d intra -a bdomina l ma s s e s with or without concomita nt a s cite s
a nd inva s ion of tis s ue pla ne s .
• Endo s c o py (es o phag o duo de no s c o py or c olo no s c o py) ha s
become the ma ins ta y for eva lua ting s ymptoms rela te d to the
ga s trointe s tina l tra ct.
• For tumors invo lving the s tomac h, upper endo s c o py with
endos copic ultra s onogra phy a nd biops y a re importa nt dia gnos tic
tes ts us ed to dis tinguis h ga s trointe s tina l s a rcoma from
a denoca rcinoma of the s toma ch.
• This dis tinction is clinica lly s ignifica nt beca us e the exte nt of
res e ction (loca l excis ion vers us ga s trectomy) a nd the role of regiona l
lympha de ne ctomy differ for the s e two conditions .
• For g as trointe s tinal s arc omas lymphatic s pread is not the
prima ry route of meta s ta s is ; cons e que ntly, lympha de ne ctomy is not
routine ly performe d a s pa rt of res e ction.
• The ge ne ra l re comme nda tion for ga s trointe s tina l s a rcoma , ba s e d on
publis he d da ta a nd the prima ry pa tte rn of dis ta nt (vs . loca l) fa ilure , is to
re s e ct the tumor with a 2- to 4-c m margin o f no rmal tis s ue .
• Howe ve r, s ome ca s e s ma y be te chnica lly cha lle nging be ca us e of the
tumo r’s anato mic lo c atio n o r s ize .
• For e xa mple , for gas tric tumo rs lo c ate d ne ar the gas tro e s o phag e al
junc tio n, a chie ving a de qua te s urgica l ma rgins ma y not be pos s ible
without a to tal o r pro ximal s ubto tal gas tre c to my.
• Simila rly, la rge le iomyos a rcoma s a ris ing from the s toma ch with inva s ion of
a dja ce nt orga ns s ho uld be re s e c te d to ge the r with the adjac e nt
invo lve d vis c e ra e n blo c .
• For s a rcoma s of the s ma ll or la rge inte s tine , s e gme ntal bo we l re s e c tio n
is the s ta nda rd tre a tme nt.
• For s a rcoma s of the je junum, ile um, and co lo n, the tumor is
e xcis e d e n bloc with the involve d s e gme nt of inte s tine and
its me s e nte ry; radical me s e nte ric lymphade ne c to my is
not a tte mpte d.
• For s a rcoma s origina ting in the re ctum, the tumor re s e ction
te chnique is ba s e d on the a na tomic loca tion a nd s ize of the
tumor.
– For s ma ll, low re cta l le s ions , cle a r ma rgins ma y be a chie va ble with a
trans anal e xcis io n.
– La rge or loca lly inva s ive le s ions ma y re quire more e xte ns ive
ope ra tions for comple te tumor e xtirpa tion.
• Bre a s t Sa rcoma
– Sa rcoma s of the bre a s t a re ra re tumors , a ccounting for le s s than 1% o f all
bre as t maligna ncie s a nd le s s tha n 5% o f all s o ft tis s ue s arco mas .
– A va rie ty of his tologic s ubtype s ha ve be e n re porte d within the bre a s t, including
angio s arc o ma, s tro mal s arco ma, fibro s arco ma, and malignant fibro us
his tio c yto ma.
– Angio s arc o ma of the bre a s t a ccounts for a bout 50% o f all s arco mas o f the
bre as t a nd ha s incre a s ingly be e n a s s ocia te d with ra dia tion the ra py for tre a tme nt
of prima ry bre a s t ca nce r.
– The pe riod be twe e n ra dia tion the ra py a nd dia gnos is of ra dia tion a s s ocia te d
bre a s t s a rcoma ha s be e n re porte d to range fro m 3 to 20 ye ars , with a n
incide nce of 0.3% at 10 ye ars and 0.5% at 15 ye ars .
– In a re tros pe ctive s tudy of 55 pa tie nts with a ngios a rcoma of the bre a s t, pa tie nts
with ra dia tion-a s s ocia te d a ngios a rcoma we re on a ve ra ge 30 ye a rs olde r a nd
we re le s s like ly to pre s e nt with dis tant me tas tas e s than radiatio n-naive
patie nts .
• Clinica lly, ra dia tion-a s s ocia te d a ngios a rcoma of the bre a s t ma y occur in the
irra dia te d che s t wall a fte r ma s te ctomy or in the irra dia te d bre a s t following s e gme nta l
re s e ction.
• The findings a t pre s e nta tion of a pa tie nt with cuta ne ous a ngios a rcoma ofte n include
a n e xpa nding e rythe ma tous pa tch, re d pa pula r e ruptions , bluis hbla ck le s ions , or
bruis e -like dis colora tion ove rlying a n a re a of indura tion.
• Ma mmogra phy is ofte n nons pe cific, a nd dia gnos is re quire s punch or incis iona l
biops y.
• Cys tos a rcoma phyllode s a re ge ne ra lly not cons ide re d to be s a rcoma s , be ca us e
the s e tumors a re thought to origina te from hormona lly re s pons ive s troma l ce lls of
the bre a s t a nd a re us ually be nign.
