Diagnosis, Classification

& Management of
Soft Tissue Sarcoma

Henry J. Mankin MD
Francis J. Hornicek MD, Ph.D
Massachusetts, General Hospital Boston
Harvard Medical School
( Cancer Control, Vol 12 No 1, Jan/ Feb 2005
)

Journal Reading
Oncology Sub Division
Orthopaedic & Traumatology Department
Dr. Hasan Sadikin Hospital / UNPAD Medical Faculty
2005
Abstract
 Introduction
Soft tissue sarcoma
Major group of lesions :
- subtle presentation
- wide variation
Relative infrequent ( < 5000 /year
USA )
Confused : malignant benign
excessive or inadequate treatment
Introduction
Relationship with normal soft tissue
structure
fascia, elastic tissue, fat, smooth muscle,
fibrous capsule, blood vessel & nerve
Symptoms may related to effect to
function of normal tissue
Malignant bone tumor : less frequent, more
easily D/
Some soft tissue lesion : no well defined cell
of origin
Introduction
Harvard Orthopaedic Oncology group
29 years data
160.000 connective tissue tumor
Identified 2000 soft tissue sarcoma
 Types of Soft Tissue
Sarcoma
Malignant Fibrous Histiocytoma
Most common STS
530 cases , M : F = 52 : 48
Age 3 96 yrs ( 58 + 18 yrs )
Often undifferentiated, broad range histo appearance
4 Sub Types
- Storiform
- Myxoid
- Giant cell
- Inflammatory
MFH
Late adult, Men
Location :
thigh, pelvis, arm, trunk
occasionally bellow elbow or knee
Painless, non-tender, rapid enlarging
May involve adjacent structure : bone femur, pelvis
Imunohisto-chemical marker : not helpful
BMP-2 : better prognosis
Relation w/ radiation exposure, bone infarction
Implanted Metallic & especially plastic devices
MFH
 Liposarcoma
2nd most common
M:F ratio = 57 : 43
5 94 yrs ( m : 51 + 17 yrs )
Sub types ( WHO ) : 5
Well diff Dedefferentiated
Myxoid Pleomorphic
Round cell
Potential under or over-treatment
Liposarcoma

Myxoid & round cell chromosom

12 , 16
Anatomic site = MFH, more distal
Lower tendency of metastasis
No connection : radiation, implanted
devices
or to Lipomas
Liposarcoma
 Synovial sarcoma
Orthopaedic oncology group : 177 ps
2 80 yrs ( 33 + 16 yrs )
M : F = 55 : 45
Often occur on : joints, tendons, ligamentous structure
regions.
No evidence : origin from synovial cells or synovial
joints.
Types ( 3 ) :
Biphasic
Monophasic epithelial type
Monophasic fibrous type
No difference : malignant character or anatomic location
Synovial sarcoma
Myxoid character, contain Hyaluronic acid
+ heparan
Irregular small flecks of calcification
radiographic clue
Immuno-reactive to cytokeratin &
epithelial membrane antigene
Translocation : 11, 12, 18 chromosome
distinguish from other STT
Dormant long period clinical aggressive
Synovial sarcoma
 Neurofibrosarcoma
= Malignant schwannoma
= Malignant peripheral nerve sheath tumor
Frequently w/ neurofibromatosis type 1
After radiation exposure
Series : 93 ps, 18 w/ neurofibromatosis type 1
Age : 10 85 yrs ( m : 36 + 17 yrs )
M:F = 47 : 53
Location : thigh, shoulder, spine, pelvic
Immunological :
S-100, CD57, collagen type 4, laminin
cytokeratin, P53
Neurofibrosarcoma
 Leiomyosarcoma
Uncommon malignant neoplasm of smooth muscle
Most freq : uterus, abdominal & urologic viscera
OOG Data base : 5th , 76 lesions , mostly
extremities
M : F ratio = 57 : 43
Age : 18 85 yrs ( m : 56 + 19 yrs )
Behavioral differently : visceral : peripheral
more access to metastatic spread ( smooth
muscle surrounding blood vessel )
most malignant of all STT, metastasis, poor
survival
Leiomyosarcoma
 Clear cell sarcoma
= Malignant melanoma of soft part
Often contain melanin
difficult w/ HE staining,
Immunohistochemical (+)
Deep to the surface ; Foot, ankle, close to
tendons
Highly malignant
26 ps, M : F = 58 : 42
Age : 7 78 yrs ( 39 + 21 yrs )
Histo : dark staining sites containing melanin
S 100 protein & Ag
Clear cell sarcoma
 Fibrosarcoma
Lesion w/ fibroblastic stroma , limited amount
of atypia or number of bizarre cells
A form of MFH ?
Location : Fibrous soft tissue extremities,
pelvis, inside bone
Several reports : children , young infants more
common
Identified by specific t ( 12 ; 15 ) translocation
Harvard OOG : 95 lesion
M : F = 60 : 40 , Age : 2 87 ( m : 48 + 20 yrs )
Fibrosarcoma
 Rhabdomyosarcoma
Arise from striated muscle ( w/ little
evidence )