• In pa tie nts with the s e tumors , infiltra ting tumor ma rgins , s e ve re s troma l ove rgrowth,
a typia , a nd ce llula rity ha ve all be e n ide ntifie d a s ris k fa ctors for me ta s ta s e s .
• As with s a rcoma s a t othe r anato mic s ite s , his to patho lo g ic grade and
tumo r s ize a re importa nt prognos tic fa ctors for s a rcoma s of the bre a s t.
• The like lihood of loca l re curre nce incre a s e s a s tumor s ize incre a s e s ;
tumors s malle r than 5 c m a re a s s ocia te d with be tte r ove ra ll s urviva l.
• Loca l a nd dis ta nt re curre nce s a re more common in pa tie nts with high-
gra de le s ions .
• Co mple te e xc is io n with ne ga tive ma rgins is the prima ry the ra py.
• Simple ma s te ctomy confe rs no a dditiona l be ne fit if comple te e xcis ion ca n
be a ccomplis he d by s e gme nta l ma s te ctomy.
• Be ca us e of low ra te s of re giona l lympha tic s pre a d, a xilla ry dis s e ction is
not routine ly indica te d.
• Ne oa djuva nt che mothe ra py or ra dia tion the ra py ma y be cons ide re d for
pa tie nts with large , hig h-ris k tumo rs .
• DESMOIDS
– Des moid tumors a re no t lo w-g rade s arc o mas but ca n be loca lly a ggres s ive , although
the y do not meta s ta s ize .
– Approxima tely half o f the s e tumo rs aris e in the extremitie s ; the rema ining les ions a re
loca te d on the trunk o r in the retro perito ne um.
– Abdo minal wall de s mo ids a re a ssocia te d with preg nanc y and are tho ug ht to be the
res ult o f ho rmo nal influe nc e .
– Although usua lly spora dic, de s moids ma y occur in a ss ocia tion with fa milial a de noma tous
po lypo s is , a pres e nta tion tha t is refe rre d to a s Gardne r’s s yndro me a nd is linke d to
germline muta tions in the APC gene .
– Spora dic ca s e s of de s mo id fibro mato s is a re commonly linke d to muta tions in CTNNB1,
the gene for β-ca te nin.
– The primary the rapy fo r de s mo id tumo rs ha s long be e n cons ide re d surgica l res e ction
with wide loca l excis ion to a chie ve ne ga tive ma rgins .
– However, loca l recurrence occurs in up to o ne third of pa tients inde pe nde ntly o f the
quality o f s urg ic al marg ins .
– Up to two thirds of the pa tients opera te d on with po s itive marg ins do no t rec ur.
– This is why the re is growing evide nce tha t the prima ry a pproa ch could be more
co ns ervative .
– Func tio n-s paring o peratio ns should be the goal, eve n if a positive ma rgin is left on a
critica l structure.
• More ove r, s ome a uthors a dvoca te the pos s ibility to obs e rve pa tients
a t pres e nta tion, limiting s urgery to thos e who progre s s or fa il medica l
the ra pie s .
• It ha s in fa ct bee n reporte d tha t by this approac h, up to 50% of
patients s kip s urgica l res e ction.
• Ra dia tion the ra py ma y be effe ctive in pa tients with unres e c table
tumors or a s a djuva nt the ra py following s urgery for recurre nt
dis ea s e , a lthough long-te rm s ide effects a nd the ris k of ra dia tion-
induce d s a rcoma s hould a lwa ys be cons ide re d.
• Whe n us ed, a dos e of 50 to 54 Gy is us ually rec o mme nde d.
• Sys te mic treatme nt is ano ther optio n, whe n s urg ery is no t
indic ate d.
• Hormona l the ra pie s s uch a s tamo xife n have be e n re po rte d
to be be ne ficial, a s ha ve nons te roida l a nti-infla mma tory
drugs , which a re known to a ffe ct the β-cate nin s ig naling
pathways .
• Che mothe ra py is a ls o e ffe ctive , a lthough us ua lly re s e rve d for
pa tie nts with tumo r-as s o ciate d s ympto ms who have no t
re s po nde d to o the r inte rve ntio ns .
– Combina tions of me tho tre xate and vinblas tine ha ve be e n s hown
to ha ve a ctivity, a s ha ve s ingle -a ge nt pe gyla te d lipos oma l
doxorubicin a nd s ora fe nib.
– Ima tinib ha s a ls o be e n s tudie d with unconvincing re s ults .
From Meds ca pe
• Des mo id tumors a re cytologica lly bland fibrous ne opla s ms
origina ting from the mus c uloapo ne urotic s truc tures throughout
the body.
• The term des moid, coine d by Muller in 1838, is derive d from the
Gre e k word des mos , which mea ns tendo nlike .
• Des mo id tumors ofte n a ppea r a s infiltra tive , us ua lly we ll-
differe ntiate d, firm overg rowths of fibrous tis s ue, and the y are
loc ally ag gres s ive .
• The s ynonym a ggres s ive fibroma tos is des c ribes the marked
c ellularity a nd ag gres s ive loc al behavior.
• This cours e a nd the tende ncy for recurre nce ma ke the trea tme nt of
the s e rela tive ly ra re fibrous tumors c halle ng ing .
• Pa thophys iology
– Although de s moid tumors mos t commonly a ris e from the re ctus
abdo minis mus cle in po s tpartum wo me n and in s cars due to
abdo minal s urg ery, the y ma y a ris e in a ny s ke le ta l mus cle .
– De s moid tumors te nd to infiltra te a dja ce nt mus cle bundle s ,
fre que ntly e ntra pping the m a nd ca us ing the ir de ge ne ra tion .
– The y ma y be de rive d from me s e nchyma l s te m ce lls .
– Although fixa tion to mus culoa pone urotic s tructure s is a ppa re nt, the
ove rlying s kin is normal.
– The myo fibro blas t is the ce ll cons ide re d to be re s pons ible for the
de ve lopme nt of de s moid tumors .
• Ga rdne r s yndrome or fa milia l a denoma tous polypos is (FAP) is
cha ra cte rize d by c olore c tal adeno mato us polyps and s oft and
hard tis s ue ne o plas ms .
• The forme r ma y numbe r in the hundre ds to thous a nds .
• Ga rdne r s yndrome wa s rega rde d a s a s eparate dis eas e until the
identific atio n of the APC (adeno mato us polypo s is c oli) g ene , a t
which point muta tions in the APC gene were recognize d a s the
unde rlying ca us e of both Ga rdne r s yndrome a nd FAP.
• Some a uthors rega rd Ga rdne r s yndrome a s a s ubs et of FAP, a nd
s ome ha ve eve n s ugges te d tha t the term Ga rdne r s yndrome be
repla ce d by FAP.
• Additiona lly, evide nce a ls o exis ts for a gene tic predis pos ition to
des moid tumors in FAP, inde pe nde nt of the APC muta tion.
• Des moid tumors occur a t a ra te of 10-15% in patients with FAP, a n
a utos oma l inhe rite d dis ea s e ca us ed by germline muta tions in the
APC gene .
• Spora dic forms ha ve no he re dita ry ba ckground.
• Des moid tumors s how biallelic APC mutation, with one cha nge
us ua lly occurring dis ta l to the s econd beta -ca te nin
binding/de gra da tion repe a t of the gene .
• The rela tions hip betwe e n extrac olo nic manife s tatio ns a nd the s ite
of the APC muta tion s ugges ts a s pecific role of the APC prote in in
differe nt tis s ues .
• Howe ve r, unknown gene tic fa ctors inde pe nde nt of APC ma y be
importa nt in the s us ceptibility to des moid tumors in pa tients with
FAP.
• In de s moid tumors , 1 of the 2 muta tions us ua lly occurs dis ta l
to the s e cond be ta -ca te nin binding/de gra da tion re pe a t of the
ge ne .
• Ca te nin a nd ca te nin-binding ge ne s ha ve be e n found to be
a s s ocia te d with ne opla s tic proce s s e s in a numbe r of wa ys .
• Inde pe nde nt pre dictors of incre a s e d de s moid ris k in one
s tudy we re s a id to be
– (1) ge rmline muta tion dis ta l to codon 1399,
– (2) a ny fa mily his tory of ga s trointe s tina l dis e a s e , a nd
– (3) a s trong fa mily his tory of de s moid tumors .
• The rela tions hip be twe e n ce rta in extra colonic ma nife s ta tions a nd site s of the APC muta tion
sugge s ts spe cific roles of the APC protein in diffe rent tiss ue s .
• The s e differe nt roles ma y corre s pond to spe cific site s of miss e ns e muta tions in the APC
gene .
• For exa mple, de nta l ma nife s ta tions of Ga rdne r syndrome ha ve be e n sugge s te d to be
a ss ocia te d with muta tions a t or ne a r codon 1556.
• Howeve r, the influence of unknown gene tic fa ctors inde pe nde nt of APC in sus ce ptibility to
de s moid tumors in FAP ne e ds to be explored.
• FAP res ults from a germline muta tion in the APC gene .
• Des mo id tumo rs are as s o c iate d with a bialle lic APC mutatio n in the affec te d tis s ue .
• This usua lly res ults from a sponta ne ous soma tic muta tion in the una ffe cte d APC gene of a
single ce ll in a pa tient with the FAP syndrome.
• This proce s s is a n exa mple of the Knuds e n "two hit" hypo the s is , in which a tumor
suppre s s or gene , such a s APC, must be bia llelica lly muta ted in orde r for a spe cific type of
tumor to occur.
• In ge ne tica lly normal individua ls, with norma l ge rmline ge ne s , this ne ce s sitate s a rare combina tion of
eve nts , such tha t at lea s t 2 soma tic muta tions mus t occur in both alleles of a single tumor suppre s s or
ge ne , in this ca s e the APC ge ne .
• In FAP syndrome pa tients , one APC ge rmline ge ne is alrea dy muta te d in eve ry cell in the body (ba rring