36 cases, Age : 6 33 yrs ( m : 17 + 10 yrs

)
M : F = 44 : 56
Chromosome : 11p 15,5 diagnostic
Children w/ Rhab until 1970s Fatal
With chemo survival mostly
Rhabdomysarcoma
 Epitheloid Sarcoma
Uncommon lesion, often : upper extremity
Relative benign appearance , malignant
behavior
Often confused w/ other lesions
Predilection : subcutis & deeper tissue of
finger, hand & forearm
Ulceration resembles squamous cell ca
Some w/ calcification
49 cases, M : F = 65 : 35
Age : 8 81 yrs ( m : 34 + 18 yrs )
Epitheloid sarcoma
 Alveolar soft part
sarcoma
Unusual tumor arise from skeletal muscle
Muscle associated protein : especially desmin
Organoid pattern, crystals contain
monocarboxylate transporter protein 1 & CD
147
Adult : fascia & skeletal muscles lower
extremities, bone
Child : head & neck region
18 cases, Age 13 69 yrs ( m : 27 + 12 yrs )
M : F = 33 : 67
Alveolar soft part sarcoma
 Other Tumors
Rare, less well defined
51 ps, vascular sarcoma
Spindel cell sarcoma
Undifferentiated sarcoma of soft
part
Angiosarcoma
 Diagnosis of STS
Can be difficult :
- often painless
- difficult to examine in
obese, muscular ps
- location in prox part of
body
Symptoms :
- motion restriction
- sensory motor def
- mass
- occasionally : broken
through the skin
Diagnosis of STS

Physical exam :
May be difficult
Firmer than surrounding tissue
Often attached to bone, fibrous membrane,
neuro-vascular structure
May appear related to recent or earlier trauma
May be tender

History of radiation diagnostic

importance
 Imaging of STS
Helpful or even diagnostic
Roentgenograph large or causes injury to the bone
CT Scan : change in shape & size, soft tissue character
homogenous
irregularity : necrosis / hemorrhage
MRI : provide most info STS
clear shape & size
clue to nature of lesions
Most STS dark on T1 ( hypo-intense )
light on T2 ( hyper-intense )
Effect of fat + increased vascularity both hyper-
intense
Imaging
Imaging
Bone Scan : Positive if bone damaged or highly
vascular
PET : - Active for STS
- Seeking metastases, additional lesions
- lymph node extensions
Screening for Metastases
Essential
From 1.626 ps : 278 ( 17 % ) already have
Meta at presentation
Chest CT
PET : for multiple site tumors
Lab : provide little information
 Biopsy
Essential part of work up
Most case : identify , key info
determining treatment protocol
Open biopsies : complication risk, more
accurate
Small incision, avoid transverse inc
Obtain sufficient tissue :
Frozen section Grading
Tissue identification Immunological studies
Electron microscopy Flow cytometry
Biopsy
Needle biopsy :
- FNAB
- Core ( under CT ,
USG )
 Staging of STS
Two staging system
Musculoskeletal Tumor Society
( MTS )
GTM
American Joint Commission on
Cancer ( AJCC)
GTNM
Define extend & severity
Staging ( MTS )
 GTNM ( AJCC 5 ed) th