a rare reve rs e soma tic muta tion in some cells), and, the re fore , only one ne w soma tic muta tion is
required in the oppos ite APC ge ne for the tumor to de ve lop.
• FAP ma y be as s ociate d with muta tions in the APC ge ne , but muta tions in se ve ra l othe r ge ne s ,
pa rticularly misma tch DNA repair ge ne s , which are prima rily res ponsible for ens uring inte grity of
polyme ra s e s res ponsible for DNA replica tion, ma y also res ult in familial colonic polyposis .
• The s e pa tients with familial colonic polyposis typica lly do not show othe r ma nifes ta tions of Ga rdne r
syndrome .
• Conve rs ely, extra colonic ma nifes ta tions cha ra cte ristic of Ga rdne r syndrome ma y occur inde pe nde nt of
inte s tina l polyps or a muta tion in the APC ge ne . Nuclea r localiza tion of β-ca te nin ma y be evide nt in
pe diatric de s moids rega rdles s of muta tion sta tus , with mos t showing soma tic muta tions in CTNNB1.
• Howe ve r, ma ny ha rbor ge rmline muta tions in APC. CTNNB1 muta tions are common in spora dic
de s moid tumors
• Epide mio lo g y
• Freque nc y
• Inte rnatio nal
• Ove ra ll, de s mo id tumo rs a re reporte d to a ccount for 0.03% of a ll ne opla sms .
• Whe n pres e nt in pa tients with familial po lypo s is o f the co lo n, the preva lence of de s mo id
tumo rs is a s high a s 13%.
• Mo rtality/Mo rbidity
• Des pite the ir be nign his tologic a ppea ra nce a nd ne gligible meta s ta tic potentia l, the tende ncy
of de s moid tumors to ca us e loca l infiltra tion is significa nt in terms of
– (1) de fo rmity, morbidity, and mortality res ulting fro m pres s ure effe c ts and
– (2) po te ntial o bs truc tio n o f vital s truc tures and org ans .
• S ex
– Des moid tumors mos t commonly occur in wome n after childbirth.
– Des moid tumors are twice as common in fema les tha n in male s ; howe ve r, 60 pa tients were
de s cribe d, the female -to-male ratio was 1.2:1.
– In childre n, the se x incide nce is equa l.
• Ag e
– Although de s moid tumors are more common in pe rs ons age d 10-40 yea rs tha n in othe rs , the y do
occur in young childre n and olde r adults.
– Sixty pa tients were de s cribe d by Lee et al in 2006, with an ave ra ge age at diagnosis of 41.3 years
• His tory
– Although de s moid tumors ca n a ris e in a ny s ke le ta l mus cle , the y
mos t commonly de ve lop in the a nte rior a bdomina l wa ll a nd s houlde r
girdle .
– Re trope ritone a l ne opla s ms a re more common in fa milia l polypos is
coli a nd Ga rdne r s yndrome a fte r a bdomina l s urge ry tha n in othe r
conditions .[11]
– Clus te rs of ca s e s in fa milie s without e vide nce of a ny a s s ocia te d
s yndrome s ha ve a ls o be e n re porte d.[12]
– A his tory of tra uma (ofte n s urgica l) to the s ite of the de s moid tumor
is e licite d in 1 in 4 ca s e s .[13] . Impla nt-a s s ocia te d bre a s t de s moid
tumors ma y occur.
• Phys ica l
• Pe riphe ra l des moid tumors
– Pe riphe ra l des moid tumors a re firm, s mo o th, and mo bile.
– They often a dhere to surrounding structure s .
– The overlying skin is us ua lly una ffe cte d.
• The pres e nce of s uch a s oft tis s ue growth s hould a lert the clinicia n
to delve more dee ply into the fa mily his tory for evide nce of fa milia l
polypos is coli a nd Ga rdne r s yndrome .
• Extra -a bdomina l des moid tumors a re ra re a nd ma y be firs t evide nt
a s gra dua lly incre a s ing leg s welling.
• Des moid tumors ma y ra rely a ppea r on the foot.
• Intra -a bdomina l a nd e xtra -a bdomina l de s moid tumors
• Intra -a bdomina l de s moid tumors ma y be s e e n. Extra -a bdomina l de s moid
tumors ma y a ls o be s e e n (ra re ly) in the urologica l s ys te m, including in the
bla dde r a nd s crotum.
• Intra -a bdomina l de s moid tumors re ma in a s ymptoma tic until the ir growth
a nd infiltra tion ca us e vis ce ra l compre s s ion. Symptoms of inte s tina l,
va s cula r, ure te ric, or ne ura l involve me nt ma y be the initia l ma nife s ta tions .
An e thmoida l de s moid tumor ha s be e n de s cribe d in a pe dia tric
pa tie nt.[19]
• Bre a s t de s moid tumors
• De s moid tumors a ccount for 0.2% of prima ry bre a s t tumors , de ve loping
from mus cula r fa s cia e a nd a pone uros e s .[20] De s moid tumors ma y mimic
bre a s t ca nce r
• Ca us e s

• The ca us e of de s moid tumors is unce rta in a nd ma y be rela te d to tra uma or


hormona l fa ctors , or the y ma y ha ve a ge ne tic a s s ocia tion.

• The fa milial polypos is ge ne on chromos ome 5 ha s be e n e xte ns ive ly s tudie d.[5, 22]

• An e ndocrine e tiology is s ugge s te d. De s moid tumors mos t commonly a ppe a r in


young wome n during or a fte r pre gna ncy. The tumors re gre s s during me nopa us e [23]
a nd a fte r ta moxife n tre a tme nt.[24] De s moid tumors ma y re gre s s a fte r e xpos ure to
ora l contra ce ptive s .[25]

• The prolife ra tive re s pons e of fibrobla s ts to e s troge n ha s be e n e s ta blis he d


• Dia gnos tic Cons ide ra tions

• Fibros a rcoma

• Fa milia l polypos is of the colon

• Bre a s t ca nce r: Whe n a de s moid tumor involve s the bre a s t, it


ma y mimic bre a s t ca nce r on phys ica l e xa mina tion,
ma mmogra phy, a nd bre a s t ultra s onogra phy
• La bora tory Studie s

• Immunos ta ining with vime ntin, a lpha s mooth mus cle a ctin, mus cle a ctin,
a nd de s min a re he lpful in dis tinguis hing the tumors in the diffe re ntia l
dia gnos is of de s moid tumors .
• APC ge rmline muta tions in a ppa re ntly s pora dic de s moid tumor pa tie nts
who ha ve no clinica l or fa milia l s igns of fa milia l a de noma tous polypos is
(FAP) but ha ve a fa mily his tory of colore cta l ca rcinoma in a t le a s t one
fa mily me mbe r
• The y re porte d tha t pa tie nts with s pora dic de s moid tumors a nd no clinica l
or la bora tory s igns of FAP ma y not ne e d to be routine ly te s te d for ge rmline
muta tions of the APC ge ne . Howe ve r, pe rforming a n APC muta tiona l
a na lys is ins te a d of othe r te s ts (e g, e s opha goga s troduode nos copy,
comple te colonos copy) ma y be a more time - a nd cos t-e ffe ctive pla n
• Ima ging Studie s

• CT s ca nning a nd MRI a re us e d for the dia gnos is a nd


follow-up of de s moid tumors . The y ca n he lp de te rmine the
e xte nt of the tumor a nd its re la tions hip to ne a rby
s tructure s , e s pe cia lly prior to s urgica l re mova l. MRI is
s upe rior to CT s ca nning in de fining the pa tte rn a nd the
e xte nt of involve me nt a s we ll a s in de te rmining if
re curre nce ha s occurre d a fte r s urge ry.
• Proce dure s
• The pre fe rre d dia gnos tic te s t is biops y of the tumor. A fine-
ne e dle a s pira tion biops y s pe cime n ma y be cons ide re d.
• Ele ctron micros copy ma y be pe rforme d. On e le ctron
micros copic e xa mina tion, the s pindle ce lls of de s moid tumors
a ppe a r to be myofibrobla s ts . This finding is thought to
re pre s e nt a n a bnorma l prolife ra tion of myofibrobla s ts , which
norma lly dis a ppe a r gra dua lly during the la te r s ta ge s of wound
he a ling.
• Colonos copy a nd funda l e xa mina tion a re indica te d to
inve s tiga te for the pre s e nce of Ga rdne r s yndrome .
• His tologic Findings