STAGE Description Prognostic Factors

Low grade, small, superficial or
IA deep G1-2, T1a-1b, N0,M0 G1 well diff
IB low grade, large, superficial G1-2, T2a, N0,M0 G2 moderately diff
IIA Low grade, large, deep G1-2, T2b, N0,M0 G3 Poorly diff
High grade, small, superficial or
IIB deep G3-4, T1a-1b, N0,M0 G4 Undiff
IIC High grade, large, superficial G3-4, T2a, N0,M0 T1 Small size (< 5 cm)
T1a superficial to fascia
T1b deep to fascia
III High grade, large, deep G3-4, T2b, N0,M0 T2 Large size ( > 5 cm )
T2a superficial to fascia
T2b deep to fascia
Any G, any T, N1 or N1 Regional lymph node
IV Any metastasis M1 metastasis
M1 Systemic metastasis
 Treatment of STS
Depend on :
Age, general health status
Size, Site, Proximity to neurovacular & visceral
Patients or Family choice

Most part : Surgical, Include site of Biopsy

Intra-lesional Wide
Marginal Radical

Other procedure :
Muscle & skin graft
Vascular graft
Metallic or allograft implant
Treatment of STS
Radiation
Decrease local recurrence & possibly
metastasis
Pre-op, Intra-op, Post-op
Brachytherapy
Dosage : 40 60 Gy ( or more )
Extend of surgery
Anatomic site
Micro and Macros retention of diseased
tissue
Treatment of STS
Chemotherapy
Pre-op & Post-op
Principal agents : ifosfamide & doxorubicin
Reduce extend of resection
Connective tissue oncology service at Massachusetts GH
: MAID
Mesna 2500 mg/msq : 4 days
Doxorubicin 20 mg/msq : 3 days
Ifosfamide 2000 mg/msq : 3 days
Dacarbazine 250 mg/msq : 4 days

Substantially decrese local recurrence

Complications : skin & GIT, 1 death of neutropenia
 Treatment of STS
RADIATION I
2 days
MAID I Radiation 2 Gy/day
Rest Period
11 days ( 22 Gy)

RADIATION II
2 days MAID II
Radiation 2 Gy/day
Rest Period
11 days ( 22 Gy)

MAID II

SURGERY
( 3 weeks after MAID III)
 Results of STS Treatment
Massachusetts GH Orthopaedic
Oncology Group
1220 ps, 1972 June 2001
Survival rate overall : 72 % ( similar other
institutions )
Poorest survival :
leiomyosarcoma ( 51%), clear cell sarcoma ( 59 %),
alveolar soft part sarcoma ( 62 % ), MFH ( 64 % ).
Best survival :
epithelioid sarcoma ( 89 %), fibrosarcoma ( 85 % )
Recurrent rate : low ( < 4 % ) generally
 Results of STS treatment

Presented with Metastasis : 11,4 %

Leiomyosarcoma
Angiosarcoma
Alveolar soft part sarcoma
Life table pattern
 Discussion &
Conclusions
STS : unusual in oncology field
Major concern to connective tissue oncology
group of Massachusetts GH
Diagnostic :Staging & Grading : complex
protocol
Surgery : complex in many cases
Pre-op radiation & chemotherapy : reduce local
recurrence & metastasis
Many survive pts : still disabled
Protocols like MAID appears to improve survival
rates with moderate increase in complications
 Discussion &
Conclusions
Future : pts outcome may be improve by
addition diagnostic modalities :
- PET scanning
- genetic study
selective chemo & rad therapy
Gene identification & repair : assist
development
treatment
Thank you