• The tumors a re compos e d of a bunda nt colla ge n s urrounding poorly


circums cribed bundle s of s pindle cells . The dens e bundle s of
eos inophilic s pindle cells conta in regula r nucle i a nd pa le cytopla s m
with ne ithe r mitos e s nor gia nt cells . Ma cropha ge s , gia nt cells , a nd
lymphocyte s a re pres e nt periphe ra lly.

• The a fore me ntione d fea ture s a re in contra s t to thos e in a


fibros a rcoma , which ha s grea te r mitotic a ctivity, a n incre a s e d
nucle a r-to-cytopla s m ra tio, grea te r va s cula rity, les s colla ge n
production, a nd a pa ucity of immune cells .
Bland fibrocytic cells of a de s moid tumor growing in a
ha pha za rd-to-s toriform ma nne r and producing collage n
Des moid tumor spindle ce lls inva ding skele tal
mus cle
Dermoid tumor spindle ce lls surrounding and de s troying ske letal mus cle
ce lls
• Trea tme nt Options for Nons urgical Pa tients

– Prima ry surge ry with ne ga tive surgica l ma rgins is the most succe s s ful prima ry trea tme nt moda lity for de s moid tumors .
Pos itive ma rgins after surge ry reflect a high risk for recurre nce .[28]

– In thos e pa tients who refus e surge ry or are not surgica l ca ndida te s , the options be low ma y be conside re d.

– Ra diation the ra py ma y be us e d as a trea tme nt for recurre nt dise a s e or as primary the ra py to avoid mutilating surgica l
res e ction. It ma y be us e d postope ra tively, pre ope ra tively, or as the sole treatme nt.[29]

– Pha rma cologic the ra py with antiestroge ns and pros ta glandin inhibitors ma y also be us e d.

– In ca s e s of recurre nt extra -a bdomina l de s moid tumors in which surgery is contraindica te d or in ca s e s of recurre nce , a
che mothe ra pe utic regime n of doxorubicin, da ca rba zine , and ca rboplatin ma y be effective. Intra -a bdomina l de s moid
tumors as a pa rt of Ga rdne r syndrome ma y res pond to sys te mic doxorubicin, and ifosfamide ca n be us e ful for pa tients
with complications from the tumor.[30] Polyche mothe ra py ha s be e n us e d[31] and ca n be combine d with targete d
the ra py with imatinib.[32]

– Expa nde d knowledge of familial ade noma tosis polypos is–de s moid tumor molecular unde rpinnings ma y aid in the
de velopme nt of nove l the ra pe utic strate gies .
• Excis ion of Tumor

• Aggres s ive , wide surgica l res e ction is the trea tme nt of choice .[34, 35] Complete surgica l
excis ion of de s moid tumors is the most effe ctive method of cure . This some time s
ne ce s s ita te s remova l of most of a n a nte rior compa rtment of a leg. Exte ns ive ca s e s ma y
require excis ion plus a djuva nt trea tme nt including che mothe ra py a nd repe a t surgery.[36] In
se lecte d pa tients , ra dica l res e ction with intra opera tive ma rgin eva lua tion by froze n se ctions
followed by immedia te mes h recons truction ma y be a sa fe a nd effe ctive proce dure providing
de finitive cure yet minimizing functiona l limita tions .[37]

• Evide nce sugge s ts tha t pregna ncy doe s not a dve rs ely a ffect surgica l outcome s .[38]

• Les ions involving the extremitie s a nd de e p soft tiss ue s of the trunk ha ve a highe r risk of
recurre nce , a s do Ga rdne r syndrome–a s socia te d les ions in othe r loca tions.[39]

• For tumors tha t a re a symptoma tic or nonprogres s ive , some prefe r a wa it-a nd-s e e a pproa ch.
• DERMATOFIBROSARCOMA PROTUBERANS
• De rma tofibros a rcoma protube ra ns is a rare lo w-g rade
s arco ma aris ing in the de rmis tha t ra re ly me ta s ta s ize s but is
loca lly a ggre s s ive .
• The ove ra ll a nnua l incide nce ha s be e n e s tima te d a t ca s e s pe r
million individua ls , a nd the incide nce is highe r a mong bla cks
tha n white s (6.5 vs . 3.9 pe r millio n pe r ye ar).
• Approxima te ly 40% o f cas e s aris e o n the trunk, a nd mos t of
the re ma ining tumors a re dis tribute d be twe e n the he ad and
ne ck and the e xtre mitie s .
• De rma tofibros a rcoma protube ra ns pre s e nts a s a no dular,
c utane o us mas s tha t grows s lowly a nd pe rs is te ntly.
• Sate llite les io ns ma y be found in pa tie nts with la rge r
tumors .
• Sta nda rd tre a tme nt is wide lo c al exc is io n, which
ge ne ra lly re s ults in lo c al rec urre nc e rate s o f les s than
10%.
• Although loca l re curre nce ra te s a s high a s 30% to 50%
ha ve be e n re porte d in popula tion-ba s e d s e rie s , the
a s s ocia te d 5-ye ar s urvival rate is g reate r than 99%.
• De rma tofibros a rcoma protube ra ns a ris e s from a s pe cific chro mo s o mal
trans loc atio n involving chro mo s o me s 17 and 22, in which the colla ge n 1 α 1 ge ne
is fus e d to the ge ne for PDGF β-cha in (PDGFB).
• The re s ulta nt de re gula te d e xpre s s ion of PDGFB le ads to co ntinuo us activatio n of
the PDGFR prote in tyro s ine kinas e , which promote s tumor ce ll growth.
• The ide ntifica tion of this chromos oma l tra ns loca tion in more than 90% of cas e s of
de rma tofibros a rcoma protube ra ns ha s le d to the de velopme nt of targe te d the rapy.
• Inhibiting PDGFR with imatinib ha s be e n s hown to induce clinica l a nd ra diologic
improve me nt in pa tie nts with unre s e ctable de rmatofibro s arc o ma protube rans .
• The s e da ta ha ve re s ulte d in the a pprova l by the U.S . Food a nd Drug Adminis tra tion
of imatinib for tre a tme nt of pa tie nts with loca lly a dva nce d de rma tofibros a rcoma
protube ra ns .
• PEDIATRIC S ARCOMAS
• Soft tiss ue sa rcoma s in childre n a re rela tively ra re, a ccounting for 7% to 8% of all pedia tric
ca nce rs a nd totaling a pproxima tely 600 ne w ca s e s per yea r.
• Pe dia tric sa rcoma s ha ve tra ditiona lly be e n divide d into two groups:
– rhabdo myo s arco ma and
– No nrhabdo myo s arco ma s o ft tis s ue s arco mas .
• Rhabdo myo s arc o ma
• Ass ocia te d with skele ta l muscle, rha bdomyos a rcoma s a re the most common soft tiss ue
tumors a mong childre n younge r tha n 15 yea rs a nd ca n occur a t a ny site compris e d of
stria te d muscle.
• Pa tie nts with the s e tumors gene ra lly pres e nt with a pa inles s enla rging ma ss ;
– abo ut 24% o f tumo rs are lo cate d in the g enito urinary s ys te m,
– 20% in the extremitie s ,
– 20% in the he ad and ne c k,
– 16% in the paramening e al reg io n, and
– 22% in o ther s ite s
• Rha bdomyos a rcoma is a s mall round ce ll tumor tha t de mons tra te s mus cle
diffe re ntia tion upon light micros copy a nd immunohis toche mica l a na lys is .
• Two prima ry his tologic s ubtype s a ccount for 90% of ca s e s :
– embryo nal (70%) and
– alve o lar (20%).
• Alve ola r rha bdomyos a rcoma is a s s ocia te d with cyto g e ne tic trans loc atio n
[t(2:13)(q35:q14)] in 85% to 90% of cas e s a nd [t(1:13)(p36:q14)] in 10% of cas e s .
• The s e tra ns loca tions a ffe ct biologic a ctivity a t the le vels of prote in function a nd ge ne
e xpre s s ion, the re by a ffe cting the co ntro l of ce ll gro wth, apopto s is ,
diffe re ntiatio n, and motility and ultimate ly co ntributing to tumorig e nic
be havio r.
• Whe re a s alve olar rhabdo myo s arc o mas ofte n ha ve tra ns loca tions , mos t
e mbryona l rha bdomyos a rcoma s ha ve a n allelic los s a t chromos ome 11p15.5 tha t is
thought to ina ctiva te a tumor s uppre s s or ge ne .
• Both of the s e dis tinct mole c ular s ubtype s of rhabdo myo s arc o ma a re thought to
ha ve s imila r alte ra tions in downs tre am targe ts s uch as the p53 and Rb
pathways .
• Comple te s urgica l re s e ction is the tre a tme nt of choice for
rha bdomyos a rcoma whe n function a nd cos me s is ca n be
pre s e rve d.
• Pa tie nts who a re a ble to unde rgo a comple te tumor re s e ction
with ne ga tive (group I) or micros copic s urgica l ma rgins (group
II) a re a ble to unde rgo le s s inte ns ive s ys te mic the ra py a nd
s till ha ve ove ra ll s urviva l ra te s a pproa ching 90%.
• At s ome a na tomic s ite s , in pa rticula r the he ad and ne ck and
g e nito urinary s ys te m, s urge ry is ofte n a voide d be ca us e the
a s s ocia te d morbidity wo uld be s ubs tantial.
– Re ce nt findings s ugge s t tha t che mo the rapy alo ne ca n a de qua te ly
control ma ny s uch tumors .
• Unlike othe r s oft tis s ue s a rcoma s , rha bdomyos a rcoma s
ha ve a high pro pe ns ity fo r lymph no de me tas tas is ,
with ra te s up to 20% to 30% fo r s ites s uch a s the
e xtre mitie s , pa ra te s ticula r node s , a nd pros ta te .
• Lymph no de s ampling and, mo re rec e ntly, s e ntine l
lymph node ma pping ha ve be e n us e d to e va lua te
reg io nal no de s tatus in c hildre n with
rhabdo myo s arc o ma.
• About 15% to 20% of patie nts with rhabdo myo s arc o ma ha ve dis ta nt me ta s ta s is
a t pre s e nta tion, mos t commonly (40%–50% of cas e s ) to the lungs , followe d by
bone marrow and bone .
• Howe ve r, all patie nts with rhabdo myo s arc o ma a re a s s ume d to ha ve
microme ta s ta tic dis e a s e a t pre s e nta tion.
• The re fore , multiage nt che mo the rapy is re comme nde d for all pa tie nts with
rha bdomyos a rcoma .
• Combina tion re gime ns including vincris tine , dactino myc in, and
cyc lo pho s phamide continue to be the ba s is of e ffe ctive cura tive the ra py.
• Although va rious combina tions including doxorubicin, ifos fa mide , cis pla tin, a nd
e topos ide ha ve be e n s hown to be a ctive a ga ins t rha bdomyos a rcoma , the y ha ve not
improve d outcome s .
• Ra dia tion the ra py is give n to mos t pa tie nts with micros copic re s idual dis e a s e (group
II) a fte r re s e ction.
• The prognos is for childre n with rha bdomyos a rcoma s is
re la te d to tumor s ite , s urgica l-pa thologic grouping, a nd
tumor his tology.
• The 5-ye a r dis e a s e -fre e s urviva l ra te for a ll pa tie nts ha s
be e n re porte d to be 65%.
• Five -ye a r dis e a s e -fre e s urviva l ra te s for pa tie nts in groups
I, II, III, a nd IV ha ve be e n re porte d to be 84%, 74%, 62%,
a nd 23%, re s pe ctive ly.
• Nonrha bdomyos a rcoma Soft Tis s ue Sa rcoma s
– Approxima te ly 60% o f s o ft tis s ue s arco mas in childre n are
no nrhabdo myo s arco mas .
– The s e include nume rous his tologic s ubtype s , which a re ge ne ra lly
ca te gorize d into four groups :
• (a) fibros arc o ma,
• (b) Kapos i’s s arco ma,
• (c) othe r “s pe cifie d” s oft tis s ue s arco mas (e .g., s ynovia l, a ngios a rcoma ,
he ma ngiope ricytoma , le iomyos a rcoma , lipos a rcoma , a nd e xtra os s e ous
Ewing’s s a rcoma ), a nd
• (d)“uns pe cifie d” s oft tis s ue s arco ma.
– The mos t common s ubtype s a re s yno vial s arco ma, MPNS T, and
fibro s arco ma.
• No s ingle his tology a ccounts for more tha n 15% of a ll ca s es .
• As with a dult tumors , the eva lua tion of the s oft tis s ue ma s s begins
with a his tory and phys ic al examinatio n follo we d by imag ing ,
whic h us ually inc lude s MRI.
• A CT s ca n of the che s t is important for evaluatio n of metas tatic
dis eas e .
• A core ne e dle biops y is gene ra lly require d to es ta blis h a dia gnos is .
• Surge ry rema ins the prima ry trea tme nt of nonrha bdomyos a rcoma ,
a nd loca l control of la rge, high-gra de tumors is improve d with
ra dia tion the ra py.
• The prognos tic fa ctors for childre n with nonrha bdomyos a rcoma a re
s imila r to thos e for a dults , a nd the role of che mothe ra py for high-ris k
tumors is uncle a r, a s for a dults .